Garcinol

Scientific Name(s):Garcinol has been isolated from several Garcinia species; however, Garcinia indica is the most common source referenced in the scientific literature. 1 , 2 Family: Clusiaceae (Guttiferae)

Common Name(s): Garcinol or camboginol 2

Uses

Numerous in vitro and scientific animal studies on garcinol document anti-inflammatory, antioxidant, anticancer, and antibacterial activity. Clinical data are lacking.

Dosing

Garcinol is used as an active ingredient in various topical products for its antioxidant activity. It is also used as an additive ingredient in hydroxycitric acid, purported by some commercial manufacturers to improve lean body mass.

Contraindications

Avoid use if allergy or hypersensitivity to any of the components of garcinol exist.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

No clinical data are available.

Toxicology

No clinical data are available.

Botany

Garcinol is primarily present in family Clusiaceae and genus Garcinia . Although Garcinia indica is commonly referenced in the scientific literature, 2 it is found in other plant species. 3 The genus Garcinia includes 200 species located throughout Asia and Africa. G. indica , also known as kokum, is a slow-growing, mid-sized dioecious tree. 4 Its leaves are elliptic, oblong, and deep green. The flowers are dark pink, and the dried fruit rind contains the medicinal component of garcinol. The fruit is about the size of an orange and usually contains 6 to 8 seeds. The tree has the potential of bearing hundreds of fruits during the summer.

History

G. indica is used in culinary, pharmaceutical, and industrial applications. 2 The dried fruit rind of G. indica is used as a garnish in Indian curries. 4 , 5 , 6 The oils from the seeds are used in preparing chocolates, medicines, and cosmetics. Kokum butter is extracted from the seeds and used in the cosmetic industry for preparing lotions, creams, lip balms, and soaps. 2 Garcinol is claimed to inhibit skin glycation, thus reducing inflammation and injury to the extracellular matrix. 7 The fruit rind has also been utilized as a pink and purple food coloring agent and as a culinary spice to provide a sour and sweet taste to foods. 8 In Indian Ayurvedic medicine, the extract of the fruit rind is used to treat inflammatory and infectious disease. 8 , 9 Garcinia is also used in central African traditional medicine for infectious disease. 10

Chemistry

Analytical studies on the chemical constituents of Garcinia species are available. 11 , 12 , 13

Garcinol is also known as camboginol and is commonly found in the dried fruit rind of G. indica as a yellow oil or pigment. 13 Mass spectral analysis of garcinol has been performed. 2 Garcinol is an example of a prenylated chalcone, which has many beneficial effects in human health and disease. 2

Uses and Pharmacology

Numerous scientific studies on garcinol document antiinflammatory, antioxidant, anticancer, and antibacterial activity.

Antiinflammatory
In vitro

Aberrant arachidonic acid metabolism and nitric oxide synthesis are involved with inflammatory and carcinogenic processes. Garcinol and its derivatives inhibited release of arachidonic acid metabolites in human colon adenocarcinoma cells. Several key proteins involved in inflammation were inhibited, and the inhibitory effect on nitric oxide synthesis was concentration dependent. The proposed molecular mechanism of action of garcinol affects inflammatory processes associated with phosphorylation, inflammatory cytokines, and membrane phospholipids. 14 Garcinol is a direct and potent inhibitor of the catalytic activity of 2 crucial enzymes involved with inflammation, 5-lipoxygenase, and microsomal prostaglandin PGE 2 synthase. 9 These 2 enzymes are often overexpressed in many tumors. Cigarette smoke extract leads to airway inflammation, which may be regulated by cyclooxygenase-2 (COX-2) expression and prostaglandin E 2 (PGE 2 ) synthesis. 15 Pretreatment of tracheal smooth muscle cells with garcinol markedly inhibited COX-2 expression stimulated by the cigarette smoke extract.

Animal data

Topical application or oral administration of garcinol inhibited TPA-induced ear inflammation in a dose-dependent manner in CD-1 mice. TPA-induced expression of proinflammatory cytokine IL-6 protein was inhibited by topical application of garcinol to the ears of CD-1 mice. UVB-induced ear inflammation and proinflammatory cytokines IL-1 beta and IL-6 were inhibited in mice after oral administration of garcinol. Topical application of garcinol strongly inhibited TPA-induced skin tumor promotion in mice. 16

Antioxidant
In vitro

Garcinol has free radical scavenging activity against the hypoxanthine/xanthine oxidase system, superoxide anion, hydroxyl radical, and methyl radical. 17 The activity of emulsified garcinol was almost comparable with that of DL-alpha–tocopherol by weight but less than that of ascorbic acid. However, garcinol suppressed hydroxyl radical more strongly than that of DL-alpha–tocopherol.

The mechanism of action may be associated with garcinol reacting with peroxyl radicals followed by deprotonation of the hydroxyl group. 5 , 6 Garcinol has chelating and antiglycation activity (glycation plays a role in diabetic complications) and is a lipid-soluble superoxide anion scavenger. 3

Garcinol provided a neuroprotective effect by decreasing nitric oxide production and expression of lipopolysaccharide-induced inflammatory mediators, iNOS and COX-2, in rat cortical astrocyte cultures. 18

Cancer
In vitro and animal data

Garcinol showed potent inhibitory growth activity against HT-29 and HCT-116 colon cancer cells. 8 Focal adhesion kinase (FAK) is involved in protecting against apoptosis. Garcinol inhibited cell invasion by inhibiting the downstream signaling of FAK. 19 Elevation of the detoxifying enzyme glutathione S-transferase and quinine reductase in the liver, reduction of free radicals, and arachidonic acid metabolites by dietary garcinol in rats may suppress chemically induced colon carcinogenesis. 1 In human leukemia HL-60 cells, garcinol inhibited activity in a dose- and time-dependent manner by inducing DNA fragmentation and apoptotic cell death. 20 A similar study with human leukemia HL-60 cells documented the loss of mitochondrial membrane potential by garcinol-induced apoptosis. 21 Dietary administration of garcinol in rats inhibited development of 4-nitroquinoline 1-oxide–induced tongue carcinogenesis and preneoplasms when compared with the control diet. 22 The mechanism of action involves garcinol suppressing cell proliferation activity in affected tissues and/or COX-2 expression in the tongue lesions. Garcinol induced caspase-mediated apoptosis in highly metastatic human breast cancer cells (MDA-MD-231) through down-regulation of NF-kappaB signaling pathway. 23 A chemical study examining 2 ethers of garcinol and isogarcinol documented inhibitory activity against Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells; the activity was comparable or stronger to that of the antitumor promoter glycyrrhetic acid. 24 Dysfunction or alteration of histone acetyl transferases (HATS) may lead to diseases such as cancer and viral infections, including HIV. 25 Garcinol is a potent, nonspecific in vitro and in vivo inhibitor of HATS, a key regulatory step in gene expression in eukaryotic cells. 26 , 27 Garcinol is also the first reported cell-permeable HATS inhibitor. 28 Viral protein integrase is a critical protein for the integration of HIV-1 virus into the human genome. In one study, garcinol-derived molecules inhibited a critical step in this integration as well as HIV multiplication in T cells at nontoxic concentrations. 25 , 29

Other Pharmacologic Activity
Alzheimer disease

Inhibition of cholinesterase activity increases acetylcholine availability for nerve cell communication. Garcinol has anticholinesterase activity toward acetyl cholinesterase (AChE) and butylcholinesterase. The IC5 0 value of garcinol (0.66 mcM) versus the reference compound galanthamine (0.50 mcM) against AChE was comparable. 30

Infection

An in vitro study documents garcinol inhibition of the growth of methicillin-resistant Staphylococcus aureus , with the activity comparable to that of the antibiotic vancomycin. 31 , 32 Several concentrations of an extract from G. indica , with garcinol as the major compound, inhibited the growth of Aspergillus flavus and subsequent mycotoxin aflatoxin B1 production in a growth inhibition assay. 33 G. indica rind extracts and garcinol inhibited the growth of some foodborne gram-positive and gram-negative bacteria. 34 Garcinol has moderate antiplasmodial activity against the chloroquine-resistant strain of Plasmodium falciparum (FcB1). 35

Stomach Ulcer

Oral administration of garcinol to rats prevented acute ulceration induced by indomethacin. The mechanism of action may be associated with the interaction of garcinol with reactive oxygen species on the surface of gastric mucosa. 17 The in vitro bactericidal activities of clarithromycin and garcinol exerted time- and concentration-dependent effects on Helicobacter pylori . In the same study, garcinol exhibited greater bactericidal activity on H. pylori when compared with resveratrol. 36 , 37

Dosage

Garcinol is an active ingredient in various topical products for its antioxidant activity. It is also used as an additive to hydroxycitric acid, purported by some commercial manufacturers to improve lean body mass.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

Theoretically, when used with stomach acid–reducing medications (eg, proton pump inhibitors) garcinol may provide an additive effect, but should be used cautiously with antioxidant products or cancer medications.

Adverse Reactions

No clinical data were found in the medical literature. Avoid use if allergy or hypersensitivity to any of the components of garcinol exist.

Toxicology

Dietary administration of garcinol in animal studies did not cause any histological or pathological changes in liver, kidney, lung, heart, or esophageal organ systems. 1 , 22

Bibliography

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2. Padhye S, Ahmad A, Oswal N, Sarkar FH. Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs. J Hematol Oncol . 2009;2:38.
3. Yamaguchi F, Ariga T, Yoshimura Y, Nakazawa H. Antioxidative and anti-glycation activity of garcinol from Garcinia indica fruit rind. J Agric Food Chem . 2000;48(2):180-185.
4. Deodhar SR, Thengane RJ, Thengane SR. De novo shoot regeneration from root cultures of Garcinia indica Choiss . Indian J Exp Biol . 2008;46(6):482-486.
5. Sang S, Pan MH, Cheng X, et al. Chemical studies on antioxidant mechanism of garcinol: analysis of radical reaction products of garcinol and their antitumor activities. Tetrahedron . 2001;57(50):9931-9938.
6. Sang S, Liao CH, Pan MH, et al. Chemical studies on antioxidant mechanism of garcinol: analysis of radical reaction products of garcinol with peroxyl radicals and their antitumor activities. Tetrahedron . 2002;58(51):10095-10102.
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9. Koeberle A, Northoff H, Werz O. Identification of 5-lipoxygenase and microsomal prostaglandin E2 synthase-1 as functional targets of the anti-inflammatory and anti-carcinogenic garcinol. Biochem Pharmacol . 2009;77(9):1513-1521.
10. Khanum SA, Shashikanth S, Umesha S, Kavitha R. Synthesis and antimicrobial study of novel heterocyclic compounds from hydroxybenzophenones. Eur J Med Chem . 2005;40(11):1156-1162.
11. Xu G, Feng C, Zhou Y, et al. Bioassay and ultraperformance liquid chromatography/mass spectrometry guided isolation of apoptosis-inducing benzophenones and xanthone from the pericarp of Garcinia yunnanensis Hu . J Agric Food Chem . 2008;56(23):11144-11150.
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14. Hong J, Sang S, Park HJ, et al. Modulation of arachidonic acid metabolism and nitric oxide synthesis by garcinol and its derivatives. Carcinogenesis . 2006;27(2):278-286.
15. Yang CM, Lee IT, Lin CC, et al. Cigarette smoke extract induces COX-2 expression via a PKCalpha/c-Src/EGFR, PDGFR/PI3K/Akt/NF-kappaB pathway and p300 in tracheal smooth muscle cells. Am J Physiol Lung Cell Mol Physiol . 2009;297(5):L892-902.
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17. Yamaguchi F, Saito M, Ariga T, Yoshimura Y, Nakazawa H. Free radical scavenging activity and antiulcer activity of garcinol from Garcinia indica fruit rind. J Agric Food Chem . 2000;48(6):2320-2325.
18. Liao CH, Ho CT, Lin JK. Effects of garcinol on free radical generation and NO production in embryonic rat cortical neurons and astrocytes. Biochem Biophys Res Commun . 2005;329(4):1306-1314.
19. Liao CH, Sang S, Ho CT, Lin JK. Garcinol modulates tyrosine phosphorylation of FAK and subsequently induces apoptosis through down-regulation of Src, ERK, and Akt survival signaling in human colon cancer cells. J Cell Biochem . 2005;96(1):155-169.
20. Pan MH, Chang WL, Lin-Shiau SY, Ho CT, Lin JK. Induction of apoptosis by garcinol and curcumin through cytochrome c release and activation of caspases in human leukemia HL-60 cells. J Agric Food Chem . 2001;49(3):1464-1474.
21. Matsumoto K, Akao Y, Kobayashi E, et al. Cytotoxic benzophenone derivatives from Garcinia species display a strong apoptosis-inducing effect against human leukemia cell lines. Biol Pharm Bull . 2003;26(4):569-571.
22. Yoshida K, Tanaka T, Hirose Y, et al. Dietary garcinol inhibits 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in rats. Cancer Lett . 2005;221(1):29-39.
23. Ahmad A, Wang Z, Ali R, et al. Apoptosis-inducing effect of garcinol is mediated by NF-kappaB signaling in breast cancer cells. J Cell Biochem . 2010;109(6)1134-1141.
24. Ito C, Itoigawa M, Miyamoto Y, et al. Polyprenylated benzophenones from Garcinia assigu and their potential cancer chemopreventive activities. J Nat Prod . 2003;66(2):206-209.
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26. Balasubramanyam K, Altaf M, Varier RA, et al. Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene expression. J Biol Chem . 2004;279(32):33716-33726.
27. Arif M, Pradhan SK, Thanuja GR, et al. Mechanism of p300 specific histone acetyltransferase inhibition by small molecules. J Med Chem . 2009;52(2):267-277.
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29. Mantelingu K, Reddy BA, Swaminathan V, et al. Specific inhibition of p300-HAT alters global gene expression and represses HIV replication. Chem Biol . 2007;14(6):645-657.
30. Lenta BN, Vonthron-Sénécheau C, Weniger B, et al. Leishmanicidal and cholinesterase inhibiting activities of phenolic compounds from Allanblackia monticola and Symphonia globulifera . Molecules . 2007;12(8):1548-1557.
31. Iinuma M, Tosa H, Tanaka T, et al. Antibacterial activity of some Garcinia benzophenone derivatives against methicillin-resistant Staphylococcus aureus . Biol Pharm Bull . 1996;19(2):311-314.
32. Rukachaisirikul V, Naklue W, Sukpondma Y, Phongpaichit S. An antibacterial biphenyl derivative from Garcinia bancana MIQ. Chem Pharm Bull (Tokyo) . 2005;53(3):342-343.
33. Tamil Selvi A, Joseph AS, Jayaprakasha GK. Inhibition of growth and aflatoxin production in Aspergillus flavus by Garcinia indica extract and its antioxidant activity. Food Microbiol . 2003;20(4):455-460.
34. Negi PS, Jayaprakasha GK. Control of foodborne pathogenic and spoilage bacteria by garcinol and Garcinia indica extracts and their antioxidant activity. J Food Sci . 2004;69(3):61-65.
35. Marti G, Eparvier V, Moretti C, et al. Antiplasmodial benzophenones from the trunk latex of Moronobea coccinea (Clusiaceae). Phytochemistry . 2009;70(1):75-85.
36. Chatterjee A, Yasmin T, Bagchi D, Stohs SJ. The bactericidal effects of Lactobacillus acidophilus , garcinol and Protykin compared to clarithromycin, on Helicobacter pylori . Mol Cell Biochem . 2003;243(1-2):29-35.
37. Chatterjee A, Bagchi D, Yasmin T, Stohs SJ. Antimicrobial effects of antioxidants with and without clarithromycin on Helicobacter pylori . Mol Cell Biochem . 2005;270(1-2):125-130.

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