Anti-inflammatory and Anti-oxidative Activities of Paeonol and Its Metabolites Through Blocking MAPK/ERK/p38 Signaling Pathway

Jin, Xin; Wang, Jing; Xia, Ziming; Shang, Chang-Hui; Chao, Qiuli; Liu, Yurong; Fan, Hui; Chen, Daquan; Qiu, Feng; Zhao, Feng

doi:10.1007/s10753-015-0265-3

Cited by 82 publications

(65 citation statements)

References 24 publications

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“…Another report also showed that Ang 1-7 treated HEK 293T cells at high concentrations redistributed the MAS-1 R to intracellular vesicles and co-localized Ang 1-7 with Rab5 and the adaptor protein complex 2, suggesting regulation by a clathrin-mediated pathway [43]. Enhanced activity of members of the MAPK family, p38 MAPK and ERK1/2 as well as Akt (the downstream target of PI3K), which we observed in colonic sections post DSS treatment (Figs 8-10) has previously been reported in colonic biopsies from IBD patients [44][45][46][47]. Treatment with inhibitors of these signaling molecules ameliorated colitis severity in mice and reduced the disease activity index in patients, underlining their role in IBD pathogenesis [44][45][46][47].…”

Section: Discussionsupporting

confidence: 73%

Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis

et al. 2016

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BackgroundThere is evidence to support a role for angiotensin (Ang) 1–7 in reducing the activity of inflammatory signaling molecules such as MAPK, PKC and SRC. Enhanced angiotensin converting enzyme 2 (ACE2) expression has been observed in patients with inflammatory bowel disease (IBD) suggesting a role in its pathogenesis, prompting this study.MethodsThe colonic expression/activity profile of ACE2, Ang 1–7, MAS1-receptor (MAS1-R), MAPK family and Akt were determined by western blot and immunofluorescence. The effect of either exogenous administration of Ang 1–7 or pharmacological inhibition of its function (by A779 treatment) was determined using the mouse dextran sulfate sodium model.ResultsEnhanced colonic expression of ACE2, Ang1-7 and MAS1-R was observed post-colitis induction. Daily Ang 1–7 treatment (0.01–0.06 mg/kg) resulted in significant amelioration of DSS-induced colitis. In contrast, daily administration of A779 significantly worsened features of colitis. Colitis-associated phosphorylation of p38, ERK1/2 and Akt was reduced by Ang 1–7 treatment.ConclusionOur results indicate important anti-inflammatory actions of Ang 1–7 in the pathogenesis of IBD, which may provide a future therapeutic strategy to control the disease progression.

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Section: Discussionsupporting

confidence: 73%

Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis

et al. 2016

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“…Recent research progress on the inhibitory activity of paeonol on the inflammatory reaction is significant (38,39). The mechanism by which paeonol decreases MyD88 and TLR proteins, either by inducing degradation of these proteins or blocking their synthesis, remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Paeonol ameliorates imiquimod-induced psoriasis-like skin lesions in BALB/c mice by inhibiting the maturation and activation of dendritic cells

Meng

Wang

Xie

et al. 2017

International Journal of Molecular Medicine

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Paeonol, an active component derived from the traditional Chinese medicine Cortex Moutan, possesses anti-inflammatory, analgesic, antioxidant and anti-allergic properties. Psoriasis is a chronic, recurrent, inflammatory dermatosis accompanied by excessive activation of Toll-like receptors (TLRs) in dendritic cells (DCs), which are primarily responsible for initiating an immune response. We investigated the effect of paeonol on inflammation in an imiquimod (IMQ)-induced psoriasis-like mouse model and murine bone marrow-derived dendritic cells (BMDCs) stimulated by R848. Mice were intragastrically administered 100 mg/kg (high), 50 mg/kg (medium) and 25 mg/kg (low) paeonol, respectively. We evaluated inflammation of psoriasis-like lesions based on histological changes, protein levels of myeloid differentiation factor 88 (MyD88) and TLR8 in skin lesions by western blotting, and levels of CD11c+ DCs in skin by immunoassay and in spleens by flow cytometry. Inflammatory cytokines [interleukin (IL)-23, IL-12 and IL-1β] in skin lesions and BMDCs were also assessed by RT-PCR and ELISA. Application of paeonol decreased IMQ-induced keratinocyte proliferation, and infiltration of CD3+ cells, while the treatment ameliorated CD11c+ cells in the spleen and skin, and reduced MyD88 and TLR8 proteins in skin lesions. Paeonol inhibited IMQ-induced mRNA expression of IL-23, but not IL-12 and IL-1β in BMDCs, along with significantly lower levels of DCs expressing MHCII, CD80 and CD86 in vitro. These results indicate that paeonol suppresses the maturation and activation of DCs by decreasing MyD88 and TLR8 proteins in the TLR7/8 signaling pathway which finally alleviates psoriasis-like skin lesions. The TLR7/8 signaling pathway in DCs provides an important insight into the mechanism of psoriasis, and paeonol may be a potent therapeutic drug for psoriasis.

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“…Paeonol has a wide range of biological effects, including anti-inflammatory, immune regulatory, anti-tumor, and anti-oxidative effects [15, 16]. Paeonol is used in food additive and traditional oriental medicines in treating various diseases including Alzheimer's diseases [17, 18] and atherosclerosis [19].…”

Section: Introductionmentioning

confidence: 99%

Paeonol suppresses solar ultraviolet-induced skin inflammation by targeting T-LAK cell-originated protein kinase

et al. 2017

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Excessive exposure to solar UV (SUV) is related with numerous human skin disorders, such as skin inflammation, photoaging and carcinogenesis. T-LAK cell- originated protein kinase (TOPK), an upstream of p38 mitogen-activated protein kinase (p38) and c-Jun N-terminal kinases (JNKs), plays an important role in SUV -induced skin inflammation, and targeting TOPK has already been a strategy to prevent skin inflammation. In this study, we found that the expression of TOPK, phosphorylation of p38 or JNKs was increased in human solar dermatitis tissues. The level of phosphorylation of p38 or JNKs increased in a dose and time dependent manner in HaCat cells or JB6 Cl41 cells after SUV treatment. Paeonol is an active component isolated from traditional Chinese herbal medicines, and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2H-tetrazdium) assay showed that it has no toxicity to cells. Microscale thermophoresis (MST) assay showed that paeonol can bind TOPK ex vivo. In vitro kinase assay showed paeonol can inhibit TOPK activity. Ex vivo studies further showed paeonol suppressed SUV-induced phosphorylation level of p38, JNKs, MSK1 and histone H2AX by inhibiting TOPK activity in a time and dose dependent manner. Paeonol inhibited the secretion of IL-6 and TNF-α in HaCat and JB6 cells ex vivo. In vivo studies demonstrated that paeonol inhibited SUV-induced increase of TOPK, the phosphorylation of p38, JNKs and H2AX, and the secretion of IL-6 and TNF-α in Babl/c mouse. In summary, our data indicated a protective role of paeonol against SUV-induced inflammation by targeting TOPK, and paeonol could be a promising agent for the treatment of SUV-induced skin inflammation.

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Anti-inflammatory and Anti-oxidative Activities of Paeonol and Its Metabolites Through Blocking MAPK/ERK/p38 Signaling Pathway

Cited by 82 publications

References 24 publications

Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis

Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis

Paeonol ameliorates imiquimod-induced psoriasis-like skin lesions in BALB/c mice by inhibiting the maturation and activation of dendritic cells

Paeonol suppresses solar ultraviolet-induced skin inflammation by targeting T-LAK cell-originated protein kinase

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