Anti-Atopic Dermatitis Effects of Abietic Acid Isolated from Rosin under Condition Optimized by Response Surface Methodology in DNCB-Spread BALB/c Mice. 松香中分离的松节酸在响应面方法优化条件下对DNCB扩散BALB/c小鼠的抗特应性皮炎作用。
Anti-Atopic Dermatitis Effects of Abietic Acid Isolated from Rosin under Condition Optimized by Response Surface Methodology in DNCB-Spread BALB/c Mice.
发表日期:2023 Mar 07
作者:
Jumin Park, Ji Eun Kim, You Jeong Jin, Yu Jeong Roh, Hee Jin Song, Ayun Seol, So Hae Park, Sungbaek Seo, Heeseob Lee, Dae Youn Hwang
来源:
Cell Death & Disease
摘要:
松香酸(AA)已知对炎症、光老化、骨质疏松、癌症和肥胖具有益处,但其在特应性皮炎(AD)中的疗效尚未报道。我们研究了从松香中新分离的AA在AD模型中的抗AD作用。为了实现这一目标,我们在响应面法(RSM)优化的条件下从松香中分离出AA,并在AA治疗4周后分析了其对细胞死亡、iNOS诱导的COX-2介导通路、炎症性细胞因子转录以及皮肤组织病理学结构的影响。AA通过异构化和反应结晶分离纯化,在RSM确定的条件下(HCl,2.49毫升;回流提取时间,61.7分钟;乙醇胺,7.35毫升),得到了纯度为99.33%,萃取率为58.61%的AA。AA表现出高浓度依赖性的扫除DPPH、ABTS和NO自由基以及透明质酸酶的活性。AA的抗炎症作用在脂多糖(LPS)刺激的RAW264.7巨噬细胞中得到验证,包括改善炎症反应、NO产生、iNOS诱导的COX-2介导通路激活和细胞因子转录等。在经过2,4-二硝基氯苯(DNCB)处理的AD模型中,与车辆涂布组相比,AA霜(AAC)涂布组的皮肤表型、皮炎评分、免疫器官重量和IgE浓度明显改善。此外,AAC涂布可以通过恢复真皮和表皮厚度和肥大细胞数目抑制DNCB诱导的皮肤组织病理学结构恶化。此外,DNCB + AAC处理组的皮肤中iNOS诱导的COX-2介导通路的激活和炎症性细胞因子转录的增加也得到了改善。综上所述,这些结果表明,从松香中新分离出的AA在DNCB处理的AD模型中表现出抗AD作用,并且具有成为AD相关疾病治疗选择的潜力。
Abietic acid (AA) is known to have beneficial effects on inflammation, photoaging, osteoporosis, cancer, and obesity; however, its efficacy on atopic dermatitis (AD) has not been reported. We investigated the anti-AD effects of AA, which was newly isolated from rosin, in an AD model. To achieve this, AA was isolated from rosin under conditions optimized by response surface methodology (RSM), and its effects on cell death, iNOS-induced COX-2 mediated pathway, inflammatory cytokine transcription, and the histopathological skin structure were analyzed in 2,4-dinitrochlorobenzene (DNCB)-treated BALB/c mice after treatment with AA for 4 weeks. AA was isolated and purified through isomerization and reaction-crystallization under the condition (HCl, 2.49 mL; reflux extraction time, 61.7 min; ethanolamine, 7.35 mL) established by RSM, resulting in AA with a purity and extraction yield of 99.33% and 58.61%, respectively. AA exhibited high scavenging activity against DPPH, ABTS, and NO radicals as well as hyaluronidase activity in a dose-dependent manner. The anti-inflammatory effects of AA were verified in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages through amelioration of the inflammatory response, including NO production, iNOS-induced COX-2 mediated pathway activation, and cytokine transcription. In the DNCB-treated AD model, the skin phenotypes, dermatitis score, immune organ weight, and IgE concentration were significantly ameliorated in the AA cream (AAC)-spread groups compared to the vehicle-spread group. In addition, AAC spread ameliorated DNCB-induced deterioration of skin histopathological structure through the recovery of the thickness of the dermis and epidermis and the number of mast cells. Furthermore, activation of the iNOS-induced COX-2 mediated pathway and increased inflammatory cytokine transcription were ameliorated in the skin of the DNCB+AAC-treated group. Taken together, these results indicate that AA, newly isolated from rosin, exhibits anti-AD effects in DNCB-treated AD models, and has the potential to be developed as a treatment option for AD-related diseases.