Search

Ginger is attributed with beneficial bioactivities. The aims of this study were to analyse the bioactive compounds in commercial ginger powders and assess acceptability and satiety responses to ginger-enriched wheat pasta in healthy human volunteers. Powders were extracted with methanol and extracts analysed by HPLC-UV/LC-MS. Results indicated that 6-gingerol, 8-gingerol, 10-gingerol and 10-shogaol were the principal bioactive components. The liking of pasta enriched with 1%, 3% and 5% (w/w) ginger powder was evaluated for four sensory attributes and overall liking using a 9-point hedonic scale. All pasta products were generally liked to a similar extent to the control, with the exception of the liking for colour of the pasta with 5% ginger (P < 0.02). Ten healthy subjects consumed two samples of equal weight: control and ginger-enriched pasta (3%), on two occasions. Subjective feelings of satiety were assessed pre-consumption, immediately after and for 2 h post-consumption using a 7-point intensity scale analysed using Rasch modelling. Results show that the ginger pasta sample had a similar satiety response compared to the control pasta up to 2 h after consumption. In conclusion, ginger-enriched pasta is generally accepted by consumers, but does not lead to higher satiety compared to the control.

Combination therapies, using medicinal herbs, are broadly recommended to attenuate the chemotherapy adverse effects. Based on our previous findings considering the anti‐leukaemic effects of ginger extract on acute lymphoblastic leukaemia (ALL) cells, the present study was aimed to investigate the anti‐cancer role of this pharmaceutical plant on ALL mice models. Moreover, we worked towards identifying the most anti‐leukaemic derivative of ginger and the mechanism through which it may exert its cytotoxic impact. In vivo experiments were performed using five groups of six C57BL/6 nude mice, and the anti‐leukaemic activity of ginger extract alone or in combination with methotrexate (MTX) was examined. Results showed increased survival rate and reduced damages in mice brain and liver tissues. Subsequently, MTT assay demonstrated synergistic growth inhibitory effect of 6‐shogaol (6Sh) and MTX on ALL cell lines and patients primary cells. Eventually, the molecular anti‐neoplastic mechanism of 6Sh was evaluated using Bioinformatics. Flow cytometry illustrated 6Sh‐mediated apoptosis in Nalm‐6 cells confirmed by Western blotting and RT‐PCR assays. Further analyses exhibited the generation of reactive oxygen species (ROS) through 6Sh. The current study revealed the in vivo novel anti‐leukaemic role of ginger extract, promoted by MTX. Moreover, 6‐shogaol was introduced as the major player of ginger cytotoxicity through inducing p53 activity and ROS generation.

Ginger (Zingiber officinale Roscoe) is used for a wide array of conditions in traditional medicine in Asia, but little is known about the effect on head and neck cancer. In this study, the effect of two major pharmacologically active compounds of ginger, 6-gingerol and 6-shogaol, were studied on head and neck cancer cell lines. Furthermore, experiments in combination with established treatment methods for head and neck cancer were performed. Proliferation assays showed a dose-dependent reduction of cell viability. Flow cytometry analysis revealed the induction of apoptosis. Western blot analysis indicated that the antiapoptotic protein survivin was suppressed after treatment. Although a combination of 6-shogaol with cisplatin exhibited no synergistic effect, the combination with irradiation showed a synergistic reduction of clonogenic survival. In conclusion, ginger compounds have many noteworthy effects on head and neck cancer cell lines. In particular, the enhancement of radiosensitivity is remarkable.

Tissue culture and mycorrhiza applications can provide disease-free seedlings and enhanced nutrient absorption, respectively, for organic farming. Ginger (Zingiber officinale Roscoe) is rich in phytochemicals and has various health-protective potentials. This study was aimed at determining effects of tissue culture and mycorrhiza applications alone or in combinations in organic farming on phytochemical contents (total phenolics and flavonoids [TP and TF, respectively], gingerol and shogaol homologues, phenolic acids, and carotenoids) and antioxidant capacities (DPPH [2,2-diphenyl-1-picrylhydrazyl] radical scavenging, oxygen radical absorbance (ORAC), and iron-chelating capacities [ICC]) in solvent-extractable (Free) and cell-wall-matrix-bound (Bound) fractions of ginger rhizome and Free fraction of the leaves in comparison with non-organics. Concentrations of the phytochemicals and antioxidant capacities, except for carotenoids and ICC, were significantly higher in organic ginger rhizomes and leaves than in non-organics regardless of the fractions and treatments (P < 0.05). Mycorrhiza application in organic farming significantly increased levels of TP, TF, gingerols, and ORAC in the Free fraction of the rhizome (P < 0.05). Furthermore, the combined application of tissue culture and mycorrhiza significantly increased concentrations of TF and gingerols and ORAC in the Free fraction of the rhizome (P < 0.05), suggesting their synergistic effects. Considerable amounts of phenolics were found in the Bound fractions of the rhizomes. Six-gingerol, ferulic acid, and lutein were predominant ones among gingerols, phenolic acids, and carotenoids, respectively, in ginger rhizomes. The results suggest that organic farming with mycorrhiza and tissue culture applications can increase concentrations of phytochemicals and antioxidant capacities in ginger rhizomes and leaves and therefore improve their health-protective potentials.

In this study, ginger juice powders (GJPs) were obtained from ginger juice using vacuum drying, spray drying, vacuum microwave drying (VMD), and freeze‐drying (FD). The physical properties (water content, dissolving time, and color), chemical compositions (total volatiles, gingerols and shogaol, total phenolic content [TPC]), antioxidant activity, and aerobic bacteria content of the GJPs/redissolved ginger juice were determined and the effect of the drying processes on ginger juice was evaluated. The result showed that FD was optimal at retaining the color, gingerols, shogaol, and total volatiles of the ginger juice, while both VMD and FD could retain a high yield of TPC and the antioxidant activity of the ginger juice. It was also found that all the drying methods were effective in reducing the total aerobic bacteria of the ginger juice. This study proved that the four drying methods had very different effects on the quality of the ginger juice, among which FD was optimal for processing ginger juice. PRACTICAL APPLICATIONS: In this study, four processing methods of ginger juice were compared by investigating the physical properties (water content, dissolving time, and color), chemical compositions (total volatiles, gingerols and shogaol, total phenolic content), antioxidant activity, and aerobic bacteria content of the different ginger juice powers prepared. The results will provide new reference for processing ginger.

Background and purpose Like chili peppers, gingers produce pungent stimuli by a group of vanilloid compounds that activate the nociceptive transient receptor potential vanilloid 1 (TRPV1) ion channel. How these compounds interact with TRPV1 remains unclear. Experimental approach We used computational structural modelling, functional tests (electrophysiology and calcium imaging), and mutagenesis to investigate the structural mechanisms underlying ligand-channel interactions. Key results The potency of three principal pungent compounds from ginger -shogaol, gingerol, and zingerone-depends on the same two residues in the TRPV1 channel that form a hydrogen bond with the chili pepper pungent compound, capsaicin. Computational modelling revealed binding poses of these ginger compounds similar to those of capsaicin, including a "head-down tail-up" orientation, two specific hydrogen bonds, and important contributions of van der Waals interactions by the aliphatic tail. Our study also identified a novel horizontal binding pose of zingerone that allows it to directly interact with the channel pore when bound inside the ligand-binding pocket. These observations offer a molecular level explanation for how unique structures in the ginger compounds affect their channel activation potency. Conclusions and implications Mechanistic insights into the interactions of ginger compounds and the TRPV1 cation channel should help guide drug discovery efforts to modulate nociception.

Background Ginger has been used as an herbal medicine worldwide to relieve nausea/vomiting and gastrointestinal discomfort, but the cellular and molecular mechanisms of its neuronal action remain unclear. The present study aimed to determine the effects of ginger constituent 6-shogaol on gastroesophageal vagal nodose C-fibers. Methods Extracellular single-unit recording and two-photon nodose neuron imaging were performed, respectively, in ex vivo gastroesophageal-vagal preparations from wild type and Pirt-GCaMP6 transgenic mice. The action potential discharge or calcium influx evoked by mechanical distension and chemical perfusions applied to the gastroesophageal vagal afferent nerve endings were recorded, respectively, at their intact neuronal cell soma in vagal nodose ganglia. The effects of 6-shogaol on nodose C-fiber neurons were then compared and determined. Key results Gastroesophageal application of 6-shogaol-elicited intensive calcium influxes in nodose neurons and evoked robust action potential discharges in most studied nodose C-fibers. Such activation effects were followed by a desensitized response to the second application of 6-shogaol. However, action potential discharges evoked by esophageal mechanical distension, after 6-shogaol perfusion, did not significantly change. Pretreatment with TRPA1 selective blocker HC-030031 inhibited 6-shogaol-induced action potential discharges in gastric and esophageal nodose C-fiber neurons, suggesting that TRPA1 played a role in mediating 6-shogaol-induced activation response. Conclusion and inferences This study provides evidence that ginger constituent 6-shogaol directly activates vagal afferent C-fiber peripheral gastrointestinal endings. This activation leads to desensitization to subsequent application of 6-shogaol but not subsequent esophageal mechanical distension. Further investigation is required to establish a possible contribution in its anti-emetic effects.

cope Ginger has long been used in traditional Asian medicine to treat osteoarthritis. Indeed, scientific research has reported that ginger derivatives (GDs) have the potential to control innate immune responses. Given the widespread use and demonstrated properties of GDs, we set out to study their anti-inflammatory and anticatabolic properties in chondrocytes. Methods and results 6-shogaol (6-S), the most active GD, was obtained from ginger. 6-S was not toxic as measured by MTT assay, and inhibited NO production and IL-6 and MCP-1 induced gene expression in LPSbut not in IL-1β-stimulated chondrocytes. 6-S also inhibited LPS-mediated ERK1/2 activation as well as NOS2 and MyD88 induced expression as determined by Western blot. Moreover, zymography revealed that 6-S inhibited matrix metalloproteinases (MMP) 2/9 induction in LPS-treated cells. Hydrated 6-S was modified to obtain a compound (SSi6) without 6-S potential anti-inflammatory properties. Both 6-S and SSi6 inhibited cathepsin-K activity. Conclusion 6-S blocked TLR4-mediated innate immune responses and MMP induction in chondrocytes. These results, together with GDs-mediated cathepsin-K inhibition, suggest the potential for GDs use against cartilage and bone degradation. Therefore, considering that clinical trials involving oral administration of ginger achieved relevant nontoxic GDs serum concentrations, we suggest that a ginger-supplemented diet might reduce OA symptoms.

Neuronal apoptosis induced by oxidative stress is a prominent feature of neurodegenerative disorders. [6]-shogaol, a bio-active compound in ginger, possesses potent anti-inflammatory actions and has recently emerged as a potential therapeutic agent for neurodegenerative disorders. However, the effects of [6]-shogaol on astroglial apoptosis following exogenously induced oxidative stress has not yet been investigated. Here, we show that the anti-apoptotic activity of [6]-shogaol in astrocytes following exposure to hydrogen peroxide (H2O2) involves a marked up-regulation of neurotrophic factors such as nerve growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor. Astrocytes co-treated with [6]-shogaol and H2O2 for 1 h showed decrease in reactive oxygen species production compared with those only treated with H2O2. Moreover, [6]-shogaol counteracted the reduced expression of ERK1/2 in H2O2-treated astrocytes and protected these cells from oxidative stress and apoptosis by attenuating the impairment of mitochondrial function proteins such as Bcl-2 and Bcl-xL. Additionally, [6]-shogaol inhibits the expression of the apoptotic proteins Bax and caspase-3 in H2O2-treated astrocytes. This data suggest that following oxidative stress, [6]-shogaol protects astrocytes from oxidative damage through the up-regulating levels of neurotrophic factors. These findings provide further support for the use of [6]-shogaol as a therapeutic agent in neurodegenerative disorders. Copyright © 2013 John Wiley & Sons, Ltd.

Scope Shogaols, a series of major constituents in dried ginger with the most abundant being [6]-, [8]-, and [10]-shogaols, show much higher anticancer potencies than gingerols. Previously, we reported the mercapturic acid pathway as a major metabolic route for [6]-shogaol in mice. However, it is still unclear how the side chain length affects the metabolism of shogaols and how shogaols are metabolized in humans. Methods and results We first investigate the metabolism of [10]-shogaol in mouse urine, and then investigate the biotransformation of shogaols in human urine. Our results show that eight major thiol-conjugated metabolites of [10]-shogaol were detected in mouse urine, while six major thiol-conjugated metabolites of [6]-shogaol, two thiol-conjugated metabolites of [8]-shogaol, and two thiol-conjugated metabolites of [10]-shogaol were detected in urine collected from human after drinking ginger tea, using LC/ESI-MS/MS. Our results clearly indicate the mercapturic acid pathway is a major metabolic route for [10]-shogaol in mice and for shogaols in human. Furthermore, we also investigated the regulation of glutathione (GSH) by [6]-shogaol in human colon cancer cells HCT-116. Our results show [6]-shogaol, after initially depleting glutathione levels, can subsequently restore and increase GSH levels over time. Conclusion Shogaols are metabolized extensively in mouse and human to form thiol-conjugated metabolites and GSH might play an important role in the cancer-preventive activity of ginger.

Scope There are limited data on the metabolism of [6]-shogaol (6S), a major bioactive component of ginger. This study demonstrates metabolism of 6S in liver microsomes from mouse, rat, dog, monkey, and human. Methods and results The in vitro metabolism of 6S was compared among five species using liver microsomes from mouse, rat, dog, monkey, and human. Following incubations with 6S, three major reductive metabolites 1-(4′-hydroxy-3′-methoxyphenyl)-4-decen-3-ol (M6), 1-(4′-hydroxy-3′-methoxyphenyl)-decan-3-ol (M9), and 1-(4′-hydroxy-3′-methoxyphenyl)-decan-3-one (M11), as well as two new oxidative metabolites (1E,4E)-1-(4′-hydroxy-3′-methoxyphenyl)-deca-1,4-dien-3-one (M14) and (E)-1-(4′-hydroxy-3′-methoxyphenyl)-dec-1-en-3-one (M15) were found in all species. The kinetic parameters of M6 in liver microsomes from each respective species were quantified using Michaelis–Menten theory. A broad CYP-450 inhibitor, 1-aminobenzotriazole, precluded the formation of oxidative metabolites, M14 and M15, and 18β-glycyrrhetinic acid, an aldo-keto reductase inhibitor, eradicated the formation of the reductive metabolites M6, M9, and M11 in all species. Metabolites M14 and M15 were tested for cancer cell growth inhibition and induction of apoptosis and both showed substantial activity, with M14 displaying greater potency than 6S. Conclusion We conclude that 6S is metabolized extensively in mammalian species mouse, rat, dog, monkey, and human, and that there are significant interspecies differences to consider when planning preclinical trials toward 6S chemoprevention.

Scope: Hepatocellular carcinoma is the most common type of liver cancer and is highly metastatic. Metastasis is considered to be the major cause of death in cancer patients. Ginger is a natural dietary rhizome with anti-oxidative, anti-inflammatory, and anti-carcinogenic activities. The aims of this study were to evaluate the anti-invasion activity of 6-shogaol and 6-gingerol, two compounds found in ginger, on hepatoma cells. Methods and results: The migratory and invasive abilities of phorbol 12-myristate 13-acetate (PMA)-treated HepG2 and PMA-untreated Hep3B cells were both reduced in a dose-dependent manner by treatment with 6-shogaol and 6-gingerol. Upon incubation of PMA-treated HepG2 cells and PMA-untreated Hep3B cells with 6-shogaol and 6-gingerol, matrix metalloproteinase (MMP)-9 activity decreased, whereas the expression of tissue inhibitor metalloproteinase protein (TIMP)-1 increased in both cell types. Additionally, urokinase-type plasminogen activator activity was dose-dependently decreased in Hep3B cells after incubation with 6-shogaol for 24 h. Analysis with semi-quantitative reverse transcription-PCR showed that the regulation of MMP-9 by 6-shogaol and 6-gingerol and the regulation of TIMP-1 by 6-shogaol in Hep3B cells may on the transcriptional level. Conclusions: These results suggest that 6-shogaol and 6-gingerol might both exert anti-invasive activity against hepatoma cells through regulation of MMP-9 and TIMP-1 and that 6-shogaol could further regulate urokinase-type plasminogen activity.

We previously reported that 6-shogaol strongly suppressed lipopolysaccharide-induced overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in murine macrophages. In this study, we further compared curcumin, 6-gingerol, and 6-shogaol's molecular mechanism of action and their anti-tumor properties. We demonstrate that topical application of 6-shogaol more effectively inhibited 12-O-tetradecanoylphorbol 13-acetate (TPA)-stimulated transcription of iNOS and COX-2 mRNA expression in mouse skin than curcumin and 6-gingerol. Pretreatment with 6-shogaol has resulted in the reduction of TPA-induced nuclear translocation of the nuclear factor-kappaB subunits. 6-Shogaol also reduced TPA-induced phosphorylation of IkappaBalpha and p65, and caused subsequent degradation of IkappaBalpha. Moreover, 6-shogaol markedly suppressed TPA-induced activation of extracellular signal-regulate kinase1/2, p38 mitogen-activated protein kinase, JNK1/2, and phosphatidylinositol 3-kinase/Akt, which are upstream of nuclear factor-kappaB and AP-1. Furthermore, 6-shogaol significantly inhibited 7,12-dimethylbenz[a]anthracene/TPA-induced skin tumor formation measured by the tumor multiplicity of papillomas at 20 wk. Presented data reveal for the first time that 6-shogaol is an effective anti-tumor agent that functions by down-regulating inflammatory iNOS and COX-2 gene expression in mouse skin. It is suggested that 6-shogaol is a novel functional agent capable of preventing inflammation-associated tumorigenesis.

Ginger, the rhizome of Zingiber officinale, is a traditional medicine with anti-inflammatory and anticarcinogenic properties. This study examined the growth inhibitory effects of the structurally related compounds 6-gingerol and 6-shogaol on human cancer cells. 6-Shogaol [1-(4-hydroxy-3-methoxyphenyl)-4-decen-3-one] inhibits the growth of human cancer cells and induces apoptosis in COLO 205 cells through modulation of mitochondrial functions regulated by reactive oxygen species (ROS). ROS generation occurs in the early stages of 6-shogaol-induced apoptosis, preceding cytochrome c release, caspase activation, and DNA fragmentation. Up-regulation of Bax, Fas, and FasL, as well as down-regulation of Bcl-2 and Bcl-X(L )were observed in 6-shogaol-treated COLO 205 cells. N-acetylcysteine (NAC), but not by other antioxidants, suppress 6-shogaol-induced apoptosis. The growth arrest and DNA damage (GADD)-inducible transcription factor 153 (GADD153) mRNA and protein is markedly induced in a time- and concentration-dependent manner in response to 6-shogaol.

Spinal cord injury (SCI) results in progressive waves of secondary injuries, which via the activation of a barrage of noxious pathological mechanisms exacerbate the injury to the spinal cord. Secondary injuries are associated with edema, inflammation, excitotoxicity, excessive cytokine release, caspase activation and cell apoptosis. This study was aimed at investigating the possible neuroprotective effects of 6-shogaol purified from Zingiber officinale by comparing an experimental SCI rat group with SCI control rats. Shogaol attenuated apoptotic cell death, including poly(ADP-ribose) polymerase activity, and reduced astrogliosis and hypomyelination which occurs in areas of active cell death in the spinal cords of SCI rats. The foremost protective effect of shogaol in SCI would therefore be manifested in the suppression of the acute secondary apoptotic cell death. However, it does not attenuate active microglia and macrophage infiltration. This finding is supported by a lack of histopathological changes in the areas of the lesion in the shogaol-treated SCI rats. Moreover, shogaol-mediated neuroprotection has been linked with shogaol's attenuation of p38 mitogen-activated protein kinase, p-SAPK/JNK and signal transducer, and with transcription-3 activation. Our results demonstrate that shogaol administrated immediately after SCI significantly diminishes functional deficits. The shogaol-treated group recovered hindlimb reflexes more rapidly and a higher percentage of these rats regained responses compared with the untreated injured rats. The overall hindlimb functional improvement of hindlimbs, as measured by the Basso, Beattie and Bresnahan scale, was significantly enhanced in the shogaol-treated group relative to the SCI control rats. Our data show that the therapeutic outcome of shogaol probably results from its comprehensive effects of blocking apoptotic cell death, resulting in the protection of white matter, oligodendrocytes and neurons, and inhibiting astrogliosis. Our finding that the administration of shogaol prevents secondary pathological events in traumatic SCIs and promotes recovery of motor functions in an animal model raises the issue of whether shogaol could be used therapeutically in humans after SCI.

The compound responsible for the pungency of Australian-grown ginger has been extracted using supercritical CO 2 . Methods for analysis of gingerols and shogaols by electrospray-MS have been developed and direct analysis of crude extracts without previous chromatographic separation is shown to be possible by negative ion electrospray-MS. The extracts produced by this procedure are shown to contain about 70 g kg -1 6-gingerol and less than 2 g kg -1 6-shogaol. The low concentration of shogaols, which are degradation products of gingerols, attests to the mild nature of both the extraction and the analytical procedures.

Shogaols, the pungent principle of ginger, exhibit inter- esting bioactivities. Practical preparation of shogaols is highly de- sired. Here we report the protection/deprotection-, salt-, and metal- free synthesis of shogaol in three steps by use of dimethylammoni- um dimethyl carbamate (DIMCARB), in which DIMCARB smoothly promoted Mannich-type condensation of the ketone do- nor with the aldehyde acceptor through the iminium cation interme- diate.

The products of thermal degradation of gingerols, the pungent component of the spice ginger under gas chromatographic conditions have been re-examined. Besides breakdown to zingerone and aldehydes, substantial dehydration of gingerols to shogaols has been established by improved gas chromatographic separation. The identity of the pungent and poorly pungent homologues have been clearly established as (6)- and (8)-, and (10)-gingerols/shogaols resp. Programmed temp. gas chromatography combined with TLC separation has provided a method for determining the ratio of the homologues and a possible method for estimation of gingerols and shogaols in ginger oleoresin. [See FSTA (1978) 10 6T221.]

The pungent principles of ginger —zingerone, gingerol and shogaol— are synthesized starting with vanillin in good yields by utilizing the Lewis acid-promoted cross aldol reaction in each key step.