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  • br Pharmacologically garlic can yield distinctly enriched br

    2020-08-12


    Pharmacologically, garlic can yield distinctly enriched
    [*Corresponding author] E-mails: [email protected] (WONG Nai-Kei); [email protected] (XIAO Jia) These authors have no conflict of interest to declare.
    Published by Elsevier B.V. All rights reserved
    preparations by a variety of processing methods. In the market, besides fresh garlic, there are mainly four types of commercially available garlic products, including aged garlic extract (AGE), dehydrated garlic powder, garlic oil and garlic oil macerate [8]. AGE is a processed product from aging garlic what is sliced and then extracted by water or ethanol. It mainly contains several water-soluble allyl amino Muscimol derivatives (such as SAC, SAMC and N-fructosyl arginine) and a small amount of oil-soluble compounds [9] (Fig. 1). AGE has been considered to possess immune-enhancing, hepato-protective, antioxidant and anticancer properties with proven safety [1].
    Pharmacokinetic studies suggest that SAC and SAMC may be the main active ingredients in AGE, since allicin, vinyldithiins, ajoene, and diallyl disulfide (DADS) are not detected in the blood and urine after treatment [1]. SAMC (S-allylmercaptocysteine, chemical formula: CH2=CH-CH2-S-S-CH2-CHNH2-COOH) is a stable nonvolatile sulfur-con-taining compound of AGE. It can be prepared in a rapid spon-taneous reaction between L-cysteine and allicin in aqueous solution (PH 6) (Fig. 2), with very high yield (93%) [10]. Since the pharmacological features and therapeutic perspectives of SAC have been extensively studied and reviewed [11-12], we focused on the beneficial effects of SAMC in this article.
    Fig. 1 Major components derived from aged garlic
    Fig. 2 Chemical synthesis reactions of SAMC during garlic aging process
    To date, the health-promoting effects of SAMC have been amply demonstrated in several disease models. For example, overuse of gentamicin, an aminoglycoside type of antibiotic widely used for treating bacterial infections, can give rise to adverse effects, including inner ear and kidney dysfunctions. In a gentamicin-induced rat kidney injury model, excessive production of reactive oxygen species (ROS), including superoxide (O2·–), hydrogen peroxide (H2O2), hydroxyl radi-cal (·OH), and nitrosative stress from renal mitochondria were frequently observed, resulting in severe glomerular and tubu-lar damages. Pre-treatment with SAMC significantly attenu-ated such tissue injury by upregulating the expression of anti-oxidant enzymes (e.g. GPx, GR, CAT and Mn-SOD) [13]. As an eye treatment, administration of SAMC into the corneas of rabbits decreased intraocular pressure without affecting pupil diameter. Further research revealed that SAMC caused a marked increase in atrial natriuretic peptide (ANP) concentra-tion in the aqueous humor of rabbit, which partially explained the mechanism of SAMC-induced ocular hypotension [14]. Furthermore, we characterized the hepato-protective mecha-nisms of SAMC in carbon tetrachloride (CCl4)-or acetamino-phen (APAP)-induced acute liver injury and high fat diet-induced non-alcoholic fatty liver disease (NAFLD) in rodent models [15-19]. SAMC potently alleviated hepatic injuries, by reducing symptoms such as inflammation, necro-apoptosis, fibrosis, lipid metabolism dysfunction, and oxidative stress. SAMC achieves this primarily through its anti-inflammatory, antioxidant and autophagic regulatory actions [15, 20].
    Indeed, most studies on the beneficial effects of SAMC focused on its potential anti-cancer application. In a variety of cancer types, SAMC has been shown to exert potent and specific
    anti-cancer effects on different regulating pathways (Table 1).
    Liver cancer
    The occurrence of liver cancer is mainly caused by cir-rhosis, which is associated with viral infections and chronic alcohol consumption. Recent computational findings suggest that SAMC has high docking score for the oncogene Kras (RAS) in HepG2 cells, which is a small GTPase with func-tional importance in regulating cytoskeleton dynamics, and cell growth and tissue development. However, the complex formed by SAMC and RAS is not stable, suggesting that SAMC may not have an effect on Ras activity strong or long enough for SAMC to prevent liver tumorigenesis [35]. In addi-tion, transforming growth factor-beta (TGF-β) signaling was reported to be important in SAMC-induced hepatoma cell apoptosis in vitro. Specifically, SAMC treatment potently activated TGF-β1, TβRII, p-smad2/3, smad4 and smad7 sig-naling, as well as the intrinsic apoptotic pathways (e.g. Bim and Bcl-2) in HepG2 cells, which was different from TGF-β alterations in colon cancer cell (SW620) [36].
    Gastric cancer
    Frequently asymptomatic in its early stage, gastric cancer progressively alters the micro-environment to favor tumori-genesis. This insidious nature helps ensure gastric cancer as a malignancy with the second highest fatal ratio of cancer-related diseases in the world. In experimental models, when cultured with SAMC, SGC7901 gastric cancer cells showed marked morphological changes, such as apoptosis-related atrophy, shrinkage, fragmentation and reduced cell connections. The MAPK, and intrinsic and extrinsic apoptotic pathways were