Antiophidic activity of the secondary metabolite lupeol isolated from Zanthoxylum monogynum

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 193, p. 38-47, APR 15 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 19/06172-4 - Bolsa de PD em busca de novos fármacos contra Hipercolesterolemia, baseados em marcadores genéticos e epigenéticos específicos da população brasileira
• Beneficiário: Glaucio Monteiro Ferreira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 16/12899-6 - Caracterização genômica, epigenômica e farmacogenômica de portadores de hipercolesterolemia familial na população brasileira
• Beneficiário: Mario Hiroyuki Hirata
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/24112-9 - Desenvolvimento de novos inibidores da HMG-CoA redutase, integrando estudos genéticos e modelagem molecular de pacientes dislipidêmicos
• Beneficiário: Glaucio Monteiro Ferreira
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado