Resveratrol's hepatic symphony: conducting a multi-stage intervention in liver cancer’s progression

The development of hepatocellular carcinoma (HCC) is a multistep process often associated with chronic hepatitis, liver fibrosis, and cirrhosis. Natural products, like resveratrol, have attracted considerable attention as anticancer drugs due to their diverse pharmacological activities. Resveratrol is a natural polyphenol present in plant foods, which has antioxidant, anti-inflammatory, anti-tumor, and anti-angiogenesis effects. The growing consensus shows that resveratrol plays a therapeutic role in liver diseases positively. The therapeutic effect observed in chronic hepatitis may be related to its ability to interfere with viral replication through PI3K/Akt, NF-κB, and MAPK signaling modulation, as well as to diminish hepatocellular injury by anti-inflammatory and antioxidant means. In liver fibrosis and cirrhosis, resveratrol decelerates the progression of fibrosis by suppressing the activation of hepatic stellate cells (HSC) and collagen production as well as by regulating signaling pathways, Hippo, Nrf2/Keap1, and SIRT1. Resveratrol also prevents tumor growth, induces apoptosis and inhibits migration, invasion and angiogenesis by various signaling pathways, which include PI3K/AKT, JNK, NF-κB, and p53 in advanced HCC. It is the first time that a multi-stage mechanism of resveratrol is presented in the development of HCC, which highlights its multi-target regulation and treatment capabilities.