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Garlic belonging to Alliaceae family, is an important spice crop used from
long back in Ayurveda and other forms of medicine for treatment of various
ailments such as cancer, diabetes, cardiovascular diseases etc. The medicinal
properties of garlic are mainly due to the presence of organosulfur compounds and
several polyphenolic compounds. The major organosulfur compounds in garlic
include alliin, allicin, l-γ-glutamyl-s-allyl-l-cysteine, s-allyl cysteine, s-allyl
mercapto cysteine, allyl mercaptan, diallyl disulfide, diallyl trisulfide, allyl propyl
disulfide, vinyldithiin etc. L-γ-Glutamyl-S-allyl-L-cysteine and alliin are the
precursor molecules of all other compounds, the breakdown of which produce
other compounds by several reactions with the help of enzyme allinase.
Polyphenols like apigenin, quercetin, phloroglucinol, p-coumaric-acid, ferulic-
acid, sinapic acid etc. also contribute to the medicinal effects of garlic. Though the
medical literature for garlic is well established, the exact compounds from garlic
against various diseases is not much experimented.
The study entitled “Detection of novel metabolites in garlic (Allium
sativum L.) through in silico analysis and its validation” was taken up to analyze
the medicinal effects of important compounds in garlic by inhibiting the targets
involved in lifestyle diseases such as cancerous, cardiovascular, arthritic,
hypercholesterol and diabetic complications through in silico molecular docking
analysis and validation through wet lab analysis. The experiment was performed
using a commercial software Discovery Studio version 4.0 at Distributed
Information Centre (DIC), CPBMB, KAU. For the study, 32 protein targets
involved in different diseases were selected. Wet lab experiments such as in vitro
cell line cytotoxicity test was conducted at Amala Cancer Research Centre,
Thrissur and at CPBMB, KAU. Gene expression studies were conducted for
validating the anti- cancerous properties of garlic compounds through RT-qPCR.
Seventeen compounds from garlic both of allyl nature and polyphenols
exhibited positive interaction with the targets selected for the lifestyle diseases.
The important targets most inhibited by garlic phytocompounds were DNAtopoisomerase, Epidermal growth factor receptor (EGFR), Phosphoinositide 3-
kinase Gamma (PI3Kγ) and Thymidilate synthase for cancer; Glucokinase (GK)
and Dipeptidyl peptidase (DPP4) for diabetes; Cyclooxygenase 2 (COX2) and
Nitric Oxide Synthase (NOS) for arthritis and inflammation; and Angiotensin
Converting Enzyme (ACE) and HMG CoA reductase for blood pressure and
cholesterol. It was found from the dock scores obtained, that s-allyl cysteine
(SAC), alliin/ s-allyl cysteine sulfoxide (SACS), ferulic acid (FA) and p-coumaric
acid (pCA) were found superior to other compounds and were found to inhibit
most of the targets.
These compounds (SAC, SACS, FA and pCA) which gave positive
interaction in docking studies were procured in their pure form (upto 98% HPLC
grade) from Sigma Aldrich and used for cell line studies. The three cancer cell
lines HCT-15, Raw264.7 and L929 exhibited dose dependent cytotoxicity for all
the four test compounds from garlic. The IC 50 value for true Allium compounds
such as SAC and SACS were found in the range of 71-100 μg/ml, whereas for
polyphenolic compounds such as FA and pCA, was found in the range of 145-222
μg/ml. HCT-15, the human colon cancer cell line showed more sensitivity to all
the compounds and so it was forwarded for gene expression studies. EGFR was
the gene selected for the study, which is most commonly expressed in human
colon cancer. All the compounds from garlic showed down regulation of the
EGFR gene dose dependently, except for SACS.
Overall results from both in silico and wet lab studies indicated the
medicinal effects of different compounds in garlic on various lifestyle diseases.
Thus the present study gives a strong scientific background to highlight the health
benefits of garlic.