Immunomodulatory Activity and Its Mechanisms of Two Polysaccharides from Poria cocos

Polyporaceae is an important fungal family that has been a source of natural products with a range of pharmaceutical activities in China. In our previous study, two polysaccharides, PCWPW and PCWPS, with significant antioxidant and antidepressant activity were obtained from Poria cocos. In this study, we evaluated their potential molecular mechanisms in the immunomodulation of macrophages. PCWPW and PCWPS were characterized by GC-MS analysis to contain 1,3-linked Glcp. ELISA assays results demonstrated that the secretion of TNF-alpha was significantly enhanced by PCWPW/PCWPS. RNA-seq data demonstrated that PCWPS treatment modulated the expression of immune-related genes in macrophages, which was further confirmed by RT-qPCR assays. The activation of TNF-alpha secretion was found to be mannose receptor (MR) dependent and suppressed by MR inhibitor pretreatment. Moreover, the amount of TNF-alpha cytokine secretion in PCWPW/PCWPS-induced RAW264.7 cells was decreased when pretreated with NF-kappa B or MAPK signaling pathway inhibitors. Collectively, our results suggested that PCWPW and PCWPS possessed immunomodulatory activity that regulates TNF-alpha expression through the NF-kappa B/MAPK signaling pathway by binding to mannose receptors. Therefore, PCWPW and PCWPS isolated from Poria cocos have potential as drug candidates for immune-related disease treatment.