Lee Eun Kyeong, Koh Eun Mi, Kim Yu Na, Song Jeongah, Song Chi Hun, Jung Kyung Jin
Immunotoxicology Research Group, Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, Korea.
Animal Model Research Group, Korea Institute of Toxicology, Jeongeup 56212, Korea.
Pharmaceutics. 2022 Jul 6;14(7):1423. doi: 10.3390/pharmaceutics14071423.
Hispolon is a potent anticancer, anti-inflammatory, antioxidant, and antidiabetic agent isolated from , an oriental medicinal mushroom. However, the immunomodulatory mechanisms by which hispolon affects macrophages and lymphocytes remain poorly characterized. We investigated the immunomodulatory effects of hispolon on oxidative stress, inflammatory responses, and lymphocyte proliferation using lipopolysaccharide (LPS)-treated RAW264.7 macrophages or mitogen/alloantigen-treated mouse splenocytes. Hispolon inhibited LPS-induced reactive oxygen and nitrogen species (ROS/RNS) generation and decreased total sulfhydryl (SH) levels in a cell-free system and RAW264.7 cells. Hispolon exerted significant anti-inflammatory effects by inhibiting production of the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) and activation of nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) in LPS-treated RAW264.7 cells. Hispolon also modulated NF-κB and STAT3 activation by suppressing the NF-κB p65 interaction with phospho-IκBα and the STAT3 interaction with JAK1, as determined via coimmunoprecipitation analysis. Additionally, hispolon significantly decreased lymphocyte proliferation, T cell responses and T helper type 1 (Th1)/type 2 (Th2) cytokines production in mitogen/alloantigen-treated splenocytes. We conclude that hispolon exerts immunomodulatory effects on LPS-treated macrophages or mitogen/alloantigen-treated splenocytes through antioxidant, anti-inflammatory, and antiproliferative activities. Thus, hispolon may be a therapeutic agent for treating immune-mediated inflammatory diseases.
桑黄多糖是从一种东方药用蘑菇中分离出的一种强效抗癌、抗炎、抗氧化和抗糖尿病药物。然而，桑黄多糖影响巨噬细胞和淋巴细胞的免疫调节机制仍不清楚。我们使用脂多糖（LPS）处理的RAW264.7巨噬细胞或丝裂原/同种异体抗原处理的小鼠脾细胞，研究了桑黄多糖对氧化应激、炎症反应和淋巴细胞增殖的免疫调节作用。桑黄多糖在无细胞体系和RAW264.7细胞中抑制LPS诱导的活性氧和氮物种（ROS/RNS）生成，并降低总巯基（SH）水平。桑黄多糖通过抑制LPS处理的RAW264.7细胞中促炎细胞因子白细胞介素6（IL-6）和肿瘤坏死因子α（TNF-α）的产生以及核因子κB（NF-κB）和信号转导子及转录激活子3（STAT3）的激活，发挥显著的抗炎作用。通过免疫共沉淀分析确定，桑黄多糖还通过抑制NF-κB p65与磷酸化IκBα的相互作用以及STAT3与JAK1的相互作用来调节NF-κB和STAT3的激活。此外，桑黄多糖显著降低丝裂原/同种异体抗原处理的脾细胞中的淋巴细胞增殖、T细胞反应和1型辅助性T细胞（Th1）/2型辅助性T细胞（Th2）细胞因子的产生。我们得出结论，桑黄多糖通过抗氧化、抗炎和抗增殖活性对LPS处理的巨噬细胞或丝裂原/同种异体抗原处理的脾细胞发挥免疫调节作用。因此，桑黄多糖可能是治疗免疫介导的炎症性疾病的一种治疗药物。
