Curcuma zanthorrhiza

Synonyms

No documentation

Vernacular Names

Malaysia Temu Lawas, Temu Lawak
Indonesia Temu Lawak (Java); Koneng gede (Sunda Islands)
India Kaliyaka
English Javanese Turmeric [1] [2] [41]

General Information

Description

Curcuma zanthorrhiza is a member of the Zingiberaceae family. It is a robust, perennial, erect herb that could reach up to 2m tall. The rhizome is large and with a deep orange colour inside. The primary rhizome may reach 12cm long and 10cm in diameter. The lateral rhizomes are much smaller cylindrical and reaches up to 10cm long and 3cm diameter. The leaf shoots bear up to 8 leaves. The leaf sheath is green, forms a pseudostem and can reach up to 75cm long. The petiole is 30cm long. The leaf blade is elliptical-oblong or oblong-lanceolate measuring between 25-100cm x 8-20cm, dark green above with a distinct reddish-brown central streak measingn 1-2.5cm wide. The inflorescence appears lateral to the leaves. The terminal bracts are purplish while the lower ones are light green. The flowers are in cincinni of 2-7, each cincinnus in the axil of a bract.

Plant Part Used

Rhizome. [8]

Chemical Constituents

(12R)- -12,13-dihydro-12,13-dihydroxyxanthorrhizols; (12S)-12,13-dihydro-12,13-dihydroxyxanthorrhizols;  alpha-curcumene; alpha-turmerone; arturmerone; beta-curcumene; beta-sesquiphellandrene; beta-turmerone; bis-demethoxycurcumin; curcumin; curzerenone; germacrone; mono-demethoxycurcumin;  trans-trans-1,7-diphenyl-1,3-heptadien-4-one (alnustone); trans-1,7-diphenyl-1-hepten-5-ol, and trans,trans-1,7-diphenyl-1,3-heptadien-5-ol; xanthorrhizol. [4] [5] [6]

Traditional Uses

The rhizome of C. zanthorrhiza is traditionally used in treatment of diseases related to the liver and the biliary system. It is advocated in the treatment of liver swelling, chronic gallbladder problem including the presence of gallstones, and to improve the biliary secretion. It helps improving appetite in cases of eating disorders and was used to relieve constipation, diarrhoea and flatulence.

In the Malay archipelago, it is commonly used as one of the “jamu” ingredients for women in confinement and helps in increasing the flow of milk for lactating women. The rhizome also has been promoted for reduction of cholesterol level, kidney stones, fever, joints problems, skin swelling, wounds and to treat dysfunctional uterine bleeding. [3] [42]

Pre-Clinical Data

Pharmacology


Antinociceptive activity

The ethanol extract of C. zanthorrhiza rhizome exhibited both central and peripheral antinociceptive activities associated with neurogenic pain. The extract did not show any toxic effects in mice at a dose of 5g/kg. This indicates that the medicinal use of this plant is relatively safe. [7]

Oestrogenic activity

Xanthorrhizol, a sesquiterpenoid isolated from the rhizome of C. zanthorrhiza, had been evaluated for its oestrogenic activity. It was demonstrated that the compound significantly increased Gal-4/er luciferase activity, induced endogenous estrogen receptor (ER)-oestrogen response element interaction in MCF-7 cells and significantly enhanced the expression of the pS2 gene in MCF-7 cells. All these activities were suppressed by ICI 182780, an ER antagonist. These results indicated that xanthorrhizol has oestrogenic activity and it is mediated by oestrogen-induced gene expression. [8]

Skin antiphotoaging activity

Exposure to ultraviolet (UV) irradiation is concomitant with upregulation of matrix metalloproteinases (MMP) and decreased collagen synthesis.  Xanthorrhizol and C. zanthorrhiza extract was found to have the ability to significantly decrease the expression of MMP-1 protein and increased the expression of type-1 procollagen in fibroblast cell lines irradiated with UV (20mJ/cm2). At a dose of 0.1µM, xanthorrhizol nearly completely abrogated MMP-1 expression. [9]

Antiplatelet activating factor

1-Methoxy-2-methyl-5-(1',5'-dimethylhex-4'-enyl)-benzene, synthesized by methylation of xanthorrhizol which was obtained from C. zanthorrhiza at IC50 value of 40.9 µM significantly inhibit platelet activating factor. [10]

Nephroprotective activity

The administration of xanthorrhizol at amount 200 mg/kg/day, per os for 4 days  prior to exposure of cisplatin in mice showed it significantly attenuated the latter’s nephrotoxic effects. This effect does not seem to be related to the ability of xanthorrhizol to regulate the DNA-binding activities of transcription factor. The data however advocated for the treatment of cisplatin-induced nephrotoxicity.  [11]

Hepatoprotective activity

A preliminary study of the hepatoprotective activity of C.xanthorriza proved to be true when it was found that prior treatment with extracts of the rhizome could prevent acute elevation of serum transaminases levels induced by acetaminophen and carbon tetrachloride. Xanthorrhizol seems to be one of the bioactive compounds that affords this hepatoprotective activity. It does so by regulating DNA-binding activity of nuclear factor-kappaB and activator protein a (AP-1). [12] [13]

Immunostimulating activity

Rhizome of C. zanthorrhiza exhibited immunostimulating activities. It showed that the plant contains some principle(s) that could activate T and B-cell-medicated immune function. The crude polysaccharide extract was found to increase phagocytotic activities of macrophages, an action mediated in part by specific activation of NF-kappaB. [14] [15]

Antihyperlipidaemia activity

Amongst the effects of the C. zanthorrhiza on lipid metabolism are reduction of serum triglycerides and phospholipid concentration, reduction of liver cholesterol, and increased serum high density lipoprotein cholesterol and apolipoprotein A-I. The activity of liver acid synthase was decreased but not that of glycerophosphate dehydrogenase. Curcuminoids prepared from the plant had no significant effects on serum and liver lipid. However, the hexane-soluble fraction of the plant yielded a compound, alpha-curcumene, which has the capability of lowering serum triglyceride levels. [16][17]

Antimicrobial activity

Xanthorrhizol is a sesqueterpene isolated from the rhizome of C. zanthorrhiza. It has several antimicrobial activities.

Antifugal

Xanthorrhizol is active against the growth of Candica albicansC. glabrataC. guilliermondiiC. kruselC. parapsilosis and C. tropicalis. It is also active against Aspergilus flavusA. fumigatesA. nigerFusarium oxysporumRhizopus oryzaeTrichophyton mentagrophytesMalazzezia furfur,  and M. pachydermatis comparable to amphotericin B and ketoconazole. [18-22]

Antibacterial

Xanthorrhizol again proves to be effective in controlling the spread of Streptococcus mutans responsible for dental caries. It also inhibits the growth of Bacillus cereusClostridium perfringensListeria moncytogenesStaphylococcus aureausSalmonella typhimurium and Vibrio parahaemolyticus. It confers its strong antibacterial activity with thermal and pH stability, thus qualifying it to be considered as a natural preservative to prevent the growth of foodborne pathogens. [23-26]

Antimalarial activity

The extract of C. zanthorrhiza is one among the the plants screened to exhibit antimalarial activity with an inhibition range from 89.6 to 100%, [27]

Anticancer activity

Xanthorrhizol seems to be a key element in the anticancer activity of C. zanthorrhiza. It not only shows capabilities of arresting growth of a number of cancers, but is also active in preventing metastatic spread of some of the cancers investigated. It acts in the following manners: attenuate higher expression of cyclooxygenase-2, matrix metalloproteinase-9 and extracellular signal-regulated kinase; induce apoptosis through modulating bcl-2, p53 and PARP-1 protein levels; arrest cell cycle progression in the Go/G1 and C2/M phase and induced the increase of sub-G1 peaks. This cell cycle arrest was highly correlated with the downregulation of cyclin A, cyclin B1 and cyclin D1; cyclin-dependent kinase 1 (CDK1), CDK2 and CDK3; proliferating cell nuclear antigen; and induction of p21 and p27, cyclin-dependent kinase inhibitors. It may induce caspase-independent apoptosis through ROS-mediated p38 MAPK and JNK activation seen in SCC-15 OSCC cells. [28-35]

Antiinflammatory activity

A number of compounds isolated from C. zanthorrhiza had been identified as possessing potent antiinflammatory activity. These include germacrone, the non-phenolic linear 1,7-diarylheptanoids, and xanthorrhizol. Xanthorrhizol exhibited a potent inhibition of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase activity in the assay system of prostaglandin E2 accumulation and nitric oxide production respectively. The inhibitory potential of xanthorrhizol on the COX-2 activity coincided well with the suppression of COX-2 protein expression in lipopolysaccharide-induced macrophages. The antiinflammatory activity of xanthorrhizol was also expressed in brain homogenates making this neuroprotective effect useful in treatment of Alzheimer and other neurological conditions. [36-40]

Toxicities

No documentation

Teratogenic effects

No documentation

Clinical Data

Clinical Trials

No documentation

Adverse Effects in Human:

No documentation

Used in Certain Conditions

Pregnancy / Breastfeeding

No documentation

Age Limitations

Neonates / Adolescents

No documentation

Geriatrics

No documentation

Chronic Disease Conditions

No documentation

Interactions

Interactions with drugs

No documentation

Interactions with Other Herbs / Herbal Constituents

No documentation

Contraindications

Contraindications

Biliary obstruction. Patients with cholelithiasis should seek medical advice before taking C. zanthorrhiza[2]

Case Reports

No documentation

References

  1. Hanelt P. Mansfeld’s Encyclopedia of Agricultural and Horticultural Crops, Springer, Berlin, 2001, pg. 2383
  2. ESCOP MONOGRAPH – The Scientific Foundation for Herbal Medicinal Products pg. 57 – 64
  3. Dalimartha S., Atlas Tumbuhan Obat Indonesia Jilid 2, Niaga Swadaya, Jakarta, 2000. pg. 182-190
  4. Uehara S, Yasuda I, Takeya K, Itokawa H. Terpenoids and curcuminoids of the rhizoma of Curcuma xanthorrhiza Roxb. Yakugaku Zasshi. 1992 Nov;112(11):817-23.
  5. Claeson P, Panthong A, Tuchinda P, Reutrakul V, Kanjanapothi D, Taylor WC, Santisuk T. Three non-phenolic diarylheptanoids with anti-inflammatory activity from Curcuma xanthorrhiza. Planta Med. 1993 Oct;59(5):451-4.
  6. Matsuura H, Nomura S, Subeki, Yamada K, Yamasaki M, Yamato O, Maede Y, Katakura K, Trimurningsih, Chairul, Yoshihara T, Nabeta K. Anti-babesial compounds from Curcuma xanthorrhiza. Nat Prod Res. 2007 Apr;21(4):328-33.
  7. Devaraj S, Esfahani AS, Ismail S, Ramanathan S, Yam MF. Evaluation of the antinociceptive activity and acute oral toxicity of standardized ethanolic extract of the rhizome of Curcuma xanthorrhiza Roxb. Molecules. 2010 Apr 22;15(4):2925-34.
  8. Anggakusuma, Yanti, Lee M, Hwang JK. Estrogenic activity of xanthorrhizol isolated from Curcuma xanthorrhiza ROXB. Biol Pharm Bull. 2009 Nov;32(11):1892-7.
  9. Oh HI, Shim JS, Gwon SH, Kwon HJ, Hwang JK. The effect of xanthorrhizol on the expression of matrix metalloproteinase-1 and type-I procollagen in ultraviolet-irradiated human skin fibroblasts. Phytother Res. 2009 Sep;23(9):1299-302.
  10. Jantan I, Pisar M, Sirat HM, Basar N, Jamil S, Ali RM, Jalil J. Inhibitory effects of compounds from Zingiberaceae species on platelet activating factor receptor binding. Phytother Res. 2004 Dec;18(12):1005-7.
  11. Kim SH, Hong KO, Hwang JK, Park KK. Xanthorrhizol has a potential to attenuate the high dose cisplatin-induced nephrotoxicity in mice. Food Chem Toxicol. 2005 Jan;43(1):117-22.
  12. Lin SC, Lin CC, Lin YH, Supriyatna S, Teng CW. Protective and therapeutic effects of Curcuma xanthorrhiza on hepatotoxin-induced liver damage. Am J Chin Med. 1995;23(3-4):243-54.
  13. Kim SH, Hong KO, Chung WY, Hwang JK, Park KK. Abrogation of cisplatin-induced hepatotoxicity in mice by xanthorrhizol is related to its effect on the regulation of gene transcription. Toxicol Appl Pharmacol. 2004 May 1;196(3):346-55.
  14. Yasni S, Yoshiie K, Oda H, Sugano M, Imaizumi K. Dietary Curcuma xanthorrhiza Roxb. increases mitogenic responses of splenic lymphocytes in rats, and alters populations of the lymphocytes in mice. J Nutr Sci Vitaminol (Tokyo). 1993 Aug;39(4):345-54.
  15. Kim AJ, Kim YO, Shim JS, Hwang JK. Immunostimulating activity of crude polysaccharide extract isolated from Curcuma xanthorrhiza Roxb. Biosci Biotechnol Biochem. 2007 Jun;71(6):1428-38.
  16. Yasni S, Imaizumi K, Nakamura M, Aimoto J, Sugano M. Effects of Curcuma xanthorrhiza Roxb. and curcuminoids on the level of serum and liver lipids, serum apolipoprotein A-I and lipogenic enzymes in rats. Food Chem Toxicol. 1993 Mar;31(3):213-8.
  17. Yasni S, Imaizumi K, Sin K, Sugano M, Nonaka G, Sidik. Identification of an active principle in essential oils and hexane-soluble fractions of Curcuma xanthorrhiza Roxb. showing triglyceride-lowering action in rats. Food Chem Toxicol. 1994 Mar;32(3):273-8.
  18. Rukayadi Y, Yong D, Hwang JK. In vitro anticandidal activity of xanthorrhizol isolated from Curcuma xanthorrhiza Roxb. J Antimicrob Chemother. 2006 Jun;57(6):1231-4. Epub 2006 Apr 14.
  19. Rukayadi Y, Hwang JK. In Vitro antimycotic activity of xanthorrhizol isolated from Curcuma xanthorrhiza Roxb. against opportunistic filamentous fungi. Phytother Res. 2007 May;21(5):434-8.
  20. Rukayadi Y, Hwang JK. In vitro anti-Malassezia activity of xanthorrhizol isolated from Curcuma xanthorrhiza Roxb. Lett Appl Microbiol. 2007 Feb;44(2):126-30.
  21. Rukayadi Y, Lee K, Lee MS, Yong D, Hwang JK. Synergistic anticandidal activity of xanthorrhizol in combination with ketoconazole or amphotericin B. FEMS Yeast Res. 2009 Dec;9(8):1302-11. Epub 2009 Jul 1.
  22. Rukayadi Y, Hwang JK. In Vitro Activity of Xanthorrhizol Isolated from the Rhizome of Javanese Turmeric (Curcuma xanthorrhiza Roxb.) against Candida albicans Biofilms. Phytother Res. 2012 Sep 12. doi: 10.1002/ptr.4834. [Epub ahead of print]
  23. Rukayadi Y, Hwang JK. In vitro activity of xanthorrhizol against Streptococcus mutans biofilms. Lett Appl Microbiol. 2006 Apr;42(4):400-4.
  24. Rukayadi Y, Hwang JK. Effect of coating the wells of a polystyrene microtiter plate with xanthorrhizol on the biofilm formation of Streptococcus mutans. J Basic Microbiol. 2006;46(5):410-5.
  25. Kim JE, Kim HE, Hwang JK, Lee HJ, Kwon HK, Kim BI. Antibacterial characteristics of Curcuma xanthorrhiza extract on Streptococcus mutans biofilm. J Microbiol. 2008 Apr;46(2):228-32. Epub 2008 Jun 11.
  26. Lee LY, Shim JS, Rukayadi Y, Hwang JK. Antibacterial activity of xanthorrhizol isolated from Curcuma xanthorrhiza Roxb. against foodborne pathogens. J Food Prot. 2008 Sep;71(9):1926-30.
  27. Murnigsih T, Subeki, Matsuura H, Takahashi K, Yamasaki M, Yamato O, Maede Y, Katakura K, Suzuki M, Kobayashi S, Chairul, Yoshihara T. Evaluation of the inhibitory activities of the extracts of Indonesian traditional medicinal plants against Plasmodium falciparum and Babesia gibsoni. J Vet Med Sci. 2005 Aug;67(8):829-31.
  28. Choi MA, Kim SH, Chung WY, Hwang JK, Park KK. Xanthorrhizol, a natural sesquiterpenoid from Curcuma xanthorrhiza, has an anti-metastatic potential in experimental mouse lung metastasis model. Biochem Biophys Res Commun. 2005 Jan 7;326(1):210-7.
  29. Ismail N, Pihie AH, Nallapan M. Xanthorrhizol induces apoptosis via the up-regulation of bax and p53 in HeLa cells. Anticancer Res. 2005 May-Jun;25(3B):2221-7.
  30. Cheah YH, Azimahtol HL, Abdullah NR. Xanthorrhizol exhibits antiproliferative activity on MCF-7 breast cancer cells via apoptosis induction. Anticancer Res. 2006 Nov-Dec;26(6B):4527-34.
  31. Handayani T, Sakinah S, Nallappan M, Pihie AH. Regulation of p53-, Bcl-2- and caspase-dependent signaling pathway in xanthorrhizol-induced apoptosis of HepG2 hepatoma cells. Anticancer Res. 2007 Mar-Apr;27(2):965-71.
  32. Park JH, Park KK, Kim MJ, Hwang JK, Park SK, Chung WY. Cancer chemoprotective effects of Curcuma xanthorrhiza. Phytother Res. 2008 May;22(5):695-8.
  33. Kang YJ, Park KK, Chung WY, Hwang JK, Lee SK. Xanthorrhizol, a natural sesquiterpenoid, induces apoptosis and growth arrest in HCT116 human colon cancer cells. J Pharmacol Sci. 2009 Nov;111(3):276-84.
  34. Tee TT, Cheah YH, Meenakshii N, Mohd Sharom MY, Azimahtol Hawariah LP. Xanthorrhizol induced DNA fragmentation in HepG2 cells involving Bcl-2 family proteins. Biochem Biophys Res Commun. 2012 Apr 20;420(4):834-8. Epub 2012 Mar 23.
  35. Kim JY, An JM, Chung WY, Park KK, Hwang JK, Kim DS, Seo SR, Seo JT. Xanthorrhizol Induces Apoptosis Through ROS-Mediated MAPK Activation in Human Oral Squamous Cell Carcinoma Cells and Inhibits DMBA-Induced Oral Carcinogenesis in Hamsters. Phytother Res. 2012 May 25. doi: 10.1002/ptr.4746. [Epub ahead of print]
  36. Ozaki Y. Antiinflammatory effect of Curcuma xanthorrhiza Roxb, and its active principles. Chem Pharm Bull (Tokyo). 1990 Apr;38(4):1045-8.
  37. Claeson P, Pongprayoon U, Sematong T, Tuchinada P, Reutrakul V, Soontornsaratune P, Taylor WC. Non-phenolic linear diarylheptanoids from Curcuma xanthorrhiza: a novel type of topical anti-inflammatory agents: structure-activity relationship. Planta Med. 1996 Jun;62(3):236-40
  38. Lee SK, Hong CH, Huh SK, Kim SS, Oh OJ, Min HY, Park KK, Chung WY, Hwang JK. Suppressive effect of natural sesquiterpenoids on inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) activity in mouse macrophage cells. J Environ Pathol Toxicol Oncol. 2002;21(2):141-8.
  39. Lim CS, Jin DQ, Mok H, Oh SJ, Lee JU, Hwang JK, Ha I, Han JS. Antioxidant and antiinflammatory activities of xanthorrhizol in hippocampal neurons and primary cultured microglia. J Neurosci Res. 2005 Dec 15;82(6):831-8.
  40. Chung WY, Park JH, Kim MJ, Kim HO, Hwang JK, Lee SK, Park KK. Xanthorrhizol inhibits 12-O-tetradecanoylphorbol-13-acetate-induced acute inflammation and two-stage mouse skin carcinogenesis by blocking the expression of ornithine decarboxylase, cyclooxygenase-2 and inducible nitric oxide synthasethrough mitogen-activated protein kinases and/or the nuclear factor-kappa B. Carcinogenesis. 2007 Jun;28(6):1224-31. Epub 2007 Jan 18.
  41. Wise TA, Commentary on the Hindu System of Medicine: New Issue Trubner 7 Co. London 1860 pg. 138
  42. Soedibyo BRAM, Alam Sumber Kesehatan: Manfaat dan Kegunaan Balai Pusaka Jakarta 1998 pg. 368 - 369