Role of Esterase BmeFE4 in Mediating the Alleviating Effects of Resveratrol on NaF-Induced Fluorosis in Bombyx mori.

Fluoride exposure can induce tissue injury and oxidative stress dysregulation, ultimately leading to organismal dysfunction and death, whereas resveratrol (RSV) has been reported to counteract diverse oxidative injuries. Despite its antioxidant potential, the application of RSV is limited by its low bioavailability. Here, using a silkworm model, we established NaF exposure, RSV treatment, and combined RSV+NaF groups to investigate the mechanism by which RSV attenuates fluorosis. Comparative analyses of body weight, histopathological damage, and oxidative stress indices showed that RSV markedly mitigated NaF-induced toxicity. Candidate genes and proteins exhibiting concordant expression changes were identified through integrated RNA-seq and TMT-based quantitative proteomics, and subsequently validated by qPCR and PRM. Among these candidates, the esterase BmeFE4 emerged as a key regulator of the RSV-mediated detoxification response. Spatiotemporal profiling revealed that BmeFE4 was expressed throughout silkworm development, with the highest levels in the midgut. RNAi-mediated knockdown of BmeFE4 significantly altered NaF-related phenotypes and modulated oxidative-stress-related parameters, including superoxide dismutase (SOD) and catalase (CAT) activities, reduced glutathione (GSH) content, and malondialdehyde (MDA) levels, as quantified by ELISA. Collectively, these results indicate that RSV alleviates fluoride toxicity at least in part by upregulating BmeFE4, identifying this esterase as a potential molecular target for developing defluoridation agents.