通过调节人甲状腺细胞的固有免疫反应来治疗桥本氏病的生物活性成分。（注：原文“in for treating...”表述似乎不完整，正常应是“Bioactive components in [具体物质] for treating...” ）

Bioactive components in for treating Hashimoto's disease via regulation of innate immune response in human thyrocytes.

作者信息

Chen Yongzhao, Jiang Bo, Qu Cheng, Jiang Chaoyu, Zhang Chen, Wang Yanxue, Chen Fei, Sun Xitai, Su Lei, Luo Yuqian

机构信息

Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University of Chinese Medicine, Zhongshan Road 321, Nanjing, 210008, China.

Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Zhongshan Road 321, Nanjing, 210008, China.

出版信息

Heliyon. 2024 Aug 13;10(16):e36103. doi: 10.1016/j.heliyon.2024.e36103. eCollection 2024 Aug 30.

BACKGROUND

Hashimoto's thyroiditis (HT) is a thyroid autoimmune disease characterized by lymphocytic infiltration and thyroid destruction. () is a traditional Chinese herbal medicine with documented clinical efficacy in treating HT. We previously reported an immunoregulatory effect of in thyrocytes; however, the bioactive components of remained unclear. This study aimed to elucidate key components of for treating HT and their acting mechanisms.

METHODS

Network pharmacology was used to predict key components for HT. The predicted components were tested to determine whether they could exert an immunoregulatory effect of in human thyrocytes. Limited proteolysis-mass spectrometry (Lip-MS) was used to explore interacting proteins with components in human thyrocytes. Microscale thermophoresis binding assay was used to evaluate the affinity of components with the target protein.

RESULTS

Eleven components with 192 component targets and 3415 HT-related genes were gathered from public databases. With network pharmacology, a 'component-target-disease' network was established wherein four flavonoids including quercetin, luteolin, kaempferol, morin, and a phytosterol, β-sitosterol were predicted as key components in for HT. In stimulated primary human thyrocytes or Nthy-ori-31 cells, key components inhibited gene expressions of inflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interferon-β (IFN-β), cellular apoptosis, and activation of nuclear factor κB (NF-κB) and interferon regulatory factor 3 (IRF-3). Heat shock protein 90 alpha, class A, member 1 (HSP90AA1), was identified to interact with flavonoids in by Lip-MS. Morin had the highest affinity with HSP90AA1 (K = 122.74 μM), followed by kaempferol (K = 168.53 μM), luteolin (K = 293.94 μM), and quercetin (K = 356.86 μM).

CONCLUSION

Quercetin, luteolin, kaempferol, morin, and β-sitosterol reproduced an anti-inflammatory and anti-apoptosis effect of in stimulated human thyrocytes, which potentially contributed to the treatment efficacy of in HT.

背景

桥本甲状腺炎（HT）是一种以淋巴细胞浸润和甲状腺破坏为特征的甲状腺自身免疫性疾病。（某种中药名称）是一种在治疗HT方面具有临床疗效记录的传统中药。我们之前报道了（某种中药名称）在甲状腺细胞中的免疫调节作用；然而，（某种中药名称）的生物活性成分仍不清楚。本研究旨在阐明（某种中药名称）治疗HT的关键成分及其作用机制。

方法

采用网络药理学预测治疗HT的关键（某种中药名称）成分。对预测的成分进行测试，以确定它们是否能在人甲状腺细胞中发挥（某种中药名称）的免疫调节作用。采用有限蛋白水解-质谱法（Lip-MS）探索人甲状腺细胞中与（某种中药名称）成分相互作用的蛋白质。采用微量热泳动结合试验评估（某种中药名称）成分与靶蛋白的亲和力。

结果

从公共数据库中收集了11种（某种中药名称）成分，其具有192个成分靶点和3415个与HT相关的基因。通过网络药理学，建立了一个“成分-靶点-疾病”网络，其中槲皮素、木犀草素、山奈酚、桑色素这四种黄酮类化合物以及一种植物甾醇β-谷甾醇被预测为（某种中药名称）治疗HT的关键成分。在刺激的原代人甲状腺细胞或Nthy-ori-31细胞中，关键成分抑制了包括肿瘤坏死因子α（TNF-α）、白细胞介素-6（IL-6）和干扰素-β（IFN-β）在内的炎性细胞因子的基因表达、细胞凋亡以及核因子κB（NF-κB）和干扰素调节因子3（IRF-3）的激活。通过Lip-MS鉴定出热休克蛋白90α A类成员1（HSP90AA1）与人甲状腺细胞中（某种中药名称）的黄酮类化合物相互作用。桑色素与HSP90AA1的亲和力最高（K = 122.74 μM），其次是山奈酚（K = 168.53 μM）、木犀草素（K = 293.94 μM）和槲皮素（K = 356.86 μM）。