Abstract
Background: New immunosuppressants with good efficacy and high safety are urgently needed to address immune rejection following organ transplantation. The study aimed to investigate the effect of alkali-extracted vinegar-baked Radix Bupleuri polysaccharides (KVBCPs) on organ graft rejection and their potential mechanisms. Methods: KVBCP was separated by membrane separation technology, and the physicochemical properties were analyzed by chemical and instrument method. The hyperimmune T lymphocyte model was used to screen the immunosuppressive activity of KVBCP fractions by examining the effects on lymphocyte proliferation and CD4+ T lymphocytes, and the skin graft rejection mice was used to verify the efficacy of active KVBCP fractions by detecting the CD3+ and CD4+/CD8+ infiltration, Th1/Th2 cytokines, Th17 and Tregs proportion. Results: Five KVBCP fractions (KVBCP1, KVBCP2, KVBCP3, KVBCP4 and KVBCP5) were obtained. They all showed characteristic absorption peaks of polysaccharides in the FT-IR spectra, but their molecular weights and monosaccharide compositions were different. Five KVBCPs all inhibited the proliferation of T lymphocytes and suppressed the proportion of CD4+ T lymphocytes in vitro. Among them, KVBCP3 and KVBCP4 exhibited better activity. KVBCP3 and KVBCP4 also delayed the skin scab, necrosis signs, decreased the graft rejection score, decreased CD3+ and CD4+/CD8+ infiltration in the skin allograft mice. They decreased IL-2 level (Th1 factor), increased IL-4 level (Th2 factor), decreased the proportion of Th17 cells, and increased the proportion of Treg cells after skin transplantation. Conclusion: KVBCPs, especially KVBCP3 and KVBCP4, suppress hyperimmune T lymphocytes and ameliorate skin graft rejection through correcting the imbalance of Th1/Th2 and Th17/Tregs.