Pharmaceutical Effects of Allium sativum
4 common species of Allium genus are A.sativum(garlic), A. cepa(onion), A. porrum(leek), and A. schoenoprasum(chive). I need to search more about Allium monanthum Maxim.(달래), Allium tuberosum(부추), Allium fistulosum(대파) which are usually consumed a lot in Korea.
According to this paper, their common pharmaceutical effects are antimicrobial, antithrombotic, antitumor, hypolipidaemic, antiarthritic and hypoglycemic effects. There are other many effects of Allium genus plants have in common, and the important active ingredients related to their special pharmacological effects are sulfur compounds. I got interested about these compound and after abstracting this paper, I am going to find more about them. Anyway, from now on, there will be an abstract about pharmaceutical effects of Allium sativum.
A. Traditionally A. sativum is used to treat asthma, antipyretic(해열제), sedative(진정제), aphrodisiac(정력제), diuretic, emmenagogue(월경 촉진제), carminative(장내 가스 배출제), promoting hair growth, treating dyspepsia(소화불량), urinary and respiratory infections and cardiac complains.
B. Chemical constituents of A. sativum are as the following:
A. sativum contains a lot of sulfur compounds including thiosulfinates(allicin), ajoenes(E-ajoene, Z-ajoene), vinyldithiins(2-vinyl(4H)-1,3-dithiin, 3-vinyl-(4H)-1,2-dothiin), sulfides(diallyl disulfide, diallyl trisulfide) and others. What the interesting thing is that when garlic is cut or destroyed by physical damage or just by getting eaten by other organisms, alliin is converted by the enzyme allinase(alliin lyase) to allicin. It is an odoriferous compound and the main component of freshly crushed garlic. Also garlic has S-propylcysteine-sulfoxide(PCSO) and S-methylcysteine-fulfoxide(MCSO). When PCSO, MCSO, and alliin are treated by allinase together, it produced many other molecules including allyl methane thiosulfinate, methyl methanethiosulfinate and other mixed or symmetrical thiosulfinates(R-S-S-R’, R and R’ are allyl, methyl and propyl groups). A. sativum essential oil contained di-2-propenyl disulfide 25.18%, methyl-2-propenyl trisulfide 23.80% and other compounds.
C. Pharmaceutical effects
a. antibacterial effects
Numerous reports showed that A. sativum showed antimicrobial activity against Gram positive and Gram negative microorganisms. The juice, aqueous and alcoholic extracts and the essential oil of garlic inhibited the in vitro growth of Staphylococcus auresus, Streptococcus faecalis, Bacillus species, Clostridium, Escherichia coli, Shigella sonnei, Proteus species, Pseudomonas aeruginosa, Mycobacterium tuberculosis, Candida species, Cryptococcus species, Toruloposis species, Trichosporon pullulans and Rhodotorula rubra and Aspergillus niger. Also there were antimycobaterium effect. The patients were treated by inhaling it or just taking it internally. Plus, garlic extracts prevent the formation of Staphylococcus enterotoxins A, B, and C1 and thermonulcease. In addition, it was also effective against Helicobacter pylori.
Pure allicin and other thiosulfinates produced these kind of effects. Inhibition of certain thiol-containing enzymes in the microorganisms by the rapid reaction of thiosulfinates with thiol groups was assumed to be the main mechanism. Especially, allicin inhibited other bacterial enzymes such as acetate kinase and phosphotransacetyl-CoA synthetase, and inhibited the nucleic acid synthesis(such as DNA and RNA) which means that protein synthesis could be affected.
*Things that I need to find: What’s the mechanism of antibacterial effects by thiosulfinates such as allicin->why do enzymes of bacteria got useless by thiosulfinates
b. antifungal effects
Aqueous garlic extract showed marcromlecular synthesis of Candida albicans. For example, protein and nucleic acid synthesis were inhibited but lipid synthesis was completely arrested. To inhibit the growth of fungus, it is important to inhibit their lipid synthesis. Also Cryptococcal meningitis was successfully treated by oral, muscular and intravenous administration of garlic. Not just only them. Allicin and other thiosulfinates showed synergistic fungistatic activity with amphotericin B and inhibited germination of spores and growth of hyphae.
*Things that I need to find: What’s the mechanism of inhibiting protein and nucleic synthesis and arresting lipid synthesis.
*My thought: if synthesis of marcromolecules are inhibited, germination of spores and growth of hyphae is obvious.
c. antiviral effects
Hydro-distilled essential oils of garlic showed antiviral activity against HSV1, HSV2, human cytomegalovirus, influenza B, parainfluenza virus type 3, vaccinia virus, vesicular stomatitis virus and human rhinovirus type 2. Ajoene was found to block the integrin-dependent processes in a HIV infected cell system which means replication of the virus’s nucleic acid cannot be occurred.
d. antiparasite effects
e. anticancer effects
Diallyl disulfide from garlic has been shown to have an antiproliferative effect on human tumor cells such as colon(결장), lung, skin, breast, mammary(유선) and liver origins.
There are tons of studies saying that a group consuming garlic a lot showed a low incidence of stomach, colorectal(결장.직장), prostate(전립선), esophagus cancers, and female breast and mammary carcinoma. This kind of effects are due to increase of (glutathione)GSH peroxidase activity. When garlic oil is used, sharp decline in the ratio of reduced GSH/ oxidized GSH caused by tetradecanoylphorbol-13-acetate(TPA) was inhibited.
*Need to find out the mechanism of GSH’s antioxidization.
Plus, it showed another way to inhibit cancer. Some of garlic’s constituents inhibited the nuclear factor kappa B(NF-κB) activation which is induced by various receptor agonists(things that bind to the receptor) such as lipopolysaccharide and tumor necrosis factor a(TNFa). This kind of effect is due to sulfur-containing compounds. Also, garlic extract directly inhibited the Toll-like receptors(TLRs)-mediated signaling pathway at the receptor level.
*What is NF-κB and what is the relationship between NF-κB and the cancer?
*What is the Toll-like receptors(TLRs)-mediated signaling pathway and what is the relationship between the Toll-like receptors(TLRs)-mediated signaling pathway and the cancer
*How does sulfur-containing compounds inhibit cancer and what is the mechanism of it? Plus what kind of sulfur-containing compound makes this effect?
f. cardiovascular effects
There were some studies that garlic components are good at decreasing cholesterol, triglyceride and LDL cholesterol. When garlic and garlic protein are administrated to mouses and rats with a high-cholesterol diet, significant decrease of serum cholesterol, triglyceride and LDL cholesterol were observed. Also, long term feeding of garlic led to reduction of serum lipid of a rabbit with high-cholesterol diet and atheromatous lesions of it got better.
Water soluble extract of garlic inhibited biosynthesis of cholesterol in hepatocytes. Something that is interesting is conversion of acetate into cholesterol has been decreased which proves the thing that I have just said.
Ingesting garlic oil and garlic led to decrease in LDL and VLDL levels, but increase in HDL levels.
According to these results, atherosclerosis and the blood flow of the patient would get better.
There is another important thing that is called platelet aggregation. A water, chloroform or methanol extract inhibited collagen-ADP, arachidonic acid, epinephrine and thrombin induced platelet aggregation. This kind of effect was also shown by ether extract of garlic and garlic juice. It decreased cholesterol and fibrinogen, increase fibrinolytic activity and blood coagulation time and decrease in thrombocyte aggregation in blood.
Garlic has hypotensive effects by relaxant effect on smooth muscles(if these muscles are relaxed, blood pressure decreases).
*What is the difference between HDL and LDL?
*How does blood clot formed?
*How does A. sativum and its extract make these kind of effects?
g. antioxidant effects
A. sativum activates lecithin, a cholesterol acyltransferase which converts cholesterol into HDL. Also, garlic compounds have tremendous antioxidant property by scavenging ROS, enhancing cellular antioxidant enzymes and increasing glutathione in the cells. The radical scavenging activity(% inhibition, DPPH radical scavenging assay) of the essential oil was 87.0% which is a pretty high value.
*How does it scavenge ROS?
h. antidiabetic effects
Garlic is effective at lowering serum glucose levels in streptozotocin and allozan induced diabetes in rabbits, rats and mice. S-allyl cysteine sulfoxide(allin) and allicin showed significant antidiabetic in rats. Also, garlic oil and diallyl trisufide showed hypoglycemic effects and improved glycaemic state in rats with diabetes. Allicin produced 60% of the activity of tolbutamide(a chemical that is used to treat diabetes).
*How Allin and Allicin reduce blood glucose rate.
*What is the mechanism of tolbutamide to decrease blood glucose?
*What makes the pharmacological difference of DAnS
i. detoxification effects
There was an experiment with Oreochromis niloticus which is a kind of fish, to check the relationship between garlic and heavy metals. When researchers used garlic oil, the bioaccumulation of zinc and copper decreased of the fish has been exposed to heavy metals such as zinc(ZnSO4) and copper(CuSO4).
CrCl3 is known to increase levels of ALT and AST. Then, garlic was used to check rather it is useful to decrease ALT and AST levels and as expected, it inhibited the hepatotoxicity of CrCl3 which means that it showed low rates of ALT and AST levels.
Also, garlic is known to reduce tissue lead(concentration.) When lead acetate and garlic dry powder were used together, they reduced lead concentration considerably,
*What are ALT and AST?
*How do they make heavy metals to get out of the body?
D. Abstract
To be shorten, there are lots of pharmaceutical effects of A. sativum and most of its effects are due to sulfur compounds. I need to search more about the chemical itself and the relationship between its pharmaceutical effects. Plus, I need to study more about the questions after reading this paper and things that I don’t exactly know.