Molecular Docking Study of Phytosterols in Lygodium microphyllum Towards SIRT1 and AMPK, the in vitro Brine Shrimp Toxicity Test, and the Phenols and Sterols Levels in the Extract.

Background: Lygodium microphyllum is a fern plant with various pharmacological activities, and phytosterols were reported contained in the n-hexane and ethyl acetate extract of this plant. Phytosterols are known to inhibit steatosis, oxidative stress, and inflammation. Sirtuin 1 (SIRT1) and adenosine monophosphate-activated protein kinase (AMPK) are the key proteins that control lipogenesis. However, information about L. microphyllum on SIRT1 and AMPK is still lacking. Purpose: This study aims to investigate the binding mode of phytosterols in L. microphyllum extract towards AMPK and SIRT1, and the toxicity of the extract against brine shrimp (Artemia salina) larvae, and to determine the phenols and sterols levels in the extract. Methods: The molecular docking was performed towards SIRT1 and AMPK using AutoDock v4.2.6, the toxicity of the extract was assayed against brine shrimp (Artemia salina) larvae, and the phytosterols were analyzed by employing a thin layer chromatography densitometry, and the total phenols were by spectrophotometry. Results: The molecular docking study revealed that ß-sitosterol and stigmasterol could occupy the active allosteric-binding site of SIRT1 and AMPK by binding to important residues similar to the protein's activators. The cold extraction of the plant yields 15.86% w/w. Phytochemical screening revealed the presence of phenols, steroids, flavonoids, alkaloids, and saponins. The total phenols are equivalent to 126 mg gallic acid (GAE)/g dry extract, the total sterols are 954.04 µg/g, and the ß-sitosterol level is 283.55 µg/g. The LC50 value of the extract towards A. salina larvae is 203.704 ppm. Conclusion: Lygodium microphyllum extract may have the potential to be further explored for its pharmacology activities, particularly in the discovery of plant-based anti-dyslipidemic drug candidates. However, further studies are needed to confirm their roles in alleviating lipid disorders.

Role of the AMPK/SIRT1 pathway in non­alcoholic fatty liver disease (Review).

Non­alcoholic fatty liver disease (NAFLD) is an increasingly prevalent ailment worldwide. Moreover, de novo lipogenesis (DNL) is considered a critical factor in the development of NAFLD; hence, its inhibition is a promising target for the prevention of fatty liver disease. There is evidence to indicate that AMP­activated protein kinase (AMPK) and sirtuin 1 (SIRT1) may play a crucial role in DNL and are the regulatory proteins in type 2 diabetes mellitus, obesity and cardiovascular disease. Therefore, AMPK and SIRT1 may be promising targets for the treatment of NAFLD. The present review article thus aimed to summarize the findings of clinical studies published during the past decade that suggested the beneficial effects of AMPK and SIRT1, using their specific activators and their combined effects on fatty liver disease.

Quercetin promotes behavioral recovery and biomolecular changes of melanocortin-4 receptor in mice with ischemic stroke.

OBJECTIVES: Ischemic stroke is known as a common causes of disability, lower psychological well-being as well as preventable death. The pathogenesis of ischemic stroke process becomes worse immediately after oxidative stress occurs. One of the flavonoids with antioxidant abilities is quercetin. This study was aimed to investigate quercetin administration on the behavioral functions (motor and sensory) and expression of melanocortin-4 receptor (MC4R) in mice with ischemic stroke. METHODS: Male ICR mice were divided into sham, stroke, stroke with quercetin 100, 150, and 200 mg/kg. The stroke model was performed by blocking the left common carotid artery for 2 h. Quercetin was intraperitoneally administered daily for seven days. Evaluation was conducted during two weeks after induction using ladder rung walking test and narrow beam test for motoric function and adhesive removal tape test for sensory function. On day-14 mice were sacrificed, MC4R expression in the dorsal striatum was determined using RT-PCR. RESULTS: Stroke decreased the motor, sensory function and MC4R mRNA expression in dorsal striatum. Quercetin improved motor and sensory function, and upregulated expression of MC4R. CONCLUSIONS: Quercetin administration after ischemic stroke improves behavioral function, possibly through the upregulation of MC4R in the brain.

Quercetin attenuates acute predator stress exposure-evoked innate fear and behavioral perturbation.

Background Oxidative stress plays a pivotal role in the pathophysiology and pathogenesis of mental diseases, such as depression or anxiety. Psychological stress induced by predatory stimulus is one of the models that explain how induced affective behavior is manifested as a depression-like state. Quercetin is a flavonoid that exhibits potential pharmacological activity on mental diseases. Thus, the present study was designed to investigate the effect of quercetin on innate fear and affective behavior induced by repeated predator stress exposure on mice. Materials and methods ICR mice were exposed to predatory stress for 3 days. Quercetin at a dose of 50 mg/kg was given intraperitoneally along with stress induction. The freezing behavior during the stress induction was analyzed. The anxiety-like and depressive-like behaviors and cognitive and motor functions were examined on the last day of induction. Results Predatory stress increased the affective behaviors (anxiety-like and depressive-like behaviors) and produced freezing behavior without alterations in the cognitive function and exploratory behavior. Treatment with quercetin 50 mg/kg attenuated the freezing, anxiety-like and depressive-like behaviors. Conclusions Repeated predator stress exposure causes both innate fear and depression-like state for the prey animals. Quercetin may have a protective effect against depression and alleviates the fear of traumatic events.