The rise in mental health disorders has increased interest in novel natural therapeutic approaches beyond pharmacological interventions. Psychobiotics are live microorganisms that confer mental health benefits and have emerged as a promising intervention targeting the gut-brain axis. Evidence from preclinical studies demonstrated that psychobiotics can restore neurotransmitter balance by modulating pro-inflammatory cytokines and enhancing the expression of brain-derived neurotrophic factor. However, significant challenges remain, including the limited availability of clinical studies, determining optimal dosages, and understanding the long-term benefits of specific psychobiotic strains and their application in food matrices. This review highlights the findings from recent studies to identify psychobiotics' capability on tryptophan metabolism and their role in facilitating the synthesis of serotonin to propose a mechanistic framework for microbe-driven serotonin. While the eukaryotic pathways of serotonin biosynthesis are well defined, the specific mechanism by which bacteria contribute to this synthesis remains less understood; elucidating this metabolic link is essential. Beyond mechanism, this review evaluates the synergy between psychobiotics and food matrices to showcase the therapeutic approach to address the limitations of current interventions.

Duchenne Muscular Dystrophy (DMD) is a severe X-linked genetic disorder caused by a mutation in the dystrophin gene. Current treatments primarily rely on symptomatic management of DMD pathophysiology by corticosteroid treatment, as exon skipping drugs are inaccessible to the majority of the DMD population due to their high treatment cost. However, long-term corticosteroid treatment is associated with a range of adverse effects. To address this, we developed a peptide library derived from a myogenesis-promoting micropeptide and identified M.P-2 as a lead candidate for promoting myogenesis. M.P-2 was further engineered to E.M.P-2, a mitochondrial-targeted peptide to address DMD's secondary pathologies. E.M.P-2 promotes myogenic differentiation by upregulating MyHC and MyoD at a nanomolar dose (0.156 μM) while suppressing fibrosis. It effectively chelates calcium ions to reduce mitochondrial reactive oxygen species (ROS), and maintain mitochondrial membrane potential. E.M.P-2 also demonstrates significant potential in modulating inflammation via inhibiting the expression of IL-6 and TGFβ. Mechanistically, E.M.P-2 functions through inhibition of mitoROS-driven activation of the NF-κB pathway, which collectively promotes myogenesis, suppresses fibrosis, and manages inflammation. Overall, E.M.P-2 holds potential for addressing DMD pathophysiology as the first peptide-based therapeutic providing a safer alternative to corticosteroids.

The global surge in plastic production and inadequate waste management have resulted in widespread environmental contamination with microplastics (MPs). Derived either as primary particles from consumer products or as secondary fragments from the degradation of larger plastics, MPs are now omnipresent in terrestrial, aquatic, and atmospheric ecosystems. Their small size, durability, and surface reactivity enable biofilm formation, heavy metal adsorption, and easy entry into food chains, ultimately posing significant risks to human health. This review outlines the sources, types, human exposure, including dietary intake, inhalation, and dermal contact, and their toxicological impacts on multiple organ systems. MPs can cross biological barriers, including the gastrointestinal epithelium, blood-brain barrier, and placenta, leading to distribution and bioaccumulation. Mechanistically, they induce oxidative stress, inflammation, immune dysregulation, and disruption of the gut microbiota. In the digestive system, MPs impair intestinal integrity, inhibit digestive enzymes, and promote hepatic inflammation. Inhalation alters pulmonary surfactant function, triggers cytokine release, and is implicated in asthma, fibrosis, and chronic obstructive pulmonary disease. MPs also function as endocrine-disrupting chemicals, interfering with hypothalamic–pituitary axes and reproductive hormones, thereby affecting fertility and development. Neurological consequences include oxidative stress-mediated neurotoxicity, neuroinflammation, and potential links to neurodegenerative disorders. Additionally, chronic exposure to MPs and associated additives may promote carcinogenesis by inducing DNA damage, persistent inflammation, and immune evasion. Collectively, these findings highlight MPs as emerging environmental toxins with wide-ranging adverse effects on human health. Further mechanistic studies and regulatory interventions are essential to mitigate exposure and address this growing global health threat.

Flavone derivatives of natural products are often synthesized to enhance their structural specificity, target selectivity, and bioavailability. The current study aimed to examine the neuroprotective efficacy of flavone derivative in diabetic associated neurodegenerations through systematic assessments of in-silico and in-vivo. The synthesized flavone (2-phenyl-4H-chromen-4-one) was characterized by NMR spectroscopy and FTIR. The in-vivo assessments were performed by following the serum biochemistry of homeostatic model assessment (HOMA), antioxidant and histopathology of cortex and hippocampus. The in-silico assessment of molecular docking showed -6.6 Kcal/mol with dipeptidyl peptidase-4 enzyme (DPP4), -7.8 with acetylcholinesterase (AChE), and -9.5 with butyrylcholinesterase (BuChE). The diabetic neurodegeneration model was induced by the chemical induction method and treated with the test compound at a dose of 40 mg/kg in comparison to sitagliptin. The treatment of the test compound showed significant alterations in the cortex and hippocampus region with mitigated neuronal injuries which endorsed by expressions targeted genes including glucose transporter 3 (GLUT-3), glycogen synthase kinase 3 beta (GSK-3β), microtubule associated protein (MAP)-Tau, and peroxisome proliferator-activated receptor gamma (PPARγ). Furthermore, the lipid profile and oxidative stress were ameliorated significantly by the course of treatment. In conclusion, the synthesized flavone has significant capability to promote neuroprotective effects in diabetes associated neurodegeneration through mitigating oxidative stress and modulating the expression of the targeted genes, thereby alleviating neuronal injuries.

Skeletal muscle is a highly organized tissue possessing an intrinsic regenerative capacity; however, severe injury often results in incomplete functional recovery due to persistent inflammation and fibrotic tissue deposition. Current therapeutic strategies rely on anti-inflammatory drugs, stem cell therapies, and growth factors but have shown limited clinical success. Herein, we developed a micropeptide-inspired stapled peptide, M.R., which exhibits potent regenerative capacity at nanomolar concentrations with enhanced stability and efficacy by promoting myogenic differentiation, modulating inflammation, and limiting fibrosis. Further, M.R was encapsulated within a borax-functionalized guar gum hydrogel, providing a biocompatible platform for sustained release of therapeutic lead and promoting muscle repair following a cryolesion-induced muscle injury model. Overall, this study introduces a first-in-class peptide-based therapeutic lead, M.R., encapsulated within a biocompatible hydrogel platform for promoting muscle repair through a multidimensional regenerative approach.

The current study was carried out to explore the neuroprotective efficacy of the synthesized compound 2-(1,3-benzodioxol-5-yl)-4H-chromen-4-one 5 (2BDC45) in diabetes-associated neurodegeneration through in silico and in vivo assessments. In silico exploration of molecular docking showed a significant binding energies of -8.5, -9.3, and -7.4 kcal/mol for 2BDC45 against the target enzymes, i.e., acetylcholinesterase, butyrylcholinesterase, and DPP-4, respectively. These findings were further confirmed through 100 ns molecular dynamics simulations, assessing parameters like RMSD, RMSF, SASA, MMPBSA, and PCA. Treatment with 2BDC45 exhibited the neuroprotective changes in the hippocampus and cortex regions of type 2 diabetes-associated neurodegenerations. Consequently, histopathological analysis of these brain regions, supported by molecular biological analyses of key genes such as GLUT-3, GSK, MAP, and PPARγ corroborated the neuroprotection. The lipid profile, HOMA, and antioxidants exhibited notable changes by the interference of the treatments. The treatments shown significant ameliorations in glucose metabolism by following the expressions of GLUT-3 and GSK, while MAP kinase and PPARγ showed significant restorations in the cortex and hippocampus. In conclusion, it can be implied the test flavone derivative has the capacity to amplify neural plasticity by following the scavenging of free radicals, improved glucose metabolism, and targeted genes expression.

Background Small molecule phytocompounds can potentially ameliorate degenerative changes in cerebral tissues. Thus, the current study aimed to evaluate the neuroprotective efficacy of phytocompounds of methanolic shoots extract of Calligonum polygonoides L. (MSECP) in hypercholesterolemia-associated neurodegenerations. Methods Phytochemical screening of the extract was made by LCMS/MS and validated by a repository of the chemical library. The hypercholesterolemia was induced through the intraperitoneal administration of poloxamer-407 with a high-fat diet. The in-silico assessments were accomplished by following the molecular docking, ADME and molecular dynamics. MMPBSA and PCA (Principal Component Analysis) analyzed the molecular dynamics simulations. Consequently, in-vivo studies were examined by lipid metabolism, free radical scavenging capabilities and histopathology of brain tissues (cortex and hippocampus). Results 22 leading phytocompounds were exhibited in the test extract, as revealed by LC-MS/MS scrutiny. Molecular docking evaluated significant interactions of apigenin triacetate with target proteins (HMGCR (HMG-CoA reductase), (AChE-Acetylcholinesterase) and (BuChE- Butyrylcholinesterase). Molecular dynamics examined the interactions through assessments of the radius of gyration, RSMD, RSMF and SASA at 100 ns, which were further analyzed by MMPBSA (Molecular Mechanics Poisson-Boltzmann) and PCA (Principal Component Analysis). Accordingly, the treatment of test extract caused significant alterations in lipid profile, dyslipidemia indices, antioxidant levels and histopathology of brain tissues. Conclusion It can be concluded that apigenin triacetate is a potent phytoconstituent of MSEPC and can interact with HMGCR, AChE, and BuChE, which resulted in improved hypercholesterolemia along with neuroprotective ameliorations in the cortex and hippocampus.

Phytochemicals, have long been studied for various severe metabolic illnesses and degenerative diseases like heart disease and cancer because of their significant therapeutic effects. In animal cells, cholesterol serves a critical role being a component of cell membranes and essential for the normal functioning of precursor cells to some steroid hormones. Three-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) is converted into mevalonate by the HMG-CoA Reductase (HMGCR) enzyme to produce cholesterol. However, when cholesterol levels are high, it may result in atherosclerosis. Statins, also known as synthetic drugs which decrease cholesterol, are therefore designed to work by targeting this enzyme. For patients with dyslipidemia, the side effects of excessive statin therapy have proven alarming hence using natural plant-based inhibitors is a promising alternative. Computational approach helps to identified many drugs that can target HMG-CO A Reductase. In this study, using in-silico molecular docking via auto-dock, 20 medicinal plants with 120 phytochemicals, reported as having antihyperlipidemic activity through deep literature study, were screened as HMG-CoA reductase enzyme inhibitors. The virtual molecular docking results reveals that five bioactive compounds; Sominone, Guggulsterone, Phytosterol, Withanolide A and Basilol, had higher binding affinities towards the HMG-CO A Reductase having binding energies of -9.33, -8.99, -8.87, -8.58, and -8.48 kcal/mol, respectively. ADMET properties of selected compounds were analysed using swiss adme tool. Results showed that out of five compounds three follow Lipinski rule of five, having ADMET properties. The HMG-CoA reductase-ligand complex's stability was validated by RMSD, RMSF, Rg, H-bond results and principal component analysis. The resulting trajectories of converged period of MD were further exploited in MM-P/G/BSA calculations to derive accurate estimates of binding free energies. This leads one to the conclusion that five phytochemicals, Sominone, Guggulsterone, Phytosterol, Withanolide A and Basilol can serve as potential inhibitors in regulating HMGCR's function may assist the development of effective anti-hyperlipedemic drugs.

Consumers increasingly prefer natural agents that provide health benefits beyond basic nutrition. Among naturally available bioresources, mushrooms are globally recognized as a "nutritional powerhouse" due to their significant therapeutic and nutraceutical properties. This review comprehensively explores relevant strategies for extracting bioactive compounds, including mushroom-derived polysaccharides, proteins, and peptides, detailing their well-established immunomodulatory roles pertinent to emerging health challenges. It also examines the development of mushroom bioactive-based immunity-enhancing functional foods. Furthermore, advancements in targeted delivery systems, particularly encapsulation techniques, are featured, ensuring compound stability during storage and enhancing bioavailability. The integration of mushroom bioactives into functional foods requires compliance with stringent safety and regulatory frameworks; consequently, the regulatory landscape governing mushroom-based functional products is also addressed.

Diabetes often leads to neurodegenerative complications that complicate treatment. Exploring dietary components with neuroprotective properties could offer new therapeutic avenues. This study aimed to evaluate the neuroprotective potential of β-sitosterol against diabetes-associated neurodegenerative complications using a combined in silico and in vivo approach. β-Sitosterol exhibited significant neuroprotective effects in a diabetic neuropathy model. Compared to sitagliptin, β-sitosterol demonstrated stronger binding affinities to DPP4, acetylcholinesterase, and butyrylcholinesterase, along with more stable molecular dynamics profiles. In vivo, β-sitosterol treatment markedly improved glucose tolerance, insulin sensitivity, lipid profiles, and antioxidant capacity. Histological analysis revealed reduced neurodegenerative changes and enhanced neuronal integrity in the cortex and hippocampus. These findings suggest β-sitosterol as a promising therapeutic agent for managing diabetic neurodegeneration, warranting further research and potential clinical application.

In Alzheimer's disease (AD), deposition of toxic Aβ42 oligomers causes excessive internalization of 2A subunit dominant NMDA receptors (GluN2A subtype) from the synaptic region. This causes a significant reduction of the synaptic glutamate interaction site. The absence of GluN2A propagates spillage of glutamate to the extrasynaptic space, where it interacts with the 2B subunit dominant NMDA receptor (GluN2B subtype). This interaction causes excessive Ca2+ influx and perturbation of autophagy, thus disrupting mitochondrial membrane potential and producing reactive oxygen species, causing neuronal death. In this context, our hypothesis suggests that selective inhibition of extrasynaptic GluN2B receptors could produce multifaceted outcomes against AD. Our aim is to devise a neuromelanin mimicking nanovesicle, particularly targeting extrasynaptic GluN2B. A conceptualized nanovesicle is designed to be larger than the synaptic cleft space (>100 nm) with the decoration of novel GluN2B targeting peptides. Therefore, we envision that this engineered nanomaterial will only inhibit the extrasynaptic GluN2B-mediated Ca2+ excitotoxicity and also revive homeostatic autophagy.

Calligonum polygonoides L. is a desertic plant used for the therapeutics of several metabolic disorders and ethnomedicines. Current study was assigned to examine the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition targeted hypocholesterolemic potential of Calligonum polygonoides L. through in silico, in vitro and in vivo assessments. The LC-MS/MS screening of the aqueous shoot extract showed leading compounds and structural data retrieved from an authentic repository of PubChem. The interactions of HMG-CoA reductase (HMGR) and ligands complex were examined using molecular docking. Significant interaction was shown by dihydrocelastrol with the target enzyme (HMGCR) up to a binding energy of-8.9 Kcal/mol. The assessments of Root Mean Square Deviation, Root Mean Square Fluctuation, radius of gyration, and Solvent Accessible Surface Area along with Molecular Mechanics-Poisson-Boltzmann Surface Area and PCA were examined by GROMACS 2020.2 of best-docked complexes at 100 ns with standards. Consequently, the competent HMGCR inhibition performed by the test extracts up to 75.8% (IC50 = 219.5 mu M) through in vitro assessments. Encouragingly, the treatment of test extract showed significant reductions in lipid profile, dyslipidemia indices, and glucose level along with ameliorations in oxidative stress. Subsequently, significant restorations were revealed in the arterial wall of the coronary arteries. Based on the results, it can be concluded that dihydrocelastrol is a potent bioactive phytocompound that can inhibit the HMGCR and significantly reduce hypercholesterolemia.

Abstract Traditional medicinal plants have attracted scientific interest due to their bioactive compounds, and the levels of their constituents vary with location and altitude. The present study was designed to evaluate the pharmacological potential of two traditional medicinal plants, Mikania micrantha and Ageratum huostonianum; these were collected from two sites, Murlen National Park (MNP) and Dampa Tiger Reserve (DTR), which are located at different altitudes. Both plant species are used by local traditional healers in Mizoram, Northeast India, for the treatment of various health problems. We hypothesized that altitudinal variation would affect these plants' chemical composition and bioactive potential. Plant extracts were evaluated for antioxidant, antimicrobial, and cytotoxic activities. The results show that the plants located at a higher altitude, i.e., MNP, showed higher TPC (615.7 ± 0.58 and 453.80 ± 0.95 µg gallic acid equivalents/mg of plant extract dry weight (µg GAE/mg) for M. micrantha and A. huostonium, respectively) and TFC (135.4 ± 0.46 and 120.66 ± 1.93 µg quercetin equivalents/mg of plant extract dry weight (µg GE/mg) for M. micrantha and A. huostonium, respectively). The extract of A. houstonianum (MNP) exhibited significantly greater antioxidant activity against ABTS radicals (IC50 241.6 µg/mL) as compared to the extract of A. houstonianum (DTR) (IC50 371.2 µg/mL). The composition of the bioactive compounds present in the plants was determined using UPLC-ESI MS/MS and GC/MS, which detected five and ten compounds in the A. houstonianum and M. micrantha extracts, respectively. Plant species collected from the Murlen National Park site had high bioactivity potential and contained several bioactive compounds. A distinct variation between the volatile and non-volatile compounds was revealed. The collective data in this study show the influence of altitude on the biological compound production of selected medicinal plants. The findings will be utilized in determining the plant material needed for the development of bioactive formulations.

Mental illness is a hidden epidemic in modern science that has gradually spread worldwide. According to estimates from the World Health Organization (WHO), approximately 10% of the world's population suffers from various mental diseases each year. Worldwide, financial and health burdens on society are increasing annually. Therefore, understanding the different factors that can influence mental illness is required to formulate novel and effective treatments and interventions to combat mental illness. Gut microbiota, consisting of diverse microbial communities residing in the gastrointestinal tract, exert profound effects on the central nervous system through the gut-brain axis. The gut-brain axis serves as a conduit for bidirectional communication between the two systems, enabling the gut microbiota to affect emotional and cognitive functions. Dysbiosis, or an imbalance in the gut microbiota, is associated with an increased susceptibility to mental health disorders and psychiatric illnesses. Gut microbiota is one of the most diverse and abundant groups of microbes that have been found to interact with the central nervous system and play important physiological functions in the human gut, thus greatly affecting the development of mental illnesses. The interaction between gut microbiota and mental health-related illnesses is a multifaceted and promising field of study. This review explores the mechanisms by which gut microbiota influences mental health, encompassing the modulation of neurotransmitter production, neuroinflammation, and integrity of the gut barrier. In addition, it emphasizes a thorough understanding of how the gut microbiome affects various psychiatric conditions.

Traditional medicinal plants have attracted scientific interest due to their bioactive compounds, and the levels of their constituents vary with location and altitude. The present study was designed to evaluate the pharmacological potential of two selected traditional medicinal plants, Mikania micrantha and Ageratum houstonianum collected from two sites, Murlen National Park (MNP) and Dampa Tiger Reserve (DTR), located at different altitudes. Both plant species are used by local traditional healers in Mizoram, Northeast India, to treat various health problems. We hypothesized that altitudinal variation would affect these plants’ chemical composition and bioactive potential. Plant extracts were evaluated for antioxidant and cytotoxic activities. The results show that the plants located at a higher altitude, i.e., MNP, showed higher TPC (615.7 ± 0.58 and 453.80 ± 0.95 µg gallic acid equivalents/mg of plant extract dry weight (µg GAE/mg) for M. micrantha and A. houstonianum , respectively) and TFC (135.4 ± 0.46 and 120.66 ± 1.93 µg quercetin equivalents/mg of plant extract dry weight (µg GE/mg) for M. micrantha and A. houstonianum, respectively). The extract of A. houstonianum. (MNP) exhibited significantly greater antioxidant activity against ABTS radicals (IC50 241.6 µg/mL) as compared to the extract of A. houstonianum (DTR) (IC50 371.2 µg/mL). The composition of the bioactive compounds present in the plants was determined using UPLC-ESI MS/MS and GC/MS, which detected five and ten compounds in the A. houstonianum and M. micrantha extracts, respectively. Plant species collected from the Murlen National Park site had high bioactivity potential and contained several bioactive compounds. A distinct variation between the volatile and non-volatile compounds was revealed. The collective data in this study show the influence of altitude on the biological compound production of selected medicinal plants. The findings will be utilized in the plant material needed for developing bioactive formulations.

Diabetic retinopathy is governed by abnormal apoptosis, increased capillary pressure, and other linked pathology that needs an efficient treatment by multitargeted approaches. Thus, the current study aimed to explore the potential of inhibition of targeted enzymes (DPP4, ACE-2, and aldose reductase) and free radical scavenging capabilities of selected compounds (nafronyl or naftidrofuryl) through in silico and in vivo investigations. Significant binding energies were observed in complexes of aldolase reductase, angiotensin type 1 receptor, and DPP4 against the nafronyl and sitagliptin more than -7.5 kcal/mol. Further validation of free energy was confirmed by calculations of molecular mechanics Poisson-Boltzmann surface area (MMPBSA), and configurational stabilities examined by PCA (principal component analysis). Additionally, drug-likeness was examined by the Swiss ADME web tool, which showed significant findings. Consequently, in vivo experimentations showed significant inflammation and alterations in retinal layers of inner plexiform (inner limiting membrane, nerve fibers, and ganglionic cells), inner nuclear layer (bipolar cells and horizontal cells), and photoreceptors cells. Whereas the treatments (nafronyl and sitagliptin) caused significant improvements in the histoarchitecture of the retina. Additionally, the HOMA indices (IR-insulin resistance, sensitivity, and β cells functioning) and levels of free radicals were significantly altered in the diabetic control group in comparison to intact control. Nafronyl administration showed significant ameliorations in HOMA indices as well as antioxidant levels. Based on the results, it can be concluded that nafronyl efficiently interacts with target enzymes, which may result in potent inhibition and ameliorations in retinal histology as well as glucose homeostasis and antioxidants.

Respiratory tract infections remain the leading cause of morbidity and mortality worldwide. The burden is further increased by polymicrobial infection or viral and bacterial co-infection, often exacerbating the existing condition. Way back in 1918, high morbidity due to secondary pneumonia caused by bacterial infection was known, and a similar phenomenon was observed during the recent COVID-19 pandemic in which secondary bacterial infection worsens the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) condition. It has been observed that viruses paved the way for subsequent bacterial infection; similarly, bacteria have also been found to aid in viral infection. Viruses elevate bacterial infection by impairing the host’s immune response, disrupting epithelial barrier integrity, expression of surface receptors and adhesion proteins, direct binding of virus to bacteria, altering nutritional immunity, and effecting the bacterial biofilm. Similarly, the bacteria enhance viral infection by altering the host’s immune response, up-regulation of adhesion proteins, and activation of viral proteins. During co-infection, respiratory bacterial and viral pathogens were found to adapt and co-exist in the airways of their survival and to benefit from each other, i.e., there is a cooperative existence between the two. This review comprehensively reviews the mechanisms involved in the synergistic/cooperativity relationship between viruses and bacteria and their interaction in clinically relevant respiratory infections.

Abstract The therapeutics of COVID‐2 was significantly obtained from nutraceutical approaches based on traditional knowledges and long practices. The current study was aimed to investigate antiviral potential of small molecule phytochemicals of seeds of Nelumbo nucifera against the SARS‐CoV‐2 proteins. GC–MS analysis resulted in identifying 12 dominating small molecule phytocompounds from the seed extracts of the N. nucifera. Further, we selected RNA‐dependent RNA polymerases (RdRps), spike protein, and M protein of SARS‐CoV‐2 as antiviral targets and performed in silico analyses, including protein docking (ligands), ADMET predictions, and molecular dynamics (MD). The studies revealed that the molecular interactions (protein–ligands) of three target proteins, namely, RdRp, spike protein, and M‐protein, have significant binding energies with three different substrates, namely, 1‐(8′‐methylquinolin‐2′‐yl)‐2,3,4‐tri(methoxycarbonyl)‐6‐(1″,2″‐di(methoxycarbonyl)vinyloxy)benzene (binding energy −5.84 kcal/mol) 2(1H)‐pyrimidinone, 5‐chloro‐4,6‐diphenyl (binding energy −6.60 kcal/mol), and nickel, [2,8,12,18‐tetraethyl‐3,7,13,17‐tetramethyl‐21H,23H‐porphinato(2‐)‐N21,N22,N23,N24]‐, (SP‐4‐1) (binding energy −7.02 kcal/mol), respectively. The ADMET predictions show significant pharmacokinetic profiles of the druggability of the three compounds of different targets. The pharmacokinetic activities critical to predicting stages of the drug development process are gastrointestinal absorption and brain access. The MD simulation showed that the systems were stable, referring to them as a potentially effective treatment for SARS‐CoV‐2. Therefore, a possible initiative has been taken to evaluate three potent small molecules of antiviral phytocompounds made from typically edible N. nucifera seed to support the nutraceutical approach to COVID‐19 therapeutics.

The DPP-4 inhibition is an interesting target for the development of antidiabetic agents which promotes the longevity of GPL-1(Glucagon-like peptide 1). The current study was intended to assess DPP-4(Dipeptidyl Peptidase-4) inhibition mediated antidiabetic effect of phytocompounds of an aqueous fruit extract of Withania coagulans (Stocks) Dunal by in-vitro, in-silico and in-vivo approaches. The phytoconstituents screening was executed by LCMS (Liquid Chromatography with tandem mass spectrometry). The in-vitro and in-vivo, DPP-4 assays were performed by using available kits. The in-vitro DPP-4 activity was inhibited up to 68.3% by the test extract. Accordingly, in-silico determinations of molecular docking, molecular dynamics and pharmacokinetics were performed between the target enzyme DPP-4 and leading phytocompounds. The molecular dynamics authenticated the molecular docking data by crucial parameters of cytosolic milieu by the potential energy, RSMD (Root Mean Square Deviation), RSMF (Root Mean Square Fluctuation), system density, NVT (Number of particles at fixed volume, ensemble) and NPT (Number of particles at fixed pressure, ensemble). Accordingly, ADMET predictions assessed the druggability profile. Subsequently, the course of the test extract and the sitagliptin (positive control), instigated significant (p ≤ 0.001) ameliorations in HOMA indices and the equal of antioxidants in nicotinamide-streptozotocin induced type 2 diabetic animal model. Compassionately, the histopathology represented increased pancreatic cellular mass which caused in restoration of histoarchitectures. It has been concluded that phytoconstituents in W. coagulans aqueous fruit extract can regulate DPP-4, resulting in improved glucose homeostasis and enhanced endocrinal pancreatic cellular mass.Communicated by Ramaswamy H. Sarma.

ABSTRACTThe study was aimed to examine the HMG-CoA reductase (HMGCR) inhibition potential. The in-silico investigations followed the assessments of molecular docking, druggability and molecular dynamics. The molecular dynamics was performed at 100 ns by calculating interaction free energies, RSMD, RSMF, radius of gyration and SASA. Consequently, in-vivo examinations were performed by using a hypercholesterolemic rabbit animal model. The molecular docking showed significant interaction capabilities of myricetin as revealed by binding energy data up to −8.4 Kcal/mol. Accordingly, the data of molecular dynamics i.e. free energy, solvation free energy, radius of gyration, RSMD, RSMF and SASA were shown significant interaction capabilities of myricetin with HMGCR. Supportively, significant ameliorations were made in lipid profile, dyslipidemia indices and oxidative stress by the treatments of myricetin compared to quercetin and atorvastatin. Thus, it can be concluded that myricetin is a potent flavanol with significant potential for HMGCR inhibition and free radical scavenging capability.