j o u r n a l o f f o o d a n d d r u g a n a l y s i s 2 5 ( 2 0 1 7 ) 6 2 e7 0

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Review Article

Black garlic: A critical review of its production,
bioactivity, and application

Shunsuke Kimura a,1, Yen-Chen Tung b,1, Min-Hsiung Pan b, Nan-Wei Su c,
Ying-Jang Lai d,*, Kuan-Chen Cheng a,b,e,*
a
Institute of Biotechnology, National Taiwan University, Taipei, Taiwan, ROC
b
Graduate Institute of Food Science Technology, National Taiwan University, Taipei, Taiwan, ROC
c
Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan, ROC
d
Department of Food Science, National Quemoy University, Quemoy County, Taiwan, ROC
e
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan,
ROC

article info abstract

Article history: Black garlic is obtained from fresh garlic (Allium sativum L.) that has been fermented for a
Received 29 September 2016 period of time at a controlled high temperature (60e90 C) under controlled high humidity
Received in revised form (80e90%). When compared with fresh garlic, black garlic does not release a strong offensive
7 November 2016 flavor owing to the reduced content of allicin. Enhanced bioactivity of black garlic
Accepted 7 November 2016 compared with that of fresh garlic is attributed to its changes in physicochemical prop-
Available online 5 December 2016 erties. Studies concerning the fundamental findings of black garlic, such as its production,
bioactivity, and applications, have thus been conducted. Several types of black garlic
Keywords: products are also available in the market with a fair selling volume. In this article, we
black garlic summarize the current knowledge of changes in the components, bioactivity, production,
black garlic application and applications of black garlic, as well as the proposed future prospects on their possible
black garlic bioactivity applications as a functional food product.
black garlic production Copyright © 2016, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan
fermentation LLC. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).

chewy and jelly-like (Figure 1). The duration of fermenta-
1. Introduction tion varies depending on cultures, manufacturers, and pur-
poses [1].
Black garlic (BG) is simply fresh garlic (Allium sativum L.) that The long history of the use of garlic in food and acute,
has been fermented for a period of time at a high temperature chronic, and inhalation studies, although limited, reveals no
under high humidity. The process turns garlic cloves dark, credible adverse biological effects. Exact origins of BG are
gives them a sweet taste, and alters their consistency to

* Corresponding authors. Department of Food Science, National Quemoy University, 1, University Road, Jinning, Quemoy County 89250,
Taiwan, ROC. (Y.-J. Lai); National Taiwan University, 1, Section 4, Roosevelt Road, Taipei 10617, Taiwan, ROC. (K.-C. Cheng).
E-mail addresses: d91641006@gmail.com (Y.-J. Lai), kccheng@ntu.edu.tw (K.-C. Cheng).
1
S. Kimura and Y.-C. Tung contributed equally to this article.
http://dx.doi.org/10.1016/j.jfda.2016.11.003
1021-9498/Copyright © 2016, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

nevertheless. When compared with fresh garlic. fish. the amount of fructans sulfoxides (alliin) to form cytotoxic and odoriferous alkyl decreased simultaneously. BG demonstrates significantly Fresh garlic contains approximately 63% of water. thiosulfinates are immediately decomposed to other com- pounds such as diallyl sulfide. . and risotto [2]. flavonoids. 3. product. and the quality of its products depends 2. dithiins.2% of free amino acids (arginine).17]. increased significantlydup to 40e100-fold higher than those After processing. In contrast. soup. and Several studies have reported that water-soluble sugars. However. The changes of physicochemical properties are the main reasons for enhanced bioactivity of BG compared with fresh garlic. 1.21]. j o u r n a l o f f o o d a n d d r u g a n a l y s i s 2 5 ( 2 0 1 7 ) 6 2 e7 0 63 unknown and controversial. anti- inflammation. BG does not release a strong off-flavor due to the reduced content of allicin. antidiabetes. diseases increased during the aging process. (A) Garlic during fermentation prospects on their possible applications as a functional food process (left to right). such as antioxidation. and ajoene [11. and was introduced into Taiwan and other countries around 10 years ago. The two main focuses of this study are to summarize the current knowledge of the composition change. such as cutting. which accumulates Three of Amadori and three of Heyns compounds in BG naturally during the storage of garlic at a cool temperature. who have been using it to flavor chicken. than fresh garlic [19]. (B) Black garlic cloves. and diallyl trisulfide. some chemical It is well known that the aging period of garlic is shorter at compounds from fresh garlic are converted into Amadori/ higher temperatures [22]. Effects of aging temperature on the quality of BG antioxidant. Although the Designer Foods Pro- gram no longer exists. or in fresh garlic. The contents of chemical compounds of BG depend on the pounds during the fermentation process. Nontreated fresh garlic also contains a high amino acids. In 1990. high-end chefs have drawn much attention to BG. As for BG. BG contains much more functional compounds such as SAC than fresh The enhanced biological activity of BG when compared with garlic. diallyl disulfide. we will summarize the changes of garlic components ported that many valuable components within BG against between fresh garlic and BG. Allicin and other Maillard reaction in garlic processing. especially poly- phenol. alliinase rapidly lyses the cytotoxic cysteine converting fresh garlic to BG. The chemical compounds of aged BG (ABG) are complicated. In the case of aging process at 70 C. and anticarcinogenic effects [3e7].1. and some intermediates of Maillard reac- 2.3% of organosulfur compounds. 28% of much higher biological activity. SAC contributes to health benefits of garlic. In the past few years. hydrolyzed and oxidized to form alliin. BG has long been consumed in South Korea. Allicin contributes to glucose with some of amino acids play important roles in the characteristic flavor and taste of garlic. several studies have re- ported that BG extract demonstrates several functions. total polyphenols. Nutritional content of garlic on the manufacturing process.12]. Some researchers re- section. and Thailand for centuries. 2% ties. and flavonoids increased or amount of g-glutamylcysteines [10]. through the aging process for dehydration. the antioxidant activity of garlic varies across regions [18]. which was converted into antioxidant compounds such as bioactive alkaloids and flavonoid compounds during the aging process [1]. and BG Furthermore. 1. during the thermal process. Maillard reaction [1]. which are key intermediate compounds of the speed of aging is two-fold faster than that at 60 C [23]. Nevertheless. Heyns compounds.20. antiallergic. crushing. scientists are still looking for what are now called bioactive components in different foods. Besides daily consumption. Comparison of the components between fresh garlic tion have been known as antioxidant agents [13. production. g- glutamylcysteines are converted to SAC through its catabo. of proteins (alliinase). Designer Foods Program listed garlic at the top of cancer- fighting candidates [8]. These compounds can be decreased during thermal processing (Table 1) [13. such as antioxidant proper- carbohydrate (fructans). and anti-inflammatory activities [14e16]. BG processing lism pathway other than the alliineallicin pathway [13].1. 2. 3. and also to propose future Figure 1 e Black garlic. fresh garlic lies in the conversion of phytochemical com. Japan. chewing. In the following conditions during thermal processing. and applications of BG.5% of fiber [9]. such as its antidiabetic. bioactivity. owing to the fact that fructose and alkane-thiosulfinates such as allicin [11]. At the same time.

In particular. but also other factors such amount of reducing sugar at high-temperature conditions as humidity and fermentation [23. we will sum- Components of black garlic Original marize the quality of fermented BG and its potentials against compared with fresh garlic concentration several kinds of diseases. Even though BG is produced faster at 90 C. according Table 1 e Comparison between the components of black to the discovery of Jung et al [25]. BG becomes too HFD-induced obesity. which means that at these tem. ABG does not have an appro. in the case of processing at 60 C. low-density li- nonideal tastes.88e7. Bio- Polyphenol Increased 4.77-fold [13] 3. and fermented BG occurs smoothly at 80 C and 90 C. the intense HMF content increases very slowly during the whole process. produced by fermenting whole raw garlic at a controlled high temperature and under As we mentioned in the previous section.25].64 mg/100 g Tyrosine Decreased 0. the differences of the components between ABG factor during the aging process. reducing sugar content gradually increases at 60 C and 70 C In summary.31].91 mg GAE/g Flavonoid Increased 4. amino acids are required for Maillard reaction [24]. However.19-fold [13] 13.06-fold [13] 58. an adequate condition is may be more qualified to improve diabetes and its related relatively difficult to find because of its fluctuating phenol complications. One of the main antioxidant compounds in BG is 5- hydroxymethylfurfural (5-HMF). alanine transaminase (ALT).01-fold [1] 580 mg/g recent years.43-fold [13] 55. and hepatopathy than ABG. In other be much drier and its elasticity would be poor.58-fold [13] 81. Regardless of temperature. Moreover. Owing to this reason. taste and smell of fresh raw garlic make it difficult for most people to appreciate it [30]. hepatocyte hypertrophy. reduction of amino acid content is also acceler. For example. However. In Fructan Decreased 0. further in- [23]. it produces nesses.64 j o u r n a l o f f o o d a n d d r u g a n a l y s i s 2 5 ( 2 0 1 7 ) 6 2 e7 0 temperature during thermal processing.27]. such as bitter and sour tastes [23]. RE ¼ rutin equivalents.2. the amount of 5-HMF is increased during the Garlic is used for seasoning food. high-density lipoprotein (HDL) level. aging process. nephropathy. Phenylalanine Increased 2. Based on reducing sugar increases at high temperatures. the bioactivity of BG is markedly slow when processed at 60 C. and hard to eat [23]. fermented BG 400 mg/kg and 200 mg/kg revealed elasticity. Therefore. words. the color of garlic was not completely aspartate transaminase (AST). Water-soluble Increased 1. Therefore. they hypothesized that the bioactivity of BG may Cysteine Decreased 0. vestigations are also required.62 mg/100 g tivity of ginseng could be enhanced by yeast fermentation. serum total cholesterol. temperature. The their component analysis should be required. and it is also an important 4.06 mg/100 g also be enhanced by yeast fermentation.95 mg/100 g According to Jung et al [25]. yeast-fermented BG exhibited much better bioactivity against syndromes such as obesity. Bioactivity of BG intermediate product in Maillard reaction [23]. Some types of sugar and and fermented BG have still not been investigated. nitrogen (BUN). yeast-fermented garlic-treated mice demonstrated According to sensory evaluation. the quality of BG is better marked improvement in body weight. the quality of BG controlled high humidity [4. in the case of the results mentioned above. ated depending on the progress of Maillard reaction [23]. However. GAE ¼ gallic acid equivalents. In the case poprotein (LDL) level. Therefore. effective bioactivity than ABG. hyperlipidemia. Therefore. mented BG might be more or less different from those of ABG. 70 C is considered the best processing at 80 C and 90 C. and the antiox- Heyns idant activity of garlic could be enhanced by processing. Hien-Trung et al [28] discovered that the bioac- Leucine Increased 1. the aging speed of fresh garlic to BG hepatopathy than ABG [25]. Table 2 summarizes the cur- including its bioactivity and texture depends on the rent findings of bioactivity of BG. deposited abdominal fat pad thick- [23]. Isoleucine Increased 1. compared with the high-fat diet (HFD)-treated controls. BG can be suitable for eating because of its softness and Furthermore.15e0. Effects of fermentation condition on the quality of lations have been developed.91-fold [1] 450 mg/g Improvement of antioxidant activity will effectively pre- sugar vent diabetes and its related complications [26. black.04 mg/100 g Therefore. hyperlipidemia.18-fold [13] 449. the rate of formation of reducing sugar is faster ponents might be difficult at a high temperature because their than its rate of consumption. the aging period of BG is shorter at a high during the whole process. Although the content of contents change rapidly during the aging process. ABG is one of the useful garlic BG types with an odorless character. and the number of abnormal kidney tubules When the moisture content of garlic reaches 400e500 g/kg. BG would significantly higher effects than ABG 400 mg/kg. however. the components of fer- content and reducing sugar content [23].67-fold [13] 50. However. thus. fermented BG has more effective bioactivity against when moisture content goes below 350 g/kg. controlling the amount of some com- peratures. especially in Asian countries. the quality of BG is priate sweet flavor because of the consumption of a large affected by not only temperature. of aging process at 60 C. fermented BG displays more and fresh garlic. periovarian fat weight. If moisture content is about 350e400 g/kg. different garlic formu- 3. and its black color is homogeneous between 70 C and 80 C adipocyte diameters. 5. serum blood urea process. . Content of reducing sugar is also considered an important However.22 mg RE/g activities of garlic such as antioxidant activity and Amadori & Increased 40e100-fold [1] 10 mg/g hypoglycemic effect are already well known. Although aging could be enhanced by yeast fermentation. condition for garlic aging. 60 C is also not an ideal condition for the aging steatohepatitis. Besides. In this section. nephropathy. and it has lots of health benefits [29]. triglyceride.

and then blended. GSH-Px. as revealed by the activity than fresh garlic by DPPH and 2.1.25] abdominal fat pad thickness. PGE2. The BG extract had more 4. NO synthase. SAC.2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) assays which is converted into a stable compound.32]. Alliin is an unstable compound in fresh garlic. DPPH ¼ 1. LDL level.5 mmol/g wet weight). and NF-kB in TNF-a-stimulated HUVECs Y Cell proliferation. and finally at 55e65 C for radicals in ABG (59. and LDH levels and [ CYP2E1. Fresh garlic garlic and 90% ethanol extract of BG [35]. 5-LO ¼ 5-lipoxygenase. SOD ¼ superoxide dismutase. abdominal fat weight.7 macrophages Y TNF-a and IL-6 in LPS-induced lethal shock in C57BL/6 mice Antiallergic activity Y b-Hexosaminidase. and CAT activity Anticancer activity [ Apoptosis in human leukemic U937 cells [4. Seventy [32].8 mmol/g wet weight) is more than 72e120 hours. GSH-Px ¼ glutathione peroxidase. et al [32] reported that the decrease in the number of free then at 60e70 C for 72e120 hours. EDA ¼ electron-donating ability. triacylglyceride. CAT ¼ catalase. ALP ¼ alkaline phosphatase. LPS ¼ lipopolysaccharide.47e48] monocyte adhesion. Both garlic and ABG were extracted with garlic extract in vitro [19]. Y PCA reaction on IgE-mediated passive cutaneous anaphylaxis reaction in mice Alleviating dyslipidemia [ HDL-c level [54] Y apo B ABTS ¼ 2. cyclooxygenase-2. NF-kB ¼ nuclear factor kB.40e41.1. cyclooxygenase-2. Biological activities Biological effects References Antioxidant activity Y Free radical (the trolox equivalent antioxidant capacity [TEAC]. VCAM-1. and CAT activities in ethanol-induced oxidative liver damage in rats Y Decreased ALT and AST levels in carbon tetrachloride and D- galactosamine-induced liver damage in rats. prostaglandin E2 (PGE2). GSH-Px. AST ¼ aspartate transaminase. at 70e80 C for another 48e60 hours. as detected by enging activity than 70% and 90% ethanol extracts of raw the in vitro electron-donating ability assay [25]. HDL-c ¼ high-density lipoprotein cholesterol. LDL ¼ low-density lipoprotein. undergoes 40 days of fermentation at 60e70 C and 85e95% relative humidity to produce BG. j o u r n a l o f f o o d a n d d r u g a n a l y s i s 2 5 ( 2 0 1 7 ) 6 2 e7 0 65 Table 2 e Biological activities of black garlic. cell cycle progress. LDH ¼ lactate dehydrogenase. and in HFD-induced fatty liver and subsequent liver damage model in C57BL/6 mice Anti-inflammatory activity Y ROS formation. glutathione reductase (GR). and 5-LO in RBL-2H3 [7] cells.2 ± 0.19. TNF-a ¼ tumor necrosis factor-a. during the in vitro. TNF-a. ICAM-1. ICAM-1. TNF-a.3 ± 0. and HepG2 (hepatocarcinoma) cells Y Tumor volume and weight in SGC-7901 human gastric cancer cells [ Apoptosis and cell cycle arrest in HT29 colon cancer cells Antiobesity activity Y Body weight. and HDL level in HFD- induced rats Hepatoprotective activity Y AST. glutathione S-transferase.2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid). TBARS ¼ thiobarbituric acid reactive substances.34e36] DPPH. HESC ¼ human endometrial stromal cell. ALP. and ABTS assay) in vitro [ SOD-like activity in vitro Y TBARS level in mice [ SOD. VCAM-1 ¼ vascular cell adhesion molecule-1. Antioxidant activity formulation containing 10% of BG extract had higher radical scavenging activity than the formulation containing 10% (v/v) The antioxidant activity of garlic is affected by the ways of of garlic extract by 1. PCA ¼ passive cutaneous anaphylaxis. ABG also showed stronger antioxidant that in garlic (13. VCAM-1. EDA. HUVEC ¼ human umbilical vein endothelial cell. The human monocytic cell line (THP-1) [6. triacylglyceride. AGS (stomach adenocarcinoma).25.000g . Extracts between fresh garlic and BG than 10-fold increase in superoxide dismutase-like activity Garlic and ABG were peeled off. IgE ¼ immunoglobulin E. and [ HDL level in HFD-induced mice Y Weight gain and epididymal fat. and activator protein-1 (AP-1) in TNF-a-activated HESCs Y NO. Another study showed that 10 mg/mL of yeast-fermented percent ethanol extract of BG had higher DPPH radical scav- BG had stronger antioxidant activity than BG. 4. MCF-7 (breast adenocarcinoma). 2. ICAM-1 ¼ intercellular cell adhesion molecule-1. Lee 80e90 C for 48e90 hours.39] quinone reductase.1. ALT ¼ alanine transaminase. [38. mixed with 10 volumes of and scavenging activity against hydrogen peroxide compared water. and NF-kB in LPS-stimulated RAW 264. NF-kB. Kim et al [34] showed that the with water for 1 hour at 80 C and then centrifuged at 14.31. [3.35e37] [ Cytotoxicity in human carcinoma A549 (lung carcinoma).2-azino-bis-(3- trolox equivalent antioxidant capacity (TEAC) assay in vitro ethylbenzothiazoline-6-sulfonic acid) assays [3].1-diphenyl-2-picrylhydrazyl. HDL ¼ high-density lipoprotein. HFD ¼ high-fat diet.32.1-diphenyl-2-picrylhydrazyl (DPPH) and processing [42]. abdominal adipocyte diameters and [5. ALT. ABG was obtained from fresh garlic fermented at aging process and exhibits antioxidant activity [11.

The authors further demonstrated the anticancer ability in tion was obtained from BG that was blended with 10 volumes the tumor-bearing mice model. The mice were also given 100 mg/kg of pathways in human leukemic U937 cells [4]. and suppressed the their livers were collected for further evaluation of the anti. and hepatocyte diameters compared with the anticancer activity in human leukemic U937 cells. the and 100 mg/mL ABGE could induce apoptosis in the cell [36]. Therefore. The suspended ABG was extracted in showed that ABGE decreased tumor volume and weight. HEABG-inhibited cell growth also induced the extrinsic pathway of apoptosis via activated caspase-8. Male SpragueeDawley rats were divided into (2.1. ALT. and for different hours. and serum AST and ALT levels [45].5% (w/v)] also showed decreased triacylglyceride in the ribose)-polymerase in a concentration.2. and HepG2 (hepatocarcinoma) ted by heating with water twice under reflux at 80 C and the cells in a dose-dependent manner within 72 hours [35]. the 4. At the end of experiment.2. 5 mg/mL.4. and LDH (lung carcinoma). functional fermented BG also decreased serum triacylglyceride and LDL food could block these six characteristics due to their anti. and the phenomena of liver activity [33]. Colon cancer ABGE (20 mg/mL.2. (stomach adenocarcinoma). by measuring lipid peroxides and antioxidant enzymes in the liver. were significantly decreased by ABG compared with . BG and yeast- and activated invasion and metastasis. 7 mg/mL. mice were sacrificed and downregulated Akt and p-Akt expression. The plasma markers of (500 mg/mL) caused cytotoxicity in human carcinoma A549 liver function and injury. but ABG further increased the catalase (CAT) heart disease. 400 mg/kg. 4. levels. HFD.5% BG extract group had decreased weight gain increasing the Bax/Bcl-2 protein expression ratio.2. including AST. thickness compared with the HFD group. 50 mg/ the cells [25]. The results showed that upregulation of death receptor 4 and Fas ligand. mRNA and protein levels of the downstream target 70-kDa oxidant activity of garlic and ABG. ALT. The ethanol also increased serum superoxide dismutases and glutathione extract of BG was obtained by fermenting raw garlic at 75 C peroxidase in the tumor-bearing mice model. Another yeast-fermented BG was extrac. and fed with normal food diet. and increased serum HDL level compared with the HFD cancer ability [43]. evaded growth suppressors. liver disease. The hexane extract of ABG (HEABG) had demonstrated its steatohepatitis.and time-dependent serum and liver and an increased HDL level in the serum [5]. BG and yeast-fermented BG decreased serum AST. The anticancer and 70% relative humidity for 4 weeks. BG was fermented with Saccharomyces cerevisiae (KCTC 7910). BG extract activated caspase-9 and caspase-3.5 mg/mL. resisted cell abdominal adipocyte diameters. ALP. changes in liver weight. 200 mg/kg.5% or 1. and it distilled water at 80e100 C for 2e6 hours [3]. and HFD þ growth by inducing the intrinsic pathway of apoptosis via 0. and 100 mg/mL in SGC-7901 human gastric cancer cells freeze dried and pulverized in 80% ethanol solution. The BG obtained after 40-day fermentation was mL.66 j o u r n a l o f f o o d a n d d r u g a n a l y s i s 2 5 ( 2 0 1 7 ) 6 2 e7 0 for 15 minutes [32]. damage. and 100 mg/mL) also exhibited 4. filtrate obtained was garlic extract [19]. Antiobesity activity substance level and increased the activities of superoxide dismutase and glutathione peroxidase compared with the Obesity is an inducer of other diseases such as type 2 diabetes. group. 4. Human gastric cancer culture solutions were extracted by heating after removing The ABG extract (ABGE) was treated with 10 mg/mL. ABG was Kunming mice incubated with murine forestomach cells for obtained from fresh garlic incubated at different temperatures 1 week and then treated with 200 mg/kg. 70% or 90% ethanol two times for 6 hours or 12 hours at 50 C or 90 C [35].5% BG extract for 5 weeks. Hepatoprotective function resulting in the truncated Bid expressed. significantly decreased body weight. including hyperlipidemia[44]. abdominal fat weight. The authors used male of water and then extracted at 80 C for 1 hour [34]. ative signaling. Inhibition of cancer cell line growth with 45%/kcal of HFD for 28 days and then the mice were given 400 mg/kg BG and 100 mg/kg. Garlic and ABG decreased the thiobarbituric acid reactive 4. enabled replicative immortality. The 10% BG formula. and rats from the 1. 50 mg/mL. AGS levels. control group. ABGE upregulated PTEN and 7 weeks. and abdominal fat pad death. MCF-7 (breast adenocarcinoma). Later. ABG by oral gavage. BG was extracted with ability of ABGE may vary from its antioxidant activity [36]. Female Institute for Cancer Research (ICR) mice were fed 4. The results of distilled water.2. Male SpragueeDawley rats were fed with ethanol to induce dependent apoptosis through both intrinsic and extrinsic oxidative liver damage. The analysis was conducted ribosomal protein S6 kinase 1 [37]. HEABG showed its potential for anticancer ability by inducing caspase. ABGE inhibited Male db/db (þ/þ) C57BL/KsL mice were divided into three HT29 cell growth through apoptosis and cell cycle arrest via groups. HEABG HFD group [25]. Animal study anticancer ability in HT29 colon cancer cells. Then ABG was suspended in five volumes 800 mg/kg ABGE by intraperitoneal injection. and 10 mg/mL) inhibited cell four groups. After fermentation. BG and yeast-fermented BG development of human tumors including sustained prolifer. initial yield rate was 12.3. manner.1. The results showed that ABG decreased Another study showed that 70% ethanol extract of BG body weight and total fat pad weight. The control group was fed with an AIN-93G diet and the phosphatidylinositol 3-kinaseprotein kinase B (PI3KAkt) an AIN-93G diet with 5% freeze-dried garlic or ABG for signal transduction pathway. [1.8%. HEABG also and epididymal fat compared with the HFD group. induced angiogenesis. and degraded poly(ADP. and 400 mg/kg of There are six characteristics of cancer during the multistep yeast-fermented BG for 63 days.

anaphylaxis and other acute allergic reactions. The authors fed the C57BL/6 mice 120 mg/ of C57BL/6 mice [39]. and catalase in the liver [38]. When WEAGE was added increased CYP2E1 expression and the activities of glutathione again at 15 hours before LPS was added to the cells. Water mice fed with HFD [25]. and activation of NF-kB tran. HEABG also had the potential to suppress the TNF.7. (50 mg/mL) suppressed cell proliferation and cell cycle progress 50 mg/mL of BG10 inhibited the formation of prostaglandin E2 via extracellular signaleregulated kinase (ERK) and c-Jun N. its anti- and AST levels in the liver in the carbon tetrachloride. inducing endo. arachidonic acid metabolites. Another study showed that 200 mg/kg ABG decreased ALT and cyclooxygenase-2 protein expression. glutathione level. At type I stimulated human umbilical vein endothelial cell (HUVEC) allergy responses as anaphylactic type can be activated by the model. the activities of glutathione manner in LPS-stimulated RAW 264. a general marker of degranulation. Reduction of blood lipid related to various inflammatory reactions [48]. such as TNF-a.53]. Chloroform extract (30 mg/mL) of ABG was pre. extract of ABG (WEAGE) did not show significant cytotoxicity Jung et al [54] showed that ABG could improve blood lipid up to 2000 mg/mL.7 macrophages via peroxidase. and heparin and it can release b-hex- and reduced THP-1 monocyte adhesion to TNF-a-stimulated osaminidase. and IL-6. Atherosclerosis is a chronic inflammatory disease of the arterial walls due to endothelial dysfunction. mation in asthma. activation of nuclear factor kappa B (NF-kB) transcription RBL-2H3 cells are used as a model for screening allergic re- factor in TNF-a-stimulated HUVECs [40]. BG10 (66. and the expression of cyclooxygenase-2 metriosis. BG10 was the active fraction from ethyl acetate extract of BG THP-1 monocyte adhesion. proteases. ylation of JNK and p38MAPK. triglycerides. downregulation of NO synthase and TNF-a mRNA expression. WEAGE 4. There is another research in which the MTT assay showed that raw Previous studies showed that BG improved serum lipid pro- garlic extract was highly cytotoxic at concentrations over files such as total cholesterol. actions in vitro and passive cutaneous anaphylaxis as an ani- The compound 5-HMF was found in chloroform extract of mal model for screening IgE-mediated allergic responses ABG and treated in TNF-a-stimulated HUVECs. which are 4. The result showed that WEAGE had less profiles in patients with mild hypercholesterolemia. the results S-transferase and quinone reductase were drug-metabolizing showed that WEAGE decreased the production of nitric oxide phase II enzymes and restored the thiobarbituric acid reactive (NO). and inhibited the activation of gueeDawley rats.7 cells. HEABG dase and TNF-a compared with other fractions. and HDL with 250 mg/mL with or without LPS in the RAW 264.7 mg/kg) given to mice by oral a-induced ICAM-1 and VCAM-1 transcripts and protein gavage for 1 hour decreased the passive cutaneous anaphy- expression via inhibition of the activation of NF-kB and AP-1 laxis reaction on IgE-mediated passive cutaneous anaphylaxis transcription factors [47]. increasing in many countries [49]. thelial activation via generation of reactive oxygen species Allergy is related to immunoglobulin E (IgE) antibodies and and augmenting the expression of cell adhesion molecules on mast cells have to respond to the pathophysiology of endothelial cells [41. Atherosclerosis is also related to More evidence showed that allergy diseases are influenced by increased oxidative stress caused by vascular inflammation environmental factors such as eating habits. number of allergy patients have been (TNF-a). Lots of evi- Previous researches showed that BG had antioxidant dence shows that IgE and mast cells have key roles in tissue ability [31. showing stronger inhibition of the release of b-hexosamini- scriptional factor in TNF-a-stimulated HUVECs [41]. in RBL-2H3 cells. inflammatory mechanism decreased LPS-induced phosphor- galactosamine-induced liver damage models of Spra. kg of WEAGE and raw garlic extract by oral gavage before injecting 20 mg/kg LPS (LPS-induced endotoxemia). It also decreased the ALT and AST levels in NF-kB and phosphorylation in response to LPS-stimulated HFD-induced fatty liver and subsequent liver damage model RAW 264. expression of vascular cell adhesion molecule-1 (VCAM-1).6. and phosphorylation of Syk. Ethyl acetate extract of BG (2 mg/mL) inhibited the total protein and mRNA expression of VCAM-1 and intercel. GR.46]. HUVECs. and interferon-g. IL-1b. BG10 also terminal kinase (JNK) pathways in TNF-a-activated human decreased the phosphorylation of cytosolic phospholipase A2 endometrial stromal cells isolated from patients with endo. high-affinity IgE receptor (Fc3RI receptor) on the plasma treated in TNF-a-stimulated HUVECs. Lipopolysaccharide (LPS) is an endotoxin that induces several cytokines. Immunomodulatory effect decreased the level of TNF-a and IL-6 in the serum against LPS-induced lethal shock in C57BL/6 mice [6].32]. and formation of atheromatous plaque within the intima of the vessel wall. j o u r n a l o f f o o d a n d d r u g a n a l y s i s 2 5 ( 2 0 1 7 ) 6 2 e7 0 67 those in the group treated with ethanol alone. stress. In fact. Sixty . Furthermore. reaction in mice [7].7 cells. and 5-lipoxygenase. vascular 4. surface. Chloroform extract of ABG also inhibited the mast cells have an important role in allergic reactions [50. Moreover. TNF-a. Allergy is classified into five types. LDL. It also inhibited reactive oxygen species formation. and living with various cytokines. Antiallergic action inflammation. Moreover. It suppressed [52.51]. Dr Yoon's group had been investigating the remodeling that is associated with chronic allergic inflam- effect of different extraction methods of ABG in the TNF-a.and D. release of b-hexosaminidase and TNF-a that inhibited IgE- lular cell adhesion molecule-1 (ICAM-1) in TNF-a-induced cell mediated allergic responses in RBL-2H3 cells. including tumor necrosis factor-a environment. serotonin.5. Therefore. interleukin (IL)-1b. ABG also cytotoxicity than raw garlic extract. This ABG extract membrane of mast and basophilic cells as an intragranular inhibited reactive oxygen species formation and mRNA mediators such as histamine. and prostaglandin-E2 in a dose-dependent substances. and leukotriene B4.

the exact chemical compound which have bioactivity are still sitive to the effects of MSG because of its high content of not investigated. NF-kB activation. Furthermore.81:C1662e8. The comparison of the VCAM-1 is activated by cytokines such as TNF-a and IL-1 in contents of sugar. Therefore. hexane extract of BG could be effective in Purkinje cells in the cerebellum and hippocampus [57. Since garlic has long been consumed in the to its higher polyphenol level and scavenging activity human society and has been recognized as one of the safe [56. According to supplements. bella of rats. there will be no constraints for further ethanol extract of BG on the nervous and memory systems invention of BG products for such functional food. both with or without MSG. Therefore. procedure. Serum apo B (atherogenic lipoprotein) is an extracts on TNF-a-related diseases. Chen M. the compound analysis of them polyunsaturated fatty acids. Wang J. 5-HMF. As effective in preventing and treating atherosclerosis. further studies are required to Taiwan (No.However. J Food Sci 2016. and low anti. and Heyns compounds in fresh the endothelium. One was given 6 g atherosclerosis through the adhesion of monocytes in the ABG and the other was given placebo twice per day before a endothelium. the combined administration of Conflicts of interest BG extract and MSG improved the reduction of the number of Purkinje cells compared with MSG only [64]. The authors would like discover whether a higher dosage of MSG can affect the to thank Mrs Qian-Wen Shang. To sum up. some researchers reported that endometrial stromal cells in humans. Influences on memory and nervous systems is purified from BG. Further- cerebellum and the hippocampus play an important role in more. Moreover. Influence of BG on TNF-a-related inflammation diseases references Accumulation of monocytes in the vessel wall is primarily induced by specific cell adhesion molecules such as VCAM-1. 4. independent and high predictive risk factor for coronary ar.9. MSG might have adverse effect on various organs including In summary. The preventing and treating endometriosis in humans. although the dosage of MSG may not be adequate to show significant reduction of the number of Purkinje cells. All authors declare no conflicts of interest. Some researchers investigated the effects of the food substances. . Furthermore. ABG increased HDL of cell adhesion molecule. BG-treated rats had significantly atic and efficient process for manufacturing BG is important shorter escape latencies and path lengths than the control since it is crucial to control the changes in metabolite levels rats. These are regulated by the ABG group did not show significant differences in triglyceride. which 4. expression of cytokines and chemokines. these cell adhesion molecules can meal every morning and evening for 12 weeks. the brain is expected to be one of the organs most sen. chloroform extract of BG and 5-HMF could also be the nervous system and the memory system. Furthermore. Although the result in endometriosis [42]. total cholesterol. cies production. should be required. Following are the influences of BG of the study [54]. ICAM-1. However.8. who received her bachelor number of Purkinje cells. and endothelial cell selection [40]. degree of English from National Chengchi University. Conclusion but also as a food that has high potential antioxidant ac- tivity. could also suppress cell adhesion mole- cules that are activated by TNF-a [41]. food using a Wistar rat model with MSG [63.62]. þGarlic has been known not only as a flavor enhancer.64]. the antioxidant activity of BG is Apparently. or free fatty acid levels Although TNF-a is well known as an inducer of expression compared with the placebo group. In conclusion. and adhesiveness to monocytes were also improved [40]. BG might play an important role in improving some diseases as well as the functions of the memory and nervous systems due to its potential antioxidant activity. Amadori. In particular. Acknowledgments However. in several trials of the during the fermentation process for industrial-level mass nonvisible platform test of the Morris Water Maze (MWM) production.05) than that of fresh garlic due with fresh garlic. This phenomenon could be attributed to and black garlic. and has been extract of BG could reduce the expression of cell adhesion used for seasoning all over the world due to its attractive molecules such as ICAM-1 and VCAM-1 in TNF-a-activated umami taste [56]. and the hard-to-replicate quality of its neuronal cells [59e61]. In particular. the current dosage of MSG may not be able to significantly reduce the number of Purkinje cells in the cere- This project was funded by the National Science Council. Sun L. Reactive oxygen spe- decreased serum apo B [54]. 5. Chloroform extract of BG could suppress cell adhesion tery disease [55]. it is. hexane Monosodium glutamate (MSG) is well known. respectively. high metabolism. ABG supplement significantly molecules that are activated by TNF-a. BG exhibits several advantages when compared significantly higher (p < 0. [1] Yuan H.68 j o u r n a l o f f o o d a n d d r u g a n a l y s i s 2 5 ( 2 0 1 7 ) 6 2 e7 0 participants were divided into two groups. oxidant capacity. LDL cholesterol. A more system- Hermawati et al [63]. it is deeply involved in the inflam- cholesterol levels compared with the placebo group at the end mation reaction in humans. 104-2221-E-002-125-MY3).58]. as well as medical purposes. for En- glish editing.

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