Unlocking the therapeutic potential of Catharanthus roseus leaves via in-vitro, in-vivo, and in-silico study.

Catharanthus roseus (L.) (CR), is a perennial flowering herb, has traditionally been used by local populations in South Asia, Africa, China and Malaysia to treat diabetes, cancer and microbial infection. The principal objective of this study was to investigate the antidiabetic, antilipidemic and antiarthritic effects of methanol (MCR) and ethanol (ECR) extracts and dichloromethane fraction (DCR) of Catharanthus roseus leaves by in-vitro, in-vivo, and in-silico model. The in-vivo antihyperglycemic activity of C. roseus was explored in streptozotocin (STZ)-induced Type- 1 diabetic mice model. MCR, ECR and DCR exhibited a significant ability to lower fasting blood glucose levels and normalized the altered body weight when treatment was carried out for 20 days in a dose-dependent manner. Among the experimental samples, ECR at 200 mg/kg (4.95 ± 0.31 mmol/L) showed greater fasting blood glucose lowering activity than the standard drugs metformin (6.8 ± 0.34 mmol/L), and glibenclamide (5.20 ± 0.29 mmol/L). MCR at 200 mg/kg, likewise significantly (p < 0.001) reduced the blood glucose (5.70 ± 0.12 mmol/L) compared to the control at day 20. The lipid profile (LDL, HDL, TG, and TC) of diabetic mice was significantly reduced by ECR in a biochemical study compared to the control group. The in-vitro antidiabetic study revealed a dose-dependent hypoglycemic potential of the extracts and fraction; where ECR showed the highest α-amylase and α-glucosidase inhibitory effects with the IC50 value of 0.62 ± 0.02 mg/ml and 0.64 ± 0.01 mg/ml respectively. The antiarthritic activity was assessed by using bovine serum albumin denaturation inhibition assay and the denaturation was found to be inhibited by all extracts and fraction. The MCR and DCR fractions inhibited the denaturation by 70.20% and 62.09%, respectively, at 1600 µg/mL compared to the standard aspirin (81.57%). Moreover, the Gas chromatography-Mass spectrometric (GC-MS) investigation of the extract revealed several bioactive constituents and the in-silico docking study suggested that Ergost- 5-en- 3-ol, (3.beta.)-; Stigmasterol; 9,19-Cyclolanostan- 3-ol, acetate, (3.beta.)-;.gamma.-Sitosterol, and 24-Norursa- 3,12-diene would be the probable lead compounds for hypoglycemic and antiarthritic effect in many potential targets, however, further mechanistic and experimental elucidation is needed to solidify our findings.