中国科学院上海药物研究所丁侃等研究人员合作发现，从枸杞果实中分离的肽聚糖通过调节TGF-β/Smad7信号通路和肠道菌群缓解小鼠肝纤维化。相关论文于2025年1月20日在线发表在《中国药理学报》杂志上。

研究人员从枸杞果实中提取了一种中性肽聚糖，命名为LBPW。研究人员探讨了LBPW的护肝机制。四氯化碳（CCl₄）诱导的肝纤维化小鼠接受了LBPW（50、100、200 mg/kg每天，腹腔注射或100、200、300 mg/kg每天，口服）为期6周。

结果表明，无论是腹腔注射还是口服，LBPW均能剂量依赖性地减轻CCl₄处理小鼠的肝损伤和肝纤维化。药代动力学分析显示，Cy5.5标记的LBPW（Cy5.5-LBPW）通过腹腔注射和口服途径可在肝脏中被检测到，而口服给药的Cy5.5-LBPW主要在肠道中积累。

在TGF-β1刺激的LX-2细胞以及CCl₄处理的小鼠肝脏中，研究人员发现LBPW显著上调了TGF-β/Smad信号通路的负调节因子Smad7，从而减缓了肝星状细胞（HSC）的激活并防止了肝纤维化。另一方面，LBPW显著提高了阿克曼氏菌（A. muciniphila）的丰度并强化了肠道屏障功能。研究人员证明，A. muciniphila可能是LBPW疗效的关键，因为通过抗生素减少这种细菌的丰度会阻止LBPW的效果。

总体而言，这些研究结果表明，LBPW可能通过重新平衡TGF-β/Smad7信号通路和传播肠道共生菌A. muciniphila来发挥护肝作用，暗示LBPW可能成为新型药物或营养补充剂开发的关键成分，用于对抗肝纤维化。

研究人员表示，枸杞果实的护肝作用在中国已有几千年的记载。枸杞多糖（LBP）是首次报道能减轻CCl₄处理小鼠肝纤维化的大分子。

附：英文原文

Title: Peptidoglycan isolated from the fruit of Lycium barbarum alleviates liver fibrosis in mice by regulating the TGF-β/Smad7 signaling and gut microbiota

Author: Nie, Ying-min, Zhou, Wan-qi, Niu, Ting, Mao, Meng-fei, Zhan, Yu-xue, Li, Yun, Wang, Kai-ping, Li, Mei-xia, Ding, Kan

Issue&Volume: 2025-01-20

Abstract: The hepatoprotective effect of the fruit of Lycium barbarum has been documented in China over millennia. Lycium barbarum polysaccharides (LBPs) were the first macromolecules reported to mitigate liver fibrosis in carbon tetrachloride (CCl4)-treated mice. Herein, a neutral peptidoglycan, named as LBPW, was extracted from the fruit of Lycium barbarum. In this study, we investigated the hepatoprotective mechanisms of LBPW. CCl4-induced liver fibrosis mice were administered LBPW (50, 100, 200mg·kg–1·d–1, i.p.) or (100, 200, 300mg·kg–1·d–1, i.g.) for 6 weeks. We showed that either i.p. or i.g. administration of LBPW dose-dependently attenuated liver damage and fibrosis in CCl4-treated mice. Pharmacokinetic analysis showed that cyanine 5.5 amine (Cy5.5)-labeled LBPW (Cy5.5-LBPW) could be detected in the liver through i.p. and i.g. administration with i.g.-administered Cy5.5-LBPW mainly accumulating in the intestine. In TGF-β1-stimulated LX-2 cells as well as in the liver of CCl4-treated mice, we demonstrated that LBPW significantly upregulated Smad7, a negative regulator of TGF-β/Smad signaling, to retard the activation of hepatic stellate cells (HSCs) and prevent liver fibrosis. On the other hand, LBPW significantly boosted the abundance of Akkermansia muciniphila (A. muciniphila) and fortified gut barrier function. We demonstrated that A. muciniphila might be responsible for the efficacy of LBPW since decreasing the abundance of this bacterium by antibiotics (Abs) blocked the effectiveness of LBPW. Overall, our results show that LBPW may exert the hepatoprotective effect via rebalancing TGF-β/Smad7 signaling and propagating gut commensal A. muciniphila, suggesting that LBPW could be leading components to be developed as new drug candidates or nutraceuticals against liver fibrosis.

DOI: 10.1038/s41401-024-01454-x

Source: https://www.nature.com/articles/s41401-024-01454-x