Wu Jiabin, Li Ke, Zhou Muge, Gao Haoyang, Wang Wenhong, Xiao Weihua
Shanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai, 200438, China.
J Pharm Anal. 2024 Aug;14(8):100946. doi: 10.1016/j.jpha.2024.01.014. Epub 2024 Feb 6.
Diabetic nephropathy (DN), a severe complication of diabetes, is widely recognized as a primary contributor to end-stage renal disease. Recent studies indicate that the inflammation triggered by Toll-like receptor 4 (TLR4) is of paramount importance in the onset and progression of DN. TLR4 can bind to various ligands, including exogenous ligands such as proteins and polysaccharides from bacteria or viruses, as well as endogenous ligands such as biglycan, fibrinogen, and hyaluronan. In DN, the expression or release of TLR4-related ligands is significantly elevated, resulting in excessive TLR4 activation and increased production of proinflammatory cytokines through downstream signaling pathways. This process is closely associated with the progression of DN. Natural compounds are biologically active products derived from natural sources that have advantages in the treatment of certain diseases. Various types of natural compounds, including alkaloids, flavonoids, polyphenols, terpenoids, glycosides, and polysaccharides, have demonstrated their ability to improve DN by affecting the TLR4 signaling pathway. In this review, we summarize the mechanism of action of TLR4 in DN and the natural compounds that can ameliorate DN by modulating the TLR4 signaling pathway. We specifically highlight the potential of compounds such as curcumin, paclitaxel, berberine, and ursolic acid to inhibit the TLR4 signaling pathway, which provides an important direction of research for the treatment of DN.
糖尿病肾病（DN）是糖尿病的一种严重并发症，被广泛认为是终末期肾病的主要原因。最近的研究表明，Toll样受体4（TLR4）引发的炎症在DN的发生和发展中至关重要。TLR4可以与各种配体结合，包括外源性配体，如来自细菌或病毒的蛋白质和多糖，以及内源性配体，如双糖链蛋白聚糖、纤维蛋白原和透明质酸。在DN中，TLR4相关配体的表达或释放显著升高，导致TLR4过度激活，并通过下游信号通路增加促炎细胞因子的产生。这一过程与DN的进展密切相关。天然化合物是源自天然来源的生物活性产物，在某些疾病的治疗中具有优势。各种类型的天然化合物，包括生物碱、黄酮类化合物、多酚、萜类化合物、糖苷和多糖，已证明它们能够通过影响TLR4信号通路来改善DN。在这篇综述中，我们总结了TLR4在DN中的作用机制以及可以通过调节TLR4信号通路改善DN的天然化合物。我们特别强调了姜黄素、紫杉醇、黄连素和熊果酸等化合物抑制TLR4信号通路的潜力，这为DN的治疗提供了一个重要的研究方向。
