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[Effect of Jiakangning Capsule on Thyroid Function and Akt/mTOR Signal Pathway of Graves' Disease Mice: an
Objective:
To observe the improvement of thyroid function and changes of Akt, p-Akt, mammalian target of rapamycin (mTOR), and para-mTOR (p-mTOR) expression in Graves' disease (GD) mice after intervened by Jiakangning Capsule (JC), and to explore possible mechanism for JC in treating GD.
Methods:
GD model was established by immunizing female BALB/c mice with thyroid stimulating hormone receptor A subunit (Ad-TSHRα-289). Totally 70 successfully modeled mice were divided into the model group (n =20), the JC intervened group (n =25), the Methimazole Tablet intervened group (n =25) according to random digit table. A normal control group (n =15) and a vehicle control group (n =20, injected with Ad-null) were also set up. Mice in the JC intervened group were administered with JC suspension at the daily dose of 1. 5 g/kg by gastrogavag. Mice in the Methimazole intervened group were administered with Methimazole suspension at the daily dose of 2. 5 g/kg by gastrogavage. Equal volume of normal saline was administered to mice in the rest 3 groups by gastrogavage. All intervention lasted for 5 weeks. Six mice were selected from each group to observe pathological changes of thyroid tissues. Serum levels of thyroxine (T4), triiodothyronine (T3), thyroid stimulating hormone (TSH), and thyrotropin receptor antibody (TRAb) were analyzed by radioimmunoassay. Expression levels of Akt, p-Akt, mTOR, and p-mTOR in thyroid tissues were etermined by Western blot.
Results:
(1) The thyroid gland in the GD model group showed proliferative changes, with enlarged follicles of various sizes. Interstitial stroma was filled with blood vessels. Structures of thyroid tissues in the JC intervened group and the Methimazole intervened group were significantly restored, and follicular hyperplasia was relieved. (2) Compared with the normal control group and the vehicle control group, levels of TRAb, T4, and T3 increased; ratios of P-Akt/β-actin, p-Akt/Akt, p-mTOR/β-actin, and p-mTOR/mTOR also increased in the model group (all P <0. 01). Compared with the model group, levels of TRAb, T4, and T3 decreased in the JC intervened group and the Methimazole intervened group (P <0. 01); ratios of p-mTOR/β-actin and pmTOR/mTOR decreased in the JC intervened group (P <0.01); ratios of P-Akt/β-actin, p-Akt/Akt, p-mTOR/β-actin, and p-mTOR/mTOR decreased in the Methimazole intervened group (P <0. 05, P <0. 01). Conclusion JC could reduce thyroid hormonc levels of GD mice and lower expression levels of mTOR, and its mechanism for improving thyroid function of GD mice might be associated with this influence.
Insights
Jiakangning Capsule (JC) treatment improved thyroid function in Graves' disease (GD) mice by reducing thyroid hormones and lowering mammalian target of rapamycin (mTOR) expression. This suggests JC may offer a therapeutic mechanism for GD.
Area of Science:
- Endocrinology
- Immunology
- Pharmacology
Background:
- Graves' disease (GD) is an autoimmune disorder characterized by hyperthyroidism.
- The Akt/mammalian target of rapamycin (mTOR) signaling pathway is implicated in thyroid function and autoimmune diseases.
- Investigating novel therapeutic agents for GD is crucial.
Purpose of the Study:
- To evaluate the efficacy of Jiakangning Capsule (JC) in a mouse model of Graves' disease.
- To examine the effects of JC on thyroid function and related biochemical markers.
- To explore the potential mechanism of JC action involving the Akt/mTOR pathway.
Main Methods:
- A Graves' disease mouse model was established using Ad-TSHRα-289 immunization.
- Mice were treated with JC, Methimazole, or vehicle for 5 weeks.
- Thyroid function (T4, T3, TSH, TRAb) and Akt/mTOR pathway protein expression (Akt, p-Akt, mTOR, p-mTOR) were assessed.
Main Results:
- JC treatment significantly reduced TRAb, T4, and T3 levels in GD mice.
- JC administration led to a decrease in p-mTOR expression in thyroid tissues.
- Pathological changes in thyroid glands were ameliorated by JC treatment.
Conclusions:
- Jiakangning Capsule demonstrates therapeutic potential for Graves' disease.
- JC effectively improves thyroid function and reduces key disease markers in a mouse model.
- The mechanism may involve the modulation of the Akt/mTOR signaling pathway.
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