Curcumin in Fibrosis Treatment: A Review.

Fibrosis, marked by excessive accumulation of extracellular matrix (ECM) components, ultimately leads to dysfunction and failure of multiple organs, yet effective therapeutic options remain scarce. Curcumin (CUR), a naturally occurring polyphenol with diverse biological activities, has emerged as a promising candidate for anti-fibrotic intervention. Its designation as Generally Recognized as Safe (GRAS) and widespread use as a food additive offer distinct advantages for its incorporation into functional foods or clinical formulations. Nevertheless, its therapeutic translation is significantly limited by poor aqueous solubility and low systemic bioavailability. In response, a range of advanced drug delivery platforms-such as liposomes, nanoparticles, solid dispersions, and self-microemulsifying drug delivery systems (SMEDDS)-have been developed, markedly improving the solubility, stability, and in vivo bioavailability of CUR. This narrative review systematically summarizes the mechanistic, pharmacokinetic, and safety profiles of CUR in preclinical models of hepatic fibrosis (HF), myocardial fibrosis (MF), pulmonary fibrosis (PF), and renal fibrosis (RF) over the past two decades, focusing on core cellular effectors and signaling pathways. We further highlight recent progress in formulation strategies that potentiate CUR's anti-fibrotic efficacy, as well as key translational challenges: the pathological divergence between preclinical animal and in-vitro cell models and human fibrotic lesions, plus regulatory barriers limiting clinical adoption. Notably, most available mechanistic observations are derived from short-term pre-clinical experiments, and cannot be directly extrapolated to human chronic fibrotic disease. Despite these hurdles, cumulative preclinical evidence validates CUR's therapeutic potential as a natural anti-fibrotic agent in experimental settings. Combined with continuous innovation in delivery technology, CUR shows great prospects for developing anti-fibrotic functional foods and clinical therapeutics, yet high-quality human clinical trials are still urgently needed to confirm its real-world efficacy.