Multi-target acaricidal mechanism of Myracrodruon urundeuva extracts against Rhipicephalus microplus: From reproductive interference to in silico enzyme inhibition.

Abstract

The increasing resistance of the cattle tick (Rhipicephalus microplus) to synthetic acaricides necessitates the search for effective bioproducts. This study investigated the bioactive potential of Myracrodruon urundeuva leaves, integrating traditional bioassays, histological analyses, and computational modeling to elucidate its possible mechanisms of action. Adult Immersion Tests (AIT) and Larval Packet Tests (LPT) highlighted the ethanolic extract (EE) as the most promising treatment: at concentrations of 75 and 100 mg mL-1. The EE not only eliminated over 81% of the larvae but also severely compromised the reproductive capacity of the females, achieving an efficacy of 86.05%. Although the aqueous extract (AE) demonstrated strong larvicidal action (74.03%), its efficacy regarding oviposition was limited. Histological micrographs revealed that EE treatment induces critical structural disorganization and intense vacuolization in oocytes, blocking progeny viability. UHPLC-HRMS analysis identified key flavonoids, such as quercetin, vitexin-2''-O-rhamnoside, and kaempferol-7-neohesperidoside, whose biological impacts were validated across two complementary fronts. Concurrently, in silico simulations demonstrated that these compounds possess high binding affinity for vital molecular targets, specifically acetylcholinesterase (-8.212 kcal/mol) and cytochrome P450 (-8.9 kcal/mol). Altogether, these findings support the hypothesis that M. urundeuva may act through a multi-target mechanism by potentially affecting neuromuscular and metabolic homeostasis, reinforcing the interest in EE as a potential candidate for integrated R. microplus management.