Prophylactic Effects of Garlic Oil and Onion Oil Fractions as Compared to Vitamin E on Rats Orally Fed with Lead Acetate Solution.

Heavy metal pollution is a global public health challenge due to its stable and persistent environmental contamination. Of these lead is considered to be one of the most common ubiquitous and industrial pollutants and at low concentration it exerts extensive damages to the tissues. Daily feeding of lead acetate solution (Dose: 10 mg/kg/day) to normal rats for a month adversely altered the parameters of blood, serum and tissues, viz; RBC, WBC, Hb, ɗ- ALAD (Delta amino levulinic acid dehydratase), Pb content, lipids, oxidized lipids (TBARS), vitamins C and E and GSH levels and activities of AST, ALT and antioxidant enzymes viz; catalase, GR, Gpx and SOD. In order to study whether antioxidants have any effect to counteract the toxicity of lead we have selected comparatively better active allium fractions for the study viz: polar fraction of garlic (PFG) and polar fraction of onion (PFO). On feeding of these active fractions of garlic and onion oils i.e. their polar fractions and vitamin E (Dose 100 mg/kg/day) separately for a month along with or without lead acetate to rats each nutraceutical and vitamin E counteracted the adverse effects of Pb significantly (p ≤ 0.05). Their effects are in the order of PFG > PFO > Vitamin E. All these results point out that garlic and onion oils contain natural disulfoxide compounds which act as antioxidant and anti toxic to lead compounds. Their comparative differences in action may be due to the presence and position of double bonds and disulfide oxide bonds in their molecules. i.e., in PFG the allyl disulfide oxide group is present and in PFO saturated methyl and propyl groups and unsaturated propenyl group are present in place of allyl groups. The former group confers a better antioxidant activity on PFG, while the latter groups confer a lesser activity on PFO.

A review on the role of nutraceuticals as simple as se(2+) to complex organic molecules such as glycyrrhizin that prevent as well as cure diseases.

Nutraceuticals are nutritional medicines which are present in edible food items. Most of them are antioxidants with various other biological properties viz, anti inflammatory, anti atherogenic, anticancer, anti viral, anti aging properties etc. They are as simple as minerals like Se(2+) to complex organic molecules such as glycyrrhizin (Ca(2+), K(+) salts of glycyrrhizic acid). They can prevent as well as cure various diseases. Most of the medical people are not aware of the importance of the nutraceuticals as such matters are not part of their text books. Many still think that vitamins are the major nutritional medicines. Actually other dietary principles like terpenes, carotenes, phytosterols, polyphenols, flavanoids, di and poly sulphides, their sulfoxides and their precursor amino acids are necessary to scavenge free radicals in the body which are reactive oxygen species to protect and maintain the vitamin levels in the body. They down regulate the activities of those enzymes which are increased in diseases and they increase those that remove oxidants and detoxify carcinogens. They are immune boosters too. Recently glucosinolates, non toxic alkaloids, certain proteins and even fiber are included in the list of nutraceuticals.

Antioxidant status and oxidative stress in the circulation of younger and elderly human subjects.

Extensive research has demonstrated the protective properties of antioxidants, which scavenge reactive oxygen species and their precursors, as well as up-regulate enzymes involved in the repair of cellular damage. Several case-control studies have showed higher blood levels of antioxidants and decreased oxidative stress in younger individuals when compared with older ones. Cell damage caused by free radicals appears to be a major contributor in aging and degenerative diseases of aging such as cancer, cardiovascular disease, cataracts, compromised immune system, rheumatoid arthritis and brain dysfunction. The objective of this study was to determine the variation of Circulating levels of selected antioxidants (enzymic and non enzymic) and oxidative stress marker in younger and older humans. The results showed that a majority of the younger age group participants showed a significant increase in enzymic and nonenzymic antioxidant status and a decrease in oxidative stress when compared with the older age group.

A rethinking on the benefits and drawbacks of common antioxidants and a proposal to look for the antioxidants in allium products as ideal agents: a review.

This review article on the beneficial uses of Allium antioxidants tries to give some answers to the recent doubts raised by Singh et al. (Ind J Clin Biochem 25(3):225-243, 2010) against the claim of some researchers that Antioxidants (AOs) are miraculous molecules. Many people still believe that vitamins like A, C and E are the only true AOs that play important role in the corrections of metabolic derangements in life style diseases and hence all their faults are attributed to the failures of AOs as a class. This is quite unfair as there are many other natural AOs that do equal or even better AO action than the vitamins. Such is the case with the Allium S-alkyl sulfoxide aminoacids and their breakdown products viz, the various poly sulfides and their oxides e.g. allicin and ajoene type compounds which trap electrons mainly. It is true that antioxidant vitamins and ß-carotene a precursor of Vitamin A bring about problems as prooxidant or as agents that block some metabolic pathways and gene expression. Again the argument that AOs cannot improve the level of antioxidant enzymes like SOD, catalase and glutathione Px is also not universal. Actually allium AOs can even spare the use of antioxidant vitamins in the body and enhance the action of antioxidant enzymes and supply of ATP and other nutrients to the tissues as the former are good vasodialators and promoters of membrane permeability. The use of AOs should be selective and moderate. Allium AOs satisfy the role of ideal AOs based on many of their invivo and invitro actions reported by the author and others. Their metabolits can regenerate them and recycle them for a sufficient time in the body. They have non antioxidant effects also such as antiplatelet, fibrinolytic, antiinflammatory, immunomodulatory, antiageing actions etc. Plant derived AOs may be more beneficial and better tolerated in their partially purified forms rather than in their absolutely purified forms as the accompanying principles have some protective and regulatory effects in general. This and other aspects of allium AOs are discussed in the paper.

Antiatherogenic and antiperoxidative effects of garlic and soy proteins in alcohol fed rats.

Rats fed with alcohol (18%) at 3.76 g/day for 45 days showed significant reduction in body weight, glutathione (GSH) content and activities of superoxide dismutase (SOD) and catalase in liver. Lecithin cholesterol acyltransferase (LCAT) in plasma, levels of HDL cholesterol in serum, hepatic bile acid production and fecal excretion of neutral sterols also showed significant reduction. Simultaneous feeding of garlic protein (GP) or soy protein (SP) (500 mg/kg body weight/day for 45 days) to alcohol fed groups increased each of above parameters significantly towards normal values. Increase in GSH content and catalase activity in liver, was significantly higher for SP treated group than for GP treated group. However, increase in plasma LCAT was significantly higher for GP treated group than for SP treated group. Alcohol fed rats showed significant increase in liver weight, serum and tissue cholesterol, serum triacylglycerol (TAG), phospholipids (PL) and free fatty acid (FFA) levels and activity of HMGCoA reductase in liver and intestine. Lipid peroxidation, glucose-6 phosphate dehydrogenase (G6PD), glutathione peroxidase (GPx) and glutathione reductase (GR) in liver and incorporation of labeled acetate into liver cholesterol also showed significant increase. GP and SP treated rats showed decrease in these values towards normal. GP feeding showed a better effect than SP in lowering serum and heart total cholesterol, and in maintaining GPx at near normal level, while SP feeding showed a better effect in lowering serum FFA level and maintaining GR activity at near normal level. In suppressing incorporation of labeled acetate into serum cholesterol, GP feeding showed a better effect than SP. Antiatherogenic and antiperoxidative effects of these proteins may be due to lower lysine/arginine ratio.

A study on the hypoglycemic and hypolipidemic effects of an ayurvedic drug Rajanyamalakadi in diabetic patients.

A study was undertaken for evaluating the hypoglycemic and hypolipidemic effects of an ayurvedic medicine "Rajanyamalakadi" containing Curcuma longa, Emblica officinalis and Salacia oblonga in type II diabetic patients over a period of 3 months. Ethical committee consent for the study was given by the Director, Indian Systems of Medicine, Kerala. A total of 43 patients with established diabetes mellitus as adjudged from clinical features and FBS values, appeared for the camp (Age group 35-75 yrs). An informed consent for the study was obtained from each patient. The clinical proforma was given to each patient to collect data such as height, weight, diet pattern, previous history of illness etc. The ongoing antidiabetic medications were stopped under medical supervision and the patients were provided with 'Rajanyamalakadi' tablets (dose 1-2 tablets each weighing 500mg). The dosage of the drug was decided by the supervising medical officer on a case to case basis, taking note of the clinical conditions and responsiveness of the patients. The patients were monitored for three months, who were divided into 6 groups based on their age and again into two groups, 5 & 6, based on their mean FBS values. ie; Normal Persons, Diabetics of age groups 35-45yrs, 46-55yrs, >55yrs and those with FBS < 145.9 mg% and > 145.9 mg%. The Ayurvedic medicine "Rajanyamalakadi" has showed significant antidiabetic, hypolipidemic and antioxidant effects. In addition to that significant ameliorating effects on the elevated serum AST and ALT activities were also demonstrated by the treatment. The nutraceuticals present in the drug like Terpenoids, Polyphenols, Curcumin etc are responsible for the medicinal effects.

Effects of insulin, glimepiride and combination therapy of insulin and metformin on blood sugar and lipid profile of NIDDM patients.

In the present study the efficacies of therapy with insulin, sulphonylurea or insulin + metformin on NIDDM patients are compared. One group which was on a definite dose of insulin therapy, but with uncontrolled diabetes was treated by doubling the insulin dose, a second group whose diabetes was not controlled by glibenclamide was switched over to another sulphonylurea viz; glimepiride and a third group whose diabetes was not controlled by insulin therapy was switched over to a combination therapy with insulin +metformin. After recording their initial blood parameters all the groups were treated as above for 3 months, and the parameters were again determined. The fasting blood sugar and serum lipids of the first group were controlled significantly, but the values were far above normal range. However HDL Cholesterol and atherogenic index were near normal range. In glimepiride treated group, none of the parameters showed any amelioration. In the combined therapy group, control of blood sugar and atherogenic index was more or less the same as for group 1, but hyperlipidemia remained slightly above that of the same. From the findings we can infer that in long term diabetes treatment higher doses of insulin and combined therapy with insulin and metformin may be more beneficial than with low doses of insulin or sulfonyl urea alone.

Lipid lowering effect of S-methyl cysteine sulfoxide from Allium cepa Linn in high cholesterol diet fed rats.

The lipid lowering action of S-methyl cysteine sulfoxide (SMCS) isolated from Allium cepa Linn (family: Liliaceae) was investigated in Sprague-Dawley rats fed on 1% cholesterol diet, in comparison to the hypolipidemic drug gugulipid. Administration of SMCS at a dose of 200mg/kg body weight for 45 days ameliorated the hyperlipidemic condition. The lipid profile in serum and tissues showed that concentrations of cholesterol, triglyceride and phospholipids were significantly reduced when compared to their untreated counterparts. The total lipoprotein lipase activity in the adipose tissue was decreased with also a decrease in the free fatty acid levels in serum and tissues. The activities of the lipogenic enzymes glucose 6-phosphate dehydrogenase and malic enzyme as also of HMG CoA reductase in the tissues remained low on treatment indicating that both the drugs did not favor lipogenesis and cholesterogenesis in the hyperlipidemic animals. The fecal excretion of bile acids and sterols was further increased upon treatment with the drugs. The results are directive to that both gugulipid and SMCS cause reduction of endogenous lipogenesis, increase catabolism of lipids and subsequent excretion of metabolic by-products through the intestinal tract. However, gugulipid is a better drug than SMCS at a low dose of 50mg/kg body weight.

A comparative study on the effects of diet and exercise, metformin and metformin+pioglitazone treatment on NIDDM patients.

A comparative study on two groups of newly diagnosed nonobese and obese NIDDM patients who were 15 in each group and treated by diet cum exercise and metfromin monotherapy respectively and a third group of 15 obese NIDDM patients whose hyperglycemia was not first controlled by a combination therapy of metformin and sulfonylurea and therefore changed over to a different combination therapy of metformin and ploglitazone, was carried out before and after a period of three months treatment. The mild hyperglycemia in the 1(st) group and the moderate or severe hyperglycemia with accompanied disorders of serum enzymes such as AST, ALT, GGT and the level of HBA(10) observed with 2(nd) and 3(rd) groups of obese NIDDM patients were significantly ameliorated by the respective mode of treatments. Here the efficacies of the three types of treatment are substantiated and further it specifically depicts the success with the choice of combination therapy with metformin and pioglitazone in the third group of obese diabetics.

Nutraceutical effects of garlic oil, its nonpolar fraction and a Ficus flavonoid as compared to vitamin E in CCl4 induced liver damage in rats.

Carbon tetrachloride feeding (3.2g/kg/72hr) for one month increased significantly the serum and tissue lipid profile and deranged the enzyme levels viz; alkaline phosphatase, alanine transaminase, aspartate transaminase, glutathionze reductase, HMGCoA reductase, catalase, gluc.6.PDH and malic enzyme in rats. Simultaneously the lipid peroxidation level in liver was also raised. On administration of garlic oil and its major nonpolar fraction (NPFGO) and a flavonoid isolated from the bark of Ficus bengalensis Linn, viz; leucopelargonin derivative respectively to different groups(100mg/kg/day) the deleterious effects of CCl4 were significantly ameliorated. The liver damage by CCl4 was satisfactorily prevented by these samples as effectively as Vit. E (50 mg/kg/day). The results prove that important nutraceuticals (phytonutrients) like bioflavonoids and theols i.e. allylic sulphide rich fractions give protection from toxins like CCl4. The order of beneficial effects of the drugs are Leucopelargonin > NPFGO > Garlic oil and their effects are comparable to that of vitamin E used at a minimal dose.

Beneficial effects of a polar fraction of garlic (Allium sativum Linn) oil in rats fed with two different high fat diets.

Feeding a diet containing 20% of sesame oil (SO) or coconut oil (CNO) along with 2% cholesterol to rats for two months showed differences in their serum and tissue lipid profile and certain enzyme activities. Hyperlipidemia and related oxidative effects were more pronounced in coconut oil fed rats than those fed sesame oil. Feeding a combination of the oils (10% CNO +10% SO) lowered significantly the hyperlipidemia and certain other deleterious effects of CNO. Feeding a polar fraction of garlic oil (PFGO) prepared in the same way as for ajoene and administered at a dosage of 100 mg/kg along with each of the above oil containing diets counteracted significantly the hyperlipidemic, oxidant and also most of the other deleterious effects of the oils like raised lipid levels in serum and tissues, raised serum levels of AST and tissue levels of HMGCoA reductase and the lowered serum and tissue levels of glutathione reductase. The results support the claims that ajoene, the major polar compound of garlic oil, has very good biological action, which warrants further study.

Partial identification of the fibrinolytic activators in onion.

A steam-distilled and an ether extract of onion have both been found to enhance blood fibrinolysis without depressing fibrinogen content in groups of human volunteers. Chemical analysis has shown which sulphur-containing compounds were in highest concentration and common to both and thus likely to carry this property, but their very intense and prolonged flavour precludes their clinical use. One sulphur containing but nearly odourless compound has been identified as having indirect fibrinolytic potential. A species difference in respect of fibrinolysis has been found between English and Spanish onion but is of little importance.

Effect of essential oil of onion (allyl propyl disulphide) on blood glucose, free fatty acid and insulin levels of normal subjects.

The administration of allyl propyl disulphide (APDS), a volatile substance contained in onion, to six normal volunteers after a 12 hour fast caused a significant fall in the blood glucose levels and a significant rise in the serum insulin levels during the subsequent 4 hours. It is argued that this effect is due to an insulin sparing action. The expected rise of serum free fatty acid levels after fasting did not occur after APDS administration and this effect is probably related to the simultaneous rise in the insulin levels.

Antioxidant effect of onion oil (Allium cepa. Linn) on the damages induced by nicotine in rats as compared to alpha-tocopherol.

The beneficial effects of onion oil as an antioxidant has been assessed in nicotine administered rats by studying whether the peroxidative damage caused by nicotine can be effectively combated with the onion oil and the effects compared to vitamin E, a highly efficient antioxidant. Lipid peroxidation products and antioxidant defence system have been studied in liver, lungs, and heart. The rats were injected with nicotine (0.6 mg/kg body wt.) and simultaneously given onion oil (100 mg/kg body wt.) or vitamin E (100 mg/kg body wt.) for 21 days. Concentration of free fatty acids, TBA reactive substances (TBARS), conjugated dienes and hydroperoxides were significantly increased in the tissues of nicotine treated rats as compared to normal rats. Onion oil supplemented to nicotine treated rats showed increased resistance to lipid peroxidation and the effect was near to that of vitamin E fed rats. The activity of catalase and superoxide dismutase decreased in nicotine treated rats. Antioxidants-glutathione content, vitamin C and retinol showed no significant difference but liver vitamin E content significantly decreased in nicotine treated rats. On onion oil or vitamin E supplementation, the concentration of antioxidants were significantly raised in all the tissues studied, however, a significantly increased concentration of glutathione, vitamin E and retinol was noticed in vitamin E+nicotine treated rats. Thus, these results indicate that onion oil is an effective antioxidant against the oxidative damage caused by nicotine as compared to vitamin E.

Effect of leucopelargonin derivative from Ficus bengalensis Linn. on diabetic dogs.

Dimethoxy ether of Leucopelargonidin-3-0-alpha-L rhamnoside isolated from the bark of the Indian Banyan tree Ficus bengalensis Linn. was tested for antidiabetic effect. At a medium effective dose (100 mg/kg) on oral administration, the compound showed significant hypoglycemic and serum insulin raising action in normal as also moderately diabetic dogs (induced by alloxan) during a period of two hours. The mechanism of action of the glycoside compound seems to be similar to that of drugs which stimulate insulin secretion. On acute and chronic administration in single doses of 0.2-1.8 g/kg to different groups of mice and daily administration of 100, 250 and 500 mg/kg to rats for a period of one month respectively did not show any toxic effect and the compound was not lethal even at the high dose of 1.8 g/kg in experimental animals.

Risk factors for coronary heart disease in noninsulin dependent diabetes mellitus (NIDDM).

Plasma levels of fasting and post-prandial blood sugar, serum levels of total cholesterol (TC), triglycerides (TG), HDL cholesterol (HDLc), LDL cholesterol (LDLc) and free fatty acids (FFA) were estimated in 213 diabetic patients (NIDDM) with coronary heart disease (CHD-group 4), 252 CHD patients (non-diabetic CHD-group 3), 164 non-insulin dependent diabetics (NIDDM-group 2) and 173 healthy subjects (controls-group 1) who did not have any clinical evidence of CHD, diabetes mellitus or any family history of the above diseases. Data was analysed by ANOVA along with the Duncan procedure and multiple logistic regression. Lipid profile of diabetic CHD patients was characterised by significantly higher concentration of TC, TG, LDLc, FFA, LDLc/HDLc ratio and lower concentration of HDLc. However, in a multivariate logistic regression analysis using 14 known risk factors, diastolic blood pressure (BP), body mass index (BMI), alcohol consumption and higher FFA levels seemed to be predictors of CHD in diabetics, overriding the influence of lipoprotein abnormalities. The same was true for nondiabetic patients also in whom BMI, FFA and alcohol consumption were found to be significant predictors of CHD. Thus, even though lipid abnormalities are more prominent in diabetics, the coexistence of obesity and hypertension seem to be important factors in diabetics for the development of CHD.

Therapeutic values of onion (Allium cepa L.) and garlic (Allium sativum L.).

Onion and garlic contain many sulfur containing active principles mainly in the form of cysteine derivatives, viz. S-alkyl cysteine sulfoxides which decompose into a variety of thiosulfinates and polysulfides by the action of an enzyme allinase on extraction. Decomposed products are volatile and present in the oils of onion and garlic. They possess antidiabetic, antibiotic, hypocholesterolaemic, fibrinolytic and various other biological actions. In addition to free sulfoxides in alliums, there are nonvolatile sulfur-containing peptides and proteins which possess various activities and thus make these vegetables as an important source of therapeutic agents. As allyl and related sulfoxides are inhibiting thiol group enzymes, alliums are to be used only in limited quantities.

Antidiabetic effects of S-allyl cysteine sulphoxide isolated from garlic Allium sativum Linn.

S-allyl cysteine sulphoxide (SACS), a sulphur containing amino acid of garlic which is the precursor of allicin and garlic oil, has been found to show significant antidiabetic effects in alloxan diabetic rats. Administration of it at a dose of 200 mg/kg body weight decreased significantly the concentration of serum lipids, blood glucose and activities of serum enzymes like alkaline phosphatase, acid phosphatase and lactate dehydrogenase and liver glucose-6-phosphatase. It increased significantly liver and intestinal HMG CoA reductase activity and liver hexokinase activity.

Antidiabetic and antioxidant effects of S-methyl cysteine sulfoxide isolated from onions (Allium cepa Linn) as compared to standard drugs in alloxan diabetic rats.

Antidiabetic and antoxidant effects of S-methyl cysteine sulfoxide (SMCS) isolated from A. cepa and two standard drugs, glibenclamide and insulin were studied and compared in alloxan diabetic rats after using each of them for treatment for two months. These drugs ameliorated the diabetic condition significantly, viz. maintenance of body weight and control of blood sugar in rats. Further they lowered the levels of malondialdehyde, hydroperoxide and conjugated dienes in tissues exhibiting antioxidant effect on lipid peroxidation in experimental diabetes. This is achieved by their stimulating effects on glucose utilization and the antioxidant enzymes, viz. superoxide dismutase and catalase. The probable mechanism of action of SMCS and glibenclamide may be partly dependent on the stimulation of insulin secretions and partly due to their individual actions. In the amelioration of diabetes the standard drugs showed a better action, but as an antioxidant SMCS proved to be a better one.

Biochemical effects of garlic protein diet and garlic oil on glycosaminoglycan metabolism in cholesterol fed rats.

Garlic protein diet or daily administration of garlic oil to 2% cholesterol fed rats controlled significantly the increases in sulphated glycosaminoglycans in their heart and aorta. However hyaluronic acid level increased. UDPG dehydrogenase decreased and several degrading enzymes increased in the aorta on treatment. The effects of treatment were just the reverse in liver. The high percentage of cysteine in garlic protein and the reactive disulphide group in the oil may be responsible for their beneficial effects.