关键词: 2型糖尿病；人参皂苷Rb1；免疫调节；Hippo通路；核因子-κB通路

Abstract: This study systematically evaluated the effects of ginsenoside Rb1 on glucose metabolism and immune function, focusing on its relationship with the Hippo signaling pathway. To this end, db/db diabetic mice were gavaged with ginsenoside Rb1 at doses of 40, 80 or 160 mg/kg for six weeks, and metformin was used as a positive control. The results showed that compared with the model group, ginsenoside Rb1 significantly reduced fasting blood glucose levels and decreased the area under the curve (AUC) in the oral glucose tolerance test (P < 0.01), and also inhibited the rate of body mass gain (P < 0.05). Ginsenoside Rb1 intervention effectively lowered the levels of pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α)) in serum and spleen, reduced malondialdehyde (MDA) levels, and enhanced superoxide dismutase (SOD) activity in spleen tissue (P < 0.05), thereby alleviating systemic and splenic oxidative stress damage and improving spleen index. Western blot analysis revealed that compared with the model group, ginsenoside Rb1 suppressed the phosphorylation of nuclear factor-κB (p-NF-κB) p65 protein in spleen tissue. It also upregulated the ratio of phosphorylated mammalian sterile 20-like kinase 1 (p-MST1) to total MST1 (p-MST1/MST1) and that of phosphorylated large tumor suppressor kinase (p-LATS) to total LATS (p-LATS/LATS) (both p-MST1 and p-LATS are key proteins of the Hippo signaling pathway), thereby promoting the phosphorylation of the downstream effector molecule Yes-associated protein (YAP) and leading to a significant increase in the p-YAP/YAP ratio (P < 0.01). In conclusion, ginsenoside Rb1 may ameliorate immune imbalance in diabetic mice by activating the Hippo signaling pathway and inhibiting the NF-κB inflammatory pathway. This study provides a theoretical basis for the potential use of ginsenoside Rb1 as a dietary immunomodulatory agent for the adjunctive management of diabetes.

Key words: type 2 diabetes mellitus; ginsenoside Rb1; immunomodulation; Hippo signaling pathway; nuclear factor-κB pathway