Abstract
BACKGROUND: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease involving immune dysregulation, metabolic reprogramming, and multi-organ damage. The Jieduquyuziyin prescription (JP), a contemporary Chinese herbal formula based on the Traditional Chinese Medicine principle of "Jiedu Quyu Ziyin," has shown clinical efficacy in SLE. This review aims to synthesize clinical and preclinical evidence explaining how JP achieves systemic therapeutic effects by targeting interconnected pathological pathways in SLE. METHODS: We systematically searched PubMed, Web of Science, and CNKI (January 1999-December 2025) for clinical trials, preclinical studies, and multi-omics analyses investigating JP or its bioactive compounds in SLE. RESULTS: Clinical evidence demonstrates that JP-containing regimens significantly reduce SLEDAI scores, alleviate lupus nephritis, lower glucocorticoid requirements, and improve quality of life in SLE patients. Preclinical studies in SLE-prone MRL/lpr mice reveal that JP targets key SLE pathogenic pathways: it restores Th17/Treg balance, suppresses SLE-associated pathogenic B cell proliferation via AKT/mTOR inhibition, and promotes apoptosis of double-negative T cells through UBE2M-mediated Bim upregulation. JP inhibits macrophage IRAK1/ NF-κB signaling, attenuates lupus nephritis by activating renal FXR to suppress TGF-β1/α-SMA-driven fibrosis, and mitigates oxidative damage via Nrf2 activation. Addressing SLE-associated immunometabolic dysfunction, JP reverses pathological glycolytic reprogramming in lymphocytes via AMPK signaling and restores mitochondrial function. Additionally, JP remodels gut microbiota in SLE models, enriching Akkermansia and modulating short-chain fatty acid and bile acid metabolism to reinforce immune homeostasis. CONCLUSION: This review validates JP as a system-level therapeutic strategy targeting immune dysregulation, metabolic reprogramming, and gut dysbiosis in SLE, supporting the TCM principle of "Jiedu Quyu Ziyin" and its integration with modern immunology.