STUDY ON THE MOLECULAR MECHANISM OF THE CHINESE HERBAL MEDICINE CYNANCHUM PANICULATUM FOR TREATING SNAKEBITES

C. paniculatum is a traditional Chinese herb and widely used in the remedy of venomous snakebites; however, its efficacy of snakebite envenoming lacks enough experimental evidence, and its underlying molecular mechanism remains unknown.In this study, one bioactive component was screened and isolated from C. paniculatum by organic solvent extraction, column chromatography and HPLC in combination, and finally identified as paenonlide by MS and NMR techniques.The animal experiments and histological pathological sections showed that panenonlide remarkably inhibited hemorrhage, edema and muscle tissue necrosis induced by Deinagkistrodon acutus venom; meanwhile, it exhibited potent inhibitory effects on the fibrinogenolytic and PLA 2 activities of D. acutus venom in in vitro tests.Furthermore, molecular simulation revealed that paenonlide interacted with the key components in D. acutus venom, including metalloproteinase and PLA 2 , ultimately preventing the injury induced by snakebites.Taken together, this study revealed the molecular mechanism of snakebites treatment by using a traditional Chinese herb (C.Paniculatum), and experimentally evidenced its critical role in snakebites treatment.This may also shed light on developing new drugs in clinics.