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INTERNATIONAL JOURNAL OF PHARMA WORLD RESEARCH

(An International Quarterly Published Online Research Journal)

www.ijpwr.com E-mail:editorijpwr@gmail.com

Title:

Zingiber zerumbet (L.) Sm., a reservoir plant for therapeutic uses: A Review

Rout Om Prakash *1, Acharya Rabinarayan2, Mishra Sagar Kumar3

1Deptt. of Dravyaguna, Rajiv Lochan Ayurvedic Medical College, Chandkhuri, Durg,Chhatisgarh.

2 Deptt. of Dravyaguna, I.P.G.T & R.A., Gujurat Ayurved University, Jamnagar, Gujurat, India.

3 Pharmacognosy & Phytochemistry Division, University Deptt. of Pharmaceutical Sciences,Utkal University, Vani Vihar, Bhubaneswar, Odisha, India.

*Corresponding author:

Dr. Om Prakash Rout

Lecturer

Deptt. of Dravyaguna,

Rajiv Lochan Ayurvedic Medical College & Hospital, Chandkhuri,

Gundardehi Road, Durg,

Chhatisgarh.

Mail: omprakash_rout2000@yahoo.com

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ABSTRACT

Zingiber zerumbet (L.) Sm. is a well known medicinal plant employed to cure various

diseases in Ayurvedic system of medicine. It is known to the india as Karpurharidra, Kolanjana,

Kumbhika, Sthulagranthi and Van adrak, and is a perennial herb found in many tropical

countries. Zerumbone is a monocyclic sesquiterpene that can be found abundantly in rhizomes.

The rhizome is used as stimulant, antihypertensive, carminative and flavouring agent to treat

dyspepsia wounds, hemorrhoids and flatulent colic for the cure of stomach troubles and fever.

Used in peptic ulcers and related stomach problems as well as infections. This paper presents the

botany, history & traditional uses, chemistry, pharmacology and medicinal uses of this plant.

KEYWORDS: Zingiber zerumbet, , sthulagranthi, indigenous medicine.

Introduction

Zingiber zerumbet (L) smith, a member of the family Zingiberaceae is well known as

Van Adrak. The plant is widely cultivated in village garden in the tropics for its medicinal

properties and as a marketable spice1. It grows in the edge of the forest, village thickest in the

partial shade. It is distributed in India, Bangladesh, Malaysia, Nepal, and Sri Lanka2. It has been

reported that plants from this family have anti –inflammatory3,4, anti-ulceration5, antioxidant6

and antimicrobial properties7. Rhizomes are employed against cough, stomachache, asthma and

also as a vermifuge. It is used in leprosy and other skin diseases. The rhizome yields an essential

oil, which is used as perfume in soap and other toilet articles8. It is used as stimulant, carminative

and flavorings agent; given in dyspepsia and flatulent colic; prescribed as an adjuna to many

tonic and stimulating remedies9. It is used to treat fish poisoning. It is used as a cough remedy

and to treat the bacterial diseases, thrush and diabetes. The rhizome is used as stimulant,

antihypertensive, carminative and flavouring agent; to treat dyspepsia wounds, hemorrhoids and

flatulent colic for the cure of stomach troubles and fever. It is used in peptic ulcers and related

stomach problems as well as infections10. Phytochemical investigations on this plant have

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revealed the isolation of several sesquiterpenes, flavonoids and aromatic compounds11-15. The

volatile oil of the rhizome contains zerumbone, humulene, camprene α-caryophyllene and

camphene16-18. The rhizomes of this plant are used as an anti-inflammatory agent in traditional

medicine19. A monocyclic sesquiterpene, zerumbone (2E, 6E,10E-humulatrien-1-one), which

was found as a major component of the essential oil of Z. zerumbet, has been studied intensively

for potential use in anti-inflammatory, chemopreventive, and chemotherapeutic strategies19-21.

Extracts of the rhizomes are known to have anti-inflammatory, chemopreventive, chemotherapy

applications22-23 and are anti HIV19, antitumour24, cytotoxic 25, antibacterial19 agents. It finds

prominent importance not only in Ayurvedic medicine, but also in modern medicine. During lat

two decades, the drug has been subjected to extensive phytochemical, pharmacological and

clinical investigating findings in the area of anticancer activity, antiartherosclerotic activity and

antioxidant activity are repoted.

Scientific classification26

Kingdom: Plantae – Plants

Subkingdom: Tracheobionta – Vascular plants

Superdivision: Spermatophyta – Seed plants

Division: Magnoliophyta – Flowering plants

Class: Liliopsida – Monocotyledons

Subclass: Zingiberidae

Order: Zingiberales

Family: Zingiberaceae – Ginger family

Genus: Zingiber Mill. – ginger

Species: Zingiber zerumbet (L.) Sm. – bitter ginger

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Vernacular names27, 10

Bengal: Mahabaribach, narkachur

Bicol: Laya

Canarese: Agalesunthi, Kallusunthi

French: Gingmbre, Sauvage

Hindi: Mahabaribach, Narkachur

Hora: Lakitra

Kanard: Kallusunthi

Malaya: Lammpayang

Malayalam: Katinji, kattinjikuva

Menabe: Sakarivondambo

Oriya: gada, Pasukedar

Punjab: Kachur, Narkachur

Sanskrit: Ahava, Avanti, Karpurharidra, Kolanjana, Kumbhika, Sthulagranthi, Viranam

Sinhalese: Waliguru

Tagalog: Tamo

Telgu: karallam, Karupasupu, Santapasupu, Karrallamu

Tulu: kallusonti

Uriya: Bonooda, Gondhosunthi

Visayam: dao, lampuyang

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Distribution25

It grows in the edge of the forest, village thickest in the partial shade. It is distributed

in India, Bangladesh, Malaysia, Nepal, and Sri Lanka2. Throughout India, Ceylon, Malya

peninsula-widely cultivated in the tropics of the world7. It is common in moist forests, beach

thickness, mangrove margins from sea-level to over 500 m.

Botanical and pharmacognostical descriptions10,28

Stem 0.9-1.2 m; rhizome whitish outside, pale yellow inside.

Root stock large, not much branched, hard, biennial, yellow inside, with a strong aromatic ginger

like taste, but with some bitterness; root fibrous vermiform; leafing stem 0.9-1.5 m high, about

13 mm. diameter, cylindrical, glabrous, annual.

Leaves 20-30 by 5-7.5 cm, sessile, oblong-lanceolate or oblanceolate, acuminate, glabrous, base

narrowed; ligule 111.3-2 cm. long, truncate, membranous.

Flowering stem 30-45 cm. long, stout, usually flexouous, clothed with long appressed obtuse

sheaths.

Flowers plae sulphur-yellow, in conico-oblong or ovoid obtuse spikes 7.5-10 by 5 cm; bracts

2.5-3.8cm long, closely imbricate, ovate-oblong or obovate, with rounded apex and pale

membranous margins, bright green at first but becoming red fruit.

Calyx-tube 3.2cm. long; lobes ovate-lanceloate, acuminate, the lateral smaller, adnate to the base

of the lip.

Lip shorter than the corolla-lobes and of a darker yellow, 3-fid; lobes obtuse, the midlobe the

longest.

Anther glabrous.

Style glabrous; stigma minute, funnel-shaped with ciliate mouth.

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Capsules ellipsoid, 2.5 cm long.

Seeds 4 mm. long, oblong, black.

Srivastava (2003)29 presented the pharmacognostic study. He deals with the

pharmacognostic studies including botanical description, macro and microscopic characters of

rhizome, root, physical constants, colour reaction, powder study and flurorescent analysis.

Oliveros et al. (1982)30 studied the Pharmacognostic Studies on Zingiber zerumbet (Linné) Smith

and its Proposed Variety (Family Zingiberaceae). The chemistry of the volatile oils and

morphology of Zingiber zerumbet (L.) Sm. and a second plant which is being proposed as a

variety reveals significant differences between these two plants. Their main physicochemical

differences are the following: dried rhizomes of Zingiber zerumbet (L.) Sm. yield a volatile oil

which is dextrorotatory, congeals at 3°C, and has zerumbone as its main constituent. Rhizomes

of the proposed variety yield an oil which is levorotatory, congeals at —27°C, and has 4-

terpinenol as its main constituent. Significant morphological and anatomical differences between

Zingiber zerumbet (L.) Sm. and its proposed variety are noted. On the strength of these

physicochemical and morphological differences, which are not sufficient to warrant erection of a

new species it is proposed that the other plant be classified as a variety of Zingiber zerumbet (L.)

Sm.

History and Traditional uses

No reference regarding the drug Sthulagranthi (Zingiber zerumbet (L.) Sm.) was found in

Vedic literature, Samhita granthas as well as in different Nighantu. Chopra et.al 1956:261,

Ramchandran et al. 1994:701, Kirtikar & Basu, 1935:2438, Prajapati et al., 2003: 552 have

describe this plant . Kirtikar & Basu28, 1935:2438 described vernacular names, the

morphological characters, distribution, ethno uses and its medicinal properties. Chopra et al.31

1956:261 describe the vernacular name, uses of this plant and also mentioned that, the rhizome

of the Z. zerumbet is used for same purposes as that of Z. officinale. Sharma PV’s32 1995:332;

Dravyaguna Vijnana described the plant in the Zingiber officinale under the heading types of

Sunthi. Chunekar KC 2008:4733 describe this plant in the name sthulagranthi. It is correlated

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with mahabhari bacha. It is used in kasa, swasa, krimi, kustha and othe skin diseases and also it’s

properties just like as sunthi. Prajapati et al.8 2003:552 describes the synonyms, vernacular

names, description, habitat, propagation, parts used, chemical constituents, and uses of this plant.

Sharma SK., Chunekar KC & Yadav CL., 1998:19834 described this plant in the book ‘Medicinal

plants used in Ayurveda’ as Zingiber zerumbet Rosc. Ex. Sm. syn. Amomum zerumbet Linn.,

family Zingiberaceae. It is used in Swasa, Kasa Udara sula, Krimi and kustha.

Phytochemical Contents

Dev35 isolated and determined the structure of zerumbone. Nigam and Levi36 identified,

among other constituents, α-humulene, zerumbone, and humulene monoxide. Damodaran and

Dev37 characterized humulene oxides I, II and III, humulenols I and II, caryophyllene oxide, β-

caryophyllene, dihydrophotozerumbone and photo-zerumbone. Chhabra et al.38 found

zerumbone epoxide. In oil from Fiji, Duve39 found highest levels of zerumbone (59%). Dung et

al.40 found high proportions of (Z)-nerolidol (22-36%), which was absent from rhizomes, in

extracts of stems, leaves and flowers, and found zerumbone to predominate in leaves. Srivastava

et al.17 found in similar proportions curzerenone (14.4%), zerumbone (12.6%) and camphor

(12.8%). Chane-Ming et al.41 reported that rhizomes were rich in zerumbone (37%), a -humulene

(14.4%) and camphene (13.8%) and leaves were rich in trans-nerolidol (21.4%), β-caryophyllene

(6.9%) and linalool (7.7%). The characteristics of the oils from the leaves and rhizomes of Z.

zerumbet allow them to be identified unequivocally. Vahirua Lechat et al.42 reported also the

presence of zerumbone (65.3%) as major compounds in the oil from French polynesia.

Z. zerumbet contains p-hydroxybenzaldehyde, vanillin, kaempferol-3,4',7-O-

trimethylether, kaempferol-3-O-methylether, kaempferol-3,4'-O-dimethylether, 4''-O-

acetylafzelin, kaempferol-3-O-(4-O-acetyl-alpha-L-rhamnopyranoside)], 2'',4''-O-diacetylafzelin,

kaempferol-3-O-(2,4-O-diacetyl-alpha-L-rhamnopyranoside)],3'',4''-O-diacetylafzelin,

kaempferol-3-O-(3,4-O-diacetyl-alpha-L rhamnopyranoside)], 5-hydroxyzerumbone (5-hydroxy-

2E, 6E, 9E-humulatriene-8-one) and zerumboneoxide43,44. The essential oil from the rhizomes

contained zerumbone (37%), alpha-humulene (14.4%) and camphene (13.8%) while the oils

from leaves and flowers contained (E)-nerolidol (21.4% and 34.9%, respectively), beta-

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caryophyllene (6.9% and 10.2%, respectively), and linalool (7.7% and 17.1%, respectively). The

leaf oil also contained a-and S-pinenes (10.3% and 31.4%, respectively)45. Recent study revealed

the presence of a sequiterpene, zederone in ethanol extract of rhizome46. phytochemical sceening

to the aqueous extract of rhizome was reported to contain phenolic, saponin and terpenoids47.

Pharmacological Properties

Various studies have revealed the different pharmacological potentials of Z. zerumbet in a

range of in vitro and in vivo test models. The rhizome, in particular, has been demonstrated to

possess antinociceptive, anti-inflammatory, antipyretic, hepatoprotective, antiallergic activity,

immunomodulatory activity, antiplatelet activities, antioxidant, cytotoxix activity, antiulcer,

anticancer, antimicrobial, antihyperglycemic, and at different doses/concentrations. These have

been described in detail in the following subheadings.

Acute Toxicity

Both the aqueous and ethanol extracts of Z. zerumbet were non toxic to rats at doses up to

500 mg/kg4. Zerumbone (0.1% added to food pellets) did not cause deaths in female mice given

the compound for 2 weeks48. Zerumbone showed selective cytotoxicity towards cancer cell lines

versus normal cell lines. Its IC50 values for antiproliferative effects against a liver cancer cell

line, HepG2, and non-malignant Chang liver and MDBK cells were 3.45 ± 0.026 μg/ml, 10.96 ±

0.059 μg/ml and 10.02 ± 0.03 μg/ml respectively49. The aqueous extract of Z. zerumbet at 2000

mg/kg body weight did not cause any behavioral changes to the broiler chickens immediately

after its administration indicated by normal movement and drinking behavior50.

Anti-inflammatory ActivityThe anti-inflammatory profile of intraperitoneally-administered AEZZ and EEZZ, at the

doses of 25–100 mg/kg, against prostaglandin-E2 (PGE2)-induced paw edema test has been

reported earlier by Somchit and Shukriyah4.

Analgesic and anti-pyretic activity

The ethanol extract (50 & 100 mg/kg) and the aqueous extract (25, 50 100 mg/kg) of Z.

zerumbet elicited antipyretic activity in Brewer’s yeast-induce pyrexia in rats. The antipyretic

activity of the ethanol extract was dose-dependent as a lower dose (25 mg/kg) was ineffective.

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Similarly, the ethanol extract showed a dose-dependent analgesic activity; doses of 25 and 100

mg/kg elicited similar analgesic effects as 0.2 and 0.8 mg/kg morphine, respectively, on acetic

acid-induced writhing in mice. The aqueous extract was devoid of analgesic activity. Both

analgesic and antipyretic effects of Z. zerumbet extracts may be related to its ability to inhibit

prostaglandins51.

Antiproliferative and anti-inflammatory activity

The zerumbone showed potential for the chemotherapy of human hepatoma. The IC50 of

zerumbone, an active component of Z. zerumbet, in Hep G2 cells, a human liver cancer cell line,

was 3.45 ± 0.026 µg/ml. The antiproliferative effects were time-dependent and were selective for

malignant cells as zerumbone’s IC50 values in non malignant Chang liver cells and non-

malignant MDBK cells were 10.96 ± 0.059 µg/ml and 10.02 ±0.03 µg/ml, respectively. The

mechanism of cell death in HepG2 cells was by apoptosis as zerumbone (3.45 µg/ml) up-

regulated the expression of Bax (a pro-apoptotic protein) while decreasing that of Bcl-2, anti-

apoptotic protein. This was confirmed by the finding that zerumbone enhanced DNA

fragmentation and induced a time-dependent increase in the apoptotic index which is a score of

the percentage of apoptotic cells and apoptotic bodies within the overall population of total cells.

Apoptosis-induced cell death by zerumbone was not related to the expression of p53, a tumor

suppressor protein, which was not changed by it4. Zerumbone also induced apoptosis in human

colorectal cancer cell lines52.

The zerumbone is also active as a chemopreventive through suppression of COX-2

expression, inhibition of cell proliferation in the colonic mucosa, and induction of phase II

detoxification enzymes. In this study, colonic aberrant crypt foci were induced in rats by three

weekly subcutaneous injections of azoxymethane (15 mg/kg body weight). The rats were fed

zerumbone (0.01% or 0.05% ) for five weeks beginning from a week before the first dose of

azoxymethane. The lower dose of zerumbone reduced the frequency of aberrant crypt foci by

14% while the higher dose reduced it by 46%. The expression of COX-2 and prostaglandins in

colonic mucosa were significantly reduced by zerumbone. The cell proliferation activity of

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crypts as assessed by silver-stained nucleolar organizer regions protein was also significantly

reduced by zerumbone53.

The zerumbone markedly suppressed dextran sodium sulfate (DSS)-induced colitis in

mice. Acute colitis was induced in female mice by including 5% DSS in the drinking water for 1

week. These mice showed pathological symptoms of diarrhea, bloody feces, body weight

reduction, mucosal ulceration, and shortening of the large intestine and exhibited colorectal

shortening. Zerumbone was given to the mice a week before the administration of DSS for a

total of 2 weeks. The effects of zerumbone (0.1%) given alone or in combination (0.1% each)

with nimesulide, a selective COX-2 inhibitor, on inflammatory biomarkers in colonic mucosa

and the histological alterations induced by these agents were assessed. Zerumbone given alone

suppressed DSS-induced colitis and produced significant inhibition of DSS-induced interleukin-

1b production (by 34%), reduced PGE2 formation by 73% whereas PGF2a levels were

unchanged. TNF-a levels were lowered by zerumbone (by 29%). Nimesulide alone suppressed

the histological changes induced by DSS but did not affect the inflammatory biomarkers. The

combination of zerumbone and nimesulide produced maximal suppression of inflammatory

biomarkers and also significantly suppressed colorectal shortening. Zerumbone alone or in

combination with nimesulide reduced the mean number of erosive or ulcerative lesions per colon

(by 33% and 52%, respectively) and attenuated edema formation (by 55% and 68%,

respectively) while tissue regeneration was enhanced54.

The diethyl ether extract of the fresh rhizome exhibited antiproliferative effects in

cultured P-388D cells which also showed enhanced DNA fragmentation. The diethyl ether

extract (5 mg/kg body weight) also prolonged the life span of P-388D-bearing mice. The same

findings were elicited by zerumbone which was isolated from the diethyl ether extract. The life

span of P-388D-bearing mice was also prolonged by zerumbone (2 mg/kg). The growth of HL-

60 cells, a human leukemia cell line, was inhibited by zerumbone in a time- and concentration-

dependent manner with IC50 values at 6, 12, and 18 h of 22.29, 9.12, and 2.27 µg/mL,

respectively. Zerumbone induced a time- and concentration-dependent G (2)/M cell cycle arrest

in these cells and lowered the protein levels of cyclin B1/cdk 155.

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The 6 kaempferol derivatives were extracted from Z. zerumbet, of these, kaempferol-3-O-

methyl ether and kaempferol-3,4'-O-dimethyl ether potently inhibited P-glycoprotein. This study

looked at the accumulation and efflux of 3H-daunomycin in P-glycoprotein overexpressing

multidrug resistant human breast cancer cells. The effect was similar to that of verapamil, a well

known inhibitor of P-glycoprotein. There was a three-fold increase in the accumulation of 3H-

daunomycin and a decrease in its efflux, suggesting that the kaempferol derivatives from Z.

zerumbet may form the basis for the development of anticancer agents that can reverse P-

glycoprotein -mediated multidrug resistance in human cancer chemotherapy56.

The antiproliferative and anti-inflammatory activities of zerumbone were mediated by

modulation of NF-kappaB activation. Zerumbone suppressed NF-kappaB activation induced by

tumor necrosis factor, okadaic acid, cigarette smoke condensate, phorbol myristate acetate, and

H2O2. The suppression was not cell type specific. Zerumbone also inhibited constitutively

active NF-kappaB. Consequently, NF-kappaB-regulated gene products were downregulated by

zerumbone and this lead to potentiation of apoptosis induced by cytokines and chemotherapeutic

agents. The reduced expression of NF-kappaB-regulated gene products showed correlation with

the suppression of TNF-induced invasion activity. This may be the molecular basis for the

prevention and treatment of cancer by zerumbone57.

The zerumbone (0.01-10 µM) potently inhibited Epstein Barr virus activation in Raji

cells that was induced by the tumour promoter, 12-O-tetradecanoylphorbol-13-acetate with an

IC50 value of 0.14 µM (Murakami et al,1999, Vimala et al,1999.). Concentrations of zerumbone

below 10 µM were not cytotoxic to Raji cells as well as to hepatoma cells in culture and to

normal mouse fibroblasts57-58. Structure-activity studies showed that the inhibitory activity

towards Epstein Barr virus activation was enhanced by a 100 fold with oxidation of the hydroxyl

group at C-3 of the triterpenoid, and presence of the enone group is important. An important

structural element for the chemopreventive activity of zerumbone is the presence of a carbonyl

group at the C-8 position57.

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Anthelminthic activity

The alcoholic extract of Z. zerumbet rhizomes exhibited good in vitro anthelmintic

activity against Ascaris lumbricoides59.

Antioxidant activity

Zerumbone’s potential as a chemotherapeutic agent against inflammation-related cancer

may be mediated by its antioxidant activity. Its ability to induce phase II detoxification enzymes

was determined in RL34 cells, a normal rat liver epithelial cell line. Induction of phase II

enzymes is well known to confer protection against toxicity and chemical carcinogenesis,

particularly during the initiation phase. Zerumbone (25 µM) produced a dose- and time-

dependent induction of glutathione S-transferase (by 1.5-fold) and elicited a significant increase

in the level of the GSTP1-1 protein (3.2 fold of control). Presence of thea,b-unsaturated

carbonyl group in zerumbone is essential for induction of glutathione S-transferase (GST).

CYP1A1 protein level was not affected by zerumbone indicating that it did not activate the

metabolic pathway dependent on xenobiotic response element which is contained in and is

required for carcinogen-induced expression of some cytochrome P450 isozymes. The

zerumbone also elicited significant induction in the nuclear localization of Nrf2, a transcription

factor that binds to the antioxidant response element (ARE) of phase II enzyme genes. Nrf2 is

involved in the activation of gene expression of phase II enzymes. Zerumbone (25 µM)

potentiated the gene expressions of Nrf2/ARE-dependent phase II enzyme genes, viz, g-

glutamylcysteine synthetase, glutathione peroxidase, and hemeoxygenase-1. Zerumbone did not

show scavenging activity against 1,1-diphenyl-2-picrylhydrazyl free radicals but it was able to

elicit a time-dependent increase in GSH levels. Lowering of GSH to 87% of controls was

observed at 1 hour after exposure to zerumbone (25 µM) but this was followed by a rebound

increase of up to 286% of control at 24 hour although maximal stimulation of g-glutamylcysteine

synthetase (the rate-limiting enzyme for GSH biosynthesis) had occurred at 3 hour. Glutathione

peroxidase activity was increased 2.5 fold by zerumbone (25 µM) at 24 hour. At this time,

hepatocyte lipid peroxidation induced by H2O2/Fe2+ was abolished by zerumbone (25 µM)60.

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Antiartherosclerotic activity

Zerumbone showed potential as an antiartherosclerotic agent (Eguchi et al,2007). Its

suppressive effects on TPA-induced oxidized low density lipoprotein (LDL) receptor-1 (LOX-1)

mRNA expression was studied in THP-1 human monocyte-like cells and in differentiated colonic

adenocarcinoma Caco-2 cells which models the human small intestine. Pretreatment of TPA-

treated THP-1 cells with zerumbone lead to suppression of LOX-1 mRNA levels that were

elevated by TPA with an IC50 value of 9.4 µM. A key event in artherosclerosis is the

unregulated uptake of oxidized LDL via scavenger receptors which are integral membrane

proteins. Zerumbone (10 µM) abolished or reduced the expression of several subclasses of the

macrophage scavenger receptors (SR), viz, SR-A, SR-PSOX, CD36 leading to blockade of the

uptake of a modified LDL, DiI-acLDL. The expression of other scavenger receptors, CD-68 and

CLA-1, were not affected by zerumbone. The down regulation in the expression of scavenger

receptors by zerumbone (10 µM) was postulated to be partly related to the inhibition of

transcriptional activities of activator protein-1 and nuclear factor kB52.

Antiprotozoal activity

Z. zerumbet is commonly used by AIDS patients of southern Thailand to treat diarrhoea. The

chloroform, methanol and water extracts of the rhizomes were tested for anti-giardial and for

anti-amoebic activities by incubation with trophozoites of Giardia intestinalis and with those of

E. histolytica (strains HTH-56:MUTM and HM1:IMSS), respectively, at 37oC under anaerobic

conditions for 24 hours. For anti-giardial activity, the chloroform extract of Z. zerumbet was

classified as active (IC50 of 69 µg/mL, MIC of 250 µg/mL) while the methanol and water

extracts were inactive with IC50 values of 500 µg/mL and MIC values greater than 1,000 µg/mL.

For anti- amoebic activity, the chloroform extract of Z. zerumbet was also classified as active

with a IC50 value of 200 µg/mL61-62.

Hepatoprotective activity

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Further study on hepatotoxicity potential of rhizome of Z. zerumbet demonstrated that the

crude aqueous extract, at the doses of 50 and 500 mg/kg, did not cause hepatotoxicity effect in

mice, which concurred with the insignificant changes in the serum level of ALT and AST after

treatment for 4 weeks63.

Anti-allergic Activity

The ethanol extract and aqueous extract and volatile oil of rhizome of Z. zerumbet were

subjected to an in vitro investigation for their anti-allergic activity. The extracts and oil, at the

concentrations of 0–100 β-

hexosaminidase from RBL-2H3 cell line. The ethanol extract and aqueous extract inhibited the

release of β-hexosaminidase from the cells between 10–100 µg/ml with the percentage of

inhibitory of 8.4–53.7% and 10.9–59.1%, respectively64.

Antihyperglycemic activity

Husen et al. carried out the screening of aqueous extract at doses of 50, 100 and 150

mg/kg BW, either subjected to freeze-drying process or not, for potential blood glucose lowering

effect in normoglycaemic and streptozotocin-induced hyperglycaemic rats. Comparison with

non-treated and 10 mg/kg BW-treated rats revealed that the aqueous extract caused no significant

reduction in blood glucose level in both groups of rats indicating that the aqueous extract did not

have antihyperglycemic activity65.

Medicinal uses

The rhizome is used like the officinal ginger. It is employed as a hot remedy for coughs,

asthma, special diseases worms, leprosy and other skin diseases. In Madagascars, the boiled

rhizome is given in polumnary affections66. Rhizomes employed against cough, stomachache and

asthma and also as a vermifuge. It is used in leprosy and othe skin diseases. Yields an essential

oil, used as a perfume in soaps and othe toilet articles8. It is used as stimulant, carminative &

flavorings agent; given in dyspepsia and flatulent colic; prescribed as an adjuna to many tonic

and stimulating remedies9. it is used to treat fish poisoning. It is used as a cough remedy and to

treat the bacterial disease, thrush and diabetes. The rhizome is used as stimulant,

antihypertensive, carminative and flavouring agent; to treat dyspepsia wounds, hemorrhoids and

flatulent colic for the cure of stomach troubles and fever. Used in peptic ulcers and related

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stomach problems as well as infections67. It is used to treat stomach aches in Indonesian

traditional medicine under the name Jamu. In Polynesia it is an ingredient of several medical

preparations used to treat ear inflammation and diarrhea68. It is used in local traditional medicine

as a cure for swelling, sores and loss of appetite. The juice of the boiled rhizomes has also been

used as a medicine for worm infestation in children. On Reunion Island Z. zerumbet is grown

only in gardens and is used to treat severe sprains in horses and to relieve rheumatic pain69. Z.

zerumbet is most widely known around the world as the "Shampoo Ginger". It is in fact used as a

shampoo in Asia and Hawaii, and is one of the ingredients in several commercial shampoos. Z.

zerumbet was applied for sprains, indigestion and other ailments. The pulp from the grounded

roots was wrapped in cloth and loosely bound around the injured area. The ground and strained

root material was mixed with water and drunk to ease stomach ache. In Polynesia and Hawaii, Z.

zerumbet is used against toothache and stomach ache70. For toothache or cavity, the cooked and

softened rhizome was pressed into the hollow until the pain subsides69. Z. zerumbet is also used

in local traditional medicine to treat swelling, sores and loss of appetite4. The rhizomes are

boiled and the juice used to treat worm infestation in children4. The rhizome is also used to

relieve stomachache and is macerated in alcohol for use as a tonic and depurative4,71. In some

South East Asian countries, the rhizome is used to treat inflammatory conditions72 and to relieve

fever, pain and constipation71. Young shoots and the inflorescence are used as condiments and as

a food supplement to reduce experimental ulcerative colitis4,72.

Conclusions

Zingiber zerurnbet has the distinction of being a rich source of many novel humulenoid

sesquiterpemoids and is widely cultivated in India. The rhizome of the Z. zerumbet has also been

famously used as medicinal herbs in the India, Bangladesh, Malaysia, Nepal, and Sri Lankas

traditional medicines since ancient times. The claimed medicinal uses of rhizome throughout the

world include for the treatment of inflammatory and pain-associated ailments, digestive system-

related ailments, cough, stomachache, asthma and also as a vermifuge. It is used in leprosy and

other skin diseases. The rhizomes are applied to the head of children in convulsions. In

Philippines, the pulverized rhizomes are used as antidiirrhoeal agent. This plant is widespread in

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South East Asii, Indii and Okiawa and has found use as spice and ethnomedicine. Zerumbone is

a natural cyclic sesquiterpene moiety that can be found abundantly in rhizome of the wild ginger,

Zingiber zerumbet Smith . It is known as a powerful tool in the implementation of green

chemistry with latent reactivity which contains three double bonds, two conjugated and one

isolated as well as a double conjugated carbonyl group in 11-membered ring structure. Most of

these claims have been confirmed via in vitro and in vivo techniques of biological evaluation.

Since anti HIV and cytotoxic components were isolated from Zingiber zerurnbet, the plant finds

a prominent place in modem medicine now a days.

References

1. Saadiah MS, Halijah I. Proceedings of the National Convention on Herbal medicine. Vol.

21. Kuala Lumpur: Forest Research Institute Malaysia; 1995. p. 205-207.

2. Anonymous. The wealth of India. Raw materials. Vol. 11. India: CSIR; 1976. p. 89-90.

3. Jaganath IB, Ng LT. Herbs: The green pharmacy of Malaysia. Vinpress Sdn. Bhd. and

Malaysia Agricultural Research and Development Institute, 2000, pp 95-99.

4. Somchit Nhareet M, Shukriyah Nur MH. Anti-inflammatory property of ethanol and

water extracts of Zingiber zerumbet. Indian J Pharmacol. 2003; 35: 181-82.

5. Mascolo N, Jain R, Jain SC, Capasso FJ. Ethnopharmacologic investigation of. ginger

(Zingiber officinale). Ethnopharmacology 1989; 27: 129-40.

http://dx.doi.org/10.1016/0378-8741(89)90085-8.

6. Agrawal AK, Rao CV, Sairam K, Joshi VK. Antipyretic and analgesic activities of

Zingiber zerumbet extracts. Indian J Exp Biol. 2000; 38: 994-98.

7. Nakatani N. Phenolic antioxidants from herbs and species. Biofactors 2000; 13: 141-46.

8. Prajapati ND, Purohit SS, Sharma AK, Kumar T. AGROBIOS India, 2003; 552-553.

9. Ramchandran K, Kashyapa K, Chand R. The useful Plants of India, Publication &

Information Directorate, CSIR, New Delhi, 1994; 701.

10. Kirtikar KR, Basu BD. Indian Medicinal Plants, Lalit Mohan Basu, Allahabad, India,

Vol. IV: 1935; 2438-2439.

ISSN 0976-111X

IJPWR VOL 2 ISSUE 2 (Mar-Jun) - 201117

11. Matthes HWD, Luu B, Ourisson G. Chemistry and Biochemistry of Chinese drugs,

Cytotoxic components of Zingiber zerumbet, Curcuma zedoaria and Curcuma domestica.

Phytochemistry, Part VI: 1980; 19: 2643-2650.

12. Masuda T, Jitoe A, Kato S, Nakatani N. Constituents of Zingiberaceae, Acetylated

flavonol glycosides from Zingiber zerumbet. Phytochemistry, Part 3: 1991; 30: 2391-

2392.

13. Dai JR, Cardellina IIJH, McMahon JB. Boyd MR. Zerumbone, an HIV-inhibitory and

cytotoxic sesquiterpene of Zingiber aromaticum and Z. zerumbet, Natural Product Letter,

1997; 10:115-118.

14. Jang DS, Han AR, Park G, Seo EK. Flavonoids and aromatic compounds from the

rhizomes of Zingiber zerumbet. Archives of Pharmacal Research, 2004; 27: 386-389.

15. Jang DS, Han AR, Park G, Seo EK. Potentially Bioactive Two New Natural

Sesquiterpenoids from the Rhizomes of Zingiber zerumbet. Archives of Pharmacal

Research, 2005; 28: 294-296.

16. Hasnah MS. Chemical constituents of some medicinal plants of zingiberaceae: Medicinal

products from tropical rain forest. Proceedings of the Concerence, Forest Research

Institute Malaysia, Kuala Lumpur, 1991; 2: 299-304.

17. Srivastava AK, Srivastava SK, Shah NC. Essential Oil Composition of Zingiber zerumbet

(L.) Sm. from India. The Journal of Essential Oil Research, 2000; 12: 595-97.

18. Bhuiyan NI, Chowdhury JU, Begum J. Chemical investigation of the leaf and rhizome

essential oils of Zingiber zerumbet (L.) Smith from Bangladesh. Bangladesh Journal of

Pharmacology, 2009; 4: 9-12.

19. Dai JR, Cardellina II JH, McMahon JB, Boyd M R, Zerumbone, an HIV-inhibitory and

cytotoxic sesquiterpene of Zingiber aromaticum and Z. zerumbet. Natural Product Letter,

1997; 10, 115-118.

20. Murakami A, Takahashi D, Kinoshita T, Koshimizu K, Kim HW, Yoshihiro A,

Nakamura Y, Jiwajinda S, Terao J, Ohigashi H. Zerumbone, a southeast Asian ginger

sesquiterpene, markedly suppresses free radical generation, proinflammatory protein

ISSN 0976-111X

IJPWR VOL 2 ISSUE 2 (Mar-Jun) - 201118

production, and cancer cell proliferation accompanied by apoptosis: The αβ-unsaturated

carbonyl group is a prerequisite. Carcinogenesis, 2002; 23, 795-802.

21. Tanaka T, Shimizu M, Kohno H, Yoshitani SI, Tsukio Y, Murakami A, Safitri R,

Takahashi D, Yamamoto K, Koshimizu K, Ohigashi H, Mori H. Chemoprevention of

azoxymethane-induced rat aberrant crypt foci by dietary zerumbone isolated from

Zingiber zerumbet. Life Science, 2001; 69, 1935-1945.

22. Murakami A, Takahashi M, Jiwajinda S, Koshimizu K, Ohigashi H. Identification of

zerumbone in Zingiber zerumbet Smith as a potent inhibitor of 12-O-

tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus activation. Biosci Biotechnol

Biochem, 1999; 63:1811-2.

23. Huang GGC, Chien TY, Chen LG, Wang CC. Antitumour effects of Zerumbone from

Zingiber zerumbet in P-388D1 cells in vitro and vivo. Planta Medica, 2005; 71:219-224.

24. Fujimoto V, Maruno K, Made S. (1998) Antitumour sesquiterpene extraction from ginger

roots. Jpn. Kokai Tokkyo Koho, 6pp, patent No-JP 01221344 Az.

25. Matthes HWD, Luu B, Ourisson G. Chemistry and Biochemistry of Chinese drugs. Part

VI. Cytotoxic components of Zingiber zerumbet, Curcuma zedoaria and Curcuma

domestica. Phytochemistry 1980; 19: 2643-2650.

26. www.wikipedia.com

27. Kirtikar RK, Basu BD. Indian Medicinal Plant, Lalit Mohan Basu MB. Allahabad, India,

Vol. 4: 1984; 2415-2419.

28. Fansworth NR, Bunyapraphatsara N. Thai Medicinal Plants. Prachachon, Bangkok,

Thailand, 1992; 261-263.

29. Srivastava AK., Pharmacognostic studies on Zingiber zerumbet (L.) Sm. Aryavaidyan

Vol. XVI (4), 206-211.

30. Oliveros Mildred B. and Cantoria Magdalena C. , Pharmacognostic Studies on Zingiber

zerumbet (Linné) Smith and its Proposed Variety (Family Zingiberaceae), Pharmaceutical

Biology, 1982, Vol. 20, No. 3 , Pages 141-153

31. Chopra RN., Nayar SL., Chopra IC., Glossary of Indian medicinal Plants. Council of

Scientific & Industrial Research, New Delhi, 1956, 261.

ISSN 0976-111X

IJPWR VOL 2 ISSUE 2 (Mar-Jun) - 201119

32. Sharma PV., Dravyaguna Vijnana. Chaukambha bharati Academy, Varanasi, 1995, 332.

33. Chunekar K C., Pandeya G., Bhavaprakash Nighantu. Chaukhamba Sanskrit Santhana,

Varanasi, 1979, 45.

34. Sharma Sk., Chunekar KC., Yadava C.L. Medicinal plants used in Ayurveda. Rastriya

Ayurveda Vidyapeetha, New delhi, 1998, 198.

35. Dev S. Sesquiterpenes. XVI. Zerumbone, a monocyclic sesquiterpene ketone.

Tetrahedron 1960; 8: 171-80.

36. Nigam LC, Levi L. Column and gas chromatographic analysis of oil of wild ginger:

Identification and estimation of some new constituents. Can J Chem. 1963; 41: 1726-30.

http://dx.doi.org/10.1139/v63-248.

37. Damodaran NP, Dev S. Studies in sesquiterpenes - XXXIX. Structure of humulenols.

Tetrahedron 1968; 24: 4133-42. http://dx.doi.org/10.1016/0040-4020(68)88176-1.

38. Chhabra NP, Dhillon RS, Wadia MS, Kalsi PS. Structure of zerumbone oxide: A new

sesquiterpene epoxy ketone from Zingiber zerumbet Smith (wild ginger oil). Indian J

Chem. 1975; 13: 222-24.

39. Duve RN. Highlights of the chemistry and pharmacology of wild ginger (Zingiber

zerumbet Smith). Fiji Agric J. 1980; 42: 41-43.

40. Dung NX, Chinh TD, Leclercq PA. Chemical investigation of the aerial parts of Zingiber

zerumbet (L.) Sm. from Vietnam. J Essent Oil Res. 1995, 7: 153-57.

41. Chane-Ming J, Vera R., Chalchat JC. Chemical composition of the essential oil from

rhizomes, leaves and flowers of Zingiber zerumbet Smith from Reunion Island. J Essent

Oil Res. 2003; 15: 202-05.

42. Vahirua Lechat I, Francois P, Menut C, Lamely G, Bessiere JM. Aromatic plants of

French polynesia. 1. Constituents of the essential oils of rhizomes of three Zingiberaceae:

Zingiber zerumbet Smith, Hedychium coronarium Koenig and Etlingera cevuga Smith. J

Essent Oil Res. 1993; 5: 55-59.

43. Murakami A, Takahashi D, Kinoshita T, Koshimizu K, Kim HW, Yoshihiro A,

Nakamura Y, Jiwajinda S, Terao J, Ohigashi H. Zerumbone, a Southeast Asian ginger

sesquiterpene, markedly suppresses free radical generation, proinflammatory protein

ISSN 0976-111X

IJPWR VOL 2 ISSUE 2 (Mar-Jun) - 201120

production, and cancer cell proliferation accompanied by apoptosis: the alpha,beta-

unsaturated carbonyl group is a prerequisite. Carcinogenesis. 23(5): 2002; 795-802.

44. Jang DS, Han AR, Park G, Jhon GJ, Seo EK. Flavonoids and aromatic compounds from

the rhizomes of Zingiber zerumbet. Arch Pharm Res, 27(4): 2004; 386-9.

45. Jang DS, Min HY, Kim MS, Han AR, Windono T, Jeohn GH, Sam SK, Sang KL, Seo

EK. humulene derivatives from Zingiber zerumbet with the inhibitory effects on

lipopolysaccharide-induced nitric oxide production. Chem Pharm Bull, 53(7): 2005; 829-

831.

46. M.G. Kader, M.R. habib, F.nikkon et al., Zerumbone from the rhizome of zingiber

zerumbet and its anti-staphylococcal activity, Boletin latinoamericano y del Caribe de

plantas medicinals y aromatians, vol. 9, pp 63-68, 2010.

47. S. R. Hashemi, I. Zulkilli, M.H. Bejo, A. Farida, and M.N.somchit. Acute toxicity study

and phytochemical screening of selected herbal aqueous extract in broiler chicken.

International Journal of pharmacology, vol.4, no.5, pp 352-360, 2008.

48. Murakami A, Hayashi R, Tanaka T, Kwon KH, Ohigashi H, Safitri R. Suppression of

dextran sodium sulfate-induced colitis in mice by zerumbone, a subtropical ginger

sesquiterpene, and nimesulide: separately and in combination. Biochem Pharmacol,

66(7): 2003; 1253-61.

49. Sharifah Sakinah S, Tri Handayani S, Azimahtol Hawariah L. Zerumbone induced

apoptosis in liver cancer cells via modulation of Bax/Bcl-2 ratio. Cancer Cell Int, 7:

2007; 4.

50. Hashemi SR, Zulkifli I, Hair Bejo M, Farida A and Somchit MN. Acute toxicity and

phytochemical screening of selected herbal aqueous extract in broiler chickens.

International Journal of Pharmacology 2008; 4: 352-360.

51. Vimala S, Norhanom AW, Yadav M. Anti-tumour promoter activity in Malaysian ginger

rhizobia used in traditional medicine. Br J Cancer, 80(1-2): 1999; 110-6.

52. Vahirua Lechat I, Francois P, Menut C, Lamely G, Bessiere JM. Aromatic plants of

French polynesia. 1. Constituents of the essential oils of rhizomes of three Zingiberaceae:

ISSN 0976-111X

IJPWR VOL 2 ISSUE 2 (Mar-Jun) - 201121

Zingiber zerumbet Smith, Hedychium coronarium Koenig and Etlingera cevuga Smith. J

Essent Oil Res. 1993; 5: 55-59.

53. Eguchi A, Kaneko Y, Murakami A, Ohigashi H. Zerumbone suppresses phorbol ester-

induced expression of multiple scavenger receptor genes in THP-1 human monocytic

cells. Biosci. Biotech. Biochem., 71(4): 2007; 935-945.

54. Tanaka T, Shimizu M, Kohno H, Yoshitani S, Tsukio Y, Murakami A, Safitri R,

Takahashi D, Yamamoto K, Koshimizu K, Ohigashi H, Mori H.. Chemoprevention of

azoxymethane-induced rat aberrant crypt foci by dietary zerumbone isolated from

Zingiber zerumbet. Life Sci, 69(16): 2001; 1935-45.

55. Murakami A, Hayashi R, Tanaka T, Kwon KH, Ohigashi H, Safitri R. Suppression of

dextran sodium sulfate-induced colitis in mice by zerumbone, a subtropical ginger

sesquiterpene, and nimesulide: separately and in combination. Biochem Pharmacol,

66(7): 2003; 1253-61.

56. Huang GC, Chien TY, Chen LG, Wang CC. Antitumor effects of zerumbone from

Zingiber zerumbet in P-388D1 cells in vitro and in vivo. Planta Med, 71(3): 2005; 219-

24.

57. Chung SY, Jang DS, Han AR, Jang JO, Kwon Y, Seo EK, Lee HJ. Modulation of P-

glycoprotein-mediated resistance by kaempferol derivatives isolated from Zingiber

zerumbet. Phytother Res, 21(6): 2007; 565-9.

58. Takada Y, Murakami A, Aggarwal BB. Zerumbone abolishes NF-KB and IKBα kinase

activation leading to suppression of antiapoptotic and metastatic gene expression,

upregulation of apoptosis, and downregulation of invasion. Oncogene 24: 2005; 6957–

6969.

59. Raj RK. Screening of indigenous plants for anthelmintic action against human Ascaris

lumbricoides: Part--II. 1: Indian J Physiol Pharmacol., 19(1): 1975.

60. Jang DS, Min HY, Kim MS, Han AR, Windono T, Jeohn GH, Sam SK, Sang KL, Seo

EK. humulene derivatives from Zingiber zerumbet with the inhibitory effects on

lipopolysaccharide-induced nitric oxide production. Chem Pharm Bull, 53(7): 2005; 829-

831.

ISSN 0976-111X

IJPWR VOL 2 ISSUE 2 (Mar-Jun) - 201122

61. Sawangjaroen N, Subhadhirasakul S, Phongpaichit S, Siripanth C, Jamjaroen K,

Sawangjaroen K.. The in vitro anti-giardial activity of extracts from plants that are used

for self-medication by AIDS patients in southern Thailand. Parasitol Res., 95: 2005; 17–

21.

62. Sawangjaroen N, Phongpaichit S, Subhadhirasakul S, Visutthi M, Srisuwan N,

Thammapalerd N. The anti-amoebic activity of some medicinal plants.used by AIDS

patients in southern Thailand. Parasitol Res., 98: 2006; 588–592.

63. Chaung H-C, Ho C-T, Huang T-C. Anti-hypersensitive and anti-inflammatory activities

of water extract of Zingiber zerumbet (L.) Smith. Food and Agricultural Immunology

2008; 19: 117-129.

64. Tewtrakul S, Subhadhirasakul S. Anti-allergic activity of some selected plants in the

Zingiberaceae family. Journal of Ethnopharmacology 2007; 109: 535-538.

65. Husen R, Pihie AH, Nallappan M. Screening for antihyperglycaemic activity in several

local herbs of Malaysia. Journal of Ethnopharmacology 2004; 95: 205-208.

66. plants.usda.gov

67. Chopra RN., Nayar SL., Chopra IC., Glossary of Indian medicinal Plants. Council of

Scientific & Industrial Research, New Delhi, 1956, 261.

68. Petard P. Quelques plantes utiles de la Polynesie et Ra'au Tahiti. Papeete, Haere Po no

Tahiti, 1986, p 1876.

69. Md. Nazrul Islam Bhuiyan, Jasim Uddin Chowdhury and Jaripa Begum, Chemical

investigation of the leaf and rhizome essential oils of Zingiber zerumbet (L.) Smith from

Bangladesh, Bangladesh J Pharmacol 2009; 4: 9-12

70. Floridata: Zingiber zerumbet. (http://floridata.com/ref/Z/zing_zer.cfm) Accessed on 27th

April 2007.

71. Tropilab ® Inc., Exporter & Wholesaler of Medicinal Plants, Herbs and Tropical Seeds.

“Zingiber zerumbet- shampooginger”. http://www.tropilab.com/shampooginger.html.

72. Sharifah Sakinah S, Tri Handayani S, Azimahtol Hawariah L. Zerumbone induced

apoptosis in liver cancer cells via modulation of Bax/Bcl-2 ratio. Cancer Cell Int, 7:

2007; 4.

ISSN 0976-111X

IJPWR VOL 2 ISSUE 2 (Mar-Jun) - 201123