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Zingiber officinale
CONTENTS
1. Brief literature review on Zingiber officinale. (Pg.1-4) a. Classification b. Vernacular names c. Part used d. Botanical description e. Geographical distribution f. Traditional use g. Anatomy of the Rhizome h. Pharmacology and Clinical studies i. Toxicity and Adverse reactions j. Phytochemistry k. Active Principles 2. Analytical specifications of Crude Drug (Pg.5-9) a. Macroscopic characterization b. Identification of Crude drug by TLC c. TLC profile of Ginger oil d. GC profile of Ginger oil 3. Analytical specifications for Zingiber officinale extract. (Pg.10-14) a. Identification tests b. TLC profile c. Estimation of Gingerol in Zingiber officinale extract by HPLC 4. Analytical specifications for 6-Gingerol (Pg. 15-20) a. UV Spectrum b. TLC and HPTLC c. FTIR and NMR Spectrum d. HPLC Chromatogram 5. Analytical specifications for 8-Gingerol (Pg. 21-24) a. TLC and HPTLC b. FTIR and NMR Spectrum c. HPLC Chromatogram 6. Analytical specifications for 6-Shogaol (Pg. 25-28) a. TLC and HPTLC b. FTIR and NMR Spectrum c. HPLC Chromatogram 7. References (Pg. 29-31)
Zingiber officinale
3 -07411 . 3, 0Roscoe
(a) Classification:
Kingdom Division Class Order Family Genus Species : Plantae : Angiosperma : Monocotyledoneae : Scitaminaea : Zingiberaceae : Zingiber : officinale
Zingiber officinale
brown contents occurring either singly in the ground tissue or in axial rows accompanying the vascular bundles. Vessels with spiral or reticulate thickening in the scattered vascular bundles are found. Irregularly shaped thin-walled fibers with delicate, transverse septa, yielding only slightly the reaction characteristic of lignin. Sclereids and calcium oxalate crystals absent1-2.
Fig. 1
Fig. 2
Fig. 3
Fig.1 : Transversely cut surface of the rhizome, vascular bundles represented by circles, secretion cells by dots(x3). Fig.2 : Transverse section in the region of the endodermis (x100) Fig.3 : Transverse section of the central part (x100) ct- cortex, end-endodermis, fr.b.vascular bundles, pg-pigment cell, S-stele, scl.f-sclerenchymatous fibres, secr.- secretion cell.
(h) Pharmacology and Clinical Studies Anti-emetic Activity: Early animal studies had demonstrated the anti-emetic property of fresh ginger1, but it was the clinical work of Mowrey and Clayson which generated a wider interest in this use of ginger2. They compared the effects of 1.88g of dried powdered ginger, 100mg dimenhydrinate (Dramamine) and placebo on the symptoms of motion sickness in 36 healthy subjects who reported very high susceptibility to motion sickness. Motion sickness was induced by placing the blind folded subject in a tilted rotating chair. Ginger was found to be superior to dimenhydrinate and placebo in preventing the gastrointestinal symptoms of motion sickness and the authors postulated a local effort in the gastrointestinal tract for ginger. This was particularly likely since it was given as a powder only 25 minutes before the test. The gingerols and shogaols were subsequently identified as the main anti-emetic compounds in ginger3. Improvement of digestive function: Early Chinese and Japanese research found that oral and
intragastric application of fresh ginger decoction produced a stimulant action on gastric secretion1.
German scientists found that chewing 9g of crystallised ginger had a profound effect on saliva production4. Amylase activity was also increased and the saliva was not more watery, although it contained slightly less mucroprotein. Intraduodenal doses of ginger extract increased bile secretion in rats5. Total secretion of bile solids was also increased, but not to the same extent as bile flow. 6-
Zingiber officinale
gingerol and 10-gingerol were identified as the active components5. Fresh ginger also contains a proteolytic enzyme6. Ginger, in conjunction with other pungent Ayurvedic herbs, increased the bioavailability of a number of drugs by promoting their absorption and/or protecting them from being metabolized in their first passage through the liver1. Oral doses of 6-shogaol accelerated intestinal transit in rats7. Also an extract of ginger, and isolated 6-shogaol and gingerols, enhanced gastrointestinal motility in mice after oral doses8. Anti-ulcer Activity: Ginger and 6-gingerol inhibited experimental gastric ulcers in rats9-10. Fresh ginger decocted in water resulted in symptomatic improvement in 10 patients with peptic ulcers1. Antiplatelet Activity: Srivastava and co-workers found that aqueous extract of ginger inhibited platelet aggregation induced by ADP, epinephrine, collagen and arachidonic acid in vitro 11. Ginger acted by inhibiting thromboxane synthesis12-13. It also inhibited prostacyclin synthesis in rat aorta11. The antiplatelet action of 6-gingerol was also mainly due to the inhibition of thromboxane formation14. Anti-inflammatory Activity: Ginger extract inhibited carrageenan-induced paw swelling and was as active as aspirin15. Essential oil of ginger inhibited chronic adjuvant arthritis in rats16. Ginger and its pungent components are dual inhibitors of arachiodonic acid metabolism. That is, they inhibit both cyclooxygenase (prostaglandin synthetase) and lipoxygenase enzymes of the prostaglandin and leukotriene biosynthetic pathways15,17-22. Antipyretic Activity: Ginger extract given orally reduced fever in rats by 38%, while the same dose of aspirin was effective by 44%15. The antipyretic activity of 6-shogaol and 6-gingerol has also been observed7. Cardiovascular Effects: Ginger exerted a powerful positive inotropic effect on isolated guinea pigs left atria23. Gingerols were identified as the active components23-24. Antioxidant Activity: Extracts of ginger have pronounced antioxidant activity comparable to that of synthetic antioxidant preservatives25. Other Effects: Ginger extract exhibited a prolonged hypoglycaemic activity in rabbits15. Antihepatotoxic activities of gingerols and shogaols were observed using carbon tetrachloride and galactosamine induced cytotoxicity in cultured rat hepatocytes26. Injection of 6-shogaol showed an intense antitussive action in comparison with dihydrocodeine phosphate7. Pharmacokinetics: After injection, 90% of 6-gingerol was bound to serum protein and elimination was mainly via the liver27. Oral or intraperitoneal dosage of zingerone resulted in the urinary excretion of metabolites within 24 hours, mainly as glucuronide and/or sulphate conjugates 28. Appreciable biliary excretion (40% in 12 hours) also occurred28. (i) Toxicity and Adverse Reactions: The mutagenic activity of ginger extracts has been observed in several strains22,29. As a result of component fractionation of ginger juice, it was found that 6gingerol was a potent mutagen30. When mutagenicity of gingerol or shogaol was tested in the presence of zingerone, it was observed that zingerone suppressed the mutagenic activity of both compounds22,31. 3 %&# # $ #$# %#
Zingiber officinale
Ginger extract caused no mortality at doses of up to 2.5g/kg in mice (equivalent to about 75g/kg of fresh rhizome)15. This low acute toxicity was confirmed in a separate study, which also found that ginger extract at 100mg/kg per day for three months caused no signs of chronic toxicity32. Topical application of ginger may cause contact dermatitis in sensitive patients33. (j) Phytochemistry: Ginger has been reported to contain usually 1-3% of volatile oil, pungent principles viz., gingerols and shogaols and about 6-8 lipids and others. Ginger oil contains Zingiberene and bisaboline as major constituents along with other sesqui and monoterpenes. Ginger oleoresin contains mainly the pungent principles gingerols and shogaols as well as zingiberone. Shogaols have recently been found to be twice as pungent as gingerols1-4. (k) Active principles: Gingerols, Shogaols
O H CH3O HO
[6] Gingerol [8] Gingerol [10] Gingerol n 4 6 8
OH ( )n
O CH3O HO ( )n
n 4 6 8
Fig.4
Fig.5
% 0
070 3
-:9
,8 349 -0 -00 03
;07 1 0/ -
Zingiber officinale
ANALYTICAL SPECIFICATION OF THE CRUDE DRUG Organoleptic Characters: Colour & Appearance : Yellowish Brown or light brown. Scraped rhizome with buff external surface showing longitudinal striations and occasional loose fibers, outer surface dark brown and more or less covered with cork which shows conspicuous, narrow, longitudinal and transverse ridges. Aromatic Pungent
Odour Taste
: :
Fig.6 TESTS
Tests for extraneous material
LIMITS
PROTOCOLS
Quality Control Methods for Medicinal Plant Materials -WHO -do-do-do-do-
Foreign matter Sand & Silica Insect infestation Rodent contamination Physico-chemical analysis Ash content Acid insoluble ash Moisture content Volatile oil content Successive extractive value Petroleum ether extractive value Chloroform extractive value Methanol extractive value Alcohol soluble extractive value Water soluble extractive value Phytochemical analysis
-do-do-do-do-
1.5 2.5 % w/w 3.0 - 5.0 % w/w 2.0 4.0 % w/w > 7.0%w/w > 14.0%w/w
-do-
-do-do-
6-Gingerol
By HPLC
Zingiber officinale
Sample preparation
: : : :
S Fig. 8
Zingiber officinale
: : :
Zingiber officinale crude drug Precoated silicagel (Al - Sheet) n-Hexane : Ether 40 : 60
Sample preparation
The mark from petroleum ether fraction of Zingiber officinale rhizome powder extract was successively extracted with chloroform and then by methanol. The individual extracts were concentrated and separately applied on different TLC plates. 9 cms CAMAG Linomat IV
: :
: : Methanol fraction
Fig.9
Fig.10
Zingiber officinale
1 gm of Zingiber officinale oil was dissolved in chloroform and 10l applied on the TLC plate. 9 cms
Anisaldihyde Sulphuric acid reagent (Fig.11) Vanillin sulphuric acid reagent (Fig.12)
: :
Fig. 12
Zingiber officinale
LIMITS
Light yellow to greenish yellow liquid Sharp lemony top note with persistent dry spicy note 0.866 0.880
Chromatographic conditions
1. Column 2. Temperature Capillary injector port FID Detector Column oven Program > column oven Hold time Total time 3. Control mode Split ratio 4. Column pressure 5. Column flow 6. Detector 7. Carrier gas : DB wax 0.25 mm (diameter) 30 mtr (length) : : : : : : : : : : : : 2600C 2750C 400 C initial for 2 min. 40C /min up to 2250C 5 min 53 min. Split 1 : 50 134 kPa 2.2 ml / min. F.I.D. Nitrogen
Fig.13
Zingiber officinale
LIMITS
< 4% w/w 3.5 % w/w < 1% w/w
PROTOCOL
As per I.P / B.P As per I.P / B.P As per I.P / B.P
As per I.P / B.P As per I.P / B.P As per B.P. As per I.P / B.P As per I.P / B.P As per I.P / B.P By GC
< 102 cfu g-1 Absent Absent Absent < 200 ppm
Gingerols
20.0%w/w
10
Zingiber officinale
TLC PROFILE
Sample detail Adsorbant Solvent system : : : Zingiber officinale extract Precoated silicagel (Al - Sheet) n Hexane : Ether 40 : 60 1 gm of Zingiber officinale extract was dissolved in 25 ml of methanol. 10l of this solution was applied on the TLC plate. 9 cms Vanillin sulphuric acid reagent. (Fig.14) Densitometer 254 nm (Fig. 15) CAMAG Linomat IV
Sample preparation
: : : :
T Fig. 15
Rf. 0.9 Zingiberene (dark purple spot) Fig.14 Rf. 0.3 Gingerols (violet spot) Fig.14
11
Zingiber officinale
ESTIMATION OF GINGEROL IN ZINGIBER OFFICINALE EXTRACT BY HPLC Summary: Gingerol is separated from its related compounds like Shagaol, by reverse phase chromatography. The separated compounds are identified with the retention times in comparison with the pure compound and quantified with the corresponding peak area. The results were found to be accurate and reproducible. Analysis Chromatographic system: High Performance Liquid Chromatographic system equipped with LC8A pump, SPD-M 10Avp Photo Array Detector in combination with Class LC 10A software. Mobile phase: Acetonitrile 55 : : Water 45
Column
: C18 - ODS (Octadecylsilane) (Lichrocart 250-4, Lichrospher RP-18e-5 (Merck) Art.No: 1.50216 : SPD-M 10Avp Photo diode array detector : 1.3 ml/min : 280 nm : 10 L
Standard preparation: Weigh accurately 100mg of working standard (contains 40% w/w of Gingerol) to a 25ml volumetric flask. Dissolve and make upto 25ml with HPLC grade methanol.
Sample preparation: Weigh accurately a sample quantity equivalent to 40 mg of gingerol to a 25 ml volumetric flask. Dissolve and make upto 25ml with HPLC grade methanol. Procedure: Set the instrument as per the chromatographic condition prescribed above. By means of suitable syringe inject 10 l of standard solution. Record the chromatogram repeat the injections for another 4 times and calculate the RSD of the area. It should not be more than 2%. Inject 10L of sample preparation and record the chromatogram. Calculate the % of gingerol from the peak areas.
12
Zingiber officinale
HPLC PROFILE
WORKING STANDARD
Fig.16 Chromatogram
Fig.18
3-D View
13
Zingiber officinale
HPLC PROFILE
SAMPLE (Zingiber officinale extract 20% Gingerols)
Fig.19 Chromatogram
Fig.21
3-D View
PKNO R.TIME 1 4.75 k' 4.7 NAME 6-Gingerol Plate # Tailing 7357 1.02
10.275
3.47
11281 0.91
14
Zingiber officinale
Sparingly soluble in petroleum ether, soluble in alcohol, chloroform, ether and almost insoluble in water.
Exhibits maxima at 282nm Gives a single spot Characteristic of 6-Gingerol Characteristic of 6-Gingerol UV spectra of the principal peak matches with the 6-Gingerol Characteristic of 6-Gingerol < 0.5%w/w
Purity References:
> 97%w/w
1. Merck Index. 12th edn., 1996 2. D.W. Connell et al., Aust. J. Chem., 1969; 22 : 1033-1043
15
Zingiber officinale
UV SPECTRUM
Fig. 22 UV absorption of 0.01788 % w/v solution in alcohol reported at : 282nm 2560 calculated at : 282nm 2620
Created Data
: :
No. 1 2
16
Zingiber officinale
TLC PROFILE
Sample detail Adsorbant Solvent system : : : 6-Gingerol Precoated silicagel (Al - Sheet) n Hexane : Ether 40 : 60 10 mg of 6-Gingerol was dissolved in 1 ml of methanol. 10l of this solution was applied on the TLC plate. 9 cms Vanillin sulphuric acid reagent. (Fig.22) Densitometer 280 nm (Fig. 23) CAMAG Linomat IV
Sample preparation
: : : :
Fig. 23
Fig. 24
17
Zingiber officinale
FTIR SPECTRUM
NMR SPECTRUM
Fig. 26- NMR SPECTRUM IN CDCl3 NMR SPECTRUM MATCHES WITH THE DETAILS PROVIDED IN D.W. CONNELL, AUST. J. CHEM., 1969; 22 : 1041 6.35 to 6.75 (3H, multiplet), 3.7(3H, s), 2.6(4H, s), 2.4(2H, d, j6 c/s), 1.25 (8-9H, 0.87 p.p.m(3H).
18
Zingiber officinale
CHROMATOGRAM
PDA SPECTRUM
Fig. 27
Fig. 28
CHROMATOGRAM IN 3D VIEW
Fig. 29
PEAK TABLE
19
Zingiber officinale
CHROMATOGRAM
Fig. 30
Fig. 31
PEAK TABLE
MASS SPECTRUM
Fig. 32
20
Zingiber officinale
TESTS
Description Solubility Yellow oily liquid
RESULTS
Sparingly soluble in petroleum ether, soluble in alcohol, chloroform, ether and almost insoluble in water.
Gives a single spot Characteristic of 8-Gingerol Characteristic of 8-Gingerol UV spectra of the principal peak matches with the 8-Gingerol Characteristic of 8-Gingerol < 0.5%w/w
Purity
> 96%w/w
21
Zingiber officinale
TLC PROFILE
Sample detail Adsorbant Solvent system : : : 8-Gingerol Precoated silicagel (Al - Sheet) n Hexane : Ether 40 : 60 10 mg of 8-Gingerol was dissolved in 1 ml of methanol. 10l of this solution was applied on the TLC plate. 9 cms Vanillin sulphuric acid reagent. (Fig.33) Densitometer 280 nm (Fig. 34) CAMAG Linomat IV
Sample preparation
: : : :
Fig. 33
Fig. 34
22
Zingiber officinale
FTIR SPECTRUM
Fig. 35
NMR SPECTRUM
Fig. 36
MASS SPECTRUM
Fig. 37
23
Zingiber officinale
CHROMATOGRAM
PDA SPECTRUM
Fig. 38
Fig. 39
CHROMATOGRAM IN 3D VIEW
Fig. 40
** Peak Report ** GINGE28.K02 99/09/28 19:38:24 PKNO ChNO 1 1 TIME 10.463 TOTAL AREA 2308591 2308591 HEIGHT 100744 100744 CONC 100.0000 100.0000 NAME 8-Gingerol
24
Zingiber officinale
6-Shogaol is another important pungent and active principle isolated from the rhizome of Zingiber officinale Roscoe. Normally obtained as yellow oil.
O CH3O HO
3 [6] Shogaol [8] Sh l n 4 6 C17H24O 3 C H O 276.3 304 4
( )n
TESTS
Description Solubility Yellow oily liquid
RESULTS
Sparingly soluble in petroleum ether, soluble in alcohol, chloroform, ether and almost insoluble in water.
Gives a single spot Characteristic of 6-Shogaol Characteristic of 6-Shogaol UV spectra of the principal peak matches with the 6-Shogaol Characteristic of 6-Shogaol < 0.5%w/w
HPLC
(using PDA detector)
Purity References:
> 96%w/w
25
Zingiber officinale
TLC PROFILE
Sample detail Adsorbant Solvent system : : : 6-Shogaol Precoated silicagel (Al - Sheet) n-Hexane : Ether 40 : 60 10 mg of 6-Shogaol was dissolved in 1 ml of methanol. 10l of this solution was applied on the TLC plate. 9 cms Vanillin sulphuric acid reagent. (Fig.41) Densitometer 280 nm (Fig. 42) CAMAG Linomat IV
Sample preparation
: : : :
Fig. 41
Fig. 42
26
Zingiber officinale
FTIR SPECTRUM
Fig. 43
NMR SPECTRUM
Fig. 44
MASS SPECTRUM
Fig. 45
27
Zingiber officinale
CHROMATOGRAM
PDA SPECTRUM
Fig. 46
Fig. 47
CHROMATOGRAM IN 3D VIEW
Fig. 48
28
Zingiber officinale
References:
Botanical Description 1. Schauenberg P & Paris F, Guide to Medicinal Plants, Keats Publishing,New Canaan CT,1977
Geographical Distribution 1. Kokate C.K, et.al, Pharmacognosy, Nirali Prakashan, 4th edition, 1996 Traditional Use 1. Misra B, Bhavaprakasha Nighantu , 5th edition,1969, p.14 2. Sharma P.V. Dravyagunavigna, Part II, Chowkamba Publications, 1993, p. 331 3. Indian Medicinal Plants, A Compendium of 500 species, Part V, by Orient Longman Publications, 1997, p. 431. 4. Nadakarni, Indian Materia Medica, Vol. I, 1993, p. 1308.
Anatomy of the Rhizome 1. British Herbal Pharmacopoeia, B.H.M.A., 1983, 239-240 2. Wallis T.E., Textbook of Pharmacognosy, C.B.S. Publishers, 5th edition, 1985
Pharmacology and Clinical Studies, Toxicity and Adverse Reactions 1. Chang, H.M et al, Pharmacology and Applications of Chinese Materia Medica. World Scientific, Singapore, 1987 2. Mowrey, D.B, et al, Motion Sickness, Ginger, and Psychophysics Lancet, 1982, 1(8273); 655-657 3. Kawai, T, et al, Anti-emetic principles of Magnolia obovata Bark and Zingiber officinale Rhizome, Planta Medica, 1994, 60; 17-20 4. Blumberger, W, et al, The Physiology of Spices and Condiments. The Action of Ginger on the Amount and Condition of the Saliva , Nutritio et Dieta (European Review of Nutrition and Dietetics), 1965, 7(3); 222-237 5. Yamahara, J, et al, Cholagogic Effect of Ginger and its Active Constituents, Journal of Ethnopharmacology, 1985, 13(2); 217-225 6. Thompson, E.H, et al, Ginger Rhizome : A New Source of Proteolytic Enzyme, Journal of Food Science, 1973, 38; 652-655 7. Suekawa, M, et al, Pharmacological Action of Pungent Constituents, (6)-Gingerol and (6)-Shogaol, Journal of Pharmacobio-Dynamics, 1984, 7(11), 836-848 8. Desai, H.G, et al, Effect of Ginger and Garlic on DNA Content of Gastric Aspirate, Indian Journal of Medical Research, 1990, 92; 139-141
29
Zingiber officinale
9. Yamahara, J, et al, The Anti-ulcer Effect in Rats of Ginger Constituents, Journal of Ethnopharmacology, 1988, 23(2-3); 299-304 10. al-Yahya, M.A, et al, Gastroprotective Activity of Ginger (Zingiber officinale Rose.) in Albino Rats, American Journal of Chinese Medicine, 1989, 17(1-2); 51-56 11. Srivastava, K.C, Effects of Aqueous Extracts of Onion, Garlic and Ginger on Platelet Aggregation and Metabolism of Arachidonic Acid in the Blood Vascular System; In vitro Study, Prostaglandins Leukotrienes and Medicine, 1984, 13(2); 227-235 12. Srivastava, K.C, Aqueous Extracts of Onion, Garlic and Ginger Inhibit Platelet Aggregation and Alter Arachidonic Acid Metabolism, Biomedica, Biochimica Acta, 1984, 43(8-9); S335-346 13. Srivastava, K.C, Isolation and Effects of Some Ginger Components of Platelet Aggregation and Eicosanoid Biosynthesis, Prostaglandins Leukotrienes and Medicine, 1986, 25(2-3); 187-198 14. Guh, J.H, et al, Antiplatelet Effect of Gingerol Isolated from Zingiber officinale, Journal of Pharmacy and Pharmacology, 1995, 47(4); 329-332 15. Mascolo, N, et al, Ethnopharmacologic Investigation of Ginger (Zingiber officinale), Journal of Ethnopharmacology, 1989, 27; 129-140 16. Sharma, J.N, et al, Suppressive Effects of Eugenol and Ginger Oil on Arthritic Rats, Pharmacology, 1984, 49(5), 314-318. 17. Flynn, D.L, et al, Inhibition of Neutrophil 5-Lipoxygenase Activity by Gingerdione, Shogaol, Capsaicin and Related Pungent Compounds, Prostaglandins Leukotrienes and Medicine, 1986, 24(226), 195-198 18. Kiuchi, F, et al, Inhibitors of Prostaglandin Biosynthesis from Ginger, Chemical and Pharmaceutical Bulletin, 1982,(30(2); 754-757 19. Iwakmi, S, et al, Inhibition of Arachidonate 5-Lipoxygenase by Phenolic Compounds, Chemical and Pharmaceutical Bulletin, 1986, 34(9); 3960-3963 20. Kiuchi, F, et al, Inhibition of Prostaglandin and Leukotriene Biosynthesis by Gingerols and Diarylheptanoides, Chemical and Pharmaceutical Bulletin, 1992, 40(2); 387-391 21. Suekawa, N, et al, Pharmacological Studies on Ginger IV. Effect of (6)-Shogaol on the Arachidonic Cascade, Nippon Yakurigakuzasshi (Folia Pharmacologica Japonica), 1986, 88(4); 263-269 (In Japanese) 22. Farnsworth, N.R, et al, Bunyapraphatsara, N, eds Thai Medicinal Plants. Medicinal Plant Information Centre, Bangkok, 1992. 23. Shoji, N, et al, Cardiotonic Principles of Ginger (Zingiber officinale Roscoe.), Journal of Pharmaceutical Sciences, 1982, 71(10), 1174-1175 24. Kobayashi, M, et al, Cardiotonic Action of (8)-Gingerol, An Activator of Ca2+ pumping Adenosine Triphosphatase of Sarcoplasmic Reticulum in Guinea Pig Atrial Muscle, Journal of Pharmacology and Experimental Therapeutics, 1988, 246(2), 667-673 25. Govindarajan, V.S, Ginger- Chemistry, Technology and Quality evaluation; Parts 1 & 2, CRC Critical Reviews in Food, Science and Nutrition, 1982, 17(1); 1-96: 1982, 17(3), 189-258
30
Zingiber officinale
26. Hikino, H, et al, Anti-hepatotoxic Actions of Gingerols and Diarylhepanoids, Journal of Ethnopharmacology, 1985, 14; 31-39 27. Naora, K, et al, Pharmacokinetics of (6)-Gingerol after Intravenous Administration in Rats with Acute Renal or Hepatic Failure Chemical and Pharmaceutical Bulletin, 1992, 40(5); 1295-1298 28. Monge, P, et al, The Metabolism of Zingeronem, a Pungent Principle of Ginger, Xenobiotica, 1976, 6(7); 411-423 29. Mahmoud, I, et al, Mutagenic andToxic Activities of Several Spices and Some Jordanian Medicianl Plants, International Journal of Pharmacognosy, 1992,30(2); 81-85 30. Nakamurah, H, et al, Mutagen and Anti-mutagen in Ginger, Zingiber officinale, Mutation Research, 1982, 103; 119-126 31. Qian, D.S, et al, Pharmacologic Studies of Antimotion Sickness Actions of Ginger, Chung-kuochung hsii chieh ho tsa chih, 1992, 12(2); 70, 95-98 32. Qureshi, A, et al, Studies on Herbal Aphrodisisacs Used in Arab System of Medicine American Journal of Chinese Medicine, 1989, 17(1-2); 57-63 33. Futrell, J.M, et al, Spice Allergy Evaluated by Results of Patch Tests, Cutis, 1993, 52(5); 288-290
Phytochemistry 1 2 3 4 Kiuchi F, et al ,Chem Pharm Bull, !982,30,754 Wagner H, et al, Plant Drug Analysis, Spinger, 1996, 300 British Pharmacopoeia, 305 Akhila A & Tewari, CROMAP,1984,6(3),143-156
Analytical Specifications 1. Merck Index. 12th edn., 1996 2. Wagner H, et al, Plant Drug Analysis, Spinger, 1996, 300 3. D.W. Connell et al., Aust. J. Chem., 1969; 22 : 1033-1043 4. British Pharmacopoeia, 305 5. Indian Standard Specification for Ginger Oleoresin, 1st Revision, Bureau of Indian Standards, IS: 7826 1984. 6. Indian Standard Specification for Oil of Ginger, 1st Revision, Bureau of Indian Standards, IS: 761 1988.
31