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Jiabin Wu, Ke Li, Muge Zhou, Haoyang Gao, Wenhong Wang, Weihua Xiao. Natural compounds improve diabetic nephropathy by regulating the TLR4 signaling pathway[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.01.014
Citation: Jiabin Wu, Ke Li, Muge Zhou, Haoyang Gao, Wenhong Wang, Weihua Xiao. Natural compounds improve diabetic nephropathy by regulating the TLR4 signaling pathway[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.01.014
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Natural compounds improve diabetic nephropathy by regulating the TLR4 signaling pathway

doi: 10.1016/j.jpha.2024.01.014

  • Shanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai, 200438, China

Funds:

This study was sponsored by the National Natural Science Foundation of China (Grant No.: 32371185), the Shanghai Science and Technology Plan Project, China (Project No.: 23010504200), the “Shuguang Program” (Program No.: 20SG50) funded by Shanghai Education Development Foundation and Shanghai Municipale Education Commission, China, the Shanghai Talent Development Fund, China (Grant No.: 2020125), the Key Lab of Exercise and Health Sciences of Ministry of Education (Shanghai University of Sport, China) (Grant No.: 2022KF001), and the Shanghai Key Lab of Human Performance (Shanghai University of Sport, China) (Grant No.: 11DZ2261100).

  • Received Date: Sep. 09, 2023
  • Accepted Date: Jan. 31, 2024
  • Rev Recd Date: Dec. 12, 2023
  • Available Online: Feb. 20, 2024
    Abstract
  • 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.
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