title: Lupeol derivative mitigates Echis carinatus venom-induced tissue destruction by neutralizing venom toxins and protecting collagen and angiogenic receptors on inflammatory cells.
abstract: BACKGROUND
  Echis carinatus bite is a serious threat in South-Asian countries including India, as it causes highest number of deaths and terrifying long-term tissue destruction at the bitten site. Although venom metalloproteinases and hyaluronidases are the suggested key players, studies on the effect of venom on polymorphonuclear cells, peripheral blood mononuclear cells and platelets, and their role in long-term tissue destruction are still in infancy. While, the effect of venom on collagen receptors, integrin α2β1/GP VI/DDR1 and CX3CR1 chemokine receptor present on these cells is an untouched area.
  
  
  METHODS
  Lupeol, lupeol acetate, its synthetic derivatives 2-8 were screened for inhibition of E. carinatus venom induced-hemorrhage in mouse model where compound 8 was found to be the most potent. Further, compound 8 efficiently neutralized venom induced hemorrhage, edema, dermonecrosis, myonecrosis, myotoxicity, pro-coagulant, oxidative stress, inflammatory cytokines and cleavage of collagen and CX3CR1 receptors on inflammatory cells in in vivo, in silico, ex vivo and in vitro studies.
  
  
  CONCLUSIONS
  This study for the first time demonstrated the cleavage of collagen receptors and the receptor for angiogenesis and wound healing by the venom and its inhibition by compound 8, as these are important for firm adhesion of inflammatory cells at the damaged site to resolve inflammation and promote tissue repair.
  
  
  CONCLUSIONS
  This study provides a lead in venom pharmacology, wherein, compound 8 could be a therapeutic agent for the better management of viper venom-induced long-term tissue destruction.
authors.affiliation: Department of Studies in Biochemistry, University of Mysore, Mysore, Karnataka, India.
authors.forename: G D
authors.initials: GD
authors.lastname: Katkar
authors.affiliation: Department of Studies in Biochemistry, University of Mysore, Mysore, Karnataka, India.
authors.forename: Rachana D
authors.initials: RD
authors.lastname: Sharma
authors.affiliation: Department of Studies in Biochemistry, University of Mysore, Mysore, Karnataka, India.
authors.forename: G J
authors.initials: GJ
authors.lastname: Vishalakshi
authors.affiliation: Department of Studies in Biochemistry, University of Mysore, Mysore, Karnataka, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Naveenkumar
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Madhur
authors.affiliation: Department of Studies in Biochemistry, University of Mysore, Mysore, Karnataka, India.
authors.forename: R M
authors.initials: RM
authors.lastname: Thushara
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India. Electronic address: t_narendra@cdri.res.in.
authors.forename: T
authors.initials: T
authors.lastname: Narender
authors.affiliation: Department of Studies in Biochemistry, University of Mysore, Mysore, Karnataka, India. Electronic address: ksgbaboo@gmail.com.
authors.forename: K S
authors.initials: KS
authors.lastname: Girish
authors.affiliation: Department of Studies in Biochemistry, University of Mysore, Mysore, Karnataka, India. Electronic address: kemparajuom@gmail.com.
authors.forename: K
authors.initials: K
authors.lastname: Kemparaju
mesh_terms: D000818:Animals; D000997:Antivenins / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism*; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic; D053978:Pentacyclic Triterpenes / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects*; D014757:Viper Venoms / Q000633:toxicity*; D000094042:Lupanes
chemical_list: D000997:Antivenins; D003094:Collagen; D053978:Pentacyclic Triterpenes; D011956:Receptors, Cell Surface; D014757:Viper Venoms; C010480:lupeol; D000094042:Lupanes
keywords: Collagen receptors; E. carinatus; Inflammatory cells; Local toxicity; Lupeol; Venom