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

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. This study explored the efficacy and pharmaceutical mechanism of action of EMW against periodontitis. 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 bioinformatics analysis and further confirmed by the qRT-PCR and western blotting assays. 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-κB, TNF, IL-2, and IL1B) through regulating the PI3K/AKT and NF-κB/MAPK signal pathways, which were validated using the qRT-PCR and western blotting assays. EMW could eliminate alveolar bone loss and inhibit inflammation, thereby preventing the development of periodontitis. The mechanism of action may be achieved by regulating the PI3K/AKT and NF-κB/MAPK signal pathways. Therefore, EMW was a potential therapy for the treatment of periodontitis.