Panoramic characterization and structure-activity relationship of astragalus polysaccharides: Modulating M2-to-M1...

Area of Science:

• Immunology
• Biochemistry
• Pharmacology

Background:

• Over 30 Astragalus polysaccharides are known, but studies often yield inconsistent findings, hindering structure-activity relationship (SAR) analysis.
• Previous research lacks a comprehensive understanding of how Astragalus polysaccharide structures correlate with their therapeutic efficacy.

Purpose of the Study:

• To characterize Astragalus polysaccharides at crude, fractionated, and purified levels.
• To evaluate the M2-to-M1 repolarization effects, underlying mechanisms, and SAR of these polysaccharides.
• To establish a scientific foundation for the development of Astragalus-derived immunomodulators.

Main Methods:

• Fractionation of crude Astragalus polysaccharides (ARCP) into neutral (ARN) and acidic (ARA) components.
• Characterization of molecular weights and structural features (e.g., glucans, pectins, degree of methyl esterification).
• Assessment of M2-to-M1 repolarization activity, mechanism via TLR4-NF-κB pathway activation, and SAR analysis.

Main Results:

• ARN and ARA constituted 94% of ARCP, with distinct molecular weight distributions and structural compositions (α-1,4-glucans and pectins).
• Both neutral (ARNPs) and acidic (ARAPs) purified polysaccharides significantly promoted M2-to-M1 repolarization, generating tumor-suppressive M1 macrophages.
• SAR indicated medium-molecular-weight ARNP-2 and low-DM ARAP-2 were particularly potent, with specific structural features (C-6 carboxyl group) being critical for activity.

Conclusions:

• This study provides a comprehensive structural profile of Astragalus polysaccharides and their role in M2-to-M1 repolarization.
• The findings elucidate the mechanisms involving TLR4-NF-κB pathway activation and highlight key structural determinants of activity.
• This research offers a scientific basis for the targeted development and application of Astragalus polysaccharides in immunotherapy.