Jianpi Zishen Decoction ameliorates renal damage induced by systemic lupus erythematosus through inhibition of the TLR4/MAPK pathway.

CONTEXT: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple systems. Jianpi Zishen Decoction (JZD) is a TCM formula used to improve proteinuria in SLE, which has been widely used in the treatment of renal damage in SLE.

OBJECTIVE

To investigate the potential targets and action mechanisms of JZD in ameliorating renal damage in SLE through network pharmacology and in-vivo and in-vitro experiments.

METHODS

The main components of JZD were determined using UPLC-Q-TOF-MS/MS. The potential targets and action mechanisms of JZD were explored using network pharmacology and molecular docking techniques. MRL/lpr mice were used as animal models, and their renal pathological changes were observed by HE staining, periodic acid-Schiff staining, and Masson staining. Additionally, mouse glomerular ultrastructure was observed using TEM. The level of urinary protein, immunoinflammatory indicators, and TLR4/MAPK pathway-related molecules were detected through a variety of experimental methods. Furthermore, the effects of JZD on LPS-stimulated HMCs were evaluated.

RESULTS

A total of 27 prototype components were identified in the blood-entered component of JZD. Animal experiments showed that JZD effectively ameliorated renal damage and immune disorders, reduced glomerular scores and vascular wall scores, as well as attenuated IgG and C3 deposition in the kidneys of MRL/lpr mice. Network pharmacological analysis and molecular docking identified TLR4 as a core potential target of JZD's efficacy. JZD inhibited the expression of TLR4, p38, JNK, AP-1, and pro-inflammatory factors in the kidneys of MRL/lpr mice. In-vitro experiments further showed that JZD inhibited LPS-induced HMC proliferation.

CONCLUSION

JZD could ameliorate SLE renal damage and its active ingredients exerted therapeutic effects by inhibiting the TLR4/MAPK pathway, highlighting the therapeutic potential of JZD in modulating immunoinflammation.