Malaysian Herbal Monograph

Halia Rhizome

Zingiber officinale Roscoe

Zingiberaceae

Figure 1 : Z. officinale Roscoe. (a) Whole plants; (b) flower; (c) fresh young rhizomes; (d) fresh mature rhizomes. (Photos courtesy of GlobinMed, 2012; Hawa ZE Jaafar, UPM, 2012; Thiyagu, MARDI, 2012)

DEFINITION

Halia rhizome consists of dried rhizome of Z. officinale Roscoe.

SYNONYM

Amomum zingiber L., Zingiber blancoi Massk [ 1 , 2 ].

VERNACULAR NAMES

Halia (Malay), sheng jiang (Chinese), ingi, chukku (Tamil), ginger (English) [ 3 , 4 ].

CHARACTER

The dried rhizome is yellowish brown with characteristic aromatic odour and pungent aromatic taste.

IDENTIFICATION

Plant Morphology

A soft, upright perennial herb, up to 1.50 m high. Stem non-woody, covered with leaf sheath, with a subterranean, digitately branched rhizome. Sheathing leaves linear lanceolate, about 5-30 cm long and 8-20 mm wide, dark green, alternate, smooth on the upper surface and slightly rough on the underneath which is covered with very fine hairs; ligule light green in color. Flower stems shorter than leaf stems, bearing a few flowers, each surrounded by a thin bract and situated in axils of large, greenish yellow obtuse bracts, closely arranged at end of flower stem in whorl forming collectively an ovate-oblong spike; each flower shows a superior tubular calyx, split part way down one side; corolla orange yellow, composed of a tube, divided into 3 separated blunt lobes, linear oblong, ca. 2-2.5 cm long, slightly longer than bractea; dorsal lobe broader, 12 mm by 10 mm; 6 staminodes in 2 rows, the outer row of 3 inserted at mouth of corolla; the posterior 2, small, horn-like; the anterior petaloid, purple and spotted and divided into 3 rounded lobes; an inferior, 3-celled ovary with tufted stigma. Fruit a capsule with small arillate seeds [ 1 , 5 , 6 ]. Ginger rhizome occurs in horizontal, laterally flattened, irregularly branching pieces, 3-16 cm long, 3-4 cm wide, up to 2 cm thick, sometimes split longitudinally, pale yellowish buff or light brown externally, longitudinally striated, somewhat fibrous; branches known as “fingers” arise obliquely from the rhizomes, flattish, obovate, short, about 1-3 cm long; fracture, short and starchy with projecting fibres. Internally, yellowish brown, showing a yellow endodermis separating the narrow cortex from the wide stele, and numerous scattered fibrovascular bundles; abundant scattered oleoresin cells with yellow contents and numerous larger greyish points; vascular bundles, scattered on the whole surface [ 1 , 7 , 8 , 9 , 10 ]; aromatic smell, slightly hot in taste [ 11 ].

Microscopy

The rhizome powder has numerous starch granules, almost all are simple, of various sizes from round to oval, oblong to sub-rectangular. The thin-walled septate fibers are found in groups and sometimes found associated with the vessels. The reticulate thickened vessels frequently showing regularly arranged rectangular pits and the spirally thickened vessels are much smaller and very few. The abundant parenchyma cells are composed of very thin-walled cells, rounded to oval with small intercellular spaces [ 3 , 4 ].

Figure 2 : Microscopic characters of Z. officinale rhizome powder. (a) Reticulate vessels (magnification 400X); (b) parenchyma cells containing starch grains (magnification 400X); (c) starch grains (magnification 100X); (d) fiber (magnification 100X).

Colour Tests

Observed colour of solution after treatment with various reagents:

H2SO4 (conc.)Dark brown to black
NaOH (5%)Yellow to light brown
KOH (5%)Yellow to light brown

Thin Layer Chromatography (TLC) 

Figure 3 : TLC profiles of a mixture of 6-shogaol and 6-gingerol standards (S) and methanol extract of  Z. officinale rhizome (L) after spraying with anisaldehyde-sulphuric acid reagent and observed under (a) visible light.

Test Solutions Weigh about 0.5 g of Z. officinale dried rhizome powder in a 50 mL screw-capped conical flask and add 10 mL methanol. Sonicate in a water bath of 60°C for 30 min. Cool the mixture and allow the insoluble matter to settle. Filter the mixture and use the filtrate as the test solution.
Standard solution Separately dissolve 5.0 mg of 6-gingerol and 6-shogaol standards in 10 mL of methanol to give 500 µg/mL solutions. Pipette 1 mL of 6-gingerol and 1 mL of 6-shogaol into a 5-mL volumetric flask and make up to volume with methanol to give 100 µg/mL solution.
Stationary Phase HPTLC silica gel 60 F254, 5 x 10 cm
Mobile phase Toluene-ethyl acetate, 3:1 (v/v)
Application
  1. A mixture of 6-gingerol and 6-shogaol standard solution (S); 10 µL, as a band

  2. Methanol extract of Z. officinale rhizome (L); 10 µL, as a band

Development distance 8 cm
Drying Air drying
Detection
  1. Visible light after spraying with anisaldehyde-sulphuric acid reagent

High Performance Liquid Chromatography (HPLC)

Test solution Extract about 1.0 g of Z. officinale dried rhizome powder with 20 mL of ethanol by reflux method at a temperature of 60°C for 30 min. Filter the mixture through a filter paper. Evaporate the filtrate to dryness using a rotary evaporator. Then, dissolve the dried extract in 10 mL of methanol. Sonicate the mixture for 10 min. Filter the solution through a 0.45 µm syringe filter and inject the filtrate into the HPLC column.
Standard solution Separately dissolve 5.0 mg of 6-gingerol and 6-shogaol standards in 5 mL of methanol to give 1000 µg/mL stock solutions. Sonicate the solutions for 15 min. Mix the standard solutions to produce a 100 µg/mL solution.
Chromatographic system

Detector: UV 225 nm

Column: C18 (5 µm, 4.6 mm I.D x 150 mm)

Column oven temperature: 30°C

Flow rate: 1.0 mL/min

Injection volume: 20 µL

Mobile Phase (Isocratic mode)

Isocratic elution using the mobile phase described below:

  1. A mixture of 55 volumes of acetonitrile and 44 volumes of 0.1% phosphoric acid in water and 1 volume of methanol.
  2. Run time : 25 min
System suitability requirement

Perform at least five replicate injections of the standard mixture (100 µg/mL). The requirements of the system suitability parameters are as follow:

  1. Symmetry factor (As) is not more than 1.5.
  2. Percentage of relative standard deviation (RSD) of the retention time (tr) for 6-gingerol and 6-shogaol standards is not more than 2.0%.
  3. The resolution (Rs) value between 6-gingerol and 6-shogaol should not be less than 1.5.
Acceptance criteria
  1. Retention time (tr) of 6-gingerol and 6-shogaol in the test solution is similar to the tr of the standard solution. 
  2. The resolution (Rs) value between 6-gingerol and 6-shogaol in test solution should not be less than 1.5.
hplc1

Figure 4 : HPLC chromatogram of a standard mixture (100 µg/mL) containing 6-gingerol (tr = 4.895 min) and 6-shogaol (tr = 10.637 min) standards

hplc2

Figure 5 : HPLC chromatogram of ethanol extract of Z. officinale rhizome showing peaks corresponding to 6-gingerol (tr = 4.874 min) and 6-shogaol (tr = 10.601 min)

Table 1 : The Relative Retention Time (RRT) for the four characteristic peaks

StandardRRT
6-gingerol0.46
6-shogaol (as reference)1.00

Note: The RRTs provided only serve as a guidance

PURITY TESTS

Foreign Matter
Not more than 2%
Ash Contents
Total ash Not more than 8%
Acid-insoluble ash Not more than 2%
Loss on Drying
Not more than 10%
Extractive Values
Water-soluble extracts
Hot method Not less than 22%
Cold method Not less than 17%
Ethanol-soluble extracts
Hot method Not less than 9%
Cold method Not less than 6%

SAFETY TEST

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

The aqueous extract of Z. officinale rhizome has been found to contain hexanoic phosphate and gingerlanosterol [ 12 ].

The ethanolic extracts had diarylheptanoids (e.g. (3S,5S)-3,5-diacetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane, 3,5-diacetoxy-1-(3-methoxy-4,5-dihydroxy-phenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane, (3R,5S)-3-acetoxy-5-hydroxy-1, 7-bis(4-hydroxy-3-methoxyphenyl)heptane, (3R,5S)-3,5-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane, (5S)-5-acetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptan-3-one, 5-hydroxy-1-(3,4-dihydroxy-5-methoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptan-3-one, 5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(3,4-dihydroxy-5-methoxyphenyl)heptan-3-one, 1,5-epoxy-3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl) heptane and 1,5-epoxy-3-hydroxy-1-(3,4-hydroxy-5-methoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane), acyclic diarylheptanes (e.g. (3R,5S)-3,5-di-acetoxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane, (3R,5S)-3,5-diacetoxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane, (3S,5S)-3,5-dihydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane, (3R,5S)-3,5-dihydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane), diarylheptanones (e.g. 5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(3,4-dihydroxyphenyl)heptan-3-one, 7-(3,4-dihydroxy-5-methoxyphenyl)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)heptan-3-one, 5-hydroxy-1-(3,4-dihydroxy-5-methoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptan-3-one, hexahydrocurcumin, 1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-dione), cyclic diarylheptanes (e.g. 3-acetoxy-1,5-epoxy-1-(3,4-dihydroxy-5-methoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane, 1,5-epoxy-3-hydroxy-1-(3,4-dihydroxy-5-methoxyphenyl)-7-(3,4-dihydroxyphenyl)heptane), diarylheptenones (e.g. 1,7-bis(4-hydroxy-3-methoxyphenyl)hept-4-en-3-one, gingerenone C), paradols (e.g. [6]-paradol, [8]-paradol, zingerone), gingerdiols (e.g. (3S,5S)-[6]-gingerdiol, (3R,5S)-[6]-gingerdiol, (3R,5S)-3,5-diacetoxy-[6]-gingerdiol), gingerols (e.g. [4]-gingerol, [6]-gingerol, [8]-gingerol, [10]-gingerol, 5-acetoxy-[6]-gingerol, [6]-gingeroldiacetate), gingerdione (e.g. [10]-gingerdione), dehydrogingerdiones (e.g. 1-dehydro-[6]-gingerdione, 1-dehydro-[8]-gingerdione), shogaols (e.g. [6]-shogaol, [10]-shogaol, [6]-dehydroshogaol, 6-hydroxy-[6]-shogaol), steroids (e.g. ß-sitosterol, stigmasterol, 6ß-hydroxystigmast-4-en-3-one) and others (e.g. 1-(3-methoxy-4-hydroxy-phenyl)-propan-1,2-diol, 1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-diol, 6-(hydroxymethyl)tetrahydro-2H-pyran-3,4-5-triol, 5-[4-hydroxy-6-(4-hydroxyphenethyl)tetrahydro-2H-pyran-2-yl]-3-methoxybenzene-1,2-diol, 1-(3,4-dimethoxyphenyl)-5-hydroxy-decan-3-one, 4a,5ß-dihydroxybisabola-2,10-diene, galanolactone, citrylidenmalonsaeure, shogasulfonic acid A, 6-gingesulfonic acid, (E)-geranylferulic acid, (Z)-geranylferulic acid, (2R,3R,4S,5S,6R)-2((1S,2S,4S)-4-hydroxy-2-methylcyclohexyloxy)-sodium 6-gingesulfonate, sodium (E)-7-hydroxy-1,7-bis(4-hydroxyphenyl)hept-5-ene-3S-sulfonate, sodium (E)-7-hydroxy-1,7-bis(4-hydroxyphenyl)hept-5-ene-3R-sulfonate, hydroxyl-cineole-10-O-ß-D-glucosidase, trans-ß-sesquiphellandrol, trans-sesquipiperitol) [ 13 , 14 , 15 , 16 , 17 ].

The methanol extract has been reported to have gingerols (e.g. [6]-gingerol, [8]-gingerol, [10]-gingerol), gingerdiones (e.g. dehydro-[6]-gingerdione, dehydro-[10]-gingerdione), shogaols (e.g. [6]-shogaol, [8]-shogaol, [10]-shogaol), zingerines (e.g. [6]-zingerine, [8]-zingerine, [10]-zingerine), [6]-gingediol and [6]-paradol [ 18 , 19 , 20 ]. Whereas the methanolic aqueous extract had [6]-gingerol, [8]-gingerol, [10]-gingerol, [6]-shogaol, [6]-paradol, [6]-gingeacetate, [4]-gingesulfonic acid, [6]-gingesulfonic acid and shogasulfonic acids A-D [ 21 ].

The chloroform extract had [6]-gingerol, [10]-gingerol, [6]-shogaol, [10]-shogaol and hexahydrocurcumin [ 22 ].

The dichloromethane extract had diarylheptanoids (e.g. (Z)-1,7-bis-(4’-hydroxy-3’-methoxyphenyl)-4-hepten-3-one, (E)-1,7-bis-(4’-hydroxy-3’-methoxyphenyl)-4-hepten-3-one, 1,7-bis-(4’-hydroxy-3’-methoxyphenyl)-5-methoxyheptan-3-one, 1-(4’-hydroxy-3’,5’-dimethoxyphenyl)-7-(4’-hydroxy-3’-methoxyphenyl)-4-hepten-3-one, 1,7-bis-(4’-hydroxy-3’-methoxyphenyl)-3-hydroxy-5-acetoxyheptane, 1,7-bis-(4’-hydroxy-3’-methoxyphenyl)-3,5-heptadione, meso and (3S,5S)-3,5-diacetoxy-1,7-bis-(4’-hydroxy-3’-methoxyphenyl)heptane, 3-acetoxy-1,5-epoxy-1-(3,4-dihydroxy-5-methoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane, epimer of 3-acetoxy-1,5-epoxy-1-(3,4-dihydroxy-5-methoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane at C-3, 1,5-epoxy-3-hydroxy-1-(3,4-dihydroxy-5-methoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane, epimer of 1,5-epoxy-3-hydroxy-1-(3,4-dihydroxy-5-methoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane at C-3, 1,5-epoxy-3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane), paradols (e.g. [1]-paradol, [6]-paradol, [7]-paradol, [8]-paradol, [9]-paradol, [10]-paradol, [11]-paradol, [13]-paradol, methyl [6]-paradol, methyl [8]-paradol, dihydro-[6]-paradol, acetoxydihydro-[6]-paradol, methyl ether derivative of acetoxydihydro-[6]-paradol, 1-hydroxy-[6]-paradol), gingerols (e.g. [4]-gingerol, [5]-gingerol, [6]-gingerol, [7]-gingerol, [8]-gingerol, [10]-gingerol, methyl [4]-gingerol, methyl [6]-gingerol, [4]-isogingerol, methyl [6]-isogingerol, acetoxy-[4]-gingerol, acetoxy-[6]-gingerol, acetoxy-[8]-gingerol, acetoxy-[10]-gingerol, methyl acetoxy-[6]-gingerol, methoxy-[4]-gingerol, methoxy-[6]-gingerol, methoxy-[8]-gingerol, methoxy-[10]-gingerol, demethoxy-[6]-gingerol, 5-acetoxy-3-deoxy-[6]-gingerol, 1-dehydro-[6]-gingerol, 6-dehydro-[6]-gingerol), shogaols (e.g. (E)-[4]-shogaol, (E)-[5]-shogaol, (Z)-[6]-shogaol, (E)-[6]-shogaol, (Z)-[8]-shogaol, (E)-[8]-shogaol, (Z)-[10]-shogaol, (E)-[10]-shogaol, (E)-[12]-shogaol, methyl (E)-[4]-shogaol, methyl (E)-[6]-shogaol, methyl (E)-[8]-shogaol, [6]-isoshogaol, demethoxy-[6]-shogaol, 3-acetoxy-3-dihydrodemethoxy-[6]-shogaol, 6-hydroxy-[6]-shogaol, 6-hydroxy-[8]-shogaol, 6-hydroxy-[10]-shogaol, 3-dihydro-[6]-demethoxyshogaol), gingerdiones (e.g. [6]-gingerdione, [8]-gingerdione, [10]-gingerdione, [12]-gingerdione, 1-dehydro-[3]-gingerdione, 1-dehydro-[6]-gingerdione, 1-dehydro-[8]-gingerdione, 1-dehydro-[10]-gingerdione, 1-dehydro-3-dihydro-[10]-gingerdione), gingerdioles (e.g. [4]-gingerdiol, [6]-gingerdiol, [8]-gingerdiol, [10]-gingerdiol, 5-acetoxy-[4]-gingerdiol, 3-acetoxy-[4]-gingerdiol, 5-acetoxy-[6]-gingerdiol, stereoisomer of 5-acetoxy-[6]-gingerdiol, 5-acetoxy-[7]-gingerdiol, methyl 5-acetoxy-[4]-gingerdiol, methyl 5-acetoxy-[6]-gingerdiol, diacetoxy-[4]-gingerdiol, diacetoxy-[6]-gingerdiol, diacetoxy-[8]-gingerdiol, methyl diacetoxy-[4]-gingerdiol, methyl diacetoxy-[6]-gingerdiol, methyl diacetoxy-[8]-gingerdiol, methyl diacetoxy-[10]-gingerdiol, (2E)-geranial acetal of [4]-gingerdiol, (2Z)-neral acetal of [6]-gingerdiol, (2E)-geranial acetal of [6]-gingerdiol, acetaldehyde acetal of [6]-gingerdiol, cyclic methyl orthoester [6]-gingerdiol, cyclic methyl orthoester [10]-gingerdiol) and others (e.g. 6-(4’-hydroxy-3’-methoxyphenyl)-2-nonyl-2-hydroxytetrahydropyran, 1-(4’-hydroxy-3’-methoxyphenyl)-2-nonadecen-1-one, 1-(3’,4’-dimethoxyphenyl)-2-nonadecen-1-one, 1-(4’-hydroxy-3’-methoxyphenyl)-7-decen-3-one, 1-(4-hydroxy-3-methoxyphenyl)-2,4-dehydro-6-decanone, 1-(4’-hydroxy-3’-methoxyphenyl)-7-octen-3-one, 1-(4’-Hydroxy-3’-methoxyphenyl)-7-dodecen-3-one, 3-(4’-hydroxyphenyl)-1-propanal, 3-(4’-hydroxy-3’-methoxyphenyl)-1-propanal, 3-(3’,4’-dihydroxy-5’-methoxyphenyl)-1-propanal, 3-(4’-hydroxy-3’,5’-dimethoxyphenyl)-1-propanal, 3-(3’-hydroxy-4’,5’-dimethoxyphenyl)-1-propanal, 2-dehydro-3-(3’,4’-dimethoxyphenyl)-1-propanal, 2-dehydro-3-(3’,4’,5’-trimethoxyphenyl)-1-propanal, 4-(4’-hydroxyphenyl)-2-butanone, 4-(3’,4’-dihydroxy-5’-methoxyphenyl)-2-butanone, 4-(4’-hydroxy-3’,5’-dimethoxyphenyl)-2-butanone, 4-(3’-hydroxy-4’,5’-dimethoxyphenyl)-2-butanone, 4-(3’,4’,5’-trimethoxyphenyl)-2-butanone, 5-(4’-hydroxy-3’-methoxyphenyl)-pent-2-en-1-al, 5-(4’-hydroxy-3’-methoxyphenyl)-3-hydroxy-1-pentanal, 1,7-bis-(4’-hydroxy-3’-methoxyphenyl)-4-heptene-3-one, 1,7-bis-(4’-hydroxy-3’-methoxyphenyl)-3,5-heptadione, p-hydroxybenzaldehyde, vanillin, 4-vinylguaiacol, 4-vinylpyrogallol monomethyl ether, 4-vinylsyringol, acetovanillone, methyl vanillate, 2-(4’hydroxy-3’-methoxyphenyl)ethyl acetate, ferulic acid, zingerol, zingerone, zingerone methyl ether) [ 23 , 24 , 25 ].

The petroleum ether extract had [4]-gingerol, [6]-dehydrogingerdione and [6]-dihydrogingerdione [ 26 ].

Essential oils of the rhizome composed of allo aroma dendrene, a-bergamotene, ß-besabolene, endo borneol, endo bornyl acetate, ß-bourbonene, ?-cadinene, calamenene, calarene, camphene, camphor, trans-2-caren-4-ol, 1,8-ceneole, z-citral (neral), citral (geranial), citronella, ß-citronellol, citronellyl acetate, a-copaene, ß-cubebene, cuparene, a-curcumene, cyclosativen, 1-decanol, ß-elemene, ?-elemene, elemol, (-)-epiglobulol, ß-eudesmol, ß-farnasene, farnesene, (-)-farnesol, trans-geraniol, geranyl acetate, germacrene B, a-guaen, 2-heptanol, juniper camphor, ledol, linalool, 6-methyl-5-hepten-2-one, a-muurolene, ß-myrcene, myrtenal, nerolidol, nerol, 2-nonanone, cis-ocimene, a-phellandrene, ß-phellandrene, a-pinene, 2-ß-pinene, a-selinene, ß-selinene, epibicyclo sesquiphellandrene, ß-sesquiphellandrene, cis-ß-sesquiphellandrol, trans-ß-sesquiphellandrol, terpinene-4-ol, a-terpineol, a-terpinolene, torreyol, 2-undecanone, verbenone, viridiflorol and zingiberene [ 27 , 28 , 29 ].

The rhizome has also been reported to contain diarylheptanoids (e.g. 5-hydroxy-7-(4-hydroxyphenyl)-1-(4-hydroxy-3-methoxyphenyl)-3-heptanone, 3,5-diacetoxy-7-(3,4-dihydroxyphenyl)-1-(4-hydroxy-3-methoxyphenyl)heptane, 5-hydroxy-7-(4-hydroxy-3,5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-3-heptanone, 5-hydroxy-7-(4-hydroxy-3,5-dimethoxyphenyl)-1-(4-hydroxy-3-methoxyphenyl)-3-heptanone, (3R,5S)-3,5-dihydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane, (3S,5S)-3,5-diacetoxy-1,7-bis(3,4-dihydroxyphenyl)heptane, (4E,6E)-7-(3,4-dihydroxy-5-methoxyphenyl)-1-(4-hydroxy-3-methoxyphenyl)hepta-4,6-dien-3-one, 5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptan-3-one, 7-(3,4-dihydroxyphenyl)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)heptan-3-one, (E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hept-1-ene-3,5-dione, (E)-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)-hept-1-ene-3,5-dione, 1,5-epoxy-3-hydroxy-1-(3,4-dihydroxy-5-methoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane, (3S,5S)-3,5-diacetoxy-1,7-bis(3,4-dihydroxyphenyl)heptane, curcumin, tetrahydrocurcumin, hexahydrocurcumin), diarylheptenones (e.g. gingerenone A-C, isogingerenone B), gingerdiols (e.g. [6]-gingerdiol, (3R,5S)-5-acetoxy-3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)decane, (3R,5S)-3-acetoxy-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)decane, (3R,5S)-3,5-diacetoxy-1-(4-hydroxy-3-methoxyphenyl)decane and (3R,5S)-3,5-diacetoxy-1-(3,4-dimethoxyphenyl)decane) and [10]-dehydrogingerdione [ 30 , 31 , 32 , 33 , 34 ].

On the other hand, the crude rhizome had ginger proteases (GP-I and GP-II), 1,5-epoxy-3-hydroxy-1-(3-methoxy-4,5-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptane, 10-O-ß-D-glucopyranosyl-hydroxy cineole, 1-(4-O-ß-D-glucopyranosyl-3-methoxyphenyl)-3,5-dihydroxydecane, 5-O-ß-D-glucopyranosyl-3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)decane, [6]-gingerol, [8]-gingerol, [10]-gingerol, [6]-shogaol, [8]-shogaol, [10]-shogaol, [6]-dehydroshogaol, [8]-dehydroshogaol, [10]-dehydroshogaol and [1]-dehydrogingerdione [ 35 , 36 , 37 , 38 , 39 , 40 ].

MEDICINAL USES

Uses described in folk medicine, not supported by experimental or clinical data

Traditionally taken orally to stimulate carminative effect and relief indigestion. It also consumed as a decoction for stomach ache and women after childbirth. It may be applied on the skin for rubefacient and counterirritant purpose [ 41 ].

Biological and pharmacological activities supported by experimental data

Antidiarrheal activity

Methanol extract of Z. officinale rhizome (up to 100 µg/mL) inhibited Escherichia coli heat-labile enterotoxin (LT)-induced diarrhea by blocking the binding of LTB to cell-surface receptor ganglioside GM1 with an IC50 value of 2.0 µg/mL using GM1-enzyme-linked immunosorbent assay [ 42 ].

Antihyperlipidimic acitivity

Ethanol extract of Z. officinale rhizome (200 mg/kg/day) administered orally to adult male albino rabbits for a duration of 10 weeks significantly (P<0.01) decreased serum triglycerides, serum phospholipids, low-density lipoprotein cholesterol, serum and tissue cholesterol levels and significantly increased high-density lipoprotein cholesterol [ 43 ].

Ethanol extract of Z. officinale rhizome (200 mg/kg/day) administered orally to streptozotocin-induced diabetic male and female Wistar rats for a duration of 20 days significantly (p<0.01) decreased serum total cholesterol, triglycerides, liver and pancreas thiobarbituric acid reactive substances values and significantly (p<0.01) increased the level of high-density lipoprotein [ 44 ].

Aqueous extract of Z. officinale rhizome (500 mg/kg/day) administered orally and intraperitoneally to adult female Sprague Dawley rats for a duration of 4 weeks significantly (p<0.05) decreased cholesterol level with no changes in triglycerides level [ 45 ].

Antioxidant activity

Extract of Z. officinale (100 mg/kg/day) administered orally to lead acetate-induced apoptosis male Wistar rats for a duration of 10 weeks significantly (p<0.05) increased plasma superoxides dismutase activity, plasma catalase activity and decreased the plasma malondialdehyde [ 46 ]. Antithrombotic activity Aqueous extract of Z. officinale rhizome (500 mg/kg/day) administered orally to adult female Sprague Dawley rats for a duration of 4 weeks significantly (p<0.05) decreased (50%) the synthesis of thromboxane B [ 45 ].

Aqueous extract of Z. officinale rhizome (500 mg/kg/day) administered intraperitoneally to adult female Sprague Dawley rats for a duration of 4 weeks showed no reduction of thromboxane B synthesis [ 45 ]. Pro-fertility activity Aqueous extract of Z. officinale rhizome (24 mg/mL) administered orally three times weekly to metiram induced-testicular damage of sexually mature male albino mice for a duration of 6 weeks significantly (p<0.05) increased the diameter of seminiferous tubules and epithelial height of testis, increased spermatogenic cells and decreased the percentage of Bax positive germ cells [ 47 ].

Aqueous extract of Z. officinale rhizome (500 and 1000 mg/kg/day) administered orally to adult male rats for a duration of 14 and 28 days significantly (p<0.05) increased weight of testis and epididymis, sperm count and motility, testosterone level and significantly (p<0.05) decreased malonhydialdehyde level [ 48 ].

Antidiabetic activity

Aqueous extract of Z. officinale root (500 mg/kg/day) administered orally to alloxan-induced diabetic albino rats for a duration of 6 weeks significantly (p<0.05) decreased serum glucose level [ 49 ].

The juice of Z. officinale rhizome (4mL/kg/day) administered orally to streptozotocin-induced diabetic male Sprague Dawley rats for a duration of 6 weeks significantly (p<0.05) decreased fasting blood glucose level and significantly (p<0.05) increased insulin level [ 50 ].

Antifungal activity

Ethanol extract of Z. officinale rhizome (10 mg/mL) inhibited the growth of Candida albicans with MIC values of 2 mg/mL by using antifungal disk assay [ 51 ].

Clinical studies

A clinical trial to study the antiemetic property of Z. officinale as compared to metoclopramide and placebo for day case surgery was carried out. It is a prospective, randomised double-blind controlled trial which involved 120 gynaecological patients of American Society of Anesthesiologists graded 1-3; aged over 16 years old, scheduled for elective laparoscopic surgery on a day stay basis. The patients were divided into 3 groups, they were given two capsules containing 10 mg metoclopramide, 1 g powdered Z. officinale rhizome, and 1 g lactose for three respective patient groups, at 1 hour before anaesthesia induction. The observations were made at discharge from the recovery ward, at hospital discharge and 24 hours postoperatively. Results showed a decreased in postoperative nausea or vomiting incidence. The requirement of postoperative antiemetic agents were also decreased as compared to the placebo treated patients [ 53 ].

A clinical trial to compare ginger and vitamin B6 for the treatment of nausea and vomiting in pregnancy was conducted. It is a randomised double-blind controlled trial which involved 70 pregnant women with nausea at or before 17 weeks gestation. The patients took 2 capsules containing powdered of Z. officinale root (1 g/day) or vitamin B6 (40 mg/day) after breakfast and dinner for 4 days. Z. officinale was found to be significantly more effective in alleviating the severity of nausea as compared to vitamin B6 group. Z. officinale also was equally effective with vitamin B6 group in reducing the number of vomiting episode during early pregnancy period [ 54 ].

SAFETY INFORMATION

Preclinical studies (Toxicology studies)

Acute toxicity

A patented standardized ethanol extract of Z. officinale rhizome EV.EXT™ 33 (up to 100 mg/kg) administered orally to male Wistar rats for duration of 3 hours showed no changes in systolic blood glucose or heart rate [ 52 ].

Oral single dose acute toxicity study on female Sprague Dawley rats (aged between 8 and 12 weeks old) using aqueous mixture of Z. officinale rhizome powder on the parameters observed which includes behaviors, body weight, food and water intakes. All rats were observed for 14 days prior to necropsy. No death was found throughout the study period. Necropsy revealed no significant abnormality. No-observed-adverse-effect level (NOAEL) is more than 2,000 mg/kg body weight [ 55 ].

Z. officinale root (2500 mg/ kg) in saline administered orally as a single dose to adult male albino rats for a duration of 24 hours significantly (P<0.0001) decreased blood pressures and heart rate and induced prenecrotic changes in cardiac tissues with LD50 value of > 2500 mg/kg [ 56 ]. Methanol and aqueous extract of Z. officinale root (up to 17.5 g/kg bw) administered orally as a single dose to male Swiss mice (8-10 weeks old) for a duration of 48 hours showed no toxic effect with LD50 value of 10.25 and 11.75 g/kg bw respectively [ 57 ].

Sub-acute toxicity

Dried Z. officinale roots (500 mg/kg/day) in saline administered orally to adult male albino rats for a duration of 28 days showed hypotension and bradycardia effect with degenerative changes in cardiac myocyte fibers [ 56 ]. Fine powder of Z. officinale roots (up to 2000 mg/kg/day) in gum arabic administered orally to male and female Sprague Dawley rats for a duration of 35 days showed no toxic effect in behavior, growth, and food and water consumption [ 58 ].

Teratogenicity 

Z. officinale rhizome tea (up to 50 g/L/day) administered orally to pregnant Sprague Dawley rats (8-12 weeks old) for a duration of 5 days from gestation day 6 to gestation day 15 showed no teratogenic effect with advanced skeletal development of fetuses and increased growth of surviving fetuses [ 59 ].

Others (Adverse reaction, contraindication, side effect, warning, precaution)

Precaution

Z. officinale rhizome is not recommended for children less than 6 years of age [ 3 ]. Contact dermatitis on the fingers has been found in sensitive patients [ 60 ].

DOSAGE

For motion sickness: 0.5 g, 2–4 times daily in adults and children more than 6 years [ 61 ].

For dyspepsia: 2–4 g daily, as powdered plant material or extracts [ 61 ].

STORAGE

Store below 30°C. Protect from light and moisture.

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