PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Jingyi Hu,Feng Xu,Lei Zhu,Yuan Cui,Ryan Au,Yanan Li,Yiheng Tong,Hong Shen
Angelica dahurica radix (ADR), the root of the botanical family Apiaceae (genus Angelica , species Angelica dahurica ( Hoffm .)), has been used to treat colitis in clinical practice. The immunomodulatory effects of ADR are attributed to its polysaccharides (RP). However, its mechanism of action has not been elucidated. In this study, RP's structure was determined through nuclear magnetic resonance analysis. Dextran sulfate sodium-induced colitis in mice was utilized to assess the therapeutic efficacy of RP, while experiments involving fecal microbiota transplantation (FMT) and antibiotic treatment were performed to investigate the contribution of gut microbiota to RP's protective function. Non-targeted metabolomics was utilized to identify potential targets for elucidating the underlying mechanisms. RP is likely composed of (→4)-α-D-Glcp-(1→ and →4)-α-D-Galp-(1→). It effectively alleviated DSS-induced colitis by restoring the balance of the gut microbial community, a finding validated through FMT and antibiotic intervention experiments. Imidazole propionate (ImP) emerged as a potential target for RP's efficacy in treating colitis, which inhibits the activation of peroxisome proliferator-activated receptor gamma (PPAR-γ). Our findings suggest that RP may confer protection against colitis by activating the PPAR-γ signaling pathway through alleviating the constraint imposed by ImP.
研究领域:
药理学
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微生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2022
·
IF 7.419
Jingyi Hu,Yiheng Tong,Zhaofeng Shen,Yanan Li,Cheng Cheng,Ryan Au,Feng Xu,Yajun Liu,Lei Zhu,Hong Shen
Ulcerative colitis (UC) is a chronic and relapsing inflammatory disease of the intestine. Dysbiosis, especially the expansion of facultative anaerobic Enterobacteriaceae , maybe the main pathogenesis of UC. Gegen Qinlian decoction (GD), a traditional Chinese medicinal formula chronicled in the Shang Han Lun , is commonly used to treat UC and has shown an excellent effect on inducing disease remission. However, the role of GD in regulating gut microbiota has not been fully clarified. Herein, we investigated the potential effect of GD on inhibiting the expansion of Enterobacteriaceae and further explored the potential mechanism of this action. Our study demonstrated that GD remarkably reduced body weight loss of colitis mice, shortening of colon length, and inflammation of the colon. Peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling was inactivated in colitis colon tissue, and the abundance of Escherichia coli ( E. coli, family of Enterobacteriaceae ) in colonic contents and the concentration of lipopolysaccharide (LPS) in colonic tissue were significantly upregulated after DSS-treatment. Notably, GD administration can result in the activation of PPAR-γ and inactivation of iNOS, which lead to the reduction of nitrate, the inhibition of E. coli, and less production of LPS. Combined GD with PPAR-γ antagonist, the effect of GD on the treatment of UC was weakened, and effectless in inhibiting the expansion of Enterobacteriaceae . Therefore, GD ameliorates UC by preventing a dysbiotic expansion of potentially pathogenic E. coli by reducing nitrate levels in the lumen through activating PPAR-γ signaling.
研究领域:
药理学
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微生物学
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免疫学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Lipids in Health and Disease
·
2025
·Vol. 24
·期 1
·1-16
·
IF 4.2
Li Lishuang,Ren Xing,Gao Xinyu,Zhao Yujia,Ma Yuman,Gong Junxiao,Yang Shuo,Sun Yanan,Wang Yi
Objective This study aimed to investigate the regulatory role and mechanisms of chenodeoxycholic acid (CDCA) on lipid metabolism, and to evaluate its therapeutic potential in lipid metabolism-related diseases such as acne, seborrheic alopecia, and prostate cancer, with the aim of identifying safer and more sustainable treatment alternatives. Methods Lipid-overproduction models were established using RM-1 (murine prostate cancer cells) and primary sebaceous gland cells, stimulated by linoleic acid (LA) and dihydrotestosterone (DHT), respectively. CDCA’s mechanisms were explored using transcriptomics, proteomics, and fatty acid-targeted metabolomics. In vivo validation was conducted via intradermal injection of CDCA into the sebaceous gland area of golden hamsters to assess its effect on sebaceous lipid metabolism. Results CDCA significantly reduced intracellular lipid accumulation in both murine prostate cancer cells (RM-1) and primary sebaceous gland cells, and suppressed the expression of the androgen receptor (AR), along with the downregulation of key lipogenic enzymes (SREBF1, FASN, FADS2). Mitochondrial membrane potential was restored in CDCA-treated cells. Multi-omics analyses revealed that CDCA modulated fatty acid biosynthesis and degradation, energy metabolism, mitochondrial function, and Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) signaling. Lipidomic profiling demonstrated a shift from saturated to unsaturated fatty acid dominance after CDCA treatment. In vivo, CDCA decreased sebaceous lipid accumulation and downregulated PPAR-γ expression in golden hamsters. Conclusion CDCA exerted multifaceted regulatory effects on lipid metabolism, hormone signaling, and mitochondrial dynamics. These effects contributed to the maintenance of sebaceous gland homeostasis and supported the development of innovative and potentially more biocompatible therapies for lipid-related disorders.
研究领域:
生物化学
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分子生物学
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药理学
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皮肤科学
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肿瘤学
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内分泌学
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系统生物学
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代谢组学
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转录组学
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蛋白质组学
✓ 已验证
DOI
PubMed
高影响因子
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