School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Room 101-J, 1/F, Li Wai Chun Building, Shatin, NT, China Hong Kong Special Administrative Region.
School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Room 101-J, 1/F, Li Wai Chun Building, Shatin, NT, China Hong Kong Special Administrative Region; Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, China Hong Kong Special Administrative Region.
Phytomedicine. 2022 Sep;104:154346. doi: 10.1016/j.phymed.2022.154346. Epub 2022 Jul 18.
Huang-Lian-Jie-Du Decoction is a traditional Chinese medicine formula which has long been used to treat inflammatory skin disease including AD. However, Gardeniae Fructus, a component herb of HLJDD, has noticeable toxicity in liver and kidney. We therefore replaced Gardeniae Fructus with Dictamni Cortex with a hope to derive at a modified HLJDD (MHLJDD) with better safety profile.
The present study aimed to develop MHLJDD and identify its active fraction as innovative therapeutic agents for AD using 2,4-dinitrobenzene (DNCB) and calcipotriol (MC903)-sensitized mouse models of AD.
MHLJDD and the combination of the 1-butanol-soluble-fraction and the water-soluble-fraction (MHLJDD-F) were given intragastrically to the DNCB-induced mice and MC903-induced mice for two weeks. The body weight, dorsal skin/ear thickness and severity of AD symptoms of the mice were measured throughout the study. Scratching behaviors were observed after drug treatment. The blood and dorsal skin/ear tissues of mice were harvested for histopathological examination and biochemical analyses.
The results revealed that DNCB- and MC903-induced AD symptoms, including skin thickening, dryness, erythema and excoriations, in the dorsal skin and ears were significantly alleviated in the MHLJDD and MHLJDD-F-treated mice. Ceramides content and protein expressions of filaggrin and loricrin were also up-regulated after treatment with MHLJDD and MHLJDD-F. In addition, skin inflammation induced by DNCB and MC903 were markedly suppressed in the MHLJDD and MHLJDD-F-treated mice, and the action mechanisms involve suppression of the release of inflammatory cytokines, as well as downregulation of the activation of NF-κB and MAPKs pathways. Besides, MHLJDD and MHLJDD-F could reverse the abundance of gut microbiota induced by DNCB in mice.
MHLJDD and MHLJDD-F could markedly relieve AD-like symptoms induced by DNCB and MC903 in mice through, at least in part, improving the epidermal barrier function and inhibiting skin inflammation via suppressing the activation of NF-κB and MAPKs pathways and regulation of the gut microflora dysbiosis. This study reported for the first time that MHLJDD and its active fraction could be used as innovative therapeutic agents for AD.
黄连解毒汤是一种传统的中药方剂，长期以来一直用于治疗包括 AD 在内的炎症性皮肤病。然而，黄连解毒汤的组成药栀子具有明显的肝肾毒性。因此，我们用白鲜皮代替栀子，希望得到一种安全性更好的改良黄连解毒汤（MHLJDD）。
本研究旨在开发 MHLJDD，并通过 2,4-二硝基苯（DNCB）和钙泊三醇（MC903）敏化的 AD 小鼠模型，鉴定其活性部位作为 AD 的创新治疗药物。
将 MHLJDD 和 1-丁醇可溶部分和水溶部分的组合（MHLJDD-F）灌胃给予 DNCB 诱导的小鼠和 MC903 诱导的小鼠，持续两周。在整个研究过程中，测量小鼠的体重、背部皮肤/耳朵厚度和 AD 症状的严重程度。在药物治疗后观察抓挠行为。采集小鼠的血液和背部皮肤/耳朵组织进行组织病理学检查和生化分析。
结果表明，MHLJDD 和 MHLJDD-F 处理可显著缓解 DNCB 和 MC903 诱导的 AD 症状，包括背部皮肤和耳朵的皮肤增厚、干燥、红斑和糜烂。MHLJDD 和 MHLJDD-F 还可上调角质层含量和丝聚合蛋白和兜甲蛋白的蛋白表达。此外，MHLJDD 和 MHLJDD-F 可显著抑制 DNCB 和 MC903 诱导的皮肤炎症，其作用机制涉及抑制炎症细胞因子的释放，以及下调 NF-κB 和 MAPKs 通路的激活。此外，MHLJDD 和 MHLJDD-F 可逆转 DNCB 诱导的小鼠肠道微生物群的丰度。
MHLJDD 和 MHLJDD-F 可通过改善表皮屏障功能和抑制皮肤炎症，至少部分通过抑制 NF-κB 和 MAPKs 通路的激活和调节肠道微生物群失调，显著缓解 DNCB 和 MC903 诱导的 AD 样症状。本研究首次报道，MHLJDD 和其活性部分可作为 AD 的创新治疗药物。
