Division of Pathophysiology and Pharmacology, College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
Int Immunopharmacol. 2010 Feb;10(2):147-54. doi: 10.1016/j.intimp.2009.10.009. Epub 2009 Oct 26.
We previously reported that 4-hydroxy-3-methoxybenzaldehyde has the most potent anti-inflammatory and analgesic activity of eight phenolic compounds obtained from the dried roots of Gastrodiaelata (GE) Blume (Orchidaceae); its activity may be related to inhibition of cyclooxygenase activities and oxidation. In the present study, the effects of nine phenolic compounds from GE on immediate-phase (IAR) and late-phase (LAR) asthmatic responses after aerosolized-ovalbumin (OA) challenge were evaluated by determining the specific airway resistance (sRaw) using a double-chambered plethysmograph in conscious guinea pigs with IgE-mediated asthma. Furthermore, recruitment of leukocytes, histamine release, and eosinophil peroxidase (EPO) and phospholipase A(2) (PLA(2)) activities were determined in bronchoalveolar lavage fluids (BALF) 24h after the antigen challenge. 4-Hydroxy-3-methoxybenzyl alcohol (12.5mg/kg) significantly (p<0.05) inhibited sRaw in IAR and in LAR by 51.97+/-4.96% and 39.93+/-3.46%, respectively, compared to that of the controls. Further, hydroxy-3-methoxybenzyl alcohol significantly (p<0.05) inhibited recruitment of leukocytes in accordance with amelioration of eosinophilia and neutrophilia, histamine (30.66+/-5.20%), EPO activity (21.58+/-2.02%), and specific PLA(2) activity (16.60+/-2.52%) in BALF compared with the control. In addition, bis-(4-hydroxyphenyl) methane, 4-hydroxy-3-methoxybenzoic acid, and 4-hydroxy-3-methoxybenzaldehyde (12.5mg/kg) significantly (p<0.05) inhibited sRaw, while bis-(4-hydroxyphenyl) methane, benzyl alcohol, and 4-hydroxybenzaldehyde at 12.5mg/kg significantly (p<0.05) inhibited leukocytes, histamine, EPO and PLA(2) activities in BALF compared with the controls. The phenolic glycoside, parishin had less activity compared to aglycones, 4-hydroxybenzyl compounds. These results suggest that the C(4) hydroxy and C(3) methoxy radicals in benzyl alcohols and aldehydes play important roles in mediating the anti-asthmatic activities of these compounds.
我们之前报道过,4-羟基-3-甲氧基苯甲醛是从天麻(兰科天麻属)干根中提取的 8 种酚类化合物中具有最强抗炎和镇痛活性的一种,其活性可能与抑制环氧化酶活性和氧化有关。在本研究中,我们通过使用双室 plethysmograph 在 IgE 介导的哮喘豚鼠中评估了来自天麻的 9 种酚类化合物对雾化卵白蛋白(OA)挑战后的即刻相(IAR)和迟发相(LAR)哮喘反应的影响,以确定特定气道阻力(sRaw)。此外,在抗原挑战后 24 小时,通过测定支气管肺泡灌洗液(BALF)中的白细胞募集、组胺释放以及嗜酸性粒细胞过氧化物酶(EPO)和磷脂酶 A(PLA)活性来确定 4-羟基-3-甲氧基苯甲醇(12.5mg/kg)在 IAR 和 LAR 中分别显著(p<0.05)抑制 sRaw51.97+/-4.96%和 39.93+/-3.46%,与对照组相比。此外,与对照组相比,4-羟基-3-甲氧基苯甲醇显著(p<0.05)抑制白细胞募集,并改善嗜酸性粒细胞和中性粒细胞增多症、组胺(30.66+/-5.20%)、EPO 活性(21.58+/-2.02%)和特定 PLA(2)活性(16.60+/-2.52%)。此外,双-(4-羟基苯基)甲烷、4-羟基-3-甲氧基苯甲酸和 4-羟基-3-甲氧基苯甲醛(12.5mg/kg)显著(p<0.05)抑制 sRaw,而双-(4-羟基苯基)甲烷、苯甲醇和 4-羟基苯甲醛在 12.5mg/kg 时显著(p<0.05)抑制白细胞、组胺、EPO 和 PLA(2)活性与对照组相比。酚糖苷 parishin 的活性低于苷元 4-羟基苯甲醇化合物。这些结果表明,苯甲醇和苯甲醛中的 C(4)羟基和 C(3)甲氧基自由基在介导这些化合物的抗哮喘活性中起重要作用。