Journal of ethnopharmacology · 2025
Niuhuang Jiedu Tablet's compatibility alleviates realgar-induced intestinal toxicity by activating aryl hydrocarbon receptor pathway via Akkermansia and indole-3-lactate.
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Li Jianchao, Ma Yuanjing, Deng Nuo, Wang Fei, Tao Yi, Zhu Huilin, Xu Weichen, Shan Jinjun, Li Yongming, Wu Xiao
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Realgar is a traditional Chinese medicine rich in arsenic, and long-term use may lead to arsenic poisoning. The toxicity of realgar has primarily focused on the liver and kidney, with limited studies on its intestinal toxicity. Niuhuang Jiedu Tablet (NHJDT) is a renowned realgar-containing formula for clearing heat and detoxifying. NHJDT compatibility significantly reduces the toxicity of realgar, but the detoxification effects and underlying mechanisms in reducing realgar-induced intestinal toxicity remain unclear.
AIM OF THE STUDY: The study aims to investigate the detoxification mechanism of NHJDT's compatibility in reducing the intestinal toxicity of realgar.
MATERIALS AND METHODS: To evaluate the intestinal detoxification efficacy of NHJDT, mice were orally administered 0.5 % CMC-Na, realgar (0.5 and 1.0 g/kg) or NHJDT (3.9 and 7.8 g/kg) for 14 days. The intestinal detoxification effects of NHJDT were evaluated by toxic symptoms and intestinal barrier function. Changes of body weight, colon length, histopathological damage, tight junction and MUC2 proteins, and goblet cells were determined. The inflammatory factors and DAO were detected by ELISA. Further investigations including 16S rRNA sequencing, untargeted metabolomics, targeted short-chain fatty acid metabolomics and molecular docking assays were performed to explore the underlying detoxification mechanisms of NHJDT. Additionally, targeted microbiota and its derived metabolite gavage were conducted in mice to verify the detoxification effects.
RESULTS: NHJDT's compatibility significantly mitigated realgar-induced intestinal toxicity and gut barrier damage. It restored gut microbiota homeostasis by modulating the abundance of Akkermansia and concurrently enhanced the transformation from tryptophan to indole-3- lactate (ILA). The supplementation with Akkermansia muciniphila (A. muciniphila) and its derived ILA activated the aryl hydrocarbon receptor (AhR) in mice, thereby ameliorating realgar-induced intestinal damage.
CONCLUSION: NHJDT's compatibility alleviated realgar-induced intestinal toxicity by activating the AhR pathway via A. muciniphila and ILA. This study elucidates the detoxification mechanism of NHJDT's compatibility and offers novel insights for the clinical treatment of arsenic poisoning.
AIM OF THE STUDY: The study aims to investigate the detoxification mechanism of NHJDT's compatibility in reducing the intestinal toxicity of realgar.
MATERIALS AND METHODS: To evaluate the intestinal detoxification efficacy of NHJDT, mice were orally administered 0.5 % CMC-Na, realgar (0.5 and 1.0 g/kg) or NHJDT (3.9 and 7.8 g/kg) for 14 days. The intestinal detoxification effects of NHJDT were evaluated by toxic symptoms and intestinal barrier function. Changes of body weight, colon length, histopathological damage, tight junction and MUC2 proteins, and goblet cells were determined. The inflammatory factors and DAO were detected by ELISA. Further investigations including 16S rRNA sequencing, untargeted metabolomics, targeted short-chain fatty acid metabolomics and molecular docking assays were performed to explore the underlying detoxification mechanisms of NHJDT. Additionally, targeted microbiota and its derived metabolite gavage were conducted in mice to verify the detoxification effects.
RESULTS: NHJDT's compatibility significantly mitigated realgar-induced intestinal toxicity and gut barrier damage. It restored gut microbiota homeostasis by modulating the abundance of Akkermansia and concurrently enhanced the transformation from tryptophan to indole-3- lactate (ILA). The supplementation with Akkermansia muciniphila (A. muciniphila) and its derived ILA activated the aryl hydrocarbon receptor (AhR) in mice, thereby ameliorating realgar-induced intestinal damage.
CONCLUSION: NHJDT's compatibility alleviated realgar-induced intestinal toxicity by activating the AhR pathway via A. muciniphila and ILA. This study elucidates the detoxification mechanism of NHJDT's compatibility and offers novel insights for the clinical treatment of arsenic poisoning.