Shanxi Key Laboratory for Modernization of TCVM, Department of Basic Sciences, Shanxi Agricultural University, Jinzhong 030801, China.
Molecules. 2023 Dec 20;29(1):50. doi: 10.3390/molecules29010050.
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 . 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-α 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-α secretion was found to be mannose receptor (MR) dependent and suppressed by MR inhibitor pretreatment. Moreover, the amount of TNF-α cytokine secretion in PCWPW/PCWPS-induced RAW264.7 cells was decreased when pretreated with NF-κB or MAPK signaling pathway inhibitors. Collectively, our results suggested that PCWPW and PCWPS possessed immunomodulatory activity that regulates TNF-α expression through the NF-κB/MAPK signaling pathway by binding to mannose receptors. Therefore, PCWPW and PCWPS isolated from have potential as drug candidates for immune-related disease treatment.
多孔菌科是一个重要的真菌家族，在中国一直是具有多种药物活性的天然产物的来源。在我们之前的研究中，从 中得到了两种具有显著抗氧化和抗抑郁活性的多糖 PCWPW 和 PCWPS。在本研究中，我们评估了它们在巨噬细胞免疫调节中的潜在分子机制。通过 GC-MS 分析对 PCWPW 和 PCWPS 进行了表征，结果表明它们均含有 1,3-连接的 Glcp。ELISA 检测结果表明，PCWPW/PCWPS 可显著增强 TNF-α 的分泌。RNA-seq 数据表明，PCWPS 处理可调节巨噬细胞中与免疫相关的基因表达，这进一步通过 RT-qPCR 检测得到了证实。TNF-α 分泌的激活被发现依赖于甘露糖受体（MR），并且 MR 抑制剂预处理可抑制其激活。此外，当用 NF-κB 或 MAPK 信号通路抑制剂预处理时，PCWPW/PCWPS 诱导的 RAW264.7 细胞中 TNF-α 细胞因子的分泌量减少。综上所述，我们的结果表明，PCWPW 和 PCWPS 具有免疫调节活性，通过与甘露糖受体结合，通过 NF-κB/MAPK 信号通路调节 TNF-α 的表达。因此，从 中分离得到的 PCWPW 和 PCWPS 可能成为治疗与免疫相关疾病的药物候选物。
