Qi Zhaoyao, Liu Jincun, Xu Yuanhui, Sun Hongguang, Qi Xinxin, Cong Meili, Zhang Xinxuan, Yan Yuxin, Liu Tao
School of Public Health, Xinjiang Medical University, Xinjiang, Urumqi, 830011, China.
J Ethnopharmacol. 2025 Jan 30;337(Pt 3):118925. doi: 10.1016/j.jep.2024.118925. Epub 2024 Oct 10.
Cistanche tubulosa (Schenk) Wight, a Chinese herbal medicine (Rou Cong Rong) with Xinjiang characteristics, was recorded in many medical books in ancient China and often used as a tonic medicine. Supported by the traditional Chinese medicine theory of "homology of liver and kidney," C. tubulosa (Schenk) Wight has many clinical applications in tonifying the kidney and protecting the liver. Modern pharmacological studies have also found that the protective effects of phenylethanol glycosides from C. tubulosa (Schenk) Wight (CPhGs) play an important role in ameliorating alcoholic liver injury.
We aimed to investigate whether CPhGs can enhance the therapeutic outcome of alcoholic liver disease (ALD) by targeting the "gut-liver axis," thus contributing to the knowledge of how Chinese herbs alleviate disease by influencing the gut microbiota.
An ALD mouse model was established using the Lieber-DeCarli alcohol liquid diet, and the effects of CPhGs on the intestinal barrier and gut microbiota of ALD mice were investigated in a pseudo-sterile mouse model and fecal microbiota transplantation (FMT) mouse model. We fed female C57BL/6N mice with Lieber-DeCarli ethanol liquid diet, according to the NIAAA model. Animal experiment of long-term, ethanol diet intervention for 6W, and short-term for 11d. The FMT experiments were also performed.
CPhGs significantly improved ALD manifestations. ALD mice demonstrated significant gut microbiota dysbiosis and significantly abnormal proliferation of Allobaculum compared with the control diet group in long-term NIAAA mouse model (L-Pair). In mice that received the long-term intervention, the improvement in gut barrier function in the CPhGs-treated group was accompanied by a significant decrease in the abundance of Allobaculum and a significant increase in the abundance of Akkermansia. Furthermore, compared with the mouse were gavaged fecal microbiota from the long-term NIAAA mouse donors (FMT-EtOH), the number of goblet cells, abundance of Akkermansia, and the intestinal short-chain fatty acid concentrations were significantly increased in the mouse were gavaged fecal microbiota from high (700 mg/kg) doses of CPhGs orally in long-term NIAAA model donors (FMT-EtOH-H). Network analysis and species distribution results demonstrated that Akkermansia and Allobaculum were the genera with the highest abundances in the gut microbiota and that their interaction was related to propionic acid metabolism.
The results suggest that CPhGs exert a protective effect against ALD by modulating the abundance and composition of Akkermansia and Allobaculum in the intestine, maintaining the intestinal mucus balance, and safeguarding intestinal barrier integrity.
管花肉苁蓉是一种具有新疆特色的中药材（肉苁蓉），在中国古代多部医学典籍中均有记载，常被用作滋补药物。在中医“肝肾同源”理论的支持下，管花肉苁蓉在补肾保肝方面有诸多临床应用。现代药理学研究还发现，管花肉苁蓉苯乙醇苷（CPhGs）的保护作用在改善酒精性肝损伤中发挥着重要作用。
我们旨在研究CPhGs是否能通过靶向“肠 - 肝轴”来提高酒精性肝病（ALD）的治疗效果，从而有助于了解中药如何通过影响肠道微生物群来缓解疾病。
使用Lieber - DeCarli酒精液体饲料建立ALD小鼠模型，并在伪无菌小鼠模型和粪便微生物群移植（FMT）小鼠模型中研究CPhGs对ALD小鼠肠道屏障和肠道微生物群的影响。根据NIAAA模型，我们用Lieber - DeCarli乙醇液体饲料喂养雌性C57BL / 6N小鼠。进行了为期6周的长期乙醇饮食干预和为期11天的短期动物实验。还进行了FMT实验。
CPhGs显著改善了ALD的表现。在长期NIAAA小鼠模型（L - Pair）中，与对照饮食组相比，ALD小鼠表现出明显的肠道微生物群失调，Allobaculum显著异常增殖。在接受长期干预的小鼠中，CPhGs治疗组肠道屏障功能的改善伴随着Allobaculum丰度的显著降低和Akkermansia丰度的显著增加。此外，与接受来自长期NIAAA小鼠供体的粪便微生物群灌胃的小鼠（FMT - EtOH）相比，在长期NIAAA模型供体中接受高剂量（700mg / kg）CPhGs口服粪便微生物群灌胃的小鼠（FMT - EtOH - H）中，杯状细胞数量、Akkermansia丰度和肠道短链脂肪酸浓度显著增加。网络分析和物种分布结果表明，Akkermansia和Allobaculum是肠道微生物群中丰度最高的属，它们的相互作用与丙酸代谢有关。
结果表明，CPhGs通过调节肠道中Akkermansia和Allobaculum的丰度和组成、维持肠道黏液平衡以及保护肠道屏障完整性，对ALD发挥保护作用。
