Anti-asthmatic action of hesperidin and hesperidin-3’-O-methylether

• Main Authors: Chao-Sian Wang, 王超賢
• Other Authors: 林建煌
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/60631207013657367116

碩士 === 臺北醫學大學 === 醫學科學研究所 === 96 === Hesperidin is a flavanone glycoside. Hesperidin has been reported to possess significant anti-inflammatory and analgesic effects. Our previous study has indicated hesperetin possess antiasthmatic effect. Hesperidin is an abundant and inexpensive by-product of Citrus cultivation and is the major flavonoid in sweet orange and lemon. Hesperidin-3’-O-methylether is a methylation product of hesperidin. We just know hesperidin-3’-O-methylether possess the vasodilation of coronary artery and the relaxation of some smooth muscle now, but these is little study about antiasthmatic effect. In the sensitized and OVA-primary challenged BALB/c mice, an asthmatic animal model, the airway hyperresponsiveness (AHR) was measured in unrestrained animals by barometric plethysmography using a whole-body plethysmograph after exposure of methacholine (MCh, 6.25~50 mg/ml) and enhanced pause (Penh) values were determined. First, hesperidin (100 μmol/kg, p.o.) and hesperidin-3’-O-methylether (30~100 μmol/kg, p.o.) significantly suppressed the enhancement of MCh -induced Penh values and significantly suppressed the increase of total inflammatory cells, eosinophils, neutrophils, and lymphocytes, and also significantly attenuated the release of interleukin (IL)-2, IL-4, IL-5 and tumor necrosis factor (TNF)-α in bronchoalveolar lavage fluid (BALF) of the mice, but the release of interferon (IFN)-γ is increased. They also significantly reduced total and OVA-specific IgE levels in the serum and in the BALF. In the opposite, it significantly increased IgG2a levels in the serum suggesting that the anti-inflammation was potentiated. Hesperidin displaced [3H]-rolipram from high affinity rolipram binding sites (HARBS) of particulates of whole brains isolated from sensitized guinea pigs, with an EC50 value beyond 300 ?嵱, and the EC50 value of hesperidin-3’-O-methylether is 218.3 ± 32.1 μM. Therefore, its therapeutic ratio (PDE4H/PDE4L) was calculated to be 15.7. Hesperidin and hesperidin-3’-O-methylether did not shorten the duration of anathesia induced by xylazine/ketamine, suggesting that its adverse effect, such as nausea, vomiting and gastric hypersecretion, may be little. Hesperidin (100 ?嵱) and hesperidin-3’-O-methylether (100 ?嵱) significantly relaxed the baseline tension, but did not suppress cumulative OVA (10~100 ?慊/ml)-induced contractions in isolated sensitized guinea pig trachealis, suggesting that they can not prevent the degranulation of mast cells. In conclusion, both of hesperidin and hesperidin-3’-O-methylether possessed anti-inflammatory and anti-asthmatic effects. Hesperidin-3’ -O-methylether had better anti-inflammatory effects than hesperidin.