Journal of ethnopharmacology · 2025
Ethyl acetate extract from Herpetospermun cardigerum wall. Ameliorated concanavalin A-induced autoimmune hepatitis in mice by reprofiling gut microenvironment to modulate IDO1/KYN and PI3K/AKT/NF-κB pathways.
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Xiao Yu, Luo Tianfeng, Duan Changsong, Wang Xinhui, Yang Yixi, Li Rui, Deng Jinpeng, Zhao Qi
Аннотация
BACKGROUND: Autoimmune hepatitis (AIH) is an immunoinflammatory chronic liver disease with increasing prevalence worldwidely, lacking of effective medicine. Herpetospermum caudigerum Wall. (HC) is a traditional Tibetan medicine used to treat liver diseases for thousands of years. However, investigation into the effects of HC in AIH remains scarce.
PURPOSE: Our study aimed to explore the effects and mechanisms of ethyl acetate extract from the seeds of HC (HCDEAE) against concanavalin A (Con A)-induced liver impairment in mouse.
STUDY DESIGN AND METHODS: HCDEAE was extracted from the seeds of HC, then characterized by UPLC-Q-TOF/MS. Con A-induced AIH mice were used to investigate the impacts of HCDEAE on liver impairment, T cells differentiation, gut microbiota and its derived metabolites, intestinal barrier impairment and inflammation, as well as the mechanisms of HCDEAE in liver in AIH.
RESULTS: HCDEAE (90 mg/kg, i.g.) effectively alleviated Con A-induced hepatic pathological damage, suppressed elevation of serum ALT, AST, IFN-γ, and TNF-α; in spleen, HCDEAE attenuated spleen impairment, elevated the percentage of CD4+CD25+ cells and FOXP3 gene expression, inhibited up-regulation of RORγt gene expression and IL-17; in liver, HCDEAE down-regulated IL-17, elevated FOXP3 gene expression and IL-10, increased the protein and gene expression of TGF-β1; in colon, HCDEAE attenuated intestinal barrier impairment, inhibited down-regulation of Occludin and ZO-1, and relieved elevation of IL-1β, as well as re-profiled the gut microenvironment. Furthermore, HCDEAE demonstrated the ability to elevate tryptophan metabolism among kynurenine pathway, activate IDO1/KYN pathway and inhibit PI3K/AKT/NF-κB signaling pathway in liver of AIH mice.
CONCLUSION: Pretreatment with HCDEAE (90 mg/kg·d-1, i.g.) for 9 days could effectively alleviate the liver inflammation and injure, protect intestinal barriers, attenuate spleen impairment, maintain Treg-Th17 cell equilibrium in Con A-induced AIH mice, via re-profiling gut microbiota, modulation of tryptophan metabolism in the gastrointestinal tract and in liver, to activate IDO1/KYN pathway and inhibit the abnormal activation of PI3K/AKT/NF-κB signaling pathway in liver. The present study highlighted the potential of HCDEAE as a drug candidate for AIH.
PURPOSE: Our study aimed to explore the effects and mechanisms of ethyl acetate extract from the seeds of HC (HCDEAE) against concanavalin A (Con A)-induced liver impairment in mouse.
STUDY DESIGN AND METHODS: HCDEAE was extracted from the seeds of HC, then characterized by UPLC-Q-TOF/MS. Con A-induced AIH mice were used to investigate the impacts of HCDEAE on liver impairment, T cells differentiation, gut microbiota and its derived metabolites, intestinal barrier impairment and inflammation, as well as the mechanisms of HCDEAE in liver in AIH.
RESULTS: HCDEAE (90 mg/kg, i.g.) effectively alleviated Con A-induced hepatic pathological damage, suppressed elevation of serum ALT, AST, IFN-γ, and TNF-α; in spleen, HCDEAE attenuated spleen impairment, elevated the percentage of CD4+CD25+ cells and FOXP3 gene expression, inhibited up-regulation of RORγt gene expression and IL-17; in liver, HCDEAE down-regulated IL-17, elevated FOXP3 gene expression and IL-10, increased the protein and gene expression of TGF-β1; in colon, HCDEAE attenuated intestinal barrier impairment, inhibited down-regulation of Occludin and ZO-1, and relieved elevation of IL-1β, as well as re-profiled the gut microenvironment. Furthermore, HCDEAE demonstrated the ability to elevate tryptophan metabolism among kynurenine pathway, activate IDO1/KYN pathway and inhibit PI3K/AKT/NF-κB signaling pathway in liver of AIH mice.
CONCLUSION: Pretreatment with HCDEAE (90 mg/kg·d-1, i.g.) for 9 days could effectively alleviate the liver inflammation and injure, protect intestinal barriers, attenuate spleen impairment, maintain Treg-Th17 cell equilibrium in Con A-induced AIH mice, via re-profiling gut microbiota, modulation of tryptophan metabolism in the gastrointestinal tract and in liver, to activate IDO1/KYN pathway and inhibit the abnormal activation of PI3K/AKT/NF-κB signaling pathway in liver. The present study highlighted the potential of HCDEAE as a drug candidate for AIH.