Phytomedicine Plus (Aug 2022)
Regulation of PTU-induced hypothyroidism in rats by caffeic acid primarily by activating thyrotropin receptors and by inhibiting oxidative stress
Abstract
Background: Earlier, nothing was known on the thyroid-regulatory potential of caffeic acid (CA). We investigated its role in 6-propyl-thiouracil (PTU)-induced hypothyroid rats and also worked out the possible involvement of 5’-deiodinase I (5’-DI) and thyrotropin receptor (TSHR) in its mode of action. Methods: A pre-standardized dose (100 mg/kg) of CA was orally administered to PTU-induced rats for 30 days and its effects were evaluated on the alterations in the levels of serum triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH) and hepatic 5’-D1activity; expression of thyroid TSHR, aspartate transaminase (AST), alanine transaminase (ALT), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), total cholesterol (CHOL), triglycerides (TG) and hepatic lipid peroxidation (LPO). For the first time an interaction of CA with TSHR was studied in silico. Results: PTU significantly reduced serum levels of thyroid hormones (TH), hepatic 5’-D1 and antioxidant activities as well as TSHR expression, but increased the serum TSH, AST, ALT, TNF-α, IL-6, CHOL, TG and hepatic LPO. However, CA treatment ameliorated all these PTU-induced alterations near to normal levels. Further, the distorted histo-architecture of thyroid gland by PTU was corrected by this compound. The molecular docking study indicated that CA possesses a high binding free energy with target TSHR. These results were comparable to that of a standard pro-thyroid drug, thyroxine. Conclusion: CA potentially stimulated thyroid function by increasing TH levels, hepatic 5’-D1 activity and upregulation of TSHR protein expression. In addition, it attenuated the increase in oxidative stress markers, liver markers, lipids and improved the thyroid histo-architecture, thus protected from PTU-induced adverse effects. In silico studies suggested the interaction of CA with TSHR that yielded the binding energy (-6.51 kcal/mol) as compared to thyroxine (-6.10 kcal/mol) suggesting it as a highly potent thyro-stimulatory drug.
