基于靶向代谢组学探究广藿香活性成分治疗炎症性肠病的作用和机理

广藿香是历代医家治疗脘痞呕吐、腹痛吐泻的要药，但其治疗腹泻腹痛的物质基础和作用机理尚不清楚。前期代谢轮廓分析发现，在TNBS诱导的IBD大鼠血液和尿液中检测到11个代谢标志物，分别与肠道菌群失衡、免疫炎性反应和肠屏障损伤等IBD病理机制密切相关；而广藿香的主要成分广藿香醇可显著减轻IBD模型动物的疾病指数、改善炎性症状，具有明确的抗IBD作用；广藿香酮和芹菜素分别具有抗病原微生物和抗炎、抗氧化等生物活性，可能是广藿香抗IBD活性成分。本课题提出"广藿香醇等广藿香有效成分群通过保护肠屏障功能、调节菌群和免疫炎性反应而发挥抗IBD的作用；可以影响IBD相关的内源性代谢物水平"。拟采用TNBS大鼠对上述主要活性组分进行抗IBD作用考察，结合靶向代谢分析，明确其对IBD相关代谢标志物的调节作用，探讨其可能的作用机制。本研究将进一步阐明广藿香的物质作用基础，为应用代谢组学进行中药研究提供新思路。

Pogostemon cablin has been used for thousands of years to treat diarrhea, abdominal pain and vomiting in China, but its effective components and uderlying mechanism remains obscure. Our previous metabonomic profiling find a total number of 11 metabolite markers in plasma and urine of rats with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD). These markers indicate intestinal barrier damage, microbiosis and inflammatory response in TNBS rats. Whereas, patchouli alcohol, the major volatile effective component of Pogostemon cablin with established anti-inflammatory and antimicrobial effects, attenuated the disease activity index and alleviated inflammtion in TNBS rats. This result revealed that patchouli alcohol has a significant anti-IBD activity. Pogostone, another major volatile ingredient, has potent anti-microbial activity. Apigenin, a major flavonoid constituent, is well known for its anti-inflammatory, anti-oxidative and anti-microbial activities. Based on these facts, it can be speculated that patchouli alcohol, pogostone, and apigenin are possible effective components, by which Pogostemon cablin exert a protective effect against IBD, and these components can modulate IBD-related metabolite markers. In this study, we will examine the anti-IBD activity of the three patchouli ingredients in TNBS rat model, and investigate whether the three patchouli ingredients exerted their anti-IBD effects by protecting intestinal barrier, restoring host-microbiota homeostasis and inhibiting inflammation. To further clarify the protective mechanism of the three patchouli ingredients, a metabolomic analysis targeting on the previously discovered 11 IBD-related metabolite markers and critical upstream or downstream metabolites will be conducted. This study aims to identify the effective anti-IBD components in Pogostemon cablin, and explore the underlying mechanism using a targeted metabolomic approach.