In Silico and In Vitro Evaluation of Antiobesogenic and Osteoprotective Effect of Pomegranate Juice Fermented by Tannin Acyl Hydrolase and Lactobacillus vespulae DCY75 via the Wnt/β-Catenin Pathway

Obesity is associated with chronic inflammation, which can disrupt bone homeostasis, leading to osteoporosis. In this study, we investigated the potential antiobesogenic and osteoprotective effects of fermented pomegranate (PG-F) juice by elucidating its impact on the Wnt/β-catenin signaling pathway. First, employing molecular docking and dynamics, we confirmed the stable binding of ellagic acid and gallic acid with target proteins for both obesity and osteoporosis. In vitro experiments on 3T3-L1 adipocytes demonstrated that PG-F effectively inhibited adipocyte differentiation by downregulating adipogenic transcription factors and suppressing inflammatory cytokines, including TNF-α and IL-6. Furthermore, PG-F treatment promoted osteoblast differentiation in MC3T3-E1 cells, evidenced by an elevated alkaline phosphatase activity and upregulated osteogenic gene expression. Importantly, PG-F treatment led to significant activation of the Wnt/β-catenin pathway during adipogenesis and osteogenesis, as evidenced by increased β-catenin and LRP6 expression. These promising findings highlight the potential of PG-F juice as a novel therapeutic agent for managing both obesity and osteoporosis by modulating the Wnt/β-catenin pathway.