Saraca asoca Alleviates PTU-Induced Hypothyroidism in Rats: Integrated LC-MS Profiling: In Vivo and Molecular Docking Analyses.

Hypothyroidism (HT) is a common endocrine disorder that adversely affects different body functions. Saraca asoca (SA) is traditionally used as a remedy for gynaecological disorders. Although thyroid hormones are essential for reproductive function, no data are available so far on the impact of SA on thyroid function. Therefore, the current study attempted to evaluate the effects of SA in regulating HT through in vivo and in silico approaches. HT was induced in rats by administering 0.05% 6-propyl-thiouracil (PTU) in their drinking water for 4 weeks and the effects of standardized dose of SA extract (100 mg/kg), derived after a preliminary study, were examined in HT-induced rats for 14 days. LC-MS/MS analysis identified the two triterpenoids in SA. Molecular docking was used to predict the interaction between betulinic acid (BA) and lupeol (LPL) with the thyroid hormone receptors TSHR and TRβ. Oral administration of SA effectively ameliorated PTU-induced HT as revealed by decreased TSH, increased thyroid hormones,5'D1 activity, antioxidants and decreased inflammatory marker, TNF-α with improved liver histology. LC-MS analysis identified the notable presence of (BA) and (LPL) in the test extract. Molecular docking study predicted strong binding energies between BA and LPL and thyroid receptors, TRβ and TSHR, supporting the role of BA and LPL in the management of hypothyroidism. Our study proposed for the first time that BA and LPL may act as potential thyroid agonists, playing a crucial role in the thyroid stimulatory nature of SA. However, further mechanistic study is needed to solidify our findings.