Aged garlic extract enhances production of nitric oxide
Introduction
Nitric oxide (NO) is an important intercellular and intracellular messenger with a major role in controlling the physiological function of the cardiovascular system [1], [2]. It is synthesized from L-arginine by NO synthases (NOSs) in many of the cells of the cardiovascular system, including endothelial cells, macrophages, smooth muscle cells, platelets and fibroblasts [1]. Three kinds of NOSs, neuronal constitutive NOS (ncNOS), inducible NOS (iNOS) and endothelial constitutive NOS (ecNOS), were recently reported to be responsible for NO biosynthesis in these cells [3]. NO derived from ncNOS and ecNOS was reported to modulate vasomotor tone, the inhibition of platelet or leukocyte aggregation and adhesion to the endothelium, suggesting properties of anti-atherogenicity [1]. The study found that iNOS remained unexpressed until induced by cytokines or lipopolysaccharides in some pathological process such as circulatory shock or inflammation [4], [5].
Since ancient times, people of many different cultures have considered garlic (Allium sativum L.) as a valuable healing agent. Garlic has been used as a cure for various ailments, including heart disease, cancer and infection [6]. Its curative properties have been attributed to its ability to increase physiological levels of NO, which acts as an anti-arteriosclerotic and anti-inflammation agent [7], [8], [9], [10], [11]. It may also reduce damage in diseased blood vessel walls. A large number of pharmacological studies have been reported that aged garlic extract (AGE) possesses anti-hyperlipidemic [12], anti-oxidative [13], [14], [15], cardiovascular [16], [17], [18] and hepato-protective [19], [20], [21] properties.
In this study, we examined the effect of AGE on NO production in mice. As NO is instantaneously oxidized to nitrate and nitrite within the body, we examined by measuring levels of the stable end-products of NO metabolites, nitrite and nitrate, in the plasma of mice after experimental treatment.
Section snippets
Aged garlic extract
AGE was manufactured by Wakunaga Pharmaceutical Co. Ltd. (Osaka, Japan) by slicing garlic cloves (Allium sativum L.) and soaking them in a water-ethanol mixture, which was then naturally extracted/aged for more than 10 months at room temperature. The AGE we used contained approximately 28.6% (w/v, 286 mg/ml) solid material, 0.63% (6.3 mg/ml) arginine and 0.1% S-allylcysteine (calculated on a dry weight basis) as a marker compound for standardization [22].
Chemicals
( ±
Effect of drugs on NO production
Fluctuation in NO production was investigated after administration of AGE, NOR3 and L-NMMA. AGE as well as NOR3, NO donor, significantly increased NO levels in the plasma compared to the control (p < 0.05 and p < 0.01, respectively). On the other hand, the NOS inhibitor L-NMMA significantly reduced NO levels in the plasma compared to the control (p < 0.01, Table 1).
Effect of AGE and LPS on NO production
We examined the effect of AGE on NO production over time. AGE significantly increased NO levels in the plasma at 15 (by 44%, p <
Discussion
In the present study, we investigated NO production in the body by surveying stable NO metabolites in the blood. We confirmed that levels of NO metabolites are related to the presence of NO donor or NOS inhibitor. Both AGE and NO donor significantly show increasing NO levels (Table 1). AGE rapidly increased NO production about 30–40% after administration and was returned to the basal value at 2 h after administration (Fig. 1). The period for this rapidly response was supported by the result
References (39)
- et al.
Regulation of biosynthesis of nitric oxide
J. Biol. Chem.
(1994) - et al.
Purification of nitric oxide synthase from rat macrophages
J. Biol. Chem.
(1991) - et al.
Garlic: a review of its relationship to malignant disease
Prev. Med.
(1990) - et al.
Effect of an odormodified garlic preparation on blood lipids
Nutr. Res.
(1987) - et al.
Dairy supplementation with aged garlic extract, but not raw garlic, protects low density lipoprotein against in vitro oxidation
Atherosclerosis
(1999) - et al.
Dietary supplementation with aged garlic extract inhibits ADP-induced platelet aggregation in humans
J. Nutr.
(2000) Suppression of LDL oxidation by garlic
J. Nutr.
(2001)- et al.
Treatment with aged garlic extract protects against bromobenzene toxicity to precision cut liver slice
Toxicology
(1999) - et al.
Therapeutic effect of S-allylmercaptocysteine on acetaminophen-induced liver injury in mice
Eur. J. Pharmacol.
(2001) - et al.
Arginine is not responsible for the activation of nitric oxide synthase by garlic
J. Ethnophamacol.
(1996)
A double-blind crossover study in moderately hypercholesterolemic men that compared the effect of aged garlic extract and placebo administration on blood lipids
Am. J. Clin. Nutr.
Aged garlic extract, a modulator of cardiovascular risk factors: a dose-finding study on the effects of AGE on platelet functions
J. Nutr.
Effects of exercise training of 8 weeks and detraining on plasma level of endothelium-derived factors, endothelin-1 and nitric oxide, in healthy young humans
Life Sci.
Nitric oxide: physiology, pathophysiology, and pharmacology
Pharmacol. Rev.
Nitric oxide release accounts for the biologic activity of endothelium-derived relaxing factor
Nature
Nitric oxide: a new paradigm for second messengers
J. Med. Chem.
Potent activation of nitric oxide synthase by garlic: a basis for its therapeutic applications
Curr. Med. Res. Opin.
Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene
Proc. Natl. Acad. Sci. U. S. A.
Antiatherogenic effects of L-arginine in the hypercholesterolemic rabbit
J. Clin. Invest.
Cited by (92)
Effect of the nitrogen-fixing bacterium Pseudomonas protegens CHA0-ΔretS-nif on garlic growth under different field conditions
2020, Industrial Crops and ProductsCitation Excerpt :Vitamin C content was measured based on the method of Montano et al. (2004). Allicin content of cloves was analyzed according to the method of Akan et al. (2019), and nitrate (NO3-) levels were determined using the method of Morihara et al. (2002). At the seedling and harvest stages, soils were randomly sampled at different layers (0–20 and 20–40 cm) using a 5 cm inside-diameter corer.
Antidiabetic role of a novel protein from garlic via NO in expression of Glut-4/insulin in liver of alloxan induced diabetic mice
2019, Biomedicine and PharmacotherapyCitation Excerpt :Values of p < 0.05 were defined as statistically significant. It was previously reported that garlic extract was a potent activator of NO synthesis in various cells [33,34]. To determine the effect of AEG on blood sugar, NO and insulin levels in alloxan treated mice, when the AEG (0.4 gm/kg body weight) was injected in the circulation of the test animal, it was found that the blood sugar level in the alloxan treated diabetic mice that weighs 550 ± 10 mg/dL before the injection of AEG decreased to 290 ± 8 mg/dL at 8 h and to 125 ± 10 mg/dL after 16 h (Fig. 1A) that was quantitatively equal to 0.022 ± 0.002μUnit of insulin (monocomponent human insulin of r-DNA origin).
In vivo therapeutic efficacy of the Allium sativum ME in experimentally Echinococcus granulosus infected mice
2018, Comparative Immunology, Microbiology and Infectious DiseasesGarlic and Gaseous Mediators
2018, Trends in Pharmacological SciencesCitation Excerpt :AGE is a commercially available standardised garlic supplement that contains water-soluble sulfur compounds such as SAC, S-1-propenylcysteine (S1PC), and S-allylmercaptocysteine (SAMC). This supplement increases blood NO concentrations in mice [57] and causes vasorelaxation in isolated rat aortic rings [60]. Similarly, DADS and DATS, which are constituents of garlic oils, protect eNOS from inactivation and proteasomal degradation in cells treated with oxLDL [61].
Immunomodulatory Attributes of Aged Garlic Extract and Its Components
2018, Immunology: Immunotoxicology, Immunopathology, and Immunotherapy