1: Biomed Chromatogr. 2007 Feb;21(2):139/63.
High/performance liquid chromatography and LC/ESI/MS method for the
identification and quantification of two biologically active polyisoprenylated
benzophenones xanthochymol and isoxanthochymol in different parts of Garcinia
indica.
Kumar S, Chattopadhyay SK.
Central Institute of Medicinal and Aromatic Plants, PO CIMAP, Lucknow/226015,
India.
A reverse/phase high/performance liquid chromatographic method was developed for
qualitative and quantitative analysis of xanthochymol (1), and isoxanthochymol
(2) in the fruit rinds, leaves and seed pericarps of Garcinia indica with
confirmation using PDA detection and electrospray ionization MS. Absorption at
276 nm was chosen as the measuring wavelength at which resolution and baseline
separation of compounds (1) and (2) could be obtained. The identity of the above
two isomeric compounds (1) and (2) in the samples was unambiguously determined
by their respective quasi/molecular ion [M / H]/ in ESI/MS. Compounds (1) and
(2) were qualitatively and quantitatively analyzed in the above three samples of
Garcinia indica. The overall analytical procedure is rapid and reproducible and
is considered for the analysis of the above two compounds. Copyright 2006 John
Wiley & Sons, Ltd.
PMID: 17120303 [PubMed / in process]
2: J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Nov 21;844(1):67/83. Epub
2006 Aug 22.
Identification and quantification of two biologically active polyisoprenylated
benzophenones xanthochymol and isoxanthochymol in Garcinia species using liquid
chromatography/tandem mass spectrometry.
Chattopadhyay SK, Kumar S.
Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow 226015,
India. chattsk@yahoo.com
A sensitive liquid chromatography/electrospray ionization tandem mass
spectrometrical (LC/ESI/MS/MS) method was developed for the identification and
quantification of two polyisoprenylated benzophenones xanthochymol and
isoxanthochymol in the extracts of the fruit rinds, stem bark, seed pericarps
and leaves of Garcinia indica and in the fruit rinds of Garcinia cambogia. The
separation of xanthochymol and isoxanthochymol was achieved on a RP/18 column
using the solvent system consisting of a mixture of acetonitrile/water (9:1) and
methanol/acetic acid (99.5:0.5) as a mobile phase at a flow rate of 0.4ml/min. A
multiple reaction monitoring (MRM) method was developed for quantification of
xanthochymol and isoxanthochymol in the above extracts of Garcinia species. On
the basis of signal to noise ratio of 3, the limits of detection in MRM mode for
xanthochymol and isoxanthochymol were 1.0ng/ml and 0.5ng/ml, respectively. The
method was validated in terms of linearity, accuracy and precision for 6 days.
The method developed was found to be useful for identification and
quantification of xanthochymol and isoxanthochymol in the extracts of the fruit
rinds, stem bark, seed pericarps and leaves of G. indica and in the fruit rinds
of G. cambogia.
Publication Types:
Validation Studies
PMID: 16920410 [PubMed / indexed for MEDLINE]
3: Mol Nutr Food Res. 2005 Oct;49(10):950/6.
Influence of food acidulants on bioaccessibility of zinc and iron from selected
food grains.
Hemalatha S, Platel K, Srinivasan K.
Department of Biochemistry and Nutrition, Central Food Technological Research
Institute, Mysore 570/020, India.
Four common acidulants in Indian dietary, i. e., citric acid, tamarind
(Tamarindus indica), amchur (Mangifera indica), and kokum (Garcinia indica) were
examined for a possible influence on the bioaccessibility of zinc from selected
food grains. Among the four acidulants examined, amchur and citric acid
generally enhanced the bioaccessibility of zinc and iron from all the food
grains studied. The increase in zinc bioaccessibility produced by citric acid
was around 40% in rice and chickpea, while amchur produced around 60% increase
from decorticated green gram. This positive influence of acidulants on zinc
bioaccessibility from food grains was seen both in the raw and cooked form.
Tamarind and kokum, the other two acidulants tested, generally did not have a
favourable influence on zinc and iron bioaccessibility. This lack of positive
influence of these two acidulants on mineral availability could be attributable
to the presence of significant amounts of tannin in them. Citric acid and amchur
also generally enhanced the bioaccessibility of iron from these food grains.
Publication Types:
In Vitro
PMID: 16189798 [PubMed / indexed for MEDLINE]
4: J Cell Biochem. 2005 Sep 1;96(1):155/69.
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.
Liao CH, Sang S, Ho CT, Lin JK.
Institute of Biochemistry and Molecular Biology, College of Medicine, National
Taiwan University, Taipei, Taiwan.
Garcinol, from the fruit rind of Garcinia indica and other species, has been
reported to suppress colonic aberrant crypt foci (ACF) formation in rats. In
this study, we investigate the beneficial effects of tumor prevention by
garcinol on the human colorectal cancer cell line, HT/29. Focal adhesion kinase
(FAK) is the major signaling mediator of integrin/mediated cell/matrix
contact/regulated cellular proliferation, migration, and apoptosis in adherent
cells. Results of Matrigel analysis show that exposure of HT/29 cells to 10
microM garcinol inhibited cell invasion, and decreased the dose/dependent
tyrosine phosphorylation of FAK. We further demonstrate by Western blot analysis
that garcinol inhibited activation of the Src, MAPK/ERK, and PI3K/Akt signaling
pathways. To investigate whether the loss of integrin/mediated cell/matrix
contact can induce apoptosis, we demonstrate that garcinol induced it in HT/29
cells. The apoptotic dose of garcinol (20 microM) changed the ratio of the
anti/apoptotic Bcl/2 and proapoptotic BAX proteins within 12 h, which correlated
with a release of cytochrome c from the mitochondria to the cytosol, and with
PARP cleavage. Additionally, we demonstrate that a decreasing MMP/7 protein
level in HT/29 cells results in sensitization to garcinol. Garcinol also
significantly inhibited the expression of MMP/7 in IL/1beta/induced HT/29 cells.
These results suggest that garcinol reduces cell invasion and survival through
the inhibition of FAK's downstream signaling. Copyright 2005 Wiley/Liss, Inc
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16052481 [PubMed / in process]
5: Cancer Lett. 2005 Apr 18;221(1):29/39.
Dietary garcinol inhibits 4/nitroquinoline 1/oxide/induced tongue carcinogenesis
in rats.
Yoshida K, Tanaka T, Hirose Y, Yamaguchi F, Kohno H, Toida M, Hara A, Sugie S,
Shibata T, Mori H.
Department of Oral and Maxillofacial Surgery, Gifu University School of
Medicine, 40 Tsukasa/machi, Gifu 500/8705, Japan.
The effects of dietary feeding with a polyisoprenylated benzophenone, garcinol,
isolated from Garcinia indica fruit rind on the development of 4/nitroquinoline
1/oxide (4/NQO)/induced oral carcinogenesis were investigated in male F344 rats.
At 7 weeks of age, animals were given 4/NQO at 20 ppm in the drinking water for
8 weeks to induce tongue neoplasms. They also received the diets containing 100
or 500 ppm garcinol either during (for 10 weeks) or after (for 22 weeks) the
carcinogen exposure. The other rats were given tap water without 4/NQO
throughout the experiment, and fed garcinol (500 ppm)/containing diet or basal
diet alone. At the end of the study (week 32), incidences of tongue neoplasms
and preneoplastic lesions, cell proliferation activity in the normal/like tongue
epithelium estimated by 5/bromodeoxyurideine (BrdU)/labeling index and cyclin
D1/positive cell ratio, and immunohistochemical expression of cyclooxygenase/2
(COX/2) in the tongue lesions were determined. Dietary garcinol significantly
decreased the incidence and multiplicity of 4/NQO/induced tongue neoplasms
and/or preneoplasms as compared to the control diet. Dietary administration of
garcinol also significantly reduced the BrdU/labeling index and cyclin
D1/positive cell ratio, suggesting reduction in cell proliferation activity in
the tongue by garcinol. The COX/2 expression in the tongue lesions was also
suppressed by feeding with garcinol. These results indicate that dietary
administration of garcinol inhibited 4/NQO/induced tongue carcinogenesis through
suppression of increased cell proliferation activity in the target tissues
and/or COX/2 expression in the tongue lesions.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 15797624 [PubMed / indexed for MEDLINE]
6: Biochem Biophys Res Commun. 2005 Apr 22;329(4):1306/14.
Effects of garcinol on free radical generation and NO production in embryonic
rat cortical neurons and astrocytes.
Liao CH, Ho CT, Lin JK.
Institute of Biochemistry and Molecular Biology, College of Medicine, National
Taiwan University, Taipei, Taiwan.
Garcinol (camboginol) is a polyisoprenylated benzophenone derivative isolated
from fruit rind of Garcinia indica. This study was to elucidate the
anti/oxidative and neuroprotective properties of garcinol in rat cortical neuron
cultures. First, garcinol protects DNA from Fenton reaction/induced breakage in
a dose/dependent manner, with an IC(50) value of 0.32 microM. Garcinol also
inhibits xanthine oxidase activity with an IC(50) value of 52 microM and
exhibits competitive inhibition. To further ascertain the neuroprotective
effects of garcinol in inflammatory/mediated neurotoxicity, we utilized primary
neuron/astrocyte co/cultures treated with LPS or cytokine. Our data implicate
that treatment with garcinol (5 microM) for 7 days promotes neuronal attachment
and neurite extension. The formation of nitric oxide (NO) by LPS in rat
astrocytes has been suggested to correlate with the neurodegenerative process.
In identifying the effect of neuroprotection, we found that garcinol prevented
NO accumulation in LPS/treated astrocytes. Garcinol significantly reduced the
expression of LPS/induced inflammatory mediators, such as iNOS and COX/2.
Consequently, our results suggest that the neuroprotective effects of garcinol
are associated with anti/oxidation and inhibition of iNOS induction in
astrocytic cells. Garcinol may exert a similar anti/inflammatory effect and may
be neuroprotective against brain injury.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 15766569 [PubMed / indexed for MEDLINE]
7: Mol Carcinog. 2004 Nov;41(3):140/9.
Suppression of inducible nitric oxide synthase and cyclooxygenase/2 in
downregulating nuclear factor/kappa B pathway by Garcinol.
Liao CH, Sang S, Liang YC, Ho CT, Lin JK.
Institute of Biochemistry and Molecular Biology, College of Medicine, National
Taiwan University, Taipei 10018, Taiwan.
Garcinol is a polyisoprenylated benzophenone derivative of Garcinia indica fruit
rind and other species. Recent studies have demonstrated that garcinol exhibited
antioxidative effects in vitro. In this study, we found that garcinol inhibited
the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase/2
(COX/2) in lipopolysaccharide (LPS)/activated macrophages. Western blot analyzes
and gel/shift assays revealed that garcinol strongly blocks the activation of
eukaryotic transcription factor nuclear factor/kappa B (NF/kappa B)/induced by
LPS. Moreover, transient transfection experiments showed that garcinol inhibited
the NF/kappa B/dependent transcriptional activity. Based on these data, we
demonstrated that inhibition of LPS/induced NF/kappa B activation occurred
through suppressing the phosphorylation of I kappa B alpha and p38
mitogen/activated kinase (MAPK). Garcinol also lowers the LPS/induced increase
of intracellular reactive oxygen species (ROS), which contributes to the
activation of NF/kappa B. The NF/kappa B signaling pathway leads to inflammatory
reaction and our results suggest that garcinol suppresses the expression of iNOS
in this pathway.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 15390082 [PubMed / indexed for MEDLINE]
8: J Biol Chem. 2004 Aug 6;279(32):33716/26. Epub 2004 May 19.
Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase
inhibitor, represses chromatin transcription and alters global gene expression.
Balasubramanyam K, Altaf M, Varier RA, Swaminathan V, Ravindran A, Sadhale PP,
Kundu TK.
Transcription and Disease Laboratory, Molecular Biology and Genetics Unit,
Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur,
Bangalore/560064, India.
Histone acetylation is a diagnostic feature of transcriptionally active genes.
The proper recruitment and function of histone acetyltransferases (HATs) and
deacetylases (HDACs) are key regulatory steps for gene expression and cell
cycle. Functional defects of either of these enzymes may lead to several
diseases, including cancer. HATs and HDACs thus are potential therapeutic
targets. Here we report that garcinol, a polyisoprenylated benzophenone
derivative from Garcinia indica fruit rind, is a potent inhibitor of histone
acetyltransferases p300 (IC50 approximately 7 microm) and PCAF (IC50
approximately 5 microm) both in vitro and in vivo. The kinetic analysis shows
that it is a mixed type of inhibitor with an increased affinity for PCAF
compared with p300. HAT activity/dependent chromatin transcription was strongly
inhibited by garcinol, whereas transcription from DNA template was not affected.
Furthermore, it was found to be a potent inducer of apoptosis, and it alters
(predominantly down/regulates) the global gene expression in HeLa cells.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 15155757 [PubMed / indexed for MEDLINE]
9: J Pharm Biomed Anal. 2002 Apr 15;28(2):379/84.
Determination of organic acids in leaves and rinds of Garcinia indica (Desr.) by
LC.
Jayaprakasha GK, Sakariah KK.
Human Resource Development, Central Food Technological Research Institute,
Mysore 570 013, India. gkjp@yahoo.com
Organic acids in leaves and rinds of Garcinia indica (Kokam) were determined by
high/performance liquid chromatography. The major organic acid in leaves and
rinds has been found to be (/)/hydroxycitric acid present to the extent of
4.1/4.6 and 10.3/12.7%, respectively, by isocratic elution with 8 mM sulfuric
acid as mobile phase with a flow rate of 1.0 ml/min using UV detection at 210
nm. Hydroxycitric acid lactone and citric acid are present in leaves and rinds
in minor quantities. This method has been shown to be very reproducible with the
coefficient of variation ranging from 2.8 to 4.2%. This is the first report on
the composition of organic acids in the leaves and rinds of G. indica by HPLC.
PMID: 11929682 [PubMed / indexed for MEDLINE]
10: J Agric Food Chem. 2002 Jan 2;50(1):10/22.
Chemistry and biochemistry of (/)/hydroxycitric acid from Garcinia.
Jena BS, Jayaprakasha GK, Singh RP, Sakariah KK.
Human Resource Development, Central Food Technological Research Institute,
Mysore 570 013, India.
(/)/Hydroxycitric acid [(/)/HCA] is the principal acid of fruit rinds of
Garcinia cambogia, Garcinia indica, and Garcinia atroviridis. (/)/HCA was shown
to be a potent inhibitor of ATP citrate lyase (EC 4.1.3.8), which catalyzes the
extramitochondrial cleavage of citrate to oxaloacetate and acetyl/CoA: citrate +
ATP + CoA //> acetyl/CoA + ADP + P(i) + oxaloacetate. The inhibition of this
reaction limits the availability of acetyl/CoA units required for fatty acid
synthesis and lipogenesis during a lipogenic diet, that is, a diet high in
carbohydrates. Extensive animal studies indicated that (/)/HCA suppresses the
fatty acid synthesis, lipogenesis, food intake, and induced weight loss. In
vitro studies revealed the inhibitions of fatty acid synthesis and lipogenesis
from various precursors. However, a few clinical studies have shown
controversial findings. This review explores the literature on a number of
topics: the source of (/)/HCA; the discovery of (/)/HCA; the isolation,
stereochemistry, properties, methods of estimation, and derivatives of (/)/HCA;
and its biochemistry, which includes inhibition of the citrate cleavage enzyme,
effects on fatty acid synthesis and lipogenesis, effects on ketogenesis, other
biological effects, possible modes of action on the reduction of food intake,
promotion of glycogenesis, gluconeogenesis, and lipid oxidation, (/)/HCA as
weight/controlling agent, and some possible concerns about (/)/HCA, which
provides a coherent presentation of scattered literature on (/)/HCA and its
plausible mechanism of action and is provocative of further research.
Publication Types:
Review
PMID: 11754536 [PubMed / indexed for MEDLINE]
11: J Agric Food Chem. 2001 Mar;49(3):1464/74.
Induction of apoptosis by garcinol and curcumin through cytochrome c release and
activation of caspases in human leukemia HL/60 cells.
Pan MH, Chang WL, Lin/Shiau SY, Ho CT, Lin JK.
Institutes of Biochemistry and Toxicology, College of Medicine, National Taiwan
University, Taipei, Taiwan.
Garcinol, a polyisoprenylated benzophenone, was purified from Garcinia indica
fruit rind. The effects of garcinol and curcumin on cell viability in human
leukemia HL/60 cells were investigated. Garcinol and curcumin displayed strong
growth inhibitory effects against human leukemia HL/60 cells, with estimated
IC(50) values of 9.42 and 19.5 microM, respectively. Garcinol was able to induce
apoptosis in a concentration/ and time/dependent manner; however, curcumin was
less effective. Treatment with garcinol caused induction of caspase/3/CPP32
activity in a dose/ and time/dependent manner, but not caspase/1 activity, and
induced the degradation of poly(ADP/ribose) polymerase (PARP). Pretreatment with
caspase/3 inhibitor inhibited garcinol/induced DNA fragmentation. Treatment with
garcinol (20 microM) caused a rapid loss of mitochondrial transmembrane
potential, release of mitochondrial cytochrome c into cytosol, and subsequent
induction of procaspase/9 processing. The cleavage of D4/GDI, an abundant
hematopoietic cell GDP dissociation inhibitor for the Ras/related Rho family
GTPases, occurred simultaneously with the activation of caspase/3 but preceded
DNA fragmentation and the morphological changes associated with apoptotic cell
death. Of these, Bcl/2, Bad, and Bax were studied. The level of expression of
Bcl/2 slightly decreased, while the levels of Bad and Bax were dramatically
increased in cells treated with garcinol. These results indicate that garcinol
allows caspase/activated deoxyribonuclease to enter the nucleus and degrade
chromosomal DNA and induces DFF/45 (DNA fragmentation factor) degradation. It is
suggested that garcinol/induced apoptosis is triggered by the release of
cytochrome c into the cytosol, procaspase/9 processing, activation of caspase/3
and caspase/2, degradation of PARP, and DNA fragmentation caused by the
caspase/activated deoxyribonuclease through the digestion of DFF/45. The
induction of apoptosis by garcinol may provide a pivotal mechanism for its
cancer chemopreventive action.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 11312881 [PubMed / indexed for MEDLINE]
12: J Agric Food Chem. 2000 Jun;48(6):2320/5.
Free radical scavenging activity and antiulcer activity of garcinol from
Garcinia indica fruit rind.
Yamaguchi F, Saito M, Ariga T, Yoshimura Y, Nakazawa H.
Research and Development Division of Kikkoman Corporation, Noda/shi, Chiba
Prefecture, Japan. fyamaguchi@mail.kikkoman.co.jp
Garcinol, a polyisoprenylated benzophenone derivative, was purified from
Garcinia indica fruit rind, and its free radical scavenging activity was studied
using electron spin resonance (ESR) spectrometry. In the hypoxanthine/xanthine
oxidase system, emulsified garcinol suppressed superoxide anion to almost the
same extent as DL/alpha/tocopherol by weight. In the Fenton reaction system,
garcinol also suppressed hydroxyl radical more strongly than
DL/alpha/tocopherol. In the H(2)O(2)/NaOH/DMSO system, garcinol suppressed
superoxide anion, hydroxyl radical, and methyl radical. It was thus confirmed
that this derivative is a potent free radical scavenger and able to scavenge
both hydrophilic and hydrophobic ones including reactive oxygen species. Orally
administered garcinol prevented acute ulceration in rats induced by indomethacin
and water immersion stress caused by radical formation. These results suggested
garcinol might have potential as a free radical scavenger and clinical
application as an antiulcer drug.
PMID: 10888544 [PubMed / indexed for MEDLINE]
13: Carcinogenesis. 2000 Jun;21(6):1183/9.
Prevention of colonic aberrant crypt foci by dietary feeding of garcinol in male
F344 rats.
Tanaka T, Kohno H, Shimada R, Kagami S, Yamaguchi F, Kataoka S, Ariga T,
Murakami A, Koshimizu K, Ohigashi H.
Department of Pathology, Kanazawa Medical University, 1/1 Daigaku, Uchinada,
Ishikawa 920/0293, Japan. takutt@kanazawa/med.ac.jp
The modifying effects of dietary feeding of a polyisoprenylated benzophenone,
garcinol, isolated from Garcinia indica fruit rind on the development of
azoxymethane (AOM)/induced colonic aberrant crypt foci (ACF) were investigated
in male F344 rats. We also assessed the effects of garcinol on proliferating
cell nuclear antigen (PCNA) index in ACF and activities of detoxifying enzymes
of glutathione S/transferase (GST) and quinone reductase (QR) in liver. In
addition, we examined the effects of garcinol on
12/O/tetradecanoylphorbol/13/acetate/induced O(2)(/) generation in
differentiated human promyelocytic HL/60 cells and lipopolysaccharide (LPS)/ and
interferon (IFN)/gamma/induced nitric oxide (NO) generation in mouse macrophage
RAW 264.7 cells. Western blotting analysis of inducible nitric oxide synthase
(iNOS) and cyclooxygenase/2 (COX/2) expression was done in LPS/ and
IFN/gamma/treated mouse macrophage RAW 264.7 cells. Rats were given subcutaneous
injections of AOM (15 mg/kg body wt) once a week for 3 weeks to induce ACF. They
also received the experimental diet containing 0.01 or 0.05% garcinol for 5
weeks, starting 1 week before the first dosing of AOM. AOM exposure produced 97
+// 15 ACF/rat at the end of the study (week 5). Dietary administration of
garcinol caused significant reduction in the frequency of ACF: 72 +// 15 (26%
reduction, P < 0.01) at a dose of 0.01% and 58 +// 8 (40% reduction, P < 0.001)
at a dose of 0.05%. Garcinol administration significantly lowered PCNA index in
ACF. Feeding of garcinol significantly elevated liver GST and QR activities. In
addition, garcinol could suppress O(2)(/) and NO generation and expression of
iNOS and COX/2 proteins. These findings might suggest possible chemopreventive
ability of garcinol, through induction of liver GST and QR, inhibition of
O(2)(/) and NO generation and/or suppression of iNOS and COX/2 expression, on
colon tumorigenesis.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 10837008 [PubMed / indexed for MEDLINE]
14: J Agric Food Chem. 2000 Feb;48(2):180/5.
Antioxidative and anti/glycation activity of garcinol from Garcinia indica fruit
rind.
Yamaguchi F, Ariga T, Yoshimura Y, Nakazawa H.
Research and Development Division, Kikkoman Corporation, Noda 399, Noda/shi,
Chiba Pref. 278/0037, Japan. fyamaguchi@mail.kikkoman.co.jp
Garcinol, a polyisoprenylated benzophenone derivative, was purified from
Garcinia indica fruit rind, and its antioxidative activity, chelating activity,
free radical scavenging activity, and anti/glycation activity were studied.
Garcinol exhibited moderate antioxidative activity in the micellar linoleic acid
peroxidation system and also exhibited chelating activity at almost the same
level as citrate. It also showed nearly 3 times greater DPPH (1,
1/diphenyl/2/picrylhydrazyl) free radical scavenging activity than
DL/alpha/tocopherol by weight in aqueous ethanol solution. In a phenazine
methosulfate/NADH/nitroblue tetrazolium system, garcinol exhibited superoxide
anion scavenging activity and suppressed protein glycation in a bovine serum
albumin/fructose system. Thus, garcinol might be beneficial as a potent
antioxidant and a glycation inhibitor under specified conditions.
PMID: 10691613 [PubMed / indexed for MEDLINE]
