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This study aims to assess the antidepressant and modulatory activities of citronellal (CIT) on duloxetine (DUX) and its possible underlying mechanisms through in vivo and in silico studies. Hence, the forced swimming test (FST), tail suspension test (TST), and open field test (OFT) were carried out. Mice were treated with different doses of CIT (50, 100, and 200 mg/kg, p.o.), while DUX (15 mg/kg, p.o.) was used as a positive control and a vehicle served as a negative control. Additionally, molecular docking was conducted to evaluate binding interactions. Results demonstrated that CIT dose‐dependently and significantly (p < 0.05) alleviated immobility time in both the FST and TST. At a dose of 200 mg/kg, CIT showed notable effects with immobility times of 42.17 ± 3.70 and 70.17 ± 2.56 s in the FST and TST, respectively. In combination therapy, CIT (100 mg/kg) modulated the activity of DUX. However, antidepressant activity is confirmed by the OFT test, which reduced the locomotion activity. Further, CIT exhibited a moderate binding affinity (−6.1 kcal/mol) toward both the serotonin and norepinephrine reuptake transporters (SRT and NRT) by forming several bonds. In conclusion, CIT demonstrated moderate antidepressant activity, possibly by interacting with SRT and NRT. [ABSTRACT FROM AUTHOR]

Background: Cheilanthes tenuifolia (Burm.f.), commonly known as the Sword Fern or Narrow‐leaved Cloak Fern, is a little evergreen fern that belongs to the Pteridaceae family and is abundant in various bioactive compounds exerting promising medicinal properties. The current study is designed to evaluate in vivo analgesic and antidiarrheal activity of the methanol leaf extract of C. tenuifolia (MCT). Methods: For this purpose, Swiss albino mice were used to investigate the analgesic and antidiarrheal properties using acetic acid‐induced writhing and castor oil‐induced diarrhea methods, respectively. The mice were administered orally with different doses of MCT (125, 250, and 500 mg/kg). The vehicle performed as a negative control (NC), while diclofenac sodium (DCN) (25 mg/kg), loperamide (LOP) (3 mg/kg), bismuth subsalicylate (BSS) (10 mg/kg), and nifedipine (NDP) (2.5 mg/kg) were supplied as positive controls (PC) (p.o.). In both models, combination treatment of MCT (higher dose) and PC was also administered to different groups of animals for assessing potential antagonistic or synergistic activity. Results: Findings of the in vivo study demonstrated that MCT dose‐dependently significantly (p < 0.05) exhibited analgesic and antidiarrheal properties by reduction in the number of writhing and reductions in the total fecal output in contrast to the NC group. Moreover, in combination treatment, MCT significantly (p < 0.05) synergized the activity of PC in both models, exerting potential analgesic and antidiarrheal activity. Conclusion: In conclusion, MCT has analgesic and antidiarrheal activity; it might be beneficial for the management of pain and diarrhea. [ABSTRACT FROM AUTHOR]

Schizophrenia affects identification and disturbs our thinking and motivational capacity. Long‐term use of daidzin (DZN) is evident to enhance attention and memory in experimental animals. This study aimed to investigate the effect of DZN on Swiss mice. To check animals' attention, identification, thinking, and motivational ability, we performed behavioral studies using marble burying, dust removal, and trained swimming protocols. For this, a total of 36 male Swiss albino mice were randomly divided into six groups, consisting of 6 animals in each group, as follows: control (vehicle), DZN‐1.25, DZN‐2.5, DZN‐5 mg/kg, olanzapine (OLN)‐2, and a combination of DZN‐1.25 with OLN‐2. Additionally, in silico studies are also performed to understand the possible molecular mechanisms behind this neurological effect. Findings suggest that DZN dose‐dependently and significantly (p <.05) increased marble burying and removed dust while reducing the time to reach the target point. DZN‐1.25 was found to enhance OLN's effect significantly (p <.05), possibly via agonizing its activity in animals. In silico findings suggest that DZN has strong binding affinities of ‐10.1 and ‐10.4 kcal/mol against human serotonin 2 A (5‐HT2A) and dopamine 2 (D2) receptors, respectively. Additionally, DZN exhibits favorable pharmacokinetic and toxicity properties. We suppose that DZN may exert its attention‐ and memory‐enhancing abilities by interacting with 5‐HT2A and D2 receptors. It may exert a synergistic antischizophrenia‐like effect with the standard drug, OLN. Further studies are required to discover the exact molecular mechanism for this neurological function in animals. [ABSTRACT FROM AUTHOR]

Insomnia is a sleep disorder in which you have trouble falling and/or staying asleep. This research aims to evaluate the sedative effects of fraxin (FX) on sleeping mice induced by thiopental sodium (TS). In addition, a molecular docking study was conducted to investigate the molecular processes underlying these effects. The study used adult male Swiss albino mice and administered FX (10 and 20 mg/kg, i.p.) and diazepam (DZP) (2 mg/kg) either separately or in combination within the different groups to examine their modulatory effects. After a period of 30 min, the mice that had been treated were administered (TS: 20 mg/kg, i.p.) to induce sleep. The onset of sleep for the mice and the length of their sleep were manually recorded. Additionally, a computational analysis was conducted to predict the role of gamma‐aminobutyric acid (GABA) receptors in the sleep process and evaluate their pharmacokinetics and toxicity. The outcomes indicated that FX extended the length of sleep and reduced the time it took to fall asleep. When the combined treatment of FX and DZP showed synergistic sedative action. Also, FX had a binding affinity of −7.2 kcal/mol, while DZP showed −8.4 kcal/mol. The pharmacokinetic investigation of FX demonstrated favorable drug‐likeness and strong pharmacokinetic characteristics. Ultimately, FX demonstrated a strong sedative impact in the mouse model, likely via interacting with the GABAA receptor pathways. [ABSTRACT FROM AUTHOR]

The nano size Cu-Zn ferrite particles substituted to Mg2+ and La3+ having general chemical formula MgxCu0.3Zn0.7-xLayFe2-yO4 (x = 0.1, 0.2, 0.3, 0.4, 0.5; and y = 0.0, 0.025, 0.050, 0.075, 0.10) prepared through sol-gel method. The prepared mixed metal oxide nanoparticles were characterized employing techniques such as X-ray diffraction (XRD), scanning electron microscopy (SEM) and vibrating sample magnetometer (VSM) analyses. The prepared MgxCu0.3Zn0.7-xLayFe2-yO4 magnetic nanoparticles were used as a efficient, recoverable and heterogeneous catalyst for the one-pot synthesis of quinoxalines 3(a–g) and 1,5-benzodiazepines 5(a–h) under mild reaction conditions in good yields. The recyclability of catalyst was tested for five times without significant decrease in the catalytic activity. Catalyst has been used for the synthesis of different derivatives of quinoxalines in short time (20 to 30 min) with 90 -97% yield. Also, different derivatives of 1,5-benzodiazepines have been synthesized in short time (15 to 30 min) with 89 -98% yield using the catalyst. [ABSTRACT FROM AUTHOR]

Thymol (THY), as the natural monoterpene phenol, acts against oxidative stress and inflammatory processes. This study aimed to evaluate the anti-inflammatory effects and possible molecular mechanisms of THY via formalin-induced mouse and egg albumin-induced chick models alongside molecular docking and molecular dynamic (MD) simulations. THY (7.5, 15, and 30 mg/kg) was investigated, compared to celecoxib and ketoprofen (42 mg/kg), as antiinflammatory standards. THY dose-dependently and significantly (p < 0.05) decreased paw-licking and edema diameter parameters in formalin (phases I and II) and egg albumin-induced models. Moreover, THY (15 mg/kg) exerted better anti-inflammatory effects in combination with the standard drug ketoprofen than alone and with celecoxib. In silico studies demonstrated elevated binding affinities of THY with cyclooxygenase-2 (COX-2) than the COX-1 enzyme, and the ligand binds at a similar location where ketoprofen and celecoxib interact. The results of MD simulations confirmed the stability of the test ligand. THY exerted anti-inflammatory effects on Swiss mice and young chicks, possibly by interacting with COX-2. As a conclusion, THY might be a hopeful drug candidate for the management of inflammatory disorders. [ABSTRACT FROM AUTHOR]

The present study was designed to evaluate the antiemetic activity of abietic acid (AA) using in vivo and in silico studies. To assess the effect, doses of 50 mg/kg b.w. copper sulfate (CuSO4⋅5H2O) were given orally to 2-day-old chicks. The test compound (AA) was given orally at two doses of 20 and 40 mg/kg b.w. On the other hand, aprepitant (16 mg/kg), domperidone (6 mg/kg), diphenhydramine (10 mg/kg), hyoscine (21 mg/kg), and ondansetron (5 mg/kg) were administered orally as positive controls (PCs). The vehicle was used as a control group. Combination therapies with the referral drugs were also given to three separate groups of animals to see the synergistic and antagonizing activity of the test compound. Molecular docking and visualization of ligand-receptor interaction were performed using different computational tools against various emesis-inducing receptors (D2, D3, 5HT3, H1, and M1–M5). Furthermore, the pharmacokinetics and toxicity properties of the selected ligands were predicted by using the SwissADME and Protox-II online servers. Findings indicated that AA dose-dependently enhances the latency of emetic retching and reduces the number of retching compared to the vehicle group. Among the different treatments, animals treated with AA (40 mg/kg) exhibited the highest latency (98 ± 2.44 s) and reduced the number of retching (11.66 ± 2.52 times) compared to the control groups. Additionally, the molecular docking study indicated that AA exhibits the highest binding affinity (− 10.2 kcal/mol) toward the M4 receptors and an elevated binding affinity toward the receptors 5HT3 (− 8.1 kcal/mol), M1 (− 7.7 kcal/mol), M2 (− 8.7 kcal/mol), and H1 (− 8.5 kcal/mol) than the referral ligands. Taken together, our study suggests that AA has potent antiemetic effects by interacting with the 5TH3 and muscarinic receptor interaction pathways. However, additional extensive pre-clinical and clinical studies are required to evaluate the efficacy and toxicity of AA. [ABSTRACT FROM AUTHOR]

Numerous previous studies reported that ferulic acid exerts anxiolytic activity. However, the mechanisms have yet to be elucidated. The current study aimed to investigate the anxiolytic effect of trans-ferulic acid (TFA), a stereoisomer of ferulic acid, and evaluated its underlying mechanism using in vivo and computational studies. For this, different experimental doses of TFA (25, 50, and 75 mg/kg) were administered orally to Swiss albino mice, and various behavioral methods of open field, hole board, swing box, and light–dark tests were carried out. Diazepam (DZP), a positive allosteric modulator of the GABAA receptor, was employed as a positive control at a dose of 2 mg/kg, and distilled water served as a vehicle. Additionally, molecular docking was performed to estimate the binding affinities of the TFA and DZP toward the GABAA receptor subunits of α2 and α3, which are associated with the anxiolytic effect; visualizations of the ligand-receptor interaction were carried out using various computational tools. Our findings indicate that TFA dose-dependently reduces the locomotor activity of the animals in comparison with the controls, calming their behaviors. In addition, TFA exerted the highest binding affinity (−5.8 kcal/mol) to the α2 subunit of the GABAA receptor by forming several hydrogen and hydrophobic bonds. Taken together, our findings suggest that TFA exerts a similar effect to DZP, and the compound exerts moderate anxiolytic activity through the GABAergic interaction pathway. We suggest further clinical studies to develop TFA as a reliable anxiolytic agent. [ABSTRACT FROM AUTHOR]

Anxiety is a natural response to stress, characterized by feelings of worry, fear, or unease. The current research was conducted to investigate the anxiolytic effect of indirubin (IND) in different behavioral paradigms in Swiss albino mice. To observe the animal's behavioural response to assess anxiolytic activity, different tests were performed, such as the open‐field (square cross, grooming, and rearing), swing, dark‐light, and hole cross tests. The experimental mice were administered IND (5 and 10 mg/kg, p.o.), where diazepam (DZP) and vehicle were used as positive and negative controls, respectively. In addition, a combination treatment (DZP+IND‐10) was provided to the animals to determine the modulatory effect of IND on DZP. Molecular docking approach was also conducted to determine the binding energy of IND with the GABAA receptor (α2 and α3 subunits) and pharmacokinetics were also estimated. The findings revealed that IND dose‐dependently significantly (p<0.05) reduced the animal's movement exerting calming behavior like DZP. IND also demonstrated the highest docking score (−7.7 kcal/mol) against the α3 subunit, while DZP showed a lower docking value (−6.4 kcal/mol) than IND. The ADMET analysis revealed that IND has proper drug‐likeness and pharmacokinetic characteristics. In conclusion, IND exerted anxiolytic effects through GABAergic Pathways. [ABSTRACT FROM AUTHOR]

This study explores the effectiveness of mid-infrared (MIR) spectroscopy in combination with chemometrics as an alternative to sensory analysis for detecting camel's milk adulteration with cow's milk. A paired comparison test involving various concentrations of adulterants was initially conducted to assess consumers' ability to detect such adulteration. The analysis successfully classified samples into adulterated and authentic camel's milk using principal component (PC) analysis and hierarchical cluster analysis. Moreover, the application of partial least squares regression and PC regression calibration models demonstrated high-performance capabilities in revealing the level of adulteration. These findings highlight the potential of MIR spectroscopy combined with chemometrics for the authentication of camel's milk. [ABSTRACT FROM AUTHOR]

Sesamol (SES) and linalool (LIN) are aromatic compounds that have neuroprotective effects. The main purpose of this study is to evaluate the anxiolytic activity of LIN and SES co-treatment on Swiss albino mice and analyze its possible mechanism through in silico study. In this sense, the mice were given the gamma-aminobutyric acid type A receptors (GABA A ) agonist diazepam (DZP; 3 mg/kg, p.o.) as a positive control. A vehicle (10 mL/kg) was served as control. The tested chemicals, single-dose LIN (50 mg/kg) and SES (50 mg/kg), as well as a combination (LIN + SES) and (DZP + LIN + SES), were administered orally in order to conduct several behavioral tests, including open-field, swings box, hole-crossing, and dark-resident time tests. Further, molecular docking studies of LIN, SES, and DZP were carried out through different software. The results showed that LIN and SES individually have significant anxiolytic-like activity in mice. Further, when LIN was combined with SES and with (SES + DZP), it exhibited a relatively lower locomotor activity in mice compared to individual treatment groups, indicating a synergistic action. In addition, the molecular docking analysis revealed that LIN and SES have a moderate binding affinity (-5.0 and -5.1 kcal/mol) toward the GABA A receptor α3 subunit. In conclusion, our findings suggest that LIN and SES exerted synergistic anxiolytic activity on Swiss albino mice, possibly through the GABAergic interaction pathways., (© 2024 Wiley Periodicals LLC.)

This study evaluates the anti-inflammatory effects of a natural product, piperine (PPN), using in vivo and in silico methodologies. In the in vivo segment, inflammation was induced in the right hind paw of young chicks via a formalin (50 μL) injection. PPN was orally administered at doses of 25 and 50 mg/kg with or without celecoxib (CXB) and/or ketoprofen (KPN) (42 mg/kg). The vehicle acted as the negative control group (NC). The in silico analysis predicted the drug-likeness, pharmacokinetics, and toxicity profile of PPN, along with evaluating its binding affinity and ligand-receptor interactions. Results indicate that PPN significantly ( p  < 0.05) reduced licking frequency and paw edoema in a dose-dependent manner. However, in combination therapy, PPN diminished the effects of both CXB and KPN. PPN showed high affinity (-8.6 kcal/mol) towards the COX-2 enzyme. Therefore, PPN exerts anti-inflammatory effects in chicks through COX-2 inhibition pathways and antagonises CXB and KPN activities.

Introduction: The area of "Green Synthesis of Nano-medicine," as compared to its synthetic counterparts, is a relatively safer research technology for various biomedical applications, including identification, therapeutic application, and prevention of pathological conditions, pain control, safety, and development of human wellness. The present study explored the synthesis and characterization of AgNPs using the ethanolic extract of Piper cubeba fruit as a reducing and stabilizing agent and its potential as an enzyme inhibitory agent. Urease inhibitors are helpful against many severe diseases, including gastric ulcers induced by Helicobacter pylori. Method: The fruits of the Piper cubeba plant were taken and ground to a fine powder. Plant material was added to 500 ml ethanol, and the mixture was filtered. The solvent of the filtrate was evaporated, and a thick, gummy extract was obtained and stored at 4°C in the refrigerator. AgNPs were green synthesized from solutions of AgNO3 using the P. cubeba extract, which was indicated by a change in the color from light brown to deep brown. The synthesized AgNPs were characterized via Ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM). Results and Discussion: Analysis showed the reduction of Ag+ to Ag0 at room temperature (25°C), and the average particle size of AgNPs was in the range of 40-80 nm. Consequently, the synthesized AgNPs were evaluated for their anti-urease activity. The maximum urease inhibition of the Piper cubeba ethanolic extract was 88.5% at 5 mg conc., and of derived nanoparticles was 78.6% at 0.05 mg conc. The results were nearly similar to the control drug, i.e., thiourea (0.5 and 0.6 mM conc., respectively). Conclusion: The study concluded that the P. cubeba extract, as well as its green-derived AgNPs, might prove to be a better and safer substitute for their enzyme inhibitory potential in emerging medicine and novel drug delivery techniques to improve and maintain human health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor TW declared a past co-authorship with the author MK., (Copyright © 2023 Ahmad, Asif, Afzal, Khan, Younus, Khurshid, Safdar, Saifulah, Ahmad, Sufyan, Ansari, Alkahtani and Ansari.)