Huangqin decoction inhibits colorectal inflammatory cancer transformation by improving gut microbiome-mediated metabolic dysfunction.

Journal of pharmaceutical analysis Pub Date : 2025-05-01 Epub Date: 2024-11-04 DOI:10.1016/j.jpha.2024.101138
Lu Lu, Yuan Li, Hang Su, Sisi Ren, Yujing Liu, Gaoxuan Shao, Weiwei Liu, Guang Ji, Hanchen Xu
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Abstract

Colorectal inflammatory cancer transformation poses a major risk to patients with colitis. Patients with chronic intestinal inflammation have an approximately 2-3 folds increased risk of developing colorectal cancer (CRC). Unfortunately, there is currently no effective intervention available. Huangqin decoction (HQD), a well-known traditional Chinese medicine (TCM) formula, is frequently clinically prescribed for treating patients with colitis, and its active ingredients have effective antitumour efficacy. Nonetheless, the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear. A strategy integrating metagenomic, lipidomic, and messenger RNA (mRNA) sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome, metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation. Our study revealed that HQD suppressed colorectal inflammatory cancer transformation, which was associated with enhanced intestinal barrier function, decreased the inflammatory response, and regulation of the gut microbiome. Notably, cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis. Moreover, gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism, especially the remodeling of arachidonic acid metabolism, which was associated with the amelioration of pathological transformation. Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase (ALOX12) were affected by HQD treatment, and no obvious protective effect of HQD was observed in Alox 12 -/- mice, which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation. In summary, multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.

黄芩汤通过改善肠道微生物介导的代谢功能障碍抑制结直肠癌的转化。
结直肠炎性癌转化是结肠炎患者的主要风险。慢性肠道炎症患者发生结直肠癌(CRC)的风险增加约2-3倍。不幸的是,目前还没有有效的干预措施。黄芩汤(HQD)是一种著名的中药方剂,临床上常用于治疗结肠炎患者,其有效成分具有有效的抗肿瘤功效。然而,hqd介导的预防结直肠癌炎性转化的机制尚不清楚。采用宏基因组学、脂质组学和信使RNA (mRNA)测序分析相结合的策略,研究HQD对肠道微生物组、代谢的调节作用以及参与结直肠癌炎症转化的潜在机制。我们的研究表明,HQD抑制结直肠癌炎性癌的转化,这与增强肠道屏障功能,降低炎症反应和调节肠道微生物群有关。值得注意的是,共居实验显示,hqd处理小鼠肠道微生物组的转移在很大程度上抑制了结肠炎的病理转化。此外,hqd处理小鼠的肠道微生物组转移主要导致脂肪酸代谢调节的改变,特别是花生四烯酸代谢的重塑,这与病理转化的改善有关。花生四烯酸代谢及关键代谢酶花生四烯酸12-脂氧合酶(ALOX12)均受到HQD处理的影响,而在Alox 12- /-小鼠中未观察到HQD的明显保护作用,提示ALOX12是HQD保护结直肠癌炎性转化的关键介质。综上所述,多组学分析为HQD作为炎性结直肠癌转化的一种有希望的干预手段提供了有价值的数据和理论支持。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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