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Prunella vulgaris L. attenuates experimental autoimmune thyroiditis by inducing indoleamine 2,3-dioxygenase 1 expression and regulatory T cell expansion - 18/06/20

Doi : 10.1016/j.biopha.2020.110288 
Huanbing Qiu a , Jingping Zhang b , Qingling Guo c , Yongsheng Zhang a , Xia Zhong a,
a Department of General Practice, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China 
b Department of Endocrinology, Shandong Provincial Hospital (West District), Jinan, Shandong Province, China 
c Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China 

Corresponding author. Postal address: No. 324 Jingwu Road, Huaiyin Distinct, Jinan, Shandong Province, 250021, China.No. 324 Jingwu RoadHuaiyin DistinctJinanShandong Province250021China

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Highlights

Prunella vulgaris L. attenuates thyroiditis and goitre in Tg-immunized EAT model.
Prunella vulgaris L. increased proportion of Treg cells in EAT model.
Prunella vulgaris L. elevated serum levels of IL-10 and TGF-βin EAT model.
Prunella vulgaris L. elevated IDO1 expression and activity in EAT model.

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Abstract

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 CD4+CD25+Foxp3+ 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.

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Keywords : Autoimmune thyroiditis, Experimental autoimmune thyroiditis, Prunella vulgaris L., Regulatory T cell (Treg), Indoleamine 2,3-dioxygenase 1 (IDO1)


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