IMPLAD, Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine from Ministry of Education, CAMS, Beijing 100193, China; IMPLAD, Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, CAMS, Beijing 100193, China.
Institute of Medicinal Plant Development (IMPLAD), State Key Laboratory of Quality Ensurance and Sustainable Use of Dao-Di herbs, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS), Beijing 100193, China; IMPLAD, Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine from Ministry of Education, CAMS, Beijing 100193, China.
Int J Biol Macromol. 2024 Oct;278(Pt 2):134491. doi: 10.1016/j.ijbiomac.2024.134491. Epub 2024 Aug 5.
The macrophage to myofibroblasts transition (MMT) has been reported as a newly key target in renal fibrosis. Lycium barbarum L. is a traditional Chinese medicine for improving renal function, in which its polysaccharides (LBPs) are the mainly active components. However, whether the role of LBPs in treating renal fibrosis is related to MMT process remain unclear. The purpose of this study was to explore the relationship between the regulating effect on MMT process and the anti-fibrotic effect of LBPs. Initially, small molecular weight LBPs fractions (LBP-S) were firstly isolated via Sephadex G-100 column. Then, the potent inhibitory effect of LBP-S on MMT process was revealed on bone marrow-derived macrophages (BMDM) model induced by TGF-β. Subsequently, the chemical structure of LBP-S was elucidated through monosaccharide, methylation and NMR spectrum analysis. In vivo biodistribution characteristics studies demonstrated that LBP-S exhibited effectively accumulation in kidney via intraperitoneal administration. Finally, LBP-S showed a satisfactory anti-renal fibrotic effect on unilateral ureteral obstruction operation (UUO) mice, which was significantly reduced following macrophage depletion. Overall, our findings indicated that LPB-S could alleviate renal fibrosis through regulating MMT process and providing new candidate agents for chronic kidney disease (CKD) related fibrosis treatment.
巨噬细胞向肌成纤维细胞的转化（MMT）已被报道为肾脏纤维化的一个新的关键靶点。枸杞是一种改善肾功能的中药，其多糖（LBPs）是主要的活性成分。然而，LBPs 在治疗肾纤维化中的作用是否与 MMT 过程有关尚不清楚。本研究旨在探讨调节 MMT 过程与 LBPs 抗纤维化作用之间的关系。首先，通过 Sephadex G-100 柱首次分离出小分子质量 LBPs 级分（LBP-S）。然后，在 TGF-β诱导的骨髓来源巨噬细胞（BMDM）模型上揭示了 LBP-S 对 MMT 过程的强烈抑制作用。随后，通过单糖、甲基化和 NMR 谱分析阐明了 LBP-S 的化学结构。体内分布特征研究表明，LBP-S 通过腹腔注射可有效积聚在肾脏中。最后，LBP-S 对单侧输尿管梗阻手术（UUO）小鼠表现出令人满意的抗肾纤维化作用，在巨噬细胞耗竭后显著减少。总之，我们的研究结果表明，LPB-S 可以通过调节 MMT 过程减轻肾脏纤维化，并为慢性肾病（CKD）相关纤维化治疗提供新的候选药物。
