Natural Products Exhibit Therapeutic Potential in Treating Rheumatoid Arthritis by Targeting the PI3K /Akt Signaling Pathway

ABSTRACT Rheumatoid arthritis (RA) is a persistent, systemic autoimmune disorder that primarily affects the joints. The progression of RA is driven by the activation of various intracellular signaling pathways, among which the PI3K/Akt signaling pathway regulates crucial biological processes associated with RA. According to reports, GSK3, Bcl‐2, FOXOs, p53, mTOR, and NF‐κB, the downstream targets of PI3K/Akt, are closely related to the pathological process of synovial inflammation, hyperplasia, angiogenesis, and bone destruction in RA. In recent years, many natural products, primarily flavonoids, terpenoids, alkaloids, and polyphenols, have been found to play a role in treating RA through the PI3K/Akt pathway. Unlike conventional treatments, natural products exert multi‐target effects and possess structural diversity, making them valuable sources for drug discovery. Therefore, we summarized the studies on treatment of RA through the PI3K/Akt signaling pathway, suggesting that natural monomeric compounds, herbal extracts, and traditional drug prescriptions modulating the downstream targets of the PI3K/Akt pathway, mainly mTOR, Bcl‐2, and NF‐κB, are promising strategies for RA treatment. This review was conducted with the aim of providing a scientific foundation and methods for the treatment of RA.