Garcinol

Yamaguchi F, Ariga T, Yoshimura Y and Nakazawa H. 2000. Antioxidative and anti-glycation activity of garcinol from Garcinia indica fruit rind. J Agric Food Chem 48(2) 180—185. 

Further HAT inhibitors are the naturally occurring compounds curcumin 14 and garcinol IS (Figure 11.4). They show equal activity in vitro and in vivo. 

Curcumin represents a covalent inhibitor of CBP. Beyond, it showed anti-angiogenic effects and is currently in phase II/III of clinical trials for cancer therapy, as well as in phase II for Alzheimer s disease and psoriasis [21, 22[. Garcinol, a potent inhibitor of PCAF and p300 (IC50 = 5 and 7 J-M, respectively) was found to induce apoptosis and alter global gene expression in HeLa cells. It was identified to repress chromatin transcription. N one of these inhibitors had effects on H D AC activity or on histone-free DNA transcription [23]. 

Balasubramanyam, K., Altaf, M. and Varier, R.A. (2004) Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene expression. The Journal of Biological Chemistry, 279, 33716-33726. 

Pan MH, Chang WL, Lin-Shiau SY, Ho CT, Lin JK. 2001. 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 49 1464-1474. 

Bark known xanthone (rheediaxanthone A) and two known benzophenones (garcinol and isogarcinol) (Iinuma et al., 1998). 

Sang, S., Liao, C.H., Ran, M.H., Rosen, R.T., Shiau, S.Y.L., Lin, J.K. and Ho, C.T. (2002) Chemical studies on antioxidant mechanism of garcinol analysis of radical reaction products of garcinol with peroxyl radicals and their antitumor activities. Tetrahedron 58(51), 10095-10102. 

Yoshida, K., Tanaka, T., Hirose, Y., Yamaguchi, F., Kohno, H., Toida, M., Hara, A., Sugie, S., Shibata, T. and Mori, H. (2005) Dietary garcinol inhibits 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in rats. Cancer Letters 221 (1), 29-39. 

Recently garcinol (46), also called camboginol, has attracted considerable interest because of its associated beneficial health properties, including antiulcer activity [59], anti-glycation activity [60], cancer chemopreventive activity against colonic aberrant crypt foci (ACF) in an animal model [63], induction of apoptosis through cytochrome c release and activation of caspases in human leukemia cells [61]. It also showed strong antioxidant activity [59,60]. 

Krishnamurthy [73] observed that garcinol had no antioxidative activity in lipid peroxidation. Yamaguchi et al. evaluated the chelating, antioxidative and radical scavenging activities of garcinol, demonstrating that it has a strong antioxidant activity [59,60],... 

Their confirmed these results in the mycellar system [60]. Garcinol exhibited weak antioxidative activity in measurement of lipid peroxidation in mycellar system, being at most one-half as strong as a-tocopherol and weaker than catechin. 

In the DPPH (l,l-diphenyl-2-picrylhydrazyl) assay, garcinol exhibited potent radical scavenging activity at an extent almost 3 times higher than a-tocopherol and comparable to 85% of the activity of ascorbic acid [84],... 

Also in the superoxide anion scavenging assay in the phenazine methosulfate/NADH-nitroblue tetrazolium system, garcinol exhibited potent superoxide anion scavenging activity almost comparable to that of gallic acid and stronger than that of (+)-catcchin [60]. 

The radical scavenging activity of garcinol have been confirmed using the electron spin resonance (ESR) spin trapping method which observe the reaction between superoxide anion and radical scavenger more directly. 

In the Fenton reaction system, garcinol suppressed hydroxyl radical formation, dose-dependently, more strongly than a-tocopherol and catechin [59]. The suppression of hydroxyl radical in this system may be caused by direct scavenge but also by inhibition of the Fenton reaction by Fe2+ chelation for chelating activity of garcinol. 

In the FECh/NaOH/DMSO system, designed to evaluate both water-soluble and oil-soluble free radical scavengers, garcinol also suppressed the formation of free radicals such as methyl radical, hydroxyl radical and superoxide anion [59]. Garcinol suppressed hydroxyl radical in this non-Fenton type ROS generating system, in this case the reaction mechanism... 

---