Objective This study aims to elucidate the therapeutic potential of osthole for the treatment of atopic dermatitis(AD),focusing on its ability to alleviate chronic pruritus(CP)and the underlying molecular mechanisms.M...Objective This study aims to elucidate the therapeutic potential of osthole for the treatment of atopic dermatitis(AD),focusing on its ability to alleviate chronic pruritus(CP)and the underlying molecular mechanisms.Methods In this study,we investigated the anti-inflammatory effects of osthole in both a 2,4-dichloronitrobenzene(DNCB)-induced AD mouse model and tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)stimulated huma immortalized epidermal(HaCaT)cells.The anti-itch effect of osthole was specifically assessed in the AD mouse model.Using methods such as hematoxylin and eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA),western blot(WB),quantitative real-time PCR(qRT-PCR),and immunofluorescence staining.Results Osthole improved skin damage and clinical dermatitis scores,reduced scratching bouts,and decreased epidermal thickness AD-like mice.It also reduced the levels of interleukin(IL)-31 and IL-31 receptor A(IL-31 RA)in both skin tissues and HaCaT cells.Furthermore,Osthole suppressed the protein expression levels of phosphor-p65(p-p65)and phosphor-inhibitor of nuclear factor kappa-Bα(p-IκBα).Meanwhile,it increased the protein expression levels of peroxisome proliferator-activated receptorα(PPARα)and PPARγin HaCaT cells.Conclusion These findings indicated that osthole effectively inhibited CP in AD by activating PPARα,PPARγ,repressing the NF-κB signaling pathway,as well as the expression of IL-31 and IL-31 RA.展开更多
基金supported by the Natural Science Foundation of China(NSFC)to Guanyi Wu(No.82060768)the Natural Science Foundation of Guangxi Zhuang Autonomous Region(No.2020GXNSFAA297244)+4 种基金Innovation Project of Guangxi Graduate Education(No.YCSW2023392)an Open Project of the Guangxi University of Chinese Medicine Top Disciplines Construction Project(No.2018XK022)an Open Project of the Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine(No.GXZYKF2020-07)Guipai Traditional Chinese Medicine Top-Notch Talent Funding Project from Guangxi University of Chinese Medicine(No.2022C001)the Second and Third Batch of the“Qihuang Project”High-Level Talent Team Cultivation Project of Guangxi University of Traditional Chinese Medicine(No.2021001 and No.202402)。
文摘Objective This study aims to elucidate the therapeutic potential of osthole for the treatment of atopic dermatitis(AD),focusing on its ability to alleviate chronic pruritus(CP)and the underlying molecular mechanisms.Methods In this study,we investigated the anti-inflammatory effects of osthole in both a 2,4-dichloronitrobenzene(DNCB)-induced AD mouse model and tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)stimulated huma immortalized epidermal(HaCaT)cells.The anti-itch effect of osthole was specifically assessed in the AD mouse model.Using methods such as hematoxylin and eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA),western blot(WB),quantitative real-time PCR(qRT-PCR),and immunofluorescence staining.Results Osthole improved skin damage and clinical dermatitis scores,reduced scratching bouts,and decreased epidermal thickness AD-like mice.It also reduced the levels of interleukin(IL)-31 and IL-31 receptor A(IL-31 RA)in both skin tissues and HaCaT cells.Furthermore,Osthole suppressed the protein expression levels of phosphor-p65(p-p65)and phosphor-inhibitor of nuclear factor kappa-Bα(p-IκBα).Meanwhile,it increased the protein expression levels of peroxisome proliferator-activated receptorα(PPARα)and PPARγin HaCaT cells.Conclusion These findings indicated that osthole effectively inhibited CP in AD by activating PPARα,PPARγ,repressing the NF-κB signaling pathway,as well as the expression of IL-31 and IL-31 RA.
