龍眼花、殼、種子、葉與枝椏萃取物之降尿酸研究

人類在演化過程中失去可將尿酸轉化為尿素排出的尿酸酶，故尿酸合成過多或排泄減少是高尿酸血症主要形成的原因，而因營養過剩所造成的高尿酸血症與痛風更是現代人常見的文明病。主要位於肝臟的黃嘌呤酶是人體內嘌呤代謝過程產生尿酸的關鍵酵素，如果能抑制黃嘌呤酶作用便可以減低尿酸的形成，多餘的嘌呤可經由體內其他酵素回收利用，避免尿酸其在體內累積對關節、腎臟和心血管系統造成傷害。近年來天然物萃物和自然保健食品已蔚為風潮，而植物化學成分中之抗氧化劑更是許多研究重心。龍眼除了是常見的熱帶水果更是中國傳統醫學中常見補神健胃的藥方，目前已有研究發現龍眼萃取物含有多種抗氧化成分，而抗氧化劑也被證實對許多酵素會產生影響。目前臨床常用之抗高尿酸血症藥物多為化學合成物質，有許多如：過敏、皮疹和肝腎傷害等不良副作用。由天然物中萃取能夠抗高尿酸血症又無副作用的植物化學成分是許多研究的目標。本實驗為證實民間偏方龍眼花茶之降尿酸療效，對其萃取物進行體外和體內之生物活性試驗，且為了充分利用生物資源，一併對龍眼種子、果殼、枝枒和樹葉進行研究。實驗先以風乾龍眼﹙花、種子、果殼、枝枒和樹葉﹚甲醇萃取物在295nm波長下進行黃嘌呤酶抑制試驗測試龍眼萃取物抑制尿酸形成作用，發現五種龍眼萃取物都具有程度不等之黃嘌呤酶抑制效果，其中以龍眼花效果最佳，其IC50 為115.76 μg/ml。另外測試龍眼花所含已知十種化合物之黃嘌呤酶抑制率，發現以proanthocyanidin A2效果最佳，其抑制率可達70.67%。之後進行生物體內活性試驗，在分別口服五種龍眼萃取物1小時後，以腹腔注射尿酸酶抑制劑oxonic acid，建立囓齒類動物﹙大鼠和小鼠﹚高尿酸血症模式，2小時後測量小鼠血中尿酸值的變化並和對照組比較，發現在100mg/kg劑量下五種龍眼甲醇萃取物都有降低小鼠血中尿酸值的效果﹙p< 0.01﹚。另外以高尿酸血症模式大鼠進行尿酸促進排除試驗，注射oxonic acid 2.5小時後，每30分鐘抽取膀胱尿液連續三小時。尿液分析結果顯示龍眼萃取物對促進尿酸排泄並無影響。綜合本研究之實驗結果，可以推測龍眼萃取物主要是藉由抑制黃嘌呤酶作用來降低血中尿酸值，並以龍眼花萃取物效果最佳，其作用主要是由具強抗氧化活性的proanthocyanidin A2對黃嘌呤酶產生抑制效果。

關鍵字

龍眼；降尿酸；黃嘌呤酶

並列摘要

Hyperuricemia results from over production or/and underexcretion of uric acid. Uric acid production is catalyzed by xanthine oxidase (XO) in the liver, which is a key enzyme in the oxidizing process of xanthine into uric acid. This study investigated anti-hyperuricemia bioactivity of Dimocarpus longan Lour. Longan pulp is a Chinese medicinal plant used for the treatment of amnesia and its flower is folklorically made into drinking tea to lower serum uric acid level. Therefore, the methanol extracts of the flower, seed, shell, stem and leaf of Longan were tested in vitro and in vivo to confirm its anti-hyperuricemic effect. Firstly, xanthine oxidase suppression rates were evaluated by the xanthine oxidase inhibition assay. The results showed that all Longan extracts reduced blood uric acid level as compared to the control group (p < 0.01). The flower extract exibited the best blood uric acid lowering effect and IC50 of XO inhibition was 115.76 μg/ml. 10 compounds have been previously isolated from Longan flower in other studies; in this study, we also examined them by the xanthine oxidase inhibition assay, revealing that proanthocyanidin A2 had the strongest inhibitory effect (70.67%). In the in vivo part of this study, the methanol extracts from 5 different Longan parts were orally administrated to different groups of mice at 50 mg/kg or 100 mg/kg 1 hour before oxonic acid was injected. The blood uric acid levels in mice were then detected 2 h later. Furthermore, we carried out the urine uric acid excretion test in rats to find out whether the Longan extracts could promote the excretion of uric acid; however no significant effect on the excretion of uric acid was observed. According to these results, the mechanism behind the antihyperuricemic effect of Longan methanol extracts was indicated to be associated with the inhibition of xanthine oxidase which results in decreased production of uric acid. This study not only revealed the existence of antihyperuricemic effect of of Dimocarpus longan, but also explored possible mechanisms. Our results showed that Dimocarpus longan has a great potential to be developed into novel therapeutic agents for the treatment of hyperuricemia.

並列關鍵字

Dimocarpus longan ； antihyperuricemia ； xanthine oxidase inhibition

參考文獻

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龍眼花、殼、種子、葉與枝椏萃取物之降尿酸研究

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