Oksana Zaitseva, Marta Sergushkina, Tatyana Polezhaeva, Olga Solomina, Andrey Khudyakov
This review characterizes the mechanisms of action of animal polysaccharides (chitin, chitosan, hyaluronan, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparin/heparan sulfate) based on their structural and conformational features. A systematic search was conducted in PubMed, Scopus, Web of Science, and the Russian Citation Index (2015-2026). The review organizes polysaccharides according to three structure-dependent targeting paradigms: (1) charge-mediated targeting (chitosan, dermatan sulfate), where cationic or anionic density determines electrostatic interactions; (2) molecular weight-dependent receptor selection (hyaluronan, chitosan), where chain length dictates receptor engagement and signaling outcomes; and (3) sulfation pattern-directed protein recognition (heparin/heparan sulfate, chondroitin sulfate, keratan sulfate), where specific O- and N-sulfation codes enable selective protein binding. Key findings reveal that biological activity depends largely on molecular weight, sulfation pattern, and charge density, with concentration-dependent reversal of immunomodulatory effects - low doses elicit anti-inflammatory while high doses induce pro-inflammatory activation - representing a critical consideration for therapeutic design. Recent methodological advances (UPLC-MS/MS, chemical synthesis, chemoenzymatic synthesis) now enable detailed structure-activity studies, particularly for keratan sulfate, though knowledge gaps remain. The convergence of mechanisms across polysaccharide classes - particularly NF-κB pathway modulation - suggests common principles underlying bioactivity. The review also addresses major obstacles to clinical translation, including polydispersity, batch variability, and characterization challenges, and proposes future research directions to overcome these limitations.