**4. Mechanisms**

Apoptosis is a physiological term used to explain programmed cell death [50]. Caspase 3 formation is a vital step in the activation of the apoptotic pathway and an increase in crude garlic intake leads to an increase in caspase 3 formation. Apoptosis effects the formation of spermatocytes and spermatids and the testes have shown an increase in apoptotic germ calls after the rat is exposed to crude garlic feeding [51].It was shown that supplementing the diet with crude garlic induced apoptosis in both spermatocytes and spermatids [51]. Dixit & Joshi [48] again noted that treating rats with garlic powder impaired spermatogenesis and led to an early arrest in the development of spermatozoa. This in turn reduced the amount of round spermatids converted into elongated spermatids furthermore impairing spermatogenesis. With regards to the testicular function, garlic and its metabolites have a protective function. The effects of garlic on the testes include prevention of hypogonadism caused by heat and protection against cadmium-induced testicular damage by reversing the alterations in the biochemical parameters [52]. Other beneficial properties are its ability to restore testicular histology and decrease free radicals in the testes which are detrimental when in large amounts.

Garlic feeding has both positive and negative effects on testosterone production. It is important to note that between the different studies that were performed, different preparations, amounts and concentrations of garlic were administered. The preparation of the garlic could possibly be the key factor involved in the impact it will have. By administering crude garlic to Rat models it was recorded that there was a decrease in testosterone formation due to the decrease in responsiveness of the leydig cells to the luteinizing hormone. This decrease in responsive‐ ness is due to the histological alteration in the testes (Figure 1). In contrast Oi et al. [53] showed an increase in testosterone levels due to the increase in the luteinizing hormones after admin‐ istration of 8g of garlic powder. Again, the different preparations of the garlic plant are vital.

Garlic's effects on the reproductive system have led to contradictory results. According to Hammami et al. [51] garlic has been used to improve male sexual dysfunction and this includes impotence. Heated garlic juice is effective in recovering testicular function after experimental hypogonadism, but powder or crude garlic (in large amounts) impairs male reproductive tract

Benign prostatic hyperplasia (BHP) is an extremely common condition in older men and can affect the male reproductive system. Milk and other dairy products have been related to an increase in BHP but the results found are very inconsistent. The same trend applies for garlic as studies have shown that cooked garlic can decrease the onset of BPH but RG can increase the onset [54]. Aqueous garlic extract has however shown to improve disease parameters in patients with BPH [55]. Garlic extract also decreases the onset of prostatic cancers and other malignancies [56]. The results are however inconclusive and very contrasting amongst published articles and no real conclusion can be drawn until more research is done on the

effects of vegetable- more specific garlic – has on the male reproductive system.

*3.6.2. Hormonal levels and libido*

268 Antioxidant-Antidiabetic Agents and Human Health

functions [51].

The scientific and pharmacologic explanations for most of the medicinal effects attributed to garlic treatment are still eluding researchers. There is however a few mechanisms via which garlic more than likely exert its effects which are worth mentioning and highly plausible.

### **4.1. Antioxidant properties**

An antioxidant is a molecule that inhibits the oxidation of other molecules in the human body [57]. A chemical reaction known as oxidation occurs when electrons or hydrogen atoms are transferred from a substance to an oxidizing agent. Once this oxidation reaction occurs, free radicals are produced and realised into the body. In turn, these radicals can start chain reactions. Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions [58]. Antioxidants are present in most of the foods we eat and drink like spinach, oranges, whole wheat bread and tea. Garlic is also very rich in antioxidants [59] (Table 1). The powerful odour that fresh garlic possesses is due to the amount of allicin that is present. This odour as well as the unique acquired flavour of garlic has resulted that not every one favours it [20]. This led to the emergence of the AGE. As mentioned previously AGE is obtained via a long and tedious process. The extract obtained through this process does not have the pungent flavour of garlic and is also odourless [60]. This is due to the fact that a large amount of allicin is lost and therefor it loses a lot of its beneficial properties. However, due to the amount of allicin lost, this means that the most prominent component in AGE is the organosulfurs like SAC and SAMC. These compounds are said to have potent antioxidant effects in the body. S-allylcysteine and S-allylmercaptocysteine increase with aging of the garlic. Therefore, the longer the garlic is aged the less allicin it will contain, but the more antioxidant effect it will have. This makes AGE the most potent form of garlic with regards to antioxidant ability.

Oxidative stress is the term used to describe the process that transpires when there are too many free radicals or not enough antioxidant agents in the body [20]. This oxidative damage is often associated with aging and age-degenerative conditions such as dementia and AD. AGE has shown to inhibit this oxidative damaged caused and helps with reducing the risk factor or onset of neurodegenerative disease as well as slowing down the aging process or to be more specific the onset of deteriorating skin. However, the administration of garlic did not decrease the levels of iron mediated oxidative stress [61]. The antioxidant actions of AGE are based on decreasing the amounts of ROS and reactive nitrogen species (RNS) as well as inhibiting LDL oxidation and lipid peroxide formation. An increase in ROS in the body can lead to a host of issues including endothelial dysfunction which is a key marker in the development of cardiac injury. Likewise LDL oxidation could lead to vascular dysfunction and promotes the onset of atherosclerosis and possibly myocardial infarction [20].

A study was done to compare the antioxidant potential of the different garlic preparations. AGE which is predominantly SAC and SAMC was compared to a water extract of fresh garlic containing mostly alliin and RG that contains allicin [62]. AGE had the highest antioxidant effect and surprisingly the other two preparations served more as an oxidant [62]. Although

the majority of the antioxidant affects are from the AGE there are incidents where other preparations were used as an antibiotic/antioxidant. A lot of the mechanisms by which garlic acquired its medicinal properties have been specifically ascribed to this potent antioxidant action. It has the ability to stimulate immunological responsiveness and its modulation of prostanoids synthesis. The antioxidant properties of garlic have been studied extensively and it does have a beneficial role in the body. AGE is however more effective in removing free radicals and LDL cholesterol than other preparations of the garlic root, but that does not mean the other preparations aren't important as well.

more detrimental. Some of the results found showed that the administration of garlic affected testicular function, histological properties and sperm quality [46, 48 & 51]. Hormone levels were subsequently also altered and an increase in testicular tissue apoptosis was recorded [51]. Furthermore crude garlic extracts and garlic juice showed to cause sperm immobilization (administered as 15g/100g and 30g/100g respectively) [51, 67, 68]. More research definitely needs to be performed on the effect of garlic on acrosome and DNA

Garlic and Its Effects on Health with Special Reference to the Reproductive System

http://dx.doi.org/10.5772/57191

271

In general it can be said that garlic's therapeutic properties warrants further investigation in order to develop its full treatment potential as a phytotherapeutical agent impacting on human health and used for the treatment of various disease conditions. The specific mechanism of action also need to be identified as it can possible shed more light on and help with the development of more effective pharmacological agents. Additional human studies on AGE and its constituents are needed to elucidate their role in protecting human health, and

**Product Source of commercial sample Lot# % Inhibition2 (SD)**

1Laboratory Report, Wakunaga Pharmaceutical, Hiroshima, Japan, October 1995. Courtesy of Wakunaga of America Company. Garlic products were purchased from stores, as in Freeman and Kodera 1995. Each analysis was performed

<sup>2</sup>Antioxidant properties were measured by the ability of the various products to inhibit the emission of low level chem‐ iluminescence, in a liver microsomal fraction, initiated by t-butyl hydroperoxide (Imai et al. 1994). Inhibition (+) de‐ notes antioxidant activity, resulting from scavenging of reactive oxygen species (ROS) and reflected in the inhibition of light emission. Inhibition (-) denotes prooxidant activity of a product as reflected in an increased light emission, in‐

\*Table reproduced from ''Recent Advances on the Nutritional Benefits Accompanying the Use of Garlic as a Supple‐ ment" held November 15–17, 1998 in Newport Beach, CA. The conference was supported by educational grants from Pennsylvania State University, Wakunaga of America, Ltd. and the National Cancer Institute. The proceedings of this

conference are published as a supplement to *The Journal of Nutrition 131:1010S–1015S, 2001*.

**Table 1.** Antioxidant effects of aged garlic extract (AGE) compared with other garlic supplements1\*

AGE Kyolic liquid (Mission Viejo) 5LO1 +121.8 (2.73) A Garlinase 4000 (Enzymatic Therapy, Green Bay, WI) 213Y46QD -213.0 (4.67) B Garlic powder (McCormick, Baltimore, MD) 0208A -217.2 (5.20) C Quintessence caplet (Pur- Gar, Takoma, WA) 36698 -239.5 (4.85) D Quintessence capsule (Pur- Gar, Takoma, WA) 63121 -242.1 (5.15) E Garlicin (Nature's Way Product, Springville, UT) 503369 -246.8 (9.24) F Kwai (Lichtwerpharma, Berlin, Germany) 94080700 -250.7 (3.01) G Garlique (Sunsource HealthProducts, Kihei, HI) 5J0010 -251.0 (10.6) H Garlic Time (ArizonaNatural Products,Scottsdale, AZ) 896210 -254.4 (7.14)

molecular studies should be intensified to reveal the underlying mechanisms.

integrity of spermatozoa.

three times.

duced by increased ROS activity.

### **4.2. Antibiotic properties**

Allicin, found in the garlic bulb, serves as a powerful antibiotic which aids the body in inhibiting the growth and reproduction of bacteria [63]. One milligram of allicin is equal to 15 standard units of penicillin [63]. Allicin attacks over 23 types of bacteria, such as staph and salmonella, 60 types of fungi and yeast and is also effective against 17 of the most dangerous fungi [64]. Another example of where allicin serves as a potent antibiotic is in the treatment of Streptolysin O (SLO). SLO is a powerful cytolytic toxin found in almost all group A streptococci. Treatment of SLO with Allicin completely neutralized the haemolytic activity of the bacteria, while the aqueous garlic extract inhibited it altogether [65]. From these results it can be deducted that garlic and its metabolites have antibiotic properties. Extracts of fresh garlic contain antioxidant phytochemicals that prevent oxidative damage.

### **4.3. NO and H2S**

NO and H2S play major roles in the progression of diseases, both NO and H2S are considered to be important vasodilators. In a recent study both serum NO and H2S were measured in diabetic rats and it was shown that chronic administration of garlic normalised both gaseous molecules [26] and this decreased hypertension by inhibiting certain enzymes such as N omega-nitro-L-arginine-methyl-ester (L-NAME) [66].
