Network pharmacology, molecular docking, and experimental pharmacology explored Ermiao wan protected against periodontitis via the PI3K/AKT and NF-ΚB/MAPK signal pathways

Ethnopharmacological relevance: Ermiao Wan (EMW), a classic and famous traditional Chinese medicine (TCM)-based herbal formula combined Phellodendron chinense C.K.Schneid. (Cortex Phellodendri Chinsis, CP) and Atractylodes lancea (Thunb.) DC. (Rhizoma Atractylodis, RA) with the weight composition of 1:1, has been used for the treatment of periodontitis in China for a long time. However, its efficacy and mechanism of action are still unclear now. Aim of the study: This study explored the efficacy and pharmaceutical mechanism of action of EMW against periodontitis. Materials and methods: The efficacy of EMW against periodontitis was evaluated using the ligature-induced periodontitis (LIP) mice, and inflammatory-related factors in gingiva and alveolar bone loss were determined using the qRT-PCR and micro-CT assays. The potential pharmacological mechanisms were predicted by bioin-formatics analysis and further confirmed by the qRT-PCR and western blotting assays.Results: EMW exhibited inhibitory effects on periodontitis in the LIP mice. Bio-informational analysis showed the core compounds (berberine and chlorogenic acid) targeted the key genes (AKT, MAPK1, MAPK14, NF-Kappa B, TNF, IL-2, and IL1B) through regulating the PI3K/AKT and NF-Kappa B/MAPK signal pathways, which were validated using the qRT-PCR and western blotting assays.Conclusions: EMW could eliminate alveolar bone loss and inhibit inflammation, thereby preventing the devel-opment of periodontitis. The mechanism of action may be achieved by regulating the PI3K/AKT and NF-Kappa B/ MAPK signal pathways. Therefore, EMW was a potential therapy for the treatment of periodontitis.