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护肝清脂方饮片汤剂与配方颗粒的化学成分、药效一致性及机制研究
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| 篇名： | 护肝清脂方饮片汤剂与配方颗粒的化学成分、药效一致性及机制研究 |
| TITLE： | Study on chemical composition，pharmacodynamic consistency and mechanism between Hugan qingzhi formula decoction and its formulated granules |
| 摘要： | 目的 研究护肝清脂方（HGQZ）饮片汤剂与配方颗粒的特征成分含量及对高脂饮食诱导的非酒精性脂肪性肝病（NAFLD）模型小鼠药效的一致性，并探讨其潜在作用机制。方法运用液相色谱-串联三重四极杆质谱技术，分析、比较HGQZ饮片汤剂与配方颗粒中6种特征成分的含量。将雄性C57BL/6小鼠分为正常对照组、模型组、HGQZ饮片汤剂低/高剂量组（13、26g/kg，以生药量计）、HGQZ配方颗粒低/高剂量组（13、26g/kg，以生药量计），每组6只。除正常对照组小鼠给予普通维持饲料外，其余各组小鼠均给予高脂饲料20周以建立NAFLD模型；造模同时，各组小鼠灌胃相应药液或等体积水1次。检测其空腹血糖（FBG）水平和葡萄糖、胰岛素耐量，体重和肝指数、白色脂肪指数和棕色脂肪指数，以及脂质指标（总胆固醇、甘油三酯）和肝功能指标（天冬氨酸转氨酶、丙氨酸转氨酶）水平，观察其肝组织病理学形态和脂质堆积情况。取模型组、HGQZ饮片汤剂高剂量组、HGQZ配方颗粒高剂量组小鼠血清样品，进行代谢组学分析，并针对潜在机制进行验证。结果HGQZ饮片汤剂与配方颗粒中，人参皂苷Rb1、香蒲新苷、异鼠李素-3-O-新橙皮苷、金丝桃苷、荷叶碱、23-乙酰泽泻醇B含量比较，差异均无统计学意义（P＞0.05）。与模型组比较，HGQZ饮片汤剂组与配方颗粒各剂量组小鼠的肝组织病理改变均有所缓解，炎症细胞浸润和脂肪空泡均有所减少，其FBG水平、葡萄糖耐量、胰岛素耐量、体重、肝指数、白色/棕色脂肪指数、脂质和肝功能指标水平均普遍改善（P＜0.05），但组间比较差异均无统计学意义（P＞0.05）。模型组与HGQZ饮片汤剂高剂量组、模型组与HGQZ配方颗粒高剂量组分别有234、136个血清差异代谢物，取交集后得共同差异代谢物65种，富集于嘌呤代谢、三羧酸代谢等代谢通路；其中，模型组柠檬酸的含量均显著低于HGQZ饮片汤剂和配方颗粒的高剂量组（P＜0.05）；高剂量的HGQZ饮片汤剂与配方颗粒均可显著升高腺苷一磷酸活化的蛋白激酶（AMPK）的磷酸化水平（P＜0.05）。结论HGQZ饮片汤剂和配方颗粒的特征成分含量相当，对NAFLD模型小鼠的改善作用相似，且其抗NAFLD作用发挥均与激活AMPK能量代谢通路有关。 |
| ABSTRACT： | OBJECTIVE To evaluate the contents of characteristic components in Hugan qingzhi formula （HGQZ） decoction and formulated granules and the pharmacodynamic consistency of them on high-fat diet-induced non-alcoholic fatty liver disease （NAFLD） model mice， and explore their potential underlying mechanisms of action. METHODS Liquid chromatography-tandem mass spectrometry was used to analyze and compare the contents of six characteristic components in HGQZ decoction and formulated granules. Male C57BL/6 mice were randomly divided into normal control group， model group， HGQZ decoction low- dose and high-dose groups （13， 26 g/kg， calculated by crude drugs）， and HGQZ formulated granules low-dose and high-dose groups （13， 26 g/kg， calculated by crude drugs）， with 6 mice in each group. Except for the normal control group， which was fed a regular diet， the mice in the other groups were fed a high-fat diet for 20 weeks to establish the NAFLD model； at the same time， the mice in each group were gavaged with the corresponding drugs/water once. The fasting blood glucose （FBG） levels， glucose and insulin tolerance， body weight， liver index， white adipose Δ 基金项目 国家自然科学基金项目（No.82074078）；广东省基础 tissue index， brown adipose tissue index， as well as lipid levels （total cholesterol， triglycerides） and liver function indicators （aspartate transaminase， alanine transaminase） were measured. Additionally， histopathological changes and lipid accumulation in liver tissues were observed. The serum samples of mice in the model group， HGQZ decoction high-dose group and HGQZ formulated granules high-dose group were taken for metabolomics analysis， and validation of the underlying mechanisms was conducted. RESULTS There were no statistically significant differences in the contents of ginsenoside Rb1， typhaneoside， isorhamnetin-3-O-neohesperidoside， hyperoside， nuciferine， and 23-acetylalismol B between HGQZ decoction and HGQZ formulated granules （P＞0.05）. Compared with the model group， the hepatic histopathological changes in mice were alleviated in both the HGQZ decoction group and all dose groups of HGQZ formulated granules. Inflammatory cell infiltration and lipid vacuoles were reduced. Additionally， there was a general improvement in FBG levels， glucose tolerance， insulin tolerance， body weight， liver index， white/brown adipose tissue index， lipid levels， and liver function indicators （P＜0.05）. However， no statistically significant differences were observed between these treatment groups （P＞0.05）. There were 234 and 136 differentially expressed serum metabolites identified in the model group versus HGQZ decoction high-dose group， and model group versus HGQZ formulated granules high-dose group， respectively. After taking the intersection， 65 common differentially expressed metabolites were obtained， which were enriched in metabolic pathways such as purine metabolism and tricarboxylic acid cycle metabolism. Among these， the content of citrate in the model group was significantly lower than that in both the HGQZ decoction group and HGQZ formulated granules high-dose group （P＜0.05）. Both high-dose HGQZ decoction and formulated granules could significantly elevate the phosphorylation levels of AMP-activated protein kinase （AMPK） （P＜0.05）. CONCLUSIONS HGQZ decoction and formulated granules contain comparable amounts of characteristic components， and both exhibit equivalent efficacy on NAFLD model mice. The anti-NAFLD effects of HGQZ are associated with the activation of the AMPK energy metabolism pathway. |
| 期刊： | 2025年第36卷第12期 |
| 作者： | 张振华；龙昌锐；吴辉星；乡世健；周本杰 |
| AUTHORS： | ZHANG Zhenhua，LONG Changrui，WU Huixing，XIANG Shijian，ZHOU Benjie |
| 关键字： | 护肝清脂方；非酒精性脂肪性肝病；饮片汤剂；配方颗粒；一致性研究；含量；药效 |
| KEYWORDS： | Hugan qingzhi formula； non-alcoholic fatty liver disease； decoction； formulated granules； consistency study； |
| 阅读数： | 6 次 |
| 本月下载数： | 1 次 |
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