Re-evaluation of cyclooxygenase-2-inhibiting activity of vanillin and guaiacol in macrophages stimulated with lipopolysaccharide.
Re-evaluation of cyclooxygenase-2-inhibiting activity of vanillin and guaiacol in macrophages stimulated with lipopolysaccharide.
复制标题
DOI：
--
复制
发表时间：
2007-03
影响因子：
2
通讯作者：
Y. Murakami;A. Hirata;S. Ito;Masao Shoji;Shoji Tanaka;T. Yasui;M. Machino;S. Fujisawa
中科院分区：
文献类型：
--
作者：
Y. Murakami;A. Hirata;S. Ito;Masao Shoji;Shoji Tanaka;T. Yasui;M. Machino;S. Fujisawa
植物酚如对位取代的2-甲氧基酚具有抗氧化和抗炎活性，然而，它们的生物活性是浓度依赖性的，可能是由于它们既是抗氧化剂又是促氧化剂的双重性质。丁香酚（2-烯丙基-2-甲氧基苯酚）和异丁香酚（4-丙烯基-2-甲氧基苯酚）在脂多糖（LPS）刺激的巨噬细胞中未显示出环氧合酶-2（考克斯-2）抑制活性。与此相反，香草醛（2-羟基-3-甲氧基苯甲醛）和愈创木酚（2-甲氧基苯酚），尤其是前者，抑制LPS刺激的核因子κ B（NF-κ B）激活和环加氧酶（考克斯）-2基因表达的RAW 264.7小鼠巨噬细胞系的细胞。在2-甲氧基酚类化合物中，香草醛表现出有效的抗炎活性。检测酚类O-H键解离焓（BDE）和分子轨道能（化学硬度[eta]、电负性[chi]和亲电性[omega]）以阐明负责抑制考克斯-2表达的机制。香草醛的BDE、chi和omega值明显高于其他2-甲氧基苯酚的相应值。2-甲氧基酚类化合物的抗炎活性依赖于BDE，而酚类化合物的功能对激发其抗炎活性至关重要。此外，抗炎活性取决于chi和omega。这些发现使得香草醛作为候选治疗剂具有吸引力。
Phytophenols such as para-substituted 2-methoxyphenols exhibit antioxidant and anti-inflammatory activities, however, their biological activities are concentration-dependent, possibly due to their dual property of being both antioxidant and prooxidant. Eugenol (2-allyl-2-methoxyphenol) and isoeugenol (4-propenyl-2-methoxyphenol) did not reveal cyclooxygenase-2 (COX-2)-inhibiting activity in macrophages stimulated with lipopolysaccharide (LPS). In contrast, vanillin (2-hydroxy-3-methoxybenzaldehyde) and guaiacol (2-methoxyphenol), especially the former, inhibited LPS-stimulated nuclear factor kappa B (NF-kappaB) activation and cyclooxygenase (COX)-2 gene expression in cells of the RAW 264.7 murine macrophage cell line. Among the 2-methoxyphenols, vanillin demonstrated a potent anti-inflammatory activity. The phenolic O-H bond dissociation enthalpy (BDE) and molecular orbital energies (chemical hardness [eta], electronegativity [chi], and electrophilicity [omega]) were examined to clarify the mechanism responsible for inhibition of COX-2 expression. The BDE, chi, and omega values for vanillin were significantly higher than the corresponding values for the other 2-methoxyphenols. The anti-inflammatory activity of 2-methoxyphenols depended on the BDE and the phenol function was crucial for eliciting this activity. In addition, the anti-inflammatory activity depended on the chi and omega. These findings make vanillin attractive as a candidate therapeutic agent.