Chemical characterization of aconite polysaccharide and its ameliorative effect on ulcerative colitis by regulating gut microbiota and THDCA-driven TGR5/cAMP/PKA/NLRP3 pathway

Hao Cheng; Dandan Zhang; Jinlu Wu; Hui Feng; Yaochuan Zhou; Yan Wan; Yuzhu Tan; Wuwen Feng; Cheng Peng

doi:10.1016/j.jpha.2026.101642

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Hao Cheng, Dandan Zhang, Jinlu Wu, Hui Feng, Yaochuan Zhou, Yan Wan, Yuzhu Tan, Wuwen Feng, Cheng Peng. Chemical characterization of aconite polysaccharide and its ameliorative effect on ulcerative colitis by regulating gut microbiota and THDCA-driven TGR5/cAMP/PKA/NLRP3 pathway[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101642

Citation:

Hao Cheng, Dandan Zhang, Jinlu Wu, Hui Feng, Yaochuan Zhou, Yan Wan, Yuzhu Tan, Wuwen Feng, Cheng Peng. Chemical characterization of aconite polysaccharide and its ameliorative effect on ulcerative colitis by regulating gut microbiota and THDCA-driven TGR5/cAMP/PKA/NLRP3 pathway[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101642

Citation:

Hao Cheng, Dandan Zhang, Jinlu Wu, Hui Feng, Yaochuan Zhou, Yan Wan, Yuzhu Tan, Wuwen Feng, Cheng Peng. Chemical characterization of aconite polysaccharide and its ameliorative effect on ulcerative colitis by regulating gut microbiota and THDCA-driven TGR5/cAMP/PKA/NLRP3 pathway[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101642

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Chemical characterization of aconite polysaccharide and its ameliorative effect on ulcerative colitis by regulating gut microbiota and THDCA-driven TGR5/cAMP/PKA/NLRP3 pathway

doi: 10.1016/j.jpha.2026.101642

Hao Cheng^a,b,c,
Dandan Zhang^a,
Jinlu Wu^a,
Hui Feng^a,
Yaochuan Zhou^d,
Yan Wan^a,
Yuzhu Tan^a,
Wuwen Feng^{a
,
,},
Cheng Peng^{a
,
,}

a. Chinese Medicine Germplasm Resources Innovation and Effective Uses Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China;
b. North Sichuan Medical College, Nanchong, Sichuan, 637000, China;
c. The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China;
d. School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China

Funds:

This work was supported by the National Natural Science Foundation of China (Grant Nos.: U24A20790 and 82574683), Sichuan Science and Technology Program, China (Grant Nos.: 2024NSFJQ0044 and 2024NSFSC0054), Sichuan Provincial Administration of Traditional Chinese Medicine, China (Grant No.: 2024ZD02), and the Doctoral Research Initiation Fund of North Sichuan Medical College, China (Grant No.: CBY25-QDA40).

Received Date: Aug. 05, 2025
Accepted Date: Apr. 20, 2026
Rev Recd Date: Apr. 17, 2026
Available Online: Apr. 22, 2026

Abstract

Abstract

Aconite shows potential to improve Ulcerative colitis (UC). However, the specific impact and mechanisms of aconite polysaccharides (APs) on UC remain poorly understood. This study aims to elucidate the chemical structures of APs, among which one was further evaluated for its effects on dextran sulfate sodium (DSS)-induced UC, and the underlying mechanism was explored with a focus on gut microbiota (GM). Four distinct APs were isolated, among which aconite polysaccharide A-1 (APA-1) was the predominant one. APA-1 is characterized as a glucan composed of →4)-α-glucose (Glc)-(1→, with residues such as →3, 4)-α-Glc-(1→, →2, 4)-α-Glc-(1→, and →4, 6)-α-Glc-(1→ functioning as branching points. APA-1 significantly ameliorated disease symptoms and colonic pathological alterations in UC mice. Furthermore, APA-1 restored GM diversity and richness, counteracting dysbiosis marked by a decrease in beneficial microorganisms such as Dubosiella and Lactobacillus, and an increase in potentially pathogenic ones including Proteobacteria and Escherichia-Shigella. Fecal microbiota transplantation recapitulated the effects of APA-1 on UC mice, thereby confirming the role of APA-1-regulated GM in UC. Metabolomic analysis revealed that APA-1 may exert its effects by enhancing microbial metabolite taurohyodeoxycholic acid (THDCA). Oral administration of THDCA, in conjunction with transcriptomic and Western blotting analyses, demonstrated that both APA-1 and THDCA ameliorate UC by inhibiting the nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome through the Takeda G protein-coupled receptor 5/cyclic adenosine monophosphate/protein kinase A (TGR5/cAMP/PKA) signaling pathway. In summary, APA-1 effectively mitigates UC by modulating GM and microbial metabolite THDCA, which subsequently targets the NLRP3 inflammasome via the TGR5/cAMP/PKA pathway.
- Aconite,
- Ulcerative colitis,
- Gut microbiota,
- Bile acids,
- Inflammasome,
- Taurohyodeoxycholic acid

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References(50)

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