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醋炙柴胡三种多糖的结构及协同抗肝癌作用比较

Comparison of structure and the synergistic anti-hepatocellular carcinoma effect of three polysaccharides from vinegar-baked Radix Bupleuri.

作者信息

Wang Xiaoshuang, Gan Jianfeng, Han Minghui, Wu Yayun, Liu Lijuan, Zhao Ya, Zhao Ruizhi

机构信息

State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, China; The Second Clinical Medical School of Guangzhou University of Chinese Medicine, China.

State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, China.

出版信息

Int J Biol Macromol. 2024 Dec;282(Pt 1):136755. doi: 10.1016/j.ijbiomac.2024.136755. Epub 2024 Oct 21.

Abstract

Three polysaccharides from Vinegar-baked Radix Bupleuri (VR) and their combined effects were studied. VRP3-3 was a branched polysaccharide with a molecular weight (Mw) of 16.05 kDa characterized by 1,5 linked-α-Araf, 1,2,4 linked-α-Rhap and 1,4 linked-α-GalpA as main chain with a small amount of esterification and acetylation groups. And side chains were connected to the O-3 of Araf, O-4 of Rhap. VRP2-3 had a Mw of 95.35 kDa, its backbone comprised of 1,2 linked-α-Galp, 1,4 linked-β-GalpA(O-Ac), 1,2,4 linked-α-Rhap and 1,5 linked α-Araf. The residues of 1,4 linked-β-Galp,1,3 linked-β-Galp and 1,6 linked-β-D-Galp were connected at O-4 of α-L-Rhap and O-3 of α-L-Araf as its side chain. VRP2-4 was a pectin polysaccharide with a Mw of 57.90 kDa. Its main chain was constituted of 1,4 linked-α-Galp, 1,4 linked-α-GalpA(OMe), 1,4 linked-α-GalpA and 1,2,4 linked-α-Rhap, with some acetylation. As the major side chain, 1,5 linked-α-Araf was connected to O-4 of α-Rhap, a small amount of t-α-Galp and t-α-Manp were also included. VRP3-3 showed superior synergistic effect in combination with paclitaxel, methotrexate and cisplatin than the other two polysaccharides. The VR polysaccharide with a ~16 kDa molecular weight, a larger polymerization degree of arabinan in the backbone and the triple helix structure are the key structures for activity. Together, our findings clarify the pharmacodynamic basis of VR and provide promising adjuvants for Hepatocellular Carcinoma (HCC) chemotherapy.

摘要

对醋炙柴胡(VR)中的三种多糖及其联合作用进行了研究。VRP3 - 3是一种支链多糖,分子量(Mw)为16.05 kDa,其特征是以1,5连接的α - 阿拉伯呋喃糖、1,2,4连接的α - 鼠李糖和1,4连接的α - 半乳糖醛酸为主链,带有少量酯化和乙酰化基团。侧链连接在阿拉伯呋喃糖的O - 3位、鼠李糖的O - 4位。VRP2 - 3的Mw为95.35 kDa,其主链由1,2连接的α - 半乳糖、1,4连接的β - 半乳糖醛酸(O - Ac)、1,2,4连接的α - 鼠李糖和1,5连接的α - 阿拉伯呋喃糖组成。1,4连接的β - 半乳糖、1,3连接的β - 半乳糖和1,6连接的β - D - 半乳糖残基作为侧链连接在α - L - 鼠李糖的O - 4位和α - L - 阿拉伯呋喃糖的O - 3位。VRP2 - 4是一种果胶多糖,Mw为57.90 kDa。其主链由1,4连接的α - 半乳糖、1,4连接的α - 半乳糖醛酸甲酯(OMe)、1,4连接的α - 半乳糖醛酸和1,2,4连接的α - 鼠李糖组成,并带有一些乙酰化。作为主要侧链,1,5连接的α - 阿拉伯呋喃糖连接在α - 鼠李糖的O - 4位,还包含少量的t - α - 半乳糖和t - α - 甘露糖。VRP3 - 3与紫杉醇、甲氨蝶呤和顺铂联合使用时显示出比其他两种多糖更好的协同作用。分子量约为16 kDa、主链中阿拉伯聚糖聚合度较大且具有三螺旋结构的VR多糖是活性的关键结构。总之,我们的研究结果阐明了VR的药效学基础,并为肝细胞癌(HCC)化疗提供了有前景的佐剂。

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