Home Oleic acid and linoleic acid nanosomes boost immunity and provoke cell death via the upregulation of beta-defensin-4 at genetic and epigenetic levels
Article Open Access

Oleic acid and linoleic acid nanosomes boost immunity and provoke cell death via the upregulation of beta-defensin-4 at genetic and epigenetic levels

  • Gamaleldin I. Harisa EMAIL logo , Ibrahim Najashi , Ahmed H. Bakheit , Sabry M. Attia , Fars K. Alanazi , Salim S. Al-Rejaie and Mohamed Mohany
Published/Copyright: December 23, 2023
Download Article (PDF)
Open Chemistry
From the journal Open Chemistry Volume 21 Issue 1

Abstract

Host defense peptides (HDPs) are encouraged as anticancer and antimicrobial agents. Thus, this study aimed to investigate the effect of oleic acid (OA)- and linoleic acid (LA)-loaded nanosomes on the gene expression of beta-defensin-4 (BD-4) as a member of HDPs. The OA and LA nanosomes were prepared and characterized in terms of particle size and surface charge as lymphatic delivery systems. Afterwards, the effect of fatty acid (FA)-loaded nanosomes on BD-4 gene expression in mice dermal cells was investigated using polymerase chain reaction at 6, 12, and 24 h intervals. The epigenetic effect of OA and LA on histone deacetylase-6 (HDAC6) was studied using the molecular operating environment (MOE) docking. Moreover, the cytotoxic effect of free and FA-loaded nanosomes was investigated using 375 cell lines. The present results indicated that the prepared OA and LA nanosomes have a nanosize range (258–275 nm), negative zeta potential (−26 to −32 mV), and are homogenous polydispersity index (0.200–0.400). Moreover, free, and FA-loaded nanosomes induced significant upregulation of BD-4 mRNA expression after 6 and 12 h compared to the control mice BD-4 gene expression by several folds. However, after 24 h, the BD-4 mRNA expression significantly decreased compared to 12 h. Molecular docking studies revealed that OA and LA inhibit HDAC6 by binding with the active site. Treating the melanoma cell line with free or OL- and LA-loaded nanosomes induced significant cell death compared to negative control. This study suggests new insight into the effect of OA and LA on HDPs production. Consequently, the consumption of oils enriched with OL and LA stimulates the host immune system to fight microbial invasion and cancer. Moreover, Nanosomes are suggested as influential tactics for the specific lymphatic delivery of cytotoxic medicines.

Graphical abstract

Keywords: lymphatic delivery; beta-defensin-4; HDAC6; cytotoxicity

1 Introduction

Skin cells permit crosstalk between an organism and the environment, protect internal organs, maintain homeostasis, are essential for thermoregulation, and are involved in immunity [1]. Moreover, dermal cells are enriched with sensory nerves and receptors that can sense pain, temperature, touch, and other stimuli [2]. Parallel intestinal epithelial cells and dermal keratinocytes recognize pathogenic agents using pathogen recognition receptors [3]. Consequently, the skin cells represent another first line of defense against harsh conditions [1,3]. In response to pathogenic agents, skin residents are orchestrated with the other immune cells to boost the host’s immune defense in pathogenic battles [4]. Skin resident immune cells such as keratinocytes, melanocytes, dendritic cells, Merkle cells, and mast cells release the host defense peptides (HDPs) and other chemokines [3]. In particular, skin-associated lymphatic tissues (SALT) secrete mediators such as HDPs, which exert direct and indirect cytotoxic effects [1]. In addition, SALT release cytotoxic molecules, such as reactive oxygen species, lysozymes, interleukins, and other mediators that are essential for host defense [4]. Specifically, during infection, SALT overexpress HDPs, which trigger crosstalk between residents and recruited immune cells [5].

HDPs are small molecules that augment host immunity against and have cytotoxic activity [6]. Therefore, HDPs are a promising therapeutic avenue for the development of natural antimicrobial and anticancer agents [6]. Interestingly, HDPs have direct microbicidal effects by neutralizing microbial toxins, and they can maintain the microbiome balance [7]. Furthermore, HDPs provide a guide for engineering novel vaccines [8]. Chemically, HDPs include α- and β-defensins (BDs) that are constitutively produced by neutrophils, lymphocytes, SALT, and mucous membranes [7]. α-Defensins play a key role in local and systemic innate immunity and pathogen destruction [7]. BDs are members of HDPs, and they are produced by diverse combinations of epithelial and immune cell populations [8]. They are primarily expressed in SALT and mucous membranes during microbial infection [7]. BDs are multifunctional cationic peptides that manage crosstalk between the host and microbes to maintain a dynamic equilibrium across mucosal systems [8]. Thus, BDs are natural antimicrobials, which act as barriers in oral, dermal, respiratory, and reproductive tissues [8]. Furthermore, BDs elicit cytotoxic effects by interacting with the negatively charged membranes of cancer cells, bacteria, fungi, and viral envelopes to induce cell mortality [8].

The use of traditional antimicrobial agents for microbial eradication is usually associated with anaphylaxis, gastrointestinal upset, antimicrobial resistance, secondary infections, and disruption of the host microbiome [9]. For example, antimicrobial therapies eliminate microbial infections; however, they may induce drug resistance, dyslipidemia, insulin intolerance, and other harmful effect on humans [10,11]. Thus, agents that trigger HDP production could provide new insight into therapy instead of cytotoxic therapeutics [5]. In this context, dietary compounds such as essential oils, fatty acids (FAs), amino acids, trace elements, antioxidants, and probiotics modulate the gene expression of BDs as endogenous cytotoxic agents [5]. Among the dietary elements, oils are enriched with FAs, which are essential for cell growth, health, and metabolic regulation [12]. Generally, FAs are considered antimicrobial agents because of their ability to augment physical, chemical, and biological barriers to immune defense [12]. In particular, long-chain FAs are essential for immune response and body health [13]. These FAs are precursors of membrane phospholipids and second messengers that modulate gene expression and immune responses [13]. It has been reported that FA-enriched diets increase the expression of HDP genes [14,15]. In this context, oleic acid (OA) is 18 carbon atom mono-unsaturated FA at position 9 (OA; 18:1 n − 9), and linoleic acid (LA; 18:2, n − 6) is 18 carbon atom di-unsaturated FA at position 6. These FAs are reported as immunomodulatory agents with health benefits for disease prevention [16]. Figure 1 depicts the biological roles of FA in the host defense, besides their role in the upregulation of defensins as members of HDPs.

Figure 1 The biological roles of FAs in the host defense, besides their role in the upregulation of defensins as members of HDPs.
Figure 1

The biological roles of FAs in the host defense, besides their role in the upregulation of defensins as members of HDPs.

Nanoparticles have many advantages in medical applications, they have variability in size, shape, and high drug-loading capacity of both hydrophilic and hydrophobic medicines. Moreover, nanoparticles form stable interactions with ample ligands; therefore, nanoparticles elicit target-specific and controlled delivery of small and large molecule therapeutics [17]. As well, nanoparticles combined with the therapeutic agents overcome problems associated with conventional therapy. Drug nanocarriers have high therapeutic efficacy, safety, and reduced toxicity compared to classical therapeutic delivery systems [18]. Nanocarriers could deliver small drugs, peptides, antibodies, or aptamers with reduced immunogenicity [18]. Nanocarriers improve the solubility of insoluble drugs, sustain drug plasma life, and release drugs at a sustained rate. Moreover, nanoparticles deliver drugs in codelivery, targeted, and triggered approaches [18]. This minimizes systemic side effects, generates a synergistic effect, and suppresses multi-drug resistance [18]. In this context, nanoparticles are used in diagnosis, imaging, and advanced drug delivery systems for specific treatment of ample diseases including malignancy, microbial, autoimmune, cardiovascular, neurodegenerative, ophthalmic, respiratory, and other diseases [17]. It has been documented that nanoparticles improve the pharmacokinetic properties of medicines. Furthermore, they can target specific cells, easily penetrate cell membranes, and accumulate into subcellular organelles to modify cellular processes [19]. This is a valuable approach in treating diabetes, cancer, kidney diseases, and other health problems [19]. Interestingly, nanoparticles can encapsulate therapeutic nucleic acids such as DNA, mRNA, gene knockdown, and gene knockout tools for gene therapy [19]. Recently, nanoparticles have been involved in the successful delivery of nucleic acid in the coronavirus vaccine. This provides perspective for eradicating viral infection, malaria, and future pandemics [20,21]. Moreover, the progress in nanoparticle technology is promising for the development and delivery of therapy for genetic diseases [20,21]. Specifically, nanoparticles are used for the delivery of gene editing tools for genetic diseases, pandemics, cancer, hopeless diseases, and organ failure by the production of gene-modified cells, tissues, and animals as spare human organs [20,21]. Additionally, nano-robots can precisely target tumor cells by anticancer agents. Moreover, nano-robots can treat cardiovascular diseases and induce blood vessel repair [19].

Importantly, nanoscale lymphatic drug cargoes accumulate drugs in lymph nodes based on particle size (PS) and surface charge [6]. The lymphatic system is the main channel for microbial and cancer invasion; therefore, lymphatic drug transport is a promising strategy for the delivery of cytotoxic and immunomodulatory agents [22,23]. In this regard, nanosomal drug delivery systems efficiently transport drugs to target sites compared to conventional dosage forms [24]. Nanoscale lymphatic drug cargoes include lipid-based formulations that are lymphotropic agents and could deliver the drugs into lymph nodes. The microbial and cancer cells are colonized in the lymph nodes [22,23]. It has been reported that lipid-based formulations can enhance bioavailability and therapeutic drug effects by several folds [25]. Among lipid-based formulations, liposomes are excellent cargoes for FAs as therapeutic agents [25]. Consequently, liposomes are suggested as cargoes of antimicrobial agents and evade the challenges associated with classical drug cargoes [26].

Dietary oils enhance the skin’s immunological functions, but the exact mechanism is still unclear. Therefore, this study aimed to investigate the effects of OA- and LA-loaded nanosomes on the gene expression of beta-defensin-4 (BD-4) in mice skin. Both OA and LA are loaded into nanoliposomes and nanoemulsions, and then the nanosomes are characterized in terms of PS and zeta potential (ZP) as a nanoscale lymphatic delivery system. Afterwards, the FA nanosomes were injected into the mice, and the skin specimens were collected for BD-4 gene expression using real-time polymerase chain reaction (rtPCR) and compared to positive and negative control mice. Moreover, the effect of OA and LA on histone deacetylase-6 (HDAC6) was studied using molecular operating environment (MOE) docking studies. Finally, the cytotoxic effect of OA and LA free and nanosomes loaded was investigated using 375 cell lines as surrogate models for human melanoma.

2 Materials and methods

The materials used in this study include 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG2000), which were purchased from Lipoid GmbH (Ludwigshafen, Germany). Cholesterol, OA, LA, and linseed oil were purchased from Sigma-Aldrich (UK). Transcutol HP was purchased from Gattefosse (France). Chloroform high-performance liquid chromatography (HPLC) grade, methanol HPLC grade, and Tween 80 were purchased from Thermo Fisher Scientific (UK). All remaining chemicals were of analytical grade.

2.1 Preparation of FA nanosomes

Nanoliposomes were prepared using the lipid film hydration technique [27]. Briefly, a lipid mixture composed of DPPC, cholesterol, DSPE-PEG2000, and Tween 80 (65:25:5:2 molar ratio) was dissolved in 5 mL of chloroform/methanol (2:1 v/v). OA and LA (10 mg/mL) were added to the lipid mixture. The chloroform/methanol was slowly evaporated using a Rotavapor® (Buechi, Flawil, Switzerland) and maintained at 60°C at a speed of 100 rpm under vacuum for 1 h, allowing the formation of a thin film layer. The dried lipid film was hydrated with 5 mL of Milli-Q® water; multilamellar vesicles of liposomes were obtained and incubated at 60°C for 2 h to anneal the bilayer structure. Size reduction in the lamellarity of liposomes was performed using a bath sonicator for 30 min at 25°C. The plain nanoliposomes were free of OA and called Formula 1 (P-nanoliposome); however, in the case of FA-loaded liposomes both OA and called LA are present, Formula 2 (OL-nanoliposome).

Nanoemulsions were prepared using hot homogenization followed by ultrasonication. All the required ingredients were weighed, and the oil and aqueous phases were obtained separately. The oil phase comprised OA and/or LA (10 mg/mL), linseed oil (10%), and soybean oil (2%) as the lipid phase. The aqueous phase consisted of a mixture of the surfactant and cosurfactant (4%), Tween 80, and Transcutol (6:1) dissolved in water. The tonicity was adjusted by adding glycerol (2.25%, w/w) to the aqueous phase. Both phases were then warmed to 70°C. The aqueous phase was slowly poured dropwise into the lipid phase with stirring and then homogenized for approximately 5 min using a homogenizer. The coarse emulsion was sonicated for approximately 20 min at 60% amplitude using a probe sonicator. The plain nanoemulsions were free of OA and LA called Formula 3 (P-nanoemulsions). On the other side, FA-loaded nanoemulsions both OA and LA are present and called Formula 4 (OL-nanoemulsions).

2.2 Characterization of FA nanosomes

The mean PS and poly-diversity index (PDI) of the obtained nanosomes were determined using photon correlation spectroscopy using the Zetasizer Nano ZS (Malvern Instruments, Malvern, UK) at 25°C. The dispersions were diluted with deionized water to avoid multiple scattering. Additionally, the ZP was assessed based on electrophoretic mobility [27]. All results represent the averages of three measurements.

2.3 Animals’ treatment with nanosomes

This study included 36 male albino mice with body weights in the range of 50 ± 6.0 g and aged approximately 34 weeks. The mice were housed under conditions of controlled temperature (25 ± 2°C) with a 12:12-h day–night cycle, where they had ad libitum access to food and water until the mice acclimatized to the laboratory conditions. The mice were housed and maintained following the institutional and national guidelines and protocols approved by the Institutional Animal Ethical Committee. The experimental protocol was approved by the Research Ethics Committee (REC) (Ref. No.: KSU-SE-23-107) at King Saud University, Riyadh, Saudi Arabia. The mice were fed ad libitum with a commercial diet for 5 days, and the dietary components of the food included carbohydrates (72.2%), lipids (3.4%), proteins (19.8%), cellulose (3.6%), vitamins and minerals (0.5%), and salts (0.5%). The animals were acclimatized for 2 weeks.

Subsequently, the mice were divided into six groups with six mice per group.

Group 1: The mice received a normal saline solution as a negative control.

Group 2: The mice were administered a mixture of pure OA and LA dissolved in ethanol 0.5%.

Group 3: The mice were administered plain nanoemulsions that were free of OA and LA (P-nanoemulsions).

Group 4: The mice were administered OA–LA-loaded nanoemulsions (OL-nanoemulsion).

Group 5: The mice were administered plain nanoliposomes that were free of OA and LA (P-nanoliposomes).

Group 6: The mice were administered OA–LA-loaded nanoliposomes (OL-nanoliposomes).

The mice were intraperitoneally injected with OA and LA at a dose of 280 mg/kg. The doses were selected based on the previous published study [28].

2.3.1 Collection of mice skin biopsies

Skin biopsies were obtained from mice under light anesthesia at intervals of 6, 12, and 24 h after injecting nanosomes. Skin biopsies were collected after shaving and cleaning the skin from hair and dirt residue. The area was sterilized using an iodine sterilizer, and the specimens were collected for ribonucleic acid (RNA) extraction.

2.3.2 BD-4 RNA extraction from the dermal tissues

Total RNA was extracted from skin tissues using Trizol (Invitrogen), according to the manufacturer’s instructions. The RNA concentrations were measured using NanoDrop and expressed in µg/µL. RNA expressions were determined based on reverse transcription and the complement deoxyribonucleic acid (cDNA) synthesis. The cDNA molecules were created using SuperScript™ VILO™ cDNA Synthesis Kit (Invitrogen). The reaction tubes were mixed gently and incubated at 25°C for 10 min, followed by 42°C for 60 min; the reactions were terminated by incubation at 85°C for 5 min.

2.3.3 Mice mBD-4 gene expression

cDNA concentrations were measured using NanoDrop, and tubes were stored at −20°C until further use. The mice BD-4 (mBD-4) gene was expressed using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as the control. The assay was performed using TaqMan Gene Expression Master Mix (Invitrogen) and a Rotor-Gene Q rtPCR machine (QIAGEN). The thermal conditions were as follows: an incubation step at 50°C for 2 min, followed by incubation at 95°C for 10 min, then two steps 40 cycles, denaturation at 95°C for 15 s, and annealing/extension step at 60°C for 1 min. Table 1 shows the PCR primer sequences for mBD-4 designed against the housekeeping gene, GAPDH.

Table 1

rtPCR primer sequences of mBD4 designed against the housekeeping gene GAPDH

Genes Forward primer Reverse primer
GAPDH 5′-CCAAAAGGGTCATCATCTCC-3′ 5′-ACAGTCTTCTGGGTGGCAG-3′
mBD4 5′-GCAGCCTTTACCCAAATTATC-3′ 5′-ACAATTGCCAATCTGTCGAA-3′

2.4 Study of HDAC6 molecular docking

MOE docking was used to predict the degree of inhibition before therapeutic application. The MOE-docking module (vs 2015) was implemented in this study against 6WSJ proteins in the protein data bank format. HDAC6 protein is more abundant in cancerous cells than in healthy cells [29]. The configuration of each docking site was determined using the docking regulations applicable to this process. First, energy minimization was performed for each tested compound. After minimization, the charges were allocated to the atoms, the potential energy was modified, and the protonation states (pH 7.4) were assigned using MOE Protonate 3D, an assignment of Macromolecular Protonation State and Geometry, which is available online at: http://www.ccl.net/cca/documents/proton/.

The oriented compound was then saved in Microsoft Access Database format as a new database. The other parameters were controlled using the Merck Molecular Force Field 94 extended (MMFF94x force field). In addition, each protein co-crystal was constructed by first placing H atoms on top of specific receptors and then connecting the receptor types. The potential energy was then subjected to fixation, which was followed using a co-crystal ligand as the site marker. The docking process may begin requiring 30 postures per process. These poses, which were controlled by the London dG scoring function, were changed twice using the Matcher triangle. For each docking process, interaction data, validity patterns, and surface mapping have been exported. Data showing the real interaction validity determined the inhibition grade. True H-bond lengths did not exceed 3.5 Å. The placement method and scoring function were set as a triangular matcher and London dG, respectively, whereas the refinement method and scoring function were set to induce the Fit and GBVI/WSA dG, respectively [30,31].

2.5 Cell mortality studies

The 375 cell lines were used as surrogate models for human melanoma. A375 cells were cultured in Dulbecco’s modified Eagle’s medium without sodium pyruvate, supplemented with 10% fetal bovine serum, and 1% penicillin/streptomycin (all from Gibco; Thermo Fisher Scientific, Waltham, MA, USA). The 375 cells were seeded in 24-well plates at a density of 1 × 105 cells/well and grown in a humidified incubator at 37°C, 5% CO2 atmosphere. The 375 cells were treated as follows:

Group 1: Negative control, the 375 cell lines were treated with ethanol 0.5%. This concentration of ethanol was not toxic to the cells.

Group 2: The 375 cell lines were treated with a mixture of pure OA and LA dissolved in ethanol 0.5%.

Group 3: The 375 cell lines were treated with plain nanoemulsions that do not contain OA and LA (P-nanoemulsions).

Group 4: The 375 cell lines were treated with OA–LA-loaded nanoemulsions (OL-loaded nanoemulsion).

Group 5: The 375 cell lines were treated with plain nanoliposomes that do not contain OA and LA (P-nanoliposomes).

Group 6: The 375 cell lines were treated with OA–LA-loaded nanoliposomes (OL-loaded nanoliposomes).

At the end of the experiment, the cells were incubated with 1 mg/mL of MTT reagent, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, at 37°C for 4 h, after which it was discarded. The formed formazan crystals were dissolved using 100 mL of DMSO, followed by incubation and shaking. Finally, colorimetric analysis using a multi-plate reader was performed, and the absorbance was measured at 540 nm. The dose of OA and LA was 200 µM, and it was selected based on the previously published work [32]. The OA and LA were dissolved in ethanol at the final concentration of ethanol in the culture medium did not exceed 0.05%. This concentration of ethanol was not toxic to the cells [32].

2.6 Statistical analyses

Data were analyzed using GraphPad InStat software, version 4 (GraphPad, ISI Software Inc., La Jolla, CA, USA). The results were compared using a one-way analysis of variance. Data were expressed as mean ± SD, and p-value < 0.05 was used as criteria for significance.

3 Results and discussion

Microbial infections are predominantly treated using traditional antimicrobial agents such as antibiotics, antivirals, and antifungals [6,12]. However, extensive therapeutic utilization of conventional antimicrobial agents represents a global problem due to the incidence of antimicrobial resistance [6,12]. Remarkably, HDP expression levels are influenced by endogenous and exogenous factors. Herein, the upregulation of BD expression is a promising strategy to minimize the therapeutic use of cytotoxic agents [7]. In this regard, dietary agents are an alternative approach to boosting human immunity and controlling disease [5,12]. Dietary FAs are documented as immunomodulatory and cytotoxic agents [33]. However, the precise mechanism by which FA induces host defenses is still unclear. Consequently, this study was conducted to investigate the effect of OA and LA nanosomes on the gene expression of mBD-4, a member of HDPs.

3.1 FA nanosomes as a lymphatic delivery system

Nanosomes, including nanoemulsions and nanoliposomes, have been developed as smart delivery systems for therapeutic agents [34]. Incorporating OA and LA into nanosomes enhances their bioavailability and lymphatic delivery [28,35]. Lymphatic drug delivery depends on the log P of the drug, PS, and surface charge of the drug cargoes. Herein, nanoscale lipid-based delivery systems exhibit an inherent lymphatic tropism [22]. Biochemical and physiological fundamentals demonstrated that the absorption and distribution of long-chain FAs are mediated through lymphatic uptake [22,23]. Furthermore, the lipid nanosomes are lipoproteins that mimic nanoparticles that take the lymphatic system as a channel for distribution in biological systems [22,23]. The lymphatic system is a gateway for the spread of microbes and cancer cell metastasis. In this context, bacteria, viruses, parasites, and tumor cells colonize lymph nodes as hotspots for disease relapse after therapy [22]. Under pathological conditions, the gaps between lymphatic endothelial cells can reach up to 500 nm. Consequently, lymphatic delivery is considered an effective drug delivery method for cytotoxic agents [22].

FAs are essential components of the plasma membrane structure and influence membrane fluidity, receptors, and channel functions. Moreover, FA act as a source of signaling molecules, which affect cellular functions and modulate gene expression [36]. In the present study, OA and LA were assembled into nanosomes with nanoscale sizes, negative ZPs, and PDI, as shown in Table 2. Therefore, they could travel in the lymphatic system. The use of nanosomes as cargo for the delivery of antimicrobial agents has gained significant attention recently and is a promising tool for the selective delivery of cytotoxic drugs. These nanoscales enhance the pharmacokinetic characteristics and lymphatic distribution of the drug [26,35]. In the present study, OA and LA nanosomes were lipid-based formulations in the nanoscale range (Table 2). Therefore, they are suggested to deliver FA into the lymphatic system.

Table 2

Main components and characterization in terms of PS, ZP, and PDI of plain OA and LA-loaded nanosomes

Plain liposome OL-liposome Plain-nanoemulsion OL-nanoemulsion
DPPC + + − −
CH + + − −
DSPE-PEG2000 + + − −
Tween-80 (%) 2 2 4 4
Linseed oil − − + −
Soybean oil − − + +
OA − + − +
LA − + − +
PS (nm) 258.0 ± 64.24 260.0 ± 54.32 269.0 ± 76.14 275.00 ± 63.25
PDI 0.232 ± 0.031 0.201 ± 0.024 0.441 ± 0.22 0.343 ± 0.027
ZP (mV) −25.67 ± 0.084 −27.95 ± 0.78 −27.85 ± 0.52 −31.45 ± 0.49

Data were expressed as mean ± SD, N = 3. OA: oleic acid, LA: linoleic acid, PS: particle size, PDI: polydispersity index, ZP: zeta potential.

Additionally, the ZP of the cargoes is critical for lymphatic delivery; ZP of −30 mV indicates a strongly anionic nature, whereas +30 mV indicates the cationic nature of drug cargoes. Values between (+10 and −10 mV) indicate neutral behavior [37]. Despite the high cellular uptake of cationic particles, negatively charged nanoparticles are susceptible to lymphatic uptake [35,37]. In the present study, the prepared OA and LA nanosomes had a negative ZP (Table 2); hence, they were considered vectors for lymphatic delivery. In agreement with these suggestions, anionic liposomes show improved lymphatic uptake [37]. Moreover, the uptake of lymphatic nanosomes by lymph nodes is ordered as follows: negative, positive, and neutral charges [37,38]. Accordingly, administering antimicrobial or cytotoxic agents to nanocargoes ensures complete lymphatic deposition to eradicate microbial or cancer cells [37].

The routes of administration for lymphatic delivery cargoes include subcutaneous, intraperitoneal, or intradermal routes [22]. The lymphatic disposition of administered nanosomes could target cancers and infectious agents [38]. However, the skin has high lymph flow and is enriched with SALT, which is involved in adaptive and innate immunity [1]. Moreover, the skin acts as a physical, chemical, mechanical, biological, and immunological barrier [1]. In this regard, the acidic pH of the skin makes it an inhospitable environment for pathogens and acts as a secondary defensive mechanism [3]. The skin microbiome regulates immunity and modulates gene expression by secreting cell-signaling molecules such as cytokines, HDPs, and FA [3]. Collectively, FA play an important role in the regulation of pH, microbiome balance, and diverse skin functions as one of the first lines of host defense against pathogens.

3.2 Effect of FA on BD-4 gene expression

Real-time PCR results revealed that, compared to the control mice, mice injected with OA and LA nanosomes showed significantly upregulated mBD-4 gene expression at 6 and 12 h after intraperitoneal injection (Figures 2 and 3). However, the mBD-4 mRNA expression significantly decreased after 24 h of treatment with OA and LA nanosomes, compared to those at 6 and 12 h intervals (Figure 4). The present results were consistent with a previous study, which reported the upregulation of mBD-4 expression on treatment with FA [33]. Similarly, Linde et al. demonstrated that a fatty diet upregulates BD4 gene expression in rodents [39]. In addition, the upregulation of mBD-4 expression may be a potential mechanism of OA- and LA-induced antimicrobial action [40]. Correspondingly, it has been reported that FA enhance innate defense by inducing the expression of human BD [33,41].

Figure 2 Effect of free OA, LA, as well as OA-LA-loaded nanosomes on the expression of mRNA of BD-4 expression compared to negative and positive control after 6 h of treatment. Data were expressed as mean ± SD, 6 rats/group. (a) Significant increase from the negative control, and plain nanosome groups. (b) Significant increase from the negative control, and plain nanosomes, positive control groups. Abbreviations: P: plain, SD: standard deviation, OA: oleic acid, LA: linoleic acid, mRNA: messenger RNA, BD-4: beta defensin-4.
Figure 2

Effect of free OA, LA, as well as OA-LA-loaded nanosomes on the expression of mRNA of BD-4 expression compared to negative and positive control after 6 h of treatment. Data were expressed as mean ± SD, 6 rats/group. (a) Significant increase from the negative control, and plain nanosome groups. (b) Significant increase from the negative control, and plain nanosomes, positive control groups. Abbreviations: P: plain, SD: standard deviation, OA: oleic acid, LA: linoleic acid, mRNA: messenger RNA, BD-4: beta defensin-4.

Figure 3 Effect of free OA, LA, and OA–LA-loaded nanosomes on the expression of mRNA of BD-4 expression compared to negative and positive control after 12 h of treatment. Data were expressed as mean ± SD, 6 rats/group. (a) Significant increase from the negative control, and plain nanosomes groups. (b) Significant increase from the negative control, and plain nanosomes, positive control groups. (c) Significant increase from the negative control, plain nanosomes, positive control groups, and OL-nanoemulsion group. Abbreviations: P: plain, SD: standard deviation, OA: oleic acid, LA: linoleic acid, mRNA: messenger RNA, BD-4: beta defensin-4.
Figure 3

Effect of free OA, LA, and OA–LA-loaded nanosomes on the expression of mRNA of BD-4 expression compared to negative and positive control after 12 h of treatment. Data were expressed as mean ± SD, 6 rats/group. (a) Significant increase from the negative control, and plain nanosomes groups. (b) Significant increase from the negative control, and plain nanosomes, positive control groups. (c) Significant increase from the negative control, plain nanosomes, positive control groups, and OL-nanoemulsion group. Abbreviations: P: plain, SD: standard deviation, OA: oleic acid, LA: linoleic acid, mRNA: messenger RNA, BD-4: beta defensin-4.

Figure 4 Effect of OA, LA, and OA–LA-loaded nanosomes on the expression of mRNA of BD-4 expression compared to negative and positive control after 24 h of treatment. Data were expressed as mean ± SD, 6 rats/group. (a) Significant increase from the negative control, and plain nanosomes groups. (b) Significant increase from the negative control, and plain nanosomes, positive control groups. (c) Significant increase from the negative control, plain nanosomes, positive control groups, and OL-nanoemulsion group. Abbreviations: P: plain, SD: standard deviation, OA: oleic acid, LA: linoleic acid, mRNA: messenger RNA, BD-4: beta defensin-4.
Figure 4

Effect of OA, LA, and OA–LA-loaded nanosomes on the expression of mRNA of BD-4 expression compared to negative and positive control after 24 h of treatment. Data were expressed as mean ± SD, 6 rats/group. (a) Significant increase from the negative control, and plain nanosomes groups. (b) Significant increase from the negative control, and plain nanosomes, positive control groups. (c) Significant increase from the negative control, plain nanosomes, positive control groups, and OL-nanoemulsion group. Abbreviations: P: plain, SD: standard deviation, OA: oleic acid, LA: linoleic acid, mRNA: messenger RNA, BD-4: beta defensin-4.

Specifically, BDs are overexpressed in resident skin cells and sebaceous glands in response to pathogens, inflammation, or homeostatic stimulation [2]. Under such conditions, skin keratinocytes activate immune cells and counteract microbial invasion by producing BDs [3], which can destroy the viral capsid and block viral receptors [7]. In this regard, human BDs prevent the coronavirus host cell attack [7]. In addition to the upregulation of BD expression, FAs are known inhibitors of the early-stage viral replication cycle [42]. Moreover, FAs are documented to block cluster differentiation-4 receptors and prevent viral entry [38]. Consequently, FAs have been exploited as safe and potent inhibitors of viral host cell invasion [43]. Equally, the natural oils enriched with essential FAs prevent the entry of human immunodeficiency virus into host cells [44]. Moreover, FAs inactivate enveloped viruses and elicit a noticeable direct inhibitory effect on viral host proteases [45]. HDPs not only function as antimicrobials but also play a role in tissue repair, aging, memory, and apoptosis [2]. Taken together, this study suggests new insight into the effect of OA and LA on BD production at genetic and epigenetic levels.

3.3 Effect of FA on HDA6

Molecular modeling can be used to study the biological activities of bioactive substances and ligand-receptor/enzyme-binding approaches. FAs are ligands for peroxisome proliferator activating receptors, which play essential roles in gene expression, differentiation, and the regulation of immune cell function [46]. Moreover, FAs can modulate HDAC6 activity, which plays an important role in the epigenetic control of gene expression. In this regard, the modulation of HDAC6 participates in the regulation of immunity, inflammation, and neurodegeneration [47]. Consequently, in the present study, OA and LA were used as ligands for HDAC6 as the target protein involved in the epigenetic regulation of HDPs. Similarly, it has been documented that FAs upregulate BD expressions [2].

In this study, molecular docking was used to study the binding modes and orientations of OA and LA with amino acids in the probable binding sites of HDACs. OA, LA, and co-crystallized bound inhibitors were added to the HDAC6 active site to ensure docking accuracy and orientation. The docking score and hydrogen bond formation between the docked molecules and amino acids in the putative active pocket of the protein predict the manner of the interaction. The bound inhibitors were subjected to a single docking run at the binding sites to test and confirm the docking procedure. The Chemical Computing Group Inc.’s MOE 2015.10 program protocol with default docking placement parameters was followed by force field posture refinement and rescoring using the GBVI/WSA dG scoring tool [48]. The docking scores, hydrogen bonding, and a list of zinc-binding group-carbonyl group interactions significantly contributed to the dock scores for OA and LA are displayed in Table 3.

Table 3

Molecular docking scores and interactions of active site residual amino acid against compounds OA, LA for histone deacetylase (HDAC6) receptors

Ligand Receptor Interaction Distance E (kcal/mol) Scoring (kcal/mol)
OA
O 1 OH TYR 745 (A) H-acceptor 2.92 −0.4 −8.203
O 2 NE2 HIS 573 (A) H-acceptor 2.94 −12.7
O 2 NE2 HIS 574 (A) H-acceptor 2.7 −4.7
O 2 ZN ZN 801 (A) Metal 2.35 −2
O 2 NE2 HIS 573 (A) Ionic 2.94 −4.9
O 2 NE2 HIS 574 (A) Ionic 2.7 −6.8
O 2 ZN ZN 801 (A) Ionic 2.35 −10.7
C 24 6-ring PHE 583 (A) H-pi 3.94 −0.5
LA
O 1 NE2 HIS 573 (A) H-acceptor 3.02 −12 −7.962
O 1 NE2 HIS 574 (A) H-acceptor 2.73 −4.7
O 2 OH TYR 745 (A) H-acceptor 2.87 −0.4
O 1 ZN ZN 801 (A) Metal 2.36 −2
O 1 NE2 HIS 573 (A) Ionic 3.02 −4.3
O 1 NE2 HIS 574 (A) Ionic 2.73 −6.5
O 1 ZN ZN 801 (A) Ionic 2.36 −10.6
C 3 5-ring HIS 614 (A) H-pi 4 −0.3
C 9 6-ring PHE 583 (A) H-pi 3.96 −0.4
C 24 5-ring HIS 463 (A) H-pi 4.43 −0.4

The docking score for the OA molecule was −8.203 kcal/mol (HDAC6), as shown in Figure 5(a) and (c) and Table 3. In the interaction with HDAC6, the carbonyl group of OA formed many strong ionic bonds with the Zn ion and H-bonds with His573, His573, and Tyr745 residues (Figure 5a and c). In addition, the OA hydrocarbon chain formed an H–π connection with Phe583. In addition, the docking score for LA was −7.962 (HDAC6) (Figure 5b and d) and Table 3. In addition to multiple H-bonds with the His573, His574, and Tyr745 residues of HDAC6, the carbonyl group of LA formed several strong ionic interactions with the Zn ion (Figure 5b and d). Moreover, the hydrocarbon chain of LA formed an H-bond with His614, in addition to an H–π bond with the Phe583 residue of the HDAC6 [49,50]. These findings agree with those of a previous study demonstrating that FA elicit HDAC6 inhibition. The HDAC6 inhibitory potential of OA and LA may be attributed to the presence of ample methylene groups in the side chains, which form strong hydrophobic interactions with protein residues. In addition, the aliphatic carbon chain length of FA induces inhibitory potentials against HDAC [51].

Figure 5 The predicted ligand–receptor interactions of compound OA with the HDAC6 2D and 3D (a)–(c), respectively, LA with HDAC6 (b) and (d) for 2D and 3D, respectively.
Figure 5

The predicted ligand–receptor interactions of compound OA with the HDAC6 2D and 3D (a)–(c), respectively, LA with HDAC6 (b) and (d) for 2D and 3D, respectively.

Figure 6 Effect of free OA, LA, OA–LA-loaded nanosomes on cell mortality percent compared to control after 72 h of treatment. Data were expressed as mean ± SD, 6 rats/group. (a) Significant increase from the negative control, and plain nanosome groups. (b) Significant increase from the negative control, and plain nanosomes, positive control groups. Abbreviations: P: plain, SD: standard deviation, OA: oleic acid, LA: linoleic acid, mRNA: messenger RNA, BD-4: beta defensin-4.
Figure 6

Effect of free OA, LA, OA–LA-loaded nanosomes on cell mortality percent compared to control after 72 h of treatment. Data were expressed as mean ± SD, 6 rats/group. (a) Significant increase from the negative control, and plain nanosome groups. (b) Significant increase from the negative control, and plain nanosomes, positive control groups. Abbreviations: P: plain, SD: standard deviation, OA: oleic acid, LA: linoleic acid, mRNA: messenger RNA, BD-4: beta defensin-4.

3.4 Effect FA on the mortality of melanoma cells

The present study revealed that the free OA and LA induced death of melanoma cell lines compared to the control cells. Remarkably, the treatment of the melanoma cell line with OA- and LA-loaded nanosomes increases cell death compared to both negative and positive control cell. Figure 6 shows the effect of FA on the mortality of melanoma cells. The present results are synchronized with ample studies investigating the effect of FA on cell mortality. In this regard, a previous study demonstrated that both OA and LA promote cell death by apoptosis and necrosis. Moreover, these FAs induced mitochondrial depolarization and lipid accumulation intracellularly [52]. Similarly, it has been documented that treatment of the cells with OA and LA induced lipotoxicity, peroxisome proliferator activating receptors, activation, increased caspase activities, and TNF-alpha production [32]. Furthermore, OA significantly induced autophagy and reduced the migration and invasion of cancer cells without effects on healthy cells [53]. FA-loaded nanostructured cargoes increase the antimetastatic potential of FA. Therefore, nanosomes are suggested as an influential tactic for the specific delivery of cytotoxic medicines [54]. However, microbial cells and tumor cells colonize lymph nodes as hotspots for disease relapse after therapy.

Taken together, FAs are involved in the biosynthesis of phospholipids, sphingomyelin, glucosylceramides, sphingosine, and other mediators involved in cell signaling and immune cell differentiation and function [2]. Specifically, FAs are essential for the functioning of sebocytes, which secrete sebum via the sebaceous glands. Sebum is enriched with other lipids, including triacylglycerol, wax esters, ceramides, cholesterol, and squalene, which serve as immunological and physical barriers [2], preventing pathogen entry into the deeper layers of the skin [2]. Furthermore, triacylglycerol in sebum can be hydrolyzed into free FA to create an acidic environment as part of the immunological role [2].

Finally, OA and LA elicit immunomodulatory and cytotoxic effects by the upregulation of BDs that induce pore formation, interference with cell wall synthesis, and depolarization of foreign cells [8]. This attributed to the amphipathic nature of BDs enables their insertion into the phospholipid membrane, thereby destroying foreign cells [8]. Moreover, BDs can disrupt energy manufacture, nucleic acids, and protein production by cancer and microbial cells [7]. BDs can trigger reactive metabolite production and dysregulation of ionic homeostasis as a mechanism for cancer and microbial cell death [9]. Consequently, human diet enrichment with olive oil, linseed, walnut oil, and fish products is beneficial to propagate the human and increase the cell’s longevity [55,56].

4 Conclusions

This study concluded that the prepared nanoscale OA and LA nanosomes (258–275 nm) had negative ZP values (−26 to −32 mV); therefore, they are promising lymphatic delivery vectors. OA and LA nanosomes upregulated BD-4 gene expression by several folds. This study suggests new insight into the effect of OA and LA on the production of HDPs as endogenous cytotoxic agents. Therefore, OA and LA supplementation could be used as a supportive approach with antimicrobial and cytotoxic therapy. Dietary oils such as olive oil and linseed oil enriched with OA and LA are recommended as immunomodulatory agents for patients with infectious diseases and cancer. Collectively, OA and LA could be dietary interventions to protect against microbial infections and cancer as alternative methods for minimizing the use of antimicrobials. Nanosomes are suggested as influential tactics for the specific lymphatic delivery of cytotoxic medicines. However, microbial cells and tumor cells colonize lymph nodes as hotspots for disease relapse after therapy.

4.1 Study limitations

Regardless of the hopeful results of this work, numerous limitations should be acknowledged. First, the investigation focused on the gene expression of BD-4 as a member of HDPs, without exploring the broader impact on other HDPs or the overall host defense system. Therefore, the generalizability of the findings to the entire HDPs range may be limited. Additionally, the study utilized mice dermal cells as the experimental model, which may not fully replicate the complexities of human skin or the interactions between the immune system and FA-loaded nanosomes. Furthermore, the cytotoxic effects of the free and FA-loaded nanosomes were only evaluated on one cell line, limiting the understanding of their effectiveness across different cancer cell types. Finally, while molecular docking studies provided insights into the potential epigenetic effect of OA and LA on HDAC6, therefore, further experimental validation is necessary to confirm these interactions in vivo. These limitations highlight opportunities for future research to explore the broader implications of HDP modulation, utilize more representative model systems, investigate diverse cancer cell lines, and validate the epigenetic effects observed in this study.

tel: +966 546269544; fax: +966 (11)4676295

Acknowledgments

The authors extend their appreciation to the Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia for funding this research (IFKSURC-1-0811).

  1. Funding information: The authors extend their appreciation to the Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia for funding this research (IFKSURC-1-0811).

  2. Author contributions: Gamaleldin I. Harisa and Ibrahim Najashi contributed to the study’s conception, design, collection, and writing. Ahmed H. Bakheit achieved the molecular docking, Fars K. Alanazi, Sabry M. Attia and Salim S. Al-Rejaie involved in manuscript revision, and Mohamed Mohany contributed to software and formal analysis. All authors read, revised, and approved the final manuscript.

  3. Conflict of interest: The authors declare no conflict of interest.

  4. Ethical approval: The experimental protocol was approved by the Research Ethics Committee (REC) (Ref. No.: KSU-SE-23-107) at King Saud University, Riyadh, Saudi Arabia.

  5. Data availability statement: All data are embedded in the manuscript.

References

[1] Mestrallet G, Rouas-Freiss N, LeMaoult J, Fortunel NO, Martin MT. Skin immunity and tolerance: Focus on epidermal keratinocytes expressing HLA-G. Front Immunol. 2021;12:5166.10.3389/fimmu.2021.772516Search in Google Scholar PubMed PubMed Central

[2] Nguyen AV, Soulika AM. The dynamics of the skin’s immune system. Int J Mol Sci. 2019;20(8):1811.10.3390/ijms20081811Search in Google Scholar PubMed PubMed Central

[3] Quaresma JAS. Organization of the skin immune system and compartmentalized immune responses in infectious diseases. Clin Microbiol Rev. 2019;32(4):e00034-18.10.1128/CMR.00034-18Search in Google Scholar PubMed PubMed Central

[4] Kabashima K, Honda T, Ginhoux F, Egawa G. The immunological anatomy of the skin. Nat Rev Immunol. 2019;19(1):19–30.10.1038/s41577-018-0084-5Search in Google Scholar PubMed

[5] Zeng X, Sunkara LT, Jiang W, Bible M, Carter S, Ma X, et al. Induction of porcine host defense peptide gene expression by short-chain fatty acids and their analogs. PLoS One. 2013;8(8):e72922.10.1371/journal.pone.0072922Search in Google Scholar PubMed PubMed Central

[6] Zhang Z, Lu Y, Qi J, Wu W. An update on oral drug delivery via intestinal lymphatic transport. Acta Pharm Sin B. 2021;11(8):2449–68.10.1016/j.apsb.2020.12.022Search in Google Scholar PubMed PubMed Central

[7] Guryanova SV, Ovchinnikova TV. Immunomodulatory and allergenic properties of antimicrobial peptides. Int J Mol Sci. 2022;23(5):2499.10.3390/ijms23052499Search in Google Scholar PubMed PubMed Central

[8] Meade KG, O’Farrelly C. β-Defensins: Farming the microbiome for homeostasis and health. Front Immunol. 2019;9:3072.10.3389/fimmu.2018.03072Search in Google Scholar PubMed PubMed Central

[9] Mohsen S, Dickinson JA, Somayaji R. Update on the adverse effects of antimicrobial therapies in community practice. Can Fam Physician. 2020;66(9):651–9.Search in Google Scholar

[10] Gleason Jr RL, Caulk AW, Seifu D, Parker I, Vidakovic B, Getenet H, et al. Current Efavirenz (EFV) or ritonavir-boosted lopinavir (LPV/r) use correlates with elevate markers of atherosclerosis in HIV-infected subjects in Addis Ababa, Ethiopia. PLoS One. 2015;10(4):e0117125.10.1371/journal.pone.0117125Search in Google Scholar PubMed PubMed Central

[11] Vieira ADS, Silveira GRMD. Effectiveness of n-3 fatty acids in the treatment of hypertriglyceridemia in HIV/AIDS patients: a meta-analysis. Cienc Saude Colet. 2017;22:2659–69.10.1590/1413-81232017228.21752015Search in Google Scholar PubMed

[12] Saleri R, Borghetti P, Ravanetti F, Cavalli V, Ferrari L, De Angelis E, et al. Effects of different short-chain fatty acids (SCFA) on gene expression of proteins involved in barrier function in IPEC-J2. Porc Health Manag. 2022;8(1):21.10.1186/s40813-022-00264-zSearch in Google Scholar PubMed PubMed Central

[13] da Costa BT, Araújo GRL, da Silva Júnior RT, de Sá Santos LK, de Souza Gonçalves VL, Lima DBA, et al. Effects of nutrients on immunomodulation in patients with severe COVID-19: Current knowledge. World J Crit Care Med. 2022;11(4):201.10.5492/wjccm.v11.i4.201Search in Google Scholar PubMed PubMed Central

[14] De Pablo MA, De Cienfuegos GÁ. Modulatory effects of dietary lipids on immune system functions. Immunol Cell Biol. 2000;78(1):31–9.10.1046/j.1440-1711.2000.00875.xSearch in Google Scholar PubMed

[15] Sunkara LT, Jiang W, Zhang G. Modulation of antimicrobial host defense peptide gene expression by free fatty acids. PLoS One. 2012;7(11):e49558.10.1371/journal.pone.0049558Search in Google Scholar PubMed PubMed Central

[16] Piccinin E, Cariello M, De Santis S, Ducheix S, Sabbà C, Ntambi JM, et al. Role of oleic acid in the gut-liver axis: from diet to the regulation of its synthesis via stearoyl-CoA desaturase 1 (SCD1). Nutrients. 2019;11(10):2283.10.3390/nu11102283Search in Google Scholar PubMed PubMed Central

[17] Yetisgin AA, Cetinel S, Zuvin M, Kosar A, Kutlu O. Therapeutic nanoparticles and their targeted delivery applications. Molecules. 2020;25(9):2193.10.3390/molecules25092193Search in Google Scholar PubMed PubMed Central

[18] Utreja P, Verma S, Rahman M, Kumar L. Use of nanoparticles in medicine. Curr Biochem Eng. 2020;6(1):7–24.10.2174/2212711906666190724145101Search in Google Scholar

[19] Yusuf A, Almotairy ARZ, Henidi H, Alshehri OY, Aldughaim MS. Nanoparticles as Drug Delivery Systems: A Review of the implication of nanoparticles’ physicochemical properties on responses in biological systems. Polymers. 2023;15(7):1596.10.3390/polym15071596Search in Google Scholar PubMed PubMed Central

[20] Harisa GI, Faris TM, Sherif AY, Alzhrani RF, Alanazi SA, Kohaf NA, et al. Gene-editing technology, from macromolecule therapeutics to organ transplantation: Applications, limitations, and prospective uses. Int J Biol Macromol. 2023;253:127055.10.1016/j.ijbiomac.2023.127055Search in Google Scholar PubMed

[21] Harisa GI, Faris TM, Sherif AY, Alzhrani RF, Alanazi SA, Kohaf NA, et al. Coding therapeutic nucleic acids from recombinant proteins to next-generation vaccines: Current uses, limitations, and future horizons. Mol Biotechnol. 2023;1–19. 10.1007/s12033-023-00821-z. Search in Google Scholar PubMed

[22] Sherif AY, Harisa GI, Alanazi FK, Nasr FA, Alqahtani AS. Engineered nanoscale lipid-based formulation as potential enhancer of gefitinib lymphatic delivery: Cytotoxicity and apoptotic studies against the A549 cell line. AAPS PharmSciTech. 2022;23(6):183.10.1208/s12249-022-02332-7Search in Google Scholar PubMed PubMed Central

[23] Sherif AY, Harisa GI, Alanazi FK, Nasr FA, Alqahtani AS. PEGylated SLN as a promising approach for lymphatic delivery of gefitinib to lung cancer. Int J Nanomed. 2022;17:3287–311.10.2147/IJN.S365974Search in Google Scholar PubMed PubMed Central

[24] Harisa GI, Badran MM, Alanazi FK, Attia SM. An overview of nanosomes delivery mechanisms: trafficking, orders, barriers and cellular effects. Artif Cells Nanomed Biotechnol. 2018;46(4):669–79.10.1080/21691401.2017.1354301Search in Google Scholar PubMed

[25] Yang D, Pornpattananangkul D, Nakatsuji T, Chan M, Carson D, Huang C-M, et al. The antimicrobial activity of liposomal lauric acids against Propionibacterium acnes. Biomaterials. 2009;30(30):6035–40.10.1016/j.biomaterials.2009.07.033Search in Google Scholar PubMed PubMed Central

[26] Chopra S, Venkatesan N, Betageri GV. Liposomes as nanocarriers for anti-HIV therapy. Drug Deliv Transl Res. 2013;3:471–8.10.1007/s13346-013-0134-2Search in Google Scholar PubMed

[27] AlQahtani SA, Harisa GI, Badran MM, AlGhamdi KM, Kumar A, Salem-Bekhit MM, et al. Nano-erythrocyte membrane-chaperoned 5-fluorouracil liposomes as biomimetic delivery platforms to target hepatocellular carcinoma cell lines. Artif Cells Nanomed Biotechnol. 2019;47(1):989–96.10.1080/21691401.2019.1577887Search in Google Scholar PubMed

[28] Su H, Zhang Y, Huang W, Wen L, Zhuang Z, Chen G. Pharmacokinetics and tissue distribution of oleic and linoleic acids following oral and rectal administration of Brucea javanica oil in rats. Int J Pharmacol. 2016;12(5):461–82.10.3923/ijp.2016.461.482Search in Google Scholar

[29] Watson PJ, Millard CJ, Riley AM, Robertson NS, Wright LC, Godage HY, et al. Insights into the activation mechanism of class I HDAC complexes by inositol phosphates. Nat Commun. 2016;7(1):1–13.10.1038/ncomms11262Search in Google Scholar PubMed PubMed Central

[30] Alanazi AM, Abdelhameed AS, Bakheit AH, Darwish IA. Exploring the interaction forces involved in the binding of the multiple myeloma drug lenalidomide to bovine serum albumin. J Mol Liq. 2017;238:3–10.10.1016/j.molliq.2017.04.110Search in Google Scholar

[31] Wani TA, Alsaif NA, Alanazi MM, Bakheit AH, Khan AA, Zargar S. Binding of colchicine and ascorbic acid (vitamin C) to bovine serum albumin: An in-vitro interaction study using multispectroscopic, molecular docking and molecular dynamics simulation study. J Mol Liq. 2021;342:117542.10.1016/j.molliq.2021.117542Search in Google Scholar

[32] Cury-Boaventura MF, Kanunfre CC, Gorjão R, de Lima TM, Curi R. Mechanisms involved in Jurkat cell death induced by oleic and linoleic acids. Clin Nutr. 2006;25(6):1004–14.10.1016/j.clnu.2006.05.008Search in Google Scholar PubMed

[33] Nakatsuji T, Kao MC, Zhang L, Zouboulis CC, Gallo RL, Huang C-M. Sebum free fatty acids enhance the innate immune defense of human sebocytes by upregulating β-defensin-2 expression. J Investig Dermatol. 2010;130(4):985–94.10.1038/jid.2009.384Search in Google Scholar PubMed PubMed Central

[34] Jackman JA, Yoon BK, Li D, Cho N-J. Nanotechnology formulations for antibacterial free fatty acids and monoglycerides. Molecules. 2016;21(3):305.10.3390/molecules21030305Search in Google Scholar PubMed PubMed Central

[35] Harisa GI, Sherif AY, Alanazi FK, Ali EA, Omran GA, Nasr FA, et al. TPGS decorated NLC shift gefitinib from portal absorption into lymphatic delivery: Intracellular trafficking, biodistribution and bioavailability studies. Colloids Surf B Biointerfaces. 2023;223:113148.10.1016/j.colsurfb.2023.113148Search in Google Scholar PubMed

[36] Duplus E, Glorian M, Forest C. Fatty acid regulation of gene transcription. J Biol Chem. 2000;275(40):30749–52.10.1074/jbc.R000015200Search in Google Scholar PubMed

[37] Khan AA, Mudassir J, Mohtar N, Darwis Y. Advanced drug delivery to the lymphatic system: lipid-based nanoformulations. Int J Nanomedicine. 2013;8:2733–44.10.2147/IJN.S41521Search in Google Scholar PubMed PubMed Central

[38] Lee G, Han S, Inocencio I, Cao E, Hong J, Phillips AR, et al. Lymphatic uptake of liposomes after intraperitoneal administration primarily occurs via the diaphragmatic lymphatics and is dependent on liposome surface properties. Mol Pharmaceutics. 2019;16(12):4987–99.10.1021/acs.molpharmaceut.9b00855Search in Google Scholar PubMed

[39] Linde A, Ross C, Blecha F, Lushington GH, Melgarejo T. Cardiac beta-defensins upregulate with a high fat diet and influence monocyte migration. Open J Intern Med. 2013;3(2):81–94.10.4236/ojim.2013.32021Search in Google Scholar

[40] Quiñones-Mateu ME, Lederman MM, Feng Z, Chakraborty B, Weber J, Rangel HR, et al. Human epithelial β-defensins 2 and 3 inhibit HIV-1 replication. Aids. 2003;17(16):F39–48.10.1097/00002030-200311070-00001Search in Google Scholar PubMed

[41] Nguyen MT, Hanzelmann D, Härtner T, Peschel A, Götz F. Skin-specific unsaturated fatty acids boost the Staphylococcus aureus innate immune response. Infect Immun. 2016;84(1):205–15.10.1128/IAI.00822-15Search in Google Scholar PubMed PubMed Central

[42] Sun L, Finnegan CM, Kish-Catalone T, Blumenthal R, Garzino-Demo P, La Terra Maggiore GM, et al. Human β-defensins suppress human immunodeficiency virus infection: potential role in mucosal protection. J Virol. 2005;79(22):14318–29.10.1128/JVI.79.22.14318-14329.2005Search in Google Scholar PubMed PubMed Central

[43] Lin X, Paskaleva EE, Chang W, Shekhtman A, Canki M. Inhibition of HIV-1 infection in ex vivo cervical tissue model of human vagina by palmitic acid; implications for a microbicide development. PLoS One. 2011;6(9):e24803.10.1371/journal.pone.0024803Search in Google Scholar PubMed PubMed Central

[44] Omar SH. Oleuropein in olive and its pharmacological effects. Sci Pharm. 2010;78(2):133–54.10.3797/scipharm.0912-18Search in Google Scholar PubMed PubMed Central

[45] Goc A, Niedzwiecki A, Rath M. Polyunsaturated ω-3 fatty acids inhibit ACE2-controlled SARS-CoV-2 binding and cellular entry. Sci Rep. 2021;11(1):1–12.10.1038/s41598-021-84850-1Search in Google Scholar PubMed PubMed Central

[46] Zouboulis CC. Sebaceous gland receptors. Derm-Endocrinol. 2009;1(2):77–80.10.4161/derm.1.2.7804Search in Google Scholar PubMed PubMed Central

[47] Lernoux M, Schnekenburger M, Dicato M, Diederich M. Anti-cancer effects of naturally derived compounds targeting histone deacetylase 6-related pathways. Pharmacol Res. 2018;129:337–56.10.1016/j.phrs.2017.11.004Search in Google Scholar PubMed

[48] Dahhas MA, Alkahtani HM, Malik A, Almehizia AA, Bakheit AH, Ansar SA, et al. Screening and identification of potential MERS-CoV papain-like protease (PLpro) inhibitors; Steady-state kinetic and Molecular dynamic studies. Saudi Pharm J. 2022;31(2):228–44.10.1016/j.jsps.2022.12.007Search in Google Scholar PubMed PubMed Central

[49] Hamdi A, Elhusseiny WM, Othman DI, Haikal A, Bakheit AH, El-Azab AS, et al. Synthesis, antitumor, and apoptosis-inducing activities of novel 5-arylidenethiazolidine-2, 4-dione derivatives: histone deacetylases inhibitory activity and molecular docking study. Eur J Med Chem. 2022;244:114827.10.1016/j.ejmech.2022.114827Search in Google Scholar PubMed

[50] Ahmed AF, Wen Z-H, Bakheit AH, Basudan OA, Ghabbour HA, Al-Ahmari A, et al. A Major diplotaxis harra-derived bioflavonoid glycoside as a protective agent against chemically induced neurotoxicity and parkinson’s models; in silico target prediction; and biphasic HPTLC-based quantification. Plants. 2022;11(5):648.10.3390/plants11050648Search in Google Scholar PubMed PubMed Central

[51] Ediriweera MK, To NB, Lim Y, Cho SK. Odd-chain fatty acids as novel histone deacetylase 6 (HDAC6) inhibitors. Biochimie. 2021;186:147–56.10.1016/j.biochi.2021.04.011Search in Google Scholar PubMed

[52] Coniglio S, Shumskaya M, Vassiliou E. Unsaturated fatty acids and their immunomodulatory properties. Biology. 2023;12(2):279.10.3390/biology12020279Search in Google Scholar PubMed PubMed Central

[53] Giulitti F, Petrungaro S, Mandatori S, Tomaipitinca L, De Franchis V, D’Amore A, et al. Anti-tumor effect of oleic acid in hepatocellular carcinoma cell lines via autophagy reduction. Front Cell Dev Biol. 2021;9:629182.10.3389/fcell.2021.629182Search in Google Scholar PubMed PubMed Central

[54] Rinaldi F, Forte J, Pontecorvi G, Hanieh PN, Carè A, Bellenghi M, et al. pH-responsive oleic acid based nanocarriers: Melanoma treatment strategies. Int J Pharm. 2022;613:121391.10.1016/j.ijpharm.2021.121391Search in Google Scholar PubMed

[55] Wu J, Ma N, Johnston LJ, Ma X. Dietary nutrients mediate intestinal host defense peptide expression. Adv Nutr. 2020;11(1):92–102.10.1093/advances/nmz057Search in Google Scholar PubMed PubMed Central

[56] Cury-Boaventura MF, Pompéia C, Curi R. Comparative toxicity of oleic acid and linoleic acid on Jurkat cells. Clin Nutr. 2004;23(4):721–32.10.1016/j.clnu.2003.12.004Search in Google Scholar PubMed

Received: 2023-09-26
Revised: 2023-11-28
Accepted: 2023-12-04
Published Online: 2023-12-23

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

  1. Characteristics, source, and health risk assessment of aerosol polyaromatic hydrocarbons in the rural and urban regions of western Saudi Arabia
  2. Regular Articles
  3. A network-based correlation research between element electronegativity and node importance
  4. Pomegranate attenuates kidney injury in cyclosporine-induced nephrotoxicity in rats by suppressing oxidative stress
  5. Ab initio study of fundamental properties of XInO3 (X = K, Rb, Cs) perovskites
  6. Responses of feldspathic sandstone and sand-reconstituted soil C and N to freeze–thaw cycles
  7. Robust fractional control based on high gain observers design (RNFC) for a Spirulina maxima culture interfaced with an advanced oxidation process
  8. Study on arsenic speciation and redistribution mechanism in Lonicera japonica plants via synchrotron techniques
  9. Optimization of machining Nilo 36 superalloy parameters in turning operation
  10. Vacuum impregnation pre-treatment: A novel method for incorporating mono- and divalent cations into potato strips to reduce the acrylamide formation in French fries
  11. Characterization of effective constituents in Acanthopanax senticosus fruit for blood deficiency syndrome based on the chinmedomics strategy
  12. Comparative analysis of the metabolites in Pinellia ternata from two producing regions using ultra-high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry
  13. The assessment of environmental parameter along the desalination plants in the Kingdom of Saudi Arabia
  14. Effects of harpin and carbendazim on antioxidant accumulation in young jujube leaves
  15. The effects of in ovo injected with sodium borate on hatching performance and small intestine morphology in broiler chicks
  16. Optimization of cutting forces and surface roughness via ANOVA and grey relational analysis in machining of In718
  17. Essential oils of Origanum compactum Benth: Chemical characterization, in vitro, in silico, antioxidant, and antibacterial activities
  18. Translocation of tungsten(vi) oxide/gadolinium(iii) fluoride in tellurite glasses towards improvement of gamma-ray attenuation features in high-density glass shields
  19. Mechanical properties, elastic moduli, and gamma ray attenuation competencies of some TeO2–WO3–GdF3 glasses: Tailoring WO3–GdF3 substitution toward optimum behavioral state range
  20. Comparison between the CIDR or sponge with hormone injection to induce estrus synchronization for twining and sex preselection in Naimi sheep
  21. Exergetic performance analyses of three different cogeneration plants
  22. Psoralea corylifolia (babchi) seeds enhance proliferation of normal human cultured melanocytes: GC–MS profiling and biological investigation
  23. A novel electrochemical micro-titration method for quantitative evaluation of the DPPH free radical scavenging capacity of caffeic acid
  24. Comparative study between supported bimetallic catalysts for nitrate remediation in water
  25. Persicaline, an alkaloid from Salvadora persica, inhibits proliferation and induces apoptosis and cell-cycle arrest in MCF-7 cells
  26. Determination of nicotine content in locally produced smokeless tobacco (Shammah) samples from Jazan region of Saudi Arabia using a convenient HPLC-MS/MS method
  27. Changes in oxidative stress markers in pediatric burn injury over a 1-week period
  28. Integrated geophysical techniques applied for petroleum basins structural characterization in the central part of the Western Desert, Egypt
  29. The impact of chemical modifications on gamma-ray attenuation properties of some WO3-reinforced tellurite glasses
  30. Microwave and Cs+-assisted chemo selective reaction protocol for synthesizing 2-styryl quinoline biorelevant molecules
  31. Structural, physical, and radiation absorption properties of a significant nuclear power plant component: A comparison between REX-734 and 316L SS austenitic stainless steels
  32. Effect of Moringa oleifera on serum YKL-40 level: In vivo rat periodontitis model
  33. Investigating the impact of CO2 emissions on the COVID-19 pandemic by generalized linear mixed model approach with inverse Gaussian and gamma distributions
  34. Influence of WO3 content on gamma rays attenuation characteristics of phosphate glasses at low energy range
  35. Study on CO2 absorption performance of ternary DES formed based on DEA as promoting factor
  36. Performance analyses of detonation engine cogeneration cycles
  37. Sterols from Centaurea pumilio L. with cell proliferative activity: In vitro and in silico studies
  38. Untargeted metabolomics revealing changes in aroma substances in flue-cured tobacco
  39. Effect of pumpkin enriched with calcium lactate on iron status in an animal model of postmenopausal osteoporosis
  40. Energy consumption, mechanical and metallographic properties of cryogenically treated tool steels
  41. Optimization of ultra-high pressure-assisted extraction of total phenols from Eucommia ulmoides leaves by response surface methodology
  42. Harpin enhances antioxidant nutrient accumulation and decreases enzymatic browning in stored soybean sprouts
  43. Physicochemical and biological properties of carvacrol
  44. Radix puerariae in the treatment of diabetic nephropathy: A network pharmacology analysis and experimental validation
  45. Anti-Alzheimer, antioxidants, glucose-6-phosphate dehydrogenase effects of Taverniera glabra mediated ZnO and Fe2O3 nanoparticles in alloxan-induced diabetic rats
  46. Experimental study on photocatalytic CO2 reduction performance of ZnS/CdS-TiO2 nanotube array thin films
  47. Epoxy-reinforced heavy metal oxides for gamma ray shielding purposes
  48. Black mulberry (Morus nigra L.) fruits: As a medicinal plant rich in human health-promoting compounds
  49. Promising antioxidant and antimicrobial effects of essential oils extracted from fruits of Juniperus thurifera: In vitro and in silico investigations
  50. Chloramine-T-induced oxidation of Rizatriptan Benzoate: An integral chemical and spectroscopic study of products, mechanisms and kinetics
  51. Study on antioxidant and antimicrobial potential of chemically profiled essential oils extracted from Juniperus phoenicea (L.) by use of in vitro and in silico approaches
  52. Screening and characterization of fungal taxol-producing endophytic fungi for evaluation of antimicrobial and anticancer activities
  53. Mineral composition, principal polyphenolic components, and evaluation of the anti-inflammatory, analgesic, and antioxidant properties of Cytisus villosus Pourr leaf extracts
  54. In vitro antiproliferative efficacy of Annona muricata seed and fruit extracts on several cancer cell lines
  55. An experimental study for chemical characterization of artificial anterior cruciate ligament with coated chitosan as biomaterial
  56. Prevalence of residual risks of the transfusion-transmitted infections in Riyadh hospitals: A two-year retrospective study
  57. Computational and experimental investigation of antibacterial and antifungal properties of Nicotiana tabacum extracts
  58. Reinforcement of cementitious mortars with hemp fibers and shives
  59. X-ray shielding properties of bismuth-borate glass doped with rare earth ions
  60. Green supported silver nanoparticles over modified reduced graphene oxide: Investigation of its antioxidant and anti-ovarian cancer effects
  61. Orthogonal synthesis of a versatile building block for dual functionalization of targeting vectors
  62. Thymbra spicata leaf extract driven biogenic synthesis of Au/Fe3O4 nanocomposite and its bio-application in the treatment of different types of leukemia
  63. The role of Ag2O incorporation in nuclear radiation shielding behaviors of the Li2O–Pb3O4–SiO2 glass system: A multi-step characterization study
  64. A stimuli-responsive in situ spray hydrogel co-loaded with naringenin and gentamicin for chronic wounds
  65. Assessment of the impact of γ-irradiation on the piperine content and microbial quality of black pepper
  66. Antioxidant, sensory, and functional properties of low-alcoholic IPA beer with Pinus sylvestris L. shoots addition fermented using unconventional yeast
  67. Screening and optimization of extracellular pectinase produced by Bacillus thuringiensis SH7
  68. Determination of polyphenols in Chinese jujube using ultra-performance liquid chromatography–mass spectrometry
  69. Synergistic effects of harpin and NaCl in determining soybean sprout quality under non-sterile conditions
  70. Field evaluation of different eco-friendly alternative control methods against Panonychus citri [Acari: Tetranychidae] spider mite and its predators in citrus orchards
  71. Exploring the antimicrobial potential of biologically synthesized zero valent iron nanoparticles
  72. NaCl regulates goldfish growth and survival at three food supply levels under hypoxia
  73. An exploration of the physical, optical, mechanical, and radiation shielding properties of PbO–MgO–ZnO–B2O3 glasses
  74. A novel statistical modeling of air pollution and the COVID-19 pandemic mortality data by Poisson, geometric, and negative binomial regression models with fixed and random effects
  75. Treatment activity of the injectable hydrogels loaded with dexamethasone In(iii) complex on glioma by inhibiting the VEGF signaling pathway
  76. An alternative approach for the excess lifetime cancer risk and prediction of radiological parameters
  77. Panax ginseng leaf aqueous extract mediated green synthesis of AgNPs under ultrasound condition and investigation of its anti-lung adenocarcinoma effects
  78. Study of hydrolysis and production of instant ginger (Zingiber officinale) tea
  79. Novel green synthesis of zinc oxide nanoparticles using Salvia rosmarinus extract for treatment of human lung cancer
  80. Evaluation of second trimester plasma lipoxin A4, VEGFR-1, IL-6, and TNF-α levels in pregnant women with gestational diabetes mellitus
  81. Antidiabetic, antioxidant and cytotoxicity activities of ortho- and para-substituted Schiff bases derived from metformin hydrochloride: Validation by molecular docking and in silico ADME studies
  82. Antioxidant, antidiabetic, antiglaucoma, and anticholinergic effects of Tayfi grape (Vitis vinifera): A phytochemical screening by LC-MS/MS analysis
  83. Identification of genetic polymorphisms in the stearoyl CoA desaturase gene and its association with milk quality traits in Najdi sheep
  84. Cold-acclimation effect on cadmium absorption and biosynthesis of polyphenolics, and free proline and photosynthetic pigments in Spirogyra aequinoctialis
  85. Analysis of secondary metabolites in Xinjiang Morus nigra leaves using different extraction methods with UPLC-Q/TOF-MS/MS technology
  86. Nanoarchitectonics and performance evaluation of a Fe3O4-stabilized Pickering emulsion-type differential pressure plugging agent
  87. Investigating pyrolysis characteristics of Shengdong coal through Py-GC/MS
  88. Extraction, phytochemical characterization, and antifungal activity of Salvia rosmarinus extract
  89. Introducing a novel and natural antibiotic for the treatment of oral pathogens: Abelmoschus esculentus green-formulated silver nanoparticles
  90. Optimization of gallic acid-enriched ultrasonic-assisted extraction from mango peels
  91. Effect of gamma rays irradiation in the structure, optical, and electrical properties of samarium doped bismuth titanate ceramics
  92. Combinatory in silico investigation for potential inhibitors from Curcuma sahuynhensis Škorničk. & N.S. Lý volatile phytoconstituents against influenza A hemagglutinin, SARS-CoV-2 main protease, and Omicron-variant spike protein
  93. Physical, mechanical, and gamma ray shielding properties of the Bi2O3–BaO–B2O3–ZnO–As2O3–MgO–Na2O glass system
  94. Twofold interpenetrated 3D Cd(ii) complex: Crystal structure and luminescent property
  95. Study on the microstructure and soil quality variation of composite soil with soft rock and sand
  96. Ancient spring waters still emerging and accessible in the Roman Forum area: Chemical–physical and microbiological characterization
  97. Extraction and characterization of type I collagen from scales of Mexican Biajaiba fish
  98. Finding small molecular compounds to decrease trimethylamine oxide levels in atherosclerosis by virtual screening
  99. Prefatory in silico studies and in vitro insecticidal effect of Nigella sativa (L.) essential oil and its active compound (carvacrol) against the Callosobruchus maculatus adults (Fab), a major pest of chickpea
  100. Polymerized methyl imidazole silver bromide (CH3C6H5AgBr)6: Synthesis, crystal structures, and catalytic activity
  101. Using calcined waste fish bones as a green solid catalyst for biodiesel production from date seed oil
  102. Influence of the addition of WO3 on TeO2–Na2O glass systems in view of the feature of mechanical, optical, and photon attenuation
  103. Naringin ameliorates 5-fluorouracil elicited neurotoxicity by curtailing oxidative stress and iNOS/NF-ĸB/caspase-3 pathway
  104. GC-MS profile of extracts of an endophytic fungus Alternaria and evaluation of its anticancer and antibacterial potentialities
  105. Green synthesis, chemical characterization, and antioxidant and anti-colorectal cancer effects of vanadium nanoparticles
  106. Determination of caffeine content in coffee drinks prepared in some coffee shops in the local market in Jeddah City, Saudi Arabia
  107. A new 3D supramolecular Cu(ii) framework: Crystal structure and photocatalytic characteristics
  108. Bordeaux mixture accelerates ripening, delays senescence, and promotes metabolite accumulation in jujube fruit
  109. Important application value of injectable hydrogels loaded with omeprazole Schiff base complex in the treatment of pancreatitis
  110. Color tunable benzothiadiazole-based small molecules for lightening applications
  111. Investigation of structural, dielectric, impedance, and mechanical properties of hydroxyapatite-modified barium titanate composites for biomedical applications
  112. Metal gel particles loaded with epidermal cell growth factor promote skin wound repair mechanism by regulating miRNA
  113. In vitro exploration of Hypsizygus ulmarius (Bull.) mushroom fruiting bodies: Potential antidiabetic and anti-inflammatory agent
  114. Alteration in the molecular structure of the adenine base exposed to gamma irradiation: An ESR study
  115. Comprehensive study of optical, thermal, and gamma-ray shielding properties of Bi2O3–ZnO–PbO–B2O3 glasses
  116. Lewis acids as co-catalysts in Pd-based catalyzed systems of the octene-1 hydroethoxycarbonylation reaction
  117. Synthesis, Hirshfeld surface analysis, thermal, and selective α-glucosidase inhibitory studies of Schiff base transition metal complexes
  118. Protective properties of AgNPs green-synthesized by Abelmoschus esculentus on retinal damage on the virtue of its anti-inflammatory and antioxidant effects in diabetic rat
  119. Effects of green decorated AgNPs on lignin-modified magnetic nanoparticles mediated by Cydonia on cecal ligation and puncture-induced sepsis
  120. Treatment of gastric cancer by green mediated silver nanoparticles using Pistacia atlantica bark aqueous extract
  121. Preparation of newly developed porcelain ceramics containing WO3 nanoparticles for radiation shielding applications
  122. Utilization of computational methods for the identification of new natural inhibitors of human neutrophil elastase in inflammation therapy
  123. Some anticancer agents as effective glutathione S-transferase (GST) inhibitors
  124. Clay-based bricks’ rich illite mineral for gamma-ray shielding applications: An experimental evaluation of the effect of pressure rates on gamma-ray attenuation parameters
  125. Stability kinetics of orevactaene pigments produced by Epicoccum nigrum in solid-state fermentation
  126. Treatment of denture stomatitis using iron nanoparticles green-synthesized by Silybum marianum extract
  127. Characterization and antioxidant potential of white mustard (Brassica hirta) leaf extract and stabilization of sunflower oil
  128. Characteristics of Langmuir monomolecular monolayers formed by the novel oil blends
  129. Strategies for optimizing the single GdSrFeO4 phase synthesis
  130. Oleic acid and linoleic acid nanosomes boost immunity and provoke cell death via the upregulation of beta-defensin-4 at genetic and epigenetic levels
  131. Unraveling the therapeutic potential of Bombax ceiba roots: A comprehensive study of chemical composition, heavy metal content, antibacterial activity, and in silico analysis
  132. Green synthesis of AgNPs using plant extract and investigation of its anti-human colorectal cancer application
  133. The adsorption of naproxen on adsorbents obtained from pepper stalk extract by green synthesis
  134. Treatment of gastric cancer by silver nanoparticles encapsulated by chitosan polymers mediated by Pistacia atlantica extract under ultrasound condition
  135. In vitro protective and anti-inflammatory effects of Capparis spinosa and its flavonoids profile
  136. Wear and corrosion behavior of TiC and WC coatings deposited on high-speed steels by electro-spark deposition
  137. Therapeutic effects of green-formulated gold nanoparticles by Origanum majorana on spinal cord injury in rats
  138. Melanin antibacterial activity of two new strains, SN1 and SN2, of Exophiala phaeomuriformis against five human pathogens
  139. Evaluation of the analgesic and anesthetic properties of silver nanoparticles supported over biodegradable acacia gum-modified magnetic nanoparticles
  140. Review Articles
  141. Role and mechanism of fruit waste polyphenols in diabetes management
  142. A comprehensive review of non-alkaloidal metabolites from the subfamily Amaryllidoideae (Amaryllidaceae)
  143. Discovery of the chemical constituents, structural characteristics, and pharmacological functions of Chinese caterpillar fungus
  144. Eco-friendly green approach of nickel oxide nanoparticles for biomedical applications
  145. Advances in the pharmaceutical research of curcumin for oral administration
  146. Rapid Communication
  147. Determination of the contents of bioactive compounds in St. John’s wort (Hypericum perforatum): Comparison of commercial and wild samples
  148. Retraction
  149. Retraction of “Two mixed-ligand coordination polymers based on 2,5-thiophenedicarboxylic acid and flexible N-donor ligands: The protective effect on periodontitis via reducing the release of IL-1β and TNF-α”
  150. Topical Issue on Phytochemicals, biological and toxicological analysis of aromatic medicinal plants
  151. Anti-plasmodial potential of selected medicinal plants and a compound Atropine isolated from Eucalyptus obliqua
  152. Anthocyanin extract from black rice attenuates chronic inflammation in DSS-induced colitis mouse model by modulating the gut microbiota
  153. Evaluation of antibiofilm and cytotoxicity effect of Rumex vesicarius methanol extract
  154. Chemical compositions of Litsea umbellata and inhibition activities
  155. Green synthesis, characterization of silver nanoparticles using Rhynchosia capitata leaf extract and their biological activities
  156. GC-MS analysis and antibacterial activities of some plants belonging to the genus Euphorbia on selected bacterial isolates
  157. The abrogative effect of propolis on acrylamide-induced toxicity in male albino rats: Histological study
  158. A phytoconstituent 6-aminoflavone ameliorates lipopolysaccharide-induced oxidative stress mediated synapse and memory dysfunction via p-Akt/NF-kB pathway in albino mice
  159. Anti-diabetic potentials of Sorbaria tomentosa Lindl. Rehder: Phytochemistry (GC-MS analysis), α-amylase, α-glucosidase inhibitory, in vivo hypoglycemic, and biochemical analysis
  160. Assessment of cytotoxic and apoptotic activities of the Cassia angustifolia aqueous extract against SW480 colon cancer
  161. Biochemical analysis, antioxidant, and antibacterial efficacy of the bee propolis extract (Hymenoptera: Apis mellifera) against Staphylococcus aureus-induced infection in BALB/c mice: In vitro and in vivo study
  162. Assessment of essential elements and heavy metals in Saudi Arabian rice samples underwent various processing methods
  163. Two new compounds from leaves of Capparis dongvanensis (Sy, B. H. Quang & D. V. Hai) and inhibition activities
  164. Hydroxyquinoline sulfanilamide ameliorates STZ-induced hyperglycemia-mediated amyleoid beta burden and memory impairment in adult mice
  165. An automated reading of semi-quantitative hemagglutination results in microplates: Micro-assay for plant lectins
  166. Inductively coupled plasma mass spectrometry assessment of essential and toxic trace elements in traditional spices consumed by the population of the Middle Eastern region in their recipes
  167. Phytochemical analysis and anticancer activity of the Pithecellobium dulce seed extract in colorectal cancer cells
  168. Impact of climatic disturbances on the chemical compositions and metabolites of Salvia officinalis
  169. Physicochemical characterization, antioxidant and antifungal activities of essential oils of Urginea maritima and Allium sativum
  170. Phytochemical analysis and antifungal efficiency of Origanum majorana extracts against some phytopathogenic fungi causing tomato damping-off diseases
  171. Special Issue on 4th IC3PE
  172. Graphene quantum dots: A comprehensive overview
  173. Studies on the intercalation of calcium–aluminium layered double hydroxide-MCPA and its controlled release mechanism as a potential green herbicide
  174. Synergetic effect of adsorption and photocatalysis by zinc ferrite-anchored graphitic carbon nitride nanosheet for the removal of ciprofloxacin under visible light irradiation
  175. Exploring anticancer activity of the Indonesian guava leaf (Psidium guajava L.) fraction on various human cancer cell lines in an in vitro cell-based approach
  176. The comparison of gold extraction methods from the rock using thiourea and thiosulfate
  177. Special Issue on Marine environmental sciences and significance of the multidisciplinary approaches
  178. Sorption of alkylphenols and estrogens on microplastics in marine conditions
  179. Cytotoxic ketosteroids from the Red Sea soft coral Dendronephthya sp.
  180. Antibacterial and biofilm prevention metabolites from Acanthophora spicifera
  181. Characteristics, source, and health risk assessment of aerosol polyaromatic hydrocarbons in the rural and urban regions of western Saudi Arabia
  182. Special Issue on Advanced Nanomaterials for Energy, Environmental and Biological Applications - Part II
  183. Green synthesis, characterization, and evaluation of antibacterial activities of cobalt nanoparticles produced by marine fungal species Periconia prolifica
  184. Combustion-mediated sol–gel preparation of cobalt-doped ZnO nanohybrids for the degradation of acid red and antibacterial performance
  185. Perinatal supplementation with selenium nanoparticles modified with ascorbic acid improves hepatotoxicity in rat gestational diabetes
  186. Evaluation and chemical characterization of bioactive secondary metabolites from endophytic fungi associated with the ethnomedicinal plant Bergenia ciliata
  187. Enhancing photovoltaic efficiency with SQI-Br and SQI-I sensitizers: A comparative analysis
  188. Nanostructured p-PbS/p-CuO sulfide/oxide bilayer heterojunction as a promising photoelectrode for hydrogen gas generation
https://doi.org/10.1515/chem-2023-0176
Keywords for this article
lymphatic delivery; beta-defensin-4; HDAC6; cytotoxicity
Creative Commons
BY 4.0

Articles in the same Issue

  1. Characteristics, source, and health risk assessment of aerosol polyaromatic hydrocarbons in the rural and urban regions of western Saudi Arabia
  2. Regular Articles
  3. A network-based correlation research between element electronegativity and node importance
  4. Pomegranate attenuates kidney injury in cyclosporine-induced nephrotoxicity in rats by suppressing oxidative stress
  5. Ab initio study of fundamental properties of XInO3 (X = K, Rb, Cs) perovskites
  6. Responses of feldspathic sandstone and sand-reconstituted soil C and N to freeze–thaw cycles
  7. Robust fractional control based on high gain observers design (RNFC) for a Spirulina maxima culture interfaced with an advanced oxidation process
  8. Study on arsenic speciation and redistribution mechanism in Lonicera japonica plants via synchrotron techniques
  9. Optimization of machining Nilo 36 superalloy parameters in turning operation
  10. Vacuum impregnation pre-treatment: A novel method for incorporating mono- and divalent cations into potato strips to reduce the acrylamide formation in French fries
  11. Characterization of effective constituents in Acanthopanax senticosus fruit for blood deficiency syndrome based on the chinmedomics strategy
  12. Comparative analysis of the metabolites in Pinellia ternata from two producing regions using ultra-high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry
  13. The assessment of environmental parameter along the desalination plants in the Kingdom of Saudi Arabia
  14. Effects of harpin and carbendazim on antioxidant accumulation in young jujube leaves
  15. The effects of in ovo injected with sodium borate on hatching performance and small intestine morphology in broiler chicks
  16. Optimization of cutting forces and surface roughness via ANOVA and grey relational analysis in machining of In718
  17. Essential oils of Origanum compactum Benth: Chemical characterization, in vitro, in silico, antioxidant, and antibacterial activities
  18. Translocation of tungsten(vi) oxide/gadolinium(iii) fluoride in tellurite glasses towards improvement of gamma-ray attenuation features in high-density glass shields
  19. Mechanical properties, elastic moduli, and gamma ray attenuation competencies of some TeO2–WO3–GdF3 glasses: Tailoring WO3–GdF3 substitution toward optimum behavioral state range
  20. Comparison between the CIDR or sponge with hormone injection to induce estrus synchronization for twining and sex preselection in Naimi sheep
  21. Exergetic performance analyses of three different cogeneration plants
  22. Psoralea corylifolia (babchi) seeds enhance proliferation of normal human cultured melanocytes: GC–MS profiling and biological investigation
  23. A novel electrochemical micro-titration method for quantitative evaluation of the DPPH free radical scavenging capacity of caffeic acid
  24. Comparative study between supported bimetallic catalysts for nitrate remediation in water
  25. Persicaline, an alkaloid from Salvadora persica, inhibits proliferation and induces apoptosis and cell-cycle arrest in MCF-7 cells
  26. Determination of nicotine content in locally produced smokeless tobacco (Shammah) samples from Jazan region of Saudi Arabia using a convenient HPLC-MS/MS method
  27. Changes in oxidative stress markers in pediatric burn injury over a 1-week period
  28. Integrated geophysical techniques applied for petroleum basins structural characterization in the central part of the Western Desert, Egypt
  29. The impact of chemical modifications on gamma-ray attenuation properties of some WO3-reinforced tellurite glasses
  30. Microwave and Cs+-assisted chemo selective reaction protocol for synthesizing 2-styryl quinoline biorelevant molecules
  31. Structural, physical, and radiation absorption properties of a significant nuclear power plant component: A comparison between REX-734 and 316L SS austenitic stainless steels
  32. Effect of Moringa oleifera on serum YKL-40 level: In vivo rat periodontitis model
  33. Investigating the impact of CO2 emissions on the COVID-19 pandemic by generalized linear mixed model approach with inverse Gaussian and gamma distributions
  34. Influence of WO3 content on gamma rays attenuation characteristics of phosphate glasses at low energy range
  35. Study on CO2 absorption performance of ternary DES formed based on DEA as promoting factor
  36. Performance analyses of detonation engine cogeneration cycles
  37. Sterols from Centaurea pumilio L. with cell proliferative activity: In vitro and in silico studies
  38. Untargeted metabolomics revealing changes in aroma substances in flue-cured tobacco
  39. Effect of pumpkin enriched with calcium lactate on iron status in an animal model of postmenopausal osteoporosis
  40. Energy consumption, mechanical and metallographic properties of cryogenically treated tool steels
  41. Optimization of ultra-high pressure-assisted extraction of total phenols from Eucommia ulmoides leaves by response surface methodology
  42. Harpin enhances antioxidant nutrient accumulation and decreases enzymatic browning in stored soybean sprouts
  43. Physicochemical and biological properties of carvacrol
  44. Radix puerariae in the treatment of diabetic nephropathy: A network pharmacology analysis and experimental validation
  45. Anti-Alzheimer, antioxidants, glucose-6-phosphate dehydrogenase effects of Taverniera glabra mediated ZnO and Fe2O3 nanoparticles in alloxan-induced diabetic rats
  46. Experimental study on photocatalytic CO2 reduction performance of ZnS/CdS-TiO2 nanotube array thin films
  47. Epoxy-reinforced heavy metal oxides for gamma ray shielding purposes
  48. Black mulberry (Morus nigra L.) fruits: As a medicinal plant rich in human health-promoting compounds
  49. Promising antioxidant and antimicrobial effects of essential oils extracted from fruits of Juniperus thurifera: In vitro and in silico investigations
  50. Chloramine-T-induced oxidation of Rizatriptan Benzoate: An integral chemical and spectroscopic study of products, mechanisms and kinetics
  51. Study on antioxidant and antimicrobial potential of chemically profiled essential oils extracted from Juniperus phoenicea (L.) by use of in vitro and in silico approaches
  52. Screening and characterization of fungal taxol-producing endophytic fungi for evaluation of antimicrobial and anticancer activities
  53. Mineral composition, principal polyphenolic components, and evaluation of the anti-inflammatory, analgesic, and antioxidant properties of Cytisus villosus Pourr leaf extracts
  54. In vitro antiproliferative efficacy of Annona muricata seed and fruit extracts on several cancer cell lines
  55. An experimental study for chemical characterization of artificial anterior cruciate ligament with coated chitosan as biomaterial
  56. Prevalence of residual risks of the transfusion-transmitted infections in Riyadh hospitals: A two-year retrospective study
  57. Computational and experimental investigation of antibacterial and antifungal properties of Nicotiana tabacum extracts
  58. Reinforcement of cementitious mortars with hemp fibers and shives
  59. X-ray shielding properties of bismuth-borate glass doped with rare earth ions
  60. Green supported silver nanoparticles over modified reduced graphene oxide: Investigation of its antioxidant and anti-ovarian cancer effects
  61. Orthogonal synthesis of a versatile building block for dual functionalization of targeting vectors
  62. Thymbra spicata leaf extract driven biogenic synthesis of Au/Fe3O4 nanocomposite and its bio-application in the treatment of different types of leukemia
  63. The role of Ag2O incorporation in nuclear radiation shielding behaviors of the Li2O–Pb3O4–SiO2 glass system: A multi-step characterization study
  64. A stimuli-responsive in situ spray hydrogel co-loaded with naringenin and gentamicin for chronic wounds
  65. Assessment of the impact of γ-irradiation on the piperine content and microbial quality of black pepper
  66. Antioxidant, sensory, and functional properties of low-alcoholic IPA beer with Pinus sylvestris L. shoots addition fermented using unconventional yeast
  67. Screening and optimization of extracellular pectinase produced by Bacillus thuringiensis SH7
  68. Determination of polyphenols in Chinese jujube using ultra-performance liquid chromatography–mass spectrometry
  69. Synergistic effects of harpin and NaCl in determining soybean sprout quality under non-sterile conditions
  70. Field evaluation of different eco-friendly alternative control methods against Panonychus citri [Acari: Tetranychidae] spider mite and its predators in citrus orchards
  71. Exploring the antimicrobial potential of biologically synthesized zero valent iron nanoparticles
  72. NaCl regulates goldfish growth and survival at three food supply levels under hypoxia
  73. An exploration of the physical, optical, mechanical, and radiation shielding properties of PbO–MgO–ZnO–B2O3 glasses
  74. A novel statistical modeling of air pollution and the COVID-19 pandemic mortality data by Poisson, geometric, and negative binomial regression models with fixed and random effects
  75. Treatment activity of the injectable hydrogels loaded with dexamethasone In(iii) complex on glioma by inhibiting the VEGF signaling pathway
  76. An alternative approach for the excess lifetime cancer risk and prediction of radiological parameters
  77. Panax ginseng leaf aqueous extract mediated green synthesis of AgNPs under ultrasound condition and investigation of its anti-lung adenocarcinoma effects
  78. Study of hydrolysis and production of instant ginger (Zingiber officinale) tea
  79. Novel green synthesis of zinc oxide nanoparticles using Salvia rosmarinus extract for treatment of human lung cancer
  80. Evaluation of second trimester plasma lipoxin A4, VEGFR-1, IL-6, and TNF-α levels in pregnant women with gestational diabetes mellitus
  81. Antidiabetic, antioxidant and cytotoxicity activities of ortho- and para-substituted Schiff bases derived from metformin hydrochloride: Validation by molecular docking and in silico ADME studies
  82. Antioxidant, antidiabetic, antiglaucoma, and anticholinergic effects of Tayfi grape (Vitis vinifera): A phytochemical screening by LC-MS/MS analysis
  83. Identification of genetic polymorphisms in the stearoyl CoA desaturase gene and its association with milk quality traits in Najdi sheep
  84. Cold-acclimation effect on cadmium absorption and biosynthesis of polyphenolics, and free proline and photosynthetic pigments in Spirogyra aequinoctialis
  85. Analysis of secondary metabolites in Xinjiang Morus nigra leaves using different extraction methods with UPLC-Q/TOF-MS/MS technology
  86. Nanoarchitectonics and performance evaluation of a Fe3O4-stabilized Pickering emulsion-type differential pressure plugging agent
  87. Investigating pyrolysis characteristics of Shengdong coal through Py-GC/MS
  88. Extraction, phytochemical characterization, and antifungal activity of Salvia rosmarinus extract
  89. Introducing a novel and natural antibiotic for the treatment of oral pathogens: Abelmoschus esculentus green-formulated silver nanoparticles
  90. Optimization of gallic acid-enriched ultrasonic-assisted extraction from mango peels
  91. Effect of gamma rays irradiation in the structure, optical, and electrical properties of samarium doped bismuth titanate ceramics
  92. Combinatory in silico investigation for potential inhibitors from Curcuma sahuynhensis Škorničk. & N.S. Lý volatile phytoconstituents against influenza A hemagglutinin, SARS-CoV-2 main protease, and Omicron-variant spike protein
  93. Physical, mechanical, and gamma ray shielding properties of the Bi2O3–BaO–B2O3–ZnO–As2O3–MgO–Na2O glass system
  94. Twofold interpenetrated 3D Cd(ii) complex: Crystal structure and luminescent property
  95. Study on the microstructure and soil quality variation of composite soil with soft rock and sand
  96. Ancient spring waters still emerging and accessible in the Roman Forum area: Chemical–physical and microbiological characterization
  97. Extraction and characterization of type I collagen from scales of Mexican Biajaiba fish
  98. Finding small molecular compounds to decrease trimethylamine oxide levels in atherosclerosis by virtual screening
  99. Prefatory in silico studies and in vitro insecticidal effect of Nigella sativa (L.) essential oil and its active compound (carvacrol) against the Callosobruchus maculatus adults (Fab), a major pest of chickpea
  100. Polymerized methyl imidazole silver bromide (CH3C6H5AgBr)6: Synthesis, crystal structures, and catalytic activity
  101. Using calcined waste fish bones as a green solid catalyst for biodiesel production from date seed oil
  102. Influence of the addition of WO3 on TeO2–Na2O glass systems in view of the feature of mechanical, optical, and photon attenuation
  103. Naringin ameliorates 5-fluorouracil elicited neurotoxicity by curtailing oxidative stress and iNOS/NF-ĸB/caspase-3 pathway
  104. GC-MS profile of extracts of an endophytic fungus Alternaria and evaluation of its anticancer and antibacterial potentialities
  105. Green synthesis, chemical characterization, and antioxidant and anti-colorectal cancer effects of vanadium nanoparticles
  106. Determination of caffeine content in coffee drinks prepared in some coffee shops in the local market in Jeddah City, Saudi Arabia
  107. A new 3D supramolecular Cu(ii) framework: Crystal structure and photocatalytic characteristics
  108. Bordeaux mixture accelerates ripening, delays senescence, and promotes metabolite accumulation in jujube fruit
  109. Important application value of injectable hydrogels loaded with omeprazole Schiff base complex in the treatment of pancreatitis
  110. Color tunable benzothiadiazole-based small molecules for lightening applications
  111. Investigation of structural, dielectric, impedance, and mechanical properties of hydroxyapatite-modified barium titanate composites for biomedical applications
  112. Metal gel particles loaded with epidermal cell growth factor promote skin wound repair mechanism by regulating miRNA
  113. In vitro exploration of Hypsizygus ulmarius (Bull.) mushroom fruiting bodies: Potential antidiabetic and anti-inflammatory agent
  114. Alteration in the molecular structure of the adenine base exposed to gamma irradiation: An ESR study
  115. Comprehensive study of optical, thermal, and gamma-ray shielding properties of Bi2O3–ZnO–PbO–B2O3 glasses
  116. Lewis acids as co-catalysts in Pd-based catalyzed systems of the octene-1 hydroethoxycarbonylation reaction
  117. Synthesis, Hirshfeld surface analysis, thermal, and selective α-glucosidase inhibitory studies of Schiff base transition metal complexes
  118. Protective properties of AgNPs green-synthesized by Abelmoschus esculentus on retinal damage on the virtue of its anti-inflammatory and antioxidant effects in diabetic rat
  119. Effects of green decorated AgNPs on lignin-modified magnetic nanoparticles mediated by Cydonia on cecal ligation and puncture-induced sepsis
  120. Treatment of gastric cancer by green mediated silver nanoparticles using Pistacia atlantica bark aqueous extract
  121. Preparation of newly developed porcelain ceramics containing WO3 nanoparticles for radiation shielding applications
  122. Utilization of computational methods for the identification of new natural inhibitors of human neutrophil elastase in inflammation therapy
  123. Some anticancer agents as effective glutathione S-transferase (GST) inhibitors
  124. Clay-based bricks’ rich illite mineral for gamma-ray shielding applications: An experimental evaluation of the effect of pressure rates on gamma-ray attenuation parameters
  125. Stability kinetics of orevactaene pigments produced by Epicoccum nigrum in solid-state fermentation
  126. Treatment of denture stomatitis using iron nanoparticles green-synthesized by Silybum marianum extract
  127. Characterization and antioxidant potential of white mustard (Brassica hirta) leaf extract and stabilization of sunflower oil
  128. Characteristics of Langmuir monomolecular monolayers formed by the novel oil blends
  129. Strategies for optimizing the single GdSrFeO4 phase synthesis
  130. Oleic acid and linoleic acid nanosomes boost immunity and provoke cell death via the upregulation of beta-defensin-4 at genetic and epigenetic levels
  131. Unraveling the therapeutic potential of Bombax ceiba roots: A comprehensive study of chemical composition, heavy metal content, antibacterial activity, and in silico analysis
  132. Green synthesis of AgNPs using plant extract and investigation of its anti-human colorectal cancer application
  133. The adsorption of naproxen on adsorbents obtained from pepper stalk extract by green synthesis
  134. Treatment of gastric cancer by silver nanoparticles encapsulated by chitosan polymers mediated by Pistacia atlantica extract under ultrasound condition
  135. In vitro protective and anti-inflammatory effects of Capparis spinosa and its flavonoids profile
  136. Wear and corrosion behavior of TiC and WC coatings deposited on high-speed steels by electro-spark deposition
  137. Therapeutic effects of green-formulated gold nanoparticles by Origanum majorana on spinal cord injury in rats
  138. Melanin antibacterial activity of two new strains, SN1 and SN2, of Exophiala phaeomuriformis against five human pathogens
  139. Evaluation of the analgesic and anesthetic properties of silver nanoparticles supported over biodegradable acacia gum-modified magnetic nanoparticles
  140. Review Articles
  141. Role and mechanism of fruit waste polyphenols in diabetes management
  142. A comprehensive review of non-alkaloidal metabolites from the subfamily Amaryllidoideae (Amaryllidaceae)
  143. Discovery of the chemical constituents, structural characteristics, and pharmacological functions of Chinese caterpillar fungus
  144. Eco-friendly green approach of nickel oxide nanoparticles for biomedical applications
  145. Advances in the pharmaceutical research of curcumin for oral administration
  146. Rapid Communication
  147. Determination of the contents of bioactive compounds in St. John’s wort (Hypericum perforatum): Comparison of commercial and wild samples
  148. Retraction
  149. Retraction of “Two mixed-ligand coordination polymers based on 2,5-thiophenedicarboxylic acid and flexible N-donor ligands: The protective effect on periodontitis via reducing the release of IL-1β and TNF-α”
  150. Topical Issue on Phytochemicals, biological and toxicological analysis of aromatic medicinal plants
  151. Anti-plasmodial potential of selected medicinal plants and a compound Atropine isolated from Eucalyptus obliqua
  152. Anthocyanin extract from black rice attenuates chronic inflammation in DSS-induced colitis mouse model by modulating the gut microbiota
  153. Evaluation of antibiofilm and cytotoxicity effect of Rumex vesicarius methanol extract
  154. Chemical compositions of Litsea umbellata and inhibition activities
  155. Green synthesis, characterization of silver nanoparticles using Rhynchosia capitata leaf extract and their biological activities
  156. GC-MS analysis and antibacterial activities of some plants belonging to the genus Euphorbia on selected bacterial isolates
  157. The abrogative effect of propolis on acrylamide-induced toxicity in male albino rats: Histological study
  158. A phytoconstituent 6-aminoflavone ameliorates lipopolysaccharide-induced oxidative stress mediated synapse and memory dysfunction via p-Akt/NF-kB pathway in albino mice
  159. Anti-diabetic potentials of Sorbaria tomentosa Lindl. Rehder: Phytochemistry (GC-MS analysis), α-amylase, α-glucosidase inhibitory, in vivo hypoglycemic, and biochemical analysis
  160. Assessment of cytotoxic and apoptotic activities of the Cassia angustifolia aqueous extract against SW480 colon cancer
  161. Biochemical analysis, antioxidant, and antibacterial efficacy of the bee propolis extract (Hymenoptera: Apis mellifera) against Staphylococcus aureus-induced infection in BALB/c mice: In vitro and in vivo study
  162. Assessment of essential elements and heavy metals in Saudi Arabian rice samples underwent various processing methods
  163. Two new compounds from leaves of Capparis dongvanensis (Sy, B. H. Quang & D. V. Hai) and inhibition activities
  164. Hydroxyquinoline sulfanilamide ameliorates STZ-induced hyperglycemia-mediated amyleoid beta burden and memory impairment in adult mice
  165. An automated reading of semi-quantitative hemagglutination results in microplates: Micro-assay for plant lectins
  166. Inductively coupled plasma mass spectrometry assessment of essential and toxic trace elements in traditional spices consumed by the population of the Middle Eastern region in their recipes
  167. Phytochemical analysis and anticancer activity of the Pithecellobium dulce seed extract in colorectal cancer cells
  168. Impact of climatic disturbances on the chemical compositions and metabolites of Salvia officinalis
  169. Physicochemical characterization, antioxidant and antifungal activities of essential oils of Urginea maritima and Allium sativum
  170. Phytochemical analysis and antifungal efficiency of Origanum majorana extracts against some phytopathogenic fungi causing tomato damping-off diseases
  171. Special Issue on 4th IC3PE
  172. Graphene quantum dots: A comprehensive overview
  173. Studies on the intercalation of calcium–aluminium layered double hydroxide-MCPA and its controlled release mechanism as a potential green herbicide
  174. Synergetic effect of adsorption and photocatalysis by zinc ferrite-anchored graphitic carbon nitride nanosheet for the removal of ciprofloxacin under visible light irradiation
  175. Exploring anticancer activity of the Indonesian guava leaf (Psidium guajava L.) fraction on various human cancer cell lines in an in vitro cell-based approach
  176. The comparison of gold extraction methods from the rock using thiourea and thiosulfate
  177. Special Issue on Marine environmental sciences and significance of the multidisciplinary approaches
  178. Sorption of alkylphenols and estrogens on microplastics in marine conditions
  179. Cytotoxic ketosteroids from the Red Sea soft coral Dendronephthya sp.
  180. Antibacterial and biofilm prevention metabolites from Acanthophora spicifera
  181. Characteristics, source, and health risk assessment of aerosol polyaromatic hydrocarbons in the rural and urban regions of western Saudi Arabia
  182. Special Issue on Advanced Nanomaterials for Energy, Environmental and Biological Applications - Part II
  183. Green synthesis, characterization, and evaluation of antibacterial activities of cobalt nanoparticles produced by marine fungal species Periconia prolifica
  184. Combustion-mediated sol–gel preparation of cobalt-doped ZnO nanohybrids for the degradation of acid red and antibacterial performance
  185. Perinatal supplementation with selenium nanoparticles modified with ascorbic acid improves hepatotoxicity in rat gestational diabetes
  186. Evaluation and chemical characterization of bioactive secondary metabolites from endophytic fungi associated with the ethnomedicinal plant Bergenia ciliata
  187. Enhancing photovoltaic efficiency with SQI-Br and SQI-I sensitizers: A comparative analysis
  188. Nanostructured p-PbS/p-CuO sulfide/oxide bilayer heterojunction as a promising photoelectrode for hydrogen gas generation
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 29.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/chem-2023-0176/html
Scroll to top button