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整合代谢组学策略和靶标预测,揭示四种典型“寒”性中药对甲状腺功能亢进症大鼠的改善作用。

Integrate metabolomics strategy and target prediction to reveal the ameliorate effect of four typical 'cold' property herbs on hyperthyroidism rats.

机构信息

Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin, 150040, Heilongjiang, China.

School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, Guangdong, China.

出版信息

J Ethnopharmacol. 2023 Jan 30;301:115772. doi: 10.1016/j.jep.2022.115772. Epub 2022 Oct 4.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

The 'cold' property herbs are commonly applied in heat syndrome. Unfortunately, the underlying mechanisms of the 'cold' property herbs on heat syndrome has not been investigated.

AIM OF THE STUDY

The study aimed to probe the activities of the four typical 'cold' property herbs on hyperthyroidism.

MATERIALS AND METHODS

Firstly, the four typical 'heat' property herbs were set as contrasting experiment. Then. the physical sign, thyroid function and metabolism profile (multivariate statistical analysis) were assessing the difference between the four typical 'cod' property herbs and the four typical 'heat' property herbs. H&E staining were used to confirmed the influence of the typical 'cold' property herbs on hyperthyroidism. A metabolomics approach combine with network pharmacology were explored the effected mechanism of the typical 'cold' property herbs on hyperthyroidism. the gene expression of UCP-1 was detected by RT-PCR. The metabolites pathway and target-associated metabolites were verified Na/K-ATP enzyme and GSH, as well IL6, IL17, MAPK and PPAR-γ, which detected by commercial kits and Western blot.

RESULTS

It is proved that the four typical 'cold' property herbs effectively ameliorate the physical sign, thyroid function and metabolism profile in hyperthyroidism rats, but the four typical 'heat' property herbs showed no benefit. Moreover, the four typical 'cold' property herbs regulated energy metabolism, glutathione metabolism, taurine hypotaurine metabolism, thyroid hormone synthesis, arachidonic acid metabolism and linoleic acid metabolism and the inflammation mediated by inflammatory factor (IL6, IL17), Ca and MAPK signaling pathway. And the levels of UCP-1, Na/K-ATP enzyme, GSH, and the targets protein of IL6, IL17, MAPK and PPAR-γ were ameliorated by the four typical 'cold' property herbs.

CONCLUSION

The four typical 'cold' property herbs could alleviate hyperthyroidism by ameliorate thyroid hormone synthesis, restraining inflammation and oxidative stress via regulating energy metabolism, glutathione metabolism, taurine hypotaurine metabolism, arachidonic acid metabolism and linoleic acid metabolism and Ca /MAPK signaling pathway, which might be a useful strategy for treating hyperthyroidism.

摘要

民族药理学相关性

“寒”性草药通常应用于热症。遗憾的是,“寒”性草药治疗热症的潜在机制尚未得到研究。

研究目的

本研究旨在探究四种典型“寒”性草药对甲状腺功能亢进的作用。

材料与方法

首先,将四种典型“热”性草药作为对比实验。然后,通过评估四种典型“寒”性草药和四种典型“热”性草药之间的体征、甲状腺功能和代谢谱(多变量统计分析)来探究它们之间的差异。通过 H&E 染色来证实典型“寒”性草药对甲状腺功能亢进的影响。采用代谢组学方法结合网络药理学探究典型“寒”性草药治疗甲状腺功能亢进的作用机制,通过 RT-PCR 检测 UCP-1 的基因表达,利用商业试剂盒和 Western blot 检测 Na/K-ATP 酶和 GSH 以及 IL6、IL17、MAPK 和 PPAR-γ 等相关代谢物和靶向代谢物。

结果

研究证实,四种典型“寒”性草药可有效改善甲状腺功能亢进大鼠的体征、甲状腺功能和代谢谱,但四种典型“热”性草药则没有益处。此外,四种典型“寒”性草药调节了能量代谢、谷胱甘肽代谢、牛磺酸-高牛磺酸代谢、甲状腺激素合成、花生四烯酸代谢和亚油酸代谢,以及炎症因子(IL6、IL17)、Ca 和 MAPK 信号通路介导的炎症。四种典型“寒”性草药还可改善 UCP-1、Na/K-ATP 酶、GSH 以及 IL6、IL17、MAPK 和 PPAR-γ 的靶蛋白水平。

结论

四种典型“寒”性草药可通过改善甲状腺激素合成、抑制炎症和氧化应激,从而缓解甲状腺功能亢进,其作用机制可能与调节能量代谢、谷胱甘肽代谢、牛磺酸-高牛磺酸代谢、花生四烯酸代谢和亚油酸代谢以及 Ca/MAPK 信号通路有关,这可能为治疗甲状腺功能亢进提供一种有效的策略。

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