Curcumin and analogues in mitigating liver injury and disease consequences: From molecular mechanisms to clinical perspectives

Liver injury is a prevalent global health concern, impacting a substantial number of individuals and leading to elevated mortality rates and socioeconomic burdens. Traditional primary treatment options encounter resource constraints and high costs, prompting exploration of alternative adjunct therapies, such as phytotherapy. Curcumin demonstrates significant therapeutic potential across various medical conditions, particularly emerging as a promising candidate for liver injury treatment. This study aims to provide current evidence maps of curcumin and its analogs in the context of liver injury, covering aspects of biosafety, toxicology, and clinical trials. Importantly, it seeks to summarize the intricate mechanisms modulated by curcumin. We conducted a comprehensive search of MEDLINE, Web of Science, and Embase up to July 2023. Titles and abstracts were reviewed to identify studies that met our eligibility criteria. The screening process involved three authors independently assessing the potential of curcumin mitigating liver injury and its disease consequences by reviewing titles, abstracts, and full texts. Curcumin and its analogs have demonstrated low toxicity in vitro and in vivo. However, the limited bioavailability has hindered their advanced use in liver injury. This limitation can potentially be addressed by nano-curcumin and emerging drug delivery systems. Curcumin plays a role in alleviating liver injury by modulating the antioxidant system, as well as cellular and molecular pathways. The specific mechanisms involve multiple pathways, such as NF-κB, p38/MAPK, and JAK2/STAT3, and the pro-apoptosis Bcl-2/Bax/caspase-3 axis in damaged cells. Additionally, curcumin targets nutritional metabolism, regulating the substance in liver cells and tissues. The microenvironment associated with liver injury, like extracellular matrix and immune cells and factors, is also regulated by curcumin. Initial evaluation of curcumin and its analogs through 12 clinical trials demonstrates their potential application in liver injury. Curcumin emerges as a promising phytomedicine for liver injury owing to its effectiveness in hepatoprotection and low toxicity profile. Nevertheless, in-depth investigations are warranted to unravel the complex mechanisms through which curcumin influences liver tissues and overall physiological milieu. Moreover, extensive clinical trials are essential to determine optimal curcumin dosage forms, maximizing its benefits and achieving favorable clinical outcomes.