Caracterização química, atividades biológicas e mecanismos de ação do óleo essencial de Piper cyrtopodon (Miq.) C.DC (Piperaceae) contra Aedes aegypti (Diptera: Culicidae)

Abstract

Arboviral diseases transmitted by the mosquito Aedes aegypti, such as dengue, Zika, and chikungunya, continue to represent a major public health challenge, further aggravated by the vector’s resistance to synthetic insecticides. In this context, plant-derived products, particularly essential oils (EOs), have emerged as promising alternatives for vector control. Thus, this study evaluated the larvicidal and repellent potential of the EO from Piper cyrtopodon and its major constituents against A. aegypti, as well as their mechanisms of action and safety profile. The EO, obtained with a yield of 1.4%, was mainly composed of germacrene D (57.46%), cadina-1(10),4-diene (10.57%), and δ- Elemene (8.00%), which exhibited larvicidal activity, with LC50 values ranging from 20.78 to 146.61 µg/mL, with cadina-1(10),4-diene being the most active compound. This toxicity was associated with the induction of oxidative stress, evidenced by increased production of reactive oxygen species (ROS), lipid peroxidation, and alterations in antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). In repellent assays, the EO and its constituents showed significant activity, with a protection time of up to 270 minutes, comparable to N,Ndiethyl-meta-toluamide (DEET), with cadina-1(10),4-diene standing out due to its lowest EC50 value (2.31 mg/cm2). Molecular docking studies with odorant-binding proteins (OBP1 and OBP22) revealed strong binding affinities of the constituents, particularly cadina-1(10),4-diene, with binding energies of –8.4 and –7.3 kcal/mol, respectively, supporting a mechanism involving interference with the mosquito olfactory system. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses indicated high lipophilicity and low polarity of the constituents, favoring skin retention, with a variable predicted toxicological profile. Cytotoxicity assays in Vero and PBMC cells demonstrated high cell viability at lower concentrations, with dose-dependent reduction at higher levels observed only for the EO and cadina-1(10),4-diene. Overall, the results demonstrate that the EO from P. cyrtopodon acts through an integrated mechanism against the vector, combining larvicidal toxicity and repellent effects, highlighting its potential as a promising source of natural compounds for sustainable A. aegypti control strategies.