Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
The Scutellaria baicalensis-Coptis chinensis herb pair ameliorates ulcerative colitis via integrated modulation of the aryl hydrocarbon receptor/NLRP3 inflammasome axis with tryptophan metabolites.
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Fang Dan, Sheng Xianjie, Li Xinru, Tan Bingyan, Zhang Jingyan, Ding Kang, Kang An
Аннотация
BACKGROUND: The Scutellaria baicalensis Georgi and Coptis chinensis Franch (SC) herb pair constitutes a vital component in many classic formulas exhibited well-documented synergistic therapeutic efficacy against bacterial infections and various inflammatory conditions. However, the precise mechanism of this herb pair in treating ulcerative colitis (UC) is unknown.
PURPOSE: To investigate the therapeutic potential and elucidate the mechanistic basis of SC herb pair treating UC.
METHODS: A dextran sulfate sodium (DSS)-induced UC mouse model was established to evaluate the therapeutic effect of SC herb pair. Colonic inflammation, tight junction proteins, NOD-like receptor protein 3 (NLRP3) inflammasome, and the Aryl hydrocarbon receptor (AHR) - Cytochrome P450 1A1 (CYP1A1) axis were assessed. AHR activation by principal bioactive compounds in SC was verified, while endogenous AHR ligands affected by SC herb pair treatment were monitored by HPLC-MS. The role of AHR in suppressing NLRP3 inflammasome activation and mediating SC herb pair's therapeutic effects was validated using the AHR antagonist CH223191 and AHR-knockout (AHR-/-) mice.
RESULTS: Compared with the UC model, SC herb pair administration effectively alleviated the weight loss, colon shortening and mucosal injury. It also markedly suppressed mRNA levels of pro-inflammatory mediators (IL-1β, IL-6 and TNF-α), as well as the protein expression of iNOS and COX-2, and inhibited the NLRP3 inflammasome activation, a key driver of UC pathogenesis. SC herb pair enhanced tight junction protein expression in colitis mice and upregulated AHR and its target gene CYP1A1 in colitis mice. Luciferase assays confirmed direct activation of AHR by key bioactive ingredients in SC screened by molecular docking. Additionally, SC herb pair treatment restored tryptophan metabolite (kynurenine and indole-3-acetic acid) homeostasis and these metabolites also could activate AHR signaling. Crucially, both pharmacological inhibition with CH223191 and genetic ablation of AHR abrogated the beneficial effects of SC herb pair in UC mice.
CONCLUSION: The SC herb pair ameliorates UC thorough AHR activation, which is achieved both directly via its bioactive constituents and indirectly through the restoration of AHR-activating tryptophan metabolites. Subsequently, AHR activation suppresses the NLRP3 inflammasome-driven colonic inflammation and restores intestinal barrier, thereby providing a mechanistic basis for its therapeutic effects against UC.
PURPOSE: To investigate the therapeutic potential and elucidate the mechanistic basis of SC herb pair treating UC.
METHODS: A dextran sulfate sodium (DSS)-induced UC mouse model was established to evaluate the therapeutic effect of SC herb pair. Colonic inflammation, tight junction proteins, NOD-like receptor protein 3 (NLRP3) inflammasome, and the Aryl hydrocarbon receptor (AHR) - Cytochrome P450 1A1 (CYP1A1) axis were assessed. AHR activation by principal bioactive compounds in SC was verified, while endogenous AHR ligands affected by SC herb pair treatment were monitored by HPLC-MS. The role of AHR in suppressing NLRP3 inflammasome activation and mediating SC herb pair's therapeutic effects was validated using the AHR antagonist CH223191 and AHR-knockout (AHR-/-) mice.
RESULTS: Compared with the UC model, SC herb pair administration effectively alleviated the weight loss, colon shortening and mucosal injury. It also markedly suppressed mRNA levels of pro-inflammatory mediators (IL-1β, IL-6 and TNF-α), as well as the protein expression of iNOS and COX-2, and inhibited the NLRP3 inflammasome activation, a key driver of UC pathogenesis. SC herb pair enhanced tight junction protein expression in colitis mice and upregulated AHR and its target gene CYP1A1 in colitis mice. Luciferase assays confirmed direct activation of AHR by key bioactive ingredients in SC screened by molecular docking. Additionally, SC herb pair treatment restored tryptophan metabolite (kynurenine and indole-3-acetic acid) homeostasis and these metabolites also could activate AHR signaling. Crucially, both pharmacological inhibition with CH223191 and genetic ablation of AHR abrogated the beneficial effects of SC herb pair in UC mice.
CONCLUSION: The SC herb pair ameliorates UC thorough AHR activation, which is achieved both directly via its bioactive constituents and indirectly through the restoration of AHR-activating tryptophan metabolites. Subsequently, AHR activation suppresses the NLRP3 inflammasome-driven colonic inflammation and restores intestinal barrier, thereby providing a mechanistic basis for its therapeutic effects against UC.