Therapeutic Potential of Resveratrol in Cancer and Neurodegenerative Disorders: A Current Review

TL;DR

Resveratrol shows promise in treating cancer and neurodegenerative diseases by targeting multiple biological pathways, but its effectiveness is limited by poor solubility and bioavailability.

Contribution

This review highlights resveratrol's multi-target therapeutic potential and the need for improved delivery methods to enhance its clinical application.

Findings

Resveratrol modulates pathways like TP53, NRF2, and NF-κB to induce cancer cell death.

Poor bioavailability and stability of resveratrol require advanced delivery strategies like nanoencapsulation.

Resveratrol's antioxidant effects involve ROS regulation and activation of SIRT1 and AMPK signaling.

Abstract

Resveratrol (RSV; 3,5,4′‐trihydroxy‐trans‐stilbene) is a natural polyphenolic compound with notable antioxidant, anti‐inflammatory, and immunomodulatory properties. It has been investigated for therapeutic applications in cardiovascular disease, cancer, and neurodegenerative disorders. This review emphasizes the potential of RSV in oncology and neuroprotection, synthesizing evidence from systematic database searches and experimental studies. Despite promising biological activities, RSV is limited by poor stability, low aqueous solubility, rapid metabolism, and restricted bioavailability, necessitating improved delivery strategies such as nanoencapsulation, nanocrystals, prodrugs, and structural analogues. Mechanistically, RSV exerts anticancer and neuroprotective effects through modulation of p53, STAT3, NF‐κB, and mitochondrial‐mediated apoptosis. Its antioxidant actions involve regulation of reactive oxygen species (ROS), activation of NRF2, AMPK signaling, and SIRT1. RSV and related antioxidants act on multiple molecular pathways, including TP53, β‐catenin, STAT3, NF‐κB, NRF2–AMPK, PI3K/AKT, and SIRT1, to regulate inflammation and cell death. The balance between oxidative and antioxidative processes is critical for therapeutic efficacy. Notably, RSV‐induced ROS‐mediated cell death, particularly in the context of TP53 mutations, represents a promising target for future interventions. Overall, RSV demonstrates multi‐target potential for cancer and neurodegenerative disease therapy, though optimization of its pharmacological profile remains essential.

Resveratrol induces the expressions of TP53, NRF2, and JDP2 axis in cancer cells to control ROS balance in mitochondria. The antioxidation responses were induced through SRIT1/3, HDAC, STAT3, TGFβ, and so on, to trigger the inflammation, and NFkB response to lead to the cell death of cancers or neuro‐damaged cells.

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