Home Physical Sciences 6-Methoxyflavone improves anxiety, depression, and memory by increasing monoamines in mice brain: HPLC analysis and in silico studies
Article Open Access

6-Methoxyflavone improves anxiety, depression, and memory by increasing monoamines in mice brain: HPLC analysis and in silico studies

  • Mehreen Arif , Naeem Ur Rehman , Irfan Anjum , Khalid Rauf EMAIL logo , Amal Alotaibi and Ghala Alhmidani
Published/Copyright: October 25, 2024
Download Article (PDF)
Open Chemistry
From the journal Open Chemistry Volume 22 Issue 1

Abstract

6-Methoxyflavone (6-MOF) is a flavonoid that has been reported to be a GABA-A receptor agonist and reverses cisplatin-induced hyperalgesia and allodynia. Considering the varied neuropharmacological profile of 6-MOF, this study was intended to determine the pharmacological effects of 6-MOF on locomotion, anxiety, novel object recognition (NOR), depression, spatial memory, socialization behavior, nest-building behavior, and depression in various groups of mice. Selected groups of mice were injected with 25, 50, and 75 mg/kg 6-MOF. Using HPLC-UV, the frontal cortex, striatum, and hippocampus of the sacrificed mice were analyzed for the levels of vitamin C, dopamine, serotonin, noradrenaline, adenosine, and its metabolites. Statistical analysis showed significant results in socialization behavior and elevated plus maze with 75 mg/kg. In Y-maze, NOR 6-MOF showed significant results at all three doses, while in tail suspension test (TST), 50 and 75 mg/kg showed significant results; however, no statistical significance was observed in nest-building behavior; 50 and 75 mg/kg 6-MOF showed significant results in the Morris water maze. 6-MOF raised vitamin C levels in the frontal cortex and hippocampus. Serotonin, dopamine, and nor-adrenaline levels were raised in the hippocampus and striatum. It has also imparted region-specific neuroprotection by improving adenosine and its metabolite levels. In silico studies performed using PyRx have shown that the minimum binding energy of 6-MOF with antioxidant enzyme is −7.1 k/cal/mol. The binding energy showed that 6-MOF was successfully docked with an anti-oxidant enzyme. In conclusion, in silico and behavioral studies showed that 6-MOF can be a potential candidate for the treatment of cognitive decline, anxiety, and depression.

Keywords: serotonin; dopamine; noradrenaline; 6-methoxyflavone; adenosine

1 Introduction

Flavonoids are secondary metabolites found in the organs and tissues of plants. These naturally occurring metabolites are the most common and exhibit several advantageous physiological effects, making them frequently enticing in several scientific domains [1]. Flavonoids are TrkB receptor agonists as well as acetylcholine esterase inhibitors [2]. Flavonoids have varied pharmacological properties like antioxidants [3,4], antidepressants, memory enhancers [5], antiviral [6], anti-inflammatory [4,7], anticancerous [6], anxiolytic [8], and neuroprotective because of which they have been used in the treatment of several ailments [9] and antiapoptotic activities [10,11]. They have an effective role in traumatic brain injury [12] and have significant effects on methamphetamine and glutamate-induced neurotoxicity [13,14]. By interrelating with serotonin, γ-aminobutyric acid, dopamine, and glycine, they regulate the functioning of neurons [15]. Even though flavonoids improve cognitive abilities in humans and animals, the mechanism by which flavonoids influence cognitive function has not yet been fully understood [16].

6-Methoxyflavone (6-MOF; Figure 2) is isolated from Anvillea garcini leaves [17], P. decora leaf [18], Pimelea simplex and F. Muell [19], and ray flower of Helianthus series Corona-Solis, and is a flavonoid [20]. In the aerial parts of Centaurea bruguierana, 6-MOF derivatives, cirsimaritin, cirsilineol, and hispidulin, have been identified [21]. It has reported activity against ethanol-induced cognitive decline and has been shown to improve brain neurochemistry, including dopamine, noradrenaline, and serotonin. 6-MOF has also imparted antioxidant effect by improving vitamin-C levels [22]. It has been reported to alleviate cisplatin-induced neuropathies [23]. 6-MOF has been reported to act as a GABA modulator at the GABAA receptor, which is a flumazenil-insensitive allosteric modulator of human recombinant α1β2γ2L and α2β2γ2L that are expressed in the oocytes of Xenopus laevis [24,25]. It has been reported that 6-MOF has immunomodulatory effects because of the suppression of NFAT-mediated T-cell activation [26]. It has antioxidant and anti-inflammatory activities [27]. Studies have also reported the anti-apoptotic mechanism of 6-MOF in HeLa cells [28]. 6-MOF imparts neuroprotection in brain areas by improving the levels of adenosine, inosine, and hypoxanthine [22]. 6-MOF extracted from the leaves of Stevia rebaudiana has antidiabetic activity [29]. It also has antifungal activity against oral Candida albicans infection [30]. Although 6-MOF has poor water solubility [31,32], still upon parenteral administration, stable serum levels above 1 μg persist with higher levels found in key brain areas [33]. 6-MOF (6-methoxy-2-phenylchromen-4-one) is a colorless white powdered solid and has a molecular weight of 252.26, non-water soluble, soluble in chloroform, dichloromethane, ethyl acetate, dimethylsulfoxide (DMSO), acetone [34] and crosses the blood–brain barrier, prevents neuroinflammation, blocks nitric oxide centrally [27], antiallodynic [25] and has an LD50 >4 g/kg [35].

Figure 1 Three-dimensional structure of the antioxidant SOD spike receptor-binding domain with PDB ID: 1gv3.
Figure 1

Three-dimensional structure of the antioxidant SOD spike receptor-binding domain with PDB ID: 1gv3.

This study was intended to determine the pharmacological effects of 6-MOF on locomotion, anxiety via elevated plus maze (EPM), novel object recognition (NOR), depression via tail suspension test (TST), spatial memory, socialization behavior, nest-building behavior, and depression.

2 Methods

2.1 In silico screening of 6-MOF

2.1.1 Selection of target proteins

The 3-D structure of the antioxidant enzyme superoxide dismutase (SOD) (Figure 1) was downloaded as PDB files from the protein data bank (http://www.rcsb.org/pdb/home/home.do). In the 3-D structure of PDB, all water molecules that were not involved in ligand interaction were removed and all the missing atoms and valences were corrected (Figure 2).

Figure 2 Ligand 6-MOF from PubChem.
Figure 2

Ligand 6-MOF from PubChem.

2.1.2 Selection of ligands

The chemical structure of 6-MOF was downloaded from PubChem compound database in SDF format (Figure 2) (https://pubchem.ncbi.nlm.nih.gov/). It was then converted to a PDBQT file using the PyRx tool to generate atomic coordinates.

2.1.3 Target and ligand optimization

Drug Discovery Studio version 3.0 software was used to optimize the PDB coordinates of the target proteins and 6-MOF for docking studies (missing residues were added). These coordinates exhibited stable conformation and the least amount of energy.

2.1.4 Analysis of target active binding sites

The target protein’s active binding sites were examined using the Biovia Drug Discovery Studio version 3.0. The active sites are the ligand’s coordinates in the initial target protein grids (https://discover.3ds.com/discovery-studio-visualizer).

2.1.5 Molecular docking studies

The ligand- and protein-binding affinities, as well as the binding of pharmacological targets, protein receptors, or enzymes for interactions, are studied through virtual screening. We have studied molecular docking using PyRx, a free version of the program. The coordinates X = 119.202, Y = 1.0971, and Z = 8.1660 were all established in the grids that were placed in the active site pocket center, and the lowest binding energies were the most appropriate for interactions. All default docking techniques were employed [36].

2.2 Behavioral evaluation studies

2.2.1 Animals

Male BALB/c mice (22–28 g) were procured from the Veterinary Research Institute Peshawar, Pakistan (n = 6/group). The temperature in the animals’ housing was kept at 22 ± 2.0°C; they had freely available food and water and maintained a circadian rhythm. Experimental protocols were approved under the ethical number PHM.Eth/CS-M03-015-1106, and the ethical committee of the COMSATS University Islamabad, Abbottabad campus, provided approval for all experiments that follow the UK’s Animals Scientific Procedure Act (1986).

2.3 Experimental protocol

Animals were distributed into four groups. A vehicle containing DMSO, Tween 80, and normal saline (5:1:94) was used to dissolve 6-MOF [23,37]. Group 1 was administered normal saline/vehicle (10 mL/kg p.o.), and Groups 2, 3, and 4 were administered 25, 50, and 75 mg/kg of 6-MOF, respectively, orally [37]. Group 6 received fluoxetine 5 mg/kg [38] as a positive control for depression (TST), and Group 7 received diazepam 1 mg/kg [39] as a positive control for anxiety (EPM). Then, 1-h post-drug/vehicle administration, behavioral tests were performed, and after the completion of the behavioral section, animals were killed by cervical decapitation. The frontal cortex, hippocampus, and striatum were excised and stored at −80°C for neurotransmitter quantification.

2.4 Behavioral activity tests

2.4.1 Spontaneous alternation Y-maze

Three equal-length arms positioned at a 120° angle (21 cm long, 8.5 cm wide, 40 cm tall) were used. A total of 5 min was given for each animal to freely investigate each arm after being placed in the center. The camera was used to record how much time was spent on each arm. The algorithm for calculating alternations, entries in each arm, and alternation numbers was used to investigate spontaneous Y-maze activity [22].

% alternations = Total alternations Number of arm entries × 100 .

2.4.2 NOR

An open arena (60 cm × 50 cm × 40 cm) was used for a 3-day protocol. On day 1, the animals spent 10 min examining the test boxes (acclimatization phase). The animals were familiarized with two objects for 10 min on day 2 (training phase). On day 3, a familiar object was swapped with a new one, and each animal spent 10 min analyzing it. An overhead camera recorded the duration of each [22].

2.4.3 Socialization test

The procedure used a male juvenile mouse as the presenter animal, and the mice were accustomed for 30 min. The investigational animal was first introduced to a presenter and allowed for a 5-min interaction (sampling phase). The novel male adolescent mouse was introduced for a 5-min encounter after an hour in the recognition phase, and sniffing time was recorded [22].

2.4.4 Nest building behavior

Animals were individually given a piece of cotton nesting (5 cm × 5 cm) and then left for the night. Every single nest was evaluated according to the standards set forth by Kraeuter et al. [22].

2.4.5 Measurement of Morris water maze (MWM)

For this test, an opaque circular pool measuring 120 cm in circumference ×60 cm in height was employed. In addition to being separated into four quadrants, the pool’s walls were covered with geometric shapes that functioned as special cues. Mice were trained for 5 days in the first phase (training) to locate a platform position that was 1 cm below the water’s surface (13 cm wide and 34 cm high). During every training session, the platform was placed in the unchanged quadrant. In Phase 2 (Trial), there were five trials per day, with a 10-min break in between each. In each trial, one of the quadrants and a random starting point were selected, with the mice facing the wall. A secret platform had to be located and occupied by each animal within 90 s. When the animals could not locate the hidden platform, they were left there for 20 s (Phase 3). On the probe trial day, the platform and mice were permitted to delve freely for 90 s. Platform location crossings, time spent, and the number of entries in the target quadrant were recorded using a video camera [22].

2.4.6 TST

To assess the test compound’s anti-depressant properties, the tail suspension method was used. With the aid of adhesive tape, each animal was held for 6 min while being suspended from its tail to a wooden apparatus that was 59 cm above the ground. A camera was used to record mobility time. Following a minute of acclimation, mobility time was recorded [40,41].

2.4.7 EPM

Anxiety-like behavior was performed using EPM. Two open arms and two closed arms (16 × 5) made up the apparatus, and 12 cm high, black-painted walls encircled closed arms. The maze was raised around 25 cm from the ground. Using a video camera placed at a height of 100 cm, the behavior was captured for 5 min. The total number of entries in the closed and open arms for each mouse was calculated. When all four of the mouse’s limbs were in the arm, it was deemed legitimate [42,43].

2.4.8 Locomotor activity test (open field)

Boxes (45 cm × 45 cm) with internal line markings that divided the field into four quadrants were used to measure the locomotor activity (22.5 cm × 22.5 cm). A video camera was positioned 230 cm above each animal’s locomotor box to record the event as it transpired. Each animal was then placed inside. The equipment was thoroughly cleaned with 70% ethanol in between animal examinations, and the times the lines crossed at a rate of 30 per minute were recorded [22].

2.5 Neurotransmitter and vitamin C quantification using HPLC

2.5.1 Sample and standard preparation

Following the behavioral assessment, the mice were decapitated, frontal cortical, striatal, and hippocampal tissues were excised, precisely weighed, and maintained at −80°C. Homogenization of the tissues was carried out on chilled perchloric acid (0.2%) following cold centrifugation (4°C; 12,000 rpm), and the supernatant was separated. The standard stock solutions were made by dissolving 1 mg of each of the following substances in 10 mL of HPLC-grade water. The standard solution of all neurotransmitters was then diluted to provide various concentrations ranging from 100 to 500 ng/mL [22].

2.5.2 Chromatographic conditions

For the chromatographic analysis, a Waters Alliance 2690 separation module with a UV detector was utilized (USA). A 5 µm particle size (250 × 4.6 mm) C18 stainless steel column was utilized. HPLC grade water and 20 mM monobasic sodium phosphate (5:95, v/v) were employed with isocratic elution at 280 nm and a column temperature of 35°C, and the elution rate of 0.5 mL/min for vitamin C, dopamine, noradrenaline, and vitamin C methanol. HPLC grade water and 0.01 M monobasic sodium phosphate (5:95 v/v) were employed for the measurement of adenosine, inosine, hypoxanthine, acetonitrile, and isocratic elution at 260 nm, the column was at room temperature, and a flow rate was 1 mL/min [22].

2.6 Statistical analysis

Graph Pad Prism-8 was used, and the results are presented as ±SEM. ANOVA (one-way) and a post hoc Dunnett’s test were used. Data significance was as follows: *p > 0.05, **p > 0.01 and ***p > 0.001.

The target proteins were inserted using the PyRx program, and the imaging was done with Discovery Studio (Accelrys, San Diego, CA, USA), a potent simulation tool.

3 Results

3.1 Effect of 6-MOF on the spontaneous alternation of Y-maze

6-MOF showed considerable improvement in spontaneous alternations with the highest dose (**p < 0.01) (Figure 3a). However, no substantial disparity in the number of entries was observed (Figure 3b). A considerable improvement in the percentage of alternations was observed with the two highest tested doses of 6-MOF (***p < 0.01) (Figure 3c) relative to the saline group.

Figure 3 Effect of 6-MOF on Y-Maze: (a) number of alternations, (b) number of entries in each arm, and (c) percentage of alternations. **p < 0.01 and ***p < 0.01.
Figure 3

Effect of 6-MOF on Y-Maze: (a) number of alternations, (b) number of entries in each arm, and (c) percentage of alternations. **p < 0.01 and ***p < 0.01.

3.2 Effect of 6-MOF on NOR

Following the administration of 6-MOF, a notable increase in the amount of time spent investigating novel objects relative to a familiar one was noticed with 25 mg/kg (*p < 0.05), 50, and 75 mg/kg (***p < 0.001) relative to the saline group (Figure 4).

Figure 4 Effect of 6-MOF on NOR test. *p < 0.05 and ***p < 0.001.
Figure 4

Effect of 6-MOF on NOR test. *p < 0.05 and ***p < 0.001.

3.3 Effect of 6-MOF on socialization behavior

6-MOF showed significant improvement in the socialization behavior, as the treatment showed improved recognition of previously presented mice but results are not statistically significant. However, compared to a novel mouse, significantly enhanced socialization was observed with the highest dose of 6-MOF, i.e., 75 mg/kg (*p < 0.05) of 6-MOF compared to the saline group (Figure 5).

Figure 5 Effect of 6-MOF on socialization behavior; *p < 0.05.
Figure 5

Effect of 6-MOF on socialization behavior; *p < 0.05.

3.4 Effect of 6-MOF on nest-building behavior

Treatment with 6-MOF showed a marked positive emotional state and improved skilled-based learning as the height, width, and quality of the nest built by treated mice were significant relative to the saline group. However, the results are statistically not significant (Figure 6a–c).

Figure 6 Effect of 6-MOF on the nest building behavior: (a) height of the nest, (b) width of the nest, and (c) nest building score. *p < 0.05, **p < 0.01, ***p < 0.001, and (d–g) represents the nest builds.
Figure 6 Effect of 6-MOF on the nest building behavior: (a) height of the nest, (b) width of the nest, and (c) nest building score. *p < 0.05, **p < 0.01, ***p < 0.001, and (d–g) represents the nest builds.
Figure 6

Effect of 6-MOF on the nest building behavior: (a) height of the nest, (b) width of the nest, and (c) nest building score. *p < 0.05, **p < 0.01, ***p < 0.001, and (d–g) represents the nest builds.

3.5 Effect of 6-MOF on the MWM

The highest dose of 6-MOF, 75 mg/kg, significantly augmented the amount of time spent in the target quadrant (**p < 0.01) (Figure 7a). The two highest doses have shown considerable improvement in the overall number of entries in the target quadrant (**p < 0.01) (Figure 7b), as well as the number of platform location crossings (***p < 0.001) (Figure 7c) compared to the saline group.

Figure 7 Effect of 6-MOF on MWM. (a) Time spent in the target quadrant, (b) the number of entries in the target quadrant, and (c) the number of platform location crossings. *p < 0.05, **p < 0.01, and ***p < 0.001.
Figure 7 Effect of 6-MOF on MWM. (a) Time spent in the target quadrant, (b) the number of entries in the target quadrant, and (c) the number of platform location crossings. *p < 0.05, **p < 0.01, and ***p < 0.001.
Figure 7

Effect of 6-MOF on MWM. (a) Time spent in the target quadrant, (b) the number of entries in the target quadrant, and (c) the number of platform location crossings. *p < 0.05, **p < 0.01, and ***p < 0.001.

3.6 Effect of 6-MOF on the TST

A momentous intensification in mobility time was observed with the two highest doses of 50 mg/kg (**p < 0.01) and 75 mg/kg (***p < 0.001) as well as fluoxetine 5 mg/kg (***p < 0.001) relative to the saline group (Figure 8).

Figure 8 Effect of 6-MOF on the TST. **p < 0.01 and ***p < 0.001.
Figure 8

Effect of 6-MOF on the TST. **p < 0.01 and ***p < 0.001.

3.7 Effect of 6-MOF on the EPM

6-MOF showed a noteworthy anxiolytic effect as animals showed significant improvement in time spent in open arms with the highest tested dose (*p < 0.05); diazepam also showed a significant anxiolytic effect (***p < 0.001) relative to the saline group (Figure 9).

Figure 9 Effect of 6-MOF on the elevated plus-maze; *p < 0.05 and ***p < 0.001.
Figure 9

Effect of 6-MOF on the elevated plus-maze; *p < 0.05 and ***p < 0.001.

3.8 Effect of 6-MOF on the locomotor activity (open field test)

6-MOF showed significant improvement in locomotion as a momentous hyperlocomotion was observed at all three doses (**p < 0.01, ***p < 0.001) relative to the saline group (Figure 10).

Figure 10 Effect of 6-MOF on the locomotor activity. **p < 0.01 and ***p < 0.001.
Figure 10

Effect of 6-MOF on the locomotor activity. **p < 0.01 and ***p < 0.001.

3.9 Effect of 6-MOF on the frontal cortex tissue levels of dopamine, noradrenaline, serotonin, and vitamin C

A substantial increase in frontal cortical noradrenaline levels was observed with 75 mg/kg (***p < 0.001) 6-MOF. Frontal cortical vitamin C levels were also boosted at all three doses (*p < 0.05). However, no effect was observed on dopamine and serotonin relative to the saline group (Table 1).

Table 1

Levels of neurotransmitters and vitamin C expressed in the frontal cortex tissue

Treatments Dopamine (ng/mg of wet tissue) Noradrenaline (ng/mg of wet tissue) Vitamin C (ng/mg of wet tissue) Serotonin (ng/mg of wet tissue)
Saline (vehicle) 23.1 ± 1.6 74.2 ± 3.1 18.6 ± 2.7 32.3 ± 4.4
6-MOF (25 mg/kg) 14.4 ± 1.4 45.8 ± 2.3 27.7 ± 2.8* 9.2 ± 0.9
6-MOF (50 mg/kg) 19.3 ± 1.8 50.4 ± 2.3 28.6 ± 3.1* 17.4 ± 2.6
6-MOF (75 mg/kg 20.96 ± 1.6 96.0 ± 0.4*** 31.1 ± 2.2* 26.0 ± 3.9

*p < 0.05 and ***p < 0.001.

3.10 Effect of 6-methoxyflavone on the hippocampal tissue levels of dopamine, noradrenaline, and vitamin C

6-MOF has remarkably improved hippocampal dopamine and noradrenaline levels with the highest tested dose (***p < 0.001 and **p < 0.01). An increase in serotonin levels was observed at all three doses (*p < 0.05 and ***p < 0.001), respectively. However, all three doses have shown marked improvement in the hippocampal vitamin C levels (**p < 0.01 and ***p < 0.001) relative to the saline group (Table 2).

Table 2

Levels of neurotransmitters and vitamin C expressed in the hippocampal tissue

Treatments Dopamine (ng/mg of wet tissue) Noradrenaline (ng/mg of wet tissue) Vitamin C (ng/mg of wet tissue) Serotonin (ng/mg of wet tissue)
Saline (10 mL/kg) 3.3 ± 0.1 264.5 ± 8.0 33.4 ± 5.4 8.7 ± 1.1
6-MOF (25 mg/kg) 3.6 ± 0.2 211.5 ± 3.0 67.8 ± 6.6** 17.9 ± 1.1*
6-MOF (50 mg/kg) 3.8 ± 0.1 237.8 ± 10.8 86.4 ± 5.5*** 18.6 ± 1.1*
6-MOF (75 mg/kg) 14.6 ± 0.2*** 308.8 ± 10.2** 110.5 ± 5.0*** 35.2 ± 5.8***

**p < 0.01 and ***p < 0.001.

3.11 Effect of 6-MOF on the striatal tissue levels of dopamine, noradrenaline, serotonin, and vitamin C

Considerable improvement in the striatal dopamine levels was observed at 75 mg/kg (***p < 0.001). All three administered doses showed improvement in the noradrenaline levels (*p < 0.05 and ***p < 0.001). The highest dose of 6-MOF improved striatal vitamin C and serotonin levels (*p < 0.05 and ***p < 0.001), respectively, relative to the saline group (Table 3).

Table 3

Levels of neurotransmitters and vitamin C expressed in the striatal tissue

Treatments Dopamine (ng/mg of wet tissue) Noradrenaline (ng/mg of wet tissue) Vitamin C (ng/mg of wet tissue) Serotonin (ng/mg of wet tissue)
Saline (10 mL/kg) 3.4 ± 0.2 219.5 ± 4 65.2 ± 4.1 59.7 ± 2.3
6-MOF (25 mg/kg) 3.4 ± 0.2 225.2 ± 6.5* 23.3 ± 1.6 16.5 ± 2.6
6-MOF (50 mg/kg) 3.7 ± 0.1 238.4 ± 4.1*** 49.8 ± 6.5 21.0 ± 3.8
6-MOF (75 mg/kg) 63.8 ± 0.1*** 240.6 ± 8.6*** 74.8 ± 11.1* 88.1 ± 3.4***

*p < 0.05 and ***p < 0.001.

3.12 Effect of 6-MOF on the frontal cortex tissue levels of adenosine, inosine, and hypoxanthine

A notable frontal cortical neuroprotection was imparted at all three doses of 6-MOF, as a significant decrease in adenosine and hypoxanthine levels was observed T all three doses of 6-MOF (***p < 0.001). Inosine levels were also significantly decreased AT all three doses (*p < 0.05 and ***p < 0.001) as well as hypoxanthine levels were also decreased AT all three doses (***p < 0.001) relative to the saline group (Table 4).

Table 4

Levels of adenosine, inosine, and hypoxanthine expressed in the frontal cortex tissue

Treatments Adenosine (ng/mg of wet tissue) Inosine (ng/mg of wet tissue) Hypoxanthine (ng/mg of wet tissue)
Saline (10 mL/kg) 40.1 ± 2.9 3.3 ± 0.4 7.4 ± 0.7
6-MOF (25 mg/kg) 28.9 ± 1.6*** 2.1 ± 0.1* 4.1 ± 0.1***
6-MOF (50 mg/kg) 26.4 ± 0.5*** 1.9 ± 0.1* 2.6 ± 0.4***
6-MOF (75 mg/kg) 26.9 ± 1.0*** 1.3 ± 0.4*** 2.4 ± 0.4***

*p < 0.05 and ***p < 0.001.

3.13 Effect of 6-MOF on the hippocampal tissue levels of adenosine, inosine, and hypoxanthine

6-MOF imparted considerable neuroprotection in the hippocampus as all three doses have considerably decreased hippocampal adenosine, inosine, and hypoxanthine (***p < 0.001) relative to the saline group (Table 5).

Table 5

Levels of adenosine, inosine, and hypoxanthine expressed in the hippocampal tissue

Treatments Adenosine (ng/mg of wet tissue) Inosine (ng/mg of wet tissue) Hypoxanthine (ng/mg of wet tissue)
Saline (10 mL/kg) 17.0 ± 2.2 2.7 ± 0.4 1.4 ± 0.1
6-MOF (25 mg/kg) 5.1 ± 0.2*** 0.5 ± 0.1*** 0.3 ± 0.4***
6-MOF (50 mg/kg) 8.9 ± 0.4*** 0.4 ± 0.8*** 0.3 ± 0.7***
6-MOF (75 mg/kg) 7.2 ± 0.5*** 0.3 ± 0.0*** 0.1 ± 0.1***

***p < 0.001.

3.14 Effect of 6-MOF on the striatal tissue levels of adenosine, inosine, and hypoxanthine

Striatal neuroprotection was imparted at all three doses of 6-MOF, as adenosine inosine and hypoxanthine levels were significantly decreased at all three doses (***p < 0.001) relative to the saline group (Table 6).

Table 6

Levels of adenosine, inosine, and hypoxanthine expressed in the striatal tissue

Treatments Adenosine (ng/mg of wet tissue) Inosine (ng/mg of wet tissue) Hypoxanthine (ng/mg of wet tissue)
Saline (10 mL/kg) 20.1 ± 3.8 10.7 ± 2.2 11.0 ± 1.4
6-MOF (25 mg/kg) 9.0 ± 0.8*** 8.3 ± 0.5*** 6.8 ± 1.3***
6-MOF (50 mg/kg) 5.8 ± 0.3*** 6.5 ± 1.1*** 4.9 ± 0.6***
6-MOF (75 mg/kg) 1.7 ± 0.2*** 5.2 ± 0.4*** 3.4 ± 1.8***

***p < 0.001.

3.15 In silico binding affinity of 6-MOF with SOD

The minimum binding energy indicated that the SOD protein (target enzyme) was successfully docked with 6-MOF flavonoid (Table 7 and Figure 11).

Table 7

Binding affinity of 6-MOF with SOD

Docking pose Protein–ligand complex Binding affinity rmsd/uba rmsd/lbb
1 1gv3–protein-6-MOF −7.1 0 0
2 1gv3–protein-6-MOF −7.1 2.358 1.737
3 1gv3–protein-6-MOF −6.8 23.524 21.578
4 1gv3–protein-6-MOF −6.7 6.649 1.832
5 1gv3–protein-6-MOF −6.6 30.708 27.896
6 1gv3–protein-6-MOF −6.4 2.603 1.997
7 1gv3–protein-6-MOF −6.4 23.886 21.23
8 1gv3–protein-6-MOF −6.4 6.72 2.079
9 1gv3–protein-6-MOF −6.4 7.616 5.026

armsd/ub: root mean square deviation/upper bond; brmsd/lb: root mean square deviation/lower bond: 1gv3: superoxide dismutase (SOD); 6-MOF: 6-methoxyflavone.

Figure 11 Conformational changes observed due to the binding of 6-MOF with PDB ID: 1gv3: (a) surface area interactions of 6-MOF with the receptor binding domain of SOD and (b) 2D interaction between 6-MOF and the receptor protein.
Figure 11

Conformational changes observed due to the binding of 6-MOF with PDB ID: 1gv3: (a) surface area interactions of 6-MOF with the receptor binding domain of SOD and (b) 2D interaction between 6-MOF and the receptor protein.

4 Discussion

The therapeutic potential of flavonoids in the management and prevention of cancer, cerebrovascular illnesses, cardiovascular diseases, and neurodegenerative diseases is supported by an enormous amount of scientific evidence [44]. Decision-making ability, short-term working memory, and learning have all been assessed using Y-Maze [45]. In the current study, our findings have shown that 6-MOF has significant results in the spontaneous alternations task (Figure 3a–c). The processes of memory retrieval, consolidation, and acquisition include a variety of neurotransmitters, such as dopamine, acetylcholine, glutamate, noradrenaline, and serotonin [46]. The prefrontal cortex and hippocampal regions are largely involved in the establishment of working memory. The cholinergic neural system influences, and the glutamatergic circuit mediates this entire process [47,48]. In the hippocampus, 6-MOF was found to have significantly increased levels of dopamine, noradrenaline, serotonin, and vitamin C (Table 2). Previous research has indicated that activating dopamine D1-like receptors in the hippocampus enhances memory formation in that area, and inhibitors of monoamine oxidase-B were found to increase dopamine levels outside of hippocampus cells [49]. 6-MOF had an inhibitory effect on MAO-B [50] that could indicate higher dopamine levels in the hippocampal regions, confirming the importance of D1 dopamine receptors for improved spatial memory, as assessed by the Y-maze. By protecting the hippocampal antioxidant system, which was demonstrated to have an anti-oxidant effect against memory-related deficits in numerous disorders, vitamin C improves memory [51], which indicates that 6-MOF’s antioxidant action also contributes to neuroprotection. Additionally, it has been noted that medications that increase noradrenaline levels in the brain enhance cognition [52]. 6-MOF considerably increased the hippocampal noradrenaline levels (Table 2), which is one of the reasons for improving cognitive abilities. It is generally known that adenosine has a modulatory influence on the hippocampus and striatum, two important brain regions involved in memory [53]. Adenosine has been documented to play an important role in neuronal activity inhibition [54], axon formation [55], and neuroprotection [56]. Adenosine receptors A1 are widely distributed hippocampus, cerebellum, and cerebral cortex [57]. Studies have shown that A2A receptor antagonists improve spatial memory in Y-maze [53]. Flavonoids are reported to have an antagonist effect on A2A and A1 receptors [58] and have been shown to improve Y-maze performance [59]. 6-MOF improved Y-maze performance by modulating adenosine and its metabolites in the hippocampus, frontal cortex, and striatum (Tables 4–6), which may have contributed toward significant Y-maze performance. An NOR task was used to evaluate object recognition memory; it is a non-spatial and non-aversive test [60]. 6-MOF improved the time spent with the novel object (Figure 4). Relational, episodic, and contextual memory formation are all critical functions of the middle prefrontal cortex [61]. The prefrontal cortex and perirhinal cortex are neurologically connected to the hippocampus, which allows it to function as a functional component in memory task recognition by activating the executive center [62]. The frontal cortex and hippocampal levels of vitamin C increased (Tables 1 and 2). Vitamin C enhances cognition and memory by protecting against free radical damage, preserving oxidative processes and stored in the frontal cortex [51,63]. The hippocampus is involved in learning, memory formation, consolidation, and retrieval through the release of dopamine, serotonin, and noradrenaline [46]. The hippocampus has higher amounts of serotonin, dopamine, and noradrenaline (Table 2), which is explained by the increased time spent interacting with new objects and enhanced object recognition memory. Research has demonstrated that long-term cannabis usage causes memory impairments in the detection of novel objects, which are counteracted by antagonistic interactions with the adenosine A2AR receptor [64]. Adenosine receptor antagonism plays a key role spectrum of biological activities of reported flavonoids [65], and 6-MOF has a regulatory effect on adenosine and its metabolites (Tables 4–6), which may have contributed to enhanced object recognition memory. Survival, social cooperation, reproduction, and social behavior adaption all depend on socialization. In rodents, this behavior is the natural animal tendency to spend more time exploring unfamiliar subjects rather than familiar ones [66]. In our study, 6-MOF has improved socialization behavior (Figure 5) as well as enhanced dopamine and noradrenaline in the hippocampus (Table 2). The basolateral amygdala and the dorsal hippocampus CA1 area are of extreme importance for the control of social behavior [67]. Nonetheless, dopamine works on D1/D5 receptors, and noradrenaline acts on β-receptors in these regions, both of which are essential for social recognition [66]. This may be one of the reasons that socialization behavior is improved with 6-MOF. Adenosine is a reported neuromodulator and plays a noteworthy role in neuronal excitability and synaptic transmission [68,69]. A1 and A2A receptors are widely distributed in the brain primarily striatum hippocampus and olfactory bulb [69]; these brain areas are involved in the regulation of motivation [70] and the process of social behaviors [71]. A1 receptors are abundantly distributed in the hippocampus [72]. It has been reported that antagonism at A1 and A2A receptors improves social memory [73]. Flavonoids are reported as A2A and A1 receptor antagonists [58]. 6-MOF improved social recognition, possibly by modulating adenosine, inosine, and hypoxanthine levels in the frontal cortex, hippocampus, and striatum (Tables 4–6). To assess thermoregulatory and affective behavior, positive emotional states nest-building behavior test was performed. Dopaminergic and noradrenergic systems play a significant role in nest-building behavior [74]. Adenosine receptors are thickly articulated in the striatum and have a modulatory impact on dopamine neurotransmission. There is substantial confirmation of antagonistic interaction among A2A and D2 and also A1 and D1 receptors in the striatum [75]. 6-MOF has shown an increase in the levels of noradrenaline and dopamine (Table 1) and also a decrease in adenosine and its metabolite levels (Table 6), which may have contributed toward no alternation in the executive functions. All three doses of 6-MOF have not shown any alternation in nest-building behavior (Figure 6). Literature shreds of evidence specified that the hippocampus is important for the acquisition and consolidation of spatial memory, and spatial performance, in general and specifically in MWM, is dependent on the functional integrity of the hippocampus. Abrasions in the forebrain, hippocampus, striatum, cerebral cortex, and cerebellum were reported to impair MWM performance [76]. It has been reported that a spur in the noradrenergic system augments MWM acquisition [77]. Previous studies have reported that l-deprenyl, an MAO-B inhibitor, alleviated scopolamine-induced deficits in MWM [76,77]. According to studies in rats, lesions in the mesohippocampal dopaminergic system cause impairments in spatial memory [78]. The extracellular levels of dopamine in the hippocampus have been reported to be elevated in response to the use of monoamine oxidase-B inhibitors [49]. 6-MOF, being a flavonoid and an inhibitor of MAO-B [50], increased dopamine levels in the hippocampus (Table 2), thereby contributing toward the significant MWM performance (Figure 7a–c). Adenosine receptors A2A are extensively distributed in the striatum. It has also been reported that A1 receptor activation in the hippocampus inhibits the release of acetylcholine, and consumption of A1 antagonist caffeine has a modulatory effect on spatial memory [79]. Literature has already reported that fluoxetine improves the levels of noradrenaline and dopamine in the frontal cortex, thereby imparting an antidepressant effect [80]. Swertisin, an isolated flavonoid, has shown improvement in the MWM task by blocking the A1 receptor [59]. 6-MOF decreased adenosine levels in the hippocampus and striatum (Tables 5 and 6), which may be the contributing factor in spatial memory enhancement. Activation of the GABAA receptor has shown anxiolytic effects [81]. 6-MOF has been reported to have a GABAA agonist effect [25], so it can be an aspect toward anxiolytic effect of 6-MOF (Figure 8). Additionally, 6-MOF has improved monoamine levels in the frontal cortex and hippocampus (Tables 1 and 2), which can be a contributing factor in the anxiolytic effect. 6-MOF has shown an increase in the levels of vitamin C in the frontal cortex (Table 1). Dihydroxyascorabte is metabolized to vitamin C in CNS cells. Among the brain areas, the hippocampus and prefrontal cortex are the main areas that have maximum stores of ascorbic acid, thereby imparting the antioxidant effect [63]. Studies have shown that the antioxidant effect of vitamin C improves mood and cognition by modulating monoaminergic and glutamatergic neurotransmitter systems that play a pivotal role in antidepressant and anxiolytic effects, which is attributed to the frontal cortex’s ability to cope with stress and fear [82]. Adenosine has a direct relationship with anxiety, and the anxiogenic effect of adenosine receptor antagonists, caffeine, has been accredited to adenosine A1 receptor blockade [83]. 6-MOF considerably increased mobility time and decreased immobility time to elicit antidepressant effects (Figure 9). Literature has reported that the inhibitory impact that GABA typically has on some dopaminergic neurons will be lowered by diazepam and increase dopamine release. Therefore, using benzodiazepines will raise the release of dopamine, which enhances the feeling of pleasure and reward using diazepam [84]. Serotonin reuptake inhibitors, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors are recommended for the treatment of depression and anxiety-like behavior [85]. The amygdala, hippocampus, and frontal cortex are some of the brain regions that are largely involved in regulating and expressing anxiety-like behavior [86]. Anxiety is mediated by D1 and D2 receptors, and studies have linked anxiety to dopaminergic systems [87]. Literature studies have also shown that postsynaptic 5-HT1A receptors located at the dorsal hippocampus arbitrate anxiogenic effects, while endogenous dorsal hippocampal cholinergic neurons arbitrate anxiolytic effects [88]. 6-MOF significantly increased the levels of dopamine, noradrenaline, and serotonin in the hippocampus (Table 2), which might be involved in the antidepressant effect of 6-MOF. In the current study, our findings showed that 6-MOF produced significant hyper-locomotion (Figure 10). Elevated extracellular noradrenaline levels in the hippocampal region due to postsynaptic activation of 5-HT1A receptors induce hyperlocomotion and hyperexcitation [89]. Our study showed an increase in noradrenaline levels in the hippocampus (Table 2), which can be attributed to hyperlocomotion caused by 6-MOF. Earlier, the same compound has been reported to significantly reverse cisplatin-induced allodynia in the same doses orally [23]. The three most significant natural antioxidants that aid in scavenging these free radicals are glutathione (GSH), catalase (CAT), and SOD. Superoxide radicals and NO can react to form the highly reactive peroxynitrite anions (ONOO−). This highly reactive radical is created when NO and superoxide anion react, and it can cause cytotoxicity, neurotoxicity, and apoptotic cells [90]. Furthermore, flavonoids activate enzymes that scavenge free radicals, such as CAT and SOD, which lower the concentrations of free radical oxygen species, such as singlet oxygen, hydroxyl radical, and superoxide radical [91]. An in silico study was performed to determine the binding affinity of 6-MOF with SOD enzyme. Results have shown that the minimum binding energy of 6-MOF with antioxidant enzyme is −7.1 k/cal/mol (Table 7). The binding energy showed that 6-MOF was successfully docked with an antioxidant enzyme (Figure 10a and b), thereby showing the antioxidant effect of 6-MOF.

5 Conclusion

6-MOF showed notable effects in improving the cognitive aspects, modulating decision making, short-term memory, long-term memory, spatial memory, motor and skilled-based memory, anxiety, and depression, which was evaluated via behavioral evaluation. Neurochemically, 6-MOF showed profound results in modulating key neurotransmitters in the frontal cortex, hippocampus, and striatum, as well as imparted generalized neuroprotection by modulating adenosine and its metabolite levels. Thus, 6-MOF would be a potential novel candidate for managing cognitive decline, anxiety, and depression.

6 Limitations

More significant molecular-level studies are required to gain insight into the molecular mechanisms by which 6-MOF exerts significant pharmacological effects.

Acknowledgments

The authors wish to thank Princess Nourah bint Abdulrahman University Researchers Supporting Project (number PNURSP2024R33), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

  1. Funding information: Authors state no funding involved.

  2. Author contributions: Mehreen Arif: data curation, formal analysis, investigation, methodology, sources, software, validation, visualization, and writing – original draft. Dr. Khalid Rauf: supervision, conceptualization, and writing – review and editing. Dr. Naeem Ur Rehman: formal HPLC analysis. Irfan Anjum: resources, validation, and visualization. Amal Alotaibi: resources, validation, and writing. Ghala Alhmidani: writing and visualization.

  3. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose.

  4. Data availability statement: All raw/original data will be provided on demand.

References

[1] Okoye CO, Jiang H, Wu Y, Li X, Gao L, Wang Y, et al. Bacterial biosynthesis of flavonoids: overview, current biotechnology applications, challenges, and prospects. J Cell Physiol. 2023;238(4):671.10.1002/jcp.31006Search in Google Scholar PubMed

[2] Chiang N-N, Lin TH, Teng YS, Sun YC, Chang KH, Lin CY, et al. Flavones 7, 8-DHF, quercetin, and apigenin against Tau toxicity via activation of TRKB signaling in ΔK280 TauRD-DsRed SH-SY5Y cells. Front Aging Neurosci. 2021;13:758895.10.3389/fnagi.2021.758895Search in Google Scholar PubMed PubMed Central

[3] Heim KE, Tagliaferro AR, Bobilya DJ. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J Nutr Biochem. 2002;13(10):572–84.10.1016/S0955-2863(02)00208-5Search in Google Scholar

[4] Zhou M, Konigsberg WH, Hao C, Pan Y, Sun J, Wang X. Bioactivity and mechanisms of flavonoids in decreasing insulin resistance. J Enzyme Inhib Med Chem. 2023;38(1):2199168.10.1080/14756366.2023.2199168Search in Google Scholar PubMed PubMed Central

[5] Kaur R, Sood A, Lang DK, Bhatia S, Al-Harrasi A, Aleya L, et al. Potential of flavonoids as anti-Alzheimer’s agents: bench to bedside. Environ Sci Pollut Res. 2022;29:1–15.10.1007/s11356-021-18165-zSearch in Google Scholar PubMed

[6] Ma EZ, Khachemoune A. Flavonoids and their therapeutic applications in skin diseases. Arch Dermatological Res. 2023;315(3):321–31.10.1007/s00403-022-02395-3Search in Google Scholar PubMed

[7] Wang D, Tang W, Yang GM, Cai BC. Anti-inflammatory, antioxidant and cytotoxic activities of flavonoids from Oxytropis falcata Bunge. Chin J Nat Med. 2010;8(6):461–5.10.1016/S1875-5364(11)60008-3Search in Google Scholar

[8] Ognibene E, Bovicelli P, Adriani W, Saso L, Laviola G. Behavioral effects of 6-bromoflavanone and 5-methoxy-6, 8-dibromoflavanone as anxiolytic compounds. Prog Neuro-psychopharmacol Biol Psychiatry. 2008;32(1):128–34.10.1016/j.pnpbp.2007.07.023Search in Google Scholar PubMed

[9] Cho N, Lee KY, Huh J, Choi JH, Yang H, Jeong EJ, et al. Cognitive-enhancing effects of Rhus verniciflua bark extract and its active flavonoids with neuroprotective and anti-inflammatory activities. Food Chem Toxicol. 2013;58:355–61.10.1016/j.fct.2013.05.007Search in Google Scholar PubMed

[10] Cho SJ, Kang KA, Piao MJ, Ryu YS, Fernando P, Zhen AX, et al. 7, 8-dihydroxyflavone protects high glucose-damaged neuronal cells against oxidative stress. Biomol Ther. 2019;27(1):85–91.10.4062/biomolther.2018.202Search in Google Scholar PubMed PubMed Central

[11] Jang S-W, Liu X, Yepes M, Shepherd KR, Miller GW, Liu Y, et al. A selective TrkB agonist with potent neurotrophic activities by 7, 8-dihydroxyflavone. Proc Natl Acad Sci. 2010;107(6):2687–92.10.1073/pnas.0913572107Search in Google Scholar PubMed PubMed Central

[12] Wu C-H, Hung TH, Chen CC, Ke CH, Lee CY, Wang PY, et al. Post-injury treatment with 7, 8-dihydroxyflavone, a TrkB receptor agonist, protects against experimental traumatic brain injury via PI3K/Akt signaling. PLoS One. 2014;9(11):e113397.10.1371/journal.pone.0113397Search in Google Scholar PubMed PubMed Central

[13] Chen J, Chua KW, Chua CC, Yu H, Pei A, Chua BH, et al. Antioxidant activity of 7, 8-dihydroxyflavone provides neuroprotection against glutamate-induced toxicity. Neurosci Lett. 2011;499(3):181–5.10.1016/j.neulet.2011.05.054Search in Google Scholar PubMed

[14] Ren Q, Zhang JC, Ma M, Fujita Y, Wu J, Hashimoto K. 7, 8-Dihydroxyflavone, a TrkB agonist, attenuates behavioral abnormalities and neurotoxicity in mice after administration of methamphetamine. Psychopharmacology. 2014;231(1):159–66.10.1007/s00213-013-3221-7Search in Google Scholar PubMed

[15] Johnston GA. Flavonoid nutraceuticals and ionotropic receptors for the inhibitory neurotransmitter GABA. Neurochem Int. 2015;89:120–5.10.1016/j.neuint.2015.07.013Search in Google Scholar PubMed

[16] Rendeiro C, Rhodes JS, Spencer JP. The mechanisms of action of flavonoids in the brain: direct versus indirect effects. Neurochem Int. 2015;89:126–39.10.1016/j.neuint.2015.08.002Search in Google Scholar PubMed

[17] Ulubelen A, Mabry T, Aynehchi Y. Flavonoids of Anvillea garcini. J Nat Products. 1979;42(6):624–6.10.1021/np50006a007Search in Google Scholar

[18] Freeman P, Murphy S, Nemorin J, Taylor W. The constituents of Australian Pimelea species. II. The isolation of unusual flavones from P. simplex and P. decora. Aust J Chem. 1981;34(8):1779–84.10.1071/CH9811779Search in Google Scholar

[19] Wang X, Wang Z, Sidhu PS, Desai UR, Zhou Q. 6-Hydroxyflavone and derivatives exhibit potent anti-inflammatory activity among mono-, di-and polyhydroxylated flavones in kidney mesangial cells. PLoS One. 2015;10(3):e0116409.10.1371/journal.pone.0116409Search in Google Scholar PubMed PubMed Central

[20] Schilling EE, Mabry TJ. Flavonoids of Helianthus series Corona-solis. Biochem Syst Ecol. 1981;9(2–3):161–3.10.1016/0305-1978(81)90034-XSearch in Google Scholar

[21] Harraz FM, Kassem FF, El Shaer NS. Sesquiterpene lactones and Flavonoids from centaurea bruguierana. Alexandria J Pharm Sci. 1994;8(3):219–22.Search in Google Scholar

[22] Arif M, Rauf K, Rehman NU, Tokhi A, Ikram M, Sewell RD. 6-Methoxyflavone and donepezil behavioral plus neurochemical correlates in reversing chronic ethanol and withdrawal induced cognitive impairment. Drug Design, Dev Ther. 2022;16:1573–93.10.2147/DDDT.S360677Search in Google Scholar PubMed PubMed Central

[23] Shahid M, Subhan F, Ahmad N, Sewell R. The flavonoid 6-methoxyflavone allays cisplatin-induced neuropathic allodynia and hypoalgesia. Biomed Pharmacother. 2017;95:1725–33.10.1016/j.biopha.2017.09.108Search in Google Scholar PubMed

[24] Barroso LK, Esmeraldo MA, de Oliveira IC, Junior MC, Silva NS. Systematic review of the antidepressant activity and associated antioxidant and anti-inflammatory effects of flavonoids in rodents. Res, Soc Dev. 2021;10(12):e410101220673.10.33448/rsd-v10i12.20673Search in Google Scholar

[25] Hall BJ, Karim N, Chebib M, Johnston GA, Hanrahan JR. Modulation of ionotropic GABA receptors by 6-methoxyflavanone and 6-methoxyflavone. Neurochem Res. 2014;39(6):1068–78.10.1007/s11064-013-1157-2Search in Google Scholar PubMed

[26] So J-S, Kim GC, Song M, Lee CG, Park E, Kim HJ, et al. 6-Methoxyflavone inhibits NFAT translocation into the nucleus and suppresses T cell activation. J Immunol. 2014;193(6):2772–83.10.4049/jimmunol.1400285Search in Google Scholar PubMed

[27] Chen W-F, Shih YH, Liu HC, Cheng CI, Chang CI, Chen CY, et al. 6-methoxyflavone suppresses neuroinflammation in lipopolysaccharide-stimulated microglia through the inhibition of TLR4/MyD88/p38 MAPK/NF-κB dependent pathways and the activation of HO-1/NQO-1 signaling. Phytomedicine. 2022;99:154025.10.1016/j.phymed.2022.154025Search in Google Scholar PubMed

[28] Zhang C, Quan Y, Bai Y, Yang L, Yang Y. The effect and apoptosis mechanism of 6-methoxyflavone in HeLa cells. Biomarkers. 2022;27:1–34.10.1080/1354750X.2022.2062448Search in Google Scholar PubMed

[29] Benoite T, Vigasini N. Antioxidant and antidiabetic activities of ethanolic extract of Hibiscus sabdariffa calyx and Stevia rebaudiana leaf. Asian J Biol Life Sci. 2021;10(1):217–24.10.5530/ajbls.2021.10.31Search in Google Scholar

[30] Meenambiga S, Rajagopal K. Antibiofilm activity and molecular docking studies of bioactive secondary metabolites from endophytic fungus Aspergillus nidulans on oral Candida albicans. J Appl Pharm Sci. 2018;8:37–45.Search in Google Scholar

[31] Tuzcu M, Baydas G. Effect of melatonin and vitamin E on diabetes-induced learning and memory impairment in rats. Eur J Pharmacol. 2006;537(1–3):106–10.10.1016/j.ejphar.2006.03.024Search in Google Scholar PubMed

[32] Ryu S, Jin M, Lee HK, Wang MH, Baek JS, Cho CW. Effects of lipid nanoparticles on physicochemical properties, cellular uptake, and lymphatic uptake of 6-methoxflavone. J Pharm Invest. 2022;52:1–9.10.1007/s40005-021-00557-5Search in Google Scholar

[33] Akbar S, Subhan F, Karim N, Aman U, Ullah S, Shahid M, et al. Characterization of 6-methoxyflavanone as a novel anxiolytic agent: A behavioral and pharmacokinetic approach. Eur J Pharmacol. 2017;801:19–27.10.1016/j.ejphar.2017.02.047Search in Google Scholar PubMed

[34] Kim S, Thiessen PA, Bolton EE, Chen J, Fu G, Gindulyte A, et al. PubChem substance and compound databases. Nucleic Acids Res. 2016;44(D1):D1202–13.10.1093/nar/gkv951Search in Google Scholar PubMed PubMed Central

[35] Cheng F, Li W, Zhou Y, Shen J, Wu Z, Liu G, et al. admetSAR: a comprehensive source and free tool for assessment of chemical ADMET properties. Washington, D.C.: ACS Publications; 2012.10.1021/ci300367aSearch in Google Scholar PubMed

[36] Tuli H, Sood S, Pundir A, Choudhary D, Dhama K, Kaur G, et al. Molecular Docking studies of Apigenin, Kaempferol, and Quercetin as potential target against spike receptor protein of SARS COV. J Exp Biol Agric Sci. 2022;10(1):144–9.10.18006/2022.10(1).144.149Search in Google Scholar

[37] Shahid M, Subhan F, Ahmad N, Din ZU, Ullah I, Ur Rahman S, et al. 6-methoxyflavone antagonizes chronic constriction injury and diabetes associated neuropathic nociception expression. Biochem Biophys Res Commun. 2024;724:150217.10.1016/j.bbrc.2024.150217Search in Google Scholar PubMed

[38] Jarrar Q, Jarrar Y, Balasmeh R, Alhussine K, Al-Sheikh I, Ayoub R, et al. Anxiolytic effect of ethanolic extract of Medjool dates of Phoenix dactylifera in mice. Jordan J Pharm Sci. 2023;16(1):46–60.10.35516/jjps.v16i1.1035Search in Google Scholar

[39] Inavally AT, Sadananda M. Differential strain sensitivity to low-dose anxiolytic diazepam in anxiety-related behaviour in male Wistar and Wistar-Kyoto, a rat model of endogenous depression. Indian J Physiol Pharmacol. 2024;68(2):108–17.10.25259/IJPP_431_2023Search in Google Scholar

[40] Mayorga AJ, Dalvi A, Page ME, Zimov-Levinson S, Hen R, Lucki I. Antidepressant-like behavioral effects in 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptor mutant mice. J Pharmacol Exp Ther. 2001;298(3):1101–7.Search in Google Scholar

[41] Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology. 1985;85(3):367–70.10.1007/BF00428203Search in Google Scholar PubMed

[42] Walia V, Garg C, Garg M. NO-sGC-cGMP signaling influence the anxiolytic like effect of lithium in mice in light and dark box and elevated plus maze. Brain Res. 2019;1704:114–26.10.1016/j.brainres.2018.10.002Search in Google Scholar PubMed

[43] Ahmed Z, Tokhi A, Arif M, Rehman NU, Sheibani V, Rauf K, et al. Fraxetin attenuates disrupted behavioral and central neurochemical activity in a model of chronic unpredictable stress. Front Pharmacology. 2023;14:1135497.10.3389/fphar.2023.1135497Search in Google Scholar PubMed PubMed Central

[44] Zhou D, Bai Z, Guo T, Li J, Li Y, Hou Y, et al. Dietary flavonoids and human top-ranked diseases: The perspective of in vivo bioactivity and bioavailability. Trends Food Sci Technol. 2022;120:374–86.10.1016/j.tifs.2022.01.019Search in Google Scholar

[45] Alsikhan RS, Aldubayan MA, Almami IS, Alhowail AH. Protective effect of galantamine against doxorubicin-induced neurotoxicity. Brain Sci. 2023;13(6):971.10.3390/brainsci13060971Search in Google Scholar PubMed PubMed Central

[46] Hamidkhaniha S, Bashiri H, Omidi A, Hosseini-Chegeni A, Tavangar SM, Sabouri S, et al. Effect of pretreatment with intracerebroventricular injection of minocycline on morphine‐induced memory impairment in passive avoidance test: Role of P‐CREB and c‐Fos expression in the dorsal hippocampus and basolateral amygdala regions. Clin Exp Pharmacol Physiol. 2019;46(8):711–22.10.1111/1440-1681.13090Search in Google Scholar PubMed

[47] Meldrum BS. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr. 2000;130(4):1007S–15S.10.1093/jn/130.4.1007SSearch in Google Scholar PubMed

[48] Kalita J, Kumar V, Misra UK, Bora HK. Memory and learning dysfunction following copper toxicity: Biochemical and immunohistochemical basis. Mol Neurobiol. 2018;55(5):3800–11.10.1007/s12035-017-0619-ySearch in Google Scholar PubMed

[49] Ayabe T, Ano Y, Ohya R, Kitaoka S, Furuyashiki T. The lacto-tetrapeptide Gly–Thr–Trp–Tyr, β-lactolin, improves spatial memory functions via dopamine release and D1 receptor activation in the hippocampus. Nutrients. 2019;11(10):2469.10.3390/nu11102469Search in Google Scholar PubMed PubMed Central

[50] Pogodin PV, Lagunin AA, Filimonov DA, Poroikov VV. PASS targets: Ligand-based multi-target computational system based on a public data and naïve Bayes approach. SAR QSAR Environ Res. 2015;26(10):783–93.10.1080/1062936X.2015.1078407Search in Google Scholar PubMed

[51] Alqudah M, Alzoubi KH, Ma'abrih GM, Khabour OF. Vitamin C prevents memory impairment induced by waterpipe smoke: role of oxidative stress. Inhalation Toxicol. 2018;30(4–5):141–8.10.1080/08958378.2018.1474977Search in Google Scholar PubMed

[52] O’Callaghan C, Hezemans FH, Ye R, Rua C, Jones PS, Murley AG, et al. Locus coeruleus integrity and the effect of atomoxetine on response inhibition in Parkinson’s disease. medRxiv. London: Oxford university press; 2020.10.1101/2020.09.03.20176800Search in Google Scholar

[53] Wang JH, Ma YY, van den Buuse M. Improved spatial recognition memory in mice lacking adenosine A2A receptors. Exp Neurol. 2006;199(2):438–45.10.1016/j.expneurol.2006.01.005Search in Google Scholar PubMed

[54] Fisone G, Borgkvist A, Usiello A. Caffeine as a psychomotor stimulant: mechanism of action. Cell Mol Life Sci CMLS. 2004;61(7):857–72.10.1007/s00018-003-3269-3Search in Google Scholar PubMed PubMed Central

[55] Turner CP, Yan H, Schwartz M, Othman T, Rivkees SA. A1 adenosine receptor activation induces ventriculomegaly and white matter loss. Neuroreport. 2002;13(9):1199–204.10.1097/00001756-200207020-00026Search in Google Scholar PubMed

[56] Rivkees SA, Zhao Z, Porter G, Turner C. Influences of adenosine on the fetus and newborn. Mol Genet Metab. 2001;74(1–2):160–71.10.1006/mgme.2001.3217Search in Google Scholar PubMed

[57] Soellner DE, Grandys T, Nuñez JL. Chronic prenatal caffeine exposure impairs novel object recognition and radial arm maze behaviors in adult rats. Behav Brain Res. 2009;205(1):191–9.10.1016/j.bbr.2009.08.012Search in Google Scholar PubMed PubMed Central

[58] Alexander SP. Flavonoids as antagonists at A1 adenosine receptors. Phytother Res: An Int J Devoted Pharmacol Toxicol Eval Nat Product Derivatives. 2006;20(11):1009–12.10.1002/ptr.1975Search in Google Scholar PubMed

[59] Lee HE, Jeon SJ, Ryu B, Park SJ, Ko SY, Lee Y, et al. Swertisin, a C-glucosylflavone, ameliorates scopolamine-induced memory impairment in mice with its adenosine A1 receptor antagonistic property. Behav Brain Res. 2016;306:137–45.10.1016/j.bbr.2016.03.030Search in Google Scholar PubMed

[60] Yu X-D, Mo YX, He Z, Reilly J, Tian SW, Shu X. Urocanic acid enhances memory consolidation and reconsolidation in novel object recognition task. Biochem Biophys Res Commun. 2021;579:62–8.10.1016/j.bbrc.2021.09.055Search in Google Scholar PubMed

[61] Spanswick SC, Dyck RH. Object/context specific memory deficits following medial frontal cortex damage in mice. PLoS One. 2012;7(8):e43698.10.1371/journal.pone.0043698Search in Google Scholar PubMed PubMed Central

[62] Barker GR, Warburton EC. When is the hippocampus involved in recognition memory? J Neurosci. 2011;31(29):10721–31.10.1523/JNEUROSCI.6413-10.2011Search in Google Scholar PubMed PubMed Central

[63] Rice ME. Ascorbate regulation and its neuroprotective role in the brain. Trends Neurosci. 2000;23(5):209–16.10.1016/S0166-2236(99)01543-XSearch in Google Scholar PubMed

[64] Mouro FM, Köfalvi A, André LA, Baqi Y, Müller CE, Ribeiro JA, et al. Memory deficits induced by chronic cannabinoid exposure are prevented by adenosine A2AR receptor antagonism. Neuropharmacology. 2019;155:10–21.10.1016/j.neuropharm.2019.05.003Search in Google Scholar PubMed

[65] Jacobson KA, Moro S, Manthey JA, West PL, Ji XD. Interactions of flavones and other phytochemicals with adenosine receptors. Flavonoids Cell Funct. 2002;505:163–71.10.1007/978-1-4757-5235-9_15Search in Google Scholar PubMed PubMed Central

[66] Garrido Zinn C, Clairis N, Silva Cavalcante LE, Furini CR, de Carvalho Myskiw J, Izquierdo I. Major neurotransmitter systems in dorsal hippocampus and basolateral amygdala control social recognition memory. Proc National Acad Sci. 2016;113(33):E4914–9.10.1073/pnas.1609883113Search in Google Scholar PubMed PubMed Central

[67] Towfighi A, Saver JL. Stroke declines from third to fourth leading cause of death in the United States: historical perspective and challenges ahead. Stroke. 2011;42(8):2351–5.10.1161/STROKEAHA.111.621904Search in Google Scholar PubMed

[68] Cunha R. Adenosine as a neuromodulator and as a homeostatic regulator in the nervous system: different roles, different sources and different receptors. Neurochem Int. 2001;38(2):107–25.10.1016/S0197-0186(00)00034-6Search in Google Scholar

[69] López-Cruz L, San-Miguel N, Bayarri P, Baqi Y, Müller CE, Salamone JD, et al. Ethanol and caffeine effects on social interaction and recognition in mice: involvement of adenosine A2A and A1 receptors. Front Behav Neurosci. 2016;10:206.10.3389/fnbeh.2016.00206Search in Google Scholar PubMed PubMed Central

[70] Salamone JD, Correa M. The mysterious motivational functions of mesolimbic dopamine. Neuron. 2012;76(3):470–85.10.1016/j.neuron.2012.10.021Search in Google Scholar PubMed PubMed Central

[71] Pena RR, Pereira-Caixeta AR, Moraes MF, Pereira GS. Anisomycin administered in the olfactory bulb and dorsal hippocampus impaired social recognition memory consolidation in different time-points. Brain Res Bull. 2014;109:151–7.10.1016/j.brainresbull.2014.10.009Search in Google Scholar PubMed

[72] Schwarzschild MA, Agnati L, Fuxe K, Chen JF, Morelli M. Targeting adenosine A2A receptors in Parkinson’s disease. Trends Neurosci. 2006;29(11):647–54.10.1016/j.tins.2006.09.004Search in Google Scholar PubMed

[73] Prediger RD, Takahashi RN. Modulation of short-term social memory in rats by adenosine A1 and A2A receptors. Neurosci Lett. 2005;376(3):160–5.10.1016/j.neulet.2004.11.049Search in Google Scholar PubMed

[74] Greenberg GD, Phillips TJ, Crabbe JC. Effects of acute alcohol withdrawal on nest building in mice selectively bred for alcohol withdrawal severity. Physiol Behav. 2016;165:257–66.10.1016/j.physbeh.2016.08.006Search in Google Scholar PubMed PubMed Central

[75] Takahashi RN, Pamplona FA, Prediger R. Adenosine receptor antagonists for cognitive dysfunction: a review of animal studies. Front Biosci. 2008;13(26):2614–32.10.2741/2870Search in Google Scholar PubMed

[76] D’Hooge R, De Deyn PP. Applications of the Morris water maze in the study of learning and memory. Brain Res Rev. 2001;36(1):60–90.10.1016/S0165-0173(01)00067-4Search in Google Scholar PubMed

[77] Yavich L, Sirviö J, Heinonen E, Riekkinen P Sr. The interaction of L-deprenyl and scopolamine on spatial learning/memory in rats. J Neural Transm-Parkinson’s Dis Dement Sect. 1993;6(3):189–97.10.1007/BF02260921Search in Google Scholar PubMed

[78] Gasbarri A, Sulli A, Innocenzi R, Pacitti C, Brioni JD. Spatial memory impairment induced by lesion of the mesohippocampal dopaminergic system in the rat. Neuroscience. 1996;74(4):1037–44.10.1016/0306-4522(96)00202-3Search in Google Scholar PubMed

[79] Angelucci ME, Cesário C, Hiroi RH, Rosalen PL, Da Cunha C. Effects of caffeine on learning and memory in rats tested in the Morris water maze. Braz J Med Biol Res. 2002;35(10):1201–8.10.1590/S0100-879X2002001000013Search in Google Scholar PubMed

[80] Bymaster FP, Zhang W, Carter PA, Shaw J, Chernet E, Phebus L, et al. Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex. Psychopharmacology. 2002;160:353–61.10.1007/s00213-001-0986-xSearch in Google Scholar PubMed

[81] Rezayat M, Roohbakhsh A, Zarrindast MR, Massoudi R, Djahanguiri B. Cholecystokinin and GABA interaction in the dorsal hippocampus of rats in the elevated plus-maze test of anxiety. Physiol Behav. 2005;84(5):775–82.10.1016/j.physbeh.2005.03.002Search in Google Scholar PubMed

[82] Moritz B, Schmitz AE, Rodrigues A, Dafre AL, Cunha MP. The role of vitamin C in stress-related disorders. J Nutr Biochem. 2020;85:108459.10.1016/j.jnutbio.2020.108459Search in Google Scholar PubMed

[83] Prediger RD, Batista LC, Takahashi RN. Adenosine A1 receptors modulate the anxiolytic-like effect of ethanol in the elevated plus-maze in mice. Eur J Pharmacol. 2004;499(1–2):147–54.10.1016/j.ejphar.2004.07.106Search in Google Scholar PubMed

[84] Staff NN. Well-known mechanism underlies benzodiazepines’ addictive properties. NIDA Notes. 2012;24(2):1–2.Search in Google Scholar

[85] Singh KP, Singh P, Agrawal P, Agarwal BP. Neurodevelopmental and neurobehavioral sequelae associated with in utero exposure to second-generation antidepressants: A systematic review. J Appl Biol Biotechnol. 2024;471:115128.10.7324/JABB.2023.11502Search in Google Scholar

[86] Winzenried ET, Everett AC, Saito ER, Miller RM, Johnson T, Neal E, et al. Effects of a true prophylactic treatment on hippocampal and amygdala synaptic plasticity and gene expression in a rodent chronic stress model of social defeat. Int J Mol Sci. 2023;24(13):11193.10.3390/ijms241311193Search in Google Scholar PubMed PubMed Central

[87] Zarrindast M-R, Khakpai F. The modulatory role of dopamine in anxiety-like behavior. Arch Iran Med. 2015;18(9):591–603.Search in Google Scholar

[88] File SE, Kenny PJ, Cheeta S. The role of the dorsal hippocampal serotonergic and cholinergic systems in the modulation of anxiety. Pharmacol Biochem Behav. 2000;66(1):65–72.10.1016/S0091-3057(00)00198-2Search in Google Scholar

[89] Suwabe A, Kubota M, Niwa M, Kobayashi K, Kanba S. Effect of a 5-HT1A receptor agonist, flesinoxan, on the extracellular noradrenaline level in the hippocampus and on the locomotor activity of rats. Brain Res. 2000;858(2):393–401.10.1016/S0006-8993(00)01941-7Search in Google Scholar

[90] Diniz TC, Silva JC, de Lima-Saraiva SR, Ribeiro FP, Pacheco AG, de Freitas RM, et al. The role of flavonoids on oxidative stress in epilepsy. Oxid Med Cell Longev. 2015;2015(1):171756.10.1155/2015/171756Search in Google Scholar PubMed PubMed Central

[91] Sen S, Chakraborty R, Sridhar C, Reddy YS, De B. Free radicals, antioxidants, diseases and phytomedicines: current status and future prospect. Int J Pharm Sci Rev Res. 2010;3(1):91–100.10.5530/ax.2011.1.14Search in Google Scholar
Received: 2024-04-01
Revised: 2024-08-26
Accepted: 2024-09-13
Published Online: 2024-10-25

© 2024 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. Regular Articles
  2. Porous silicon nanostructures: Synthesis, characterization, and their antifungal activity
  3. Biochar from de-oiled Chlorella vulgaris and its adsorption on antibiotics
  4. Phytochemicals profiling, in vitro and in vivo antidiabetic activity, and in silico studies on Ajuga iva (L.) Schreb.: A comprehensive approach
  5. Synthesis, characterization, in silico and in vitro studies of novel glycoconjugates as potential antibacterial, antifungal, and antileishmanial agents
  6. Sonochemical synthesis of gold nanoparticles mediated by potato starch: Its performance in the treatment of esophageal cancer
  7. Computational study of ADME-Tox prediction of selected phytochemicals from Punica granatum peels
  8. Phytochemical analysis, in vitro antioxidant and antifungal activities of extracts and essential oil derived from Artemisia herba-alba Asso
  9. Two triazole-based coordination polymers: Synthesis and crystal structure characterization
  10. Phytochemical and physicochemical studies of different apple varieties grown in Morocco
  11. Synthesis of multi-template molecularly imprinted polymers (MT-MIPs) for isolating ethyl para-methoxycinnamate and ethyl cinnamate from Kaempferia galanga L., extract with methacrylic acid as functional monomer
  12. Nutraceutical potential of Mesembryanthemum forsskaolii Hochst. ex Bioss.: Insights into its nutritional composition, phytochemical contents, and antioxidant activity
  13. Evaluation of influence of Butea monosperma floral extract on inflammatory biomarkers
  14. Cannabis sativa L. essential oil: Chemical composition, anti-oxidant, anti-microbial properties, and acute toxicity: In vitro, in vivo, and in silico study
  15. The effect of gamma radiation on 5-hydroxymethylfurfural conversion in water and dimethyl sulfoxide
  16. Hollow mushroom nanomaterials for potentiometric sensing of Pb2+ ions in water via the intercalation of iodide ions into the polypyrrole matrix
  17. Determination of essential oil and chemical composition of St. John’s Wort
  18. Computational design and in vitro assay of lantadene-based novel inhibitors of NS3 protease of dengue virus
  19. Anti-parasitic activity and computational studies on a novel labdane diterpene from the roots of Vachellia nilotica
  20. Microbial dynamics and dehydrogenase activity in tomato (Lycopersicon esculentum Mill.) rhizospheres: Impacts on growth and soil health across different soil types
  21. Correlation between in vitro anti-urease activity and in silico molecular modeling approach of novel imidazopyridine–oxadiazole hybrids derivatives
  22. Spatial mapping of indoor air quality in a light metro system using the geographic information system method
  23. Iron indices and hemogram in renal anemia and the improvement with Tribulus terrestris green-formulated silver nanoparticles applied on rat model
  24. Integrated track of nano-informatics coupling with the enrichment concept in developing a novel nanoparticle targeting ERK protein in Naegleria fowleri
  25. Cytotoxic and phytochemical screening of Solanum lycopersicum–Daucus carota hydro-ethanolic extract and in silico evaluation of its lycopene content as anticancer agent
  26. Protective activities of silver nanoparticles containing Panax japonicus on apoptotic, inflammatory, and oxidative alterations in isoproterenol-induced cardiotoxicity
  27. pH-based colorimetric detection of monofunctional aldehydes in liquid and gas phases
  28. Investigating the effect of resveratrol on apoptosis and regulation of gene expression of Caco-2 cells: Unravelling potential implications for colorectal cancer treatment
  29. Metformin inhibits knee osteoarthritis induced by type 2 diabetes mellitus in rats: S100A8/9 and S100A12 as players and therapeutic targets
  30. Effect of silver nanoparticles formulated by Silybum marianum on menopausal urinary incontinence in ovariectomized rats
  31. Synthesis of new analogs of N-substituted(benzoylamino)-1,2,3,6-tetrahydropyridines
  32. Response of yield and quality of Japonica rice to different gradients of moisture deficit at grain-filling stage in cold regions
  33. Preparation of an inclusion complex of nickel-based β-cyclodextrin: Characterization and accelerating the osteoarthritis articular cartilage repair
  34. Empagliflozin-loaded nanomicelles responsive to reactive oxygen species for renal ischemia/reperfusion injury protection
  35. Preparation and pharmacodynamic evaluation of sodium aescinate solid lipid nanoparticles
  36. Assessment of potentially toxic elements and health risks of agricultural soil in Southwest Riyadh, Saudi Arabia
  37. Theoretical investigation of hydrogen-rich fuel production through ammonia decomposition
  38. Biosynthesis and screening of cobalt nanoparticles using citrus species for antimicrobial activity
  39. Investigating the interplay of genetic variations, MCP-1 polymorphism, and docking with phytochemical inhibitors for combatting dengue virus pathogenicity through in silico analysis
  40. Ultrasound induced biosynthesis of silver nanoparticles embedded into chitosan polymers: Investigation of its anti-cutaneous squamous cell carcinoma effects
  41. Copper oxide nanoparticles-mediated Heliotropium bacciferum leaf extract: Antifungal activity and molecular docking assays against strawberry pathogens
  42. Sprouted wheat flour for improving physical, chemical, rheological, microbial load, and quality properties of fino bread
  43. Comparative toxicity assessment of fisetin-aided artificial intelligence-assisted drug design targeting epibulbar dermoid through phytochemicals
  44. Acute toxicity and anti-inflammatory activity of bis-thiourea derivatives
  45. Anti-diabetic activity-guided isolation of α-amylase and α-glucosidase inhibitory terpenes from Capsella bursa-pastoris Linn.
  46. GC–MS analysis of Lactobacillus plantarum YW11 metabolites and its computational analysis on familial pulmonary fibrosis hub genes
  47. Green formulation of copper nanoparticles by Pistacia khinjuk leaf aqueous extract: Introducing a novel chemotherapeutic drug for the treatment of prostate cancer
  48. Improved photocatalytic properties of WO3 nanoparticles for Malachite green dye degradation under visible light irradiation: An effect of La doping
  49. One-pot synthesis of a network of Mn2O3–MnO2–poly(m-methylaniline) composite nanorods on a polypyrrole film presents a promising and efficient optoelectronic and solar cell device
  50. Groundwater quality and health risk assessment of nitrate and fluoride in Al Qaseem area, Saudi Arabia
  51. A comparative study of the antifungal efficacy and phytochemical composition of date palm leaflet extracts
  52. Processing of alcohol pomelo beverage (Citrus grandis (L.) Osbeck) using saccharomyces yeast: Optimization, physicochemical quality, and sensory characteristics
  53. Specialized compounds of four Cameroonian spices: Isolation, characterization, and in silico evaluation as prospective SARS-CoV-2 inhibitors
  54. Identification of a novel drug target in Porphyromonas gingivalis by a computational genome analysis approach
  55. Physico-chemical properties and durability of a fly-ash-based geopolymer
  56. FMS-like tyrosine kinase 3 inhibitory potentials of some phytochemicals from anti-leukemic plants using computational chemical methodologies
  57. Wild Thymus zygis L. ssp. gracilis and Eucalyptus camaldulensis Dehnh.: Chemical composition, antioxidant and antibacterial activities of essential oils
  58. 3D-QSAR, molecular docking, ADMET, simulation dynamic, and retrosynthesis studies on new styrylquinolines derivatives against breast cancer
  59. Deciphering the influenza neuraminidase inhibitory potential of naturally occurring biflavonoids: An in silico approach
  60. Determination of heavy elements in agricultural regions, Saudi Arabia
  61. Synthesis and characterization of antioxidant-enriched Moringa oil-based edible oleogel
  62. Ameliorative effects of thistle and thyme honeys on cyclophosphamide-induced toxicity in mice
  63. Study of phytochemical compound and antipyretic activity of Chenopodium ambrosioides L. fractions
  64. Investigating the adsorption mechanism of zinc chloride-modified porous carbon for sulfadiazine removal from water
  65. Performance repair of building materials using alumina and silica composite nanomaterials with electrodynamic properties
  66. Effects of nanoparticles on the activity and resistance genes of anaerobic digestion enzymes in livestock and poultry manure containing the antibiotic tetracycline
  67. Effect of copper nanoparticles green-synthesized using Ocimum basilicum against Pseudomonas aeruginosa in mice lung infection model
  68. Cardioprotective effects of nanoparticles green formulated by Spinacia oleracea extract on isoproterenol-induced myocardial infarction in mice by the determination of PPAR-γ/NF-κB pathway
  69. Anti-OTC antibody-conjugated fluorescent magnetic/silica and fluorescent hybrid silica nanoparticles for oxytetracycline detection
  70. Curcumin conjugated zinc nanoparticles for the treatment of myocardial infarction
  71. Identification and in silico screening of natural phloroglucinols as potential PI3Kα inhibitors: A computational approach for drug discovery
  72. Exploring the phytochemical profile and antioxidant evaluation: Molecular docking and ADMET analysis of main compounds from three Solanum species in Saudi Arabia
  73. Unveiling the molecular composition and biological properties of essential oil derived from the leaves of wild Mentha aquatica L.: A comprehensive in vitro and in silico exploration
  74. Analysis of bioactive compounds present in Boerhavia elegans seeds by GC-MS
  75. Homology modeling and molecular docking study of corticotrophin-releasing hormone: An approach to treat stress-related diseases
  76. LncRNA MIR17HG alleviates heart failure via targeting MIR17HG/miR-153-3p/SIRT1 axis in in vitro model
  77. Development and validation of a stability indicating UPLC-DAD method coupled with MS-TQD for ramipril and thymoquinone in bioactive SNEDDS with in silico toxicity analysis of ramipril degradation products
  78. Biosynthesis of Ag/Cu nanocomposite mediated by Curcuma longa: Evaluation of its antibacterial properties against oral pathogens
  79. Development of AMBER-compliant transferable force field parameters for polytetrafluoroethylene
  80. Treatment of gestational diabetes by Acroptilon repens leaf aqueous extract green-formulated iron nanoparticles in rats
  81. Development and characterization of new ecological adsorbents based on cardoon wastes: Application to brilliant green adsorption
  82. A fast, sensitive, greener, and stability-indicating HPLC method for the standardization and quantitative determination of chlorhexidine acetate in commercial products
  83. Assessment of Se, As, Cd, Cr, Hg, and Pb content status in Ankang tea plantations of China
  84. Effect of transition metal chloride (ZnCl2) on low-temperature pyrolysis of high ash bituminous coal
  85. Evaluating polyphenol and ascorbic acid contents, tannin removal ability, and physical properties during hydrolysis and convective hot-air drying of cashew apple powder
  86. Development and characterization of functional low-fat frozen dairy dessert enhanced with dried lemongrass powder
  87. Scrutinizing the effect of additive and synergistic antibiotics against carbapenem-resistant Pseudomonas aeruginosa
  88. Preparation, characterization, and determination of the therapeutic effects of copper nanoparticles green-formulated by Pistacia atlantica in diabetes-induced cardiac dysfunction in rat
  89. Antioxidant and antidiabetic potentials of methoxy-substituted Schiff bases using in vitro, in vivo, and molecular simulation approaches
  90. Anti-melanoma cancer activity and chemical profile of the essential oil of Seseli yunnanense Franch
  91. Molecular docking analysis of subtilisin-like alkaline serine protease (SLASP) and laccase with natural biopolymers
  92. Overcoming methicillin resistance by methicillin-resistant Staphylococcus aureus: Computational evaluation of napthyridine and oxadiazoles compounds for potential dual inhibition of PBP-2a and FemA proteins
  93. Exploring novel antitubercular agents: Innovative design of 2,3-diaryl-quinoxalines targeting DprE1 for effective tuberculosis treatment
  94. Drimia maritima flowers as a source of biologically potent components: Optimization of bioactive compound extractions, isolation, UPLC–ESI–MS/MS, and pharmacological properties
  95. Estimating molecular properties, drug-likeness, cardiotoxic risk, liability profile, and molecular docking study to characterize binding process of key phyto-compounds against serotonin 5-HT2A receptor
  96. Fabrication of β-cyclodextrin-based microgels for enhancing solubility of Terbinafine: An in-vitro and in-vivo toxicological evaluation
  97. Phyto-mediated synthesis of ZnO nanoparticles and their sunlight-driven photocatalytic degradation of cationic and anionic dyes
  98. Monosodium glutamate induces hypothalamic–pituitary–adrenal axis hyperactivation, glucocorticoid receptors down-regulation, and systemic inflammatory response in young male rats: Impact on miR-155 and miR-218
  99. Quality control analyses of selected honey samples from Serbia based on their mineral and flavonoid profiles, and the invertase activity
  100. Eco-friendly synthesis of silver nanoparticles using Phyllanthus niruri leaf extract: Assessment of antimicrobial activity, effectiveness on tropical neglected mosquito vector control, and biocompatibility using a fibroblast cell line model
  101. Green synthesis of silver nanoparticles containing Cichorium intybus to treat the sepsis-induced DNA damage in the liver of Wistar albino rats
  102. Quality changes of durian pulp (Durio ziberhinus Murr.) in cold storage
  103. Study on recrystallization process of nitroguanidine by directly adding cold water to control temperature
  104. Determination of heavy metals and health risk assessment in drinking water in Bukayriyah City, Saudi Arabia
  105. Larvicidal properties of essential oils of three Artemisia species against the chemically insecticide-resistant Nile fever vector Culex pipiens (L.) (Diptera: Culicidae): In vitro and in silico studies
  106. Design, synthesis, characterization, and theoretical calculations, along with in silico and in vitro antimicrobial proprieties of new isoxazole-amide conjugates
  107. The impact of drying and extraction methods on total lipid, fatty acid profile, and cytotoxicity of Tenebrio molitor larvae
  108. A zinc oxide–tin oxide–nerolidol hybrid nanomaterial: Efficacy against esophageal squamous cell carcinoma
  109. Research on technological process for production of muskmelon juice (Cucumis melo L.)
  110. Physicochemical components, antioxidant activity, and predictive models for quality of soursop tea (Annona muricata L.) during heat pump drying
  111. Characterization and application of Fe1−xCoxFe2O4 nanoparticles in Direct Red 79 adsorption
  112. Torilis arvensis ethanolic extract: Phytochemical analysis, antifungal efficacy, and cytotoxicity properties
  113. Magnetite–poly-1H pyrrole dendritic nanocomposite seeded on poly-1H pyrrole: A promising photocathode for green hydrogen generation from sanitation water without using external sacrificing agent
  114. HPLC and GC–MS analyses of phytochemical compounds in Haloxylon salicornicum extract: Antibacterial and antifungal activity assessment of phytopathogens
  115. Efficient and stable to coking catalysts of ethanol steam reforming comprised of Ni + Ru loaded on MgAl2O4 + LnFe0.7Ni0.3O3 (Ln = La, Pr) nanocomposites prepared via cost-effective procedure with Pluronic P123 copolymer
  116. Nitrogen and boron co-doped carbon dots probe for selectively detecting Hg2+ in water samples and the detection mechanism
  117. Heavy metals in road dust from typical old industrial areas of Wuhan: Seasonal distribution and bioaccessibility-based health risk assessment
  118. Phytochemical profiling and bioactivity evaluation of CBD- and THC-enriched Cannabis sativa extracts: In vitro and in silico investigation of antioxidant and anti-inflammatory effects
  119. Investigating dye adsorption: The role of surface-modified montmorillonite nanoclay in kinetics, isotherms, and thermodynamics
  120. Antimicrobial activity, induction of ROS generation in HepG2 liver cancer cells, and chemical composition of Pterospermum heterophyllum
  121. Study on the performance of nanoparticle-modified PVDF membrane in delaying membrane aging
  122. Impact of cholesterol in encapsulated vitamin E acetate within cocoliposomes
  123. Review Articles
  124. Structural aspects of Pt(η3-X1N1X2)(PL) (X1,2 = O, C, or Se) and Pt(η3-N1N2X1)(PL) (X1 = C, S, or Se) derivatives
  125. Biosurfactants in biocorrosion and corrosion mitigation of metals: An overview
  126. Stimulus-responsive MOF–hydrogel composites: Classification, preparation, characterization, and their advancement in medical treatments
  127. Electrochemical dissolution of titanium under alternating current polarization to obtain its dioxide
  128. Special Issue on Recent Trends in Green Chemistry
  129. Phytochemical screening and antioxidant activity of Vitex agnus-castus L.
  130. Phytochemical study, antioxidant activity, and dermoprotective activity of Chenopodium ambrosioides (L.)
  131. Exploitation of mangliculous marine fungi, Amarenographium solium, for the green synthesis of silver nanoparticles and their activity against multiple drug-resistant bacteria
  132. Study of the phytotoxicity of margines on Pistia stratiotes L.
  133. Special Issue on Advanced Nanomaterials for Energy, Environmental and Biological Applications - Part III
  134. Impact of biogenic zinc oxide nanoparticles on growth, development, and antioxidant system of high protein content crop (Lablab purpureus L.) sweet
  135. Green synthesis, characterization, and application of iron and molybdenum nanoparticles and their composites for enhancing the growth of Solanum lycopersicum
  136. Green synthesis of silver nanoparticles from Olea europaea L. extracted polysaccharides, characterization, and its assessment as an antimicrobial agent against multiple pathogenic microbes
  137. Photocatalytic treatment of organic dyes using metal oxides and nanocomposites: A quantitative study
  138. Antifungal, antioxidant, and photocatalytic activities of greenly synthesized iron oxide nanoparticles
  139. Special Issue on Phytochemical and Pharmacological Scrutinization of Medicinal Plants
  140. Hepatoprotective effects of safranal on acetaminophen-induced hepatotoxicity in rats
  141. Chemical composition and biological properties of Thymus capitatus plants from Algerian high plains: A comparative and analytical study
  142. Chemical composition and bioactivities of the methanol root extracts of Saussurea costus
  143. In vivo protective effects of vitamin C against cyto-genotoxicity induced by Dysphania ambrosioides aqueous extract
  144. Insights about the deleterious impact of a carbamate pesticide on some metabolic immune and antioxidant functions and a focus on the protective ability of a Saharan shrub and its anti-edematous property
  145. A comprehensive review uncovering the anticancerous potential of genkwanin (plant-derived compound) in several human carcinomas
  146. A study to investigate the anticancer potential of carvacrol via targeting Notch signaling in breast cancer
  147. Assessment of anti-diabetic properties of Ziziphus oenopolia (L.) wild edible fruit extract: In vitro and in silico investigations through molecular docking analysis
  148. Optimization of polyphenol extraction, phenolic profile by LC-ESI-MS/MS, antioxidant, anti-enzymatic, and cytotoxic activities of Physalis acutifolia
  149. Phytochemical screening, antioxidant properties, and photo-protective activities of Salvia balansae de Noé ex Coss
  150. Antihyperglycemic, antiglycation, anti-hypercholesteremic, and toxicity evaluation with gas chromatography mass spectrometry profiling for Aloe armatissima leaves
  151. Phyto-fabrication and characterization of gold nanoparticles by using Timur (Zanthoxylum armatum DC) and their effect on wound healing
  152. Does Erodium trifolium (Cav.) Guitt exhibit medicinal properties? Response elements from phytochemical profiling, enzyme-inhibiting, and antioxidant and antimicrobial activities
  153. Integrative in silico evaluation of the antiviral potential of terpenoids and its metal complexes derived from Homalomena aromatica based on main protease of SARS-CoV-2
  154. 6-Methoxyflavone improves anxiety, depression, and memory by increasing monoamines in mice brain: HPLC analysis and in silico studies
  155. Simultaneous extraction and quantification of hydrophilic and lipophilic antioxidants in Solanum lycopersicum L. varieties marketed in Saudi Arabia
  156. Biological evaluation of CH3OH and C2H5OH of Berberis vulgaris for in vivo antileishmanial potential against Leishmania tropica in murine models
https://doi.org/10.1515/chem-2024-0098
Keywords for this article
serotonin; dopamine; noradrenaline; 6-methoxyflavone; adenosine
Creative Commons
BY 4.0

Articles in the same Issue

  1. Regular Articles
  2. Porous silicon nanostructures: Synthesis, characterization, and their antifungal activity
  3. Biochar from de-oiled Chlorella vulgaris and its adsorption on antibiotics
  4. Phytochemicals profiling, in vitro and in vivo antidiabetic activity, and in silico studies on Ajuga iva (L.) Schreb.: A comprehensive approach
  5. Synthesis, characterization, in silico and in vitro studies of novel glycoconjugates as potential antibacterial, antifungal, and antileishmanial agents
  6. Sonochemical synthesis of gold nanoparticles mediated by potato starch: Its performance in the treatment of esophageal cancer
  7. Computational study of ADME-Tox prediction of selected phytochemicals from Punica granatum peels
  8. Phytochemical analysis, in vitro antioxidant and antifungal activities of extracts and essential oil derived from Artemisia herba-alba Asso
  9. Two triazole-based coordination polymers: Synthesis and crystal structure characterization
  10. Phytochemical and physicochemical studies of different apple varieties grown in Morocco
  11. Synthesis of multi-template molecularly imprinted polymers (MT-MIPs) for isolating ethyl para-methoxycinnamate and ethyl cinnamate from Kaempferia galanga L., extract with methacrylic acid as functional monomer
  12. Nutraceutical potential of Mesembryanthemum forsskaolii Hochst. ex Bioss.: Insights into its nutritional composition, phytochemical contents, and antioxidant activity
  13. Evaluation of influence of Butea monosperma floral extract on inflammatory biomarkers
  14. Cannabis sativa L. essential oil: Chemical composition, anti-oxidant, anti-microbial properties, and acute toxicity: In vitro, in vivo, and in silico study
  15. The effect of gamma radiation on 5-hydroxymethylfurfural conversion in water and dimethyl sulfoxide
  16. Hollow mushroom nanomaterials for potentiometric sensing of Pb2+ ions in water via the intercalation of iodide ions into the polypyrrole matrix
  17. Determination of essential oil and chemical composition of St. John’s Wort
  18. Computational design and in vitro assay of lantadene-based novel inhibitors of NS3 protease of dengue virus
  19. Anti-parasitic activity and computational studies on a novel labdane diterpene from the roots of Vachellia nilotica
  20. Microbial dynamics and dehydrogenase activity in tomato (Lycopersicon esculentum Mill.) rhizospheres: Impacts on growth and soil health across different soil types
  21. Correlation between in vitro anti-urease activity and in silico molecular modeling approach of novel imidazopyridine–oxadiazole hybrids derivatives
  22. Spatial mapping of indoor air quality in a light metro system using the geographic information system method
  23. Iron indices and hemogram in renal anemia and the improvement with Tribulus terrestris green-formulated silver nanoparticles applied on rat model
  24. Integrated track of nano-informatics coupling with the enrichment concept in developing a novel nanoparticle targeting ERK protein in Naegleria fowleri
  25. Cytotoxic and phytochemical screening of Solanum lycopersicum–Daucus carota hydro-ethanolic extract and in silico evaluation of its lycopene content as anticancer agent
  26. Protective activities of silver nanoparticles containing Panax japonicus on apoptotic, inflammatory, and oxidative alterations in isoproterenol-induced cardiotoxicity
  27. pH-based colorimetric detection of monofunctional aldehydes in liquid and gas phases
  28. Investigating the effect of resveratrol on apoptosis and regulation of gene expression of Caco-2 cells: Unravelling potential implications for colorectal cancer treatment
  29. Metformin inhibits knee osteoarthritis induced by type 2 diabetes mellitus in rats: S100A8/9 and S100A12 as players and therapeutic targets
  30. Effect of silver nanoparticles formulated by Silybum marianum on menopausal urinary incontinence in ovariectomized rats
  31. Synthesis of new analogs of N-substituted(benzoylamino)-1,2,3,6-tetrahydropyridines
  32. Response of yield and quality of Japonica rice to different gradients of moisture deficit at grain-filling stage in cold regions
  33. Preparation of an inclusion complex of nickel-based β-cyclodextrin: Characterization and accelerating the osteoarthritis articular cartilage repair
  34. Empagliflozin-loaded nanomicelles responsive to reactive oxygen species for renal ischemia/reperfusion injury protection
  35. Preparation and pharmacodynamic evaluation of sodium aescinate solid lipid nanoparticles
  36. Assessment of potentially toxic elements and health risks of agricultural soil in Southwest Riyadh, Saudi Arabia
  37. Theoretical investigation of hydrogen-rich fuel production through ammonia decomposition
  38. Biosynthesis and screening of cobalt nanoparticles using citrus species for antimicrobial activity
  39. Investigating the interplay of genetic variations, MCP-1 polymorphism, and docking with phytochemical inhibitors for combatting dengue virus pathogenicity through in silico analysis
  40. Ultrasound induced biosynthesis of silver nanoparticles embedded into chitosan polymers: Investigation of its anti-cutaneous squamous cell carcinoma effects
  41. Copper oxide nanoparticles-mediated Heliotropium bacciferum leaf extract: Antifungal activity and molecular docking assays against strawberry pathogens
  42. Sprouted wheat flour for improving physical, chemical, rheological, microbial load, and quality properties of fino bread
  43. Comparative toxicity assessment of fisetin-aided artificial intelligence-assisted drug design targeting epibulbar dermoid through phytochemicals
  44. Acute toxicity and anti-inflammatory activity of bis-thiourea derivatives
  45. Anti-diabetic activity-guided isolation of α-amylase and α-glucosidase inhibitory terpenes from Capsella bursa-pastoris Linn.
  46. GC–MS analysis of Lactobacillus plantarum YW11 metabolites and its computational analysis on familial pulmonary fibrosis hub genes
  47. Green formulation of copper nanoparticles by Pistacia khinjuk leaf aqueous extract: Introducing a novel chemotherapeutic drug for the treatment of prostate cancer
  48. Improved photocatalytic properties of WO3 nanoparticles for Malachite green dye degradation under visible light irradiation: An effect of La doping
  49. One-pot synthesis of a network of Mn2O3–MnO2–poly(m-methylaniline) composite nanorods on a polypyrrole film presents a promising and efficient optoelectronic and solar cell device
  50. Groundwater quality and health risk assessment of nitrate and fluoride in Al Qaseem area, Saudi Arabia
  51. A comparative study of the antifungal efficacy and phytochemical composition of date palm leaflet extracts
  52. Processing of alcohol pomelo beverage (Citrus grandis (L.) Osbeck) using saccharomyces yeast: Optimization, physicochemical quality, and sensory characteristics
  53. Specialized compounds of four Cameroonian spices: Isolation, characterization, and in silico evaluation as prospective SARS-CoV-2 inhibitors
  54. Identification of a novel drug target in Porphyromonas gingivalis by a computational genome analysis approach
  55. Physico-chemical properties and durability of a fly-ash-based geopolymer
  56. FMS-like tyrosine kinase 3 inhibitory potentials of some phytochemicals from anti-leukemic plants using computational chemical methodologies
  57. Wild Thymus zygis L. ssp. gracilis and Eucalyptus camaldulensis Dehnh.: Chemical composition, antioxidant and antibacterial activities of essential oils
  58. 3D-QSAR, molecular docking, ADMET, simulation dynamic, and retrosynthesis studies on new styrylquinolines derivatives against breast cancer
  59. Deciphering the influenza neuraminidase inhibitory potential of naturally occurring biflavonoids: An in silico approach
  60. Determination of heavy elements in agricultural regions, Saudi Arabia
  61. Synthesis and characterization of antioxidant-enriched Moringa oil-based edible oleogel
  62. Ameliorative effects of thistle and thyme honeys on cyclophosphamide-induced toxicity in mice
  63. Study of phytochemical compound and antipyretic activity of Chenopodium ambrosioides L. fractions
  64. Investigating the adsorption mechanism of zinc chloride-modified porous carbon for sulfadiazine removal from water
  65. Performance repair of building materials using alumina and silica composite nanomaterials with electrodynamic properties
  66. Effects of nanoparticles on the activity and resistance genes of anaerobic digestion enzymes in livestock and poultry manure containing the antibiotic tetracycline
  67. Effect of copper nanoparticles green-synthesized using Ocimum basilicum against Pseudomonas aeruginosa in mice lung infection model
  68. Cardioprotective effects of nanoparticles green formulated by Spinacia oleracea extract on isoproterenol-induced myocardial infarction in mice by the determination of PPAR-γ/NF-κB pathway
  69. Anti-OTC antibody-conjugated fluorescent magnetic/silica and fluorescent hybrid silica nanoparticles for oxytetracycline detection
  70. Curcumin conjugated zinc nanoparticles for the treatment of myocardial infarction
  71. Identification and in silico screening of natural phloroglucinols as potential PI3Kα inhibitors: A computational approach for drug discovery
  72. Exploring the phytochemical profile and antioxidant evaluation: Molecular docking and ADMET analysis of main compounds from three Solanum species in Saudi Arabia
  73. Unveiling the molecular composition and biological properties of essential oil derived from the leaves of wild Mentha aquatica L.: A comprehensive in vitro and in silico exploration
  74. Analysis of bioactive compounds present in Boerhavia elegans seeds by GC-MS
  75. Homology modeling and molecular docking study of corticotrophin-releasing hormone: An approach to treat stress-related diseases
  76. LncRNA MIR17HG alleviates heart failure via targeting MIR17HG/miR-153-3p/SIRT1 axis in in vitro model
  77. Development and validation of a stability indicating UPLC-DAD method coupled with MS-TQD for ramipril and thymoquinone in bioactive SNEDDS with in silico toxicity analysis of ramipril degradation products
  78. Biosynthesis of Ag/Cu nanocomposite mediated by Curcuma longa: Evaluation of its antibacterial properties against oral pathogens
  79. Development of AMBER-compliant transferable force field parameters for polytetrafluoroethylene
  80. Treatment of gestational diabetes by Acroptilon repens leaf aqueous extract green-formulated iron nanoparticles in rats
  81. Development and characterization of new ecological adsorbents based on cardoon wastes: Application to brilliant green adsorption
  82. A fast, sensitive, greener, and stability-indicating HPLC method for the standardization and quantitative determination of chlorhexidine acetate in commercial products
  83. Assessment of Se, As, Cd, Cr, Hg, and Pb content status in Ankang tea plantations of China
  84. Effect of transition metal chloride (ZnCl2) on low-temperature pyrolysis of high ash bituminous coal
  85. Evaluating polyphenol and ascorbic acid contents, tannin removal ability, and physical properties during hydrolysis and convective hot-air drying of cashew apple powder
  86. Development and characterization of functional low-fat frozen dairy dessert enhanced with dried lemongrass powder
  87. Scrutinizing the effect of additive and synergistic antibiotics against carbapenem-resistant Pseudomonas aeruginosa
  88. Preparation, characterization, and determination of the therapeutic effects of copper nanoparticles green-formulated by Pistacia atlantica in diabetes-induced cardiac dysfunction in rat
  89. Antioxidant and antidiabetic potentials of methoxy-substituted Schiff bases using in vitro, in vivo, and molecular simulation approaches
  90. Anti-melanoma cancer activity and chemical profile of the essential oil of Seseli yunnanense Franch
  91. Molecular docking analysis of subtilisin-like alkaline serine protease (SLASP) and laccase with natural biopolymers
  92. Overcoming methicillin resistance by methicillin-resistant Staphylococcus aureus: Computational evaluation of napthyridine and oxadiazoles compounds for potential dual inhibition of PBP-2a and FemA proteins
  93. Exploring novel antitubercular agents: Innovative design of 2,3-diaryl-quinoxalines targeting DprE1 for effective tuberculosis treatment
  94. Drimia maritima flowers as a source of biologically potent components: Optimization of bioactive compound extractions, isolation, UPLC–ESI–MS/MS, and pharmacological properties
  95. Estimating molecular properties, drug-likeness, cardiotoxic risk, liability profile, and molecular docking study to characterize binding process of key phyto-compounds against serotonin 5-HT2A receptor
  96. Fabrication of β-cyclodextrin-based microgels for enhancing solubility of Terbinafine: An in-vitro and in-vivo toxicological evaluation
  97. Phyto-mediated synthesis of ZnO nanoparticles and their sunlight-driven photocatalytic degradation of cationic and anionic dyes
  98. Monosodium glutamate induces hypothalamic–pituitary–adrenal axis hyperactivation, glucocorticoid receptors down-regulation, and systemic inflammatory response in young male rats: Impact on miR-155 and miR-218
  99. Quality control analyses of selected honey samples from Serbia based on their mineral and flavonoid profiles, and the invertase activity
  100. Eco-friendly synthesis of silver nanoparticles using Phyllanthus niruri leaf extract: Assessment of antimicrobial activity, effectiveness on tropical neglected mosquito vector control, and biocompatibility using a fibroblast cell line model
  101. Green synthesis of silver nanoparticles containing Cichorium intybus to treat the sepsis-induced DNA damage in the liver of Wistar albino rats
  102. Quality changes of durian pulp (Durio ziberhinus Murr.) in cold storage
  103. Study on recrystallization process of nitroguanidine by directly adding cold water to control temperature
  104. Determination of heavy metals and health risk assessment in drinking water in Bukayriyah City, Saudi Arabia
  105. Larvicidal properties of essential oils of three Artemisia species against the chemically insecticide-resistant Nile fever vector Culex pipiens (L.) (Diptera: Culicidae): In vitro and in silico studies
  106. Design, synthesis, characterization, and theoretical calculations, along with in silico and in vitro antimicrobial proprieties of new isoxazole-amide conjugates
  107. The impact of drying and extraction methods on total lipid, fatty acid profile, and cytotoxicity of Tenebrio molitor larvae
  108. A zinc oxide–tin oxide–nerolidol hybrid nanomaterial: Efficacy against esophageal squamous cell carcinoma
  109. Research on technological process for production of muskmelon juice (Cucumis melo L.)
  110. Physicochemical components, antioxidant activity, and predictive models for quality of soursop tea (Annona muricata L.) during heat pump drying
  111. Characterization and application of Fe1−xCoxFe2O4 nanoparticles in Direct Red 79 adsorption
  112. Torilis arvensis ethanolic extract: Phytochemical analysis, antifungal efficacy, and cytotoxicity properties
  113. Magnetite–poly-1H pyrrole dendritic nanocomposite seeded on poly-1H pyrrole: A promising photocathode for green hydrogen generation from sanitation water without using external sacrificing agent
  114. HPLC and GC–MS analyses of phytochemical compounds in Haloxylon salicornicum extract: Antibacterial and antifungal activity assessment of phytopathogens
  115. Efficient and stable to coking catalysts of ethanol steam reforming comprised of Ni + Ru loaded on MgAl2O4 + LnFe0.7Ni0.3O3 (Ln = La, Pr) nanocomposites prepared via cost-effective procedure with Pluronic P123 copolymer
  116. Nitrogen and boron co-doped carbon dots probe for selectively detecting Hg2+ in water samples and the detection mechanism
  117. Heavy metals in road dust from typical old industrial areas of Wuhan: Seasonal distribution and bioaccessibility-based health risk assessment
  118. Phytochemical profiling and bioactivity evaluation of CBD- and THC-enriched Cannabis sativa extracts: In vitro and in silico investigation of antioxidant and anti-inflammatory effects
  119. Investigating dye adsorption: The role of surface-modified montmorillonite nanoclay in kinetics, isotherms, and thermodynamics
  120. Antimicrobial activity, induction of ROS generation in HepG2 liver cancer cells, and chemical composition of Pterospermum heterophyllum
  121. Study on the performance of nanoparticle-modified PVDF membrane in delaying membrane aging
  122. Impact of cholesterol in encapsulated vitamin E acetate within cocoliposomes
  123. Review Articles
  124. Structural aspects of Pt(η3-X1N1X2)(PL) (X1,2 = O, C, or Se) and Pt(η3-N1N2X1)(PL) (X1 = C, S, or Se) derivatives
  125. Biosurfactants in biocorrosion and corrosion mitigation of metals: An overview
  126. Stimulus-responsive MOF–hydrogel composites: Classification, preparation, characterization, and their advancement in medical treatments
  127. Electrochemical dissolution of titanium under alternating current polarization to obtain its dioxide
  128. Special Issue on Recent Trends in Green Chemistry
  129. Phytochemical screening and antioxidant activity of Vitex agnus-castus L.
  130. Phytochemical study, antioxidant activity, and dermoprotective activity of Chenopodium ambrosioides (L.)
  131. Exploitation of mangliculous marine fungi, Amarenographium solium, for the green synthesis of silver nanoparticles and their activity against multiple drug-resistant bacteria
  132. Study of the phytotoxicity of margines on Pistia stratiotes L.
  133. Special Issue on Advanced Nanomaterials for Energy, Environmental and Biological Applications - Part III
  134. Impact of biogenic zinc oxide nanoparticles on growth, development, and antioxidant system of high protein content crop (Lablab purpureus L.) sweet
  135. Green synthesis, characterization, and application of iron and molybdenum nanoparticles and their composites for enhancing the growth of Solanum lycopersicum
  136. Green synthesis of silver nanoparticles from Olea europaea L. extracted polysaccharides, characterization, and its assessment as an antimicrobial agent against multiple pathogenic microbes
  137. Photocatalytic treatment of organic dyes using metal oxides and nanocomposites: A quantitative study
  138. Antifungal, antioxidant, and photocatalytic activities of greenly synthesized iron oxide nanoparticles
  139. Special Issue on Phytochemical and Pharmacological Scrutinization of Medicinal Plants
  140. Hepatoprotective effects of safranal on acetaminophen-induced hepatotoxicity in rats
  141. Chemical composition and biological properties of Thymus capitatus plants from Algerian high plains: A comparative and analytical study
  142. Chemical composition and bioactivities of the methanol root extracts of Saussurea costus
  143. In vivo protective effects of vitamin C against cyto-genotoxicity induced by Dysphania ambrosioides aqueous extract
  144. Insights about the deleterious impact of a carbamate pesticide on some metabolic immune and antioxidant functions and a focus on the protective ability of a Saharan shrub and its anti-edematous property
  145. A comprehensive review uncovering the anticancerous potential of genkwanin (plant-derived compound) in several human carcinomas
  146. A study to investigate the anticancer potential of carvacrol via targeting Notch signaling in breast cancer
  147. Assessment of anti-diabetic properties of Ziziphus oenopolia (L.) wild edible fruit extract: In vitro and in silico investigations through molecular docking analysis
  148. Optimization of polyphenol extraction, phenolic profile by LC-ESI-MS/MS, antioxidant, anti-enzymatic, and cytotoxic activities of Physalis acutifolia
  149. Phytochemical screening, antioxidant properties, and photo-protective activities of Salvia balansae de Noé ex Coss
  150. Antihyperglycemic, antiglycation, anti-hypercholesteremic, and toxicity evaluation with gas chromatography mass spectrometry profiling for Aloe armatissima leaves
  151. Phyto-fabrication and characterization of gold nanoparticles by using Timur (Zanthoxylum armatum DC) and their effect on wound healing
  152. Does Erodium trifolium (Cav.) Guitt exhibit medicinal properties? Response elements from phytochemical profiling, enzyme-inhibiting, and antioxidant and antimicrobial activities
  153. Integrative in silico evaluation of the antiviral potential of terpenoids and its metal complexes derived from Homalomena aromatica based on main protease of SARS-CoV-2
  154. 6-Methoxyflavone improves anxiety, depression, and memory by increasing monoamines in mice brain: HPLC analysis and in silico studies
  155. Simultaneous extraction and quantification of hydrophilic and lipophilic antioxidants in Solanum lycopersicum L. varieties marketed in Saudi Arabia
  156. Biological evaluation of CH3OH and C2H5OH of Berberis vulgaris for in vivo antileishmanial potential against Leishmania tropica in murine models
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 6.12.2025 from https://www.degruyterbrill.com/document/doi/10.1515/chem-2024-0098/html
Scroll to top button