Li Xiaoxuan, Zhang Hongyun, Deng Yufei, Fang Qian, Zhang Xiaohui, Ding Shuiping, Hou Xiaoying, Du Hongzhi
School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, People's Republic of China.
School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, People's Republic of China; Cancer Institute, School of Medicine, Jianghan University, 430056, People's Republic of China.
Int J Biol Macromol. 2025 Mar;293:139357. doi: 10.1016/j.ijbiomac.2024.139357. Epub 2024 Dec 30.
Liver cancer was the third cause of global cancer death, while China has the largest number of patients. And traditional Chinese medicine is an important strategy for liver cancer. There into, Huaier polysaccharides (HP), the major component of Trametes robiniophila Murr., as a preparation of Huaier granule, is recommended by clinical guidelines for Hepatocellular carcinoma (HCC). However, the anti-HCC mechanism remains unclear. Herein, we investigated whether HP could suppress HCC and revealed the underlying mechanism. Firstly, HP showed a weaker proliferation inhibitory effect on the mouse source and human HCC cells in vitro, but exhibited stronger anti-HCC effects in animals. And nude mice models confirmed that macrophages play an important role in the anti-HCC effect of HP. Then, we observed that HP reduced the polarization of M2 macrophages in tumor microenvironment and increased the secretion of pro-inflammatory factors by macrophages. Moreover, 16 s rRNA gene sequencing and non-targeted metabolomics analysis revealed that HP altered the gut microbiota and related metabolites. Eventually, antibiotic intervention eliminated the efficacy and reduced the expression of pro-inflammatory factors, confirming that the gut microbiota is a key molecule for HP efficacy. In addition, MTT and EdU assay indicated that Chenodeoxycholic acid (CDCA) were potential microbial metabolites influencing efficacy of HP. In conclusion, our data revealed that Huaier polysaccharides inhibited HCC via gut microbiota mediated M2 macrophage polarization, providing sufficient scientific support for Huaier polysaccharides clinical application and indicating the indispensable role of polysaccharides in life health.
肝癌是全球癌症死亡的第三大原因，而中国的肝癌患者数量最多。中医药是肝癌治疗的一项重要策略。其中，槐耳多糖（HP）作为槐耳颗粒制剂的主要成分，是肝细胞癌（HCC）临床指南推荐用药。然而，其抗肝癌机制仍不清楚。在此，我们研究了HP是否能抑制肝癌并揭示其潜在机制。首先，HP在体外对小鼠源和人肝癌细胞的增殖抑制作用较弱，但在动物实验中表现出较强的抗肝癌作用。裸鼠模型证实巨噬细胞在HP的抗肝癌作用中起重要作用。然后，我们观察到HP减少了肿瘤微环境中M2巨噬细胞的极化，并增加了巨噬细胞促炎因子的分泌。此外，16S rRNA基因测序和非靶向代谢组学分析表明，HP改变了肠道微生物群及其相关代谢产物。最终，抗生素干预消除了HP的疗效并降低了促炎因子的表达，证实肠道微生物群是HP发挥疗效的关键分子。此外，MTT和EdU实验表明，鹅去氧胆酸（CDCA）是影响HP疗效的潜在微生物代谢产物。总之，我们的数据表明，槐耳多糖通过肠道微生物群介导的M2巨噬细胞极化抑制肝癌，为槐耳多糖的临床应用提供了充分的科学依据，并表明多糖在生命健康中不可或缺的作用。
