Background: Aegle marmelos Corr. (Rutaceae) commonly known as ‘Indian Bael’ has been used as a brain tonic traditionally. However, despite this traditional use, not enough scientific report is present that can confirm the use of this plant in neurological disorders. Thus, the total sterols fraction and stigmasterol from the leaves of Aegle marmelos were investigated for antidepressant-like effect along with their possible mechanism(s) of action by primarily performing acute toxicity study of total sterols. Methods: An acute toxicological study was carried out at a single oral dose of 2000 mg/kg. Sign of toxicity was observed by estimating biochemical and performing histopathological analysis. For the antidepressant-like effect, different doses of total sterols (50-200 mg/kg, p.o. for seven days) and stigmasterol (5- 20 mg/kg, i.p. acute) were administered in mice using TST and FST models. To evaluate the mechanism of action, mice were pretreated with GABA, 5-HT, DA, adrenergic antagonists, and glutamate agonists. Furthermore, a neurochemical study was performed following TST and molecular docking study was also performed to determine the binding affinity of stigmasterol. Results: Total sterols fraction presents no sign of toxicity up to the oral dose of 2000 mg/kg. Oral treatment of total sterols and acute intraperitoneal treatment of stigmasterol (except 5 mg/kg) reduced the immobility time significantly. Pretreatment with pCPA (5-HT synthesis inhibitor) and NMDA (an agonist of the glutamate site) effectively reversed the immobility time of total sterols and stigmasterol (except pCPA) in TST. However, bicuculline (competitive GABA antagonist), haloperidol (D2 dopaminergic antagonist) and prazosin (α1 adrenergic antagonist) could not reverse the immobility time. Meanwhile, total sterols also effectively altered the hippocampus 5-HT and Glu levels. Also, the result of the molecular docking study depicted that stigmasterol has an affinity to the NMDA receptor. Conclusions: The present study suggests that the total sterols fraction did not produce any acute toxicity in rats. Also, we reported that total sterols, stigmasterol and sub-effective stigmasterol co-administration with fluoxetine significantly reduced the time of immobility in TST and FST confirmed the antidepressant-like effect of total sterols fraction and stigmasterol. Moreover, further findings suggest that the antidepressant-like effect of total sterols might be mediated by the serotonergic and glutamatergic systems. Whereas only the glutamatergic system was involved in the antidepressant activity of stigmasterol.

Heterocyclic compounds have been an interesting area for the study of synthesis and biological activity of novel oxadiazole derivatives for a long time. Heterocyclic compounds possess diverse biological properties that have led to intense study and research of these compounds. One of these compounds 1,3,4-Oxadiazole is a versatile heterocyclic nucleus is a novel molecule which attract the medicinal chemist to search a new therapeutic molecule. 1,3,4-oxadizole exhibited a wide range of biological activities which includes antimicrobial activity, anti-tubercular, anticonvulsant, antidiabetic, anti-allergic, enzyme inhibitors, anti-HIV activity, antipyretic activity, Immunosuppressive activity, Spasmolytic Activity, antioxidant activity, Anti-Alzheimer's activity cardiovascular acivity, anti-inflammatory, anti-tumor activity, insecticidal activity, CGRP receptor antagonists, anti-anthelmintic activities. Results of various derivatives of different oxadiazole and their substitutions with diverse biological activities are reviewed in present article.

Substituted N-acetyl-4-amino-benzenesulfonamide derivatives were designed using ChemDraw Ultra 7.0 and energy minimization of derivatives was achieved with Chem3D Pro of ChemOffice suit, keeping in view the structural requirements of pharmacophore. Their proposed synthesis along with in-silico study (docking analysis) in favor of antimicrobial activity has been shown in this work with the possible mechanism of reaction. Docking studies were carried out to study the binding properties of drugs with molecular targets with the help of AutoDock Vina (Python-Prescription 0.8). Titled compounds (CS, DPS, SRS and TS) exhibited good binding properties with molecular target pseudomonas aeruginosa exotoxin A in Lamarckian genetic algorithm based flexible docking studies.

In this study, the anxiolytic activity of Piper nigrum essential oil (PNEO) was evaluated in the elevated plus maze (EPM) and the antidepressant-like effect was evaluated through tail suspension test (TST) in mice. Flumazenil, a competitive inhibitor of GABA A receptor in the benzodiazepine site and WAY-100635 maleate salt, a 5-HT 1A receptor antagonist were used to find out the possible mechanism(s) of action of PNEO. To exclude the false-positive results due to the enhancement of the locomotor activity, the animals were submitted to open field test (OFT). We also measured monoamines levels of the mice brain after acute PNEO treatment. The data obtained from the study suggest that the anxiolytics and antidepressant-like effect of PNEO have observed in EPM and TST respectively in a dose-dependent manner after oral acute and repetitive treatment. WAY-100635, but not flumazenil was able to reverse the effect of PNEO in EPM and TST both, indicating the possible involvement of 5-HT 1A receptor. The neurochemical analysis showed no alteration in monoamine levels in mice brains. Furthermore, no locomotor impairment or sign of toxicity or changes in body weight or abnormalities in the biochemical parameters, except for a significant decrease in total cholesterol level was observed after treatment with PNEO. The findings suggest that Piper nigrum EO possesses a dual anxiolytic and antidepressant-like effect through the possible involvement of serotonergic transmission.

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