大蒜對倉鼠脂質代謝、抗氧化及抗血栓特性之探討

大蒜對倉鼠脂質代謝、抗氧化及抗血栓特性之探討

The Study of Garlic on Lipid Metabolism, Antioxidative and Antithrombotic Properties in Hamsters.

中文摘要

大蒜 (Allium sativum L.) 由於具含硫化合物而有特殊的風味，數千年來在國 內外被當作具有傳統療效。大蒜及其萃取物在一些醫學文獻中被認為可降低血脂 質、

防止血栓及具有抗氧化作用等，而可能預防或延緩心血管性疾病及動脈硬化之 發展。

本論文選擇臺灣產之軟骨黑葉大蒜，經由熱風乾燥處理之大蒜粉末，探討其對 倉鼠降

血脂、抗血栓及抗氧化之整體影響，並藉以瞭解其可能之作用機轉。

在前人的研究中，利用大蒜、其溶劑萃取物、油及含硫化合物等作為實驗材料，

但因考慮其有機溶劑殘留的毒性、經濟效率、製備、接受性、烹調後成份改變等問 題

是否會影響大蒜的功效？故首先比較熱風乾燥及冷凍乾燥之大蒜粉末在 0.5% 膽 固醇

飼料之下，對五週大倉鼠之生長、抗氧化效應及脂質代謝的影響，並決定以後實 驗之

材料來源。實驗結果顯示，不論是熱蒜或冷蒜組在高膽固醇攝取下，並不會造成 血漿

脂質增加，且能顯著地抑制肝臟膽固醇 (TC) 及三酸甘油酯 (TG) 的蓄積並可促 進糞

便總膽酸及總中性固醇的排出。另外，可觀察到顯著的體重增加，有較佳的飼料 利用

效率；在抗氧化作用方面，均有較低的血漿麩胱甘 過氧化  (GSH-Px) 活性及 肝臟

脂質過氧化物。在肝臟脂肪酸組成上發現，二組 n-6/n-3 脂肪酸比例減少，DHA ( 22:6，n-3 ) 則有增加的趨勢，而造成出血及凝血時間延長。熱蒜組及冷蒜組對 倉

鼠生長、出血及凝血時間、抗氧化及脂質代謝上都極類似。但因考慮熱風乾燥處 理在

製備上較便利及成本低，較接近國人的烹調習慣，故在探討大蒜功效的實驗上，

選擇

熱風乾燥大蒜粉末可當作理想的研究材料。

流行病學的調查已證實，血液脂質的含量與動脈硬化及癌症的發生關係密切；

飲

食中不同飽和程度的油脂來源，不但會影響血脂質濃度，也會改變體內抗氧化 狀態。

因此選擇四種代表不同飽和程度的油脂：黃豆油 (含 PUFA 較多)、豬油 (含 SFA 較

多)、魚油 (含 n-3 脂肪酸較多) 與芥花油 (含 MUFA 較多) 當作飲食中不同的油脂 來源；探討在不同油脂及 0.1% 膽固醇飼料之下添加大蒜後，對成鼠生長、脂質 代謝

及體內抗氧化狀況的影響，藉以了解，大蒜粉末是否會影響不同飲食油脂對體 內脂質

代謝及抗氧化作用的效應。結果顯示：在四大蒜組中，豬油大蒜 (LG) 組比其它 三組

有顯著最高之血漿 TC、磷脂質 (PL)、總脂質 (TL)、低密度脂蛋白-膽固醇 (LDL- C)

、LDL-C/HDL-C、TG、極低密度脂蛋白-三酸甘油酯 (VLDL-TG)、LDL-TG 及肝臟 TL，

但與黃豆油 (S) 組無統計差異。肝臟 TC，則以魚油大蒜 (FG) 組顯著最低；另外 血漿麩胺酸丙酮酸轉胺 (GPT) 及麩胺酸草醋酸轉胺 (GOT) 活性並無顯著差 異。

所有大蒜組的糞便總膽酸的排泄量均較黃豆油 (S) 組高；且蓄積較少的肝臟總 膽固醇

、磷脂質及三酸甘油酯；並具有較高的血漿總抗氧化狀態 (TAS)，較低的血漿 GPT、

過氧化物歧化 (SOD) 和 GSH-Px 活性，以及較低的肝臟脂質過氧化物指標 (TBARS)

值。大蒜粉末的添加可能會影響不同飽和程度油脂對倉鼠脂質代謝及體內抗氧化 的狀

況，而能減少肝臟脂質的蓄積及促進糞膽酸的排出，並有較高的抗氧化能力；

但會受

到食用油脂的種類而有不同的影響。

大蒜與洋蔥都屬於百合科，在許多的研究報告中被認為可能具有降血脂、改變脂 蛋白之比例及抗氧化等生理功能，而可預防動脈粥狀硬化的發生。故探討大蒜及 洋蔥

在 0.1% 膽固醇飼料之下，是否具有降低血漿膽固醇及增加 HDL 濃度的效果，

並比較

其對血漿抗氧化酵素活性及肝臟脂質過氧化物的影響。實驗結果顯示，大蒜及洋

蔥的

添加有顯著較低的血漿總膽固醇、VLDL-C、LDL-C、LDL-C/HDL-C 與 TG，及較 低的肝

臟 PL 與 TC 濃度；而有較高的血漿 HDL-C 及 TAS，且有顯著較低的血漿 GSH-Px、

GPT 與 SOD 活性及肝臟脂質過氧化物指標 TBARS 值含量；另外，有顯著較多 的糞便

總膽酸及總中性固醇的排泄量。此外，大蒜組比洋蔥組有顯著較低的血漿 LDL- C 及肝

臟脂質含量。添加大蒜或洋蔥有益於促進倉鼠的降血脂及抗氧化功效；但大蒜更 能顯

著地降低血脂質及抑制肝臟脂質的蓄積，並有較低的抗氧化酵素活性。

早期動脈硬化病灶的泡沫細胞形成的原因與血中膽固醇濃度過高、 LDL 易被氧 化

及傾向血栓形成等有密切的關係。文獻指出大蒜的有效成份對心血管性疾病及動 脈硬

化之危險因子可能具有預防或降低的作用。因此，選擇二種代表不同飽和程度的 油脂

：黃豆油 (含 PUFA 較多) 與芥花油 (含 MUFA 較多) 當作飲食中不同的油脂來 源，

探討大蒜的添加在不同時期 (6 週及 12 週)，於不同油脂及 0.1% 膽固醇飼料下，

對

九週大倉鼠體內脂質代謝、抗血栓效應及 LDL 氧化的影響。結果顯示：大蒜的 添加會

顯著降低血漿 TL、PL、游離脂肪酸（NEFA）、TC、VLDL-C、LDL-C/HDL- C 、TG、

VLDL-TG 及 LDL-TG；同時，有顯著較高的血漿 HDL-C 。除此之外，大蒜組比 控制組

有顯著較高的纖維蛋白溶解活性及前列環素 I2 （PG I2）含量，以及顯著較高 的血漿

及肝臟 n-3 脂肪酸含量，較低的 TX A2 及 n-6/n-3 脂肪酸比例，而造成較長之出 血

及凝血時間，有利預防血栓之形成；另一方面，可降低肝臟脂肪酸合成

（FAS）及葡

萄糖-6-磷酸去氫（G6PDH）的活性，並促進糞便總膽酸排泄，而可減少肝臟 脂質的

蓄積；此外，有顯著較低的肝臟脂質過氧化指標 TBARS 值及顯著較長的 LDL

氧化共

軛雙鍵形成之延遲期。大蒜的添加確可降血脂質、減少肝臟脂質蓄積及預防血漿 LDL

氧化，有利於預防脂肝、血栓及阻礙動脈粥狀硬化之形成，且不會傷害胃腸道黏 膜。

而芥花油組降血脂、抗血栓及抗氧化的效果顯著優於黃豆油組；且隨著實驗週期 的延

長，有顯著降血脂的作用。

綜合本文之結論：以熱風乾燥的大蒜粉末當作理想之實驗材料，發現大蒜的添 加

可促進幼鼠的生長及發育；大蒜可抑制肝臟 FAS 及 G6PDH 活性而減少肝臟脂 質的蓄

積，並促進糞便總膽酸及總中性固醇的排泄。大蒜可提高血漿 TAS 並降低血漿 抗氧化

酵素 (GSH-Px、SOD) 之活性及抑制肝臟脂質過氧化；且大蒜的添加顯示對肝毒 性影響

很小。另一方面，大蒜會造成血漿及肝臟脂肪酸組成分的改變，導致 n-6/n-3 脂 肪酸

比例下降；並減少血漿 TX A2 及增加 PG I2 含量，且有較高的纖維蛋白溶解活 性；

可能有利於抑制血小板的凝集及防止血栓的形成。大蒜的添加有利預防脂肝及阻 礙動

脈粥狀硬化之發展，且對胃腸道黏膜不會造成刺激；但可能會受到飼料中油脂 種類及

膽固醇含量的差異而有不同的效應。此外，大蒜比洋蔥更具降血脂與抗氧化的功 效。

英文摘要

Garlic (Allium Sativum L.), with a unique flavor due to the sulfur

compounds, has received considerable attention from traditional medicine in many countries for thousands of years. Recently medical reports also demonstrated that the garlic extracts might lower the concentration of blood lipids, inhibit platelet aggregation and activate the fibrinolytic activities that result in antithrombotic effects. In addition, the antioxidative effects may prevent or retard the development of

cardiovascular diseases or arteriosclerosis. The lipid-lowering function may be related to the inhibition of lipid biosynthesis in liver and the

increased secretion of fecal neutral steroids and bile acids. We chose one of the Taiwan*s native garlic species as the experimental material to study the effects of the heat-dried garlic powder on lipid-lowering,

antithrombotic and antioxidative effects in hamsters, and through these results its possible mechanism might be suggested.

Garlic, garlic extracts, garlic oil and the sulfur compounds are the

most common by used experimental materials in the published literatures and known researches. Yet, there are several aspects remain unclear. Such as the residual toxicity of the organic solvent, marginal benefits of

these garlic derived products, preparation methods, acceptability of the consumers toward the flavor of these products, and the cooking effect on the biological functions of garlic. Thus, in this series of studies we first determined the choice of the experimental materials by comparing the effects of heat-dried garlic powder (HDGP) and freeze-dried garlic powder (FDGP) with added 0.5% cholesterol in the test diets on the growth, antioxidant status and lipid metabolism in five-week old hamsters. The

results are as follows, after 6 weeks of feeding, both HDGP and FDGP groups with high cholesterol intake had similar blood lipid levels as the control group, but an inhibition of cholesterol (TC) and triglyceride (TG) accumulation in liver, and an increase in total bile acids and neutral steroids excretion in feces were observed. Both garlic-treated groups gained more weight and had better feed efficiency than the control group.

Regarding the antioxidative effects, both HDGP and FDGP groups had lower plasma glutathione peroxidase (GSH-Px) activities and lower liver peroxides (TBARS) levels than the control group. We also found the ratio of n-6/n-3 fatty acids decreased and DHA (22:6, n-3) concentration increased in liver, and the bleeding and clotting time were longer compared to the control group. Although FDGP group had better feed efficiency and accumulated less liver triglyceride than HDGP group, both HDGP and FDGP showed similar growth, bleeding time, clotting time and antioxidative effect in hamsters.

We considered that HDGP is more facility and cheaper and as usual cooking custom, so we chose HDGP as the ideal material in studying on garlic effectiveness.

Epidemiological studies verified that there is a significant

relationship between blood lipid concentration and the atherosclerosis and cancer incidence. The dietary oils with various degree of saturation effect

not only the blood lipids concentration but also the antioxidative status in vivo. Thus, soybean oil (more PUFA), lard (more SFA), fish oil (more n-3 fatty acids, EPA and DHA) and canola oil (more MUFA), these four different saturation degree of oils were chosen as different sources of dietary oils.

The objective of this research is to study the influence of garlic powder on growth, lipids metabolism and antioxidative status in hamsters in vivo under different saturation degree oils with added 0.1% cholesterol in the diet. After 6 weeks, the animals were scarified, comparing each garlic subgroup, the LG group had the highest plasma TC, phospholipid (PL), total lipids (TL), low density lipoprotein-cholesterol (LDL-C), LDL-C/HDL-C, TG, very low density lipoprotein-triglyceride (VLDL-TG), LDL-TG and liver total lipids than other groups, but no significantly differences with S group.

The FG group showed the lowest liver TC. The activities of plasma glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) showed no significantly differences. All garlic groups exhibited an increase in the excretion of total bile acids in feces, and an inhibition in the accumulation of TC, PL, and TG in liver as compared to the control group. Hamsters consumed garlic powder showed higher plasma total antioxidative status (TAS), less activities of plasma glutamic-pyruvic transaminase (GPT), superoxide dismutase (SOD) and GSH-Px, and lower liver lipid peroxides (TBARS). Garlic powder affected the lipid metabolism and antioxidative status while hamster fed with various lipids-containing diets.

Garlic powder consumption may decrease the accumulation of lipids in liver, increase the excretion of total bile acids in feces, and elevate the

antioxidative capacity while hamsters fed with various lipid-containing diets.

Garlic (Allium sativum) and onion (Allium capa) both belong to

Liliaceae. Many previous studies indicated that both may have physiological functions such as hypolipidemic, anatioxidative, and fibrinolytic activity etc. Furthermore, both garlic and onion may increase the HDL/LDL ratio in serum which has been demonstrated to prevent the occurrence of

atherosclerosis. Thus, the dissertation followed by investigating the

effect of both garlic and onion with added 0.1% cholesterol on lowering the serum cholesterol and increasing the HDL concentration, and compares their influence on antioxidative enzymes and liver peroxides in hamsters. The results indicated that both garlic and onion groups did significantly lower the plasma TC, VLDL-C, LDL-C, LDL-C/HDL-C, TG, and liver TC and PL as

compared to the control group. In addition, the garlic and onion groups significantly lowered the activities of plasma GSH-Px, GPT, SOD and liver lipid peroxides (TBARS). Furthermore, both groups showed higher

concentration of plasma HDL-C and TAS. The garlic and onion groups present more facilitate the secretion of total bile acids and neutral steroids.

Garlic group showed significantly lower plasma LDL-C and liver lipids compared to the onion groups. The addition of garlic or onion facilitated lowering plasma lipids concentrations and enhanced the antioxidant function;

suggesting that garlic had more effectiveness on lowering plasma lipids and inhibiting the accumulation of liver lipids, and suppressing antioxidative enzyme activities than onion.

Pre-arteriosclerosis results in the formation of foam cells are closely related to the concentration of serum cholesterol, oxidation potential of LDL and formation of LDL. Previous results indicated that the active ingredients of garlic may reduce the risk factors from cardiovascular diseases and atherosclerosis. To study the effect of garlic on lipids

metabolism, antithrombosis and LDL oxidation and on 9-week-old hamsters under different saturated degree of oils (soybean oil and canola oil) with 0.1% cholesterol in diets, and in different period (6 and 12 weeks). The experimental results showed that the garlic-fortified diets reduced the

plasma TL, PL, non-esterfied fatty acid (NEFA), TC, VLDL-C, LDL-C/HDL-C and TG but VLDL-TG and LDL-TG, significantly. The results also showed the

decrease of blood sugar (BS) and the increase of HDL-C and hemoglobin (Hb) concentration. The meanwhile, the garlic groups present higher significant fibrinolytic activity and prostacyclin I2 (PG I2), also lower thromboxane A2 (TX A2) and n-6/n-3 fatty acids ratio in plasma and liver, and longer bleeding and clotting time, can prevent the formation of thrombus. On the other hand, additional garlic inhibit the activity of fatty acids synthetase

(FAS) and glucose-6-phosphate dehydrogenase (G6PDH) in liver and promoted the excretion of fecal bile acid, reduced the storage of hepatic lipids.

The garlic groups have lower hepatic TBARS and longer lag time of LDL oxidation. In conclusion, garlic supplement indeed reduced the plasma lipids, stored less hepatic lipids and prevent LDL oxidation, but restrained the processes of fatty liver, thrombosis and atherosclerosis, and no harmful processes to gastric-intestinal mucous. Canola oil groups present more effectiveness of lipids antioxidation and antithrombosis, and 12-week treatment also showed more lipid-lowering function than 6-week

treatment.

In conclusion, HDGP as the ideal material in studying on garlic

effectiveness, garlic group gained more growth; garlic inhibit the activity of FAS and G6PDH in liver and promoted the excretion of fecal bile acid, reduced the storage of hepatic lipids. Garlic powder showed higher plasma TAS, less activities of plasma SOD and GSH-Px, and lower liver lipid peroxides (TBARS), and less effect in hepatocytosis. On the other hand, the garlic groups change the fatty acid composition of plasma and liver, decreased n-6/n-3 ratio, higher PG I2 and lower TX A2, higher significant fibrinolytic activity, can prevent the aggregation of platelet and

formation of thrombus. On the other hand, garlic can restrain the processes of fatty liver, thrombosis and atherosclerosis, and no harmful processes to gastric-intestinal mucosa, but while hamsters fed with various lipid and cholesterol in diets will effect the function of garlic. The Garlic had

more effectiveness on lowering-lipids and antioxidative function than onion.