What are the pharmacological properties of garlic extract?

What are the pharmacological properties of garlic extract?

Garlic (Allium sativum) has been used as a spice, food, and medicine for over 5,000 years, and is one of the earliest documented herbs utilized for the maintenance of health and treatment of disease^[1]. Garlic and their active components are reported to reduce the risk of diabetes and cardiovascular diseases, protect against infections by activating the immune system and have antimicrobial, antifungal, as well as anticancer properties which confirmed by epidemiological data from human clinical studies^[2].

Chemical constituents of garlic.

Garlic is considered as a functional spice because of its diverse array of nutritional constituents, phytochemicals, and fiber. It contains high levels of potassium, phosphorus zinc, and sulfur, moderate levels of selenium, calcium, magnesium, manganese, iron, and low levels of sodium, vitamin A and C and B-complex^[3]. Bulbs of garlic are reported to contain hundreds of phytochemicals including sulfur-containing compounds such as ajoenes, thiosulfinates (allicin), vinyldithiins (2-vinyl-(4H) -1,3-dithiin, 3-vinyl-(4H)-1,2-dithiin), sulfides (diallyl disulfide (DADS), diallyl trisulfide (DATS)) and which amounted for 82 percent of the total sulfur content in garlic. Alliin, the main cysteine sulfoxide is transformed to allicin by allinase enzyme after cutting off the garlic and breaking down the parenchyma. S-propyl-cysteine-sulfoxide (PCSO), allicin and S-methyl cysteine-sulfoxide (MCSO) are the main odoriferous molecules of freshly milled garlic homogenates. Garlic also consist of several organosulfur compounds, N-acetylcysteine (NAC), S-allyl-cysteine (SAC), and S-ally-mercapto cysteine (SAMC), which are derived from alliin^[2]. 

Furthermore, garlic contains more than twenty well-known polyphenolic compounds, including kaempferol 3,7-di-O-rhamnoside, kaempferol-3 glucuronide, kaempferol-3-O-glucoside, kaempferol-3-O-beta-d-glucoside-7-O-alpha-L-rhamnoside, luteoline, and apigenine. It also contains 17 amino acids, eight of which are essential. Generally, bioactive compounds are present in intact garlic, but after chopping or crushing, a higher number of compounds, such as allicin, DAS, DADS, dithiins, and ajoene have been found after different types of chemical reactions^[3].

Pharmacological activities of garlic and its related compounds.

1. Activities related to infectious diseases.

1.1 Antibacterial activity.

The antimicrobial activity of garlic is attributed to allicin activity which has been shown to be effective against a wide range of microorganisms including antibiotic-resistant, gram-positive and gram-negative bacteria. Moreover, garlic extracts prevented the growth of enterotoxigenic E. coli strains and other pathogenic intestinal bacteria, which are the main cause of diarrhea in humans and animals^[2].

1.2 Antifungal activity

Garlic extracts were found to have a broad spectrum fungicidal impact on Candida, Torulopsis, Trichophyton, Cryptococcus, Aspergillus, Trichosporon, and Rhodotorula species. The garlic extract acted by affecting the fungal cell wall and causing irreversible ultrastructural changes in the fungal cells, which lead to loss of structural integrity and affected the germination ability. The damage to the nucleus and cell organelles caused by these changes in cytoplasmic composition eventually leads to cell death. Moreover, allicin and garlic oil were found to have potent antifungal effects against Candida albicans, Ascosphaera apisin, and a. niger and they acted by penetrating the cellular membrane as well as organelles membranes such as the mitochondria and leading to organelles destruction and cell death^[2].

1.3 Antiprotozoal activity.

Several studies have shown that garlic extracts and phytochemicals have antiprotozoal efficacy against a variety of protozoan parasites. Allicin also acts by preventing the parasite’s RNA as well as DNA and protein synthesis. Furthermore, phytochemicals extracted from garlic extract, allicin and DATS, showed antiparasitic activity against Entamoeba histolytica, Plasmodium falciparum, Babesia, Theleria, Trypanosoma brucei, and Giardia lamblia^[2].

1.4 Antiviral activity.

The antiviral activity of garlic extracts has been evaluated against influenza B, human rhinovirus type 2, human cytomegalovirus (HCMV), Parainfluenza virus type 3, herpes simplex type 1 and 2, vaccinia virus, and vesicular stomatitis virus^[2].

2. Antioxidant and anti-inflammatory activities.

2.1 Antioxidant activity

The study reported that the frequent garlic intake promotes internal antioxidant activities and reduces oxidative adverse effects by either increasing the endogenous antioxidant synthesis or reducing the production of oxidizers such as oxygen-free radical species (ROS). Because ROS seems to be at the core of many ailments, it is justified to assume that the antioxidant effect of garlic might be through modulation of ROS, increasing glutathione and cellular antioxidant enzymes. The principal antioxidative substances that showed an antioxidant action at the physiological level are allicin, DADS, and DATS^[2].

2.2 Anti-inflammatory activity

Inflammatory processes are linked to a variety of chronic disorders, including cancer and cardiovascular disease; in these cases, many pharmacological and natural techniques have been used to prevent them. In this context, garlic has shown to have anti-inflammatory properties by decreasing the inflammatory biomarkers in patients with end-stage renal disease and adults^[3].

3. Anticancer activity

The anticancer mechanisms of garlic extracts were attributed to the inhibition of cell growth and proliferation, regulation of carcinogen metabolism, stimulation of apoptosis, prevention of angiogenesis, invasion, and migration and thus reducing the anticancer agent’s negative effects^[2].

Numerous mechanisms have been recommended to explain the chemo-preventive effects of garlic, including the inhibition of DNA adduct formation, the inhibition of mutagenesis by blocking metabolism, through its free-radical scavenging, or by decreasing cell proliferation and tumor growth^[3].

4. Effect on cardiovascular disease

Cardiovascular disease (CVD), a multifactorial and complicated disease, has recently emerged as one of the most serious threats to human health, with annual increases in incidence and mortality. According to World Health Organization statistics, hypertension, high cholesterol, alcohol consumption, and cigarette use, etc. are the most prominent risk factors for CVD^[4]. Dyslipidemia is known to be the main cause of CVD and it is defined by high levels of triglyceride (TG), low-density lipoprotein (LDL), total cholesterol (TC), and low high-density lipoprotein (HDL) level^[2]. 

Garlic may decrease the absorption of cholesterol, and the synthesis of cholesterol and fatty acid, and thereby reduces the level of cholesterol. Garlic and its components can inhibit human enzymes involved in cholesterol biosynthesis such as squalene monooxygenase and HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase. Garlic may decrease the level of LDL by reduction of hepatic cholesterol 7a-hydroxylase, HMG-CoA reductase, pentose-phosphate path-way activities, enhancement of bile acid excretion, microsomal triglyceride transfer protein, cholesteryl ester transfer protein activity, bile acid excretion, and prohibiting hepatic fatty acid synthesis, which was conducted by allicin and/or other components in garlic^[4]. Garlic was found to have an important effect on dyslipidemia by significantly decreased serum TC, TG, and LDL levels and moderately elevated HDL cholesterol^[2].

5. Effect on diabetes mellitus

Allyl propyl disulfide, allicin, cysteine sulfoxide, and S-allyl cysteine sulfoxide which are the component of garlic decreased the blood glucose level by preventing the insulin activation caused by liver, enhancing the secretion of insulin from pancreatic beta cells, isolation of insulin from the bonded forms, and increasing the cell sensitivity to insulin^[2].

6. Antihypertensive Activity

The mechanism of antihypertensive effect of garlic extracts is that garlic contains many active sulfur molecules that have been shown to stimulate endothelium-constricting and relaxing factors leading to lower blood pressure^[2]. The antihypertensive properties of garlic have been linked to stimulation of intracellular nitric oxide (NO) and hydrogen sulphide (H₂S) production, and blockage of angiotensin II production, which in turn promote vasodilation and thus reduction in BP^[5].

Garlic was found to be superior to placebo in decreasing BP in hypertensive individuals by 8–9 mmHg in systolic blood pressure (SBP) and 6–7 mmHg in diastolic blood pressure (DBP) in a meta-analysis of 20 clinical trials. While garlic supplementation decreased blood pressure in hypertensive patients, it had no effect on patients with normal blood pressure^[1].

Furthermore, garlic exhibited a significant role in inhibiting thrombosis as well as platelet adhesion or aggregation in humans^[2].

Adverse effect and Drug Interaction

Although the US Food and Drug Administration (FDA) considers garlic safe for humans, it can induce gastric agitation especially if ingested in high doses by sensitive people^[2].

Garlic extract has been shown in human studies to decrease concentrations of drugs that are transported by P-gp, but it has shown no effects on CYP1A2, CYP2D6, or CYP3A4. Medications that are transported by P-gp (e.g., colchicine, digoxin, doxorubicin, quinidine, rosuvastatin, tacrolimus, verapamil) should not be combined with garlic supplements^[6].

References.

1. Ried K, Fakler P. Potential of garlic (Allium sativum) in lowering high blood pressure: mechanisms of action and clinical relevance. Integrated Blood Pressure Control. [Internet]. 2014 [cited 2022 Jan 24] ; 7: 71-82. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266250/    
2. El-Saber Batiha G, Magdy Beshbishy A, G Wasef L, Elewa YHA, A Al-Sagan A, Abd El-Hack ME, et al. Chemical Constituents and Pharmacological Activities of Garlic (Allium sativum L.): A Review. Nutrients. [Internet]. 2020 [cited 2022 Jan 24] ; 12: 1-21. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146530/
3. Ansary J, Forbes-Hernández TY, Gil E, Cianciosi D, Zhang J, Elexpuru-Zabaleta M, et al. Potential Health Benefit of Garlic Based on Human Intervention Studies: A Brief Overview. Antioxidants (Basel). [Internet]. 2020 [cited 2022 Jan 24] ; 9: 1-31. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402177/  
4. Sun YE, Wang W, Qin J. Anti-hyperlipidemia of garlic by reducing the level of total cholesterol and low-density lipoprotein: A meta-analysis. Medicine (Baltimore). [Internet]. 2018 [cited 2022 Jan 24] ; 97: 1-8. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392629/   
5. Ried K, Frank OR, Stocks NP. Aged garlic extract reduces blood pressure in hypertensives: a dose-response trial. European Journal of Clinical Nutrition. [Internet]. 2013 [cited 2022 Jan 24]; 67(1): 64-70. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561616/          
6. Asher GN, Corbett AH, Hawke RL. Common Herbal Dietary Supplement-Drug Interactions. Am Fam Physician. [Internet]. 2017 [cited 2022 Jan 26] ; 96: 101-7. Available form: http://www.aafp.org/afp/2017/0715/p101.html