Li Xiaolin, Liu Tianlong, Liang Keke, Wang Renjie, Yang Jun, Chen Yidan, Wang Rong, Li Maoxing
College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, China.
Department of Pharmacy, The 940th Hospital of Joint Logistic Support Force of Chinese People's Liberation Army, Gansu Plateau Pharmaceutical Technology Center, Lanzhou, China.
Front Pharmacol. 2025 Apr 28;16:1482323. doi: 10.3389/fphar.2025.1482323. eCollection 2025.
(Benth. ex Hook.f.) Mathiesen (syn. (Benth. ex Hook.f.) Kudô) () is a traditional Tibetan medicine known for its hemostatic, analgesic, and anti-inflammatory effects, as well as its high content of 8--Acetyl Shanzhiside methyl ester (8-aS). Clinical and experimental studies have reported gastrointestinal side effects, such as diarrhea, loose stools, even to black stools, associated with . Given the bitter taste characteristic, laxative and antipyretic effects of iridoid glycosides, this study aims to investigate the antipyretic and anti-inflammatory effects of 8-aS (the primary iridoid glycosides of ) on yeast-induced pyrexia in rats. Additionally, the role 8-aS in modulating the intestinal flora composition and metabolome profile is explored.
The pyretic rat model was established by injected subcutaneously with 20% dry yeast suspension. Serum, hypothalamic tissues and colon content were collected for the assessment of relevant indicators. The peripheral inflammatory factors and central thermoregulatory mediators were assessed using enzyme-linked immunosorbent assay (ELISA). The expressions of mRNA and protein in hypothalamic tissue were evaluated through polymerase chain reaction (PCR), immunohistochemistry, and western blotting. 16S rDNA sequencing and LC-MS/MS were performed to determine the alteration and correlation of the intestinal flora and neurotransmitters in the colonic contents and hypothalamus.
Results show that 8-aS treatment reduced pyrogenic cytokines (such as IL-6, IL-1β), and down-regulated the level of central thermoregulatory mediators (PGE), via multiply involved in TLR4/NF-κB and HSP70/NF-κB signaling pathways. Crucially, 8-aS treatment significantly reduced the relative abundance of ( < 0.01), ( < 0.05) and ( < 0.05) in the intestinal flora. The correlation analysis demonstrated that 8-aS treatment significantly correlated with the increasing on the abundance of and levels of 5-hydroxytryptamine ( < 0.01), and tryptamine ( < 0.01). Our findings indicate that 8-aS exhibits significant antipyretic and anti-inflammatory properties, potentially mediated by intestinal flora and metabolites of neurotransmitters. The results of this study may help to elucidate the antipyretic and anti-inflammatory mechanism of 8-aS based on intestinal flora and metabolomics analysis.
（由本瑟姆（Benth. ex Hook.f.）命名）马蒂森（Mathiesen）（同义词：（由本瑟姆（Benth. ex Hook.f.）命名）库多（Kudô））（）是一种传统藏药，以其止血、镇痛和抗炎作用以及高含量的8 - 乙酰山栀苷甲酯（8 - aS）而闻名。临床和实验研究报告了与相关的胃肠道副作用，如腹泻、稀便，甚至黑便。鉴于环烯醚萜苷的苦味特征、泻药和解热作用，本研究旨在探讨8 - aS（的主要环烯醚萜苷）对酵母诱导的大鼠发热的解热和抗炎作用。此外，还探讨了8 - aS在调节肠道菌群组成和代谢组谱方面的作用。
通过皮下注射20%干酵母悬液建立发热大鼠模型。收集血清、下丘脑组织和结肠内容物以评估相关指标。使用酶联免疫吸附测定（ELISA）评估外周炎症因子和中枢体温调节介质。通过聚合酶链反应（PCR）、免疫组织化学和蛋白质印迹法评估下丘脑组织中mRNA和蛋白质的表达。进行16S rDNA测序和液相色谱 - 串联质谱（LC - MS/MS）以确定结肠内容物和下丘脑中肠道菌群和神经递质的变化及相关性。
结果表明，8 - aS处理可降低致热细胞因子（如IL - 6、IL - 1β），并通过多种途径参与TLR4/NF - κB和HSP70/NF - κB信号通路下调中枢体温调节介质（PGE）的水平。至关重要的是，8 - aS处理显著降低了肠道菌群中（<0.01）、（<0.05）和（<0.05）的相对丰度。相关性分析表明，8 - aS处理与和5 - 羟色胺水平（<0.01）以及色胺水平（<0.01）的增加显著相关。我们的研究结果表明，8 - aS具有显著的解热和抗炎特性，可能由肠道菌群和神经递质代谢产物介导。本研究结果可能有助于基于肠道菌群和代谢组学分析阐明8 - aS的解热和抗炎机制。
