Articles

Zingiber zerumbet

Synonyms

Zingiber spurium, Zingiber littorale, Zingiber aromaticum, Amomum zerumbet L., Amomum zingiber Lour.  

Vernacular Names:

Malaysia: Lempoyang
English: Shampoo ginger, wild ginger, pain ginger, horse ginger, zerumbet ginger, pinecone ginger, pinecone lily
Others: Opuhi, zerumbet, gingembre fou, gingembre blanc, jenjibre-amargo, lampuyang, lempuyang, lampojang, khnhei phtu, prateal vong prenh atit, hva:nz ph'ai chai hlüang, barik, langkawas, kathue, kathue-pa, kawaen

General Information

Description

Zingiber zerumbet can reach measuring 9 feet tall. It has long narrow leaves with cone shaped bracts. It is known as shampoo ginger due to the creamy liquid substance in the cones which is excellent as a natural hair conditioner. Z. zerumbet grows widely in Southeast Asia. [1]   

Plant Part Used

Rhizomes and cones. [1]

Chemical Constituents

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 zerumboneoxide. [2],[3]

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-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). [4]

Traditional Use:

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 ache. [5] For toothache or cavity, the cooked and softened rhizome was pressed into the hollow until the pain subsides. [1] 

Z. zerumbet is also used in local traditional medicine to treat swelling, sores and loss of appetite. [6] The rhizomes are boiled and the juice used to treat worm infestation in children. [6] The rhizome is also used to relieve stomachache and is macerated in alcohol for use as a tonic and depurative. [6],[7] In some South East Asian countries, the rhizome is used to treat inflammatory conditions [8] and to relieve fever, pain and constipation. [6] Young shoots and the inflorescence are used as condiments and as a food supplement to reduce experimental ulcerative colitis. [7],[8]

Pre-Clinical Data

Pharmacology

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 it. [7] Zerumbone also induced apoptosis in human colorectal cancer cell lines. [9] 

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 crypts as assessed by silver-stained nucleolar organizer regions protein was also significantly reduced by zerumbone. [10]

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 enhanced. [11]

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 1. [12]

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 chemotherapy. [13]

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 zerumbone. [14]

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 fibroblasts. [15],[16] 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 position. [15]

The anti-inflammatory and chemopreventive potential of zerumbone were further investigated in various cell lines.  Zerumbone inhibited TPA-induced superoxide generation from NADPH-oxidase in dimethylsulfoxide differentiated HL-60 human acute promyelocytic leukemia cells and from xanthine oxidase in AS52 Chinese hamster ovary cells. Thus the chemopreventive effects of zerumbone may be attributed to its ability to mitigate oxidative damage and/or to disrupt signal transduction pathways for carcinogenesis.  Zerumbone also markedly reduced lipopolysaccharide- and interferon-g-stimulated protein expressions of inducible nitric oxide synthase and cyclooxygenase (COX)-2 in RAW 264.7 mouse macrophages.  The release of tumour necrosis factor a was also reduced.  The concentration of nitrites and prostaglandin E2 in the medium were reduced by zerumbone while COX-1 expression levels remained unchanged.  Zerumbone exhibited dose-dependent antiproliferative effects on human colonic adenocarcinoma cell lines (LS174T, LS180, COLO 205, COLO320DM) but had less effect on the growth of normal human dermal (2F0C25) and colon (CCD-18 Co) fibroblasts.  Apoptosis was induced in COLO 205 cells as evidenced by mitochondrial transmembrane dysfunction, translocation of phosphatidyl serine and condensation of chromatin. [8]

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.  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 prostaglandins. [17] The aqueous extract (50 100 mg/kg) given intraperitoneally (i.p.) produced significant antiinflammatory activity, similar to that elicited by mefenamic acid (20 mg/kg, i.p.), in a prostaglandin E2-induced rat paw edema model with maximal effects seen at 0.5-1 hour. The antiinflammatory activity of the aqueous extract was dose-dependent as a low dose (25 mg/kg) did not produce significant changes.  The ethanol extract (25-100 mg/kg) did not exhibit antiinflammatory effects in this model. [6]

Anthelminthic activity

The alcoholic extract of Z. zerumbet rhizomes exhibited good in vitro anthelmintic activity against Ascaris lumbricoides. [18]

 

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). [19]

5-Hydroxyzerumbone, zerumboneoxide and zerumbone, all isolated from the rhizomes, inhibited lipopolysaccharide-induced nitric oxide production in murine macrophage RAW 264.7 cells with IC50 values of 14.1, 23.5 and 5.4 µM, respectively. [3]

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 kB. [9]

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/mL. [20],[21]

Toxicities

Both the aqueous and ethanol extracts of Z. zerumbet were non toxic to rats at doses up to 500 mg/kg. [6] Zerumbone (0.1% added to food pellets) did not cause deaths in female mice given the compound for 2 weeks. [11]

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 respectively. [7]

Genotoxicities and Mutagenicity Studies

No documentation

Clinical Data

Clinical Trials

No documentation

Adverse Effects in Human:

No documentation

Use in Certain Conditions

Pregnancy / Breastfeeding

No documentation

Age Limitations

No documentation

Chronic Disease Conditions

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Interactions

Interactions with drugs

No documentation

Interactions with Other Herbs / Herbal Constituents

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Contraindications

Contraindications

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Case Reports

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  1)  Botanical Info

References

  1. Floridata: Zingiber zerumbet. (http://floridata.com/ref/Z/zing_zer.cfm) Accessed on 27th April 2007.
  2. 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.
  3. 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.
  4. 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. Journal of Essential Oil Research, 2003.
  5. Tropilab ® Inc., Exporter & Wholesaler of Medicinal Plants, Herbs and Tropical Seeds. “Zingiber zerumbet-shampoo ginger”. (http://www.tropilab.com/shampooginger.html) Accessed on 4th May  2007.
  6. Somchit MN, Nur Shukriyah MH.  Anti-inflammatory property of ethanol and water extracts of Zingiber zerumbet. Indian J Pharmacol, 35: 2003; 181-182.
  7. 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.
  8. 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 production, and cancer cell proliferation accompanied by apoptosis: the alpha,beta-unsaturated carbonyl group is a prerequisite. Carcinogenesis. 23(5): 2002; 795-802.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. Murakami A, Takahashi, M, Jiwajinda, S, Koshimizu, K, Ohigashi H.  Identification of zerumbone in Zingiber zerumber Smith as a potent inhibitor of 12-O-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus activation. Biosci Biotech Biochem, 63(10): 1999; 1811-1812.
  16. 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.
  17. Somchit MN, Shukriyah MHN, Bustaman AA, Zuraini A. Anti-pyretic and analgesic activity of Zingiber zerumbet. Int J Pharmacol, 1(3): 2005; 277-280.
  18. Raj RK. Screening of indigenous plants for anthelmintic action against human Ascaris lumbricoides: Part--II. 1: Indian J Physiol Pharmacol., 19(1): 1975.
  19. Nakamura Y, Yoshida C, Murakami A, Ohigashi H, Osawa T, Uchida K.  Zerumbone, a tropical ginger sesquiterpene, activates phase II drug metabolizing enzymes. FEBS Lett., 572(1-3): 2004; 245-50.
  20. 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.
  21. 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.

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-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). [4]