A Review of Component and Pharmacology Activities of Black Garlic

Abstract

Black garlic is garlic fermented in high temperature and humidity, and the fermentation compound chemical in garlic changes to new chemicals, such as S-allyl cysteine (SAC), S-allylmercapto-cysteine, and arginine. The color changed to dark brown during the aging period because of the Maillard reaction, known as non-enzymatic browning reaction. Black garlic has 57.14% of fructose, 6.78% of glucose, and 7.62% of sucrose, which were mainly saccharides in black garlic to answer for its sweet taste. It is such a pharmacological activity which contains antioxidant, anti-cancer, hepatoprotective, can improve the immune system, reduce hyperglycemia, dyslipidemia, and anti-allergic. We summarize the current knowledge of a change in the components, bioactivity, production, and applications of black garlic, as well as the proposed future prospects on their possible applications as a functional pharmacy product.

Full text

Trad. Med. J., September-December 2019
Vol. 24(3), p 178-183
ISSN-p : 1410-5918 ISSN-e : 2406-9086
178 DOI: 10.22146/mot.45277 | Traditional Medicine Journal, 24(3), 2019
Submitted : 22-04-2019
Revised : 09-11-2019
Accepted : 20-11-2019
A Review of Component and Pharmacology Activities of Black Garlic
Novitaria Sembiring1,2*, Yoppi Iskandar2
1 Master Program of Pharmacy, Faculty of Pharmacy, Universitas Padjajaran, Sumedang, Indonesia
2 Department of Biology Pharmacy, Faculty of Pharmacy, Universitas Padjajaran, Sumedang, Indonesia
ABSTRACT
Black garlic is garlic fermented in high temperature and humidity, and the fermentation compound
chemical in garlic changes to new chemicals, such as S-allyl cysteine (SAC), S-allylmercapto-cysteine, and
arginine. The color changed to dark brown during the aging period because of the Maillard reaction, known
as non-enzymatic browning reaction. Black garlic has 57.14% of fructose, 6.78% of glucose, and 7.62% of
sucrose, which were mainly saccharides in black garlic to answer for its sweet taste. It is such a
pharmacological activity which contains antioxidant, anti-cancer, hepatoprotective, can improve the
immune system, reduce hyperglycemia, dyslipidemia, and anti-allergic. We summarize the current
knowledge of a change in the components, bioactivity, production, and applications of black garlic, as well
as the proposed future prospects on their possible applications as a functional pharmacy product.
Keywords: Antioxidant; Black garlic; Immune system; S-allyl cysteine;
INTRODUCTION
Indonesian had long consumed garlic as
traditional medicine. For instance, the Baduy
ethnic who consumes 3 cloves of garlic to treat high
blood pressure. To deal with gout and rheumatism
ethnic, Batak uses finely ground garlic with salt
then rub on the affected part. In the ethnic of
Talang Mamak, garlic gutters are used to treat
diarrhea, while ethnics in Palembang uses garlic oil
to cure abdominal pain, swollen flatulence,
shortness of breath, vomiting, lumbago,
miscarriage (Moelyono, 2004). Asian countries
such as South Korea, Japan, and Thailand, has
consumed black garlic as food for centuries, for it
tastes sweeter, more jelly-like, and the odor is not
like garlic.
Black garlic is fresh garlic fermented in high
temperatures and humidity. It contains DL-Lactic
acid, 5-hydroxymethyl-2-furfural, adenosine,
uridine, (1S,3S)-1methyl-1,2,3,4-tetrahydro-β-
carboline-3-carboxylic acid, (1R,3S)-1methyl-
1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid,
and 2-Acetylpyrrole, which have higher
antioxidant (Lu et al., 2017). Concentration alliin
content in the black garlic sample decreases
because alliin converted into S-allyl cysteine (SAC),
S-allylmercapto-cysteine, arginine, and other
undefined compounds when subjected to thermal
processing (Zhang et al., 2015). The amount of SAC
in black garlic is generally five to six times higher
than that in fresh garlic and is thought to have the
beneficial effects of black garlic.
Pharmacological activities such as lowering
cholesterol, anti-allergic, high antioxidant activity,
*Corresponding author : Novitaria Sembiring
Email : novitaria18001@mail.unpad.ac.id
can improve the immune system, inhibit HT29 cell
growth in colon cancer, anti-tumor, reduce
hyperglycemia, dyslipidemia, hepatoprotective,
and induce apoptosis in cell human leukemia U937
(Tran et al., 2018). The main focus of this study is
to summarize the current knowledge of the
component of black garlic and activity
pharmacology.
To cause extracellular matrix accumulation
by enhancing the mesangial cell production of COL
and FN, TGF-β mediated fibronectin is expressed in
mesangial cells (Uchiyama-Tanaka et al., 2002).
Reactive Oxygen Species (ROS) also underlies as a
common pathogenic component and accelerates
kidney disease progression and complications
(Dounousi et al., 2006). Soybean seed showed an
antioxidant effect and an antifibrotic effect in the
remnant kidney, which resulted in the
improvement of the renal function. Oxidative
stress is regulated by the balance between
prooxidant and antioxidant systems (Peng et al.,
2017; Hayata et al., 2012).
Soybean seed (Glycine max L. Merr) has been
known for its beneficial effects in health due to its
compounds. Previous studies reported that
soybean contains antinutritional factors (ANF)
which include lipase inhibitors, protease
inhibitors, amylase inhibitors, oxalic acid, phytic
acid, glucosinolates, flavonoid, and saponin. The
ethanol extract of soybean also known to contain
natural compounds such as flavonoid, phenolic,
triterpenoid, saponin, steroid, tannin, and quinone
(Gemede and Ratta, 2014). In this study, we used
Glycine max L. merr ethanol extract (EEDS) to
evaluate the potency for therapy chronic kidney
disease due to the measure of cytotoxic effects,

A Review of Component and Pharmacology Activities of Black Garlic
Traditional Medicine Journal, 24(3), 2019 179
fibronectin, TGF-β1, and ROS-DCFDA inhibition
potential of EEDS on glucose-induced Mesangial
cells (SV-40).
Component of Black Garlic
Color is one of the most important
psychological properties of food products that
affect the perception of eating in consumers, clarify
how black garlic (BG) changes during the 35-day
aging were evaluated under controlled conditions
of 70oC and 90% relative humidity. Lightness and
yellowness values of black garlic radically
decreased during the aging period, whereas
redness values increased significantly. The color of
black garlic changed to dark brown during the
aging period, whereas the pH decreased
continually from 6.25 to 4.25, which contributed a
characteristic black appearance and a sour taste
mouthfeel. Color changes and decrease of pH
resulting from heat treatment are typically due to
the Maillard reaction, known as non-enzymatic
browning reaction. It is same with (Zhang et al.,
2015), the contents of alliin and polysaccharides
black garlic decreased significantly after 10 days of
heat treatment heating at 70-800C because of alliin
content black garlic converted into SAC, S-
allylmercapto-cysteine, arginine, and other
undefined compounds when subjected to thermal
processing, whereas the content of reducing sugars
increased correspondingly. The 57,14% of
fructose, 6,78% of glucose and 7,62% of sucrose
were mainly saccharides in black garlic to answer
for its sweet taste.
Antioxidant components, including the
polyphenol and total flavonoids contents of BG,
increased significantly until 21st day of aging
(p<0,05) and correspondingly, the antioxidant
activities of BG, measured by DPPH, ABTS, FRAB,
and reducing power assays, were highest on the
21st day of aging (Sook et al., 2014). Aged black
garlic extract (ABGE) which has the strongest
antioxidant effects among garlic extract.
Among the five black garlic fractions extracted
by chloroform and methanol mixed at different
ratios, F3 and F4 showed the strongest antioxidant
activities in a DPPH system. Seven substances were
purified from F3 and F4 are DL-Lactic acid, 5-
hydroxymethyl-2-furfural, adenosine, uridine,
(1S,3S)-1 methyl-1,2,3,4-tetrahydro-β-carboline-
3-carboxylic acid, (1R,3S)-1 methyl-1,2,3,4-
tetrahydro-β-carboline-3-carboxylic acid and 2-
Acetylpyrrole (Table I).
ACTIVITY PHARMACOLOGY
Antioxidant effect
Sasaki et al., (2007) compare activity
antioxidant extracts fresh garlic and black garlic
from Japanese and Chinese using DPPH (Table II).
Potency antioxidant aged black garlic extracts both
countries increased, even activity aged black garlic
extracts Japanese reached 28-fold more compared
with that of fresh garlic.
Jeong et al., (2016) reported the antioxidant
capacity extract ethanol 70% fresh garlic and aged
black garlic using four different approaches;
exhibited increased the electron-donating ability,
ferricyanide reducing power and hydroxyl radical
scavenging activity. At a concentration of 0,2
mg/mL and 2 mg/mL, the aged garlic extract
exhibited a marked increase in the electron-
donating ability 2-fold more than fresh garlic.
Then, the ability reducing the power of black garlic
0,2 mg/mL and 2 mg/mL 7-fold more than fresh
garlic, even reducing the power of fresh garlic at 2
mg/mL is 0,43±0,01 similar with the black garlic at
a lower concentration of 0.2 mg/mL is 0,42±0.00
(Table III).
Lee et al., (2009) determined the
antioxidant effect in vivo of garlic and aged black
garlic, an animal model of type 2 diabetes that
shows insulin resistance, hyperglycemia, and
obesity. Consumption of aged black garlic
significantly increased insulin levels, decreased
serum glucose, decreased homeostasis model
assessment for insulin resistance (HOMA-IR) and
decrease serum glucose levels than garlic.
Figure 1. Change color of garlic during 35 days (Choi et al., 2014)

Novitaria Sembiring
180 Traditional Medicine Journal, 24(3), 2019
Table I. Structure Compound Black Garlic (Liang et al., 2015 and Zhang et al., 2015)
Name
Structure
S-allil sistein
Aliin
Alicin
DL-Lactic acid
5-hydroxymethyl-2-furfural
Adenosine
Uridine
(1S,3S)-1 methyl-1,2,3,4-tetrahydro-β-
carboline-3-carboxylic acid
(1R,3S)-1 methyl-1,2,3,4-tetrahydro-β-
carboline-3-carboxylic acid
2-Acetylpyrrole

A Review of Component and Pharmacology Activities of Black Garlic
Traditional Medicine Journal, 24(3), 2019 181
Anti-Cancer Activity
Dong et al., (2014) reported aged black
garlic extracts (ABGE) may regulate the function of
the PI3K/Akt pathway through upregulating PTEN
and downregulating Akt and p-Akt expression, as
well as suppressing its downstream target, 70-kDa
ribosomal protein S6 kinase 1, at the mRNA and
protein levels. The HT29 cells growth inhibition
rate at ABGE concentrations of 20, 50, and 100
mg/mL. ABGE inhibited the growth and induced
apoptosis in HT29 cells through the inhibition of
the PI3K/Akt pathway. Numerous studies
demonstrated that allicin, an organosulfur
compound obtained from garlic, has the ability to
promote the apoptosis of tumor cells, cause cell
cycle arrest and improve the antioxidant activity.
Qian et al., (2004) reported the tumor cure rate by
black garlic water extracts attained 50% against
Meth A fibrosarcoma of BALB/c mouse by intra-
tumor injection of 1 mg extracts, three times every
other day. By contrast, fresh garlic extracts (FGE)
used as a reference, failed to induce tumor-free
animals, even though the reduced tumor size to
60% to compare with the tumor mass in a non-
treated control mouse. That garlic organo-sulfur
compounds test (5-100 µM) worked to protect
against DNA damage (Belloir et al., 2006).
Park et al., (2014) reported U937 cells were
exposed to various concentrations of hexane
extract aged black garlic (HEABG) for 24 h or 10
µg/mL of HEABG for the indicated times. The MTT
assay was used to examine the effect of HEABG on
cell viability. Resulted showed that the viability of
HEABG-treated cells decreased in time and
concentration-dependent manners. Consistent
with these effects, after treatment with HEABG,
U937 cells showed changes in morphology,
including blebbing of the cell membrane and
shrinkage of the cells, in a time-dependent manner.
HEABG-induced apoptosis signaling pathway in
human leukemia U937 cells. First, the death
receptor-mediated extrinsic pathway is initiated
by ligation of the transmembrane death receptor to
activate effector caspases, such as caspases-3.
Second, the mitochondrial membrane, which
induces activation of caspase-9, and thereby
initiates the apoptotic caspase cascade. Gastric
cancer is one of the most common human
malignant tumors. Epidemiological investigations
have provided evidence that gastric carcinogenesis
is a complex, multistep and multifactorial event
(Nagaoka et al., 2009). Wang et al., (2012) reported
that ABGE treatment inhibits the growth of SGC-
7901 cells by inducing apoptosis in vitro. Flow
cytometry (FCM) with PI staining revealed that the
apoptosis rates of SGC-7901 cell line treated with
10, 50 or 100 mg/ml ABGE for 48 h were
10.9±3.9%, 16.7±4.8%, and 22.7±5.8, respectively
and were significantly higher than that in the
negative control. ROS are also involved in the
pathogenesis of gastric malignancies. To date, the
correlation between the administration of ABGE
and its effect on the status of SOD and GSH-Px has
yet to be fully investigated. The activities of SOD
and GSH-Px were significantly increased by the
administration of ABGE in an animal model.
Hepaprotective Activity
Wang et al., (2012) report aged black garlic
(ABG) caused a significant decrease in the alcohol-
Table II. Activity antioxidant black garlic every country (Sasaki et al., 2007)
Sample
RS50%a
Aged black garlic
Japanese
4,1
Chinese
7,3
Fresh garlic
Japanese
114,9
Chinese
88,5
an mg used to reduce 50% of 1,1-diphenyl-2-picrylhydrazzy
Table III. 1,1-diphenyl-2-picrylhydrazyl and hydroxyl radicals scavenging activities, ferricyanide power and
ferrous ion-chelating ability of fresh garlic and aged black garlic extracts (Jeong et al., 2016.
Fresh garlic
Aged black garlic
0.2 mg/mL
2 mg/mL
0.2 mg/mL
2 mg/Ml
Electron-donating ability (%)
8.70±0.34
35.10±0.66
19.79±0.22
82.53±0.47
Reducing power (OD 700 nm)
0.06±0.02
0.43±0.01
0.42±0.00
2.60±0.01
(-OH) scavenging ability (%)
24.45±0.22
60.72±0.20
60.85±0.36
74.95±0.68
Fe2+ chelating ability (%)
46.04±0.94
30.62±1.35
29.54±1.15
18.24±0.86

Novitaria Sembiring
182 Traditional Medicine Journal, 24(3), 2019
induced increase in hepatic activities of aspartate
aminotransferase, alanine, aminotransferase,
alkaline phosphates, and lactate dehydrogenase.
ABG treatment significantly decreased the
thiobarbituric acid–reactive substances level in the
liver, heart, and plasma. Glutathione content and
the activities of antioxidant enzymes such as
glutathione peroxidase, glutathione reductase, and
catalase in liver were significantly enhanced.
Furthermore, the oxidative damage to blood
lymphocyte DNA caused by chronic alcohol
ingestion was significantly decreased in the ET +
ABG group. In conclusion, ABG has strong
antioxidative properties and may be a promising
agent for protecting against chronic alcohol-
induced liver damage.
Enhance the Immune System
Black garlic activity to increase the immune
system was tested by measuring the increase in
natural killer (NK) cell, cytokine IFN-ᵧ, TNF-α, and
IL-2. 10-day treatment black garlic extract is the
maximum time of activated natural killer (NK) cells
increased. Cytokines IFN-ᵧ, TNF-α, and IL-2, which
were generated from Th1 (T lymphocytes helper
1), and NO generated from macrophages reached a
maximum 8 days later (3 days after ceasing the
treatment of the extract), and that of IL-2 6 days
later. This indicates that the black garlic extracts
worked first on both T lymphocytes and
macrophages to activate them, and cytokines
released from these activated cells enhanced the
activity of NK cells to attack abnormal cells like
tumor cells. Aged black garlic can enhancement of
the immune system because have rich SAC than
fresh garlic (Wang et al., 2010)
Hyperglycemia and Dyslipidemia Effect
Seo et al., (2009) reported consumption of
aged black garlic (ABG) significantly decreased
homeostasis model assessment for insulin
resistance (HOMA-IR) and tended to decrease
serum glucose. Garlic consumption significantly
decreased total cholesterol but did not decrease
triglyceride and HDL-cholesterol levels, while aged
black garlic significantly reduced serum total
cholesterol and triglyceride and increased HDL-
cholesterol levels. ABG alleviated insulin resistance
in db/db mice, obese-diabetic animals with insulin
resistance. Insulin resistance is an important
initiating pathogenic mechanism of type 2
diabetes.
Antiinflammatory Effect
Kim et al., (2014) aged black garlic extract
(ABGE) was weaker than fresh raw garlic extract
(FRGE) in inhibition of cyclooxygenase-2 and 5-
lipooxygenase activities. FRGE reduced PGE2, NO,
IL-6, IL-1β, LTD4, and LTE4 production in LPS-
activated RAW 264,7 cells more than did ABGE.
Treatment with glucose or fructose inhibited
neither the activation of NF-kB nor the expression
of Inos, COX-2, and IL-1. ABGE has higher
component fructose, glucose, sucrose, and main
saccharides than FRGE, so anti-inflammatory
activity in ABGE lower than FRGE. The anti-oxidant
activity of ABGE is not directly proportional to its
anti-inflammatory activity
Anti-Allergic Effect
Kim et al., (2012) reported anti-allergic aged
black garlic lower than fresh garlic at
concentrations up to 100µg/mL, was analyzed by
measuring their inhibitory effects against β-
hexosamine release. A considerably higher
suppression of β-hexosamine release was found in
fresh garlic extract at lower concentrations
compared with that of the black garlic.
CONCLUSION
The concentration of S-allyl cysteine (SAC)
levels increases due to the fermentation process in
black garlic, which has been reported as a good
source of antioxidant compounds. It has also
potential as inhibits the growth of cancer cells,
hepatoprotective, enhance the system immune,
hyperglycemia, dyslipidemia, anti-allergic and
anti-inflammatory. Black garlic needs further
exploration, particularly the mechanics of its
biological activity, to be as supplement health.
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