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Effect of ginger on bacterial enzymes in 1,2-dimethylhydrazine induced experimental colon carcinogenesis.

Colon cancer is becoming increasingly common in Asian countries and still remains the second leading cause of cancer death in the United States. Ginger, a natural spice having both antioxidant and antimutagenic property, is known to inhibit chemical carcinogenesis. This study was designed to investigate the chemopreventive efficacy of ginger on the activity of bacterial enzymes in rats induced colon cancer by 1,2-dimethylhydrazine. Twenty milligrams per kilogram body weight of 1,2-dimethylhydrazine was administered subcutaneously once a week for the first 15 weeks and then discontinued. Ginger (50 mg/kg body weight/per day, oral) was given at the initiation and also at the postinitiation stages of carcinogenesis to 1,2-dimethylhydrazine-treated rats. The animals were killed at the end of 30 weeks. The macroscopic findings in the colon and the incidence of tumors were recorded in each group, and the activity of beta-glucuronidase and mucinase was estimated in the tissues and fecal contents of rats. After a total experimental period of 32 weeks (including 2 weeks of acclimatization), tumor incidence was 100% in 1,2-dimethylhydrazine-treated rats. The incidence of cancer as well as the number of tumors in the colon was significantly reduced both in the initiation and postinitiation stages of carcinogenesis on ginger administration. The activities of bacterial enzymes beta-glucuronidase (proximal colon, distal colon, intestines, liver and colon contents) and mucinase (colon and fecal contents) were significantly elevated in 1,2-dimethylhydrazine-treated rats as compared with the control rats. The increase in beta-glucuronidase activity may augment the hydrolysis of glucuronide conjugates, liberating the toxins, while the increase in the mucinase activity may enhance the hydrolysis of the protective mucins in the colon. Ginger administration to 1,2-dimethylhydrazine-treated rats significantly decreased the incidence and number of tumors as well as the activity of beta-glucuronidase and mucinase. Thus, ginger has a chemopreventive and anticarcinogenic effect against 1,2-dimethylhydrazine-induced colon cancer by virtue of its ability to lower the activities of the microbial enzymes beta-glucuronidase and mucinase.

1,2-Dimethylhydrazine↗

Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting.

OBJECTIVE: Conventional antiemetics are burdened with the potential of teratogenic effects during the critical embryogenic period of pregnancy. Thus, a safe and effective medication would be a welcome addition to the therapeutic repertoire. This systematic review was aimed at assessing the evidence for or against the efficacy and safety of ginger (Zingiber officinale) therapy for nausea and vomiting during pregnancy. DATA SOURCES: Systematic literature searches were conducted in 3 computerized databases (MEDLINE, EMBASE, and Cochrane Library), and the reference lists of all papers located were checked for further relevant publications. METHODS OF STUDY SELECTION: For the evaluation of efficacy, only double-blind, randomized controlled trials (RCTs) were included. All retrieved clinical data, including uncontrolled trials, case reports, observational studies, and RCTs, were included in the review of safety. TABULATION, INTEGRATION, AND RESULTS: Six double-blind RCTs with a total of 675 participants and a prospective observational cohort study (n = 187) met all inclusion criteria. The methodological quality of 4 of 5 RCTs was high. Four of the 6 RCTs (n = 246) showed superiority of ginger over placebo; the other 2 RCTs (n = 429) indicated that ginger was as effective as the reference drug (vitamin B6) in relieving the severity of nausea and vomiting episodes. The observational study retrieved and RCTs (including follow-up periods) showed the absence of significant side effects or adverse effects on pregnancy outcomes. There were no spontaneous or case reports of adverse events during ginger treatment in pregnancy. CONCLUSION: Ginger may be an effective treatment for nausea and vomiting in pregnancy. However, more observational studies, with a larger sample size, are needed to confirm the encouraging preliminary data on ginger safety. LEVEL OF EVIDENCE: I.

Administration, Oral↗

[Is ginger a clinically relevant antiemetic? A systematic review of randomized controlled trials].

BACKGROUND AND OBJECTIVE: The aim of this systematic review was to evaluate the clinical impact of ginger (Zingiber officinale) as an antiemetic. METHODS: A systematic search of the literature was performed using the databases of MEDLINE, EMBASE, and the Cochrane-Library. RESULTS: Of 100 published reports discerned as potentially relevant, 24 randomized controlled trials were evaluated, covering 1073 patients which had received ginger. Of these reports, 16 contained information regarding the antiemetic activity of the phytotherapeutic agent against kinetosis, postoperative nausea and vomiting (PONV), and morning sickness and hyperemesis gravidarum, respectively. Only a few studies were eligible for a quantitative analysis (meta-analysis). Thus, the majority of the reports were analyzed descriptively. To analyze the potential side effects of the drug, 15 reports with 777 patients were eligible. Of these, 3.3% suffered from slight side effects, mainly mild gastrointestinal symptoms and sleepiness, both not requiring specific treatments. One severe adverse event was reported in a study: an abortion occurred in the 12th week of gestation. However, a total of 136 patients were treated with ginger within the first trimenon of pregnancy without complications. CONCLUSION: There is no clear evidence for the efficacy of ginger in the treatment of PONV and of kinetosis. The results for the treatment of nausea and vomiting in pregnancy are encouraging, however, ginger should be applied for the time being only in controlled clinical studies. Applied in daily doses up to 6 g ginger seems to be a drug with few side effects.

Antiemetics↗

Effects of diet, ginger root oil, and elevation on the mating competitiveness of male Mediterranean fruit flies (Diptera: Tephritidae) from a mass-reared, genetic sexing strain in Guatemala.

The release of sterile males is a key component of an areawide program to eradicate the Mediterranean fruit fly, Ceratitis capitata (Wiedemann), from Guatemala and southern Mexico. The objective of our study was to assess the effects of adult diet, exposure to ginger root oil (Zingiber officinale Roscoe), and elevation on the mating competitiveness of the sterile males used in an areawide program. Sterile males were maintained on a protein-sugar (protein-fed) or a sugar-only (protein-deprived) diet and were exposed (for 4 h 1 d before testing) or not exposed to ginger root oil. In field-cage trials conducted at a high (1,500 m) and low (700 m) site, we monitored the influence of these treatments on the mating success of sterile males in competition with wild males (reared exclusively on the protein-sugar diet and without ginger root oil exposure) for wild females. Elevation and ginger root oil exposure had significant effects, with sterile males having higher mating success at the low-elevation site and ginger root oil-exposed males having greater success than ginger root oil-deprived males at both sites. Diet did not have a significant overall effect, and its influence varied with elevation (dietary protein seemed to provide an advantage at the high-elevation site but not at the low-elevation site). Possible implications of these findings for eradication programs against the Mediterranean fruit fly are discussed.

Animals↗

The anti-motion sickness mechanism of ginger. A comparative study with placebo and dimenhydrinate.

A controlled, double-blind study was carried out to determine whether nystagmus response to optokinetic or vestibular stimuli might be altered by some agent contained in powdered ginger root (Zingiber officinale). For comparative purposes, the test subjects were examined after medication with ginger root, placebo and with dimenhydrinate. Eye movements were recorded using standard ENG equipment and evaluation was performed by automatic nystagmus analysis. It could be demonstrated that the effect of ginger root did not differ from that found at baseline, or with placebo, i.e. it had no influence on the experimentally induced nystagmus. Dimenhydrinate, on the other hand, was found to cause a reduction in the nystagmus response to caloric, rotatory and optokinetic stimuli. From the present study it can be concluded that neither the vestibular nor the oculomotor system, both of which are of decisive importance in the occurrence of motion sickness, are influenced by ginger. A CNS mechanism, which is characteristic of the conventional anti-motion sickness drugs, can thus be excluded as regards ginger root. It is more likely that any reduction of motion-sickness symptoms derives from the influence of the ginger root agents on the gastric system.

Adult↗

Ginger (Zingiber officinale Roscoe) and the gingerols inhibit the growth of Cag A+ strains of Helicobacter pylori.

BACKGROUND: Ginger root (Zingiber officinale) has been used traditionally for the treatment of gastrointestinal ailments such as motion sickness, dyspepsia and hyperemesis gravidarum, and is also reported to have chemopreventative activity in animal models. The gingerols are a group of structurally related polyphenolic compounds isolated from ginger and known to be the active constituents. Since Helicobacter pylori (HP) is the primary etiological agent associated with dyspepsia, peptic ulcer disease and the development of gastric and colon cancer, the anti-HP effects of ginger and its constituents were tested in vitro. MATERIALS AND METHODS: A methanol extract of the dried powdered ginger rhizome, fractions of the extract and the isolated constituents, 6-,8-,10-gingerol and 6-shogoal, were tested against 19 strains of HP, including 5 CagA+ strains. RESULTS: The methanol extract of ginger rhizome inhibited the growth of all 19 strains in vitro with a minimum inhibitory concentration range of 6.25-50 micrograms/ml. One fraction of the crude extract, containing the gingerols, was active and inhibited the growth of all HP strains with an MIC range of 0.78 to 12.5 micrograms/ml and with significant activity against the CagA+ strains. CONCLUSION: These data demonstrate that ginger root extracts containing the gingerols inhibit the growth of H. pylori CagA+ strains in vitro and this activity may contribute to its chemopreventative effects.

Antigens, Bacterial↗

Clastogenic effect of ginger rhizome in mice.

The present study focuses on the clastogenic effect of ginger rhizome. Crude aqueous extracts of ginger were gavaged at doses of 0. 5, 1, 2, 5, 10 g/kg body weight and ginger oil (0.625, 1.250 and 2. 50 ml/kg body weight) was administered by intraperitoneal injection to male mice. Chromosome damage was studied in a preparation made from bone marrow cells following colchicine injection to all mice and examination of the cells after pretreatment in hypotonic solution, fixation, air drying and staining in Giemsa solution. Attention is drawn to the weakness of the clastogenic activity expressed by the ginger extract. In comparison ginger oil gave a higher frequency of chromosomal aberrations. It is suggested therefore, that the extract may contain substance(s) that suppress clastogenesis in the bone marrow cells of mice.

Animals↗

Determination of 6-gingerol in ginger (Zingiber officinale) using high-performance thin-layer chromatography.

A sensitive and accurate High-Performance TLC (HPTLC) method has been developed to determine the quantity of 6-gingerol in rhizomes of Zingiber officinale (family: Zingiberaceae), commonly known as ginger. Methanol extracts of rhizomes from three different sources were used for HPTLC, n-hexane, and diethyl ether (40:60 v/v) as the mobile phase. The Rf of 6-gingerol was found to be 0.40. The calibration plot was linear in the range of 250-1200 ng of 6-gingerol and the correlation coefficient of 0.9997 was indicative of good linear dependence of peak area on concentration. The mean quantity of 6-gingerol was found to be 60.44+/-2.53 mg/g of ginger extract. The method permits reliable quantification of 6-gingerol and good resolution and separation of 6-gingerol from other constituents of ginger. To study the accuracy and precision of the method, recovery studies were performed by the method of standard addition. Recovery values from 99.79 to 99.84% showed the excellent reliability and reproducibility of the method. The proposed HPTLC method for quantitative monitoring of 6-gingerol in ginger can be used for routine quality testing of ginger extracts.

Catechols↗

The efficacy of ginger for the prevention of postoperative nausea and vomiting: a meta-analysis.

OBJECTIVE: The aim of this study was to specifically determine the impact of a fixed dose of ginger administration, compared with placebo, on the 24-hour postoperative nausea and vomiting. STUDY DESIGN: The design was a systematic review and metaanalysis of trials revealed by searches. Randomized controlled trials comparing ginger with placebo to prevent postoperative nausea and vomiting and postoperative vomiting from Medline, IPA, CINAHL, Cochrane CENTRAL, HealthStar, Current Contents, bibliographies of retrieved articles, contact of authors, and experts in the field. Two reviewers selected studies for inclusion and independently extracted data. RESULTS: Five randomized trials including a total of 363 patients were pooled for analysis of preventing postoperative nausea and vomiting and postoperative vomiting. The summary relative risks of ginger for postoperative nausea and vomiting and postoperative vomiting were 0.69 (95% confidence interval 0.54 to 0.89) and 0.61 (95% confidence interval 0.45 to 0.84), respectively. Only one side effect, abdominal discomfort, was reported. CONCLUSIONS: This meta-analysis demonstrates that a fixed dose at least 1 g of ginger is more effective than placebo for the prevention of postoperative nausea and vomiting and postoperative vomiting. Use of ginger is an effective means for reducing postoperative nausea and vomiting.

Zingiber officinale↗

The modulatory effects of the volatile oil of ginger on the cellular immune response in vitro and in vivo in mice.

The aim of this study was to investigate the immunomodulatory effects of the volatile oil of ginger (Zingiber officinale Roscoe) in vitro and in vivo in mice. In vitro, the volatile oil of ginger (0.001-10 ng/mL) significantly inhibited T lymphocyte proliferation (P < 0.01), decreased the number of the total T lymphocytes and T helper cells (P < 0.01) in a concentration-dependent manner, but increased the percentage of T suppressor cells to the total T lymphocytes in the mice. In addition, the volatile oil of ginger (0.001-10 ng/mL) inhibited IL-1alpha secretion by the mice peritoneal macrophages in a concentration-dependent manner. In vivo, oral administration of the volatile oil of ginger in the doses of 0.125, 0.25 and 0.5 g/kg body weight dose-dependently weakened the delayed type of hypersensitivity response to 2,4-dinitro-1-fluorobenzene in the sensitized mice (P < 0.05). These results suggest that the volatile oil of ginger influences both cell-mediated immune response and nonspecific proliferation of T lymphocyte, and may exert beneficial effects in a number of clinical conditions, such as chronic inflammation and autoimmune diseases.

Animals↗

Development of gas chromatography-mass spectrometry with microwave distillation and simultaneous solid-phase microextraction for rapid determination of volatile constituents in ginger.

In this study, gas chromatography-mass spectrometry (GC-MS) following microwave distillation and solid-phase microextraction (MD-SPME) was developed for the analysis of essential oil compounds in fresh ginger. In the proposed method, the isolation, extraction and concentration of volatile components in ginger were carried out in one single step, using the MD-SPME technique, and the analytes on the SPME fiber were analyzed by GC-MS. Some parameters, including SPME fiber coating, microwave power and irradiation time, were optimized. The optimal experiment parameters obtained were: 65 microm PDMS/DVB SPME fiber, a microwave power of 400 W and an irradiation time of 2 min. To demonstrate its feasibility, MD-SPME was compared with conventional SPME for the extraction of essential oil compounds in fresh ginger. Using MD-SPME followed by GC-MS, 54 compounds were separated and identified in ginger, which mainly included geranial (5.25%), zingiberene (15.48%), beta-sesquiphellandrene (5.54%) and beta-phellandrene (22.84%), whereas only 39 compounds were separated and identified by conventional SPME followed by GC-MS. The relative standard deviation (R.S.D.) values of less than 10% show that the proposed method has good repeatability. The result show that MD-SPME, followed by GC-MS, is a simple, rapid, solvent-free method for the determination of volatile compounds in ginger.

Gas Chromatography-Mass Spectrometry↗

The effect of extracts from ginger rhizome on inflammatory mediator production.

Compounds from rhizomes of Zingiber officinale, commonly called ginger, have been purported to have anti-inflammatory actions. We have used an in vitro test system to test the anti-inflammatory activity of compounds isolated from ginger rhizome. U937 cells were differentiated and exposed to lipopolysaccharide (LPS) from Escherichia coli (1 microg/ml) in the presence or absence of organic extracts or standard compounds found in ginger (6-, 8-, 10-gingerol or 6-shogaol) for 24 h. Supernatants were collected and analyzed for the production of prostaglandin E(2) (PGE(2)) and tumor necrosis factor alpha (TNF-alpha) by standard ELISA assays. Predominant compounds in the organic extracts were identified as 6-, 8- 10-gingerols and 6-, 8-, 10-shogaols. Organic extracts or standards containing gingerols were not cytotoxic, while extracts or standards containing predominantly shogaols were cytotoxic at concentrations above 20 microg/ml. Crude organic extracts of ginger were capable of inhibiting LPS induced PGE(2) (IC(50)<0.1 microg/ml) production. However, extracts were not nearly as effective at inhibiting TNF-alpha (IC(50)>30 microg/ml). Thirty three fractions and subfractions, prepared by column chromatography, were analyzed for bioactivity. Extracts containing either predominantly gingerols or shogaols (identified by HPLC) were both highly active at inhibiting LPS-induced PGE(2) production (IC(50)<0.1 microg/ml), while extracts that contained unknown compounds were less effective (IC(50)<3.2 microg/ml). Extracts or standards containing predominantly gingerols were capable of inhibiting LPS-induced COX-2 expression while shogaol containing extracts had no effect on COX-2 expression. These data demonstrate that compounds found in ginger are capable of inhibiting PGE(2) production and that the compounds may act at several sites.

Anti-Inflammatory Agents, Non-Steroidal↗

The effects of Zintona EC (a ginger extract) on symptomatic gonarthritis.

OBJECTIVE: Evaluation of the effect of a ginger extract (Zintona EC) on patients suffering from gonarthritis. MATERIAL AND METHODS: Twenty-nine patients (6 men and 23 women) with symptomatic gonarthritis (ACR criteria), in the age range 42-85 years, were included after randomization in a double blind, placebo controlled, crossover study of 6 months' duration. The treatment group was given a ginger extract (250 mg of Zingiberis Rhizoma per capsule, qid), while the placebo group received the same number of identical looking capsules per day. The crossover occurred after 3 months of therapy. Results were evaluated by a 100mm visual analog scale (VAS) of pain on movement and of handicap. RESULTS: Eight patients dropped out because of inefficacy, three from group 1 (ginger extract first) and five from group 2 (placebo first). One patient from group 1 and one from group 2 dropped out because of heartburn (while they were on ginger extract). Twenty patients completed the study period of 24 weeks and 19 that of 48 weeks follow-up. By the end of 24 weeks there was a highly statistically significant difference between the VAS of pain and handicap of the two groups (P<0.001). However, at crossover both groups showed a statistically significant decrease in VAS of pain on movement and of handicap, but the differences between the groups did not reach statistical significance. CONCLUSIONS: Zintona EC was as effective as placebo during the first 3 months of the study, but at the end of 6 months, 3 months after crossover, the ginger extract group showed a significant superiority over the placebo group.

Adult↗

Geraniol dehydrogenase activity related to aroma formation in ginger (Zingiber officinale Roscoe).

Geranial is one of the potent odor compounds in fresh ginger. To clarify the generation of geranial in ginger, the alcohol dehydrogenase activity was measured in a crude enzymatic system of ginger. This enzyme solution was found to contain geraniol dehydrogenase (GeDH) specifically acting on geraniol as a substrate with NADP as a coenzyme. Geranial generation and GeDH activity were investigated for different maturity stages and storage periods of ginger. Both were at maximum levels from just after harvesting to initial storage. The GeDH activity subsequently dropped, and the generation of geranial also stopped. These results suggest that the GeDH activity in ginger is related to the generation of geranial.

Acyclic Monoterpenes↗

Gingerol content of diploid and tetraploid clones of ginger (Zingiber officinale Roscoe).

Ginger (Zingiber officinale Roscoe), a monocotyledonous, sterile cultigen, is widely used as a spice, flavoring agent, and herbal medicine. The pungency of fresh ginger is due to a series of homologous phenolic ketones of which [6]-gingerol is the major one. The gingerols are thermally unstable and can be converted to their corresponding shogaols, which are present in dried ginger. Fresh rhizomes of 17 clones of Australian ginger, including commercial cultivars and experimental tetraploid clones, were assayed by HPLC for gingerols and shogaols. [6]-Gingerol was identified as the major pungent phenolic compound in all samples, while [8]- and [10]-gingerol occurred in lower concentrations. One cultivar known as "Jamaican" contained the highest concentrations of all three gingerols and was the most pungent of the clones analyzed. Gingerols were stable in ethanolic solution over a 5-month period when stored at 4 degrees C. Shogaols were not identified in the extracts prepared from fresh rhizomes at ambient temperature, confirming that these compounds are not native constituents of fresh ginger. In contrast to previous findings, this study did not find significant differences in gingerol concentrations between the tetraploid clones and their parent diploid cultivar.

Australia↗

The efficacy of ginger root in the prevention of postoperative nausea and vomiting after outpatient gynaecological laparoscopy.

To determine the anti-emetic effect of ginger as compared to droperidol, 120 patients scheduled to have gynaecological diagnostic laparoscopy as day cases were randomly allocated into placebo, droperidol, ginger and ginger plus droperidol groups to receive either 2 g of ginger or 1.25 mg of droperidol or both. There were no significant differences in the incidences of postoperative nausea which were 32%, 20%, 22% and 33%, and vomiting which were 35%, 15%, 25% and 25% in the four groups, respectively. We conclude that ginger powder, in the dose of 2 g, droperidol 1.25 mg or both are ineffective in reducing the incidence of postoperative nausea and vomiting after day case gynaecological laparoscopy.

Adult↗

Prospective comparative study of the safety and effectiveness of ginger for the treatment of nausea and vomiting in pregnancy.

OBJECTIVES: The primary objective of our study was to examine the safety and the secondary objective was to examine the effectiveness of ginger for nausea and vomiting of pregnancy (NVP). STUDY DESIGN: Pregnant women who called the Motherisk Program who were taking ginger during the first trimester of pregnancy were enrolled in the study. The women were compared with a group of women who were exposed to nonteratogenic drugs that were not antiemetic medications. The women were followed up to ascertain the outcome of the pregnancy and the health of their infants. They were also asked on a scale of 0 to 10 how effective the ginger was for their symptoms of NVP. RESULTS: We were able to ascertain the outcome of 187 pregnancies. There were 181 live births, 2 stillbirths, 3 spontaneous abortions, and 1 therapeutic abortion. The mean birth weight was 3542+/-543 g, the mean gestational age was 39+/-2 weeks, and there were three major malformations. There were no statistical differences in the outcomes between the ginger group and the comparison group with the exception of more infants weighing less than 2500 g in the comparison group (12 vs 3, P < or =.001). There were a total of 66 completed effectiveness scores with the mean score of 3.3+/-2.9 SD. CONCLUSION: These results suggest that ginger does not appear to increase the rates of major malformations above the baseline rate of 1% to 3% and that it has a mild effect in the treatment of NVP.

Birth Weight↗

Antiemetic effect of ginger in gynecologic oncology patients receiving cisplatin.

To determine whether ginger had antiemetic effect in cisplatin-induced emesis, we conducted a randomized, double-blinded crossover study in 48 gynecologic cancer patients receiving cisplatin-based chemotherapy. Subjects were randomly allocated to regimen A or regimen B in their first cycle of the study. All patients received standard antiemetics in the first day of cisplatin administration. In regimen A, capsules of ginger root powder were given orally 1 g /day for 5 days, starting on the first day of chemotherapy. In regimen B, placebo was given on the first day and metoclopramide was given orally thereafter for 4 days. The patients were then crossed over to receive the other antiemetic regimen in their next cycle of chemotherapy. Among 43 evaluable patients who received both cycles of treatment, success in controls of nausea and emesis were not significantly different between the two regimens in both acute and delayed phases. Restlessness, as a side effect, occurred more often in metoclopramide arm compared to ginger arm (P=0.109). In conclusion, addition of ginger to standard antiemetic regimen has no advantage in reducing nausea or vomiting in acute phase of cisplatin-induced emesis. In delayed phase, ginger and metoclopramide have no statistically significant difference in efficacy.

Administration, Oral↗