<i>Gungha-tang</i> alleviates inflammatory response by suppressing TLR4 associated with the NF-<sub><i>κ</i></sub>B and MAPK signaling pathways

Objectives: <i>Gungha-tang</i> (GHT) is a traditional herbal medicine used to expel dampness form the body. It is commonly used in Korea to alleviate pain associated with various medical conditions and to treat gastrointestinal disorders and palpitations. However, there has been limited experimental and clinical research conducted on it. In the present study, we investigated the anti-inflammatory effect and molecular mechanism of GHT.Methods: To assess the effect of GHT on inflammatory effects, we used lipopolysaccharide (LPS)-stimulated macrophages (RAW 264.7). The levels of TNF-<i>α</i>, IL-6, IL-1<i>β</i>, NO, and PGE<sub>2</sub> were measured in the cultured cell supernatants. To comprehend the cellular mechanism of inflammatory activity, TLR4-mediated NF-<sub><i>κ</i></sub>B and MAPK pathways were explored using Western blotting in the cell lysates.Results: GHT effectively decreased the release of inflammatory cytokine (TNF-<i>α</i>, IL-6, and IL-1<i>β</i>) in LPS-stimulated macrophages. Furthermore, GHT inhibited the levels of inflammatory mediators (NO and PGE<sub>2</sub>) by regulating iNOS and COX-2 expressions. GHT mitigated the expression of TLR4 as well as MyD88, subsequently suppressing the NF-<sub><i>κ</i></sub>B activation and the phosphorylation of MAPKs (p38, ERK, and JNK).Conclusions: Our findings demonstrate that GHT exerts anti-inflammatory effect by modulating TLR4 associated with the NF-<sub><i>κ</i></sub>B and MAPK signal transduction and consequently can offer a therapeutic strategy for overcoming inflammation-related disorders.