Ayanin及biochanin A抗氣喘的作用

Anti-asthmatic actions of ayanin and biochanin A

沈欣儀(Hsin-Yi Shen)

指導教授 ： 柯文昌 ； 林建煌

臺北醫學大學/醫學院/醫學科學研究所/碩士(2008年)

https://doi.org/10.6831/TMU.2008.00006

摘要

Ayanin (quercetin-3,4′,7-O-trimethylether)為quercetin之甲基衍生物。報告指出它對phosphodiesterase (PDE) 有抑制作用，它的PDE4H/PDE4L比值大於19； Biochanin A為紅花苜蓿(red clover，Trifolium pretense L.)之主成分，除了有植物性雌激素的功能外，亦有抑制PDE的作用，它的PDE4H/PDE4L比值則大於35。因此，我們有興趣探討它們是否具有抗氣喘的作用。
在雌性的BALB/c小鼠因注射卵蛋白 (ovalbumin, OVA)引起的過敏性氣喘(allergic asthma) 模式，顯示ayanin (30~100 μg/kg, p.o.)可以有意義且劑量依存性地減少小白鼠由MCh (25~50 mg/ml)所增加的enhanced pause (Penh)值，亦可有意義地減少肺泡灌洗液(BALF)中總發炎細胞、巨噬細胞、淋巴球、嗜中性白血球和嗜酸性白血球的數目。Ayanin 10~100 μmol/kg有意義地減少BALF中IL-2、IL-4、IL-5及TNF-α的含量，但少劑量(10 μmol/kg)不能有意義地減少TNF-α的含量，是唯一例外。Ayanin 高劑量(100 μmol/kg)會增加IFN-γ的含量。Ayanin 30~100 μmol/kg有意義地減少血清和BALF中total及OVA-specific IgE 的含量，但它會增加血清中total IgG2a的含量。皮下注射ayanin 300 μmol/kg並不會縮短小白鼠因xylazine (10 mg/kg)/ ketamine (70 mg/kg)引起的麻醉時間。
口服給予Biochanin A 100 μmol/kg可以有意義地減少小白鼠由MCh (25~50 mg/ml)所增加的enhanced pause (Penh)值，亦可有意義地減少肺泡灌洗液中總發炎細胞、嗜中性白血球和嗜酸性白血球的數目。細胞激素方面，biochanin A 在30~100 μmol/kg 能有意義地減少BALF中IL-2、IL-4、IL-5及TNF-α的含量，但30 μmol/kg不能有意義地減少IL-2及TNF-α的含量，是例外。 Biochanin A 30~100 μmol/kg都不會減少IFN-γ含量。Biochanin A 100 μmol/kg，但非30 μmol/kg ，能有意義地減少血清和BALF中total 及OVA-specific IgE 的含量。高劑量(100 μmol/kg)的biochanin A能有意義地使total IgG2a含量上升。皮下注射biochanin A 300 μmol/kg時不會縮短小白鼠因xylazine (10 mg/kg)/ ketamine (70 mg/kg)引起的麻醉時間。
Ayanin及biochanin A高濃度 (100 μM) 時均可抑制卵蛋白累加所引起之離體天竺鼠氣管的收縮。
結論，Ayanin與biochanin A具有防止氣道過度反應及抗發炎的作用，亦有可能安定肥胖細胞，使其避免去顆粒化 (degranulation)。兩者均不縮短麻醉時間，也顯示嘔吐等副作用可能不明顯，故均具有抗氣喘發展的潛力。

關鍵字

氣喘 ； 類黃酮

並列摘要

Ayanin (quercetin-3,4′,7-O-trimethylether) is a methyl derivative of quercetin, it have been reported to inhibit phosphodiesterase (PDE) activities. The PDE4H/PDE4L ratio of ayanin was reported to be more than 19. Biochanin A, known as one of phytoestrogens, is the main ingredient of the red clover (Trifolium pretense L.), and has been reported to inhibit PDE activities. The PDE4H/PDE4L ratio of biochanin A was reported to be more than 35. Therefore we are interested in their mechanisms of anti-asthmatic effect.
In the OVA-induced allergic asthma model of BALB/c mice, ayanin (30~100 μmol/kg, p.o.) revealed it dose-dependently and significantly attenuated the enhance pause (Penh) value induced by MCh (25~50 mg/ml). Ayanin (30~100 μmol/kg, p.o.) also significantly reduced total inflammatory cells, macrophages, lymphocytes, neutrophils and eosinophils. Ayanin (10~100 μmol/kg, p.o.) significantly attenuated the release of IL-2、IL-4, IL-5 and TNF-α, with the exception that ayanin (10 μmol/kg) did not attenuate the release of TNF-α. Ayanin at 100 μmol/kg significantly increased the release of IFN-γ. Ayanin (30~100 μmol/kg, p.o.) also significantly reduced total and OVA-specific IgE levels in the BALF and the serum, but increased IgG2a level in the serum. In the present results, ayanin (300 μmol/kg, s.c.) did not significantly shorten duration of anesthesia induced by xylazine (10 mg/kg)/ketamine (70 mg/kg).
Biochanin A (100 μmol/ml, p.o.) significantly attenuated the enhanced pause (Penh) value induced by MCh (25~50 mg/ml), and also significantly reduced total inflammatory cells, neutrophils and eosinophils. Biochanin A (30~100 μmol/kg p.o.) significantly attenuated the release of IL-2, IL-4, IL-5, and TNF-α, with the exceptions that it at 30 μmol/kg did not significantly inhibit the release of IL-2 and TNF-α. Biochanin A 100, but not 30 μmol/kg, p.o., significantly reduced total and OVA-specific IgE levels in the BALF and the serum, but increased IgG2a levels in the serum. In the present results, Biochanin A (300 μmol/kg s.c.) did not significantly shorten the duration of anesthesia induced by xylazine (10 mg/kg)/ketamine (70 mg/kg).
Ayanin (100 μM) and biochanin A (100 μM) significantly relaxed the baseline tension of isolated sensitized guinea pig trachealis, and also significantly suppressed cumulative OVA (10~100 μg/ml)–induced contractions.
In conclusion, ayanin and biochanin A possessed anti-inflammatory effects and prevented airway hyperresponsiveness. Furthermore, they may prevent from degranulation of mast cells. Therefore, they have the potential in treating asthma.

並列關鍵字

ayanin ； biochanin A ； asthma

參考文獻

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