Volume 22, Issue 2

Atopic dermatitis is acknowledged as a vital inflammatory disorder associated with the integumentary system of the body and is characterized by the formation of thick reddish-grey scars and erythema formation on skin, prevalent amidst the populace. Numerous synthetic drugs are available for treatment like antihistamines, immunosuppressants, glucocorticoids etc., but contrarily, essential oil therapy is exclusively lime lighted to favour the purpose. The utilization of available engineered drugs, possess the marked adverse effects owing to prolonged duration of therapy and therefore, essential oils are explored well and proved to exhibit the anti-eczematic, anti-inflammatory and antipruritic properties. Ethereal distillates own the assorted and selective therapeutic properties attributable to presence of bioactive compounds liable to treat this torturous and integumentary disorder, likely lavender oil, patchouli oil, frankincense oil etc., have been found to exert their pharmacological actions by impeding the liberation and action of inflammatory mediators and immunological hyperactivities that are engaged in exacerbating this idiopathic illness. The current attempt provided the update with the aim to bring forth the naturally originated treatment that is pertinent to provide the invulnerable therapy by circumventing the noxious symptoms i.e. erythema formation and inflamed lesions.

Introduction Diabetes mellitus is a complex disease in terms of its causes and pathophysiological processes, it produces a significant impact on health and leads to complications that are difficult to manage. Content This review summarizes and analyzes recent advances in the understanding of the mechanisms of diabetes mellitus and how apitherapy affects them. Also present the available clinical evidence on its application. Summary Apitherapy (complementary-integral use of beehive products) is a potentially useful therapeutic system with a significant level of evidence. This review shows and analyzes the preclinical and clinical evidence on the use of apitherapy in diabetes mellitus. Outlook Apitherapy shows significant effects on epigenetics, chronic inflammation, oxidative stress, metabolic control, dysbiosis, premature cell death and tissue remodeling. Clinical evidence shows an impact on these mechanisms. Apitherapy is a very useful complementary medicine in the treatment of diabetes mellitus.

Skin carcinoma, which includes basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma, is influenced by various factors such as genetic predisposition, chemical exposures, immune system imbalances, and ultraviolet (UV) radiation. This review delves into the mechanisms behind the development of these cancers, exploring the therapeutic potential of microbial, plant derived compounds and nanoparticles in advancing skin cancer treatments. Special attention is given to the cytotoxic effects of anti-neoplastic agents from microbial sources on different cancer cell lines, particularly melanoma. Additionally, the review highlights the role of phytochemicals – such as quercetin, resveratrol, and curcumin alongside vitamins, terpenoids, and sulforaphane, in management of skin cancers through mechanisms like apoptosis induction and cell cycle regulation. Recent advancements in nanotechnology-based drug delivery systems, including NP and microemulsion formulations, are also discussed for their enhanced ability to specifically target cancer cells. The diverse roles of NPs in skin cancer therapy, especially in terms of targeted drug delivery and immune modulation, are reviewed. These innovative NPs formulations have showed improved skin penetration and tumor-specific delivery, reduced systemic toxicity and enhanced therapeutic effectiveness.

Objectives Pain affects about one in every five persons and is considered a major global health burden. Hyphaene thebaica (Arecaceae), is a medicinal plant used in Cameroon, fruit pulp are macerated and orally administered in traditional medicine to treat various ailments, including hypertension, pain, and inflammation. This study aimed to evaluate the pain-killing effect of fruit pulp extracts of H. thebaica in mice. Methods Aqueous (AEHT) and methanol (MEHT) extracts were prepared from fruit pulp of H. thebaica , followed by a qualitative phytochemical analysis. The extracts were given orally at doses of 100, 200, and 400 mg/kg in acute pain models such as acetic acid, formalin, hotplate, and capsaicin. Control groups included distilled water (negative), and diclofenac, morphine, ruthenium red, diazepam (positive). Naloxone pretreatment was used to assess opioid pathway involvement. Locomotor and sedative effects were evaluated using rota-rod and open-field tests. Acute toxicity was assessed at 2,000 mg/kg. Results Phytochemical tests revealed saponins, flavonoids, tannins, and phenols. Both extracts greatly decreased the writhing induced by acetic acid. MEHT inhibited both phases of formalin-induced pain (p<0.01). Both extracts significantly inhibited hotplate-induced nociception (p<0.001), partially reversed by naloxone, except for MEHT. In the capsaicin test, extracts produced a remarkable reduction of paw licking time (p<0.01). No motor coordination alteration or acute toxicity effects were observed. Conclusions The findings demonstrated the analgesic activity of AEHT and MEHT, mediated by the stimulation of opioids and blockage of vanilloid receptors pathways.

Objectives To evaluate the antidepressant-like effects of Phenylthiazolyl-1,3,5-triazine derivatives through behavioral tests, molecular docking, and histopathological analysis in a rat brain model of depression. Methods Phenylthiazolyl-1,3,5-triazine derivatives were synthesized and administered at a dose of 30 mg/kg in albino rats. Behavioral effects were assessed using the Forced Swim Test and Tail Suspension Test. Molecular docking with MD simulations via CDocker was employed to analyze ligand-receptor interactions. Histological analysis of brain tissues was conducted to assess structural and vascular changes. Results Among the derivatives, PS1 and PS5 showed significant antidepressant-like activity compared to standard imipramine. Molecular docking revealed that hydrogen bonding, pi-pi interactions, and intermolecular neighbor effects stabilized the ligand-receptor complexes. Histopathological analysis of PS1-treated rats demonstrated preserved vascular integrity, reduced edema, and the absence of hydrophobic alterations. Conclusions Phenylthiazolyl-1,3,5-triazines, particularly PS1, exhibit promising potential as antidepressant agents. Their behavioral efficacy and protective histological effects suggest therapeutic relevance. Further studies integrating biomarkers and gene expression analyses are needed to optimize these derivatives for clinical application.

Objectives To lessen the negative effects of the medication, we assessed the neuroprotective impact of amifostine nanoparticles against the neurotoxicity generated by cisplatin. Methods 60 adult male albino Wistar rats were arranged into six groups. Group 1; received saline intraperitonealy (IP) and served as negative control. Group 2; received IP injection of silica nano-emulsion, Group 3 received cispatin for three consecutive days at the end of the study, Group 4 received amifostine intrapretonealy (IP) before cisplatin injection, Group 5 received silica nano-emulsion alone for one month, group 6 received silica nano-emulsion in combination with cisplatin for three consecutive days at the end of the study. Monocyte chemoattractant protein-1 (MCP-1) and glial fibrillary acidic protein (GFAP) were estimated by ELISA, butrylcholinesterase (BChE) by spectrophotometric method while caspase-3 as a marker of apoptosis by PCR. Results The mean levels of brain GFAP, MCP-1, and caspase-3 in the cisplatin group were considerably higher than those in the control group. However, there was a drop in the average level of brain BChE activity. Additionally, the injection of (SiNPs@AMF + cisplatin) increased BChE activities while reducing GFAP, MCP-1, and caspase-3 levels, thereby reversing the negative effects of cisplatin on the brain tissue. On the other hand, the group treated with SiNPs@AMF + cisplatin showed improvement in overall brain structure and minimal pyknotic nuclei and apoptotic neurons were found. Conclusions These outcomes demonstrated amifostine’s ability to lessen the histological changes brought on by cisplatin. To sum up, SiNPs@AMF may be a suitable and secure supplemental treatment agent to lessen cisplatin’s toxicity in the brain and enhance the treatment’s effects throughout chemotherapy.

Objectives This study was conducted in response to the increasing interest in understanding the effects of both modern and traditional complementary medicine on incisional wound healing. Herein, it was aimed to investigate the wound healing effects of medicinal leech therapy and leech saliva in an experimentally created incisional skin wound model. Methods Fifteen rats underwent full-thickness incisions on their dorsal regions and were randomly assigned to five equal groups, as the Leech Saliva (LS) group, where wounds were treated topically with leech saliva once daily; Leech Therapy-1 (LT-1) group, where leech therapy was administered once at the beginning of the experiment; Leech Therapy-2 (LT-2) group, where leech therapy was applied twice, on days 0 and 3; Positive Control (PC) group, where wounds were treated daily with Phyto cream containing Triticum vulgare ; and Negative Control (NC) group, where no treatment was given. Results Wound healing was assessed daily, and the experiment continued until complete healing was observed. At the conclusion, the wound size, appearance, and histological features were analyzed to compare healing progress across the groups. Conclusions Medicinal leech therapy was observed to have a positive wound healing effect in the rat model.

Objectives The liver is vital for metabolism, detoxification, storage, and secretion. Cholestasis, in which bile flow is hindered, can cause serious harm to the liver. This study examines the potential of ellagic acid to prevent cholestasis in male rats that has been caused by alpha-naphthyl isothiocyanate (ANIT). Method Male rats were divided into four groups for an 8-day study. The control group received 5 % dimethyl sulfoxide (DMSO) orally for eight days and maize oil (1 mL/kg, orally) 48 h before sacrifice. The ANIT Group received 5 % DMSO orally for 8 days, the ANIT (100 mg/kg, orally) administered on the 6th day, 48 h before sacrifice. The low-Dose Ellagic Acid + ANIT Group was given ellagic acid (5 mg/kg, orally) for eight days, with ANIT (100 mg/kg, orally) on the 6th day, 48 h prior to sacrifice. The high-Dose Ellagic Acid + ANIT Group received ellagic acid (10 mg/kg, orally) for eight days, the ANIT (100 mg/kg, orally) on the 6th day, 48 h before sacrifice. Different biochemical and histopathological analyses were conducted to assess the protective effects of ellagic acid on ANIT-induced liver injury. Results ANIT significantly elevated serum of liver enzymes. It caused severe bile duct inflammation and reduced bile salt export pump (BSEP) and Na+-taurocholate cotransporting polypeptide (NTCP) expression, indicating liver injury. Ellagic acid treatment mitigated these changes, improving biochemical parameters and reducing liver damage. ANIT-induced cholestasis results in bile acid accumulation due to decreased BSEP and NTCP expression linked to impaired farnesoid X receptor (FXR) signaling. Ellagic acid restored BSEP and NTCP levels via FXR activation, reducing bile acids and inflammatory markers IL-1β and TNF-α. Ellagic acid also enhanced SIRT1 activity, further improving FXR function and bile acid homeostasis. Conclusions Ellagic acid exhibits protective effects against cholestasis by enhancing the FXR signaling and ntcp and  bsep expression with mitigating liver damage and inflammation.

Background Wound healing is a complex biological process involving numerous cellular and molecular events. Ixora coccinea and Rhododendron arboreum flowers have been traditionally used for their medicinal properties, prompting an investigation into their combined effects on wound healing using both in vitro and in silico approaches. Methods Ixora and Rhododendron flowers were processed in a 1:1 ratio using an ethanolic solvent. Various concentrations of the extracts were applied to wounded mouse fibroblast cell monolayers (3T3-L1). Antioxidant potential was evaluated by DPPH and H 2 O 2 assays, while anti-inflammatory effects were assessed using BSA and EA assays. Wound closure kinetics were monitored with image analysis software. Molecular docking studies examined interactions between active compounds and essential wound-healing proteins. Results The formulations inhibited ROS production at a low concentration (IC 50 ∼1.38 μg/mL), indicating suitability for managing oxidative stress. The extracts also showed protein denaturation inhibition with an IC 50 value of 14.5 μg/mL for BSA and 8.3 μg/mL for EA. In vitro , the combined extracts significantly enhanced wound closure compared to control groups, with higher concentrations (40 μg/mL) accelerating closure rates (99.66 %). Molecular docking revealed interactions between key compounds (Quercetin, Rutin) and essential wound healing proteins (MMP9, TGFβ1, IGFR), suggesting mechanisms underlying their therapeutic effects. Conclusion In vitro and in silico findings suggest that Ixora and Rhododendron flower extracts promote wound closure and their interaction with key proteins in wound healing pathways, highlighting their potential therapeutic value.

Objectives Phytotherapy employs phytoconstituents/phytomedicines derived from plants for treating and preventing illnesses. Withania somnifera is known in the Indian Ayurveda Pharmacopoeia for its medicinal applications and pharmacological properties. In this study, we examined the biological activity spectrum of Withania somnifera methanolic extract of stem (WSME), which is valued as a “Rasayana” due to its extensive range of medicinal uses. Methods WSME was subjected to TPC and TFC quantification and bioactive components were characterized using LC-MS. Its antioxidant potential was gauged by DPPH and H 2 O 2 radical scavenging assays, while antibacterial efficacy was assessed against S. aureus and E. coli using disc diffusion assay. In vitro anticancer activity was evaluated against human breast cancer MDA-MB-231 cells while toxicity was evaluated against normal Vero cells using MTT assay. Results WSME, rich in Withaferin A, showed TPC of 4.73 ± 0.15 mg GAE/g and TFC of 94.94 ± 6.15 mg QE/g dry weight of extract. It exhibited significant antioxidant activity (43.28 and 66.8 % inhibition at 1,000 μg/mL using DPPH and H 2 O 2 assays, respectively) and mild antibacterial effects against S. aureus (300–500 mg/mL). WSME induced cell death in MDA-MB-231 cells and significantly inhibited their growth (IC 50 : 66 μg/mL, P value<0.05) without affecting normal Vero cells in the studied range of 25–400 μg/mL (IC 50 : 6.09 mg/mL, P value>0.05). Conclusions The present study lends support to further testing of WSME against other cancer cell lines and animal models of cancer. These preclinical studies would provide further validation to its prospective use as an adjunct in human breast cancer therapy.

Objectives Colorectal cancer and gastric cancer are one of the most prevalent types of cancer and are leading causes of cancer-related mortality worldwide. The chemotherapy is insufficient due to the poor targeting and affinity of drugs, low therapeutic effectiveness, and significant side effects. Consequently, developing effective therapeutic formulations is crucial for treating colorectal and gastric cancers. Plantago major ( P. major ) is a medicinal plant that has been investigated for medical research for cancer therapy owing to its rich phytochemical composition. Methods This study aims to evaluate the antiproliferative activity of P. major leaf extract on NIH/3T3 fibroblast cells, AGS gastric, and Caco-2 colorectal cancer cell lines for 24 h using XTT cell viability assay. The apoptotic activity of P. major was examined by detecting caspase 3/7 level in cells. The ROS levels in cells were measured using the DCFH-DA dye. Additionally, it assesses the interaction and binding affinities of the active compounds of P. major with the overexpressed EPCAM through molecular docking. Results The results demonstrate a dose-dependent anticancer effect of P. major on AGS and Caco-2 cell lines by reducing cell proliferation, increasing intracellular ROS accumulation and activating the caspase 3/7 apoptosis pathway. P. major exhibited no significant cytotoxic effects on non-cancerous NIH/3T3 fibroblast cells. Molecular docking analysis confirmed the high binding affinity of active compounds in P. major , such as apigenin, aucubin, baicalein, caffeic acid, and luteolin, towards the EpCAM protein overexpressed in gastric and colorectal cancer. Conclusions In conclusion, the P. major can be a promising effective therapeutic strategy for gastrointestinal cancers.

Objectives Thus, the study was designed to assess the ability of ICA to ameliorate MTX-induced renal toxicity in rats and determine the pathogenetic pathways of oxidative stress, inflammation, and apoptosis. Methods Mtx renal toxicity was developed following an intraperitoneal administration of 20 mg/kg MTX. ICA was orally given at 100 mg/kg/day for two consecutive weeks. Experimental indicators included: biochemical renal function – BUN, SCr; and oxidative stress – SOD, GSH-Px, MDA. Other histological studies included immunohistochemical staining for Nrf2 and HO-1, QPCR of pro-inflammatory cytokines and biomarker of kidney injury, and TUNEL assay to assess the protective effects affiliated with ICA. Results In an animal model treated with MTX, renal damage was reflected by increased oxidative stress, inflammatory-borne cytokines, and apoptotic indices. ICA treatment ameliorated these effects to a great extent by reversing changes in antioxidant enzyme activities, suppressing lipid peroxidation and regulating the Nrf2/HO-1 pathway. This was evidenced by the decrease in pro-inflammatory and kidney injury genes in the ICA-treated groups but by significant histological ameliorations of kidney structure. TUNEL assay proved the decreased apoptotic index in kidney tissue. Conclusions These findings exhibited the therapeutic efficacy of ICA for attenuating renal injury from MTX and established that it mainly exerts its cytoprotective effects through the Nrf2/HO-1 pathway.

Objectives This investigation aimed to evaluate the efficacy, key active ingredients, and mechanisms of Zuoqing San (ZQS), a traditional Chinese medicine formula, in managing sigmoid ulcerative colitis (SUC). Methods A cohort of 126 participants was recruited and treated with ZQS at a daily dosage of 100 mL for 12 weeks. The primary endpoint was the percentage of subjects achieving favorable treatment outcomes. Liquid chromatography-mass spectrometry was employed to identify the principal ingredients of ZQS. Network pharmacology was utilized to predict the central targets of its active ingredients. Protein-protein interaction networks, Gene Ontology enrichment analyses, and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted for identified core targets. Finally, molecular dynamics simulations of key active ingredients and core targets were performed. Results Following 12 weeks of therapy, with a withdrawal rate of 7.93 %, favorable treatment outcomes were observed in 31.03 % of subjects at 4 weeks, 66.37 % at 8 weeks (Odds Ratio: 1.54, 95 % Confidence Interval: 0.41–1.83), and 68.10 % at 12 weeks (Odds Ratio: 1.86, 95 % CI: 0.32–1.27). ZQS comprises 31 principal chemical constituents. Key targets within the protein-protein interaction network included TNF, AKT1, IL6, IL1β, PTGS2, TP53, JUN, MMP9, CASP3, HIF1A, and BCL1. Pathway analysis indicated ZQS primarily impacts the TNF, NF-kB, and IL-17 signaling pathways. Molecular dynamics simulation results showed oxymatrine, cynarin had higher affinity with TNF and IL1β, respectively. Conclusions This research elucidates the active components of ZQS and its potential multicomponent–multitarget–multipathway pharmacological mechanisms, demonstrating promising therapeutic potential for SUC management.

Objectives A clinical trial was conducted to address the trend of high cesarean section rates resulting from maternal fear of childbirth. This trial aimed to investigate the effectiveness of self-hypnosis in mitigating fear and pain during childbirth. Methods This study was a parallel, not blinded, randomized controlled trial conducted in 2019 in Mashhad, Iran. Ninety-three nulliparous women were selected by convenience sampling and randomized by random allocation software (4 blocking groups) to either self-hypnosis or control groups. During the clinical trial, both groups received usual care for pregnancy and childbirth. However, the self-hypnosis group also participated in two hypnosis sessions and was given two audio files to practice self-hypnosis at home until delivery. The follow-up period ranged from the 37th week of pregnancy to the postpartum period. Fear of childbirth was assessed at 39 weeks and at cervical dilatation of 8–10 cm, while labor pain was measured at the same stage of labor as the primary outcomes between two groups. Data were analyzed using SPSS 16, applying the Independent sample t-test, Mann–Whitney U test, and Chi-square test. A p-value of less than 0.05 was considered statistically significant. Results Thirty women in the self-hypnosis group, aged 24.96±5.42, and 33 women in the control group, aged 23.63±4.68, completed the study. The average scores of fear of childbirth during pregnancy at 39 weeks (self-hypnosis: 46.46±14.53, control: 73.18±17.91), during the active phase of labor at cervical dilatation of 8–10 cm (self-hypnosis: 40.80±17.37, control: 75.12±19.40), and labor pain at cervical dilatation of 8–10 cm (self-hypnosis: 83.03±16.43, control: 95.36±10.36) were significantly lower in the self-hypnosis group compared to the control group (p<0.001 for all). Conclusions Our findings suggest that self-hypnosis could be a more effective intervention than usual care alone for reducing fear and pain during natural childbirth in nulliparous women.

Objectives Cancer remains a significant global health challenge, with prostate, breast, and ovarian cancers ranking among the leading causes of morbidity and mortality. Natural products, particularly those derived from medicinal plants, have gained attention for their potential in alternative cancer therapies. The main objective of the study was an isolation and characterization of Jerantinine A, a bioactive alkaloid from Tabernaemontana coronaria , and its interactions with key protein targets involved in cancer progression. Methods Jerantinine A was isolated through column chromatography and characterized using spectroscopic techniques, including UV-visible spectroscopy, FTIR, and NMR. Molecular docking studies were performed to assess its binding affinities with six critical protein targets: PTEN and androgen receptor for prostate cancer, CXCR4 and HER2 for ovarian cancer, and CDK1 and NEK2 for breast cancer. Results Molecular docking analyses revealed that Jerantinine A exhibits strong binding affinities with all six protein targets, suggesting its potential to inhibit cancer cell proliferation by interfering with key signaling pathways. Conclusions These findings underscore the therapeutic potential of T. coronaria , particularly through Jerantinine A, as a promising candidate for cancer treatment. By targeting pivotal proteins associated with prostate, breast, and ovarian cancers, Jerantinine A offers a foundation for further research and development as a novel anti-cancer agent.

Objectives Primary dysmenorrhea is a leading cause of job and school absenteeism among young females. Despite its high prevalence, contemporary medicine offers limited treatment options. Herbaceous members of the Apiaceae family, such as Pimpinella anisum L ., Anethum sowa L ., Cuminum cyminum L ., and Foeniculum vulgare Mill., are commonly used in traditional medicine to treat primary dysmenorrhea. Currently, there is no comprehensive assessment of their therapeutic efficacy and safety. This study protocol assesses how effective and safe these herbs are in managing primary dysmenorrhea. Methods The following databases will be searched without language restriction until May 2024: Cochrane CENTRAL, PubMed, AYUSH Research Portal, and DHARA, along with grey literature, and other sources. The risk of bias tool (RoB2) will evaluate the validity and applicability of study results. The review will address publication bias by taking appropriate measures. The review will adhere to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines for transparent and systematic reporting. Results The review will incorporate randomized controlled trials (RCTs) comparing Apiaceae herbs to no treatment, placebo, medication, or standard care. It is anticipated that these herbs will significantly reduce menstrual pain severity, measured via the visual analogue scale (VAS), and exhibit fewer adverse events than nonsteroidal anti-inflammatory drugs (NSAIDs). Conclusions This review aims to compile evidence on the efficacy and safety of Apiaceae herbs for primary dysmenorrhea, highlighting the need for further studies. PROSPERO Registration number CRD42024538888.