Periplaneta americana extract in improving antigenic emulsifier-induced recurrent oral ulcers in rats by inhibiting TLR4/NF-κB and activating Nrf2/HO-1 signaling pathways

Recurrent oral ulcers (ROUs) of oral mucosa disease are difficult to cure and relapse easily, and immune imLbalance or dysfunction is considered an essential factor in their occurrence and recurrence. Periplaneta americana extract (PAD), a raw material used in Kangfuxin Liquid and Yunnan Baiyao toothpaste, contains a variety of growth factors such as polypeptides and sticky sugar amino acids that promote tissue repair; this can encourage the growth of the granulation tissue and reduce inflammation on the wound surface. This study aimed to investigate the interventional potential of PAD on recurrent oral ulcers in rats and to elucidate the underlying mechanism of action involving the TLR4/NF-κB and Nrf2/HO-1 signaling pathways. A rat model of recurrent oral ulcer (ROU) was established using an oral antigen emulsifier. Rats in the ROU group were administered PAD by gavage for 7 days. To observe the effect of PDA on ROU mice. HE staining revealed that PAD restored the structure of the oral mucosal tissue and reduced inflammatory infiltration. FCM revealed that PAD upregulated CD3+ and CD4+ levels and the CD4+/CD8+ ratio in peripheral blood T lymphocytes. ELISA revealed that PAD increased the content of IgA, IgG, IgM, VEGF, IL-2, and IL-10, while decreasing IL-6 and TNF-α content. Microplate analysis revealed that PAD significantly increased CAT content in the serum of ROU rats and reduced GSH, NO, SOD, and MDA levels. IHC staining, RT-qPCR, and Western blotting revealed that PAD downregulated Keap1 and IκBα expression, inhibited the TLR4/NF-κB signaling pathway, upregulated Nrf2 and HO-1 expression, and activated the Nrf2/HO-1 signaling pathway. These fndings suggest that PAD improved immune imbalance and oxidative stress in ROU rats by activating the Nrf2/HO-1 pathway and inhibiting the TLR4/NF-κB signaling pathway, thereby promoting the healing of oral ulcer wounds.