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RISS 인기검색어
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- 저자 : Pukar Khanal (검색결과 4 건)
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α-Glucosidase inhibitors from Duranta repens modulate p53 signaling pathway in diabetes mellitus
Khanal Pukar,Patil B. M. 경희대학교 융합한의과학연구소 2020 Oriental Pharmacy and Experimental Medicine Vol.20 No.3
Hydroalcoholic extract/fraction(s) and scutellarein, a previously reported phytoconstituent from Duranta repens were evaluated for their α-glucosidase inhibitory activity using in vitro method. The reported phytoconstituents were also screened as α-glucosidase inhibitor, probable cytotoxicity, ADMET profile, and side effects via in silico models. Further, probable gene expression profile and pathways involved in diabetes/diabetes complications were also screened. Similarly, network was constructed among α-glucosidase inhibitors, modulated proteins and respective pathways and docking study was performed using autodock4.0. Fraction rich in flavonoids was found to possess the highest α-glucosidase inhibitory activity and the mode of inhibition was uncompetitive. The predicted α-glucosidase inhibitors were less cytotoxic to normal cells with lower side effects compared to acarbose. Similarly, gene-set enrichment analysis identified p53 signaling pathway to be primarily modulated by majority of phytoconstituents. Further, docking study revealed scutellarein to have highest binding affinity with α-glucosidase enzyme. In conclusion, present study identified the fraction rich in flavonoids to possess highest α-glucosidase inhibitory activity and could modulate p53 signaling pathway in diabetic pathogenesis.
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Network pharmacology of Withania somnifera against stress associated neurodegenerative diseases
Duyu Taaza,Khanal Pukar,Dey Yadu Nandan,Jha Sajal Kumar 경희대학교 융합한의과학연구소 2021 Oriental Pharmacy and Experimental Medicine Vol.21 No.3
Withania somnifera is a Rasayana of the Ayurvedic system of medicine that is widely used to treat stress-related neurological disorders. Although its anti-stress activity is reported in experimentally-induced stress models, the probable mechanism for neuroprotection has not been elucidated yet. Hence, the present study aimed to evaluate the effect of Withania somnifera against two neurodegenerative diseases (Parkinson’s and Alzheimer’s diseases) using a network pharmacology followed by molecular docking. The bioactives were retrieved from ChEBI and PCIDB databases; targets were predicted using BindingDB and were enriched via STRING. The combination synergy analysis of the constructed network was performed using Cytoscape. Similarly, molecular docking was performed using autodock4.0. Out of 45 phytoconstituents, 23 were predicted to modulate the proteins involved in the pathogenesis of Parkinson’s disease and Alzheimer’s disease. The combination synergy identified 10 and 6 targets interacting with 22 and 18 compounds in Parkinson’s disease and Alzheimer’s disease respectively. Pathways involved in Parkinson’s disease was cholinergic synapse; further cholinergic synapse and neuroactive ligand-receptor interaction were primarily involved in Alzheimer’s disease. Further, phytoconstituents-target-pathway interaction revealed that the highly modulated protein(s) involved in Parkinson’s disease was PRKCD whereas COX-1 and 2 in Alzheimer’s disease along with some common proteins in both. Network pharmacology analysis elucidated the probable molecular mechanisms of Withania somnifera in the management of stress-associated neurodegenerative diseases, identified the lead molecules, their targets, and possible pathways. However, the current findings are based on processor simulations and further experimental validation of the constructed network is still required to confirm the present findings.
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Nikita Kanbarkar,Sanjay Mishra,Pukar Khanal 경희대학교 융합한의과학연구소 2020 Oriental Pharmacy and Experimental Medicine Vol.20 No.4
Acacia suma Roxb. (Fabaceae) is Ayurvedic medicine distributed in Karnataka, Bengal and Bihar region. Phytoconstituents of A. suma were retrieved from ChEIB databases and queried for phospholipase A2 group IIA inhibitors. The present study is an effort to find out a novel therapeutic solution for the management of obesity disorders. Out of 29 reported compounds three were identified in modulating phospholipase A2 group IIA inhibitor their drug likeness score andprobable gene expression was identified. Docking study was performed using autodock4.0 to predict binding affinity of phytoconstituents with phospholipase A2 group IIA inhibitor and compared with clinically proven drug ‘Orlistat’ as lipase inhibitor. The respected pathway to show networking between phytochemicals and target were analyse by kyoto encyclopedia of genes and genomes pathway analysis for regulated genes. Further, in silico findings were validated for hydroalcoholic extract of A. suma by in vitro lipase inhibition assay. Molecular docking result revealed the presence of three flavonoid compounds for lipase inhibition activity namely: (1) (5S,7R,8R,9R,10S)-(−)-7,8–seco-7,8–oxacassa-13,15-diene-7,17-diol (2) Fisetinidol-(4α,6)-gallocatechin and (3) Quercetin4′-O-α-l-rhamnopyranosyl-3-O-β-d-allopyranoside. However, Quercetin4′-O-α-l-rhamnopyranosyl-3-O-β- d-allopyranoside was predicted to possess the highest docking score i.e. − 7.6 kcal/mol with phospholipase A2 group IIA. The in vitro findings revealed significant anti-lipase activity with IC50 value − 46.07 μg/ml. Hence, the in silico and in vitro approaches has presented strong binding affinity and significant lipase inhibition activity respectively which supports antiobesity potential of heart wood hydroalcoholic extract of A. suma.
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Biradar Prakash,Patil Vishal Supda,Joshi Hanumanthachari,Khanal Pukar,Mallapur Shamanand 경희대학교 융합한의과학연구소 2022 Oriental Pharmacy and Experimental Medicine Vol.22 No.1
This paper aimed to elucidate the effect of Erythrina variegata L. bark on scopolamine-induced memory impairment in rats and to decipher the molecular mechanism of phytoconstituents via the utilization of gene set enrichment analysis, network pharmacology coupled with in silico docking study. First, three models i.e. Morris Water Maze (MWM), Elevated Plus Maze (EPM), and Passive Avoidance Paradigm (PA) were utilized to elucidate the memory function. Second, the level of biomarkers i.e. acetylcholinesterase enzyme, reduced glutathione, and lipid peroxidation level were measured in brain tis- sues. Third, the key bioactive phytoconstituents targeting potential protein targets and pathways were identified through gene set enrichment analysis and network pharmacology. Lastly, the interaction between bioactive phytoconstituents with their respective targets was confirmed by molecular docking analysis. The MWM, EPM, and PA activity showed, scopolamine administration increased Escape Latency Time (ELT), Transfer Latency (TL), and Step Through Latency (STL) respectively on day 0th, 7th, 14th, and 21st, whereas treatment with E. variegata extract significantly reverse the ELT, TL and STL activ- ity. The decreased level of Acetylcholinesterase (AChE) and MDA level in treated animals reflected the enhanced memory and was found to be comparable withclinically proven drug i.e. donepezil. Sixty compounds were identified in EV bark, among which twenty-two compounds are predicted to modulate potential targets involved in AD and considered potentially bioactive. Further, the docking study revealed, Alpinumisoflavone, Auriculatin, Osajin, and Scandenone to have the highest binding affinity with Tau protein, Whereas Donepezil and Glucoerysodine with acetylcholinesterase enzyme.
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