Identification of potent target and its mechanism of action of Tripterygium wilfordii Hook F in the treatment of lupus nephritis

Int J Rheum Dis. 2023 Aug;26(8):1529-1539. doi: 10.1111/1756-185X.14780. Epub 2023 Jun 14.

Abstract

Aim: The Chinese anti-rheumatic herbal remedy Tripterygium wilfordii Hook F (TWHF) has been widely shown to be effective in treating lupus nephritis (LN), but the therapeutic targets and mechanisms of action are still unclear. In this study, we aimed to combine mRNA expression profile analysis and network pharmacology analysis to screen the pathogenic genes and pathways involved in LN and to explore the potential targets of TWHF in the treatment of LN.

Methods: The mRNA expression profiles of LN patients were used to screen differentially expressed genes (DEGs) and to predict associated pathogenic pathways and networks via the Ingenuity Pathway Analysis database. Through molecular docking, we predicted the mechanism by which TWHF interacts with candidate targets.

Results: A total of 351 DEGs were screened from the glomeruli of LN patients and were mainly concentrated in the role of pattern recognition receptors in the recognition of bacteria and viruses and interferon signaling pathways. A total of 130 DEGs were screened from the tubulointerstitium of LN patients, which were concentrated in the interferon signaling pathway. TWHF might be effective in treating LN by hydrogen bonding to regulate the functions of 24 DEGs (including HMOX1, ALB, and CASP1), which are mainly concentrated in the B-cell signaling pathway.

Conclusion: The mRNA expression profile of renal tissue from LN patients revealed a large number of DEGs. TWHF has been shown to interact with the DEGs (including HMOX1, ALB and CASP1) through hydrogen bonding to treat LN.

Keywords: Ingenuity Pathway Analysis; Tripterygium wilfordii Hook F; lupus nephritis; molecular docking; network pharmacology.

MeSH terms

  • Drugs, Chinese Herbal* / pharmacology
  • Drugs, Chinese Herbal* / therapeutic use
  • Humans
  • Interferons
  • Lupus Nephritis* / drug therapy
  • Lupus Nephritis* / genetics
  • Molecular Docking Simulation
  • RNA, Messenger
  • Tripterygium

Substances

  • Interferons
  • RNA, Messenger
  • Drugs, Chinese Herbal