Niu Pilian, Zhang Xiangjun, Zhang Guannan, Jing Ruixin, Qiao Yarui, Zhou Xuezhang, Bai Mingsheng, Peng Li
Life Science School, Ningxia University, Yinchuan 750021, China; Key Laboratory of the Ministry of Education for the Conservation and Utilization of Special Biological Resources of Western China, Ningxia University, Yinchuan, Ningxia 750021, China.
Life Science School, Ningxia University, Yinchuan 750021, China; Key Laboratory of the Ministry of Education for the Conservation and Utilization of Special Biological Resources of Western China, Ningxia University, Yinchuan, Ningxia 750021, China.
Int J Biol Macromol. 2025 Jan;286:138207. doi: 10.1016/j.ijbiomac.2024.138207. Epub 2024 Nov 29.
Myocardial fibrosis (MF) is a key factor endangering public health worldwide. Glycyrrhiza uralensis polysaccharide (GPS) exhibits various biological activities. However, its activity against MF has not been reported. Herein, a neutral polysaccharide (GPS-1-1) was isolated from GPS through column chromatography, its structure was characterized and potential mechanism regarding anti-MF activity was evaluated. Notably, the molecular weight of GPS-1-1 was 14.073 kDa, and the monosaccharides consist of glucose, arabinose and galactose, with a → 4)-α-d-glucopyranose (Glcp)-(1 → and →4, 6)-α-D-Glcp-(1 → backbone. Western blotting and immunofluorescence showed that GPS-1-1 inhibited the expression of fibrosis-related proteins, such as Collagen, Vimentin, Fibronectin and α-SMA in TGF-β1-induced fibrosis of cardiac fibroblasts (CFs), and inhibited the expression of TGF-β1-induced CFs migration ability and matrix metalloproteinases (MMP-2 and MMP-9), thus inhibiting the deposition of extracellular matrix in CFs. Additionally, in vivo analysis showed that GPS-1-1 reduced inflammatory cell infiltration and collagen deposition in cardiac tissues of mice with MF, and it inhibited the expression of serum lactate dehydrogenase, creatine kinase, and fibrosis-related factors. Combined transcriptomics, molecular docking and Western blotting analysis showed that platelet-derived growth factor subunit B (PDGFB) was involved in the anti-fibrosis process of GPS-1-1. Furthermore, qRT-PCR and Western blotting showed that GPS-1-1 inhibited the expression of MAPK/PI3K/AKT pathway related proteins, such as ERK, p-ERK, JNK, PI3K and p-PI3K in TGF-β1-induced CFs through PDGFB. Altogether, this study showed that GPS-1-1 inhibits the activation of the MAPK/PI3K/AKT pathway by down-regulating PDGFB expression to exert its anti-MF activity and its potential to be developed as a functional food and drug.
心肌纤维化（MF）是危害全球公众健康的关键因素。甘草多糖（GPS）具有多种生物学活性。然而，其抗MF活性尚未见报道。在此，通过柱色谱法从GPS中分离出一种中性多糖（GPS-1-1），对其结构进行了表征，并评估了其抗MF活性的潜在机制。值得注意的是，GPS-1-1的分子量为14.073 kDa，单糖由葡萄糖、阿拉伯糖和半乳糖组成，具有→4)-α-d-吡喃葡萄糖（Glcp）-(1→和→4, 6)-α-D-葡萄糖（Glcp）-(1→主链。蛋白质印迹法和免疫荧光法显示，GPS-1-1抑制了转化生长因子-β1（TGF-β1）诱导的心脏成纤维细胞（CFs）纤维化相关蛋白的表达，如胶原蛋白、波形蛋白、纤连蛋白和α-平滑肌肌动蛋白（α-SMA），并抑制了TGF-β1诱导的CFs迁移能力和基质金属蛋白酶（MMP-2和MMP-9）的表达，从而抑制了CFs中细胞外基质的沉积。此外，体内分析表明，GPS-1-1减少了MF小鼠心脏组织中的炎性细胞浸润和胶原沉积，并抑制了血清乳酸脱氢酶、肌酸激酶和纤维化相关因子的表达。联合转录组学、分子对接和蛋白质印迹分析表明，血小板衍生生长因子亚基B（PDGFB）参与了GPS-1-1的抗纤维化过程。此外，qRT-PCR和蛋白质印迹法显示，GPS-1-1通过PDGFB抑制了TGF-β1诱导的CFs中丝裂原活化蛋白激酶/磷脂酰肌醇-3激酶/蛋白激酶B（MAPK/PI3K/AKT）信号通路相关蛋白的表达，如细胞外信号调节激酶（ERK）、磷酸化细胞外信号调节激酶（p-ERK）、c-Jun氨基末端激酶（JNK）、磷脂酰肌醇-3激酶（PI3K）和磷酸化磷脂酰肌醇-3激酶（p-PI3K）。总之，本研究表明，GPS-1-1通过下调PDGFB表达抑制MAPK/PI3K/AKT信号通路的激活，从而发挥其抗MF活性，具有开发成为功能性食品和药物的潜力。
