In silico, in vitro, and invivo study on anti-hyperglycemic effect of catharanthus roseus (L.) G.Don syndrome virus (PRRSV)

Abstract

Catharanthus roseus (L.) G. Don (C. roseus) is a notable anticancer herb possessing high alkaloid content. Besides, this plant has been also traditionally used as an effective antidiabetic treatment in many Asian nations, such as Malaysia, India, and Vietnam. Recently, although some studies have demonstrated the anti-hyperglycemic effect its fractional extracts and metabolites were done on several animal models, the missing links in medicinal chemistry of these published compounds have not been connected. The main purpose of our study is to determine and estimate the anti-hyperglycemic activity of C. roseus in both computational and experimental aspects. The in silico part of this study measures the binding affinity of the compounds of C. roseus toward four target proteins including 11β-HSD1, PTP1B, α-glucosidase, and DPPIV for anti-hyperglycemic effect with further investigation of the molecular interaction modes inside the protein’s active sites. Molecular Dynamics (MD) simulation, structure-based virtual screening, and pharmacophore analysis were done to explain and suggest potent compounds. In experiment aspect, IC50 of fractional extracts on alpha-glucosidase and alpha-amylase was carried. Besides, anti-hyperglycemic test on diabetes-induced mice models was also performed together with toxicity assessment. The in silico result suggests 8 compounds (com_05, com_07, com_16, com_26, com_27, com_28, com_46, and com_56) as potent drug candidates for experimental confirmation. Besides, com_56 (Strictosidine lactam) and com_46 (Mitraphyllline) are supposed to be two best top-hit ligands with the extremely high docked score. Additionally, 11-β-HSD1 is supposed to be the most suitable receptor for experimental confirmation. The in vitro result confirmed the α-amylase-inhibitory activity of fractional extracts with the IC50 of ETH, DCM, EA, and FW extract is 0.102, 0.102, 0.0641 and 0.0301 mg/mL respectively while α-glucosidase-inhibitory activity of fractional extracts seems not very notable and the IC50 of most of the case are incapable of evaluating. The in vivo result indicates DCM and ETH are two extracts resulting in strong anti-hyperglycemic activity on diabetesinduced mice models. The LD50 of the total extract is higher than 5000 mg/kg bw while sub-acute toxicity test gives no evidence on long-term treatment of this total extract. Key words: C. roseus; structure-based virtual screening; anti-hyperglycemic; pharmacokinetics