Sun Hui-Min, Zhang Ting, Li Zhen-Yu, Qin Xue-Mei
Shanxi Pharmaceutical Vocational College Taiyuan 030031, China.
Modern Research Center for Traditional Chinese Medicine, Shanxi University Taiyuan 030006, China.
Zhongguo Zhong Yao Za Zhi. 2022 Oct;47(19):5224-5234. doi: 10.19540/j.cnki.cjcmm.20220128.303.
This study compared the toxicity of raw Bupleuri Radix(BR) and vinegar-processed Bupleuri Radix(VPBR) based on proton nuclear magnetic resonance(1H-NMR), and explored the mechanism of toxicity. Thirty-two male Sprague-Dawley(SD) rats were randomly divided into four groups: a control group(distilled water), a raw BR group(15 g·kg(-1)·d(-1)), a rice VPBR(R-VPBR) group(15 g·kg(-1)·d(-1)), and a shanxi VPBR(S-VPBR) group(15 g·kg(-1)·d~(-1)). After administration for 30 d, pathological sections were treated and observed, and biochemical indexes related to liver and renal function were determined. The serum, liver, and kidney of rats were collected and analyzed by ~1H-NMR. The principal component analysis(PCA) and orthogonal partial least squares-discrimination analysis(OPLS-DA) were performed. The results showed that, as compared with the control group, alanine aminotransferase(ALT), aspartate aminotransferase(AST), and alkaline phosphatase(ALP) in the raw BR group were increased significantly, while ALT and ALP in the R-VPBR and S-VPBR groups were significantly decreased(P<0.05), which indicated that BR showed certain hepatotoxicity, and vinegar processing reduced its hepatotoxicity. No significant difference of blood urea nitrogen(BUN) and creatinine(CREA), the biochemical indexes related to renal function, was observed in the control group and administration groups, indicating that BR had less effect on the renal function. The results of multivariate statistical analysis showed that the biomarkers of BR affecting liver metabolism were methionine, glutamine, and glutamic acid, and affecting kidney metabolism were taurine, ornithine, and inosine. These biomarkers were mainly involved in amino acid metabolism, energy metabolism, lipid metabolism, and taurine metabolism. VPBR alleviated the effect on the biomarkers, and S-VPBR had smaller effect than R-VPBR. Combining the results of biochemical indexes and metabolomics analysis, both raw BR and VPBR showed toxic effect on rats, whereas vinegar processing reduced its toxicity. S-VPBR has smaller effect on kidney and liver metabolism than R-VPBR, which indicates that the vinegar used for processing has certain effect on the toxicity of BR.
本研究基于质子核磁共振（1H-NMR）比较了生柴胡（BR）与醋制柴胡（VPBR）的毒性，并探讨其毒性机制。将32只雄性Sprague-Dawley（SD）大鼠随机分为四组：对照组（蒸馏水）、生柴胡组（15 g·kg(-1)·d(-1)）、米制醋柴胡（R-VPBR）组（15 g·kg(-1)·d(-1)）和山西醋柴胡（S-VPBR）组（15 g·kg(-1)·d(-1)）。给药30 d后，处理并观察病理切片，测定与肝肾功能相关的生化指标。收集大鼠的血清、肝脏和肾脏，采用1H-NMR进行分析。进行主成分分析（PCA）和正交偏最小二乘判别分析（OPLS-DA）。结果显示，与对照组相比，生柴胡组的丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和碱性磷酸酶（ALP）显著升高，而R-VPBR组和S-VPBR组的ALT和ALP显著降低（P<0.05），这表明柴胡具有一定的肝毒性，醋制可降低其肝毒性。对照组与给药组中，与肾功能相关的生化指标血尿素氮（BUN）和肌酐（CREA）未见显著差异，表明柴胡对肾功能影响较小。多元统计分析结果显示，影响肝脏代谢的柴胡生物标志物为蛋氨酸、谷氨酰胺和谷氨酸，影响肾脏代谢的为牛磺酸、鸟氨酸和肌苷。这些生物标志物主要参与氨基酸代谢、能量代谢、脂质代谢和牛磺酸代谢。醋制柴胡减轻了对生物标志物的影响，且S-VPBR的影响小于R-VPBR。结合生化指标和代谢组学分析结果，生柴胡和醋制柴胡均对大鼠显示出毒性作用，而醋制可降低其毒性。S-VPBR对肾脏和肝脏代谢的影响小于R-VPBR，这表明用于炮制的醋对柴胡的毒性有一定影响。
