Garlic Antioxidant activity
Garlic has strong antioxidant properties due to its organosulfur compounds and Non-sulfur garlic phytochemicals. Mainly through the following three mechanisms.
Low cellular concentrations of glutathione, a major intracellular antioxidant, and/or overproduction of reactive oxygen species (ROS) can lead to oxidative stress-induced damage to biological macromolecules and contribute to the development and progression of pathological conditions. In endothelial cells (that line the inner wall of blood vessels), garlic-derived allicin lowered ROS production and increased the concentration of glutathione. Oral administration of allicin to mice lowered ROS production and prevented ROS-induced cardiac hypertrophy by inhibiting pro-inflammatory pathways like mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase 3β (GSK3β) signaling pathways. It is thought that, upon crossing cell membranes, allicin interacts with glutathione and forms SAMG, which could prolong the antioxidant activity of allicin.
Nrf2-dependent antioxidant pathway
Allicin was also found to upregulate the expression of glutamate-cysteine ligase (GCL), the rate-limiting enzyme in glutathione synthesis, and other Phase II detoxifying/antioxidant enzymes, likely via the activation of the nuclear factor E2-related factor 2 (Nrf2)-dependent pathway. Briefly, Nrf2 is a transcription factor that is bound to the protein Kelch-like ECH-associated protein 1 (Keap1) in the cytosol. Keap1 responds to oxidative stress signals by freeing Nrf2. Upon release, Nrf2 translocates to the nucleus and binds to the antioxidant response element (ARE) located in the promoter of genes coding for antioxidant/detoxifying enzymes and scavengers. Nrf2/ARE-dependent genes code for numerous mediators of the antioxidant response, including GCL, glutathione S-transferases (GSTs), thioredoxin, NAD(P)H quinone oxidoreductase 1 (NQO-1), and heme oxygenase 1 (HO-1). Like allicin, oil-soluble organosulfides, DADS and DATS, have been shown to stimulate Nrf2-dependent antioxidant pathway. For example, antioxidant and cytoprotective effects of DADS against acute ethanol-induced liver damage in mice were associated with the ability to trigger Nrf2-dependent HO-1 activation. DATS protected cardiac cells in vitro and in experimental diabetic rats from high glucose-induced oxidative stress and apoptosis by inducing PI3K/Akt-dependent Nrf2 antioxidant signaling .
Aged garlic extract have also been shown to increase expression of antioxidant enzymes via the Nrf2/ARE pathway. SAC, a major organosulfur compound in aged garlic extract, prevented renal damage caused by ROS in cisplatin-treated rats, by limiting cisplatin-induced reduction of glutathione level, Nrf2 expression, and activity of several antioxidant enzymes (catalase, glutathione reductase, glutathione peroxidase). SAC also protected neurons from oxidative damage and apoptosis in wild-type mice but not in mice without a functional Nrf2 signaling pathway.
Nitric oxide (NO) signaling cascade
The generation of nitric oxide (NO) catalyzed by endothelial nitric oxide synthase (eNOS) plays a critical role in protecting the vascular endothelium from oxidative and inflammatory insults. ROS-induced NO inactivation can impair vascular endothelial function, contributing to various pathologies like atherosclerosis, hypertension, cardiovascular disease, and central nervous system disorders. Interestingly, ingestion of 2 g of fresh garlic was found to increase NO plasma concentrations within two to four hours in healthy volunteers. DADS and DATS protected eNOS activity and NO bioavailability in cultured endothelial cells challenged with oxidized low-density lipoprotein (LDL). In a model of traumatic brain injury in rats, allicin attenuated brain edema, neurological deficits, and apoptotic neuronal death, and exhibited antioxidant and anti-inflammatory effects, partly by increasing Akt-mediated eNOS activation. Aged garlic extract and SAC were also found to stimulate NO production in different experimental settings. In a model of erectile dysfunction in diabetic rats, SAC restored electrically-induced penile erection by stimulating eNOS activity and inhibiting the expression of NADPH oxidase (Nox) responsible for ROS overproduction.
1. Horev-Azaria L, Eliav S, Izigov N, et al. Allicin up-regulates cellular glutathione level in vascular endothelial cells. Eur J Nutr. 2009;48(2):67-74. (PubMed)
2. Liu C, Cao F, Tang QZ, et al. Allicin protects against cardiac hypertrophy and fibrosis via attenuating reactive oxygen species-dependent signaling pathways. J Nutr Biochem. 2010;21(12):1238-1250. (PubMed)
3. Chen C, Kong AN. Dietary chemopreventive compounds and ARE/EpRE signaling. Free Radic Biol Med. 2004;36(12):1505-1516. (PubMed)
4. Zeng T, Zhang CL, Song FY, et al. The activation of HO-1/Nrf-2 contributes to the protective effects of diallyl disulfide (DADS) against ethanol-induced oxidative stress. Biochim Biophys Acta. 2013;1830(10):4848-4859. (PubMed)
5. Tsai CY, Wang CC, Lai TY, et al. Antioxidant effects of diallyl trisulfide on high glucose-induced apoptosis are mediated by the PI3K/Akt-dependent activation of Nrf2 in cardiomyocytes. Int J Cardiol. 2013;168(2):1286-1297. (PubMed)
6. Hiramatsu K, Tsuneyoshi T, Ogawa T, Morihara N. Aged garlic extract enhances heme oxygenase-1 and glutamate-cysteine ligase modifier subunit expression via the nuclear factor erythroid 2-related factor 2-antioxidant response element signaling pathway in human endothelial cells. Nutr Res. 2016;36(2):143-149. (PubMed)
7. Gomez-Sierra T, Molina-Jijon E, Tapia E, et al. S-allylcysteine prevents cisplatin-induced nephrotoxicity and oxidative stress. J Pharm Pharmacol. 2014;66(9):1271-1281. (PubMed)
8. Shi H, Jing X, Wei X, et al. S-allyl cysteine activates the Nrf2-dependent antioxidant response and protects neurons against ischemic injury in vitro and in vivo. J Neurochem. 2015;133(2):298-308. (PubMed)
9. Higashi Y, Noma K, Yoshizumi M, Kihara Y. Endothelial function and oxidative stress in cardiovascular diseases. Circ J. 2009;73(3):411-418. (PubMed)
10. Lundblad C, Grande PO, Bentzer P. Hemodynamic and histological effects of traumatic brain injury in eNOS-deficient mice. J Neurotrauma. 2009;26(11):1953-1962. (PubMed)
11. Bhattacharyya M, Girish GV, Karmohapatra SK, Samad SA, Sinha AK. Systemic production of IFN-α by garlic (Allium sativum) in humans. J Interferon Cytokine Res. 2007;27(5):377-382. (PubMed)
12. Lei YP, Liu CT, Sheen LY, Chen HW, Lii CK. Diallyl disulfide and diallyl trisulfide protect endothelial nitric oxide synthase against damage by oxidized low-density lipoprotein. Mol Nutr Food Res. 2010;54 Suppl 1:S42-52. (PubMed)
13. Chen W, Qi J, Feng F, et al. Neuroprotective effect of allicin against traumatic brain injury via Akt/endothelial nitric oxide synthase pathway-mediated anti-inflammatory and anti-oxidative activities. Neurochem Int. 2014;68:28-37. (PubMed)
14. Shouk R, Abdou A, Shetty K, Sarkar D, Eid AH. Mechanisms underlying the antihypertensive effects of garlic bioactives. Nutr Res. 2014;34(2):106-115. (PubMed)
15. Yang J, Wang T, Yang J, et al. S-allyl cysteine restores erectile function through inhibition of reactive oxygen species generation in diabetic rats. Andrology. 2013;1(3):487-494. (PubMed)
16. Ho SC, Su MS. Evaluating the anti-neuroinflammatory capacity of raw and steamed garlic as well as five organosulfur compounds. Molecules. 2014;19(11):17697-17714. (PubMed)
17. Liu KL, Chen HW, Wang RY, Lei YP, Sheen LY, Lii CK. DATS reduces LPS-induced iNOS expression, NO production, oxidative stress, and NF-κB activation in RAW 264.7 macrophages. J Agric Food Chem. 2006;54(9):3472-3478. (PubMed)
18. You S, Nakanishi E, Kuwata H, et al. Inhibitory effects and molecular mechanisms of garlic organosulfur compounds on the production of inflammatory mediators. Mol Nutr Food Res. 2013;57(11):2049-2060. (PubMed)
19. Lee HH, Han MH, Hwang HJ, et al. Diallyl trisulfide exerts anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 macrophages by suppressing the Toll-like receptor 4/nuclear factor-κB pathway. Int J Mol Med. 2015;35(2):487-495. (PubMed)