Myrrh Essential Oil Improves DSS-Induced Colitis by Modulating the MAPK Signaling Pathway: In vitro and in vivo Studies

Abstract

Tiantian Tang,1,2,* Yujiao Wang,1,2,* Taotao Li,1,2,* Ding Liu,1,2 Kai Yang,1,2 Jing Sun,1,2 Yajun Shi,1,2 Dongyan Guo,1,2 Junbo Zou,1,2 Fengyun Bai,3 Ying Sun,3 Mei Wang,1,2 Xiaofei Zhang1,2 1Key Laboratory of Basic and New Drug Research in Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China; 2Shaanxi Provincial University Engineering Research Center of Chinese Medicine Aromatic Industry, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China; 3Shaanxi Dongtai Pharmaceutical Co., Ltd., Xianyang, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mei Wang; Xiaofei Zhang, Key Laboratory of Basic and New Drug Research in Chinese Medicine; Shaanxi Provincial University Engineering Research Center of Chinese Medicine Aromatic Industry, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, 712046, People’s Republic of China, Email [email protected]; [email protected]: To explore the mechanism and active components of the anti-colitis effects of myrrh essential oil (MEO).Methods: In this study, we investigated the anti-inflammatory effects and molecular mechanisms of MEO on dextran sulfate sodium (DSS)-induced colitis with in vitro cell experiments, RNA-seq (RNA Sequencing), Weighted gene co-expression network analysis (WGCNA), combined with “weighting coefficient” network pharmacology, as and in vivo pharmacodynamic experiments. A 3% DSS solution was used to induce colitis in BALB/c mice and MEO was administered orally. We performed gas chromatography-mass spectrometry (GC-MS) analysis of the MEO components. The disease activity index (DAI) was evaluated by observing body weight, fecal characteristics, and blood in the stool of mice. The levels of inflammatory cytokines (TNF-α and IL-1β) in mouse serum were measured using ELISA (Enzyme-linked immunosorbent assay) kits. Additionally, the expression of MAPK-related proteins (JNK, p-JNK, ERK, and p-ERK) in mouse colonic tissues was detected by Western blotting and immunohistochemistry.Results: MEO (0.0625– 0.125μg/g, p.o). significantly inhibited the expression of the inflammatory mediator Nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. After treatment, there was a significant increase in body weight and alleviation of diarrhea and bloody stools in colitis mice. It also reduced inflammatory cell infiltration. Furthermore, it decreased the serum levels of TNF-α and IL-1β, and reduced the activity of p-JNK and p-ERK in the MAPK pathway.Conclusion: MEO relieved DSS-induced colitis by modulating the MAPK pathway. The experimental results indicate that the MAPK pathway might be inhibited by the synergistic effect of gamma-Muurolene, Curzerene, beta-Elemene, and Furanoeudesma 1.3-diene in MEO, which provides a novel idea for subsequent research and development of new anti-colitis drugs. Keywords: colitis, myrrh essential oil, MAPK signaling pathway, RNA sequencing, weighted gene co-expression network analysis

Keywords

• colitis
• myrrh essential oil
• mapk signaling pathway
• rna sequencing
• weighted gene co-expression network analysis