College of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, China.
China Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
BMC Complement Med Ther. 2021 Apr 12;21(1):120. doi: 10.1186/s12906-021-03276-4.
The idiosyncratic hepatotoxicity of Polygonum multiflorum (PM) has attracted considerable interest, but the idiosyncratically hepatotoxic components and endogenous metabolite changes resulting from idiosyncratic hepatotoxicity of PM are not well understood. The aim of this study was to identify the idiosyncratically hepatotoxic components and potential endogenous metabolic biomarkers for PM-induced liver injury.
Serum biochemical indicators and hematoxylin and eosin (H&E) staining were evaluated to identify pathological changes. Gas chromatography/mass spectrometry (GC-MS) was performed to identify changes in metabolic biomarkers. Orthogonal projection to latent structures discriminant analysis (OPLS-DA) was applied to determine group clustering trends and differential metabolites.
The results for the liver index, the liver function index and liver pathology showed that Polygonum multiflorum ethanol extract (PME), 50% ethanol elution fractions and tetrahydroxystilbene glucoside (TSG) from PME can induce idiosyncratic hepatotoxicity. TSG was the main idiosyncratically hepatotoxic component. Forty endogenous metabolites were identified in the rat liver. Six biomarkers, including lower levels of L-valine and higher levels of 3-hydroxybutyric acid, hexadecanoic acid, ribose, phosphoric acid and oxalic acid, were related to PM-induced liver injury. These differential biomarkers led to disruptions in amino acid, fatty acid, oxalate, energy and glucose metabolism. A total of 32 types of endogenous metabolites were identified in rat serum. Ten biomarkers were related to the liver injury induced by TSG, including lower levels of L-valine and L-proline and higher levels of urea, caproic acid, DL-malic acid, D-mannose, 3-hydroxybutyric acid, D-galactose, octadecane and hexadecanoic acid. These differential biomarkers led to disruptions in amino acid, glucose and fat metabolism. The mechanism of idiosyncratic hepatotoxicity in PM involves TSG-induced disruptions in amino acid metabolism, lipid metabolism, energy metabolism and glucose metabolism.
These findings reflect the material basis and metabolic mechanism of idiosyncratic PM hepatotoxicity.
何首乌的特异质肝毒性引起了广泛关注，但何首乌特异质肝毒性导致的特异质肝毒性成分和内源性代谢物变化尚不清楚。本研究旨在鉴定何首乌致肝损伤的特异质肝毒性成分和潜在的内源性代谢生物标志物。
通过血清生化指标和苏木精-伊红（H&E）染色评价病理变化。采用气相色谱/质谱（GC-MS）鉴定代谢生物标志物的变化。正交投影到潜在结构判别分析（OPLS-DA）用于确定组聚类趋势和差异代谢物。
肝指数、肝功能指标和肝病理结果表明，何首乌乙醇提取物（PME）、50%乙醇洗脱部位和 PME 中的四羟基二苯乙烯苷（TSG）均可诱导特异质肝毒性。TSG 是主要的特异质肝毒性成分。在大鼠肝中鉴定出 40 种内源性代谢物。6 种生物标志物，包括 L-缬氨酸水平降低和 3-羟基丁酸、十六烷酸、核糖、磷酸和草酸水平升高，与 PM 诱导的肝损伤有关。这些差异生物标志物导致氨基酸、脂肪酸、草酸盐、能量和葡萄糖代谢紊乱。在大鼠血清中鉴定出 32 种内源性代谢物。10 种生物标志物与 TSG 诱导的肝损伤有关，包括 L-缬氨酸和 L-脯氨酸水平降低和尿素、己酸、DL-苹果酸、D-甘露糖、3-羟基丁酸、D-半乳糖、十八烷和十六烷酸水平升高。这些差异生物标志物导致氨基酸、葡萄糖和脂肪代谢紊乱。PM 特异质肝毒性的机制涉及 TSG 诱导的氨基酸代谢、脂质代谢、能量代谢和葡萄糖代谢紊乱。
这些发现反映了何首乌特异质肝毒性的物质基础和代谢机制。
