title: Quercetin-3-O-rhamnoside from Euphorbia hirta protects against snake Venom induced toxicity.
abstract: BACKGROUND
  The plant Euphorbia hirta is widely used against snake envenomations in rural areas and it was proved to be effective in animal models. Therefore, the scientific validation of its phytoconstituents for their antiophidian activity is aimed in the present study.
  
  
  METHODS
  E. hirta extract was subjected to bioactivity guided fractionation and the fractions that inhibited different enzyme activities of Naja naja venom in vitro was structurally characterized using UV, FT-IR, LC-MS and NMR spectroscopy. Edema, hemorrhage and lethality inhibition activity of the compound were studied in mice model. In addition, molecular docking and molecular dynamic simulations were also performed in silico.
  
  
  RESULTS
  The bioactive fraction was identified as Quercetin-3-O-α-rhamnoside (QR, 448.38 Da). In vitro experiments indicated that protease, phospholipase-A(2), hemolytic activity and hemorrhage inducing activity of the venom were inhibited completely at a ratio of 1:20 (venom: QR) w/w. At the same concentration, the edema ratio was drastically reduced from 187% to 107%. Significant inhibition (93%) of hyaluronidase activity was also observed at a slightly higher concentration of QR (1:50). Further, in in vivo analysis, QR significantly prolonged the survival time of mice injected with snake venom.
  
  
  CONCLUSIONS
  For the first time Quercetin-3-O-α-rhamnoside, isolated from E. hirta, has been shown to exhibit anti-snake venom activity against Naja naja venom induced toxicity.
  
  
  CONCLUSIONS
  Exploring such multifunctional lead molecules with anti-venom activity would help in developing complementary medicine for snakebite treatments especially in rural areas where anti-snake venom is not readily available.
authors.affiliation: School of Bio Sciences and Technology, VIT University, Vellore, Tamil Nadu 632 014, India.
authors.forename: Kadiyala
authors.initials: K
authors.lastname: Gopi
authors.affiliation: School of Bio Sciences and Technology, VIT University, Vellore, Tamil Nadu 632 014, India.
authors.forename: K
authors.initials: K
authors.lastname: Anbarasu
authors.affiliation: School of Bio Sciences and Technology, VIT University, Vellore, Tamil Nadu 632 014, India.
authors.forename: Kadali
authors.initials: K
authors.lastname: Renu
authors.affiliation: School of Bio Sciences and Technology, VIT University, Vellore, Tamil Nadu 632 014, India.
authors.forename: S
authors.initials: S
authors.lastname: Jayanthi
authors.affiliation: Department of Biochemistry, University of Mysore, Mysuru, Karnataka, India.
authors.forename: B S
authors.initials: BS
authors.lastname: Vishwanath
authors.affiliation: School of Bio Sciences and Technology, VIT University, Vellore, Tamil Nadu 632 014, India. Electronic address: gjayaraman@vit.ac.in.
authors.forename: Gurunathan
authors.initials: G
authors.lastname: Jayaraman
mesh_terms: D000818:Animals; D001681:Biological Assay; D005591:Chemical Fractionation / Q000379:methods; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000201:enzymology / Q000517:prevention & control; D004546:Elapid Venoms; D017815:Elapidae; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D028481:Euphorbia / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects; D006470:Hemorrhage / Q000201:enzymology / Q000517:prevention & control; D006821:Hyaluronoglucosaminidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D064801:Phospholipase A2 Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D011480:Protease Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D012909:Snake Bites / Q000188:drug therapy* / Q000201:enzymology; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D004546:Elapid Venoms; D004791:Enzyme Inhibitors; D064801:Phospholipase A2 Inhibitors; D010936:Plant Extracts; D011480:Protease Inhibitors; C012526:quercitrin; D011794:Quercetin; D006821:Hyaluronoglucosaminidase
keywords: Euphorbia hirta; Naja naja; PLA(2); Quercetin-3-O-rhamnoside; Snake venom