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

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.