Li Ke, Wang Ya-Jun, Wei Kun, Li Wen-Lin, Liu Yong-Bo, Hu Jun-Nan, Chang Wen-Guang, Zhang Wen-Xuan, Chen Long, Li Wei
College of Life Sciences, Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun 130118, China.
College of Chinese Medicinal Materials, Jilin Provincial International Joint Research Center for the Development and Utilization of Authentic Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.
Am J Chin Med. 2025;53(3):909-930. doi: 10.1142/S0192415X2550034X.
Diabetes mellitus (DM) is considered to be the most widespread epidemic worldwide, and diabetic nephropathy (DN) is one of the most serious diabetic complications. Its complex pathogenesis makes treatment of DN an ongoing medical challenge. Ginseng (. C. A Meyer) is a valuable medicinal herb with a long medicinal and culinary history. Ginsenoside Rg2 (Rg2), an important active component in ginseng, has effective inhibitory effects on lipogenesis and hepatic glucose production. However, the potential effect and mechanism of Rg2 on DN remain unclear. In this study, we investigated the effect of Rg2 on DN in high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic mice and high glucose (HG)-induced human kidney 2 (HK-2) cells. The results demonstrated that Rg2 significantly improved the levels of FBG, dyslipidemia and impaired kidney function in DN mice. Additionally, Rg2 decreased the phosphorylation levels of IKKβ, IκBα, and NF-κB p65, inhibited the activation of NLRP3 inflammasomes (NLRP3, ASC, and Caspase 1), and restrained release of inflammatory factors (IL-18 and IL-1[Formula: see text]. In HG-induced HK-2 cells, Rg2 showed similar inhibitory effects on pyroptosis via NF-κB/NLRP3 signaling pathways. Moreover, the effect of Rg2 on inhibiting the activation of NF-κB/NLRP3 signaling pathways may have a relationship to reducing the overproduction of reactive oxygen species (ROS), which is further supported by the ROS inhibitor N-acetylcysteine (NAC). In conclusion, our findings clearly indicated that Rg2 could prevent the progress of DN by inhibiting the activation of pyroptosis-related NF-κB/NLRP3 signaling pathways and , suggesting that Rg2 may be a novel and promising therapeutic agent in the treatment of DN.
糖尿病（DM）被认为是全球范围内最普遍的流行病，而糖尿病肾病（DN）是最严重的糖尿病并发症之一。其复杂的发病机制使得DN的治疗成为一个持续的医学挑战。人参（Panax ginseng C. A. Meyer）是一种具有悠久药用和烹饪历史的珍贵草药。人参皂苷Rg2（Rg2）是人参中的一种重要活性成分，对脂肪生成和肝脏葡萄糖生成具有有效的抑制作用。然而，Rg2对DN的潜在作用和机制仍不清楚。在本研究中，我们研究了Rg2对高脂饮食/链脲佐菌素（HFD/STZ）诱导的2型糖尿病小鼠和高糖（HG）诱导的人肾2（HK-2）细胞中DN的影响。结果表明，Rg2显著改善了DN小鼠的空腹血糖（FBG）水平、血脂异常和肾功能损害。此外，Rg2降低了IKKβ、IκBα和NF-κB p65的磷酸化水平，抑制了NLRP3炎性小体（NLRP3、ASC和Caspase 1）的激活，并抑制了炎性因子（IL-18和IL-1β）的释放。在HG诱导的HK-2细胞中，Rg2通过NF-κB/NLRP3信号通路对细胞焦亡表现出类似的抑制作用。此外，Rg2对NF-κB/NLRP3信号通路激活的抑制作用可能与减少活性氧（ROS）的过量产生有关，ROS抑制剂N-乙酰半胱氨酸（NAC）进一步支持了这一点。总之，我们的研究结果清楚地表明，Rg2可以通过抑制与细胞焦亡相关的NF-κB/NLRP3信号通路的激活来预防DN的进展，这表明Rg2可能是一种治疗DN的新型且有前景的治疗药物。
