A novel branched galacturonan from Gardenia jasminoides alleviates liver fibrosis linked to TLR4/NF-κB signaling

Xiaonan Ma; Wanqi Zhou; Yingmin Nie; Xiaoqi Jing; Saijuan Li; Can Jin; Anming Zhu; Juan Su; Wenfeng Liao; Kan Ding

doi:10.1016/j.ijbiomac.2023.125540

A novel branched galacturonan from Gardenia jasminoides alleviates liver fibrosis linked to TLR4/NF-κB signaling

Int J Biol Macromol. 2023 Aug 1:245:125540. doi: 10.1016/j.ijbiomac.2023.125540. Epub 2023 Jun 22.

Authors

Xiaonan Ma¹, Wanqi Zhou², Yingmin Nie¹, Xiaoqi Jing³, Saijuan Li², Can Jin⁴, Anming Zhu², Juan Su³, Wenfeng Liao³, Kan Ding⁵

Affiliations

¹ Glycochemistry and Glycobiology Lab, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing 100049, China.
² Glycochemistry and Glycobiology Lab, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, Jiangsu Province 210029, China.
³ Glycochemistry and Glycobiology Lab, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
⁴ Glycochemistry and Glycobiology Lab, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, Jiangsu Province 210029, China; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, SSIP Healthcare and Medicine Demonstration Zone, Zhongshan Tsuihang New District, Zhongshan, Guangdong 528400, China.
⁵ Glycochemistry and Glycobiology Lab, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, Jiangsu Province 210029, China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing 100049, China; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, SSIP Healthcare and Medicine Demonstration Zone, Zhongshan Tsuihang New District, Zhongshan, Guangdong 528400, China. Electronic address: dingkan@simm.ac.cn.

PMID: 37355063
DOI: 10.1016/j.ijbiomac.2023.125540

Abstract

Gardenia jasminoides (GJ) is a classic edible medicine in China of which the fruit has been proved to alleviate liver damage. We hypothesized whether polysaccharide in the fruit could have comparable bioactivity. To address this, a novel polysaccharide GJE0.2-2, is purified from the fruit of Gardenia jasminoides. Indeed, GJE0.2-2 may attenuate CCl₄-induced liver fibrosis in mice and impede the expression of critical fibrogenesis associated molecules such as α-SMA, FN1, and Collagen I induced by TGF-β in human hepatic stellate LX-2 cells. Mechanism studies suggest that this bioactivity may be implicated in TLR4/NF-κB signaling pathway via directly binding to TLR4. The structure characterization shows that the backbone of this polysaccharide is mainly composed of galacturonic acid with minor rhamnose, branched with galactose and arabinose, galacturonic acid, and esterified hexenuronic acid (HexpA). These findings provide evidence for a novel pectin-linked polysaccharide-based new drug candidate development for liver fibrosis therapy.

Keywords: Gardenia jasminoides; Liver fibrosis; NF-κB; Pectin; Polysaccharides; TLR4.