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1. Food Research International 44 (2011) 1790–1799
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Food Research International
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / f o o d r e s
The chemistry and medicinal uses of the underutilized Indian fruit tree Garcinia
indica Choisy (kokum): A review
Manjeshwar Shrinath Baliga a,⁎, Harshith P. Bhat d, Ramakrishna J. Pai b, Rekha Boloor b, Princy Louis Palatty c
a
Department of Research and Development, Father Muller Road, Kankanady, Mangalore, Karnataka 575003, India
b
Department of Microbiology, Father Muller Road, Kankanady, Mangalore, Karnataka 575003, India
c
Department of Pharmacology, Father Muller Medical College, Father Muller Road, Kankanady, Mangalore, Karnataka 575003, India
d
Research Centre, Maharani Lakshmi Ammani Women's College, Malleswaram 18th Cross, Bangalore 560012, Karnataka, India
a r t i c l e i n f o a b s t r a c t
Article history: Garcinia indica Choisy Syn Brindonia indica, commonly known as kokum and belonging to Guttiferae family, is
Received 7 September 2010 a plant native to certain regions of India. The trees yield fruits annually in the summer season during the
Accepted 28 January 2011 months of March to May. The fruits are green when raw and red to dark purple when fully ripe. They are used
to prepare juice, pickles and as acidulant in curries. In the traditional Indian system of medicine the Ayurveda
Keywords:
and in various folk systems of medicine, the fruit rinds and leaves are used to treat various inflammatory
Garcinia indica Choisy Syn Brindonia indica
Kokum
ailments, rheumatic pain and bowel complaints. The kokum butter prepared from the seed is of both
Phytochemistry commercial and medicinal use. Chemical studies have shown that the rind contains protein, tannin, pectin,
Pharmaceutical uses sugars, fat, organic acids like (−)-hydroxycitric acid, hydroxycitric acid lactone and citric acid; the
Health benefits anthocyanins, cyanidin-3-glucoside and cyanidin-3-sambubioside; and the polyisoprenylated phenolics
Pharmacology garcinol and isogarcinol. Preclinical studies have shown that kokum or and some of its phytochemicals
possess antibacterial, antifungal, anti-ulcerogenic, cardioprotective, anticancer, chemopreventive, free radical
scavenging, antioxidant and anti-obesity effects. The present paper reviews the nutritional value, the
phytochemical compounds, traditional uses and validated pharmacological properties of kokum.
© 2011 Elsevier Ltd. All rights reserved.
Abbreviations: TPA, 12-O-tetradecanoylphorbol-13-acetate; AAPH, 2, 2′-azobis
1. Introduction
(2-amidino-propane) dihydrochloride; ABTS, 2,2′-azino-bis(3-ethylbenzthiazoline-6-
sulphonic acid); MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; Indigenous fruits and vegetables are a major source of nutrition to
4-NQO, 4-nitroquinoline 1-oxide; 5LO, 5-lipoxygenase; DMBA, 7,12-dimethylbenz[α] the local people and more so in the rural areas, where the availability
anthracene; DPPH, 1,1-diphenyl-2-picrylhydrazyl; AP-1, Activator protein 1; Apc,
of the food is less or is unaffordable especially to the poor people.
Adenomatous polyposis coli; AOM, Azoxymethane; LPS, Bacterial lipopolysaccharides;
CVD, Cardiovascular diseases; COX-2, Cyclooxygenase 2; cPLA2, Cytosolic phospholipases Garcinia indica Choisy Syn Brindonia indica (Fig. 1) belonging to the
A2; eNOS, Endothelial nitric oxide synthase; ERK1/2, Extracellular signal-regulated kinase family Guttiferae (in the mangosteen) is an indigenous tree of India
1/2; FRAP assay, Ferric Reducing Antioxidant Power assay; Glut 4, Glucose transporter 4; (Chandran, 1996; Padhye, Ahmad, Oswal, & Sarkar, 2009). It was
GST, Glutathione S-transferase; GSK3β, Glycogen synthase kinase 3 beta; iNOS, Inducible originally found only in the western peninsular coastal regions and
nitric oxide synthase; IC50, Inhibitory concentration 50; IFN-γ, Interferon gamma; IL1β,
Interleukin-1beta; MMP-2, Matrix matalloprotinase-2; mPGES-1, Microsomal prostaglan-
the adjoining Western Ghats in the states of Maharashtra, Goa,
din PGE2 synthase; MIC, Minimum inhibitory concentration; MAPK, Mitogen activated Karnataka and Kerala, India as well as parts of Eastern India in the
kinase; NO, Nitric Oxide; NF-kB, Nuclear factor-kappa B; ORAC assay, Oxygen Radical states of West Bengal, Assam and North Eastern Hill regions, but is
Absorbance Capacity assay; PPARγ, Peroxisome proliferator-activated receptor gamma; today found growing in other parts of peninsular India (CHEMEXCIL,
PAI, Plasminogen activator inhibitor; PCNA, Proliferating Cell Nuclear Antigen; PGE2,
1992; Chandran, 1996). It is an underexploited tree and is known as
Prostaglandin E2; PGH2, Prostaglandin H2; QR, Quinone reductase; RNS, Reactive nitrogen
species; ROS, Reactive oxygen species; RBP4, Retinol binding protein 4; STAT-1, Signal wild mangosteen, kokam, goa butter tree, kokum butter tree in
transduction and activation of transcription-1; TIMP-2, Tissue inhibitor of matrix English; Vrikshamia, Vrikshamla, Amlabija, raktavrikshamla, Amla-
matalloprotinase 2; TNF-α, Tumor necrosis factor; UVB, Ultraviolet radiation B; u-PA, pura, Amlashaka in Sanskrit; kokum in Hindi; bheranda in Marathi;
Urokinase plasminogen activator. punarpuli in tulu; bhiranda, murgal and murgal-mara in Tamil;
⁎ Corresponding author at: Department of Research and Development, Father Muller
Medical College, Father Muller Road, Kankanady, Mangalore, Karnataka 575003, India.
kaattampi in Malayalam; Goraka in Sinhala; murgina, punarpuli,
Tel.: +91 824 2238331(office); fax: +91 824 2437402, +91 824 2436352. devana huli in Kannada; tintali in Oriya; kokam in Gujarati and
E-mail address: msbaliga@gmail.com (M.S. Baliga). bhirind in Konkani (CHEMEXCIL, 1992; Chandran, 1996).
0963-9969/$ – see front matter © 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.foodres.2011.01.064

2. M.S. Baliga et al. / Food Research International 44 (2011) 1790–1799 1791
Fig. 1. Photograph of Kokum fruits and leaves. a: Plant with raw and ripe fruits; b: Raw fruits and ripe fruit with the inner seed arranged like in orange; c: Raw fruit rind and seed d:
dried rinds
2. Botanical description The fruits are round, oblong or oval with pointed tips and, are
crowned by the four parted stalkless stigma (Fig. 1a and b). When raw
Kokum is a slender but very sturdy evergreen tree and does not need they are dark to light green in color and crimson red with a yellow
elaborate irrigation or use of fertilizers, pesticides or herbicides. The tinge to dark violet or purple when fully ripe (Fig. 1a and b). The fruits
trees are normally found growing in the riversides, forests, wastelands are initially small and grow up to the size of a lemon. An average
and have been recently cultivated for their fruits. It is a slow growing kokum tree bears hundreds of fruits and each fruits weigh around
tree and the propagation is usually by sowing the seeds in the plastic 21–85 g. The fruit contains three to eight large seeds and is covered
bags/pots and then transplanting the seedlings into the pits. Plantlets with whitish sweet pulp. The seeds are placed in a pattern similar to
can also be generated by adventitious bud differentiation on mature that in orange (Fig. 1b and c) (Nayak, Rastogi, et al., 2010). The ripe
seeds and by in vitro propagation (Nayak, Rastogi, & Raghavarao, 2010). fruits are sour to taste and have a short shelf life of approximately a
From the time of planting, a seedling requires about six to seven years to week. If left unattended the fully ripe fruits drop to the ground and the
grow and fruit. The maximum yield is mostly observed in a tree that is injured fruits may be easily infested and spoilt by micro organisms
20–50 years old (Krishnamurthy, 1984). especially by the yeasts and fungi. The fruits are manually harvested,
Kokum tree is dioecious (having separate male and female plants) deseeded and the rinds sun dried. The rinds appear black in color, are
and grows up to a height of 12 to 20 m. The tree has branches that are shrunken and hard (Fig. 1d). Drying decreases the water activity
drooping and the canopy is dense with green leaves. The emerging required for the growth of microbes and concomitantly increases the
young leaves are tender and red-tinged (Chandran, 1996). The leaves shelf life of the rind. This helps in making the rinds available
are simple, opposite, elliptic or oblong and deep green in color in the throughout the year for human consumption.
upper side, while pale in the lower side. They are 5 to 8 cm in length The seed amounts to nearly a quarter of the total fruit weight and
and 2.5–3.5 cm in breadth and shining (Chandran, 1996). The flowers chemical studies have shown that it contains 23–26% oil. The oil
are fleshy, dark pink, solitary or in spreading cluster (Krishnamurthy, remains solid at room temperature and is colloquially known as
1984; Nayak, Rastogi, et al., 2010). The mature trees flower annually kokum butter. The extraction of oil is a laborious process and is
during the winter in the months of November–February. The process performed in the extractor. The kokum seeds are first decorticated
of fruiting takes approximately five months to complete and by May, and the kernels are carefully separated. The kernels are then pressed
the ripe fruits are ready for harvesting (Chandran, 1996; Nayak, in expeller to extract oil. The cake left after extraction of the kokum
Rastogi, et al., 2010). butter may be used as cattle feed and also as an organic manure for

3. 1792 M.S. Baliga et al. / Food Research International 44 (2011) 1790–1799
plantation crops. Kokum butter is light gray to yellow in color, greasy Nayak, Rastogi, et al., 2010; Nayak, Srinivas, & Rastogi, 2010). The rinds
in texture and is bland to taste (Nayak, Rastogi, et al., 2010). also contain two polyisoprenylated phenolics garcinol and isogarcinol
(Rastogi & Mehrotra, 1990). Studies have shown that (−)-hydroxycitric
3. Proximate and phytochemical composition of kokum acid (HCA) is the major organic acid in kokum leaves and rinds. It is
responsible for the savory taste of kokum and is present to the extent of
Studies have shown that the rind contains moisture (80.0 g/100 g), 4.1–4.6 and 10.3–12.7%, respectively in leaves and fruits. The plant also
protein (1%), tannin (1.7%), pectin (0.9%), Total sugars (4.1%) and fat contains hydroxycitric acid lactone and citric, but in minor quantities
(1.4%) (Krishnamurthy, Lewis, & Ravindranath, 1982; Nayak, Rastogi, (Jayaprakasha & Sakariah, 2002). Some of the important phytochemicals
et al., 2010). Kokum leaves are reported to contain 75% moisture, 2.3 g present in kokum are represented in Fig. 2.
of protein, 0.5 g of fat, 1.24 g fiber, 17.2 g of carbohydrates, 15.14 mg
of iron, 250 mg of calcium, 10 mg of ascorbic acid and 18.10 mg of 4. Culinary uses of kokum
oxalic acid (Sheela, Nath, Vijayalakshmi, Yankanchi, & Patil, 2004).
The seed is very rich in stearic, oleic and stearic triglycerides Kokum is an important culinary agent and is used as an acidulant
(Dushyantha, Girish, Suvarna, & Dushyantha, 2010). for curries by people living in Maharashtra, costal Karnataka and Goa,
Phytochemical studies have shown that when compared with any India. In summer the ripe rinds are ground in a blender with sugar and
other natural sources, kokum rind contains the highest concentration of cardamom and consumed as a cooling drink (Shenoy, 1989; Menezes,
anthocyanins (2.4 g/100 g of kokum fruit) (Nayak, Rastogi, et al., 2010; 2000, 2002; Padhye et al., 2009). Addition of kokum is supposed to
Nayak, Srinivas, et al., 2010). The anthocyanins cyanidin-3-glucoside enhance the taste of coconut-based curries and to remove the
and cyanidin-3-sambubioside are the major pigment present in kokum unpleasant smell of mackerel and sardines (Menezes, 2000, 2002).
and is reported to occur in the ratio of 4:1 (Krishnamurthy et al., 1982; They are also used in some vegetable dishes and to prepare chutneys
Fig. 2. Important phytochemicals of Kokum.

4. M.S. Baliga et al. / Food Research International 44 (2011) 1790–1799 1793
and pickles (especially with prawns and cartilaginous fishes like 7.1. Antibacterial effects
sharks, ray fish and other cartilagenous fish) (Menezes, 2000, 2002).
The Konkani community of Goa and Karnataka, India make a simple Since its discovery, antibiotics have been an important chemo-
soup like item known as birindi saar from the rinds (Shenoy, 1989). therapeutic agent for controlling pathogenic bacteria. However the
The Goans regularly prepare kokum kadi or birinda sol kadi by mincing recent development and spread of microbes that are resistant to the
the kokum rinds and coconut milk together and seasoning it with existing antibiotics are a major problem. These bacteria fail to respond
garlic, green chillies, coriander leaves and curry leaves. This curry is to treatment, which will then result in prolonged illness and increase
used with rice or like an aftermeal digestive drink. Both birindi saar the risk of death (Negi & Jayaprakasha, 2006). The aqueous extract of
and kokum kadi are supposed to be digestive and to relieve gastric the kokum rind is reported to inhibit growth of Escherichia coli,
problems (Shenoy, 1989; Menezes, 2000, 2002). Bacillus subtilis, Enterobacter aerogenes and Staphylococcus aureus. The
highest effect was observed in B. subtilis and the least on S. aureus.
5. Industrial use Moderate inhibition was shown in other bacteria (1.5 mm). Minimum
inhibition concentration studies showed that 0.5 mg/ml of the extract
The kokum rinds are commercially used to prepare concentrated concentration was required for inhibiting E. coli, while 5 mg/ml for B.
syrups which on appropriate dilution gives the ready to use cool subtilis and E. aerogenes and 50 mg/ml was required to inhibit S.
health drinks especially during the off season periods. The local Aureus (Varalakshmi, Sangeetha, Shabeena, Sunitha, & Vapika, 2010).
community of Goa also use the rinds to prepare wine. Dried rinds are The organic extract (hexane and benzene) of the spent rinds of
powdered and marketed to be used as acidulant for traditional curries kokum and the active principle garcinol are also reported to possess
(Nayak, Rastogi, et al., 2010). Kokum butter isolated from the seeds is antibacterial action (Negi & Jayaprakasha, 2006). However garcinol is
in great demand in confectionery, medicines and cosmetic industries. reported to be ineffective on gram-negative enteric bacilli (Bakana
Kokum butter has fatty acid and triacylglycerol compositions, et al., 1987). The kokum leaf extract also possesses antibacterial effect
tolerance toward milk fat and solidification properties similar to against the pathogenic Salmonella typhi, Salmonella paratyphi A, and
those of cocoa butter (Reddy & Prabhakar, 1994). These properties are Salmonella typhimurium (Pasha, Sayeed, Ali, & Khan, 2009). The
considered ideal in confectionary industry and kokum is used as a phytochemicals of kokum garcinol, isogarcinol and xanthochymol
replacement to cocoa butter in the preparation of chocolates (Reddy & inhibits growth of methicillin-resistant S. aureus with lowest
Prabhakar, 1994). Studies have also shown that kokum butter when minimum inhibitory concentration being observed in the range of
used along with cocoa butter increases the heat-resistance property of 3.1–12.5 μg/ml and equal to that of vancomycin (Iinuma et al., 1996).
cocoa butter and chocolate and is helpful in preventing the heat- Garcinol has also been observed to be effective and to enhance the
induced softening and loss of consistency of chocolates (Maheshwari antibacterial effects of clarithromycin on H. pylori (Sang et al., 2001;
& Reddy, 2005; Reddy & Prabhakar, 1994). The kokum butter is also of Sang et al., 2002). Together, these observations suggest the usefulness
use in the production of soaps and candle (Bhat, Kamat, & Shirodkar, of kokum and its phytochemicals as antibacterial agents and suggest
2005; Nayak, Rastogi, et al., 2010). the requirement for detail investigations.
7.2. Antifungal effects
6. Traditional medicinal uses
Increase in the incidence of invasive fungal infections coupled with
Kokum has a long history of use in the Indian traditional system of limited potency, drug related toxicity, non-optimal pharmacokinetics
medicine, the Ayurveda. The leaves and fruits are sour, astringent, and development of resistence to some agents by certain fungal
thermogenic, constipating and digestive. The herbal preparations made strains have necessitated the need for newer effective agents from
from kokum rinds are used in the treatment of inflammatory ailments, natural products (Perlin, 2009). With regard to kokum the aqueous
for rheumatic pains and bowel complaints. The fruit is considered to be extract was tested on Candida albicans, Aspergillus niger, Fusaruum sp.
antihelmintic and cardiotonic (CHEMEXCIL, 1992). The juice (sherbet) and Penicillium sp. The extract was effective only against C. albicans
made out of the rind is used for piles, hemorrhoids, colic problems, and Penicillium sp and the minimum inhibition concentration was
ulcers, inflammations, treat sores, dermatitis, diarrhea, dysentery, ear observed to be 0.5 mg/ml (Varalakshmi et al., 2010). Studies have also
infection, to facilitate digestion and to prevent over perspiration or shown that the chloroform extract prepared from the rinds inhibit the
hyper perspiration (CHEMEXCIL, 1992). Kokum is a natural antacid and growth of Aspergillus flavus and production of aflatoxin (Selvi, Joseph,
the preparation rind, yogurt and salt is supposed to relieve gastric & Jayaprakasha, 2003). Together these observations clearly suggest
ulcerations and burning sensation (CHEMEXCIL, 1992). The Kokum the usefulness of kokum in the prevention of fungal infections and
butter is useful in dysentery, diarrhea, phthisis pulmonalis and scorbutic possibly to increase the shelf life of grains.
diseases. Application of kokum butter on the skin is known to possess
wound healing property and to be useful in ameliorating ulcerations, 7.3. Free radical scavenging properties
fissures of the lips, hands, chapped skin and inflammatory sores. The
young leaves are useful in preventing dysentery. The leaves are also used Free radicals, consisting of ROS and RNS when generated in excess
to treat skin ulcers inflammations, hemorrhoids, diarrhea, dysentery, cause damage to DNA, lipids, proteins, and other biomolecules.
flatulent colic, dyspepsia and hyperplasia (CHEMEXCIL, 1992). Accordingly, antioxidants are needed to prevent the formation/ nullify
the deleterious effects of the ROS and RNS. Many medicinal plants and
7. Validated studies fruits rich in polyphenols like anthocyanins, flavanoids, terpens, etc.
have been reported to be effective at scavenging these free radicals
Being an indigenous tree and localized to selected geographical and to prevent the ensuing damage (Sánchez-Moreno, Larrauri, &
pockets of India, the scientific studies, especially on the pharmaco- Saura-Calixto, 1999; Alia et al., 2008; Leopoldini, Rondinelli, Russo, &
logical properties of kokum have been minimal. However some of the Toscano, 2010; Rufino, Alves, Fernandes, & Brito, in press).
phytochemicals like cyanidin-3-glucoside, garcinol and (−)-hydro- With regard to kokum, Selvi et al. (2003) showed that the
xycitric acid, which are present in other species of the family and chloroform extract prepared from the rinds of kokum possess
plants have been studied in detailed (Padhye et al., 2009). Some of the antioxidant properties. The authors used the standard β-carotene-
relevant pharmacological properties of these compounds have also linoleate and 1, DPPH assays and observed the extract was effective in
been addressed in the following sections (Table 1). scavenging the free radicals. The extract exhibited 53% and 73%

5. 1794 M.S. Baliga et al. / Food Research International 44 (2011) 1790–1799
Table 1
Effect of kokum and its phytochemicals in exerting the various pharmacological properties in experimental systems of study.
Pharmacological properties Observations and references
Antioxidant effects 1. Chloroform extract of rinds possess antioxidant properties in β-carotene-linoleate and DPPH assays in vitro (Selvi et al., 2003).
2. The marketed concentrated syrup, cold aqueous and hot (boiled) aqueous extract of kokum also possesses antioxidant effects
(Mishra et al., 2006).
3. Garcinol chelates iron (Yamaguchi et al., 2000), scavenges DPPH (Yamaguchi et al., 2000), superoxide anion (Yamaguchi et al.,
2000), hydroxyl radical (Yamaguchi et al., 2000) and inhibits activity of xanthine oxidase (Liao et al., 2004).
4. Garcinol reduces the levels of LPS-induced intracellular reactive oxygen species (Liao et al., 2004).
5. Garcinol inhibited TPA-induced superoxide generation in differentiated human promyelocytic HL-60 cells and LPS and
IFN-γ-induced nitric oxide generation in the mouse macrophage RAW 264.7 cells (Tanaka et al., 2000).
6. Cyanidin-3-glucoside scavenges UVB-induced hydroxyl and superoxide radicals in the cultured JB6 cells (Ding et al., 2006),
protected Caco-2 colon cancer cells against the peroxyl radical (AAPH)-induced oxidative damage (Elisia & Kitts, 2008).
Inhibition of lipid peroxidation 1. The marketed concentrated syrup, cold aqueous and hot (boiled) aqueous extract of kokum inhibited the
ascorbate — Fe2+-induced lipid peroxidation in the rat liver mitochondrial fraction (Mishra et al., 2006).
2. Garcinol ineffective in inhibiting lipid peroxidation in the micellar system (Yamaguchi et al., 2000), but was effective in
inhibiting peroxynitrite-induced lipid peroxidation in blood platelets and plasma (Kolodziejczyk et al., 2009).
Inhibition of carbonyl content 1. Garcinol reduces the peroxynitrite-induced carbonylation in the blood platelets and plasma (Kolodziejczyk et al., 2009).
Anticlastogenic effects 1. Garcinol scavenged the hydroxyl radical and prevented DNA damage to the pUC-19 plasmid (Liao et al., 2004).
Anti-glycation activities 1. Garcinol suppresses protein glycation in the bovine serum albumin/fructose system (Yamaguchi et al., 2000).
Inhibitory effects on elastase and 1. Methanolic extract of kokum rind as well as the ethyl acetate and water fraction possess anti-hyaluronidase and anti-elastase
hyaluronidase activities in vitro (Sahasrabudhe & Deodhar, 2010).
Antibacterial 1. Aqueous extract of kokum rind possess antibacterial effects (Varalakshmi et al., 2010).
2. The organic extract (hexane and benzene) of spent rinds and garcinol are also reported to possess antibacterial action
(Negi & Jayaprakasha, 2006).
3. Kokum leaf possesses antibacterial effects (Pasha et al., 2009).
4. The phytochemicals garcinol, isogarcinol and xanthochymol possess antibacterial activity against methicillin-resistant
Staphylococcus aureus (Iinuma et al., 1996).
5. Garcinol effective alone and in combination with clarithromycin on the H. pylori (Sang et al., 2001; Sang et al., 2002) but is
ineffective on gram-negative enteric bacilli (Bakana et al., 1987).
Antifungal activity 1. Aqueous extract possess antifungal action on Candida albicans and Penicillium sp (Varalakshmi et al., 2010).
2. The chloroform extract from spent rinds inhibits the growth of and production of aflatoxin by Aspergillus flavus
(Selvi et al., 2003).
Gastroprotective effects 1. Garcinol reduced indomethacin-induced and water immersion stress-induced gastric ulceration in rats
(Yamaguchi et al., 2000).
2. Garcinol alone (Chatterjee et al., 2003) and in combination with clarithromycin (Chatterjee et al., 2005) inhibits the growth of
H. Pylori.
Neuroprotection 1. Garcinol prevented the nitric oxide accumulation in LPS-treated astrocytes and reduced expression of LPS-induced
inflammatory mediators, iNOS and COX-2 (Liao et al., 2005).
2. Garcinol possesses anti-cholinesterase (Lenta et al., 2007).
3. Cyanidin-3-glucoside decreased ethanol-mediated activation of GSK3β, blocked ethanol-induced intracellular accumulation
of reactive oxygen species, the neurite outgrowth and expression of neurofilament proteins (Chen et al., 2009).
Anti-obesity activity 1. Hydroxycitric acid reported to possess anti-obesity effects by suppressing fatty acid synthesis, lipogenesis, food intake, and
induced weight loss (Jena et al., 2002).
2. Feeding cyanidin 3-glucoside-rich corn suppressed high fat diet-induced increase in body weight gain, and white and brown
adipose tissue weights in mice (Tsuda et al., 2003).
Antidiabetic activities 1. Aqueous extract of the kokum rind decreases streptozotocin-induced hyperglycemia (Kirana & Srinivasan, 2010).
2. Feeding cyanidin 3-glucoside caused a reduction in the blood glucose levels and enhanced insulin sensitivity, upregulated the
glucose transporter 4 (Glut4) and down regulated RBP4 in the white adipose tissue (Sasaki et al., 2007).
Cardioprotective effects 1. Cyanidin-3-glucoside causes a concentration and time dependent enhancement in the levels of endothelial nitric oxide
synthase on bovine artery endothelial cells (Xu et al., 2004).
Antineoplastic and Chemopreventive effects 1. The aqueous extract of kokum rind possesses inhibitory effect on cultured 3 T3 mouse fibroblasts (Varalakshmi et al., 2010).
2. The phytochemicals garcinol and isogarcinol affected the growth and proliferation of human leukemia cell lines (Matsumoto
et al., 2003).
3. Garcinol decrease the cell viability, increased cell death and apoptosis in human leukemia HL-60 cells (Pan et al., 2001), HeLa
cells (Balasubramanyam et al., 2004), human colorectal cancer cell line HT-29 (Liao et al., 2005) and human breast cancer cells
the ER-positive MCF-7 and ER-negative MDA-MB-231 cells (Ahmad et al., 2010).
4. Garcinol enhances TRAIL-induced apoptosis of cancer cells including the TRAIL-resistant cells (Prasad et al., 2010).
5. Garcinol inhibited Nic-induced human breast cancer (MDA-MB-231) cell proliferation (Chen et al., 2011).
6. Garcinol inhibited cell invasion reduced the levels of MMP-7 in HT-29 cells (Liao et al., 2005).
7. Cyanidin-3-glucoside also caused a dose-dependent inhibitory effect on the migration and invasion of metastatic A549 human
lung carcinoma cells (Chen et al., 2006).
8. Feeding garcinol shown to prevent 4-NQO-induced oral carcinogenesis in rats (Yoshida et al., 2005).
9. Garcinol prevented AOM-induced colonic aberrant crypt foci in rats (Tanaka et al., 2000).
10. Cyanidin-3-glucoside decreased the number of non-malignant and malignant skin tumors in the two staged skin
carcinogenesis, reduced the size of A549 tumor xenograft growth and significantly inhibited metastasis in nude mice by
inhibiting migration and invasion of A549 tumor cells (Ding et al., 2006).
11. Feeding cyanidin-3-glucoside containing diet to the Apc (Min) mouse also decreased the intestinal adenomas (Cooke et al., 2006).
antioxidant effects at 50 and 100 ppm concentrations, in the β- effective in scavenging the free radicals (Mishra, Bapat, Tilak, &
carotene-linoleate assay. In the DPPH assay it was observed that the Devasagayam, 2006). In the FRAP assay, the hot aqueous kokum
extract was very effective and caused 60 and 78% free radical extract was best followed by the syrup and the aqueous extract. In the
scavenging activity at 25 and 50 ppm concentrations respectively ABTS assay, the kokum syrup was most effective followed by the cold
(Selvi et al., 2003). aqueous extract and the hot aqueous extract radical formation. In the
Studies have also shown that the marketed concentrated syrup, ORAC assay, the cold aqueous extract was better than the hot aqueous
cold aqueous and hot (boiled) aqueous extract of kokum are also and kokum syrup (Mishra et al., 2006).

6. M.S. Baliga et al. / Food Research International 44 (2011) 1790–1799 1795
The phytochemical garcinol is also reported to chelate iron wrinkled (Sahasrabudhe & Deodhar, 2010). Exposure of skin to sun
(Yamaguchi, Ariga, Yoshimura, & Nakazawa, 2000), scavenge DPPH and detrimental chemicals also hasten the process of aging and
free radical (Yamaguchi et al., 2000), superoxide anion (Yamaguchi wrinkling and application of antioxidant rich cosmaceuticals is known
et al., 2000), hydroxyl radical (Yamaguchi et al., 2000) and inhibit to retard the process (Baliga & Katiyar, 2006).
xanthine oxidase activity (Liao, Sang, Liang, Ho, & Lin, 2004). Studies Recently, Sahasrabudhe and Deodhar (2010) have observed that the
with cultured primary neuron/astrocyte have shown that garcinol whole methanolic extract as well as the ethyl acetate and water fraction
(5 μM) treatment for 7 days promotes neuronal attachment and of the methanolic extract prepared from the rind possess anti--
causes neurite extension. It also prevented the LPS-induced formation hyaluronidase and anti-elastase activities in vitro. The authors observed
and accumulation of nitric oxide by reducing the expression of that the ethyl acetate fraction showed significant hyaluronidase
inflammatory mediators, such as iNOS and COX-2 in the macrophages inhibition and at a low concentration (25 μg/ml), while the aqueous
(Liao et al., 2004) and rat astrocytes (Liao, Ho, & Lin, 2005). fraction was effective against both elastase and hyaluronidase (90 μg/
Garcinol reduced the levels of LPS-induced intracellular ROS, ml) (Sahasrabudhe & Deodhar, 2010). Kokum pigments are also
blocked the activation of NF-kB, inhibited NF-kB-dependent tran- reported to possess UV light absorbing properties, suggesting its
scriptional activity and suppressed phosphorylation of IkBa and p38- usefulness in skin care (Bhat et al., 2005; Nayak, Rastogi, et al., 2010).
MAPK (Liao et al., 2004). Garcinol inhibited TPA-induced superoxide
generation in differentiated human promyelocytic HL-60 cells and LPS 7.6. Neuroprotective effects
and IFN-γ -induced nitric oxide generation in the mouse macrophage
RAW 264.7 cells (Tanaka et al., 2000). Together all these observations Neurodegenerative diseases as diverse as Alzheimer's, Parkinson's,
suggest the utility of garcinol as an antioxidant. and Creutzfeldt–Jakob disease are a major global health burden and
Studies have also shown that cyanidin-3-glucoside, the anthocyanins considerably affect the aging population (Aruoma, Bahorun, & Jena,
present in the rind of kokum also possess antioxidant activity. Cyanidin- 2003). Imbalanced metabolism and excess generation of ROS and RNS
3-glucoside scavenged ultraviolet B-induced hydroxyl and superoxide are known to initiate/fasten Neurodegeneration and antioxidants are
radicals in the cultured JB6 cells (Ding et al., 2006). The anthocyanins rich proven to prevent/reduce the ensuing damage to the neuronal system
in cyanidin-3-glucoside is also shown to protect the Caco-2 colon cancer (Uttara, Singh, Zamboni, & Mahajan, 2009). In vitro studies have shown
cells against the peroxyl radical (AAPH)-induced oxidative damage and that pretreatment of primary neuron/astrocyte with garcinol (5 μM for
to reduce its cytotoxicity (Elisia & Kitts, 2008). These observations clearly 7 days) promotes neuronal attachment and neurite extension. Garcinol
suggest that kokum and some of its phytochemicals possess good free prevented the nitric oxide accumulation in LPS-treated astrocytes and
radical scavenging and antioxidant effects and to be of immense use in this was due to reduction in the expression of LPS-induced inflamma-
ameliorating the various pathological ailments. tory mediators, iNOS and COX-2 (Liao et al., 2005). Garcinol is also
reported to possess anti-cholinesterase properties and the observed IC50
7.4. Anti Lipid peroxidation and anti-carbonyl activities of 0.66 μM was comparable to that of the standard Galanthamine
(0.50 μM) (Lenta et al., 2007).
Excess generation of free radicals damages the lipid membranes and Studies with mouse Neuro2a (N2a) neuroblastoma cells have also
causes loss of cell functioning and cell death. The process of lipid shown that cyanidin-3-glucoside possess neuroprotective effects.
peroxidation gives rise to a number of secondary products and one of the Cyanidin-3-glucoside blocked ethanol-induced intracellular accumula-
products, malondialdehyde is reported to be mutagenic, atherogenic and tion of ROS, reversed the ethanol-mediated activation of GSK3β,
is implicated in the pathogenesis of various diseases (Del Rio, Stewart, & inhibited the neurite outgrowth and the expression of neurofilament
Pellegrini, 2005). Therefore, prevention of lipid peroxidation is extremely proteins (Chen et al., 2009). Together these observations clearly suggest
important for the optimal functioning of the cell. Studies by Mishra et al. that cyanidin-3-glucoside and garcinol possess neuroprtotective effects
(2006) have shown that that kokum extracts and syrup inhibited the and warranty detail studies in relevant animal models.
ascorbate — Fe2+-induced lipid peroxidation in the rat liver assay in
vitro. The kokum syrup was the most effective followed by the cold 7.7. Gastroprotective effects
aqueous and hot aqueous extracts (Mishra et al., 2006). With regard to
garcinol, the observations on its anti-lipid peroxidative properties are Peptic ulcer is a multifactorial disease and affects a significant
contradictory. Garcinol is also reported to be effective in inhibiting number of the global population. Studies have shown that the oral
peroxynitrite-induced lipid peroxidation in blood platelets and plasma administration of garcinol (40–200 mg/kg) reduced the indometha-
(Kolodziejczyk, Masullo, Olas, Piacente, & Wachowicz, 2009). cin — induced gastric ulcerations in rats. The optimal effects were
The ROS and RNS also have deleterious effects on proteins and may observed at 200 mg/kg and the protective effects were better than
contribute to tissue inflammation and cell death. The glutamic that of cetraxate-HCl used as a positive control (Yamaguchi et al.,
semialdehyde (arginine and proline oxidation), and aminoadipic 2000). Garcinol was also effective in reducing water (23 °C)
semialdehyde (oxidation of lysine) are the main carbonyl products immersion-induced gastric ulceration and the effects were similar
and affect the cell functioning (Requena, Levine, & Stadtman, 2003). In to that of cetraxate-HCl used as positive control (Yamaguchi et al.,
vitro studies have shown that garcinol reduces the peroxynitrite- 2000). In vitro studies have also shown that garcinol was effective on
induced formation of carbonyl groups in the blood platelets and plasma H. Pylori, a causative agent of gastric ulcerations and cancer, both
(Kolodziejczyk et al., 2009). Together these observations suggest the alone (Chatterjee, Yasmin, Bagchi, & Stohs, 2003) and in combination
usefulness of kokum and garcinol in the prevention of diseases where with clarithromycin (Chatterjee, Bagchi, Yasmin, & Stohs, 2005).
lipid peroxidation and protein modification by ROS and RNS plays a vital Isogarcinol has also been claimed to possess antiulcer properties
role in the pathogenesis. (Sang et al., 2001). Together these observations clearly suggest the
usefulness of garcinol in the prevention of gastric ulcerogenesis and
7.5. Antiaging activities merit detail investigations.
Aging is a natural process and one of the conspicuous features is 7.8. Anti-obesity activity
the development of wrinkles and sagging of the skin. With age, due to
the action of the enzyme elastase the elasticity of the skin decreases Recent reports from the WHO suggest that globally the number of
and this gradually causes sagging. Concomitantly the levels of obese people is increasing and with it the incidence of cardiovascular
hyaluronic acid also decrease and this makes the skin dry and diseases, diabetes, digestive diseases and cancer (Nguyen & El-Serag,

7. 1796 M.S. Baliga et al. / Food Research International 44 (2011) 1790–1799
2010). In the Ayurvedic system of medicine, kokum is used to treat healers of Goa and Maharastra state, India have been using the kokum
illness related to obesity and multiple studies have shown that rind decoction in the treatment of diabetes and recent studies have
hydroxycitric acid (also known as garcinia acid) a component of validated its antidiabetic effects (Kirana & Srinivasan, 2010). Oral
kokum is reported to possess anti-obesity effects. Studies have shown administration of the aqueous extract of the kokum rind (100 mg/kg
that consumption of hydroxycitric acid reduces appetite, inhibits fat and 200 mg/kg) for a period of 4 weeks to streptozotocin-induced
synthesis, lipogenesis, decreases food intake and reduces body weight type 2 diabetic rats is shown to be effective in decreasing both fasting
(Preussa et al., 2004; Jena, Jayaprakasha, Singh, & Sakariah, 2002). and postprandial blood glucose. Kokum also restored the levels of
Mechanistic studies have shown that it is a competitive inhibitor of erythrocyte GSH, an intracellular antioxidant proved to be effective in
the extra-mitochondrial enzyme ATP-citrate lyase that catalyzes the preventing the risk of developing secondary complications and these
extramitochondrial cleavage of citrate to oxaloacetate and acetyl-CoA, observations suggest the usefulness of kokum in treating both
an important precursor involved in the initial steps of de novo hyperglycemia and other complications. To corroborate these obser-
lipogenesis in the liver (Jena et al., 2002). Hydroxycitric acid also vations, in vitro studies have also shown that garcinol suppressed the
inhibits pancreatic α-amylase and intestinal α-glucosidase, leading to protein glycation in the bovine serum albumin/fructose system
a reduction in carbohydrate metabolism (Yamada, Hida, & Yamada, (Yamaguchi et al., 2000). However detail studies are warranted to
2007). It also inhibits synthesis of fatty acid and lipogenesis from establish the usefulness of kokum in treating diabetes.
various precursors (Jena et al., 2002). Concomitantly, it also increases
the synthesis of hepatic glycogen thereby activating the glucorecep- 7.10. Cardioprotective effects
tors and causing a sensation of reduced appetite and fullness
(Lowenstein, 1971; Preussa et al., 2004). Despite incredible improvements in the diagnosis and treatment,
Hydroxycitric acid is non toxic as experimental studies have CVD account for one-third of annual global mortality. Additionally,
shown that by oral route it did not cause death or systemic or with approximately 80% of all cardiovascular-related deaths occurring
behavioral toxicity even at high dose of 5 g/kg b. wt. When in the low- and middle-income countries having limited health care
extrapolated to human dose, 5 g/kg b. wt. amounts to about 350 g, resources the impact of CVD is catastrophic (Gersh, Sliwa, Mayosi, &
which is nearly 233 times more than the recommended dose of 1.5 g/ Yusuf, 2010). In vitro studies with the bovine artery endothelial cells
day (Jena et al., 2002). Hydroxycitric acid is also reported to be devoid have shown that cyanidin-3-glucoside enhanced the levels of eNOS,
of toxic effects like nervousness, rapid heart rate, high blood pressure, an enzyme important in maintaining blood pressure homeostasis and
or insomnia symptoms in humans, thereby suggesting its non toxic vascular integrity, and concomitantly increased the nitric oxide
nature (Preussa et al., 2004). output. At molecular level cyanidin-3-glucoside stimulated the
Preclinical studies have also shown that feeding cyanidin 3- phosphorylation of Src and ERK1/2. It also enhanced the binding
glucoside-rich purple corn suppressed the high fat diet-induced activity of the transcription factor Sp1 to the GC box in the proximal
increase in body weight gain, and synthesis/accumulation white and eNOS promoter of bovine artery endothelial cells. Together these
brown adipose tissue in mice. Dietary feeding of cyanidin 3-glucoside observations suggest that cyanidin-3-glucoside induced eNOS
rich corn decreased the sterol regulatory element binding protein-1 expression and increased the NO production, may be of help in
mRNA level in white adipose tissue. It also reduced the high fat induced improving endothelial dysfunction, harmonize blood pressure and
increase in hypertrophy of the adipocytes in epididymal white adipose. may possibly prevent atherosclerosis (Xu, Ikeda, & Yamori, 2004).
Cyanidin 3-glucoside feeding decreased hyperglycemia, hyperinsuline-
mia and hyperleptinemia and concomitantly suppressed the transcrip- 7.11. Antineoplastic and chemopreventive effects
tion of TNF-α and enzymes involved in the fatty acid and triacylglycerol
synthesis (Tsuda, Horio, Uchida, Aoki, & Osawa, 2003). Cyanidin 3- Chemotherapy is an important modality of treatment in cancer
glucoside also caused a reduction in the blood glucose levels and especially when metastasis has occurred and the prognosis is poor
enhanced insulin sensitivity, upregulated the Glut4 and downregulated (Dorr & Fritz, 1980). Unfortunately, most of the chemotherapeutic
RBP4 in the white adipose tissue. A concomitant downregulation of the agents used in cancer treatment possess inherent toxic effects and
inflammatory adipocytokines (monocyte chemoattractant protein-1 compromise the therapeutic benefit and quality of life. Additionally,
and tumor necrosis factor-alpha) in the white adipose tissue was also many of the clinically used drugs are exorbitant to people living in the
observed (Sasaki et al., 2007). developing countries where primary care itself is expensive. Therefore
In vitro studies have also shown that treatment of rat adipocytes efforts are on to discover substitutes that are non toxic at effective
with cyanidin 3-glucoside enhanced adipocytokine (adiponectin and concentrations and are inexpensive (Arora, 2010).
leptin) secretion and up-regulated the adipocyte specific gene With regard to Kokum studies have shown that the phytochem-
expression without activation of PPARγ. Feeding cyanidin 3-glucoside icals garcinol, isogarcinol, and xanthochymol affected the growth and
to mice also enhanced the gene expression of adiponectin in the white proliferation of four human leukemia cell lines. The growth inhibitory
adipose tissue confirming that the in vitro mechanisms extended in to effects of isogarcinol and xanthochymol were more potent than that
the live system (Tsuda et al., 2004). Isogarcinol is also reported to of garcinol. These compounds induce apoptosis in the neoplastic cells
possess lipase inhibitory effect and antiobesity properties (Sang et al., through the activation of caspase-3. Detail studies also showed that
2001). Together all these observations suggest that the presence of apoptosis induction by garcinol and isogarcinol was mediated
hydroxycitric acid and cyanidin 3-glucoside in the kokum rind might through the loss of mitochondrial membrane potential, while that
have contributed towards the observed antiobesity effects and by xanthochymol was independent of it (Matsumoto et al., 2003).
suggest the need for translational studies. Multiple studies have also shown that garcinol possess antipro-
liferative effects on various neoplastic cells like in HeLa cells
7.9. Antidiabetic effects (Balasubramanyam et al., 2004), human colorectal cancer cell line
HT-29 (Liao et al., 2005), human leukemia HL-60 cells (Pan, Chang,
Diabetes characterized by chronic hyperglycaemia, is a disease as Lin-Shiau, Ho, & Lin, 2001) and human breast cancer cells the
old as mankind. Current reports suggest it to be the world's leading ER-positive MCF-7 and ER-negative MDA-MB-231 cells (Ahmad et al.,
endocrine disorder and affects nearly 5% of the global population. 2010). Additionally, studies have also shown that at equivalent
Chronic hyperglycemia leads to secondary complications that are concentrations garcinol did not affect the proliferation of the non-
more dangerous than hyperglycemia and meriting constant medical tumorigenic MCF-10A cells thereby suggesting it to be selectively
attention and care (King & Loeken, 2004). Since antiquity, the herbal cytotoxic only to the neoplastic cells (Ahmad et al., 2010).

8. M.S. Baliga et al. / Food Research International 44 (2011) 1790–1799 1797
Studies planned at understanding the mechanistic actions have Studies have also shown that garcinol prevented AOM-induced
shown that garcinol-mediated apoptosis in HL 60 cells was triggered colonic aberrant crypt foci in rats. Feeding garcinol (0.01 or 0.05%) for
by the release of cytochrome C into the cytosol, decrease in Bcl-2 and 5 weeks, one week before the first of the three weekly subcutaneous
increase in Bad and Bax, procaspase-9 processing, activation of injections of AOM (15 mg/kg body wt), caused a concentration
caspase-3 and caspase-2, degradation of PARP, and DNA fragmenta- dependent decrease in the PCNA index in aberrant crypt foci. Garcinol
tion caused by the caspase-activated deoxyribonuclease through the increased the activities of detoxifying enzymes GST and QR in the liver
digestion of DFF-45 (Pan et al., 2001). suggesting that garcinol enhanced the detoxification mechanisms
Studies with the human breast cancer cells have shown that (Tanaka et al., 2000).
garcinol-induced apoptosis in highly metastatic MDA-MB-231 cells To corroborate the animal studies, in vitro studies with pUC-19
and that the effect was mediated through the induction of caspase. plasmid have shown that garcinol provides a concentration-depen-
Garcinol inhibited constitutive NF-kB activity and, concomitantly dent protection against the Fenton reaction-induced clastogenesis.
down-regulated the NF-kB-regulated genes (Ahmad et al., 2010). These results clearly show that garcinol scavenged the hydroxyl
Garcinol also inhibited activation of Src, MAPK/ERK, and PI3K/Akt radical and prevented the DNA damage considered to be the initiator
signaling pathways, changed the ratio of the anti-apoptotic Bcl-2 and for carcinogenesis (Liao et al., 2004). Additionally, garcinol and its
proapoptotic BAX proteins concurrently triggered the release of oxidative derivatives, cambogin, garcim-1, and garcim-2 possess
cytochrome C from the mitochondria to the cytosol (Liao et al., 2005). potent growth-inhibitory effects on the neoplastic HT-29 and HCT-
Garcinol is a potent inhibitor of histone acetyltransferases p300 in 116 colon cancer cells, as well as in IEC-6 and INT-407 normal
both in vitro and in vivo systems (Arif et al., 2009; Mantelingu et al., immortalized intestinal cells (Hong et al., 2007).
2007). It strongly inhibited the histone acetyltransferases activity- Treatment of garcinol and its derivatives (1 μM), 1 h after LPS
dependent chromatin transcription, without affecting the transcrip- stimulation also inhibited the release of arachidonic acid and its
tion from DNA template (Balasubramanyam et al., 2004). metabolites in macrophages and the intestinal (HT-29, HCT-116 and
In addition to the observed cytotoxic effects, studies also suggest that IEC-6) cells. Garcinol inhibited the phosphorylation of cPLA2 without
garcinol potentiated TRAIL (a cytokine currently in phase II clinical altering its protein level, and the effect was due to the inhibition of
trial)-induced apoptosis of cancer cells including the TRAIL-resistant ERK1/2 phosphorylation. It also inhibited NFkB activation and COX-2
cells. Mechanistic studies showed that the observed process was expression but only when it was added to the cells before LPS
mediated through the generation of reactive oxygen species, upregula- stimulation. Garcinol also decreased the iNOS expression and NO
tion of both TRAIL receptors and the death receptor 4 (DR4) and DR5, release from LPS-stimulated macrophages, possibly by inhibiting the
downregulation of antiapoptotic proteins (survivin, bcl-2, XIAP, and STAT-1, an upstream event in the activation of iNOS synthesis (Hong
cFLIP) and concomitant induction of proapototic process like bid et al., 2006).
cleavage, bax, and cytochrome C release. However it did not affect the Cell free assays have also showed that garcinol interferes with 5-LO
normal cells suggesting its usefulness in cancer treatment (Prasad, and mPGES-1, enzymes important in the process of inflammation and
Ravindran, Sung, Pandey, & Aggarwal, 2010). Studies have also shown carcinogenesis (Koeberle, Northoff, & Werz, 2009). Garcinol inhibited
that garcinol inhibited Nic-induced human breast cancer (MDA-MB- the activity of purified 5-lipoxygenase (IC50 of 0.1 μM) and blocked the
231) cell proliferation and that this was mediated through the down- mPGES-1-mediated conversion of PGH2 to PGE2 (IC50 of 0.3 μM). Studies
regulation of α9-nAChR and cyclin D3 expression (Chen et al., 2011). with intact human neutrophils have shown that garcinol was effective in
Invasiveness and metastasis are the dangerous and unique suppressing the 5-lipoxygenase products. Garcinol reduced the forma-
property of cancer and their inhibition is thought of as an attractive tion in of PGE2 in A549 human lung carcinoma cells and in human whole
target for inhibiting spreading of cancer. Preclinical studies have also blood stimulated by IL-1β-stimulated and lipopolysaccharide, respec-
shown that garcinol inhibited cell invasion and decreased the tyrosine tively. Garcinol interfered with isolated COX-1 enzyme (IC50 of 12 μM)
phosphorylation of the focal adhesion kinase, the major signaling and inhibited the formation of COX-1-derived 12(S)-hydroxy-5-cis-8,
mediator of integrin-mediated cell-matrix contact-regulated cellular 10-trans-heptadecatrienoic acid as well as thromboxane B2 in human
proliferation, migration, and apoptosis of HT-29. Garcinol also platelets (Koeberle et al., 2009).
reduced the levels of MMP-7 protein level and inhibited expression The anthocyanins rich in cyanidin-3-glucoside is also reported to
of MMP-7 in IL-1beta-induced HT-29 cells, suggesting its usefulness protect the Caco-2 colon cancer cells against peroxyl radical (AAPH)-
(Liao et al., 2005). induced oxidative damage and associated cytotoxicity, thereby
The anthocyanins cyanidin-3-glucoside is also reported to be suggesting its potential role as an antioxidant and in preventing
effective in causing a dose-dependent inhibitory effect on the migration mutagenesis and carcinogenesis (Elisia & Kitts, 2008). Pretreatment of
and invasion, of highly metastatic A549 human lung carcinoma cells. JB6 cells with cyanidin-3-glucoside inhibited both UVB- and TPA-
Cyanidin 3-glucoside caused a dose-dependent decrease in the induced transactivation of NF-kB and AP-1 and expression of COX-2
expressions of MMP-2 and u-PA, and concomitantly enhances the and TNF-α. It also blocked TPA-induced neoplastic transformation in
expression of the TIMP-2 and PAI. Treatment with cyanidin 3-glucoside JB6 cells and inhibited proliferation of a human lung carcinoma cell
also inhibited the activation of c-Jun and NF-kB that are crucial in line A549 (Ding et al., 2006). Animal studies showed that Cyanidin-3-
carcinogenesis (Chen et al., 2006). glucoside decreased the number of non-malignant and malignant skin
Chemoprevention, the use of drugs or natural substances to retard tumors per mouse induced by TPA in DMBA-initiated mouse skin
or reverse the process of carcinogenesis, represents a promising carcinogenesis model. It also reduced the size of A549 tumor
strategy to reduce the development of cancer (Ding et al., 2006). xenograft growth and inhibited metastasis by inhibiting the migration
Preclinical studies have shown that when compared to cohorts on and invasion of A549 tumor cells (Ding et al., 2006). Feeding cyanidin-
control diet, feeding garcinol prevented the development of 4-NQO- 3-glucoside for 12 weeks in diet to the Apc (Min) mouse, a genetic
induced oral carcinogenesis in rats. Feeding garcinol (100 or model of human familial adenomatous polyposis decreased the
500 ppm) either during (for 10 weeks) or after (for 22 weeks) the intestinal adenomas, thus confirming its chemopreventive effects
carcinogen decreased the incidence and multiplicity of 4-NQO- (Cooke et al., 2006).
induced tongue neoplasms and/or preneoplasms at the end of the
study (week 32). Immunohistochemical studies confirmed that the 8. Conclusions
observed preventive effects were due to the decrease in the cell
proliferation (BrdU-labeling index and cyclin D1-positive cell ratio) Studies carried out in the past one decade indicate that kokum
and reduction in the levels of cyclooxygenase-2 (Yoshida et al., 2005). possess diverse health benefits and that the phytochemicals garcinol,

9. 1798 M.S. Baliga et al. / Food Research International 44 (2011) 1790–1799
isogarcinol, cyanidin-3-glucoside and (−)-hydroxycitric acid are Ding, M., Feng, R., Wang, S. Y., Bowman, L., Lu, Y., Qian, Y., et al. (2006). Cyanidin-3-
glucoside, a natural product derived from blackberry, exhibits chemopreventive and
useful in various medical conditions. Future studies should be on chemotherapeutic activity. The Journal of Biological Chemistry, 281, 17359−17368.
understanding the mechanism of action/s responsible for the various Dorr, R. T., & Fritz, W. (1980). Cancer chemotherapy handbook. New York and Oxford:
beneficial effects. This will enhance our knowledge and appreciation Elsevier.
Dushyantha, D. K., Girish, D. N., Suvarna, V. C., & Dushyantha, D. K. (2010). Native lactic
for the use of kokum in our daily diet. Kokum plantation does not need acid bacterial isolates of kokum for preparation of fermented beverage. E Journals of
elaborate care and as these can grow in any harsh condition farmers Academic Research & Reviews, 2, 21−24. http://www.ejarr.com/Volumes/Vol2/
should be encouraged to take up large scale cultivation. The juice of EJBS_2_04.pdf
Elisia, I., & Kitts, D. D. (2008). Anthocyanins inhibit peroxyl radical-induced apoptosis in
kokum is a delicacy and will have immense commercial benefit if Caco-2 cells. Molecular & Cellular Biochemistry, 312, 139−145.
marketed by emphasizing on the beneficial effects. Studies should be Gersh, B. J., Sliwa, K., Mayosi, B. M., & Yusuf, S. (2010). Novel therapeutic concepts: The
planned on optimizing the products from the fruits and the resulting epidemic of cardiovascular disease in the developing world: Global implications.
European Heart Journal, 31, 642−648.
observations should be implemented in industrial scale to cater to
Hong, J., Kwon, S. J., Sang, S., Ju, J., Zhou, J. N., Ho, C. T., et al. (2007). Effects of garcinol and its
both national and international consumers of kokum. derivatives on intestinal cell growth: Inhibitory effects and autoxidation-dependent
growth-stimulatory effects. Free Radical Biology and Medicine, 42, 1211−1221.
Hong, J., Sang, S., Park, H. J., Kwon, S. J., Suh, N., Huang, M. T., et al. (2006). Modulation of
Acknowledgments arachidonic acid metabolism and nitric oxide synthesis by garcinol and its derivatives.
Carcinogenesis, 27, 278−286.
Iinuma, M., Tosa, H., Tanaka, T., Kanamaru, S., Asai, F., Kobayashi, Y., et al. (1996).
The authors MSB, RJP, RB and PLP are grateful to Rev. Fr. Patrick
Antibacterial activity of some Garcinia benzophenone derivatives against methicillin-
Rodrigus (Director), Rev. Fr. Denis D'Sa (Administrator) and Dr. resistant Staphylococcus aureus. Biological Pharmaceutical Bulletin, 19, 311−314.
Jayaprakash Alva (Dean) of Father Muller Charitable Institutions for Jayaprakasha, G. K., & Sakariah, K. K. (2002). Determination of organic acids in leaves
their unstinted support. MSB and HPB are also grateful to Prof. TL and rinds of Garcinia indica (Desr.) by LC. Journal of Pharmaceutical and Biomedical
Analysis, 28, 379−384.
Shantha, director and Prof MB Nagaveni, Maharani Lakshmi Ammani Jena, B. S., Jayaprakasha, G. K., Singh, R. P., & Sakariah, K. K. (2002). Journal of agricultural
Women's College, for their help and support. and food chemistry, 50, 10−22.
King, G. L., & Loeken, M. R. (2004). Hyperglycemia-induced oxidative stress in diabetic
complications. Histochemistry and Cell Biology, 122, 333−338.
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