Synergistic inhibitory effects of naproxen in combination with magnolol on TPA-induced skin inflammation in mice

The combination of naproxen with herbs having a range of pharmacological effects is a potential alternative to improve their bioactivity and limit their adverse effects. Inspired by magnolol, an active constituent found in the bark of Magnolia officinalis , we therefore evaluated the efficacy of naproxen ( N ) plus magnolol ( M ) in 12- O -tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation. During application, treatment with N and M significantly reduced skin inflammation, and the combination of N and M resulted in a synergistic effect. Further mechanistic investigations clearly demonstrated that A3 ( N : M = 1 : 3, mol mol −1 ) markedly suppressed TPA-induced pro-inflammatory cytokines and COX-2 expressions, inhibited NF-κB activity, downregulated IκBα and IκB kinase (IKK) activities, and inhibited PI3K/Akt and PI3K/PKC signaling pathways. These results indicated that a combination of N and M effectively inhibited TPA-induced skin inflammation via blocking PI3K/Akt/IKK and PI3K/PKC/IKK signaling pathways. A combination of naproxen and magnolol effectively inhibited TPA-induced skin inflammation via blocking PI3K/Akt and PI3K/PKC signaling pathways.