Multi‑target mechanisms of paeoniflorin in inflammatory regulation: A network pharmacology (Review)

Paeoniflorin (PF), a monoterpene glycoside from Paeonia roots, shows low toxicity and broad anti‑inflammatory activity. A systematic review (PubMed, through 2025) with network pharmacology indicates that PF restores mitochondrial function, raises anti‑inflammatory mediators (IL‑10 and arginase‑1), reduces TNF‑α, IL‑1β and IL‑6, and eases oxidative stress. Its effects hinge on intertwined routes, dampening TLR4/MyD88, blocking NF‑κB nuclear entry, lowering MAPK phosphorylation, reshaping JAK‑STAT, and disrupting NLRP3 inflammasome assembly. Network mapping singles out a conserved core module (MAPK1, MAPK3, HSP90AA1, TP53, ESR1, BCL2, HIF1A, IL6, IL10 and FGF2), with HSP90AA1 and ESR1 as disease‑tailored effectors in rheumatoid arthritis and osteoarthritis (OA). PF absorbs fast and gathers in the liver with minimal toxicity, yet oral availability stays poor. Preclinical promise spans OA, colitis, and atherosclerosis, while clinical data remain thin. Synergistic pairing with other agents and structural refinement of PF broaden its reach, though such computational leads need experimental corroboration. Future efforts should improve its bioavailability, develop targeted delivery systems, and conduct rigorous clinical trials to move PF from tradition to evidence‑based medicine.