夏枯草 L. 通过诱导吲哚胺 2,3-双加氧酶 1 表达和调节性 T 细胞扩增来减轻实验性自身免疫性甲状腺炎。
Prunella vulgaris L. attenuates experimental autoimmune thyroiditis by inducing indoleamine 2,3-dioxygenase 1 expression and regulatory T cell expansion.
机构信息
Department of General Practice, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China.
Department of Endocrinology, Shandong Provincial Hospital (West District), Jinan, Shandong Province, China.
出版信息
Biomed Pharmacother. 2020 Aug;128:110288. doi: 10.1016/j.biopha.2020.110288. Epub 2020 May 29.
BACKGROUND
Prunella vulgaris L. (P. vulgaris) has traditionally been used to treat swelling and inflammation of the thyroid gland. This study aimed to evaluate the effects of P. vulgaris on experimental autoimmune thyroiditis (EAT) and explore the roles of indoleamine 2,3-dioxygenase 1 (IDO1) and regulatory T cells (Tregs) in these P. vulgaris-mediated effects.
METHODS
The main bioactive compounds in P. vulgaris were analysed by high-performance liquid chromatography. An EAT model was established by immunization of Lewis rats with thyroglobulin via subcutaneous injection. Thyroid volume was assessed by ultrasound, and lymphatic infiltration in the thyroid was evaluated by haematoxylin and eosin staining. The serum levels of thyroglobulin antibody (TgAb) and cytokines were measured by indirect enzyme-linked immunosorbent assay. The percentage of CD4CD25Foxp3 Tregs was detected by flow cytometry. The mRNA and protein levels of IDO1 were measured by qRT-PCR and Western blotting, respectively. The levels of tryptophan (Trp) and kynurenine (Kyn) in serum and faecal samples were assessed with a fluorometric kit and spectrophotometry.
RESULTS
The main bioactive compound in P. vulgaris was rosmarinic acid. The TgAb level and thyroid volume in EAT rats were significantly decreased after administration of P. vulgaris (P < 0.01). The inflammation score in EAT rats that were administered P. vulgaris was significantly lower than that in the EAT controls (P < 0.01). In addition, P. vulgaris promoted the expansion of splenic Tregs and increased the production of IL-10 and TGF-β (P < 0.01) in EAT rats. Moreover, P. vulgaris induced IDO1 mRNA and protein expression in the spleen and intestine in P. vulgaris-treated EAT rats (P < 0.01). Finally, Trp levels were reduced and Kyn levels and the Kyn/Trp ratio were increased in the serum of P. vulgaris-treated EAT rats.
CONCLUSION
We were the first to demonstrate the role of IDO1-induced Treg expansion in P. vulgaris-mediated attenuation of EAT. Our study provides insight into the immunopathogenesis of autoimmune thyroiditis and shows the potential therapeutic value of P. vulgaris.
背景
夏枯草（P. vulgaris）传统上用于治疗甲状腺肿和炎症。本研究旨在评估夏枯草对实验性自身免疫性甲状腺炎（EAT）的影响，并探讨吲哚胺 2,3-双加氧酶 1（IDO1）和调节性 T 细胞（Tregs）在这些夏枯草介导的作用中的作用。
方法
采用高效液相色谱法分析夏枯草中的主要生物活性化合物。通过皮下注射甲状腺球蛋白免疫 Lewis 大鼠建立 EAT 模型。通过超声评估甲状腺体积，通过苏木精和伊红染色评估甲状腺内淋巴浸润。通过间接酶联免疫吸附试验测定血清甲状腺球蛋白抗体（TgAb）和细胞因子水平。通过流式细胞术检测 CD4CD25Foxp3 Tregs 的百分比。通过 qRT-PCR 和 Western blot 分别测定 IDO1 的 mRNA 和蛋白水平。采用荧光法和分光光度法测定血清和粪便样本中色氨酸（Trp）和犬尿氨酸（Kyn）的水平。
结果
夏枯草的主要生物活性化合物是迷迭香酸。夏枯草给药后 EAT 大鼠的 TgAb 水平和甲状腺体积显著降低（P < 0.01）。夏枯草给药的 EAT 大鼠的炎症评分明显低于 EAT 对照组（P < 0.01）。此外，夏枯草促进了脾 Tregs 的扩增，并增加了 EAT 大鼠中 IL-10 和 TGF-β 的产生（P < 0.01）。此外，夏枯草诱导了脾和肠中 IDO1 mRNA 和蛋白表达在夏枯草治疗的 EAT 大鼠中（P < 0.01）。最后，夏枯草治疗的 EAT 大鼠血清中 Trp 水平降低，Kyn 水平和 Kyn/Trp 比值升高。
结论
我们首次证明了 IDO1 诱导的 Treg 扩增在夏枯草介导的 EAT 衰减中的作用。我们的研究为自身免疫性甲状腺炎的免疫发病机制提供了新的见解，并显示了夏枯草的潜在治疗价值。
Zotero 插件