Haizao Yuhu decoctions including three species of glycyrrhiza protected against propylthiouracil-induced goiter with hypothyroidism in rats via the AMPK/mTOR pathway
Haizao Yuhu decoctions including three species of glycyrrhiza protected against propylthiouracil-induced goiter with hypothyroidism in rats via the AMPK/mTOR pathway
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DOI：
10.1016/j.jep.2022.115443
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发表时间：
2022-10-05
影响因子：
5.4
通讯作者：
Zhong，Gansheng
中科院分区：
文献类型：
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作者：
Li，Na;Li，Muyun;Zhong，Gansheng
民族药理学相关性根据中医药理论，丹参和海藻是18种配伍禁忌之一.海藻玉壶汤虽含有甘草、海藻，但却是治疗甲状腺肿的经典方剂。根据《中国药典》，甘草分为三个品种：甘草（学名：Rhizoma uralensisFish.）甘草，海芋是否有不同的疗效或毒性时，应用在HYD.Aim的studyTo探讨是否有不同的疗效或毒性，包括三个品种的甘草HYDs用于治疗大鼠甲状腺肿和这些HYDs的潜在mechanism.Materials和methodsFor两周，甲状腺肿模型复制通过胃内丙基硫氧嘧啶（PTU）管理。实验分为正常对照组、模型组、优甲乐组、甘草水煎液组、甘草水煎液组、甘草水煎液组、甘草水煎液组。治疗4周后，评价体重、直肠温度、甲状腺/肝/肾系数、甲状腺/肝/肾功能、甲状腺/肝/肾组织形态学和甲状腺超微结构。然后，采用实时定量逆转录聚合酶链反应（RTqPCR）、免疫印迹和免疫荧光技术检测AMPK/mTOR通路中影响甲状腺细胞自噬和凋亡的基因和蛋白。结果3种HYDs均能提高甲状腺激素（TH）水平，减轻甲状腺病理组织和超微结构，并激活AMPK/mTOR通路中的重要蛋白和基因。三种HYD的疗效比较表明，HYD-U恢复TH最有效，但在抗甲状腺肿效果没有差异。3种HYDs均无明显毒性，并能促进PTU所致肝肾功能损害的恢复。3种HYDs对肝、肾功能恢复作用的比较结果一致。结论3种HYDs具有显著的抗甲状腺肿作用和保护肝、肾功能的作用。它们的抗甲状腺肿作用归因于AMPK/mTOR通路诱导的自噬和凋亡。HYD-U导致最好的THs恢复。进一步表明，本研究中的三种复方制剂中，丹参和海藻均为配伍，提示了二者在复方制剂中配伍的安全性，为18种配伍药物的研究提供了依据。
Ethnopharmacological relevanceGlycyrrhiza and sargassum are among the 18 incompatible medicaments according to traditional Chinese medicine (TCM) theory. Although it contains glycyrrhiza and sargassum, Haizao Yuhu decoction (HYD) is a classic prescription widely used as TCM to treat goiter. According to the Chinese Pharmacopoeia, glycyrrhiza is divided into three varieties:Glycyrrhiza uralensisFish.,Glycyrrhiza glabraL., andGlycyrrhiza inflataBat. Whether the three varieties of glycyrrhiza have different efficacy or toxicity when applied in the HYD is unknown.Aim of the studyTo explore whether the HYDs comprising three varieties of glycyrrhiza have different efficacy or toxicity when used to treat goiter in rats and the underlying mechanisms of these HYDs.Materials and methodsFor two weeks, the goiter model was replicated by intragastric propylthiouracil (PTU) administration. Samples were divided into the control group, model group, euthyrox group, HYD with glycyrrhiza uralensis (HYD-U) group, HYD with glycyrrhiza glabra (HYD-G) group, and HYD with glycyrrhiza inflata (HYD-I) group. After four weeks of treatment, body weight, rectal temperature, thyroid/liver/kidney coefficient, thyroid/liver/kidney function, thyroid/liver/kidney histomorphology, and thyroid ultrastructure were evaluated. Then, real-time quantitative reverse-transcription polymerase chain reaction (RTqPCR), Western blot, and immunofluorescence analyses were performed to detect genes and proteins affecting autophagy and apoptosis in thyroid cells in the AMP-activated Protein Kinases (AMPK)/Mammalian target of rapamycin (mTOR) pathway.ResultsAll three HYDs increased thyroid hormones (THs) levels, relieved thyroid pathological tissue and ultrastructure, and activated vital proteins and genes in the AMPK/mTOR pathway. Comparisons among the efficacy of the three HYDs indicated that HYD-U restored the THs most effectively; however, no difference in the anti-goiter effect was observed. Moreover, the three HYDs resulted in no toxicity and promoted the recovery of impaired liver and kidney function caused by PTU. Comparisons among the recovery effects of the three HYDs on the liver and kidney were the same.ConclusionOur experiments demonstrated that the three HYDs had outstanding anti-goiter effects and protected liver and kidney function. Their anti-goiter effects were attributed to AMPK/mTOR pathway-induced autophagy and apoptosis. HYD-U resulted in the best THs recovery. It was further indicated that in our present study, glycyrrhiza and sargassum were compatible in the three HYDs, thereby suggesting their safety of compounding in HYD and providing a basis for the research of the 18 incompatible medicaments.