Anti-atopic dermatitis effect of fraxinellone via inhibiting IL-31 in vivo and in vitro
Niuniu Yang,
Jialin Deng,
Huiwen Xu,
Huijuan Dai,
Han Jin,
Haifeng Shao,
Yanqing Liu
Affiliations
Niuniu Yang
Medical College, Yangzhou University, Yangzhou, 225009, China; The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou University, Yangzhou, 225009, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, 225009, China; Corresponding author. Department of Traditional Chinese and Western Medicine, Medical College, Yangzhou University, 136 Middle Jiangyang Road, Yangzhou, 225009, China.
Jialin Deng
Medical College, Yangzhou University, Yangzhou, 225009, China; The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou University, Yangzhou, 225009, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, 225009, China
Huiwen Xu
School of Nursing & Public Health, Yangzhou University, Yangzhou, 225009, China
Huijuan Dai
Medical College, Yangzhou University, Yangzhou, 225009, China; The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou University, Yangzhou, 225009, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, 225009, China
Han Jin
Medical College, Yangzhou University, Yangzhou, 225009, China; The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou University, Yangzhou, 225009, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, 225009, China
Haifeng Shao
Medical College, Yangzhou University, Yangzhou, 225009, China; The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou University, Yangzhou, 225009, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, 225009, China
Yanqing Liu
Medical College, Yangzhou University, Yangzhou, 225009, China; The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou University, Yangzhou, 225009, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, 225009, China
Chronic recurrent itch and skin inflammation are prominent features of atopic dermatitis (AD), which is closely related to the immune response driven by T-helper type 2 (Th2) cells. The expression of interleukin 31 (IL-31) is positively correlated with the severity of dermatitis. Anti-IL-31 receptor α (IL-31RA) targeted drugs have been used to treat AD, however, they are expensive and have side effects. Fraxinellone (FRA) is one of the main limonoid components in the dried root bark of Dictamnus dasycarpus Turcz.; however, its anti-inflammatory and antipruritic effects on atopic dermatitis (AD) have not been previously reported. In this study, we investigated the anti-dermatitis effect of FRA and its potential mechanism of action using a 2,4-dinitrofluorobenzene (DNFB)-induced AD-like mouse model and lipopolysaccharide (LPS)-stimulated HaCaT cells. FRA significantly inhibited chronic pruritus, epidermal thickening, and inflammatory infiltration in AD mice. FRA not only inhibited the levels of IL-31 in the serum and lesioned skin of AD mice but also significantly downregulated the mRNA expression and protein levels of IL-31, IL-31RA, transient receptor potential (TRP) V1, and TRPA1 in the lesioned skin and dorsal root ganglion (DRG) of AD mice. In LPS-stimulated HaCaT cells, FRA inhibited the production of iNOS and COX2, as well as the protein levels of IL-31, IL-31RA, TRPV1 and TRPA1, showing significant anti-inflammatory effects. In summary, our findings suggest that FRA exerts antipruritic and anti-inflammatory effects in AD by regulating the IL-31 pathway, and may hold promise for the clinical treatment of AD.
