INTRODUCTION:

A number of human disorders, including cardiovascular disease, are significantly influenced by dietary variables. Diets high in fruits, herbs, and spices have been linked to a lower incidence of cardiovascular disease, according to epidemiological research. Over many ages, the folklore of many civilizations developed a reputation for garlic as a potent preventative and curative medicine. Due to its broad medical use worldwide and the widely held notion that it aids in preserving good health by fending off infections and providing more vigor, garlic has drawn particular attention from modern medicine. Many positive clinical and experimental effects of garlic products, including garlic extract, have been documented to date.

These biological reactions have been generally linked to the following mechanisms: i) decreased risk factors for cancer and cardiovascular disease, ii) immune system activation, iii) improved foreign substance detoxification, iv) hepatoprotection, v) antibacterial effect, and vii) antioxidant effect. This review was written to provide a comprehensive analysis of garlic's effectiveness in treating cardiovascular disease in both humans and animals. Atherosclerosis, hyperlipidemia, thrombosis, hypertension, and diabetes are just a few of the metabolic illnesses that are prevented and treated with the help of garlic and its derivatives^1-4. Experimental Examinations on the effectiveness of garlic in cardiovascular diseases were more encouraging, which led to the inauguration of multiple clinical trials. Even though numerous clinical trials demonstrated that garlic has a beneficial impact on almost all of the cardiovascular problems listed above, a number of unfavorable studies have recently raised concerns about garlic's effectiveness, particularly with regard to its ability to decrease cholesterol. Since garlic is the least expensive method of preventing cardiovascular disease, it is a significant challenge for scientists worldwide to use it properly and get its full benefits^5-7.

APPROACH:

Electronic search has been carried out using the databases viz. Google, Google Scholar, PubMed for the study. The search will be restricted for a period of 48 years ranging from 1973-2022.

FINDINGS:

Cardiovascular Diseases as the rapid curse in the Society:

Over the past few decades, excessive societal shifts toward fast food and sedentary lifestyles have replaced farming-based diets and active lifestyles in human societies. Such a lifestyle and rising cigarette consumption together have increased the risk factors for cardiovascular illnesses⁸. Heart disease, often known as CVD, affects people's hearts and/or blood arteries all over the world. It is the primary cause of mortality and inefficiency in both the United States and many European nations. People with CVD are disproportionately affected in low and middle-income nations. About 82% of CVD-related deaths occur in low & middle-income nations, and the mortality rate is roughly the same for men and women. By the year 2030, it is anticipated that 23.6 million individuals will every year pass away from CVD⁹. The South-East Asia area will have the highest increase in mortality. An epidemiologic study carried out at Tabriz University of Medical Sciences revealed a significant frequency of risk factors among CVD patients, leading to the urgent recommendation of lifestyle change. Another study by Akgun et al. revealed that major vascular disorders are responsible for 35%–38% of mortality in Turkey¹⁰.

Cardiovascular Risks are adversely differentiated on the basis of Gender and Aging:

Older persons have a higher risk of cardiovascular disease (CVD) due to the decline of cardiovascular function brought on by aging. Along with atherosclerosis, stroke, and myocardial infarction, the frequency of CVD has also been demonstrated to rise with aging in both men and women. According to the American Heart Association (AHA), the incidence of CVD in US men as well as in women is 40% between the ages of 40 and 59,75% between the ages of 60 and 79, and 86% over the age of 80. Because of the high frequency of CVD, older persons represent a significant burden for the current healthcare system in the US. Increased mortality, morbidity, and frailty in those who have CVD are directly tied to its burden, which also translates to considerable overall healthcare expenses. Understanding the etiologies linked to CVD in older persons is crucial given that the number of older people in the US is projected to rise by up to two or three times by the year 2050¹¹. Numerous risk factors, including obesity, diabetes, and hypertension, have been associated to the emergence of CVD. However, there are also many instances where gender disparities in the development and prevalence of CVD are seen in aging adults.

Emergence of use of Functional Foods as a Medicine:

It is obvious that the idea that some meals may have therapeutic benefits is not new. Hippocrates, the founder of medicine, embraced the saying "Let food be the medicine and medicine be the food" more than two thousand years ago. The development of contemporary medication therapy in the 19th century, however, caused this "food as medicine" theory to fade into obscurity. The significance of diet in the prevention of disease and the promotion of health was once again highlighted in the 1900s. The identification of vital nutrients, especially vitamins, and their involvement in preventing various dietary deficiency disorders were the scientific focus during the first half of the 20th century. However, throughout the 1970s, when disorders associated with excess and "overnutrition" emerged as a major public health problem, the emphasis on dietary shortages or "undernutrition" dramatically changed. Additionally, scientists started to recognize physiologically active substances (known as phytochemicals and zoochemicals, respectively) in meals derived from both plants and animals that may lower risk for a number of chronic diseases. These circumstances came together in the 1990s to give rise to the phenomenon we now refer to as "functional foods," along with an aging, health-conscious population, adjustments to food regulations, a no. of technological advancements, and a market ready for the introduction of health-promoting goods. Although it is less popular with consumers, the term "nutraceuticals," which was introduced in 1991 by the Foundation for Innovation in Medicine to refer to any bioactive component that provides a health benefit, is another one that is frequently used synonymously with functional foods. The Department of Health and Human Services claims that nutrition has an impact on 5 out of the top 10 causes of death, including coronary heart disease (CHD), several cancers, stroke, diabetes (non-insulin dependent or type 2), and atherosclerosis. In the United States and other developed nations, the dietary pattern that has been related to these primary causes of death is known to be generally high in total & saturated fat, cholesterol, sodium, and refined sugars and rather low in unsaturated fat, grains, legumes, fruits, and vegetables.

Nutraceuticals:

Stephen De Felice, MD, founder and chairman of the Foundation for Innovation in Medicine (FIM), Cranford, New Jersey, first used the words "nutraceutical" and "pharmaceutical" interchangeably in 1989. A food (or component of a food) that offers medical and health benefits, including the prevention as well as treatment of an illness, is what De Felice went on to characterize as a nutraceutical. Nutraceuticals are functional foods that assist in the prevention as well as treatment of diseases and/or disorders other than anemia¹².

Consequently, the following are ways that nutraceuticals are different from dietary supplements:

· In addition to serving as dietary supplements, nutraceuticals must also help with illness prevention and/or treatment.

· The development of the functional food concept and nutraceuticals was made possible by dietary components' positive effects that go beyond basic nutrition.

· For one customer, a functional food may work as a nutraceutical. Citrus fruits and fortified dairy products (like milk) are examples of nutraceuticals ¹³.

Potential Herb Could Be Garlic:

In human history, garlic (Allium sativum) has been used both for medical and nutritional purposes. For more than 5000 years, the use of garlic (Allium sativum) as a potential herb has been recognised. For millennia, people from many different cultures have happily enjoyed garlic and its many preparations as food and spices. It was also noted that Egyptians used it as a preferred kind of medical treatment to treat a variety of illnesses. In a similar vein, it is regarded as a crucial component of Indian traditional medicine, including Ayurveda, Tibbi, Unani, and so forth. Additionally, it is asserted to be effective in preventing a number of features of cardiovascular disease, such as hypertension and dyslipidemia¹⁴.

Allicin an inhibitor to CVD:

The aroma and flavor of freshly cut or crushed garlic are attributed to allicin, a naturally occurring sulfur-containing molecule with a wide range of biological benefits. One of the reasons for their expanding consumer demand as well as their growing use in health and agriculture is the prevalent, if unfounded, notion that natural products are gentle and essentially harmless in comparison to their chemically manufactured competitors¹⁵. Cardiovascular problems are complicated since many different factors can affect them. More and more factors are being discovered through epidemiological studies that have varying degrees of influence on the development of cardiovascular issues. The oxidation of the low-density lipoprotein protein (LDL), in particular, is a common correlation between atherosclerosis and general oxidative processes. Allicin is an oxidant chemically, yet at the physiological level, it functions as an antioxidant in lower quantities. This observation can be understood by the fact that mild oxidative circumstances, such as the activation of redox-sensitive transcription factors, drive the production of so-called phase II detoxifying enzymes and develop resistance to additional and stronger oxidative shocks¹⁶. The Nrf 2/Keap1 system, which controls the expression of numerous anti-oxidative enzymes, is one illustration of how the electrophile allicin can oxidize a redox-sensitive transcription factor. Studies have demonstrated that allicin can activate the Nrf2/Keap1 system. It should be noted that the role played by allicin in activating Nrf 2 is crucial not only in the context of cardiovascular disorders but also for a number of other health-related conditions, such as neurodegenerative diseases. It has been demonstrated that allicin reduces cognitive and memory problems associated with aging by activating the Nrf 2-system in this scenario¹⁷.

The so-called "LDL-receptor theory" contends that cholesterol is a major factor in atherosclerosis, possibly as a result of oxidized LDL's ability to draw macrophages and activate them, which leads to the formation of artery-clogging plaques. Therefore, it is believed that cholesterol increases the likelihood of developing atherosclerosis and, as a result, ischemic diseases including Angina pectoris, myocardial infarction, and stroke. Reducing endogenous cholesterol-biosynthesis, typically through the use of statins, is one method for preventing the advancement of plaque buildup in arteries. Allicin also exhibits the ability to suppress cholesterol biosynthesis, which is attributed to the inhibition of the squalene-monooxygenase and acetyl-CoA synthetase enzymes. Statins in the traditional way competitively inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme-A-reductase (HMG-CoA reductase). Additionally, because coenzyme A has a thiol-group, it is likely that allicin directly reacts with unacetylated CoA, preventing it from being used in biosynthetic pathways. In a concentration-dependent manner, this would slow down the biosynthetic rates of CoA-dependent processes, including sterol biosynthesis¹⁸.

Platelet aggregation, which is crucial for cerebral and cardiac ischemia, is another significant element in cardiovascular illnesses. The process of platelet aggregation is intricately biological. Its requirement is thromboxane A2 activating the GPIIb/IIIa receptor, which results in the binding of, among other things, fibrinogen. Traditional inhibitors of platelet aggregation, such as acetylsalicylic acid (aspirin), prevent the production of endogenous thromboxane, which in turn prevents the activation of the GPIIb/IIIa receptor. It's interesting that thiosulfinates like allicin are strong inhibitors of platelet aggregation. Allicin inhibits platelet aggregation at a final concentration of 0.4mM to a degree of roughly 90%, whereas aspirin exhibits less than half this action at a final dose of 0.36 mM (35% inhibition)¹⁹. Hypertension is a final but important effect of allicin on variables causing cardiovascular disorders. Again, the reactivity of allicin is the cause of its antihypertensive effects. It has been demonstrated that a complicated reaction cascade with thiols (particularly glutathione in particular) leads in the production of hydrogen sulfide because allicin decomposes quickly to its breakdown products. Again, H2S is a well-known, powerful gaseous signaling molecule for controlling blood pressure. H₂S decreases blood pressure by relaxing the smooth muscle cells around the blood artery, which allows them to expand and lowers blood pressure as a result²⁰.

Impact of Allicin intake in the regulation Blood Pressure:

One of the main cardiovascular disease risk factors (CVD), which is the main cause of death, is high blood pressure (BP). High blood pressure is a contributing factor in roughly 54% of strokes as well as 47% of coronary heart diseases worldwide. A common medical issue, hypertension affects 65% of people under the age of 60 and is more prevalent with age. The population of the world is ageing. A projected 20% of the world's population will be over 65 by 2030. Thus, during the next few decades, it is anticipated that high blood pressure will have an increasing effect on mortality in older adults²¹. Similar to first-line standard anti-hypertensive drugs, garlic supplements have shown promise in lowering blood pressure in hypertensive patients. By lowering arterial stiffness, high cholesterol levels, and blood "stickiness," kyolic garlic has also demonstrated potential in enhancing cardiovascular health. Additionally, the prebiotic qualities of garlic promote the range and richness of the gut microbial population. The abundance of scientific evidence supports the idea that eating garlic significantly reduces blood pressure, prevents atherosclerosis, lowers serum cholesterol and triglycerides, inhibits platelet aggregation, and boosts fibrinolytic activity. These positive cardiovascular benefits on various garlic formulations have been shown in both clinical and experimental investigations.

In in vivo animal trials, garlic extracts given intravenously resulted in small drops in both systolic and diastolic pressures, and hypertensive animals given garlic extract orally had their blood pressure return to normal. More than 80% of individuals with high blood pressure had their blood pressure decreased by garlic, according to several clinical investigations. Garlic significantly reduced mean systolic blood pressure by 12 mmHg and mean supine diastolic blood pressure by 9 mmHg compared to placebo in one trial including 47 hypertensive patients²². According to some theories, garlic's antihypertensive efficacy is caused by prostaglandin-like effects that lower peripheral vascular resistance. In patients with uncontrolled hypertension, aged garlic extract reduced systolic blood pressure more effectively than a placebo. Significant blood pressure lowering was observed with a dose of 240-960 mg of old garlic extract containing 0.6-2.4 of S-allylcysteine during a 12-week period²³.

Regulation of Serum Cholesterol levels through Allicin: A way to minimize the Coronary inflammations:

Recent studies show that cardiovascular disease (CVD), a complex and diverse illness is one of the major threats to human health globally, with annual increases in incidence and mortality. According to statistics from the World Health Organization, hypertension, high cholesterol, alcohol consumption, and cigarette use are the main risk factors for CVD. One of the main contributors to CVD is dyslipidemia, which includes elevated levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and low levels of high-density lipoprotein cholesterol (HDL-C). Since a rise in LDL-C concentration is an established risk factor for CVD, preventing and treating it is thought to be the main objective. However, the majority of hypolipidemic medications today have comparatively serious adverse effects when used to treat CVD. As a result, the treatment of hyperlipidemia has increasingly focused on a specific food component with negligible or no negative effects. Garlic has drawn special interest from modern medicine due to its vast impact in preserving good health. It's significant to note that the positive effects are primarily related to the decline in CVD risk factors, the antibacterial effect, the antioxidant effect, and the reduction in cancer risk. Garlic's preventive mechanisms for preventing CVDs can be strengthened by reducing TC and TG, raising HDL, and suppressing LDL oxidation. Garlic contains a group of pharmacologically active chemical compounds that contain Sulphur, such as S-allylcysteine, alliin, ajoene, and diallyl disulfide²⁴. Some animal researches have verified the anti-hyperlipidemic effects of garlic, however they all used small sample sizes. Garlic dramatically lowered blood cholesterol, triglycerides, and LDL in rats with hypercholesterolemia brought on by a high-cholesterol diet, but it had no effect on serum HDL. Garlic therapy decreased LDL oxidation and boosted HDL in in vitro tests, which may be one of the protective mechanisms of garlic's advantageous effects on cardiovascular health. Long-term use of garlic and its preparations on animal models of atherosclerosis brought to a 50% reduction in atheromatous lesions, especially in the aorta. Garlic's ability to lower the lipid content of artery membrane has been linked to its ability to prevent atherosclerosis. The active ingredients that give aged garlic extract and garlic oil their anti-atherosclerotic effects include allicin, S-allyl cysteine, and diallyldi-sulfide. When this diet was supplemented with garlic, the plasma fibrinolytic activity in rats, which was lowered on cholesterol feeding, was significantly increased²⁵.

Possible Mechanism of Allicin during Atherosclerosis:

Garlic's ability to lower the lipid content of artery walls have been linked to its protective impact against atherosclerosis. At the level of the arterial wall, garlic has direct antiatherogenic (preventive) and antiatherosclerotic (inducing regression) actions. Malic enzyme, fatty acid synthase, glucose-6 phosphate dehydrogenase, and 3-hydroxy-3-methyl-glutaryl-CoA (HMG CoA) reductase are a few examples of the lipogenic and cholesterogenic enzymes that garlic inhibits in the liver. As evidenced by higher excretion of acidic and neutral steroids following garlic eating, garlic also boosted the excretion of cholesterol. It was discovered that LDL extracted from human patients who received AGE and aqueous garlic extract was considerably more oxidation resistant²⁶.

These findings suggest that one of the potent mechanisms underlying garlic's anti-atherosclerotic effects may be decreased LDL oxidation. The chemical ingredient responsible for the antiatherosclerotic action was initially identified as allicin. Recent in vitro research, however, has shown that water-soluble organosulfur compounds, particularly S-allyl cysteine (SAC) and diallyl-di-sulfide (DADS), which are found in old garlic extract and garlic oil, respectively, are also powerful inhibitors of cholesterol formation²⁷.

Coronary thrombosis is caused by inflammatory conditions such as atherosclerosis. Allicin and two additional thiosulphinates from onions were effective in reducing platelet aggregation, which helps to prevent atherosclerosis. A high Sulphur content was considerably positively linked with onion antiplatelet activity. The aggregation of platelets was also prevented by garlic powder. According to the studies, different garlic preparations, cloves, or commercial goods vary in their antiplatelet activity. The diverse types of organo-sulfur compounds in the environment are what cause these variances. In vitro tests on human platelets revealed that garlic extracts prevented aggregation. The cyclooxygenase thromboxane synthase activity, the levels of adenosine 3′, 5′-cyclic monophosphate, or the suppression of human platelet aggregation were unaffected²⁸.

Garlic Role on Endothelium and Vascular Dilatation:

A few studies suggest that garlic may have some effects on endothelium and arterial dilatation through suppression of oxidation process, even though it mostly protects against cardiovascular disease by lowering cholesterol levels. Allicin, the primary active component of garlic, has the potential to have positive effects on the cardiovascular system. According to researches Allicin improved the antioxidant state by reducing reactive oxygen species and boosting glutathione synthesis. Similar to how it fights cancer, garlic reduces LDL oxidation, which reduces atherosclerosis of the vessels, one of the major risk factors for cardiovascular disease. In a pilot study conducted by Budoff in 2006, patients who were already receiving statin therapy were given AGE extract of garlic or a placebo, and their degree of coronary artery calcification was measured. In the group of patients who received garlic therapy in addition to statins, as opposed to the placebo group, the rate of coronary artery calcification was found to be slower²⁹.

Effects on endogenous antioxidant defenses:

A few of the numerous researches that have looked into the antioxidant properties of garlic in various in vitro systems are included below. In vitro oxidation of isolated human LDL has been demonstrated to be prevented by garlic by scavenging superoxide (ROS) and preventing the generation of lipid peroxides. According to in vitro research, when endothelial cells are treated with oxidized LDL, AGE inhibits the depletion of intracellular glutathione (GSH). By altering the GSH redox cycle, AGE also raises GSH levels within vascular endothelial cells and boosts SOD activity and glutathione disulfide (GSSG) reductase activity³⁰. Garlic's capacity to lower markers linked to cardiovascular disease has been validated by in vitro (preclinical) investigations.

Exposure to the Immunomodulatory Effect of Allicin:

Garlic reduces some illnesses brought on by compromised immunity. Aged garlic extract has an immunomodulatory action as a result. Garlic or its compounds' immunomodulatory action demonstrates a modification of cytokine production as an inflammatory mediator. A crucial transcription factor that plays a crucial part in the expression of genes that regulate immune response is nuclear factor-KB (NF-KB). NF-KB plays a significant role in the activation and control of molecules that are linked to cancer and inflammatory disorders. Some cytokine genes' expression is increased as a result³¹. By modulating pro- and anti-inflammatory cytokines, garlic compounds indirectly influenced the suppression of NF-KB. Allicin shown anti-inflammatory effects and epithelial cells play a significant role in intestinal inflammation. Intestinal epithelial cells' natural and TNF-induced secretions of pro-inflammatory cytokines and chemokines were both reduced by allicin. There aren't many studies that show an allicin-containing pill can stop the common cold virus from attacking. Over the course of a 12-week period, 156 individuals were randomly assigned to receive either a placebo or a garlic supplement containing allicin. Compared to the placebo group, the active treatment group experienced significantly fewer colds. The number of virally challenged days and the length of the symptoms were considerably higher in the placebo group^32-35.

The Way Forward: A Future Research:

In clinical trials, it is crucial to employ standardized preparations of garlic and to determine the active ingredients' bioavailability. The correct questions need to be asked, such as if garlic is being used to treat or prevent cardiovascular disease. In order to address morbidity and mortality outcomes as well as cholesterol and thrombotic outcomes, one must also perform well-designed, long-term randomized trials. The question of whether garlic taken as a dietary supplement might either postpone or avoid cardiovascular problems in a healthy community is probably even more crucial to research. Garlic may have a distinct effect if consumed before cardiovascular disease manifests itself. This is backed up by some epidemiological data.

Last but not least, it's critical that cardiovascular disease's new biomarkers and techniques be incorporated into clinical trials. If a beneficial effect is shown, the disease parameters' underlying mechanism of action needs to be determined. Garlic has a number of qualities that may lessen cardiovascular disease, but since the condition is complex and multifaceted, clinical trials must address a number of issues.

CONCLUSION:

Epidemiologic and clinical research on the function of plant-based diets and eating habits in the prevention of CVD has grown over the last ten years. Our understanding of heart-healthy foods and the molecular pathways relating dietary variables to CVD have been completely altered by the study. Some foods that were originally considered unhealthy due to their fat content, such as nuts, have changed their reputation and now play a significant role in diets intended to regulate weight, lower blood pressure and serum cholesterol, prevent secondary coronary artery disease (CAD), as well as give flavor, variety, and texture to cuisine. Most cultures that eat garlic regularly absorb a lot of allicin, a natural substance. It is a biologically active chemical with a wide range of possible health advantages. Additionally, there is significant potential for its application in human and veterinary medicine, and the idea of farmers being able to "grow their own" plant preservation in an environmentally benign way is appealing, especially in subsistence agriculture where the price of commercial preparations might be prohibitive.

Following the discussion of the mechanisms and antiatherogenic properties of garlic in this review, it was concluded that the following areas warrant additional investigation. Allicin is the main bioactive component of garlic and is one of a number of bioactive substances found in garlic, along with DAS, DADS, and DATS.

CONFLICT OF INTEREST:

None

REFERENCES:

1. Ikewuchi CC. Ikewuchi JC. Ayalogu EO. Onyeike EN. Quantitative determination of alkaloid, allicin, glycoside and saponin constituents of the leaves of sansevieria senegambica baker by gas chromatography. Research Journal of Science and Tech. 2011; 3(6): 308-312 https://www.researchgate.net/publication/281029963_Quantitative_determination_of_alkaloid_allicin_glycoside_and_saponin_constituents_of_the_leaves_of_Sansevieria_senegambica_Baker_by_gas_chromatography

2. Senthilkumar T. Tamilselvi A. Risk factors of cardiovascular disease in adolescents: a systematic review. Asian Journal of Nursing Education and Research. 2021; 11(1):151-156. https://ajner.com/AbstractView.aspx?PID=2021-11-1-39

3. Jadhav KL. Kapare PR. Khairmode DV et al. Genetic insights of cholesterol and atherosclerosis: complex biology. Asian Journal of Pharmaceutical Research 2018; 8(3): 175-184. https://asianjpr.com/HTMLPaper.aspx?Journal=Asian%20Journal%20of%20Pharmaceutical%20Research;PID=2018-8-3-11

4. Patel V. Manek RA, Sheth. DB. Evaluation of in-vitro thrombolytic activity of methanolic extract of Prunus avium L. Asian Journal of Research in Pharmaceutical Sciences. 2021; 11(1):41-44. https://ajpsonline.com/AbstractView.aspx?PID=2021-11-1-7

5. Monago CC. Amachree I. Joshua PE. Diabinese and nicotinic acid combination reduced cardiovascular indices in Experimental Diabetes. Asian Journal of Research Chemistry 2010; 3(3): 785-790. https://ajrconline.org/HTMLPaper.aspx?Journal=Asian%20Journal%20of%20Research%20in%20Chemistry;PID=2010-3-3-69

6. Kamala M. Banu MS. Senthil R. Vijaya Anand A. Anti-Hyperglycemic and Anti–Hyperlipidemic Potentials of Psidium guajava Fruit Extract – a Review. Research Journal of Pharmacy and Technology 2011; 4(7): 1033-1036. https://rjptonline.org/HTMLPaper.aspx?Journal=Research%20Journal%20of%20Pharmacy%20and%20Technology;PID=2011-4-7-30

7. Lakshmi Prabha J. Sankari M. Role of Il-1 in Atherosclerosis. Research Journal of Pharmacy and Technology 2018; 11(7): 3163-3166. https://rjptonline.org/HTMLPaper.aspx?Journal=Research%20Journal%20of%20Pharmacy%20and%20Technology;PID=2018-11-7-80

8. Prabhakaran D. Yusuf S. Cardiovascular diseases in India: Lessons learnt and challenges ahead. Indian Journal of Medical Research. 2010; 132(5): 529-530. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028960/

9. Biglu MH. Ghavami M. Biglu S. Cardiovascular diseases in the mirror of Science. Journal of Cardiovascular and Thoracic Research. 2016; 8(4): 158-163. https://doi.org/10.15171/jcvtr.2016.32

10. Akgun S. Rao C. Yardim N. Basara BB. Aydin O. Mollahaliloglu S. Lopez AD. Estimating mortality and causes of death in Turkey: methods, results and policy implications. European Journal of Public Health. 2007; 17(6): 593-599. https://doi.org/10.1093/eurpub/ckm022

11. Yazdanyar A. Newman AB. The burden of cardiovascular diseases in the elderly: morbidity, mortality and costs. Clinics in geriatric medicine. 2009; 25(4): 563-577. https://doi.org/10.1016/j.cger.2009.07.007

12. Trottier G. Bostrom PJ. Lawrentschuk N. Fleshner NE. Nutraceuticals and prostate cancer prevention: A current review. Nature Reviews, Urology. 2010; 7(1): 21-30. https://doi.org/10.1038/nrurol.2009.234

13. Laparra JM. Sanz Y. Interactions of gut microbiota with functional food components and nutraceuticals Pharmacological Research, 2010; 61(3): 219-225 https://doi.org/10.1016/j.phrs.2009.11.001

14. Steiner M. Li W. Aged garlic extract, a modulator of cardiovascular risk factors: a dose-finding study on the effects of AGE on platelet functions. Journal of Nutrition. 2001; 131(3): 980S-984S. https://doi.org/10.1093/jn/131.3.980s

15. Slusarenko AJ. Patel A. Portz D. Control of plant diseases by natural products: Allicin from garlic as a case study. European journal Plant Pathology. 2008; 121:313-322. https://doi.org/10.1007/s10658-007-9232-7

16. Rahman K. Lowe G. Garlic and cardiovascular diseases: A critical review The Journal of Nutrition. 2006; 136: 736-740. https://doi.org/10.1093/jn/136.3.736s

17. Li X.-H. Li C.-Y. Lu J.M. Tian R.B. Wei J. Allicin ameliorates cognitive deficits ageing induced learning and memory deficits trought enhancing of Nrf2 antioxidant signaling pathways. Neuroscience Letters. 2012; 514:46-50. https://doi.org/10.1016/j.neulet.2012.02.054

18. Gebhardt R. Beck H. Wagner KG. Inhibition of cholesterol biosynthesis by allicin and ajoene in rat hepatocytes and HepG2 cells. Biochimica et Biophysica acta. 1994; 1213(1): 57-62. https://doi.org/10.1016/0005-2760(94)90222-4

19. Briggs WH. Xiao H. Parkin KL. Shen C, Goldman IL. Differential inhibition of human platelet aggregation by selected Allium thiosulfinates. Journal of Agriculture and Food Chemistry. 2000; 48(11): 5731-5735. https://doi.org/10.1021/jf0004412

20. Zoccali C. Catalano C, Rastelli S. Blood pressure control: hydrogen sulfide, a new Gastrotransmitter, takes Stage. Nephrol Dial Transplant. 2009; 24(15): 1394-1396. https://doi.org/10.1093/ndt/gfp053

21. Spillman BC. Lubitz J. The effect of longevity on spending for acute and long-term care. The New England Journal of Medicine. 2000; 342(19):1409-15. https://doi.org/10.1056/nejm200005113421906

22. Chanderkar AG. Jain PK. Analysis of hypotensive action of Allium sativum (garlic). The Indian Journal of Physiology and Pharmacology. 1973; 17:132-133. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4103721/

23. Ried K. Frank OR. Stocks NP. Aged garlic extract reduces blood pressure in hypertensives: a dose-response trial. European Journal of Clinical Nutrition. 2013; 67(1): 64-70. https://doi.org/10.1038/ejcn.2012.178

24. Iciek M. Kwiecien I. Wlodek L. Biological properties of garlic and garlic-derived organosulfur compounds. Environmental and molecular mutagenesis. 2010; 50(3):247-65. https://doi.org/10.1002/em.20474

25. Mirhadi SA. Singh S. Gupta PP. Effect of garlic supplementation to cholesterol-rich diet on development of atherosclerosis in rabbits. Indian Journal of experimental biology. 1991; 29(2):162-8. https://pubmed.ncbi.nlm.nih.gov/1869301/

26. Munday JS. James KA. Fray LM. Kirkwood SW. Thompson KG. Daily supplementation with aged extract, but not raw garlic, protects low density lipoprotein against in vitro oxidation. Atherosclerosis. 1999; 143(2): 399-404. https://doi.org/10.1016/s0021-9150(98)00293-7

27. Gebhardt R. Beck H. Differential inhibitory effects of garlic-derived organosulfur compounds on cholesterol biosynthesis in primary rat hepatocyte culture. Lipids. 1996; 31(12): 1269-76. https://doi.org/10.1007/bf02587912

28. Apitz-Castro R. Cabrera S. Cruz MR. Ledezma E. Jain MK. Effects of Garlic Extract and of Three Pure Components Isolated from it on Human Platelet Aggregation, Arachidonate Metabolism, Release Reaction and Platelet Ultrastructure. Thrombosis Research. 1983; 32(2):155-69. https://doi.org/10.1016/0049-3848(83)90027-0

29. Budoff M. Aged garlic extracts retards progression of coronary artery calcification. Journal of Nutrition. 2006; 136(3):741-744. https://doi.org/10.1093/jn/136.3.741s

30. Geng Z. Lau BHS. Aged garlic extracts modulated glutathione redox cycle and superoxidase dismutase activity in vascular endothelial cells. Phytotherapy Research. 1997; 11(1):54-56. https://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2588646

31. Li Q. Verma IM. NF-kappaB regulation in the immune system. Nature Reviews: Immunology. 2002; 2(10): 725-34. https://doi.org/10.1038/nri910

32. Josling P. Preventing the common cold with a garlic supplement: a double-blind, placebo-controlled survey. Advances in Therapy. 2001; 18(4): 189-193. https://doi.org/10.1007/bf02850113

33. Neethu V. John S. A Study to assess the knowledge regarding prevention of Cardiovascular Diseases (CVD) among obese women in selected urban community areas at Mangalore. Asian Journal of Nursing Education and Research. 2021; 11(3):387-0. https://doi.org/10.52711/2349-2996.2021.00093

34. AK Meena. MM Rao. RP Meena. P Panda. Renu. Pharmacological and phytochemical evidences for the plants of Wedelia genus– A review. Asian Journal of Pharmaceutical Research. 2011; 1 (1): 07-12s https://asianjpr.com/AbstractView.aspx?PID=2011-1-1-2

35. Bezlon G. Shanmugha SD. Rinu ER.E. Design and stabilization of natural antibacterial compound allicin against methicillin-resistant staphylococcus aureus for treatment as a novel antibiotic. Research Journal of Engineering and Technology 2013; 4(4): 179-181. https://ijersonline.org/AbstractView.aspx?PID=2013-4-4-9

Received on 03.12.2022 Modified on 06.04.2023

Research J. Pharm. and Tech 2023; 16(12):6055-6061.

DOI: 10.52711/0974-360X.2023.00983