Sharma Manju, Levenson Corey, Browning John C, Becker Emily M, Clements Ian, Castella Paul, Cox Michael E
The Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada.
Santalis Pharmaceuticals, Inc., San Antonio, TX, United States.
Front Pharmacol. 2018 Mar 9;9:200. doi: 10.3389/fphar.2018.00200. eCollection 2018.
Cyclic adenosine monophosphate phosphodiesterases (PDEs) regulate pro-inflammatory cytokine production. One isoform, PDE4, is overactive in chronic relapsing inflammatory skin diseases: psoriasis and eczema/atopic dermatitis, and in several cancers. East Indian sandalwood oil (EISO) has significant anti-inflammatory properties. Here, we report that 75% of pediatric eczema/atopic dermatitis patients treated with topical EISO formulations achieved a >50% reduction in their Eczema Area and Severity Index score. EISO treatment of a psoriasis model reduced PDE4 expression and reversed histopathology. EISO directly inhibited PDE enzymatic activity . In lipopolysaccharide-stimulated human dermal fibroblast, BEAS-2B, A549, and THP-1 cells, EISO suppressed total cellular PDE activity, PDE4, and 7 transcript levels, nuclear factor kappa B (NF-κB) activation, and pro-inflammatory cytokines/chemokine production. These results suggest that EISO anti-inflammatory activity is mediated through suppressing PDE activity, thus facilitating cAMP-regulated inhibition of NF-κB and indicate EISO as an attractive natural therapeutic for chronic and acute inflammatory disorders.
环磷酸腺苷磷酸二酯酶（PDEs）调节促炎细胞因子的产生。其中一种同工型PDE4在慢性复发性炎症性皮肤病（银屑病和湿疹/特应性皮炎）以及几种癌症中过度活跃。东印度檀香油（EISO）具有显著的抗炎特性。在此，我们报告，使用外用EISO制剂治疗的75%的儿童湿疹/特应性皮炎患者的湿疹面积和严重程度指数评分降低了50%以上。EISO对银屑病模型的治疗降低了PDE4的表达并逆转了组织病理学变化。EISO直接抑制PDE酶活性。在脂多糖刺激的人皮肤成纤维细胞、BEAS-2B细胞、A549细胞和THP-1细胞中，EISO抑制了总细胞PDE活性、PDE4和7转录水平、核因子κB（NF-κB）的激活以及促炎细胞因子/趋化因子的产生。这些结果表明，EISO的抗炎活性是通过抑制PDE活性介导的，从而促进cAMP调节的NF-κB抑制，并表明EISO是一种有吸引力的用于慢性和急性炎症性疾病的天然治疗剂。
