In Silico Evaluation Of Tetrahydro Curcumin To Target TGFBR1 In Pulmonary Fibrosis And Cancer

Abstract

Pulmonary fibrosis (PF) and cancer share common molecular mechanisms, with Transforming Growth Factor-beta (TGF-β) signaling playing a critical role in both diseases. Tetrahydrocurcumin (THC), a bioactive metabolite of curcumin, has demonstrated anti-inflammatory, antioxidant, and anti-fibrotic properties, making it a promising therapeutic candidate for PF and cancer. However, its potential as a dual-target therapy has not been fully explored. In this study, we employed in silico methods to evaluate the therapeutic potential of THC in treating both PF and cancer, focusing on TGF-β receptor 1 (TGFBR1) as a shared target. The pharmacokinetic properties of THC were assessed using SwissADME, which predicted favorable absorption, moderate solubility, and favorable drug-likeness. Toxicity predictions via ProTox indicated a low risk of acute toxicity, with no significant hepatotoxicity, neurotoxicity, or cardiotoxicity. The protein-protein interaction network analysis using STRING revealed that TGFBR1 interacts with key proteins involved in fibrosis and cancer, reinforcing its role as a central therapeutic target. SwissTargetPrediction identified additional potential targets, including IL-6 and COX-2, further supporting THC's potential as a multi-target agent. Molecular docking studies demonstrated that THC binds strongly to TGFBR1 through key interactions, suggesting that it could effectively inhibit TGF-β signaling. These findings indicate that THC holds promise as a dual-purpose therapeutic for PF and cancer. However, further experimental validation is required to confirm its efficacy in clinical applications.