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

Abstract

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.

Gold lotion from citrus peel extract ameliorates imiquimod‐induced psoriasis‐like dermatitis in murine

“…We have previously found that oral administration of GL reduces systemic Th1 immune responses and hapten‐induced CHS . This suppressive effect of GL on BMDCs may also contribute to its anti‐psoriasis activity, as paeonol has a similar effect . It is probable that GL attenuates the activation of the antigen presenting cells in skin (such as Langerhans cells and dermal DCs) and then decreases T cell proliferation and differentiation.…”

“…14 This suppressive effect of GL on BMDCs may also contribute to its anti-psoriasis activity, as paeonol has a similar effect. 40 It is probable that GL attenuates the activation of the antigen presenting cells in skin (such as Langerhans cells and dermal DCs) 41 and then decreases T cell proliferation and differentiation. On the other hand, IMQ-induced IFN-production by pDCs is essential for Th17 differentiation and psoriasis-like skin inflammation.…”

Cynanchum paniculatum and Its Major Active Constituents for Inflammatory‐Related Diseases: A Review of Traditional Use, Multiple Pathway Modulations, and Clinical Applications

“…In vivo and in vitro studies suggested a protective role of paeonol against solar ultraviolet-(SUV-) induced skin inflammation via targeting T-LAK cell-originated protein kinase (TOPK), an upstream of p38 kinases and JNKs [92]. Furthermore, paeonol inhibits IL-6 and TNF-α secretion in a skin inflammation mouse model [93]. Paeonol ameliorates imiquimod-induced psoriasis-like skin lesions by inhibiting the maturation and activation of dendritic cells in vivo [93].…”

“…Furthermore, paeonol inhibits IL-6 and TNF-α secretion in a skin inflammation mouse model [93]. Paeonol ameliorates imiquimod-induced psoriasis-like skin lesions by inhibiting the maturation and activation of dendritic cells in vivo [93]. Other clinical observational studies suggest that Cynanchum paniculatum possesses antipruritic effects in recurrent urticaria, tinea dermatosis, or pityriasis when used in decoction or external application as washing liquid [94,95].…”

Comparative Histological Study on the Preventive Role of Acarbose and Calcipotriol/Betamethasone in Mouse Model of Psoriasis-Like Skin Inflammation Induced by Imiquimod

“…Certain cells of the immune system and their inflammatory factors play the key role in psoriasis pathogenesis [12] . Researches have revealed that T helper 17 (Th17) cells and the inflammatory cytokines they produce especially interleukin (IL)-23 are detected in psoriatic lesions [10] .…”