Berberine Impedes Acute Pancreatitis Development by Suppressing VNN1 Expression and the NF-κB Signaling Pathway.

The global incidence of acute pancreatitis (AP) is progressively increasing with rising risk factors such as hyperlipidemia and alcoholism. Berberine (BBR), a quaternary ammonium alkaloid and primary antibacterial agent isolated from the traditional Chinese herb, Coptis chinensis, was investigated for its therapeutic mechanisms in AP. Cell viability was first assessed using the MTT assay at various BBR concentrations, with lactate dehydrogenase (LDH) levels measured in parallel. Then, ELISA quantified inflammatory mediators (caspase-1, IL-1β, IL-18, TNF-α, and IL-6), while western blot analyzed pyroptosis markers (NLRP3 and N-GSDMD). ROS and Fe2+ levels were detected using commercial kits. Moreover, molecular docking was performed to determine the interaction between BBR and Vanin 1 (VNN1). In vivo experiments were further conducted to assess BBR's role in AP. MTT assays confirmed BBR's non-cytotoxicity at therapeutic concentrations. BBR attenuated caerulein-induced cellular damage and pyroptosis in HPDE6-C7 cells. Molecular docking revealed strong BBR-VNN1 binding affinity (less than -6 kcal/mol). Moreover, VNN1 knockdown attenuated caerulein-induced HPDE6-C7 cell injury and pyroptosis; BBR achieved this effect by inhibiting VNN1 protein expression. BBR suppressed VNN1 expression and NF-κB pathway activation (p-p65/p65 ratio). In vivo validation confirmed BBR-mediated AP suppression via VNN1 inhibition. BBR mitigates AP by inhibiting VNN1 expression, thereby suppressing NF-κB pathway activation and attenuating caerulein-induced cellular damage and pyroptosis.