State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
China Resources Sanjiu Medical & Pharmaceutical Co. Ltd., Shenzhen, 518110, China.
J Ethnopharmacol. 2021 Dec 5;281:114567. doi: 10.1016/j.jep.2021.114567. Epub 2021 Aug 24.
Multi-source phenomenon is very common for traditional Chinese medicine (TCM). Both Murraya exotica L. (ME) and Murraya paniculata (L.) Jack (MP) are used as the source plants of Murrayae Folium et Cacumen (MFC), a traditional Chinese medicine recorded in Chinese Pharmacopoeia for promoting qi and relieving pain, mainly for the treatment of stomach pain, rheumatism and arthralgia. However, up to now, there has been no comparative study of these two plants on their efficacies and mechanisms, thus, further research is needed to evaluate their similarity and difference in order to judge the reasonability for their common usage.
This study aims to compare the effects and potential mechanisms of ME and MP, the two source plants of MFC on gastric lesions in rats by pharmacodynamics and metabolomics.
A rat model of gastric lesions induced by 70% aqueous ethanol and 150 mmol/L HCl was established and adopted to evaluate the gastric protective effects of ME and MP by analysis of the lesion index, histopathological changes (observed by H&E staining and TUNEL staining) and cytokine levels (IL-1β, IL-6, TNF-α, MTL, and GAS). The potential mechanisms were investigated by LC-MS metabolomic analysis of the rat plasma.
ME and MP showed the similar effects on improving the lesions of rat stomachs and reducing the cytokine levels related to inflammation and digestion of rats. The metabolomics results showed that the metabolism of rats with gastric lesions was abnormal mainly in lipid metabolism, energy metabolism, and amino acid metabolism. ME and MP demonstrated a similar metabolic modulation for gastric lesions by acting on the similar pathways and metabolites. Also, PLA2 pathway was proved as an important pathway for ME and MP modulation of glycerophospholipid metabolism in gastric lesions.
Our results proved that it is feasible and reasonable to use both of ME and MP as the source plants of MFC, at least for the treatment of gastric lesions, due to their similar pharmacodynamics and metabolic modulation ability. Moreover, the combination of pharmacodynamics and metabolomics is an efficient means for multi-source TCM study.
中药(TCM)的多源现象非常普遍。九里香(ME)和两面针(MP)均被用作中药九里香的来源植物,该药在中国药典中被记录用于行气止痛,主要用于胃痛、风湿关节痛的治疗。然而,到目前为止,还没有对这两种植物的功效和机制进行比较研究,因此,需要进一步研究以评估它们的相似性和差异性,从而判断它们共同使用的合理性。
本研究旨在通过药效学和代谢组学比较 ME 和 MP,即九里香的两种来源植物对大鼠胃损伤的作用及其潜在机制。
采用 70%水乙醇和 150mmol/L HCl 诱导大鼠胃损伤模型,通过分析损伤指数、组织病理学变化(H&E 染色和 TUNEL 染色观察)和细胞因子水平(IL-1β、IL-6、TNF-α、MTL 和 GAS)评价 ME 和 MP 的胃保护作用。采用 LC-MS 代谢组学分析大鼠血浆,探讨潜在机制。
ME 和 MP 对改善大鼠胃损伤和降低与炎症和消化相关的细胞因子水平具有相似作用。代谢组学结果表明,胃损伤大鼠的代谢主要异常于脂质代谢、能量代谢和氨基酸代谢。ME 和 MP 通过作用于相似的途径和代谢物对胃损伤表现出相似的代谢调节作用。此外,PLA2 途径被证明是 ME 和 MP 调节胃损伤甘油磷脂代谢的重要途径。
我们的研究结果证明,由于 ME 和 MP 具有相似的药效学和代谢调节能力,将 ME 和 MP 均作为九里香的来源植物是可行且合理的,至少在治疗胃损伤方面是如此。此外,药效学和代谢组学相结合是研究多源中药的有效手段。