Ginger Clinical Studies
Ginger--an herbal medicinal product with broad anti-inflammatory actions.Grzanna R, Lindmark L, Frondoza CG.RMG Biosciences, Inc.
J Med Food. 2005 Summer;8(2):125-32.
The anti-inflammatory properties of ginger have been known and valued for centuries. During the past 25 years, many laboratories have provided scientific support for the long-held belief that ginger contains constituents with antiinflammatory properties. The original discovery of ginger's inhibitory effects on prostaglandin biosynthesis in the early 1970s has been repeatedly confirmed. This discovery identified ginger as an herbal medicinal product that shares pharmacological properties with non-steroidal anti-inflammatory drugs. Ginger suppresses prostaglandin synthesis through inhibition of cyclooxygenase-1 and cyclooxygenase-2. An important extension of this early work was the observation that ginger also suppresses leukotriene biosynthesis by inhibiting 5-lipoxygenase. This pharmacological property distinguishes ginger from nonsteroidal anti-inflammatory drugs. This discovery preceded the observation that dual inhibitors of cyclooxygenase and 5-lipoxygenase may have a better therapeutic profile and have fewer side effects than non-steroidal anti-inflammatory drugs. The characterization of the pharmacological properties of ginger entered a new phase with the discovery that a ginger extract (EV.EXT.77) derived from Zingiber officinale (family Zingiberaceae) and Alpina galanga (family Zingiberaceae) inhibits the induction of several genes involved in the inflammatory response. These include genes encoding cytokines, chemokines, and the inducible enzyme cyclooxygenase-2. This discovery provided the first evidence that ginger modulates biochemical pathways activated in chronic inflammation. Identification of the molecular targets of individual ginger constituents provides an opportunity to optimize and standardize ginger products with respect to their effects on specific biomarkers of inflammation. Such preparations will be useful for studies in experimental animals and humans.
Gingerol, a pungent ingredient of ginger, inhibits angiogenesis in vitro and in vivo.
Kim EC, Min JK, Kim TY, Lee SJ, Yang HO, Han S, Kim YM, Kwon YG.
Department of Biochemistry, College of Natural Sciences, Yonsei University,Seoul, Republic of Korea.
Biochem Biophys Res Commun. 2005 Sep 23;335(2):300-8.
-Gingerol, a pungent ingredient of ginger (Zingiber officinale Roscoe, Zingiberaceae), has anti-bacterial, anti-inflammatory, and anti-tumor-promoting activities. Here, we describe its novel anti-angiogenic activity in vitro and in vivo. In vitro, -gingerol inhibited both the VEGF- and bFGF-induced proliferation of human endothelial cells and caused cell cycle arrest in the G1 phase. It also blocked capillary-like tube formation by endothelial cells in response to VEGF, and strongly inhibited sprouting of endothelial cells in the rat aorta and formation of new blood vessel in the mouse cornea in response to VEGF. Moreover, i.p. administration, without reaching tumor cytotoxic blood levels, to mice receiving i.v. injection of B16F10 melanoma cells, reduced the number of lung metastasis, with preservation of apparently healthy behavior.Taken together, these results demonstrate that -gingerol inhibits angiogenesis and may be useful in the treatment of tumors and other angiogenesis-dependent diseases.
Gingerol inhibits COX-2 expression by blocking the activation of p38 MAP kinase and NF-kappaB in phorbol ester-stimulated mouse skin.
Kim SO, Kundu JK, Shin YK, Park JH, Cho MH, Kim TY, Surh YJ.
College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
Oncogene. 2005 Apr 7;24(15):2558-67.
-Gingerol, a pungent ingredient of ginger (Zingiber officinale Roscoe, Zingiberaceae), has a wide array of pharmacologic effects. The present study was aimed at unraveling the molecular mechanisms underlying previously reported antitumor promoting effects of -gingerol in mouse skin in vivo. One of well-recognized molecular targets for chemoprevention is cyclooxygenase-2 (COX-2) that is abnormally upregulated in many premalignant and malignant tissues and cells. In our present study, topical application of -gingerol inhibited COX-2 expression in mouse skin stimulated with a prototype tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Since the transcription factor nuclear factor-kappaB (NF-kappaB) is known to regulate COX-2 induction, we attempted to determine the effect of -gingerol on TPA-induced activation of NF kappaB. Pretreatment with -gingerol resulted in a decrease in both TPA-induced DNA binding and transcriptional activities of NF-kappaB through suppression of IkappaBalpha degradation and p65 nuclear translocation. Phosphorylation of both IkappaBalpha and p65 was substantially blocked by -gingerol. In addition, -gingerol inhibited TPA-stimulated interaction of phospho-p65-(Ser-536) with cAMP response element binding protein-binding protein, a transcriptional coactivator of NF-kappaB. Moreover, -gingerol prevented TPA-induced phosphorylation and catalytic activity of p38 mitogen-activated protein (MAP) kinase that regulates COX-2 expression in mouse skin. The p38 MAP kinase inhibitor SB203580 attenuated NF-kappaB activation and subsequent COX-2 induction in TPA-treated mouse skin. Taken together, our data suggest that -gingerol inhibits TPA-induced COX-2 expression in mouse skin in vivo by blocking the p38 MAP kinase-NF-kappaB signaling pathway.
Analgesic and anti-inflammatory activities of -gingerol.
Young HY, Luo YL, Cheng HY, Hsieh WC, Liao JC, Peng WH.
TzuHui Institute of Technology, 926 Ping'Tung, Taiwan, ROC.
J Ethnopharmacol. 2005 Jan 4;96(1-2):207-10.
In the present study, the analgesic and anti-inflammatory effects of -gingerol, which is the pungent constituent of ginger, were performed. Intraperitoneal administration of -gingerol (25 mg/kg-50 mg/kg) produced an inhibition of acetic acid-induced writhing response and formalin-induced licking time in the late phase. -Gingerol (50 mg/kg-100 mg/kg) also produced an inhibition of paw edema induced by carrageenin. These results suggested that -gingerol possessed analgesic and anti-inflammatory activities.
Anti-tumor-promoting activities of selected pungent phenolic substances present in ginger.
Surh YJ, Park KK, Chun KS, Lee LJ, Lee E, Lee SS.
College of Pharmacy, Seoul National University, Seoul, South Korea.
J Environ Pathol Toxicol Oncol. 1999;18(2):131-9.
Ginger (Zingiber officinale Roscoe, Zingiberaceae) has been widely used as a dietary spice, as well as in traditional oriental medicine. The rhizome of ginger contains pungent vanillyl ketones, including -gingerol and -paradol, and has been reported to possess a strong anti-inflammatory activity. These pungent substances have a vanilloid structure found in other chemopreventive phytochemicals, including curcumin. In our study, we found anti-tumor-promoting properties of -gingerol and -paradol. Thus, topical application of -gingerol or -paradol 30 min prior to 12-O-tetradecanoyl-phorbol-13-acetate (TPA) attenuated the skin papillomagenesis initiated by 7,12 dimethylbenz[a]anthracene in female ICR mice. These substances also significantly inhibited the tumor-promoter-stimulated inflammation, TNF-alpha production, and activation of epidermal ornithine decarboxylase in mice. In another study, -gingerol and -paradol suppressed the superoxide production stimulated by TPA in differentiated HL-60 cells. Taken together, these findings suggest that pungent vanilloids found in ginger possess potential chemopreventive activities.
Anti-tumor promoting potential of selected spice ingredients with antioxidative and anti- inflammatory activities: a short review.
Surh YJ.Laboratory of Biochemistry and Molecular Toxicology, College of Pharmacy, Seoul ational University, 151-742, Seoul, South
Food Chem Toxicol. 2002 Aug;40(8):1091-7.
A wide variety of phenolic substances derived from spice possess potent antimutagenic and anticarcinogenic activities. Examples are curcumin, a yellow colouring agent, contained in turmeric (Curcuma longa L., Zingiberaceae), -gingerol, a pungent ingredient present in ginger (Zingiber officinale Roscoe, Zingiberaceae) and capsaicin, a principal pungent principle of hot chili pepper (Capsicum annuum L, Solanaceae). The chemopreventive effects exerted by these phytochemicals are often associated with their antioxidative and anti-inflammatory activities. Cyclo-oxygenase-2 (COX-2) has been recognized as a molecular target of many chemopreventive as well as anti-inflammatory agents. Recent studies have shown that COX-2 is regulated by the eukaryotic transcription factor NF-kappaB. This short review summarizes the molecular mechanisms underlying chemopreventive effects of the aforementioned spice ingredients in terms of their effects on intracellular signaling cascades, particularly those involving NF-kappaB and mitogen-activated protein kinases.
Cancer preventive properties of ginger: a brief review.
Shukla Y, Singh M.
Environmental Carcinogenesis Division, Industrial Toxicology Research Centre,P.O. Box 80, M.G. Marg, Lucknow 226 001, Uttar Pradesh, India.
Food Chem Toxicol. 2007 May;45(5):683-90. Epub 2006 Nov 12.
Ginger, the rhizome of Zingiber officinalis, one of the most widely used species of the ginger family, is a common condiment for various foods and beverages. Ginger has a long history of medicinal use dating back 2500 years. Ginger has been traditionally used from time immemorial for varied human ailments in different parts of the globe, to aid digestion and treat stomach upset, diarrhoea, and nausea. Some pungent constituents present in ginger and other zingiberaceous plants have potent antioxidant and anti-inflammatory activities, and some of them exhibit cancer preventive activity in experimental carcinogenesis. The anticancer properties of ginger are attributed to the presence of certain pungent vallinoids, viz. -gingerol and -paradol, as well as some other constituents like shogaols, zingerone etc. A number of mechanisms that may be involved in the chemopreventive effects of ginger and its components have been reported from the laboratory studies in a wide range of experimental models.
Chemoprotective properties of some pungent ingredients present in red pepper and ginger.
Surh YJ, Lee E, Lee JM.
College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-gu, Seoul 151-742, South Korea.
Mutat Res. 1998 Jun 18;402(1-2):259-67.
There has been a substantial body of data, supporting that dietary factors have a profound impact on prevention as well as etiology of human cancer. Capsaicin has been tested by many investigators for its effects on experimental carcinogenesis and mutagenesis. Data in the literature indicate that capsaicin has dual effects on carcinogenic and mutagenic processes. At present, there is no solid evidence that hot red and chili peppers or their principal pungent ingredient capsaicin are carcinogenic in humans although results of early investigations with experimental animals exhibit the moderate tumorigenicity of this compound. In contrast, recent studies reveal substantial antigenotoxic and anticarcinogenic effects of capsaicin, suggesting this compound as another important dietary phytochemical with a potential chemopreventive activity. Some pungent constituents present in ginger and other zingiberaceous plants have potent antioxidant and anti-inflammatory effects, and some of them exhibit anti-tumor promotional activity in experimental carcinogenesis.
Effects of 6-gingerol, an antioxidant from ginger, on inducing apoptosis in human leukemic HL-60 cells.
Wang CC, Chen LG, Lee LT, Yang LL.
Graduate Institute of Pharmacognosy Science, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan, R.O.C.
In Vivo. 2003 Nov-Dec;17(6):641-5.
6-Gingerol, a naturally occurring plant phenol, is one of the major components of fresh ginger. In this paper, the antioxidative effects of 6-gingerol were detected by DPPH and DCFH assays and, as predicted, 6-gingerol as an antioxidant was shown to protect HL-60 cells from oxidative stress. Moreover, it induced cell death in promyelocytic leukemia HL-60 cells, caused DNA fragmentation and inhibited Bcl-2 expression in HL-60 cells. These results suggested that the inhibition of Bcl-2 expression in HL-60 cells might account for the mechanism of 6-gingerol-induced apoptosis. In the inhibitory assay, the cytotoxic effect of 6-gingerol could be prevented by catalase. We suggest that 6-gingerol induced cell death by mediating reactive oxygen species such as hydrogen peroxide and the superoxide anion. Therefore, the results showed that 6-gingerol induced apoptosis in HL-60 cells, not due to its antioxidative activity.
A double-blind randomized controlled trial of ginger for the prevention of postoperative nausea and vomiting.
Arfeen Z, Owen H, Plummer JL, Ilsley AH, Sorby-Adams RA
, Doecke CJ
Department of Anaesthesia and Intensive Care, Flinders Medical Centre, Bedford Park, S.A..
Anaesth Intensive Care. 1995 Aug;23(4):449-52.
The efficacy of ginger for the prevention of postoperative nausea and vomiting was studied in a double-blind, randomized, controlled trial in 108 ASA 1 or 2 patients undergoing gynaecological laparoscopic surgery under general anaesthesia. Patients received oral placebo, ginger BP 0.5g or ginger BP 1.0g, all with oral diazepam premedication, one hour prior to surgery. Patients were assessed at three hours postoperatively. The incidence of nausea and vomiting increased slightly but nonsignificantly with increasing dose of ginger. The incidence of moderate or severe nausea was 22, 33 and 36%, while the incidence of vomiting was 17, 14 and 31% in groups receiving 0, 0.5 and 1.0g ginger, respectively (odds ratio per 0.5g ginger 1.39 for nausea and 1.55 for vomiting). These results were essentially unchanged when adjustment was made for concomitant risk factors. We conclude that ginger BP in doses of 0.5 or 1.0 gram is ineffective in reducing the incidence of postoperative nausea and vomiting.
Efficacy of ginger for nausea and vomiting: a systematic review of randomized clinical trials.
Ernst E, Pittler MH.
Department of Complementary Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter, UK.
Br J Anaesth. 2000 Mar;84(3):367-71.
Ginger (Zingiber officinale) is often advocated as beneficial for nausea and vomiting. Whether the herb is truly efficacious for this condition is, however, still a matter of debate. We have performed a systematic review of the evidence from randomized controlled trials for or against the efficacy of ginger for nausea and vomiting. Six studies met all inclusion criteria and were reviewed. Three on postoperative nausea and vomiting were identified and two of these suggested that ginger was superior to placebo and equally effective as metoclopramide. The pooled absolute risk reduction for the incidence of postoperative nausea, however, indicated a non-significant difference between the ginger and placebo groups for ginger 1 g taken before operation (absolute risk reduction 0.052 (95% confidence interval -0.082 to 0.186)). One study was found for each of the following conditions: seasickness, morning sickness and chemotherapy-induced nausea. These studies collectively favoured ginger over placebo.
The efficacy of ginger for the prevention of postoperative nausea and vomiting: a meta-analysis.
Chaiyakunapruk N, Kitikannakorn N, Nathisuwan S, Leeprakobboon K, Leelasettagool C.
Department of Pharmacy Practice, School of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand.
Am J Obstet Gynecol. 2006 Jan;194(1):95-9.
Comment in: Evid Based Nurs. 2006 Jul;9(3):80
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.
The efficacy of ginger in prevention of postoperative nausea and vomiting aftermajor gynecologic surgery.
Nanthakomon T, Pongrojpaw D.
Department of Obstetrics and Gyecology, Faculty of Medicine, Thammasat University, Bangkok 12120, Thailand.
J Med Assoc Thai. 2006 Oct;89 Suppl 4:S130-6.
OBJECTIVE: To study the efficacy of ginger in prevention of nausea and vomiting after major gynecologic surgery.
STUDY DESIGN: Double blind randomized controlled trial.
SETTING: Department of Obstetrics and Gynecology, Thammasat University Hospital, Faculty of Medicine, Thammasat University, Pathumthani, 12120, Thailand.
MATERIAL AND METHOD: From March 2005 to April 2006, 120 patients whunderwent major gynecologic surgery were randomized into group A (n = 60) and group B (n = 60). The patients in group A received two capsules of ginger taken one hour before the procedure (one capsule contains 0.5 gram of ginger powder). The patients in group B received the placebo. The visual analog nausea score (VANS) and frequency of vomiting were evaluated at 0, 2, 6, 12, and 24 hours after the operation. RESULTS: The results demonstrated the statistically significant differences in nausea between group A (48.3%) and group B (66.7%). The VANS was lower in group A compared to group B at 2, 6, 12, and 24 hours. The most statistically significant differences occurred at 2 and 6 hour. The incidence and frequency of vomiting in group A were lower than group B. Side effects caused by ginger were not detected. CONCLUSION: Ginger has efficacy in prevention of nausea and vomiting after major gynecologic surgery.
Some phytochemical, pharmacological and toxicological properties of ginger
(Zingiber officinale Roscoe): A review of recent research.
Ali BH, Blunden G, Tanira MO, Nemmar A.
Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box 35, Al Khod 123, Oman.
Food Chem Toxicol. 2008 Feb;46(2):409-20. Epub 2007 Sep 18.
Ginger (Zingiber officinale Roscoe, Zingiberacae) is a medicinal plant that has been widely used in Chinese, Ayurvedic and Tibb-Unani herbal medicines all over the world, since antiquity, for a wide array of unrelated ailments that include arthritis, rheumatism, sprains, muscular aches, pains, sore throats, cramps, constipation, indigestion, vomiting, hypertension, dementia, fever, infectious diseases and helminthiasis. Currently, there is a renewed interest in ginger, and several scientific investigations aimed at isolation and identification of active constituents of ginger, scientific verification of its pharmacological actions and of its constituents, and verification of the basis of the use of ginger in some of several diseases and conditions. This article aims at reviewing the most salient recent reports on these investigations. The main pharmacological actions of ginger and compounds isolated therefrom include immuno-modulatory, anti-tumorigenic, anti-inflammatory, anti-apoptotic, anti-hyperglycemic, anti-lipidemic and anti-emetic actions. Ginger is a strong anti-oxidant substance and may either mitigate or prevent generation of free radicals. It is considered a safe herbal medicine with only few and insignificant adverse/side effects. More studies are required in animals and humans on the kinetics of ginger and its constituents and on the effects of their consumption over a long period of time.
The safety of a ginger extract in the rat.
Weidner MS, Sigwart K.
Institute of Drug Analysis A/S, Symbion Science Park, Fruebjergvej 3, DK-2100, Copenhagen, Denmark.
J Ethnopharmacol. 2000 Dec;73(3):513-20.
In three different studies on rats, the effects of a patented standardized ginger extract, EV.EXT 33, on blood glucose, blood coagulation, blood pressure and heart rate were investigated. EV.EXT 33 had no significant effect on blood glucose levels at the doses used. It also had no significant effects on coagulation parameters or on Warfarin-induced changes in blood coagulation, indicating that it did not interact with Warfarin. EV.EXT 33 neither decreases systolic blood pressure nor increases heart rate in the rat. As also seen from the literature, ginger is thus pharmacologically safe regarding the investigated aspects.