Tao Yiwen, Wang Lijie, Xiong Shuangfeng, Ding Yin, Nhamdriel Tsedien, Zhang Yi, Zhang Jing, Fan Gang
School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
Department of Tibetan Medicine, University of Tibetan Medicine, Lhasa, 850000, China.
Phytomedicine. 2025 Sep;145:157076. doi: 10.1016/j.phymed.2025.157076. Epub 2025 Jul 14.
Immune dysfunction is linked to the progression of various diseases. Milk-processed Polygonatum cyrtonema Hua (MPC) is a traditional medicine with nourishing effects in the Qinghai-Tibet Plateau region of China. However, the immune-enhancing effect of MPC and its underlying mechanism remain unclear.
This study aims to investigate the therapeutic effect and underlying mechanism of MPC on immunosuppressed mice.
A cyclophosphamide (CY)-induced immunosuppressive mouse model was established to evaluate the effects of MPC on the gut microbiota, intestinal barrier and immune response.
The chemical composition of MPC was identified by UPLC-Q-Exactive Orbitrap MS technology. Immune organ weight, body weight, colon length, biochemical parameters, and histopathology were examined. The levels of three short-chain fatty acids (SCFAs) were quantified via HPLC. 16S rRNA sequencing, fecal microbiota transplantation (FMT), antibiotic intervention, and Western blot were applied to explore the mechanism of MPC.
MPC significantly enhanced the production of some key cytokines (IL-2, IFN-γ, IL-4, IL-10, and TGF-β3), immunoglobulins (IgM and IgG), and transcription factors (T-bet, GATA-3, RORγt, and Foxp3). Additionally, MPC maintained intestinal mucosal integrity by upregulating tight junction proteins ZO-1, Claudin-1, E-cadherin, and Occludin. 16S rRNA sequencing of fecal samples revealed that MPC increased the relative abundance of beneficial SCFA-producing bacteria, specifically Lachnospiraceae_UCG-006, while decreasing the relative abundance of several pathogenic taxa, including Prevotellaceae, Alloprevotella, and Eubacterium_coprostanoligenes_group. Notably, antibiotic intervention and FMT experiments demonstrated that the immune-enhancing effect of MPC was dependent on the gut microbiota. MPC also increased the levels of three SCFAs including acetate, propionate, and butyrate. Besides, MPC was found to activate the SCFAs/GPR43/Blimp-1 pathway, leading to the production of IL-10, which enhanced the immune response.
This study demonstrates for the first time that MPC has a significant immune-enhancing effect. The mechanisms include restoring the balance of gut microbiota, promoting the production of SCFAs, repairing intestinal mucosal damage and enhancing immune function. These findings support the potential of MPC as a natural agent for improving gut health and systemic immunity.
免疫功能障碍与多种疾病的进展相关。炮制黄精（MPC）是中国青藏高原地区具有滋补作用的传统药物。然而，MPC的免疫增强作用及其潜在机制尚不清楚。
本研究旨在探讨MPC对免疫抑制小鼠的治疗作用及其潜在机制。
建立环磷酰胺（CY）诱导的免疫抑制小鼠模型，以评估MPC对肠道微生物群、肠道屏障和免疫反应的影响。
采用超高效液相色谱-四极杆-静电场轨道阱质谱技术鉴定MPC的化学成分。检测免疫器官重量、体重、结肠长度、生化参数和组织病理学。通过高效液相色谱法定量三种短链脂肪酸（SCFA）的水平。应用16S rRNA测序、粪便微生物群移植（FMT）、抗生素干预和蛋白质免疫印迹法探讨MPC的作用机制。
MPC显著增强了一些关键细胞因子（IL-2、IFN-γ、IL-4、IL-10和TGF-β3）、免疫球蛋白（IgM和IgG）以及转录因子（T-bet、GATA-3、RORγt和Foxp3）的产生。此外，MPC通过上调紧密连接蛋白ZO-1、Claudin-1、E-钙黏蛋白和闭合蛋白来维持肠道黏膜完整性。粪便样本的16S rRNA测序显示，MPC增加了有益的产SCFA细菌的相对丰度，特别是毛螺菌科_UCG-006，同时降低了包括普雷沃氏菌科、别普雷沃氏菌属和粪甾醇真杆菌属在内的几种致病类群的相对丰度。值得注意的是，抗生素干预和FMT实验表明，MPC的免疫增强作用依赖于肠道微生物群。MPC还增加了乙酸盐、丙酸盐和丁酸盐这三种SCFA的水平。此外，发现MPC激活SCFAs/GPR43/Blimp-1通路，导致IL-10的产生，从而增强免疫反应。
本研究首次证明MPC具有显著的免疫增强作用。其机制包括恢复肠道微生物群平衡、促进SCFA产生、修复肠道黏膜损伤和增强免疫功能。这些发现支持了MPC作为改善肠道健康和全身免疫的天然药物的潜力。
