Antiophidic activity of the secondary metabolite lupeol isolated from Zanthoxylum monogynum

Author(s)

Dos Santos, Benedito Matheus ^[1] ; Ferreira, Glaucio Monteiro ^{[1, 2]} ; Tavares, Mauricio Temotheo ^[3] ; De Bona, Julio Cesar ^[4] ; Hirata, Mario Hiroyuki ^[1] ; De Paula, Vanderlucia Fonseca ^[5] ; Saturnino, Klaus Casaro ^[6] ; Soares, Andreimar Martins ^{[7, 8]} ; Mendes, Mirian Machado ^[9]

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Hosp Tubingen, Internal Med 8, Dept Oncol & Pneumonol, Otfried Muller Str 10, DE-72076 Tubingen - Germany

^[3] Scripps Res, Dept Mol Med, Jupiter, FL 33458 - USA

^[4] Univ Hosp Tubingen, Inst Ophthalm Res, Elfriede Aulhorn Str 7, D-72076 Tubingen - Germany

^[5] State Univ Bahia Southwest, Dept Sci & Technol, Lab Nat Prod, BR-45208091 Jequire, BA - Brazil

^[6] Univ Fed Goias, Special Acad Unit Agr Sci, BR-75801615 Jatai, Go - Brazil

^[7] FIOCRUZ Rondonia, Ctr Study Biomol Appl Hlth CEBio, Lab Biotechnol Prot & Bioact Cpds Western Amazon, Oswald Cruz Fdn, BR-76812245 Porto Velho, RO - Brazil

^[8] Fed Univ Rondonia UNIR, BR-76812245 Porto Velho, RO - Brazil

^[9] Univ Fed Goias, Special Acad Unit Biosci, BR-75801615 Jatai, Go - Brazil

• Document type: Journal article
• Source: Toxicon; v. 193, p. 38-47, APR 15 2021.
• Web of Science Citations: 0

Abstract

Previous studies have demonstrated the potential antiophidic activity of Zanthoxylum monogynum A.St.-Hil. a tree from the Rutaceae family native to South America. In this present contribution, we demonstrate the activity of the metabolite lupeol, a triterpenoid isolated from the stem bark of Z. monogynum against the harmful effects of the Bothrops alternatus venom. We investigated the antiophidic properties of lupeol, for this purpose, and use crude venom (Pb) incubated with lupeol in different concentrations, testing in vitro experiments and inoculated in mice for inhibitory evaluations in vivo. Besides, we tried to elucidate through the molecular dynamics the mechanism of action of lupeol with the bothmpic thrombin-like toxin Jararacussin-I; the acidic phospholipase A(2) toxin BthA-I from Bothrops jararacussu and the metalloproteinase toxin BmooMP-I from Bothrops moojeni. In our results, we demonstrated the potential inhibitory effect upon coagulant, phospholipasic and myotoxic activities of the bothropic venom, previously incubated with lupeol. We found that lupeol triterpenoid was able to partially inhibit local and systemic damage caused by snake venom toxins. Our in silico results demonstrate that lupeol is capable of interacting and altering the activity of the thrombin-like toxin Jararacussin-I, and capable of interacting with the BthA-I acidic PLA(2), both toxins present in Bothrops snakes venom, thus demonstrating the pharmacological potential of this compound for the treatment of bothropic accidents. (AU)

• FAPESP's process: 19/06172-4 - Post-doctorate fellow in search of new drugs against Hypercholesterolemia, based on specific genetic and epigenetic markers of the Brazilian population
• Grantee: Glaucio Monteiro Ferreira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/12899-6 - Genomics, epigenomics and pharmacogenomics characterization of familial hypercholesterolemia in the Brazilian population
• Grantee: Mario Hiroyuki Hirata
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/24112-9 - Novel HMG-CoA reductase inhibitors development by integrating dyslipidemic patients' genetic studies and molecular modelling
• Grantee: Glaucio Monteiro Ferreira
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor