Temu lawak Rhizome
Curcuma xanthorrhiza Roxburgh
Zingiberaceae
Figure 1 : C. xanthorrhiza (a) Branched rhizome; (b) rhizome; (c) inflorescence; (d) inner flesh of the rhizome; (e) rhizome showing adventitious roots grow; (f) field planting; (g) whole plants showing inflorescence. (Photos courtesy of Hawa ZE Jaafar, UPM, 2013)
DEFINITION
Temu lawak rhizome consists of dried rhizome of Curcuma xanthorrhiza (Roxb.) (Zingiberaceae).
SYNONYM
Curcuma zanthorrhiza Roxb.
VERNACULAR NAMES
Giant curcuma and false turmeric (English), temu lawas, temu kuning, kuncur, temu raya (Malay), shu gu jiang huang, yin ni e zhu (Chinese), menjal (Tamil) [ 1 ].
CHARACTER
| Colour | Rhizomes few, few branched, orange or orange-red inside, paler on younger parts, short; roots with large tubers |
| Odour | Pungent |
| Taste | Bitter |
IDENTIFICATION
Plant Morphology
Shrub up to 2 m tall, erect. Rhizome few branched, ovate, with both palmate and pendulous tubers deep/dark yellow, orange or orange-red inside, paler on younger parts, has pungent smell and bitter taste. Leaves semi erect, sessile on their green sheaths, broad lanceolar and oblong, sheaths of the scapes; leaf margin medium wavy; leaf blade green with purple midvein, oblong with distinct purple strip beside main green midrib, size of 10-18 x 30-80 cm, glabrous; ligule small; petiole ca. 10 cm. Inflorescense up to 25 cm, on separate shoots arising from rhizomes; peduncle 15-25 cm; spike 16-25 x 8-10 cm; fertile bracts pale green, ca. 1.4 cm, pubescent, apex 3-toothed; corolla tube ca. 3.5 cm, lobes pale purple, ovate, ca. 1.7 x 1.5 cm. Coma large, and of deep purple, or crimson colour; coma bracts dark pink; flowers yellow with pinkish corolla lobes exterior border of the corolla red; lateral staminodes yellowish tinged with purple, oblong, ca. 1.7 x 1 cm; labellum yellowish with deeply coloured, median band, square, ca. 2 x 2 cm; anther ca. 4 mm, base with spurs ca. 3 mm. Roots short with large tubers; shape of root stock oblong, short, colour reddish-yellow [ 2 , 3 , 4 , 5 , 6 , 7 ].
Microscopy
Microscopic characters of C. xanthorrhiza rhizome powder consist of fragments of colorless parenchyma cells with yellowish-brown or orange-yellow secretory cells; xylem vessels with oil-filled secretory cells; rare fragments of of cork and epidermis; numerous starch granules stratified, ovoid or irregular, about 30-50 µm long and about 10-30 µm wide, with an acentric hilum and marked, concentric striations; scalariform vessels and fragments of thick-walled unicellular acute trichomes [ 8 ].
Figure 2 : Microscopic characters of C. xanthorrhiza rhizome powder. (a) Parenchyma cells; (b) xylem vessels with oil-filled secretory cells; (c-d) starch granules; (e-f) scalariform vessels. [Magnification: a, b, f = 10x; c, d, e = 20x]
Colour Tests
Observed colour of solution after treatment with various reagents:
| H2SO4 (conc.) | Brown |
| 5% KOH | Brown |
Thin Layer Chromatography (TLC)
Figure 3 : TLC profiles of xanthorrhizol (S) and ethanol extract of C. xanthorrhiza dried rhizome powder (L) observed under (a) UV at 254 nm; (b) UV at 366 nm; (c) visible light after spray with vanillin-sulphuric acid reagent.
| Test Solutions | Weigh 0.3 g of C. xanthorrhiza dried rhizome powder in a 50 mL screw-capped conical flask and add 20 mL of absolute ethanol into the flask. Shake the mixture for 30 min then filter the mixture and evaporate the filtrate on water bath at 60°C to dryness. Reconstitute the residue with 5 mL of methanol. |
| Standard solution | Dissolve 1 mg xanthorrhizol [CAS no.: 30199-26-9] in 2 mL methanol to produce 0.5 mg/mL solution. |
| Stationary Phase | HPTLC glass silica gel 60 F254, 10 x 10 cm. |
| Mobile phase | Toluene : ethyl acetate (93:7) (v/v) |
| Application |
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| Development distance | 8 cm |
| Drying | Air drying |
| Detection |
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High Performance Liquid Chromatography (HPLC)
| Test solution | Extract about 0.3 g of C. xanthorrhiza dried rhizome powder with 20 mL of absolute ethanol in a 50 mL screw-capped conical flask. Shake the mixture for 30 min. Filter the mixture and evaporate the filtrate on a water bath at 60°C to dryness. Reconstitute the residue with 5 mL of methanol. Filter the mixture solution through a 0.45 µm syringe filter and inject the filtrate into the HPLC column. | ||||||||||||||||||
| Standard solution | Dissolve 1.0 mg of xanthorrhizol standard [CAS no.: 30199-26-9] in 2 mL of methanol to produce 0.5 mg/mL solution. | ||||||||||||||||||
| Chromatographic system |
Detector: UV 275 nm |
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| Mobile Phase (gradient mode) |
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| System suitability requirement |
Perform at least five replicate injections of xanthorrhizol (0.5 mg/mL). The requirements of the system suitability parameters are as follow:
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| Acceptance criteria |
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Figure 4 : HPLC full chromatogram of xanthorrhizol standard solution (0.5 mg/mL) at tr = 13.985 min.
Figure 5 : HPLC zoom chromatogram of xanthorrhizol standard solution (0.5 mg/mL) at tr = 13.985 min.
Figure 6 : HPLC full chromatogram of ethanol extract of C. xanthorrhiza dried rhizome showing peak corresponding to xanthorrhizol at tr = 13.975 min.
Figure 7 : HPLC zoom chromatogram of ethanol extract of C. xanthorrhiza dried rhizome showing peak corresponding to xanthorrhizol at tr = 13.975 min.
Figure 8 : UV spectrum of xanthorrhizol standard solution (0.5 mg/mL) and ethanol extract of C. xanthorrhiza dried rhizome.
PURITY TESTS
| Foreign Matter |
| Not more than 2% |
| Ash Contents | |
| Total ash | Not more than 9% |
| Acid-insoluble ash | Not more than 3% |
| Loss on Drying |
| Not more than 10% |
| Extractive Values | |
| Water-soluble extracts | |
| Hot method | Not less than 16% |
| Cold method | Not less than 14% |
| Ethanol-soluble extracts | |
| Hot method | Not less than 4% |
| Cold method | Not less than 3% |
SAFETY TESTS
| Heavy Metals | |
| Arsenic | Not more than 5.0 mg/kg |
| Mercury | Not more than 0.5 mg/kg |
| Lead | Not more than 10.0 mg/kg |
| Cadmium | Not more than 0.3 mg/kg |
| Microbial Limits | |
| Total bacterial count | Not more than 105 cfu/g |
| Total yeast and mould count | Not more than 104 cfu/g |
| Bile-tolerant gram negative | Not more than 104 cfu/g |
| Specific Pathogens | |
| Salmonella spp. | Absent in 25 g |
| Escherichia coli | Absent in 1 g |
| Staphylococcus aureus | Absent in 1 g |
| Pseudomonas aeruginosa | Absent in 1 g |
CHEMICAL CONSTITUENTS
Ethyl acetate extract of the rhizome has been found to contain curcuminoids (e.g. bisdemethoxycurcumin, demethoxycurcumin, curcumin) [ 9 , 10 ].
Acetone extract of the rhizome has been found to contain curcuminoid (e.g. curcumin) [ 10 ].
Ethanol extract of the rhizome has been found to contain monoterpene (e.g. camphor), sesquiterpenes (e.g. zingiberene, γ-elemene, trans β‐farnesene, Ar-curcumene, α‐cedrene, β‐elemenone), sesquiterpenoid (e.g. xanthorrhizol) and others (e.g. curcumin, benzofuran) [ 10 , 11 ].
Aqueous extract of the rhizome has been found to contain monoterpene (e.g. camphor), sesquiterpenes (e.g. Ar-curcumene, α‐cedrene, β‐elemenone) and sesquiterpenoid (e.g. xanthorrhizol) [ 11 , 12 ].
Essential oil of the rhizome has been found to contain monoterpenes (e.g. borneol, δ-terpineol, camphene, α-pinene, α-thujene, β-pinene, myrcene, linalool, cis-pinene, α-phellandrene, α-terpinene, (Z)-β-ocimene, β-ocimene, p-cymene, γ-terpinene, camphor, α-terpineol, terpinen-4-ol, limonene, terpinolene, ρ-cymene-8-ol, cis-dehydro-β-terpineol), curcuminoids (e.g. curcumin), sesquiterpenes (e.g. α-curcumene, zingiberene, α-cubebene, β-humulene, humulene, (Z)-β-farnesene, γ-elemene, (E)-β-farnesene, Ar-curcumene, γ-curcumene, β-bisabolene, (Z)-γ-bisabolene, β-curcumene, β-sesquiphellandrene, caryophyllene oxide, thujopsan-2-α-ol, sesquithuriferol, 1,10-di-epi-cubenol, β-bisabolol, Ar-curcumen-15-al, (E, Z)-farnesol, α-bisabolol oxide A, β-elemene, β-caryophyllene, humuleneoxide, curzerenone, trans-α-bergamotene, germacrone), sesquiterpenoids (e.g. xanthorrhizol, cubenol, α-eudesmol, α-cis-bergamotene), monoterpenoids (1,8-cineole, 6,7-epoxymyrcene), phenylpropene (e.g. (Z)-isoeugenol,), esters (e.g. methyl undecanoate, (E)-ethyl cinnamate, butyl dodecanoate), and others (e.g. ethyl-4E-octenoate, dihydro citronellol acetate, methyl perillate, 1,10-decanediol, (Z)-isoeugenol acetate, citronellyl pentanoate, cis-cadin-4-en-7-ol, (E)-amyl-cinnamic alcohol, (E)-citronellyl tiglate, 1-phenyl-hepta-1,3,5-triyne, 4-hydroxy-3-methoxycinnamaldehyde, chamazulene, α-p-dimethylstyrene, 2-nonanol) [ 13 , 14 , 15 , 16 , 17 , 18 ].
MEDICINAL USES
Uses described in folk medicine, not supported by experimental or clinical data
Traditionally, infusion of C. xanthorriza with two Zingibers and peppercorns is used for indigestion and rheumatism. It is also used as emmenagogue in amenorrhoea, as a tonic after childbirth and also applied to the body after childbirth in the form of paste. The rhizome can also cure the liver disease and sliced or grated and infused to cure gall-stones
[ 19 ].
Biological and pharmacological activities supported by experimental data
Antimetastatic activity
Xanthorrhizol isolated from rhizome of C. xanthorriza when given intraperitoneally daily to six-week-old C57BL6 mice inoculated with 2×105 B16BL6 melanoma cells suppressed the formation of intra-abdominal tumour mass with dosage 0.2 mg/kg (71% reduction) and 0.5 mg/kg (97% reduction) after 2 weeks. Xanthorrhizol (0.1-1.0 mg/kg/day) given intravenously for two weeks to Balb/c mice induced with murine colon cancer CT26 cells significantly reduced the formation of lung tumour nodules at concentration 0.1 and 1.0 mg/kg (p < 0.005) and at concentration 0.2 and 0.5mg/kg (p < 0.0001) as compared to CT26 cell alone-treated group [ 20 ].
Antifungal activity
Xanthorrhizol isolated from ethyl acetate fraction of methanol extract of C. xanthorrhiza rhizome (0.125 – 64.0 µg/mL) inhibited the growth of Aspergillus flavus (minimum inhibitory concentration (MIC) 2 µg/mL; minimum fungicidal concentration (MFC) 4 µg/mL), Aspergillus fumigatus (MIC 2 µg/mL; MFC 4 µg/mL), Aspergillus niger (MIC 2 µg/mL; MFC 4 µg/mL), Fusarium oxysporum (MIC 4 µg/mL; MFC 8 µg/mL), Rhizopus oryzae (MIC 1 µg/mL; MFC 2 µg/mL) and Trichophyton mentagrophytes (MIC 1 µg/mL; MFC 2 µg/mL) by using in vitro susceptibility test [ 21 ].
Xanthorrhizol (4.0 µg/mL) inhibited the conidial germination of R. oryzae (18%) and T. mentagrophytes (22%). The dose of 8.0 µg/mL inhibited the germination of A. flavus (22%), A. fumigatus (18%)and A. niger (16%)while the dose of 16.0 µg/mL inhibited the germination of F. oxysporum (24%) by using conidial germination assay [ 21 ].
Essential oil of C. xanthorrhiza rhizome inhibited the growth of Candida albicans (inhibition zone = 9 mm), Kluyveromyces (7 mm), A. flavus (8 mm) and Penicillium chrysogenum (8 mm) by using disc diffusion assay [ 13 ].
Xanthorrhizol isolated from ethyl acetate fraction of methanol extract of C. xanthorrhiza rhizome inhibited the growth of 18 clinical isolates of Candida albicans with sessile minimum inhibitory concentrations (SMIC50) of 4 to 16 g/mL by using 2,3-bis(2-methoxy-4-nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay after 24 hours of incubation [ 22 ].
Xanthorrhizol isolated from ethyl acetate fraction of methanol extract of rhizome of C. xanthorrhiza inhibited the growth of C. albicans (MIC of 1.0–15.0 mg/L), C. glabrata (1.0–10 mg/L), C. guilliermondii (2.0–8.0 mg/L), C. krusei (2.5–7.5 mg/L), C. parapsilosis (5.0–25 mg/L) and C. tropicalis (2.0–8.0 mg/L) byusing National Committee for Clinical Laboratory Standards (NCCLS) M27-A2 broth microdilution assay after 48 hours of incubation [ 23 ].
Antibacterial activity
Essential oil of C. xanthorrhiza rhizome inhibited the growth of Escherichia coli (inhibition zone = 14 mm), Bacillus amyloliquefaciens (14 mm), Klebsiella pnuemoniae (12 mm), Shigella sonnei (11 mm), Enterobacter aerogens (10 mm), Pseudomonas aeruginosa (9 mm), Salmonella thypi (9 mm), Xanthomonas campestris (9 mm), Mycobacterium sp. (8 mm), Proteus vulgaris (8 mm), Streptococcus thermophiles (8 mm), Staphylococcus aureus (8 mm) and Bacillus megaterium (7 mm) by using disc diffusion assay [ 13 ].
Xanthorrhizol isolated from C. xanthorrhiza rhizome (50 µmol/L) significantly (p < 0.05) inhibited biofilm formation at adherent phase of Streptococcus mutans growth (76%) after 60 min by using polystyrene microtitre plate assay [ 24 ].
Xanthorrhizol isolated from C. xanthorrhiza rhizome completely inhibited biofilm formation by Streptococcus mutans within 60 min of exposure to the xanthorrhizolat adherent phases (5-50 µmol/L) and active accumulated phase (50 µmol/L only) [ 24 ].
Anti-oxidant activity
Methanol extract of C. xanthorrhiza rhizome inhibited low density lipoprotein (LDL) oxidation with IC50 of 0.78 ± 0.03 µg/mL by using thiobarbituric acid reactive substances assay. Essential oil of the rhizome had IC50 of 2.2 ± 0.1 µg/mL while xanthorrhizol (isolated from the essential oil) had IC50 of 0.4 ± 0.1 µg/mL by using the same assay [ 15 ].
Freeze-dried curcuminoids isolated from ethyl acetate extract of C. xanthorrhiza rhizome (10 mg) inhibited lipid peroxidation with (98.4%) comparable to butylated hydroxyltoluene (BHT) (99.7%) by using ferric thiocyanate (FTC) value FTC assay, TBA value (99.7 ± 0.001%) comparable to quercetin (98.3 ± 0.010%). However, the extract has a lower DPPH scavenging activity (IC50) 62.7 ± 0.014 µg/mL compared to ascorbic acid (8.48 ± 0.012 µg/mL) [ 9 ].
Anticancer activity
Xanthorrhizol isolated from C. xanthorrhiza rhizome reduced the viability of human breast cancer cell line MCF-7 with EC50 1.71 ± 0.16 µg/mL using MTT method after 72 hours of incubation. The xanthorrhizol also reduced the viability of other malignant cell lines such as T-47D (ductal breast cancer cell), HepG2 (liver cancer cell), HM3KO (melanoma cell) and MG-63 (osteosarcoma cell) with EC50 < 5 µg/mL. The xanthorrhizol (10 µg/mL) also reduced the viability 47% of MCF-7 cells compared to untreated cells as quantified by flow cytometry analyser after annexin-V binding assay. Nuclear morphology of xanthorrhizol-treated MCF-7 cells (5 µg/mL and 10 µg/mL) using Hoechst 33258 assay showed shrinkage of cells, DNA condensations, nuclear and plasma membrane convolution and nuclear fragmentation [ 25 ].
Xanthorrhizol isolated from C. xanthorrhiza rhizome reduced the viability of HepG2 cell (IC50 4.17 ± 0.03 µg/mL), non-malignant Chang’s liver cell (IC50 8.7 ± 0.0065 µg/mL) and Vero cell (IC50 6.6 ± 0.061 µg/mL). The xanthorrhizol (4 µg/mL) also increased the level of apoptosis on HepG2 cells compared to untreated cells with apoptotic index 72% after 24 hours using Tdt-mediated dUTP nick end labelling (TUNEL) assay. The TUNEL assay also demonstrated increased intensity of fluorescence and more DNA fragmentation (apoptotic index 84%) after 48 hours treatment [ 26 ].
Xanthorrhizol isolated from C. xanthorrhiza rhizome showed antiproliferative activity on cervical cancer HeLa (HPV 18-positive) cells (EC50 = 6.16 µg/mL) using methylene blue assay. Xanthorrhizol (6 µg/mL) significantly increase apoptosis in HeLa cells as determined from nuclear morphology (using Hoechst 33258 staining) and DNA fragmentation (using TUNEL assay). The presence of P53 and Bax (pro-apoptosis proteins) was identified using Western blot analysis [ 27 ].
Xanthorrhizol isolated from C. xanthorrhiza rhizome inhibited the growth of human colon carcinoma HCT 116 cells with IC50 54.8 µM using MTT assay after 3 days. The cell cycle analysis by flow cytometry showed that xanthorrhizol-treated HCT 116 cells was highly arrested (68.5%) in the sub-G0/G1 phase at dose of 75 µM compared to 50 µM (7.8%) after 48 hours of incubation [ 28 ].
Antitumour activity
Both chloroform and ethanol extracts of C. xanthorrhiza rhizome (40 µg/mL and 160 µg/mL, respectively) inhibited antitumour promoter activity with 100% inhibitory effect by using the short-term assay of inhibition of 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) in Raji cells [ 29 ].
Anti-inflammatory activity
Freeze-dried methanol (75%) extract of C. xanthorrhiza rhizome(5.0 mg) was topically applied on the right ear of female ICR mice (aged five to six weeks) 30 minutes prior to edema induction by TPA. A significant (p < 0.05) edema inhibition was observed in treated mice compared to untreated group [ 30 ].
The freeze-dried methanol (75%) extract (1-5 mg) were topically applied on shaven back of female ICR mice (aged six weeks) 30 minutes prior to edema induction by TPA. A dose-dependent decrease in ornithine decarboxylase level was observed in treated mice [ 30 ].
Antiplatelet activity
Methanol extract of C. xanthorrhiza rhizome (18.2 µg/mL) inhibited the binding of platelet-activating factor to receptor on rabbit platelets by 57% [ 31 ].
1-methoxy-2-methyl-5-(1’,5’-dimethylhex-4’enyl)benzene isolated from the chloroform extract of C. xanthorrhiza rhizome inhibited the binding of platelet-activating factor to receptor on rabbit platelets with IC50 value of 40.9 µM [ 31 ].
Immunostimulating activity
Ethanol (100%) extract of C. xanthorrhiza rhizome (10-50 µg/mL) significantly (p < 0.01) increased the production of nitric oxide (100-160%), hydrogen peroxide (6-14 µM), prostaglandin E2 (PGE2) (303.67-320.98%) and tumor necrosis factor-α (TNF-α) (100-140%), compared to untreated control (40% NO production; <1 µM hydrogen peroxide; 100% PGE2 production; <1% TNF-α) [ 32 ].
The ethanol extract (5-50 µg/mL) also significantly (p < 0.01) increased phagocytic activity (133%-350%) and PGE2 (284%-320%) compared to untreated control (100%) [ 32 ].
Antinociceptive activity
Absolute ethanol extract of C. xanthorrhiza rhizome (200 and 400 mg/kg body weight) was administered subcutaneously in the subplantar of right hind paw of Sprague Dawley male rats 30 minutes before the induction of neurogenic pain using formalin. A significant (p < 0.05) dose dependent reduction in licking time was observed in the early phase (neurogenic pain) (10-60 s) and late phase (inflammatory pain) (30-50 s), compared to untreated control (70 s in early phase and 90 s in late phase) [ 12 ].
Estrogenic activity Methanol (75%) extract of C. xanthorrhiza rhizome (1-10 µM) had estrogenic activity by increasing luciferase activity of ERα-transfected COS-7 cells (266-517%) and luciferase activity of ERβ-transfected COS-7 cells (333-832%), compared to DMSO-control (100%) [ 33 ].
Clinical studies
Information and data not been established.
SAFETY INFORMATION
Preclinical studies (Toxicology studies)
Mutagenicity Methanol (75%) extract of C. xanthorrhiza rhizome (2.5 µg/plate) significantly (p < 0.001) inhibited the 7,12-dimethylbenz[a]anthracene (DMBA)-induced bacterial mutagenesis of Salmonella typhimurium TA98 (64%) and TA100 (62%). The extract (2.5 µg/plate) significantly (p < 0.001) inhibited S. typhimurium TA102 bacterial mutagenesis induced by H2O2 (80%) while the concentration of 50 µg/plate inhibited the mutagenesis induced by t-BOOH (97%) [ 30 ].
Acute toxicity
Oral single dose acute toxicity study on female Sprague Dawley rats (aged between 8 to 12 weeks old) using aqueous mixture of powdered C. xanthorriza rhizome showed no toxic effect on the parameters observed which included behaviours, body weight, food and water intake. All rats were observed for 14 days and no death was found throughout the study period. Approximate lethal dose (LD50) is more than 2,000 mg/kg body weight [ 34 ].
Hepatoprotective
Absolute ethanol extract of C. xanthorrhiza rhizome (500 mg/kg/day) administered orally for 7 days to male Sprague-Dawley rats before induction of hepatotoxicity by ethanol significantly prevented the increase of liver enzymes (p < 0.05) compared to ethanol control group (without extract pre-treatment). Histopathologically, the hepatocytes in pre-treated extract group showed less ballooning compared to the ethanol control group [ 35 ].
Others (Adverse reaction, contraindication, side effect, warning, precaution)
Information and data have not been established.
DOSAGE
Information and data have not been established.
STORAGE
Store below 30°C. Protect from light and moisture.
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