Anti-pruritic and anti-inflammatory effects of oxymatrine in a mouse model of allergic contact dermatitis

Xu, Xiaoyun; Xiao, Wei; Zhang, Zhe; Pan, Jianhao; Yan, Yixi; Zhu, Tao; Tang, Dan; Ye, Kaihe; Paranjpe, Manish; Qu, Lintao; Nie, Hong

doi:10.1016/j.jdermsci.2018.04.009

Cited by 24 publications

(11 citation statements)

References 26 publications

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“…Intensive pruritus is a representative clinical manifestation of AD, and a vicious itch‐scratch cycle is easily established 32,33 . During the period, scratching behaviour was measured and recorded for 10 min after treatment with DNFB.…”

Section: Resultsmentioning

confidence: 99%

Topical application with conjugated linoleic acid ameliorates 2, 4‐dinitrofluorobenzene‐induced atopic dermatitis‐like lesions in BALB/c mice

Cao

Ding

2021

Experimental Dermatology

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Atopic dermatitis (AD) is a multifactorial chronic inflammatory skin disease characterized by skin barrier dysfunction, eczematous lesions, pruritus, and abnormal immune responses. In this study, we assessed the therapeutic effect of topical applied conjugated linoleic acid (CLA) on a murine AD model that was developed by repetitive applications of 2, 4‐dinitrofluorobenzene (DNFB). 2% or 5% CLA could markedly ameliorate AD‐like skin lesions, scratching behaviour and skin inflammation as evidenced by the reduced inflammatory blood cells, IgE and Th2‐related cytokine levels, and the infiltration of mast cells and inflammatory cells to the dermal tissues. Moreover, topical application with CLA modulated skin barrier repair including maintaining a balanced skin pH and increasing skin hydration, partially mediated by upregulating skin barrier‐related protein, filaggrin (FLG). In addition, topical CLA significantly dose‐dependently inhibited pro‐inflammatory cytokines including interleukin (IL)‐6, IL‐1β, tumour necrosis factor (TNF)‐α and pro‐inflammatory enzyme expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) in inflamed mice skin. Its anti‐inflammatory effect was associated with the inhibition of DNFB‐stimulated IκBα and NF‐κB p65 phosphorylation in mouse skin. Taken together, our results suggest that locally applied CLA exerts potentially protective effects against AD lesional skin at least in part, due to regulation of skin barrier function and inflammatory response.

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Section: Resultsmentioning

confidence: 99%

Topical application with conjugated linoleic acid ameliorates 2, 4‐dinitrofluorobenzene‐induced atopic dermatitis‐like lesions in BALB/c mice

Cao

Ding

2021

Experimental Dermatology

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“…The X-ray crystal structure of p38α MAPK (PDB code: 2QD9), COX-1 (PDB code: 1PGF) and COX-2 (PDB code: 1CX2) were obtained from Protein Data Bank. Before docking, the 3 D structures of 6n was generated and the energy minimisation was carried out; removing water moleculars and adding hydrogen atoms to p38α MAPK, COX-1 and COX-2 with the AutoDock Tools 17 . Then, the docking was performed by Autodock 4.2 programme with Lamarckian genetic algorithm to sift the best ligand enzyme interaction.…”

Section: Methodsmentioning

confidence: 99%

Discovery of talmapimod analogues as polypharmacological anti-inflammatory agents

Liu

Cai-yun

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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Twenty novel talmapimod analogues were designed, synthesised and evaluated for the in vivo anti-inflammatory activities. Among them, compound 6n, the most potent one, was selected for exploring the mechanisms underlying its anti-inflammatory efficacy. In RAW264.7 cells, it effectively suppressed lipopolysaccharides-induced (LPS-induced) expressions of iNOS and COX-2. As illustrated by the western blot analysis, 6n downregulated both the NF-jB signalling and p38 MAPK phosphorylation. Further enzymatic assay identified 6n as a potent inhibitor against both p38a MAPK (IC 50 ¼1.95 mM) and COX-2 (IC 50 ¼0.036 mM). By virtue of the concomitant inhibition of p38a MAPK, its upstream effector, and COX-2, along with its capability to downregulate NF-jB and MAPK-signalling pathways, 6n, a polypharmacological anti-inflammatory agent, deserves further development as a novel anti-inflammatory drug.

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“…In addition, OMT can improve ischemia-reperfusion injury and has cardioprotective, hypoglycemic, hypolipidemic and sedative, analgesic, anti-epileptic, and other central nervous system effects (Liu et al, 2012;Guo et al, 2014;Zhou et al, 2017;Wang et al, 2022). Moreover, OMT exhibits anti-pruritic and anti-inflammatory effects in ACD mice by regulating inflammatory mediators and restoring Th1/Th2 and Th17/ Treg immunological balance, according to prior research (Xu et al, 2018). However, its effect on innate immune cells and on neutrophils and macrophages remain unknown, necessitating more investigation.…”

Section: Introductionmentioning

confidence: 96%

“…It has the chemical formula C 15 H 24 N 2 O 2 , with a molecular weight of 264.36, and a molecular structure that is depicted in Figure 2. OMT possesses a range of biological effects, including antipruritic (Xu et al, 2018;Zhu et al, 2020), antiviral (Jiang et al, 2017), anticancer (Halim et al, 2019), and antifibrosis (Liu et al, 2020). In addition, OMT can improve ischemia-reperfusion injury and has cardioprotective, hypoglycemic, hypolipidemic and sedative, analgesic, anti-epileptic, and other central nervous system effects (Liu et al, 2012;Guo et al, 2014;Zhou et al, 2017;Wang et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

The exploration of the potential mechanism of oxymatrine-mediated antipruritic effect based on network pharmacology and weighted gene co-expression network analysis

Luo

Zhao

et al. 2022

Front. Pharmacol.

Self Cite

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The treatment of chronic itch is considered to be a challenge for its non-histamine dependence and the search for alternative medicine is still striving. The pathology of the chronic itch is closely related to immune system regulation and inflammatory response. Oxymatrine (OMT) is a traditional Chinese medicine ingredient extracted from the roots of Sophora flavescens Aiton with significant antitumor, analgesic, and anti-inflammatory effects. However, the underlying mechanism of OMT on chronic itch is obscure, which limits clinical application. Hence, this study is aimed to clarify the pruritus alleviation mechanism of OMT by combining network pharmacology analysis, weighted gene co-expression analysis (WGCNA), and molecular docking. We screened 125 common targets of OMT regulating inflammation and pruritus with pharmacology technology, the GO enrichment function analysis and KEGG signaling pathway analysis to demonstrate the close relation to the signaling pathways regulating inflammation such as MAPK signaling pathway and PI3K-AKT signaling pathway. We adopted the most relevant templates for pruritus diseases, combined with network pharmacology to preliminarily screen out 3 OMT functions and regulatory targets, exerting a good connection and correlation with the target at the screened disease targets. Further experiments were conducted to explore the potential mechanism of OMT using the LPS-induced RAW264.7 cell inflammation model. The results showed that pretreatment with different concentrations of OMT (25 μM, 50 μM, and 100 μM) for 24 h, inhibited expression of IL-6, iNOS TLR4 and TGFR-1 as well as apoptosis of Raw264.7 cells induced by LPS. Moreover, OMT effectively inhibited LPS-induced MAPK pathway activation and the expression of related sites MAP2K1, MAPK8 MAP2K4, and MAPKAP-K2 in RAW 264.7 cells. The OMT also reduced the phosphorylation of p-38, associated with site in the activation of MAPK signaling pathway. These results could contribute to a better understanding of the mechanisms underlying how OMT alleviates inflammation to treat chronic pruritic diseases and provide a potential drug for the treatment of chronic itch.

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Anti-pruritic and anti-inflammatory effects of oxymatrine in a mouse model of allergic contact dermatitis

Abstract: We have demonstrated that OMT exhibits anti-pruritic and anti-inflammatory effects in ACD mice by regulating inflammatory mediators. OMT might emerge as a potential drug for the treatment of pruritus and skin inflammation in the setting of ACD.

Cited by 24 publications

References 26 publications

Topical application with conjugated linoleic acid ameliorates 2, 4‐dinitrofluorobenzene‐induced atopic dermatitis‐like lesions in BALB/c mice

Topical application with conjugated linoleic acid ameliorates 2, 4‐dinitrofluorobenzene‐induced atopic dermatitis‐like lesions in BALB/c mice

Discovery of talmapimod analogues as polypharmacological anti-inflammatory agents

The exploration of the potential mechanism of oxymatrine-mediated antipruritic effect based on network pharmacology and weighted gene co-expression network analysis

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