Molecular Insights of a Unani Formulation in Targeting Fibrosis-Associated Diseases

Abstract

Fibrosis is a pathological condition characterised by excessive deposition of the extracellular matrix (ECM) and persistent activation of myofibroblasts, and is associated with many chronic diseases. The association between fibrosis and cancer is increasingly recognised, where fibrosis contributes to the progression of cancer by increasing metastatic potential and resistance to therapy, thereby leading to poor clinical outcomes. A novel Polyherbal Unani Formulation (PUF), based on the Unani system of medicine, possesses a distinct phytochemical constitution with wide-spectrum therapeutic properties. Phytochemicals such as chebulinic acid, picrosides, flavonoids, and phenolic derivatives are reported to exert multi-targeted effects by attenuating oxidative stress, suppressing pro-fibrotic signalling pathways (TGF-β/Smad, NF-κB, PI3K/Akt), inhibiting epithelial-mesenchymal transition (EMT), and restoring fibroblast-to-myofibroblast plasticity. These individual compounds were systematically evaluated preclinically, establishing their effectiveness in modulating key molecular targets. Challenges such as phytochemical standardisation, bioavailability, and clinical validation remain significant for this distinct drug formulation, thereby improving its translational value. This review article considers PUF as a potential integrative therapeutic approach for fibrosis-related diseases and for aggressive cancers with fibrosis. In summary, we expect this PUF to target both tumour cells and the fibrotic tumour micro-environment, thereby integrating ethnopharmacological knowledge with molecular rationality.