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Garlic is used in the prevention and treatment of a variety of infectious and noninfectious diseases. 30–32

30. Thomson M, Ali M. Garlic (Allium sativum): a review of its potential use as an anti-cancer agent. Curr cancer drug targets. 2003;3(1):67-81.

31. Rivlin R S. Historical perspective on the use of garlic. J Nutr. 2001;131(3s):951S-954S.

32. RossZM,O’GaraAE,HillDJ,etal.Antimicrobialpropertiesof garlic oil against human enteric bacteria: evaluation of method- ologies and comparisons with garlic oil sulfides and garlic pow- der. Appl Environ Microbiol.
2001;67:475-480.

33. BakriIM,DouglasCW.Inhibitoryeffectofgarlicextractonoral bacteria. Arch Oral Biol. 2005;50(7):645-651.

26882663, 2021, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/mco2.82 by Nat Prov Indonesia, Wiley Online Library on [16/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-
and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable C

Allicin reduces M. tuberculosis burden in the host by increasing the activity of the enzyme, glutathione
peroxidase.37

37. Hasan N, Yusufb N, Toossi Z, Islam N. Suppression of Mycobac- terium tuberculosis induced reactive oxygen species (ROS) and TNF-α mRNA expression in human monocytes by allicin. FEBS Lett.
2006;580:2517-2522.

In 2014, Vishwanathan et al reported in an in vitro study that garlic extract and garlic oil both show decent
antimycobac- terial activity when compared to standard drugs,

Dwivedi et al has given some strong proofs to establish the therapeutic potential of allicin in the pathogenesis of
tuberculosis. Allicin/garlic extract displays direct killing of Mycobac- teria and leads to the induction of pro-
inflammatory cytokines in macrophages while also limiting M. tubercu- losis infection inside the cells by
interacting with the cell surface receptors responsible for M. tuberculosis entry.41

Experiments done in mice model establish that treatment of infected mice with allicin/garlic extract leads to a
sig- nificant reduction in bacterial burden mainly due to host protective Th1 response, which eliminates the
pathogens in a much lesser time duration compared to the conventional treatment coarse.

41. Dwivedi VP, Bhattacharya D, Singh M, et al. Allicin enhances antimicrobial activity of macrophages during Mycobacterium tuberculosis infection. J Ethnopharmacol. 2019;243:111634.

Ajoene, has shown tremendous effectiveness in TB treatment due to its ability to induce autophagy and ROS
synthesis.40–42

40. Viswanathan V, Phadatare AG, Mukne A. Antimycobacterial and antibacterial activity of Allium sativum bulbs. Ind J Pharm Sci. 2014;76(3):256-261.
41. Dwivedi VP, Bhattacharya D, Singh M, et al. Allicin enhances antimicrobial activity of macrophages during Mycobacterium tuberculosis infection. J Ethnopharmacol. 2019;243:111634.
42. Choi JA, Cho SN, Lim YJ, et al. Enhancement of the antimy- cobacterial activity of macrophages by ajoene. Innate Immun. 2018;24(1):79-88.

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Allicin is known to exert its effects as an antipathogenic agent mainly by targeting the thiol-
containing proteins or enzymes in different microorganisms and also by regulating the key
genes responsible for the virulence of the microorganism [1]

The study by Dwivedi et al. entitled “Allicin enhances antimicrobial activity of macrophages during
Mycobacterium tuberculosis infection” allicin not only inhibits the internalization of Mycobacterium
tuberculosis (M. tb) by blocking receptors on the surface but also eliminates the bacteria by its
antimycobacterial killing mechanisms. The investigators have reported that allicin not only kills the
bacteria but also acts as an immunomodulator inducing host protective immune response which
protects the host by minimizing the side-effects and immune dampening caused by the conventional
antibiotics treatment [2]

Allicin has somehow shown to be more conclusive and potent when used in combination with other
drugs used in conventional treatment [12-14]. The reason may be that allicin treatment makes the
microorganisms more vulnerable thus allowing antibiotics or antifungals to act on them and be more
effective rather than acting alone. Therefore, a combination therapy of allicin with the conventional
antimicrobial drugs may help reduce the treatment duration and thus may be quite helpful in
preventing the evolution of drug-resistant variants. The antibacterial potency of allicin is comparable,
to some conventional antibiotics such as penicillin, tetracycline and kanamycin [15-17]. Unlike the
commonly utilized antibiotics, which are a pathogen-specific or narrow spectrum, allicin has an
inhibitory effect on a broader spectrum of microorganisms encompassing bacteria (both gram-
positive and negative), yeasts, fungi, parasites and even viruses [18].

Coming towards the immunological consequences of taking garlic derivatives as combination therapy
along with the DOTS treatment regimen, we have argued that treatment with garlic extract has very
minimal effect on the predominance of CD4+ and CD8+ T cells but still is higher than that of isoniazid
treatment alone. Tousif et al. have reported that isoniazid treatment induces apoptosis of activated
CD4+T cells [23]. Here, in our study, we have confirmed that garlic reverses these adverse effects
reducing the side effects of DOTS therapy. This could be used in patients undergoing DOTS treatment
or they may be advised to take garlic throughout treatment to continuously keep boosting their
immune system and negate the chances of reactivation or relapse of TB, which is the major drawback
associated with DOTS therapy. Furthermore, we have also shown that there was an enhanced
production of IL-12 compared to only infected and isoniazid treated animals with the level of IL-10
and TNF-α which were found to be comparable in all groups. Thus, our study reports that garlic
extract/allicin acts as an immunomodulator in TB infection taking the T-cell polarization towards
protective T helper 1 (Th1) response.

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Garlic has antibacterial, anti-cancer, antioxidant, and anti-inflammatory properties, reduces blood sugar, and protects
the cardiovascular system. The antibacterial effects of garlic on different bacteria have also been reported (2

The results of the present study showed that the ethanolic extract of garlic was very effective in Mycobacterium tuberculosis.
Moreover, the most effective genes in Mycobacterium tuberculosis were ropB and rrs. As a result, for the development of
drugs effective in Mycobacterium tuberculosis, it is necessary to pay more attention to the aforementioned
genes and develop drugs on their basis. The measurementof drugresistance in clinical settings is timeconsuming and prone to
errors. Therefore, further studies are needed to examine this important issue. Although garlic is very effective in
Mycobacterium tuberculosis, it is not recommended to directly use the results of this study. Consequently, it is required to
perform further clinical trials to confirm the results.

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Garlic is an antibacterial agent against gram-positive and gramnegative bacteria. The main
component in garlic that is believed to be responsible for the antibacterial and other
therapeutic potential of garlic is the sulfur content in garlic. Among them are
Diallylthiosulfinate (alicin) and Diallyl disulfide (ajoene). Alisin is formed from the main
organosulfur compounds in garlic, namely gamma-glutamyl-sallylcysteine and Sallyl-L-
cysteins sulfoxides (alliin) through enzymatic reactions with the help of the alinase enzyme.
As an antibacterial, Allicin works by changing the composition of proteins, lipids and
polysaccharides in bacterial cell membranes (Hanif&Carolia, 2019). In a joint study
conducted by Aligarh University in India and the University of Cleveland in the US, Allicin
has proven to be a potential agent against TB infection, through its strong anti-inflammatory
effect on host mononuclear cells infected with Mycobacterium tuberculosis (MTB). Alisin
increases the activity of the enzyme glutathione peroxidase thereby decreasing the production
of reactive oxygen species and ultimately decreasing the production of inflammatory
mediators. This phenomenon is reported to occur due to the cessation of transcription of the
85B antigen at the gene and protein levels. The 85B antigen is widely released by
Mycobacterium tuberculosis and is responsible for the induction of TNF-α as an
inflammatory mediator. The suppression of 85B expression by Allicin appears to be mediated
through inhibition of glutathione. Researchers therefore suggest that the garlic compound
should be tested in an in-vivo model to evaluate its therapeutic potential in the pathogenesis
of tuberculosis. interesting in vitro test of the anti tuberculosis activity of Allium sativum was
carried out in Nigeria in 2010, where the extract of Allium sativum was expressed as a
discdiffusion method and compared with standard antibiotics. The anti-tuberculous activity of
garlic on multi-drug resistant Mycobacterium was investigated among HIV-infected
individuals and showed maximal activity against all isolates even at concentrations reduced
by the zone of inhibition diameter (IZD).

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Most studies focused on isolated allicin or aqueous garlic extracts abundant in allicin and other thiosulfinates 5. On the other
hand, there are surprisingly few reports on the antimycobacterial effect of essential oil obtained from garlic bulbs (GEO).
The phytochemical analysis of GEO showed that its composition is dominated by allyl polysulfides, including diallyl sulfide,
diallyl disulfide, diallyl trisulfide, allyl methyl disulfide and allyl methyltrisulfide 16,17.
In studies by Swapna and co-workers, isolated allylmethyl trisulfide showed the highest inhibitory activity (125 μg/mL)
against M. tuberculosis5. In another experiment, a garlic polysulfides mixture composed of 5% of diallyl monosulfide, 15%
diallyl disulfide, 60% diallyl trisulfide, 20% diallyl tetrasulfide and less than 5% of diallyl pentasulfide and diallyl
hexasulfide exhibited very strong antimycobacterial potential with the minimal inhibitory concentration of 2.5 μg/mL 6.
Nevertheless, the mechanism of action of GEO against M. tuberculosis was not explored so far.

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