A polysaccharide from Glycyrrhiza uralensis attenuates myocardial fibrosis via modulating the MAPK/PI3K/AKT signaling pathway

Pilian Niu; Xiangjun Zhang; Guannan Zhang; Ruixin Jing; Yarui Qiao; Xuezhang Zhou; Mingsheng Bai; Li Peng

doi:10.1016/j.ijbiomac.2024.138207

A polysaccharide from Glycyrrhiza uralensis attenuates myocardial fibrosis via modulating the MAPK/PI3K/AKT signaling pathway

Int J Biol Macromol. 2024 Nov 29:138207. doi: 10.1016/j.ijbiomac.2024.138207. Online ahead of print.

Authors

Pilian Niu¹, Xiangjun Zhang¹, Guannan Zhang¹, Ruixin Jing¹, Yarui Qiao¹, Xuezhang Zhou¹, Mingsheng Bai², Li Peng³

Affiliations

¹ 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.
² 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. Electronic address: baimingsheng@163.com.
³ 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. Electronic address: pengli1124@nxu.edu.cn.

PMID: 39617235
DOI: 10.1016/j.ijbiomac.2024.138207

Abstract

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.

Keywords: Glycyrrhiza uralensis polysaccharide; MAPK/PI3K/AKT pathway; Myocardial fibrosis; Structure.