Inulin-like polysaccharide ABWW may impede CCl4 induced hepatic stellate cell activation through mediating the FAK/PI3K/AKT signaling pathway in vitro & in vivo

Xiaolan Dai; Zhenyun Du; Can Jin; Bixi Tang; Xia Chen; Xiaoqi Jing; Yumei Shen; Fei He; Shunchun Wang; Jia Li; Kan Ding; Yi Zang

doi:10.1016/j.carbpol.2023.121637

Inulin-like polysaccharide ABWW may impede CCl₄ induced hepatic stellate cell activation through mediating the FAK/PI3K/AKT signaling pathway in vitro & in vivo

Carbohydr Polym. 2024 Feb 15:326:121637. doi: 10.1016/j.carbpol.2023.121637. Epub 2023 Nov 28.

Authors

Xiaolan Dai¹, Zhenyun Du², Can Jin³, Bixi Tang⁴, Xia Chen⁵, Xiaoqi Jing⁵, Yumei Shen¹, Fei He⁵, Shunchun Wang⁶, Jia Li⁷, Kan Ding⁸, Yi Zang⁹

Affiliations

¹ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China.
² Glycochemistry and Glycobiology Lab, Carbohydrate Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
³ Glycochemistry and Glycobiology Lab, Carbohydrate Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Nanjing University of Traditional Chinese Medicine, Nanjing 563003, China.
⁴ Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
⁵ Glycochemistry and Glycobiology Lab, Carbohydrate Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
⁶ Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: [email protected].
⁷ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, UCAS, Hangzhou 310024, China; ZhongShan Institute for Drug Discovery, Zhongshan Tsuihang New District, Guangdong 528400, China. Electronic address: [email protected].
⁸ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; Glycochemistry and Glycobiology Lab, Carbohydrate Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; ZhongShan Institute for Drug Discovery, Zhongshan Tsuihang New District, Guangdong 528400, China. Electronic address: [email protected].
⁹ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; Lingang Laboratory, Shanghai 201203, China; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, UCAS, Hangzhou 310024, China. Electronic address: [email protected].

PMID: 38142102
DOI: 10.1016/j.carbpol.2023.121637

Abstract

Studies have shown that terrestrial acidic polysaccharides containing carboxyl groups and seaweed sulfated polysaccharides have strong potential in anti-liver fibrosis. However, there is no investigation on the anti-liver fibrosis of fructan, a ubiquitous natural polysaccharide. The present study aimed to understand the effect of fructan in ameliorating carbon tetrachloride (CCl₄)-induced liver fibrosis in mice. Here, an inulin-like fructan ABWW from Achyranthes bidentata Bl. was characterized by fructose enzymatic hydrolysis, methylation analysis, ESI-MS, and NMR. It was composed of →2)-β-d-Fruf-(1→ and →2)-β-d-Fruf-(1, 6→, terminated with →1)-α-d-Glcp and →2)-β-d-Fruf residues. The biological studies showed that ABWW could improve liver damage and liver fibrosis induced by CCl₄in vivo and inhibit hepatic stellate cell (HSC) activation and migration in vitro. We further demonstrated that ABWW inhibited LX2 activation via suppressing the FAK/PI3K/AKT signaling pathway. Hence, ABWW might be a potential novel active compound for anti-fibrosis new drug development.

Keywords: FAK/PI3K/AKT; Fructan; Hepatic fibrosis; Hepatic stellate cells.

MeSH terms

Animals
Carbon Tetrachloride
Hepatic Stellate Cells
Inulin* / metabolism
Liver / metabolism
Liver Cirrhosis / chemically induced
Liver Cirrhosis / drug therapy
Liver Cirrhosis / metabolism
Mice
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt* / metabolism
Signal Transduction

Substances

Proto-Oncogene Proteins c-akt
Inulin
Phosphatidylinositol 3-Kinases
Carbon Tetrachloride