Structural elucidation, in vivo tracking and pharmacokinetic profiling of a novel polysaccharide with anti-migraine efficacy.

Abstract

Tianshu Capsule (TSC), a traditional Chinese medicine (TCM) formula derived from "Da Chuan Xiong Fang", has a long history in migraine treatment. Studies have shown that TSC crude polysaccharides exhibit superior anti-migraine effects, but their chemical characteristics, in vivo pharmacokinetics, and distribution profiles remain uncharacterized. In this study, we elucidated the structures of a 1,4-glucan (TSCP-1a) and a novel pectin-like polysaccharide (TSCP-4) featuring a backbone of glucogalacturonan substituted by arabinans and arabinogalactan (AG) residues from TSC. In a nitroglycerin-induced migraine animal model, the homogeneous polysaccharide TSCP-4 significantly alleviated migraine symptoms, corresponding to the consistent bioactivity of TSC formula. To track its in vivo behavior, TSCP-4 was fluorescently labeled with cyanine 5.5 amine (C-TSCP4) and FITC (F-TSCP4). Near-infrared imaging showed that orally administered C-TSCP4 was absorbed in the small intestine and distributed to liver and kidney. Furthermore, the quantitative method for F-TSCP4 was applied to the pharmacokinetic analysis, revealing that F-TSCP4 exhibited favorable absorption characteristics and prolonged mean residence time (MRT). Conclusively, this study provides a detailed analysis of the fine structure and oral absorption properties of TSC-active homogeneous polysaccharides, offering valuable insights into the material basis of compound polysaccharides in TCM formulations.