The MOE Key Laboratory for Standardization of Chinese Medicines, and SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, PR China; School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou 310053, PR China.
Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Int J Biol Macromol. 2023 Mar 1;230:123252. doi: 10.1016/j.ijbiomac.2023.123252. Epub 2023 Jan 11.
Nonalcoholic steatohepatitis (NASH) is a chronic liver disease characterized by inflammation and hepatic steatosis that may coincide with fibrotic activity. To date, no pharmacological agents have been approved for NASH treatment. Here, a homogeneous (1,3),(1,6)-β-D-glucan (PUP-W-1, Mw: 41.07 kDa) was successfully purified from Polyporus umbellatus (Pers.) Fries sclerotia and characterized. The analysis showed that the PUP-W-1 backbone consisted of a repeating chain of eight →3)-β-D-Glcp-(1 → units, with branched chains of four β-D-Glcp residues, joined by repeating 1,6-linkage units at the O-6 position of the backbone. The pharmacological effects of PUP-W-1 treatment in the context of NASH pathogenesis were explored using a methionine choline-deficient (MCD) diet-induced murine steatohepatitis model. The MCD model mice exhibited pronounced steatohepatitis, inflammatory activity, steatosis, stellate cell activation, and mild fibrotic activity. Treatment of the mice for three weeks with PUP-W-1 prevented the development of NASH due to the suppression of inflammation, lipid accumulation, and fibrosis. As suggested by these findings, PUP-W-1 may hold promise as a natural drug candidate or precursor for the treatment of NASH.
非酒精性脂肪性肝炎（NASH）是一种慢性肝病，其特征为炎症和肝脂肪变性，可能伴有纤维活性。迄今为止，尚无批准用于 NASH 治疗的药物。在这里，成功地从香菇（Polyporus umbellatus（Pers.）Fries）菌核中纯化出均一的（1,3），（1,6）-β-D-葡聚糖（PUP-W-1，Mw：41.07 kDa）并对其进行了表征。分析表明，PUP-W-1 的主链由重复的八个→3）-β-D-Glcp-（1→单元组成，带有四个β-D-Glcp 残基的支链，通过主链 O-6 位置上重复的 1,6-连接单元连接。在 NASH 发病机制的背景下，使用蛋氨酸胆碱缺乏（MCD）饮食诱导的小鼠脂肪性肝炎模型探索了 PUP-W-1 治疗的药理作用。MCD 模型小鼠表现出明显的脂肪性肝炎、炎症活性、脂肪变性、星状细胞激活和轻度纤维化活性。用 PUP-W-1 治疗三周可预防 NASH 的发生，这是由于炎症、脂质积累和纤维化的抑制。根据这些发现，PUP-W-1 可能有希望成为治疗 NASH 的天然药物候选物或前体。
