دورية أكاديمية

Alkaloids from Siparuna (Siparunaceae) are predicted as the inhibitors of proteolysis and plasma coagulation caused by snake venom and potentially counteract phospholipase A 2 activity of Bothrops jararaca.

التفاصيل البيبلوغرافية
العنوان: Alkaloids from Siparuna (Siparunaceae) are predicted as the inhibitors of proteolysis and plasma coagulation caused by snake venom and potentially counteract phospholipase A 2 activity of Bothrops jararaca.
المؤلفون: Fernandes DA; Instituto de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Bloco H, Rio de Janeiro/RJ, 21941-902, Brazil. Electronic address: diegina@ufrj.br., Gomes BA; Programa de Pós-Graduação em Biotecnologia Vegetal e Bioprocessos, Universidade Federal do Rio de Janeiro, Rio de Janeiro/RJ, 21941-902, Brazil. Electronic address: brendoo.bc@ufrj.br., Mendonça SC; Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Bloco A2, Rio de Janeiro/RJ, 21941-902, Brazil. Electronic address: sy2802@gmail.com., Pinheiro CC; Programa de Pós-Graduação em Ciências Biomédicas - Fisiologia e Farmacologia, Universidade Federal Fluminense, Niteroi/RJ, 24210-130, Brazil. Electronic address: camilacaspin@gmail.com., Sanchez EOF; Laboratório de Bioquímica de Proteínas de Animais Venenosos, Centro de Pesquisa e Desenvolvimento, Fundação Ezequiel Dias, Belo Horizonte/MG, 30510-010, Brazil. Electronic address: eladio.flores@funed.mg.gov.br., Leitão SG; Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Bloco A2, Rio de Janeiro/RJ, 21941-902, Brazil. Electronic address: sgleitao@pharma.ufrj.br., Fuly AL; Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Niteroi/RJ, 24210-201, Brazil. Electronic address: andrefuly@id.uff.br., Leitão GG; Instituto de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Bloco H, Rio de Janeiro/RJ, 21941-902, Brazil. Electronic address: ggleitao@ippn.ufrj.br.
المصدر: Journal of ethnopharmacology [J Ethnopharmacol] 2024 Oct 05; Vol. 332, pp. 118349. Date of Electronic Publication: 2024 May 16.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Sequoia Country of Publication: Ireland NLM ID: 7903310 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7573 (Electronic) Linking ISSN: 03788741 NLM ISO Abbreviation: J Ethnopharmacol Subsets: MEDLINE
أسماء مطبوعة: Publication: Limerick : Elsevier Sequoia
Original Publication: Lausanne, Elsevier Sequoia.
مواضيع طبية MeSH: Bothrops* , Blood Coagulation*/drug effects , Crotalid Venoms*/toxicity , Plant Extracts*/pharmacology , Plant Extracts*/chemistry , Alkaloids*/pharmacology , Alkaloids*/isolation & purification , Alkaloids*/chemistry, Animals ; Brazil ; Proteolysis/drug effects ; Phospholipases A2/metabolism ; Phospholipase A2 Inhibitors/pharmacology ; Phospholipase A2 Inhibitors/isolation & purification ; Plant Leaves/chemistry ; Antivenins/pharmacology ; Antivenins/isolation & purification ; Protease Inhibitors/pharmacology ; Protease Inhibitors/isolation & purification ; Tandem Mass Spectrometry ; Bothrops jararaca
مستخلص: Ethnopharmacological Relevance: Snakebite envenomation (SBE) is the world's most lethal neglected tropical disease. Bothrops jararaca is the species that causes the greatest number of SBEs in the South and Southeastern of Brazil. The main symptoms are local (inflammation, edema, hemorrhage, and myonecrosis) and systemic (hemorrhage, hemostatic alterations with consumptive coagulopathy, and death) effects. Species of the genus Siparuna, Siparunaceae, are used in folk and traditional medicine to treat SBE. However, limited information is available concerning Brazilian Siparuna species against SBE.
Aim of the Study: To investigate the correlation between the compounds present in the extracts of five Siparuna species as potential agents against proteolytic activity, plasma coagulation, and phospholipase A 2 (PLA 2 ) activity caused by B. jararaca venom, using data obtained by UHPLC-MS/MS, biological activity, and multivariate statistics.
Materials and Methods: The ethanol extracts from leaves of S. ficoides, S. decipiens, S. glycycarpa, S. reginae, and S. cymosa were fractionated by liquid-liquid extraction using different solvents of increasing polarity (hexane, dichloromethane, ethyl acetate, and n-butanol), affording their respective extracts, totaling 25 samples that were assayed through in vitro plasma coagulation and proteolytic activity assays. Moreover, the extracts were analyzed by UHPLC-MS/MS, using electrospray ionization (ESI) and atmospheric-pressure chemical ionization (APCI) in negative and positive ionization modes. The data was processed in MZmine v. 2.53 and evaluated by multivariate statistical tests (PLS) using the software UnscramblerX v. 10.4. These data were also used to build molecular networks (GNPS), and some ions of interest could be annotated using the library of molecules on the GNPS platform.
Results: A total of 19 extracts inhibited B. jararaca-induced plasma coagulation, with emphasis on S. cymosa and S. reginae (800 s). The inhibition of the proteolytic activity was also promising, ranging from 16% (S. glycycarpa) to 99% (S. cymosa, S. decipiens, and S. reginae). In addition, most extracts from S. cymosa and S. reginae inhibited 70-90% of PLA 2 activity. Based on data from positive mode APCI analyses, it was possible to obtain a statistic model with reliable predictive capacity which exhibited an average R 2 of 0.95 and a Q 2 of 0.88, indicating a robust fit. This process revealed five ions, identified as the alkaloids: coclaurine (1), stepholidine (2) O-methylisopiline (3), nornantenine (4) and laurolitsine (5). This is the first study to evidence the potential antivenom of alkaloids from Siparuna species.
Conclusions: Altogether, our results give support to the popular use of Siparuna extracts in SBE accidents, suggesting their potential as an alternative or complementary strategy against envenoming by B. jararaca venom. The predicted ions in the chemometric analysis for the assayed activities can also be correlated with the blocking activity and encourage the continuation of this study for possible isolation and testing of individual compounds on the used models.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Alkaloids; Antivenom; Bothrops jararaca; Chemometrics; Natural product; Snakebite
المشرفين على المادة: 0 (Crotalid Venoms)
0 (Plant Extracts)
0 (Alkaloids)
EC 3.1.1.4 (Phospholipases A2)
0 (Phospholipase A2 Inhibitors)
0 (Antivenins)
0 (Protease Inhibitors)
تواريخ الأحداث: Date Created: 20240518 Date Completed: 20240611 Latest Revision: 20240611
رمز التحديث: 20240612
DOI: 10.1016/j.jep.2024.118349
PMID: 38762214
قاعدة البيانات: MEDLINE
الوصف
تدمد:1872-7573
DOI:10.1016/j.jep.2024.118349