Integrated gut microbiota and serum metabolomics reveal the protective effect of oleanolic acid on liver and kidney-injured rats induced by Euphorbia pekinensis.
Integrated gut microbiota and serum metabolomics reveal the protective effect of oleanolic acid on liver and kidney-injured rats induced by Euphorbia pekinensis.
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DOI：
10.1002/ptr.7673
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发表时间：
2022-11
期刊：
影响因子：
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通讯作者：
Xiao-Fen Xu;Qiyuan Shan;Rui Ding;Q. Lyu;Lichuang Huang;Xinyi Chen;Xin Han;Qiao Yang;
中科院分区：
文献类型：
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作者：
Xiao-Fen Xu;Qiyuan Shan;Rui Ding;Q. Lyu;Lichuang Huang;Xinyi Chen;Xin Han;Qiao Yang;
大戟（EP）是一种治疗水肿的常用中药，具有潜在的肝肾毒性。但其毒性机制及预防仍有待探索。齐墩果酸 (OA) 是一种三萜酸，具有潜在的肝肾保护活性。我们研究了 OA 对 EP 诱导的肝肾毒性的保护作用和潜在机制。在这项研究中，大鼠通过灌胃给予 EP 总二萜（TDEP，16 mg/kg）和 OA（10、20、40 mg/kg），持续 4 周。结果显示，TDEP给药可导致肝肾生化参数增加3-4倍并伴有组织病理学损伤，而OA治疗可以以剂量依赖性方式改善这些参数。在微生物和代谢水平上，给予 TDEP 后，肠道菌群和宿主代谢受到干扰。胆汁酸代谢紊乱是最重要的代谢途径，次级胆汁酸增加，结合胆汁酸减少。 OA治疗可以改善肠道菌群和代谢胆汁酸谱的紊乱。进一步相关性分析筛选出大肠杆菌、志贺氏菌、棕霉属、Acetatifactor、Akkermansia与胆汁酸代谢紊乱密切相关。总之，齐墩果酸可以通过改善肠道菌群调节胆汁酸代谢紊乱来预防 EP 引起的肝肾毒性。
Euphorbia pekinensis (EP) is a commonly used Chinese medicine treating edema with potential hepatorenal toxicity. However, its toxic mechanism and prevention are remained to be explored. Oleanolic acid (OA) is a triterpene acid with potential hepatorenal protective activities. We investigated the protective effect and potential mechanism of OA on EP-induced hepatorenal toxicity. In this study, rats were given total diterpenes from EP (TDEP, 16 mg/kg) combined with OA (10, 20, 40 mg/kg) by gavage for 4 weeks. The results showed that TDEP administration could lead to a 3-4-fold increasement in hepatorenal biochemical parameters with histopathological injuries, while OA treatment could ameliorate them in a dose-dependent manner. At microbial and metabolic levels, intestinal flora and host metabolism were perturbed after TDEP administration. The disturbance of bile acid metabolism was the most significant metabolic pathway, with secondary bile acids increasing while conjugated bile acids decreased. OA treatment can improve the disorder of intestinal flora and metabolic bile acid spectrum. Further correlation analysis screened out that Escherichia-Shigella, Phascolarctobacterium, Acetatifactor, and Akkermansia were closely related to the bile acid metabolic disorder. In conclusion, oleanolic acid could prevent hepatorenal toxicity induced by EP by regulating bile acids metabolic disorder via intestinal flora improvement.