五种精油对人软骨细胞中 IL-1 诱导的 Nf-kappaB 激活和 NO 产生的潜在抑制剂的筛选：α-蒎烯抑制活性的表征。
Screening of five essential oils for identification of potential inhibitors of IL-1-induced Nf-kappaB activation and NO production in human chondrocytes: characterization of the inhibitory activity of alpha-pinene.
机构信息
Laboratory of Pharmacognosy, Faculty of Pharmacy/CEF, University of Coimbra, Coimbra, Portugal.
出版信息
Planta Med. 2010 Feb;76(3):303-8. doi: 10.1055/s-0029-1186085. Epub 2009 Sep 11.
Nuclear factor-kappaB is a key transcription factor activated by pro-inflammatory signals, like interleukin-1beta (IL-1), being required for the expression of many inflammatory and catabolic mediators, such as nitric oxide (NO), that play an important role in arthritic diseases. This work aimed at screening and identifying natural inhibitors of IL-induced NF-kappaB activation and NO production in human articular chondrocytes. Five essential oils obtained from four plants of the Iberian flora, Mentha x piperita L. (Lamiaceae), Origanum virens L. (Lamiaceae), Lavandula luiseri L. (Lamiaceae), and Juniperus oxycedrus L. subsp. oxycedrus (Cupressaceae), were screened for their ability to prevent IL-1-induced NO production. The oil showing higher inhibitory activity was fractionated, concentrated, analyzed for composition elucidation and prepared for further assays. For this purpose, the human chondrocytic cell line C-28/I2 was used to evaluate NF-kappaB activation by determining the cytoplasmic levels of the total and phosphorylated forms of the inhibitory protein, I kappaB-alpha, and the NF-kappaB-DNA binding activity. The essential oil from the leaves of J. oxycedrus in a concentration of 0.02 % (v/v) achieved the greatest inhibition (80 +/- 8%) of IL-1-induced NO production. Chemical analysis showed that this essential oil is predominantly composed of monoterpene hydrocabons, being alpha-pinene [2,6,6-trimethyl-bicyclo(3.1.1)hept-3-ene] the major constituent (76 %). Similarly to the effect of the whole oil, a fraction containing 93% alpha-pinene reduced significantly IL-1-induced I kappaB-alpha degradation. Moreover, alpha-pinene also decreased I kappaB-alpha phosphorylation, NF-kappaB-DNA binding activity, and NO production. Another fraction containing oxygenated mono- and sesquiterpenes was nearly as effective as alpha-pinene. The ability of the alpha-pinene-containing fraction to reduce IL-1-induced NF-kappaB activation and NO production warrants further studies to demonstrate the usefulness of alpha-pinene in the treatment of arthritic diseases and other conditions in which NF-kappaB and NO play pathological roles.
核因子-κB 是一种由促炎信号（如白细胞介素-1β（IL-1））激活的关键转录因子，是许多炎症和分解代谢介质（如一氧化氮（NO））表达所必需的，这些介质在关节炎疾病中起着重要作用。本工作旨在筛选和鉴定人关节软骨细胞中白细胞介素诱导的 NF-κB 激活和 NO 产生的天然抑制剂。从伊比利亚植物群的四种植物中获得的五种精油，薄荷（薄荷），牛至（牛至），薰衣草（薰衣草）和杜松（杜松）亚属（杜松）（柏科），因其预防 IL-1 诱导的 NO 产生的能力而被筛选。显示出更高抑制活性的油被分离，浓缩，分析组成阐明并准备进行进一步的测定。为此，使用人软骨细胞系 C-28/I2 通过测定抑制蛋白 IκB-α的总形式和磷酸化形式以及 NF-κB-DNA 结合活性来评估 NF-κB 的激活。杜松叶精油在 0.02％（v/v）的浓度下可实现对 IL-1 诱导的 NO 产生的最大抑制（80±8％）。化学分析表明，这种精油主要由单萜烃组成，其中α-蒎烯[2,6,6-三甲基双环（3.1.1）庚-3-烯]是主要成分（76％）。与整个油的作用类似，含有 93％α-蒎烯的馏分可显著减少 IL-1 诱导的 IκB-α降解。此外，α-蒎烯还降低了 IκB-α磷酸化，NF-κB-DNA 结合活性和 NO 产生。另一个含有单萜和倍半萜的含氧馏分与α-蒎烯几乎一样有效。含α-蒎烯的馏分降低 IL-1 诱导的 NF-κB 激活和 NO 产生的能力需要进一步研究，以证明α-蒎烯在治疗关节炎疾病和其他 NF-κB 和 NO 发挥病理作用的情况下的有用性。
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