Intake of garlic and its bioactive components.

The health benefits of garlic likely arise from a wide variety of components, possibly working synergistically. The complex chemistry of garlic makes it plausible that variations in processing can yield quite different preparations. Highly unstable thiosulfinates, such as allicin, disappear during processing and are quickly transformed into a variety of organosulfur components. The efficacy and safety of these preparations in preparing dietary supplements based on garlic are also contingent on the processing methods employed. Although there are many garlic supplements commercially available, they fall into one of four categories, i.e., dehydrated garlic powder, garlic oil, garlic oil macerate and aged garlic extract (AGE). Garlic and garlic supplements are consumed in many cultures for their hypolipidemic, antiplatelet and procirculatory effects. In addition to these proclaimed beneficial effects, some garlic preparations also appear to possess hepatoprotective, immune-enhancing, anticancer and chemopreventive activities. Some preparations appear to be antioxidative, whereas others may stimulate oxidation. These additional biological effects attributed to AGE may be due to compounds, such as S-allylcysteine, S-allylmercaptocysteine, N(alpha)-fructosyl arginine and others, formed during the extraction process. Although not all of the active ingredients are known, ample research suggests that several bioavailable components likely contribute to the observed beneficial effects of garlic.

Immunomodulatory effects of aged garlic extract.

Using various kinds of models, we examined the effects of aged garlic extract (AGE) on immune functions. In the immunoglobulin (Ig)E-mediated allergic mouse model, AGE significantly decreased the antigen-specific ear swelling induced by picryl chloride ointment to the ear and intravenous administration of antitrinitrophenyl antibody. In the transplanted carcinoma cell model, AGE significantly inhibited the growth of Sarcoma-180 (allogenic) and LL/2 lung carcinoma (syngenic) cells transplanted into mice. Concomitantly, increases in natural killer (NK) and killer activities of spleen cells were observed in Sarcoma-180--bearing mice administered AGE. In the psychological stress model, AGE significantly prevented the decrease in spleen weight and restored the reduction of anti-SRBC hemolytic plaque-forming cells caused by the electrical stress. These studies strongly suggest that AGE could be a promising candidate as an immune modifier, which maintains the homeostasis of immune functions; further studies are warranted to determine when it is most beneficial.

Pharmacologic activities of aged garlic extract in comparison with other garlic preparations.

We investigated the pharmacologic activities of four garlic preparations, raw garlic juice (RGJ), heated garlic juice (HGJ), dehydrated garlic powder (DGP) and aged garlic extract (AGE). The study used three animal models, i.e., testicular hypogonadism (hypospermatogensis and impotence) induced by warm water treatment, intoxication of acetaldehyde and growth of inoculated tumor cells. RGJ was found to be effective only in recovery of testicular function. The efficacy of HGJ was observed in three models; however, it did not improve impotence. DGP was effective in recovery of spermatogenesis and stimulated acetaldehyde detoxification. Significant beneficial effects of AGE were found in all three models. Although all four garlic preparations significantly enhanced natural killer (NK) and killer cell activities of the spleen cells of tumor-bearing mice, only AGE and HGJ inhibited the growth of inoculated tumor cells. These results suggest that different types of garlic preparations have different pharmacologic properties, and among the four garlic preparations studied, AGE could be the most useful garlic preparation.

Effects of garlic preparations on the gastrointestinal mucosa.

The effects of garlic preparations, including dehydrated raw garlic powder (RGP), dehydrated boiled garlic powder (BGP) and aged garlic extract (AGE), on the gastric mucosa were determined using a newly established endoscopic air-powder delivery system, which can deliver solid materials directly into the stomach. Among the three preparations, RGP caused severe damage, including erosion. BGP also caused reddening of the mucosa, whereas AGE did not cause any undesirable effects. The safety of enteric-coated garlic products was also determined. Direct administration of pulverized enteric-coated products on the gastric mucosa caused reddening of the mucosa. When an enteric-coated tablet was administered orally, it caused loss of epithelial cells at the top of crypts in the ileum. These results suggest that caution be used with regard to safety and effectiveness when choosing a garlic preparation because some preparations may have undesirable effects, including gastrointestinal problems.

Prenatal stress and postnatal development of neonatal rats--sex-dependent effects on emotional behavior and learning ability of neonatal rats.

Maternal sound stress (800 Hz; 77 dB, every other minute for 15 min/day, from day 10 to 18 of gestation), combined with forced swimming stress (15 min/day), was found to cause potentiation of sound-induced loss of locomotor activity, referred to as emotional behavior, of male offspring, but not that of female offspring, at 4 weeks of age. Maternal stress also caused an increase in the total number of errors by male, but not female offspring in the water-maze test at 6 weeks of age. These effects of stress on emotional behavior and learning behavior were abolished when dams were pretreated with buspirone (30 min before the stress, from day 8 to 18 of gestation). Thus, prenatal stress might have sex-dependent effects on emotional behavior and learning ability of neonatal rats.

[Effect of aged garlic extract (AGE) on hyperglycemia induced by immobilization stress in mice].

The effect of aged garlic extract (AGE) on stress induced hyperglycemia was investigated using the immobilization stress model in mice. After the exposure to immobilization stress for 16 hr per day for 2 consecutive days, the adrenal glands of the mice hypertrophied, and their serum glucose level and corticosterone secretion became elevated, but insulin secretion did not change. These results suggest that the elevation of serum glucose was probably due to the stimulation of the pituitary-adrenocortical axis by the stress. Pretreatment of AGE (5 and 10 ml/kg, p.o.) significantly prevented adrenal hypertrophy, hyperglycemia and elevation of corticosterone, but did not alter serum insulin level. The efficacy of AGE was the same as that of diazepam (5 mg/kg, p.o.). From these results, it is suggested that AGE may prevent stress-induced hyperglycemia, which is the risk of suffering from diabetes mellitus and its progression.

Prevention of psychological stress-induced immune suppression by aged garlic extract.

We determined the effect of Aged Garlic Extract (AGE) on damage caused to immune function by a psychological stress using a communication box. After four days of a psychological stress, a decrease in spleen weight and spleen cells was observed in the psychological stress-exposed mice as compared normal mice (non-stress). AGE significantly prevented the decreases in spleen weight and cells. Additionally, AGE significantly prevented the reduction of hemolytic plaque-forming-cells in spleen cells and anti-SRBC antibody titer in serum caused by this psychological stress. Moreover, a reduction in NK activities was observed in the psychological stress-exposed mice as compared with normal mice (non-stress), whereas NK activities in the AGE administered mice were almost the same as normal mice (non-stress). These results indicate that psychological stress qualitatively and quantitatively impairs immune function, and that AGE is extremely useful for preventing psychologically-induced damage.

Immunomodulation and antitumor activities of Aged Garlic Extract.

We found that Aged Garlic Extract (AGE) could be a significant immuno-potentiator, and could exhibit anti-tumor activities through immune modulation. Consequently, AGE stimulated the proliferation of mouse spleen cells and the release of cytokines, such as IL-2, TNF-alpha and IFN-gamma, increased NK activities, and enhanced phagocytosis of peritoneal macrophages. AGE treatment also stimulated the reactivity of lymphocytes in response to cytokines or mitogens. AGE was far superior to PSK in IL-2 induction, but slightly inferior to PSK in nitric oxide induction. AGE, as effectively as PSK (Krestin), significantly inhibited the growth of Sarcoma-180 (allogenic) and LL/2 lung carcinoma (syngenic) cells transplanted into mice. Concomitantly, increases in NK and killer activities of spleen cells were observed in Sarcoma-180 bearing mice treated with AGE. These results strongly suggest that AGE is as effective as PSK, and could serve as a potent biological response modifier on NK cells and T lymphocytes, and subsequently inhibit the growth of transplanted tumors.

Anti-allergic effects of aged garlic extract.

To examine the effect of Aged Garlic Extract (AGE) on the function of mast cells and activated T lymphocytes, we adopted the in vitro histamine release system, the in vivo IgE mediated skin reaction system and the in vivo late phase reaction system. Consequently, at 1.25, 2.5, and 5.0% (v/v), AGE dose-dependantly inhibited the antigen specific histamine release by mouse anti-TNP monoclonal antibody and TNP-BSA hapten carrier complex against rat basophil cell line RBL-2H3 by 50, 80, and 90 percent, respectively. In the IgE mediated skin reaction system, repeated or single intragastric administration of AGE (10 ml/kg), decreased by 25-45% the antigen specific ear swelling which was induced by a picryl chloride ointment applied to the ear of mice also given an intravenous administration of anti-TNP antibody IgE ascites. In the late phase reaction system, repeated or single intragastric administration of AGE (10 ml/kg) suppressed by 45-55% the antigen specific ear swelling induced by a secondary challenge to the ear of mice given a picryl chloride ointment seven days prior. These results suggest that AGE application could modify, directly or indirectly, the function of mast cells, basophils and activated T lymphocytes which play a leading role in allergic cascade reactions including inflammation.

Pharmacokinetics of the garlic compound S-allylcysteine.

The pharmacokinetic behavior of S-allylcysteine (SAC), one of the biologically active transformation products from garlic, was investigated after oral administration to rats, mice, and dogs. SAC was rapidly and easily absorbed in the gastrointestinal tract and distributed mainly in plasma, liver, and kidney. The bioavailability was 98.2, 103.0, and 87.2% in rats, mice, and dogs, respectively. SAC was mainly excreted into urine in the N-acetyl form in rats; however, mice excreted both SAC and the N-acetyl form. The half-life of SAC was longer in dogs than in rats and mice.

Antifungal activity of ajoene derived from garlic.

The antifungal activity of six fractions derived from garlic was investigated in an in vitro system. Ajoene had the strongest activity in these fractions. The growth of both Aspergillus niger and Candida albicans was inhibited by ajoene at less than 20 micrograms/ml.