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黄芩-黄连药对通过调控 Cyp4a 家族对高血脂症小鼠的成分协同作用机制

Mechanism of the components compatibility of Scutellariae Radix and Coptidis Rhizoma on mice with hyperlipidemia by regulating the Cyp4a family.

机构信息

The Institute of Basic Theory of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China.

Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, 100700, China.

出版信息

J Ethnopharmacol. 2024 Sep 15;331:118263. doi: 10.1016/j.jep.2024.118263. Epub 2024 Apr 25.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Scutellaria baicalensis Georgi (Scutellariae Radix, SR) and Coptis chinensis Franch (Coptidis Rhizoma, CR) is a classic herbal pair used in many Traditional Chinese Medicine formulations in the treatment of hyperlipidemia (HLP). As effective ingredients of the drug pair, the effects and mechanisms of berberine and baicalin in the treatment of HLP in the form of components compatibility are still unclear.

AIM OF THE STUDY

To explore the mechanism of the components compatibility of SR and CR in the treatment of HLP.

MATERIALS AND METHODS

The HLP model was established by a high-fat diet. Serum biochemical indexes were detected. Transcriptomics and metabolomics were detected. RT-PCR and Western Blot were used to analyze the effect of RA on the expression of the Cyp4a family during the treatment of HLP.

RESULTS

Berberine-baicalin (RA) has a good effect in the treatment of HLP. RA can significantly reduce the body weight and liver weight of HLP, reduce the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), and increase the level of high-density lipoprotein (HDL-C). Through transcriptomic analysis, RA significantly reversed the gene expression of Cyp4a10, Cyp4a12 b, Cyp4a31, and Cyp4a32 in cytochrome P450 family 4 subfamily a (Cyp4a) which related to fatty acid degradation in the liver of HLP mice. The results of fatty acid detection showed that RA could significantly regulate heptanoic acid, EPA, adrenic acid, DH-γ-linolenic acid, and DPA in the cecum of HLP mice. The Cyp4a family genes regulated by RA are closely related to a variety of fatty acids regulated by RA. RT-PCR confirmed that RA could regulate Cyp4a mRNA expression in HLP mice. WB also showed that RA can regulate the protein expression level of Cyp4a.

CONCLUSION

The components compatibility of SR and CR can effectively improve the blood lipid level of HLP mice, its mechanism may be related to regulating Cyp4a gene expression and affecting fatty acid degradation, regulating the level of fatty acid metabolism in the body.

摘要

草药关联

黄芩(黄芩根,SR)和黄连(黄连根茎,CR)是一种经典的草药组合,用于许多中药方剂中治疗高血脂(HLP)。作为药物组合的有效成分,小檗碱和黄芩苷以成分配伍形式治疗 HLP 的作用和机制尚不清楚。

研究目的

探讨 SR 和 CR 成分配伍治疗 HLP 的作用机制。

材料与方法

采用高脂饮食建立 HLP 模型,检测血清生化指标。采用转录组学和代谢组学检测。采用 RT-PCR 和 Western blot 分析 RA 对 HLP 治疗过程中 Cyp4a 家族表达的影响。

结果

小檗碱-黄芩苷(RA)在治疗 HLP 方面有较好的效果。RA 可显著降低 HLP 小鼠的体重和肝重,降低总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)水平,提高高密度脂蛋白(HDL-C)水平。通过转录组学分析,RA 显著逆转了 Cyp4a 家族中与肝内脂肪酸降解相关的 Cyp4a10、Cyp4a12b、Cyp4a31 和 Cyp4a32 基因的表达。脂肪酸检测结果表明,RA 可显著调节 HLP 小鼠盲肠中的庚酸、EPA、花生四烯酸、DH-γ-亚麻酸和 DPA。RA 调节的 Cyp4a 家族基因与 RA 调节的多种脂肪酸密切相关。RT-PCR 证实 RA 可调节 HLP 小鼠 Cyp4a mRNA 表达。WB 也显示 RA 可调节 Cyp4a 蛋白表达水平。

结论

SR 和 CR 的成分配伍能有效改善 HLP 小鼠的血脂水平,其机制可能与调节 Cyp4a 基因表达、影响脂肪酸降解、调节体内脂肪酸代谢水平有关。

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