Diosmin: A Daboia russelii venom PLA2s inhibitor- purified, and characterized from Oxalis corniculata L medicinal plant

Ethnopharmacological relevance: Oxalis corniculata L is a medicinal plant that belongs to the Oxalidaceae family. It is a little, slow-growing plant with a frail appearance typically found in mild temperate and tropical areas like Pakistan and India. This plant also includes many other bioactive substances, including alkaloids, flavonoids, terpenoids, cardiac glycosides, saponins, phlobatannins, and steroids.Aim of the study: To investigate the anti-inflammatory effects of Compound diosmin, which is derived from Oxalis corniculata L, on VRV-PL-5 and VRV-PL-8a isolated from Vipera russelli.Materials and methods: Extraction, purification, and characterization of bioactive by TLC, HPTLC, FT-IR analysis, UV-Vis spectrophotometer, LC-MS/MS Analysis, NMR, XRD Analysis, In vitro evaluation, Circular dichroism spectroscopy, in vivo, and in silico studies.Results: In this study, the extract of Oxalis corniculata was evaluated for its in vitro and in vivo anti-inflammatory effect against PLA2. The methanolic extract decreased hemolytic activity by about 60% at 1:75 w/w and neutralized the hemolytic activity completely at 1:100 w/w concentration. Diosmin inhibited VRV-PL-5 and VRV-PL-8a in a dose-dependent manner, with the extent of inhibition being about 56% for VRV-PL-5120 & mu;M and VRV-PL-8a by 62% at the same concentration with IC50 concentrations of 87.08 & mu;M for VRV-PL-5 and 82.08 & mu;M for VRV-PL-8a, while at 75 & mu;M. Diosmin inhibited the hemolytic activity of VRV-PL-5 by about 85%, and at the same concentration, VRV-PL-8a inhibited by about 75%. UV-CD spectra at the IC50 concentration of diosmin disrupted the secondary structure of VRV-PL-5 & VRV-PL-8a. In vivo, studies showed decreased myotoxicity and cardiotoxicity of the VRV-PL-5 & VRV-PL-8a, which was seen in the decrease in cytoplasmic markers LDH and CPK levels in the serum when incubated with diosmin. Furthermore, Histopathological studies of Muscles and lungs revealed that diosmin considerably protects against cellular abnormality caused by VRV-PL-5 & VRV-PL8a. Molecular docking, MM/GBSA, and molecular dynamics simulation studies show that the diosmin is a potent inhibitor for VRV-PL-5 and VRV-PL-8a.Conclusion: This study shows that diosmin is a potentially effective VRV-PL-5 and VRV-PL-8a.