洛神花萃取物抑制心血管疾病及降血脂分子機轉之研究

Effect of Hibiscus sabdariffa extract on reduced serum lipid molecular mechanism and cardiovascular protection

陳滄澤(Chang-Che Chen)

指導教授 ： 王朝鐘

中山醫學大學/醫學院/生化暨生物科技研究所/博士(2006年)

https://doi.org/10.6834/CSMU.2006.00108

摘要

洛神花(Hibiscus Sabdariffa Linnaeus) 為錦葵科(Malvaceae)植物，原產熱帶地區，分部於印度，馬來西亞、東南亞、台灣東部及南部也盛產。其花成分包含有機酸、果膠及多酚類，多酚成分包括有hibiscetin、gossypetin、quercetin，在色素部分則為cyanidin與delephidin所組成。國外之研究，在體外試驗顯示其萃取物有抗脛巒，降膽固醇，降血壓及抗菌作用。所含的原兒茶酸(protocatechuic acid；PCA)可抑制化學致癌物誘導之癌化，本研究室的實驗也發現洛神花中PCA及花青素有強的抗氧化作用，我們也發現PCA亦有抗化學性物質誘導促腫瘤作用及促進HL-60凋謝死亡之作用。
本研究顯示洛神花水萃取物具有抑制低密度之蛋白(Lowe density lipoprotein; LDL)氧化作用，抑制LDL中apo-B的fragmentation的作用，並降低TBARs的生成。動物試驗的結果顯示，高油脂或高果糖飼料等的兩種不同誘導大鼠之試驗，顯示洛神花水萃取物(1%, 2%)具顯著抑制cholesterol、LDL-cholesterol (LDL-C)與triglyceride的作用。此外，0.5%及1%洛神花水萃取物有顯著抑制藉由1.3% 膽固醇及3% lard oil餵食10週的兔子之血清triglycerise及cholesterol含量，並能增加High density lipoprotein-cholesterol (HDL-C)及降低LDL-C，進一步以病理觀察也顯示洛神花水萃取物有抑制動脈硬化斑之作用，其中包含泡沫細胞之沉積量明顯減少，且抑制血管平滑肌細胞位移及動脈硬化斑內鈣化現象消失等。倉鼠試驗也觀察到洛神花萃取物除了能降低血液cholesterol、LDL-C與triglyceride的濃度外，也能進一步的降低倉鼠肝組織中cholesterol與triglyceride的含量，並且能夠提升血中與倉鼠肝臟中脂解酶活性。細胞試驗中也發現了，洛神花萃取物能夠透過PI3K的路徑抑制fatty acid synthase (FAS)的表現，並且發現sterol regulatory element binding proteins-1c(SREBP-1c)的表現也有上升的現象，此外，洛神花萃取物也會透過Ras-MEK 的訊息傳遞，調控Peroxisome Proliferators Activated Receptor-garmmer (PPARγ)　的表現
上升，進一步的使LDL receptor mRNA表現量上升，達到降低血清
LDL-C的效用。
在安全性方面，我們長期餵食洛神花水萃取物初步的試驗也顯
示兔子及大白鼠之血清肝功能、腎功能等生化值無顯著差異，顯示洛
神花水萃取物對於肝腎功能是無毒性，可作為抑制心血管疾病之保健
用品。

關鍵字

洛神花 ； 動脈硬化 ； 心血管 ； 降血脂

並列摘要

Hibiscus sabdariffa L., a local soft drink material and medicinal herb, was usually used effectively in native medicines against hypertension, pyrexia and liver disorders. Here in our research found that an extract of Hibiscus sabdariffa contains lot of polyphenolic acids, flavonoids and anthocyanins. In our report, HSE was able to prevent LDL oxidation as evidenced by its inhibition on electrophoresis, ApoB fragmentation, cholesterol degradation, and TBARS of LDL. Taken together, HSE showed a strong potency to inhibit the production of oxidized LDL induced by copper. Furthermore, we examined the effect of HSE on the serum lipids in animal. Firest, we used high fructose (HFD)- or high cholesterol (HCD)- fed rats. HSE specifically reduce the serum triglyceride in the HFD-fed rats and the serum cholesterol in the HCD-fed animals. The level of LDL and the ratio of LDL-cholesterol (LDL-C) to HDL-cholesterol (HDL-C) were declined by HSE in both models. Then we also designed another animal model to test whether HSE exhibit hypolipidemia and antiatherosclerotic effect in rabbits with experimental atherosclerosis. New ZeaLane White (NZW) rabbits were fed with a normal diet, high cholesterol (1.3%), lard oil (3%) diet (HCD) with or without 0.5 or 1 % HSE for 10 weeks. The level of triglyceride, cholesterol and low-density lipoprotein - cholesterol (LDL-C) were lower in the serum of rabbits fed HCD plus HSE than in the serum of rabbits fed HCD. Feeding HSE (0.5 and 1% in the diet) to rabbits significantly reduced severe atherosclerosis in the aorta. Histopathological examination showed that HSE reduced foam cell formation, inhibited smooth muscle cell migration and calcification in the blood vessel of rabbits. In addition, we used hamster hyperlipidemia model found that, HSE not only reduced serum cholesterol, LDL-C and triglyceride. It can reduced hepatic cholesterol and triglyceride concentration and increase lipase activity in hamster serum and liver tissure. In Hep G2 cell, we found that, HSE can increase antioxidative enzyme expression such as catalase and SOD, suppress FAS espression via PI-3 kinase signaling pathwy, and activated Ras/ERK kinase increase PPAR expression. In
mRNA expression, we found that HSE can increase LDL receptor
expression and suppress HMG-Co A reductase and SREBP-1c
expression.
These results suggest that HSE inhibits serum lipids increase via
inhibited FAS expression and increase PPAR avtivation and shows an
antiatherosclerotic activity.

並列關鍵字

Hibiscus sabdariffa ； atherosclerosis ； cardiovascular disease ； LDL ； cholesterol

參考文獻

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