Piperine Attenuates Bmal1-Mediated Glucose Metabolism Disorder in a Trpv1-Dependent Manner in HepG2 Cells

Piperine (PIP), a pungent alkaloid found in black pepper, has various pharmacological effects by activating the transient receptor potential vanilloid 1 (TRPV1) receptor. In this study, the regulating effect of PIP on glucose metabolism and the underlying mechanism were examined using an insulin-resistant cell model. Results showed that PIP alleviated glucosamine (GlcN)-induced glucose metabolism disorder (from 59.19 ± 1.90 to 88.36 ± 6.57%), restored cellular redox balance (from 148.43 ± 3.52 to 110.47 ± 3.52%), improved mitochondrial function (from 63.76 ± 4.87 to 85.98 ± 5.12%), and mitigated circadian disruption in HepG2 cells via the mediation of circadian clock gene Bmal1 . After the knockdown of the Trpv1 gene, the modulating effect of PIP on Bmal1 -mediated glucose metabolism was weakened, indicating that PIP alleviated Bmal1 -involved insulin resistance and circadian misalignment in a Trpv1 -dependent manner in HepG2 cells.