Larvicidal mechanism of the rare sesquiterpene ishwarol B from Piper alatipetiolatum (Piperaceae) against Aedes aegypti, Anopheles darlingi, and Culex quinquefasciatus (Culicidae): oxidative damage, defense enzyme modulation, and acetylcholinesterase inhibition

IF 5.4 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
André Correa de Oliveira , Felipe Moura Araujo da Silva , Ingrity Suelen Sá , Maria Luiza Lima da Costa , Sergio Massayoshi Nunomura , Rosemary Aparecida Roque , Rita de Cássia Saraiva Nunomura
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Abstract

Dengue, Oropouche, lymphatic filariasis, and malaria remain serious public health problems in Brazil, transmitted by Aedes aegypti, Culex quinquefasciatus, and Anopheles darlingi resistant to pyrethroid insecticides. As alternatives, plant-derived natural insecticides have gained attention for their potential. In this study, we evaluated ishwarol B for its larvicidal activity and explored its mechanism of action against these mosquitoes. Ishwarol B exhibited larvicidal activity against all larvae (LC50 from 19.57 to 26.23 μg/mL) and a residual effect of approximately 50 % observed, accompanied by increased production of H2O2 (24.3 ± 5 to 41.0 ± 5 μmol of H2O2 per gram−1), lipid peroxidation (11.00 ± 2 to 22.67 ± 2 ηmol of MDA per gram−1), and protein oxidation (10.00 ± 1 to 17.00 ± nM of reactive carbonyls/mg protein). Additionally, there was an increase in the activity of SOD (14.33 ± 2 to 14.67 ± 8 mU/mg protein), CAT (10.47 ± 9 to 11.23 ± 1 mmol of H2O2 consumed/min/mg of protein), and GPx (11.91 ± 1 to 16.46 ± 2 mmol NADPH/min/mL). In contrast, AChE activity decreased (8.33 ± 1 to 6.67 ± 2 μmol/min/mg of protein), compared to negative control DMSO (105.30 ± 2 to 111.30 ± 3 μmol μmol/min/mg of protein), indicating enzymatic inhibition, further confirmed by an inhibition from 100 ± 0 to 4.41 ± 2 % (IC50 of 3.46 μg/mL). Molecular docking revealed a binding energy of −8.4 kcal/mol and Ki = 0.695 μM, indicating a favorable interaction between ishwarol B and the AChE active site including Trp441, Tyr493, Tyr494, Ser280, Phe449, Ile446, Leu444, Gly445, Pro450, and Cys447. These findings confirm the broad mechanism of action of ishwarol B, highlighting its potential as a natural larvicide against the mosquito vectors investigated.

Abstract Image

辣椒科倍半萜伊石华酚B对埃及伊蚊、达林按蚊和致倦库蚊的杀幼虫机理:氧化损伤、防御酶调节和乙酰胆碱酯酶抑制
登革热、欧罗波切病、淋巴丝虫病和疟疾仍然是巴西严重的公共卫生问题,由埃及伊蚊、致倦库蚊和对拟除虫菊酯杀虫剂具有抗药性的达林按蚊传播。作为替代品,植物源性天然杀虫剂因其潜力而备受关注。本研究对伊施沃罗B的杀幼虫活性进行了评价,并对其作用机制进行了探讨。Ishwarol B对所有幼虫均有杀幼虫活性(LC50为19.57 ~ 26.23 μg/mL),残留效应约为50%,同时H2O2产量(每克−1 H2O2含量为24.3±5 ~ 41.0±5 μmol)、脂质过氧化(每克−1 MDA含量为11.00±2 ~ 22.67±2 ηmol)和蛋白质氧化(每克−1蛋白质活性羰基含量为10.00±1 ~ 17.00±nM)增加。SOD(14.33±2 ~ 14.67±8 mU/mg蛋白)、CAT(10.47±9 ~ 11.23±1 mmol H2O2消耗/min/mg蛋白)、GPx(11.91±1 ~ 16.46±2 mmol NADPH/min/mL)活性均显著升高。与阴性对照DMSO(105.30±2 ~ 111.30±3 μmol μmol/min/mg蛋白)相比,AChE活性降低(8.33±1 ~ 6.67±2 μmol/min/mg蛋白),表明酶促抑制作用,抑制幅度为100±0 ~ 4.41±2% (IC50为3.46 μmol/ mL)。分子对接显示,ishwarol B与AChE活性位点Trp441、Tyr493、Tyr494、Ser280、Phe449、Ile446、Leu444、Gly445、Pro450、Cys447等存在良好的相互作用,结合能为−8.4 kcal/mol, Ki = 0.695 μM。这些发现证实了ishwarol B的广泛作用机制,突出了其作为一种天然杀幼虫剂对所调查的蚊虫媒介的潜力。
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来源期刊
CiteScore
7.70
自引率
3.90%
发文量
410
审稿时长
36 days
期刊介绍: Chemico-Biological Interactions publishes research reports and review articles that examine the molecular, cellular, and/or biochemical basis of toxicologically relevant outcomes. Special emphasis is placed on toxicological mechanisms associated with interactions between chemicals and biological systems. Outcomes may include all traditional endpoints caused by synthetic or naturally occurring chemicals, both in vivo and in vitro. Endpoints of interest include, but are not limited to carcinogenesis, mutagenesis, respiratory toxicology, neurotoxicology, reproductive and developmental toxicology, and immunotoxicology.
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