gingerol and Disease-Models--Animal

Since antiquity, ginger or Zingiber officinale, has been used by humans for medicinal purposes and as spice condiments to enhance flavor in cooking. Ginger contains many phenolic compounds such as gingerol, shogaol and paradol that exhibit antioxidant, anti-tumor and anti-inflammatory properties. The role of ginger and its constituents in ameliorating diseases has been the focus of study in the past two decades by many researchers who provide strong scientific evidence of its health benefit. This review discusses research findings and works devoted to gingerols, the major pungent constituent of ginger, in modulating and targeting signaling pathways with subsequent changes that ameliorate, reverse or prevent chronic diseases in human studies and animal models. The physical, chemical and biological properties of gingerols are also described. The use of ginger and especially gingerols as medicinal food derivative appears to be safe in treating or preventing chronic diseases which will benefit the common population, clinicians, patients, researchers, students and industrialists.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Catechols; Chronic Disease; Disease Models, Animal; Drug Discovery; Fatty Alcohols; Humans; Molecular Structure; Phytotherapy; Plants, Medicinal; Signal Transduction; Structure-Activity Relationship; Zingiber officinale

Gingerols are the major pungent compounds present in the rhizomes of ginger (Zingiber officinale Roscoe) and are renowned for their contribution to human health and nutrition. Medicinal properties of ginger, including the alleviation of nausea, arthritis and pain, have been associated with the gingerols. Gingerol analogues are thermally labile and easily undergo dehydration reactions to form the corresponding shogaols, which impart the characteristic pungent taste to dried ginger. Both gingerols and shogaols exhibit a host of biological activities, ranging from anticancer, anti-oxidant, antimicrobial, anti-inflammatory and anti-allergic to various central nervous system activities. Shogaols are important biomarkers used for the quality control of many ginger-containing products, due to their diverse biological activities. In this review, a large body of available knowledge on the biosynthesis, chemical synthesis and pharmacological activities, as well as on the structure-activity relationships of various gingerols and shogaols, have been collated, coherently summarised and discussed. The manuscript highlights convincing evidence indicating that these phenolic compounds could serve as important lead molecules for the development of therapeutic agents to treat various life-threatening human diseases, particularly cancer. Inclusion of ginger or ginger extracts in nutraceutical formulations could provide valuable protection against diabetes, cardiac and hepatic disorders.

Topics: Animals; Anti-Allergic Agents; Anti-Infective Agents; Anti-Obesity Agents; Antineoplastic Agents, Phytogenic; Catechols; Dietary Supplements; Disease Models, Animal; Fatty Alcohols; Humans; Hypoglycemic Agents; Plants, Medicinal; Zingiber officinale

The 6-Gingerol has significant anti-inflammatory, anti-oxidative and hypolipidemic activities and is widely used for treating cardiac-cerebral vascular diseases. However, the multi-target mechanism of 6-Gingerol in the treatment of atherosclerosis remains to be elucidated.. Firstly, the therapeutic actions of 6-Gingerol anti-atherosclerosis were researched based on an atherosclerotic ApoE-deficient mice model induced by high-fat feed. Then, network pharmacology and molecular docking were employed to reveal the anti-atherogenic mechanism of 6-Gingerol. Finally, the target for these predictions was validated by target protein expression assay in vitro and in vivo experiments and further correlation analysis.. Firstly, 6-Gingerol possessed obvious anti-atherogenic activity, which was manifested by a significant reduction in the plaque area, decrease in the atherosclerosis index and vulnerability index. Secondly, based on network pharmacology, 14 predicted intersection target genes between the targets of 6-Gingerol and atherogenic-related targets were identified. The key core targets of 6-Gingerol anti-atherosclerosis were found to be TP53, RELA, BAX, BCL2, and CASP3. Lipid and atherosclerosis pathways might play a critical role in 6-Gingerol anti-atherosclerosis. Molecular docking results also further revealed that the 6-Gingerol bound well and stable to key core targets from network pharmacological predictions. Then, the experimental results in vivo and in vitro verified that the up-regulation of TP53, RELA, BAX, CASP3, and down-regulation of BCL2 from atherosclerotic ApoE-deficient mice model can be improved by 6-Gingerol intervention. Meanwhile, the correlation analysis further confirmed that 6-Gingerol anti-atherosclerosis was closely related to these targets.. The 6-Gingerol can markedly improve atherosclerosis by modulating key multi-targets TP53, RELA, BAX, CASP3, and BCL2 in lipid and atherosclerosis pathways. These novel findings shed light on the anti-atherosclerosis mechanism of 6-Gingerol from the perspective of multiple targets and pathways.

Topics: Animals; Apolipoproteins E; Atherosclerosis; bcl-2-Associated X Protein; Caspase 3; Disease Models, Animal; Drugs, Chinese Herbal; Fatty Alcohols; Mice; Molecular Docking Simulation; Network Pharmacology

The clinical treatment of ulcerative colitis (UC) faces great challenges due to lifetime medication. In this study, Gingerol oil was extracted and purified by the process easily scale-up and cost effective, with productivity 2.72 ± 0.38% (w/w, versus crude drugs). The quality control of gingerol oil was fully established by HPLC fingerprint with 4 common peaks identified as 6-gingerol, 8-gingerol, 6-shogaol and 10-gingerol. The similarities of 6 batches of gingerol oil are within 0.931-0.999. The protective effects of gingerol oil are equivalent to or even stronger than that of 6-gingerol on inflammation and oxidative stress of HT-29 cells induced by lipopolysaccharide and H

Topics: Animals; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Hydrogen Peroxide; Mice; Mice, Inbred C57BL; Molecular Structure; Rats

Our previous studies demonstrated that autophagy alleviates cerebral I/R injury by inhibiting NLRP3 inflammasome-mediated inflammation. 6-Gingerol, a phenolic compound extracted from ginger, was reported to possess potent antiapoptotic and anti-inflammatory activities and is associated with autophagy. However, the effects of 6-Gingerol in cerebral I/R injury have not been elucidated, and whether they involve autophagy-induced NLRP3 inflammasome inhibition remains unclear.. Adult male Sprague-Dawley (SD) rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h, followed by reperfusion for 24 h. 6-Gingerol and 3-methyladenine (3-MA) were injected intraperitoneally, and si-TRPV1 was injected via the lateral ventricle. Cerebral infarct volume, brain edema, neurological deficits, HE and Nissl were used to evaluate the morphological and functional changes of brain tissue, respectively. TRPV1, FAF1, autophagy related (LC3II/I, P62, Beclin1), inflammation related (NLRP3, cleaved-caspase-1, caspase-1, cleaved-IL-1β, IL-1β, cleaved-IL-18, IL-18) and apoptosis related (Bcl-2, Bax, cleaved-caspase-3) proteins were assessed by Western blot, immunofluorescence staining and coimmunoprecipitation, respectively. Enzyme linked immunosorbent assay (ELISA) was used to evaluate the changes in the expression levels of interleukin-1 (IL-1β) and interleukin-18(IL-18), respectively. The degree of neuronal apoptosis was evaluated by TUNEL staining. Neuronal ultrastructure was examined by transmission electron microscopy.. 6-Gingerol treatment significantly reduced cerebral infarct volume, improved brain edema and neurological scores, and reversed brain histomorphological damage after I/R injury. In addition, 6-Gingerol significantly reduced NLRP3 inflammasome-derived inflammation and neuronal apoptosis and upregulated autophagy. The autophagy inhibitor 3-MA rescued the effects of 6-Gingerol on the NLRP3 inflammasome and apoptosis. Moreover, the findings illustrated that 6-Gingerol inhibited autophagy-induced NLRP3 inflammasome activation and apoptosis through the dissociation of TRPV1 from FAF1.. In brief, 6-Gingerol exerts antiapoptotic and anti-inflammatory effects via TRPV1/FAF1 complex dissociation-mediated autophagy during cerebral I/R injury. Therefore, 6-Gingerol may be an effective drug for the treatment of I/R injury.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Autophagy; Brain; Brain Edema; Catechols; Disease Models, Animal; Fatty Alcohols; Infarction, Middle Cerebral Artery; Inflammasomes; Male; Neuroprotective Agents; NLR Family, Pyrin Domain-Containing 3 Protein; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; TRPV Cation Channels

Ginger is known to have antiinflammatory and antioxidative effects and has traditionally been used as an herbal supplement in the treatment of various chronic diseases. Here, we report antineutrophil properties of 6-gingerol, the most abundant bioactive compound of ginger root, in models of lupus and antiphospholipid syndrome (APS). Specifically, we demonstrate that 6-gingerol attenuates neutrophil extracellular trap (NET) release in response to lupus- and APS-relevant stimuli through a mechanism that is at least partially dependent on inhibition of phosphodiesterases. At the same time, administration of 6-gingerol to mice reduces NET release in various models of lupus and APS, while also improving other disease-relevant endpoints, such as autoantibody formation and large-vein thrombosis. In summary, this study is the first to our knowledge to demonstrate a protective role for ginger-derived compounds in the context of lupus. Importantly, it provides a potential mechanism for these effects via phosphodiesterase inhibition and attenuation of neutrophil hyperactivity.

Topics: Animals; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Catechols; Disease Models, Animal; Extracellular Traps; Fatty Alcohols; Female; Humans; In Vitro Techniques; Lupus Erythematosus, Systemic; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neutrophils; Phosphodiesterase 4 Inhibitors; Phosphodiesterase Inhibitors; Phytotherapy; Reactive Oxygen Species; Venous Thrombosis

Although mechanical ventilation (MV) is indispensable to life-support therapy in critically ill patients, it may promote or aggravatelunginjury known asventilator-inducedlunginjury(VILI). 6-Gingerol is the principal ingredient of ginger with potential anti-inflammatory and antioxidant properties in various diseases. Nevertheless, the role and mechanism of 6-gingerol in the process of VILI has not been explicitly investigated. In the study, we found that pre-treatment with 6-gingerol significantly improved the histological changes and pulmonary oedema, inhibited neutrophil accumulation and the release of early pro-inflammatory cytokines and MPO, and reduced oxidative stress reactions after high MV. Moreover, 6-gingerol treatment also increased PPARγ expression and decreased NF-κB activation in rats subjected to high MV. Furthermore, GW9662, a specific PPARγ inhibitor, was demonstrated to activatethe NF-κB pathway and cancele the protective role of 6-gingerol in VILI. This indicates that 6-gingerol exerted anti-inflammatory and antioxidative stress effects in VILI by activating PPARγ and inhibiting the NF-κBsignalling pathway.

Topics: Animals; Anti-Inflammatory Agents; Catechols; Disease Models, Animal; Fatty Alcohols; Gene Expression Regulation; Male; NF-kappa B; Oxidative Stress; PPAR gamma; Pulmonary Edema; Rats; Rats, Wistar; Signal Transduction; Ventilator-Induced Lung Injury

Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is an inherited neuromuscular disorder that causes loss of muscle mass and motor skills. In the era of genomic medicine, there is still no known cure for DMD. In clinical practice, there is a growing awareness of the possible importance of nutrition in neuromuscular diseases. This is mostly the result of patients' or caregivers' empirical reports of how active substances derived from food have led to improved muscle strength and, thus, better quality of life. In this report, we investigate several nutraceutical principles in the

Topics: Animals; Catechols; Dietary Fiber; Dietary Supplements; Disease Models, Animal; Dystrophin; Fatty Alcohols; Female; Heme Oxygenase-1; Larva; Locomotion; Male; Muscle Strength; Muscle, Skeletal; Muscular Dystrophy, Duchenne; Quality of Life; Zebrafish

The development of nonalcoholic fatty liver disease (NAFLD) can be modulated by microRNAs (miRNA). Dietary polyphenols modulate the expression of miRNA such as miR-467b-3p in the liver. In addition, 6-gingerol (6-G), the functional polyphenol of ginger, has been reported to ameliorate hepatic steatosis; however, the exact mechanism involved and the role of miRNA remain elusive. In this study, we assessed the role of miR-467b-3p in the pathogenesis of hepatic steatosis and the regulation of miR-467b-3p by 6-G through the hepatocyte nuclear factor 4α (HNF4α).. miR-467b-3p expression was measured in free fatty acid (FFA)-treated hepatocytes or liver from high-fat diet (HFD)-fed mice. Gain- or loss-of-function of miR-467b-3p was induced using miR-467b-3p-specific miRNA mimic or miRNA inhibitor, respectively. 6-G was exposed to FFA-treated cells and HFD-fed mice. The HNF4α/miR-467b-3p/GPAT1 axis was measured in mouse and human fatty liver tissues.. We found that miR-467b-3p was down-regulated in liver tissues from HFD-fed mice and in FFA-treated Hepa1-6 cells. Overexpression of miR-467b-3p decreased intracellular lipid accumulation in FFA-treated hepatocytes and mitigated hepatic steatosis in HFD-fed mice via negative regulation of glycerol-3-phosphate acyltransferase-1 (GPAT1). In addition, miR-467b-3p up-regulation by 6-G was observed. 6-G inhibited FFA-induced lipid accumulation and mitigated hepatic steatosis. Moreover, it increased the transcriptional activity of HNF4α, resulting in the increase of miR-467b-3p and subsequent decrease of GPAT1. HNF4α/miR-467b-3p/GPAT1 signaling also was observed in human samples with hepatic steatosis.. Our findings establish a novel mechanism by which 6-G improves NAFLD. This suggests that targeting of the HNF4α/miR-467b-3p/GPAT1 cascade may be used as a potential therapeutic strategy to control NAFLD.

Topics: 1-Acylglycerol-3-Phosphate O-Acyltransferase; Animals; Catechols; Disease Models, Animal; Fatty Alcohols; Gene Expression; Gene Expression Regulation; Genes, Reporter; Hepatocyte Nuclear Factor 4; Humans; Lipid Metabolism; Male; Mice; MicroRNAs; Non-alcoholic Fatty Liver Disease; RNA Interference; Structure-Activity Relationship

Rheumatoid arthritis is an inflammatory arthropathy, autoimmune in nature, leading to disability of joints involving structural destruction of articular bone and cartilage due to inflammation in synovium resulting in joint stiffness, swelling and pain. Nanomedicine has played a crucial role in improving the efficacy of treatment by controlling the release of pharmacologically active ingredients to increase bioavailability and achieve uniform and targeted delivery of drug. In this study, we prepared celecoxib, gingerol and oleanic acid loaded PLGA nanoparticles by solvent evaporation method and nanoparticles were characterized by particle size, zeta potential, polydispersity index, entrapement efficiency and FTIR. FCA is induced in right hand paw of rats for induction of arthritis. Celecoxib, gingerol and oleanic acid loaded PLGA nanoparticles coated with chitosan were given orally to rats for the evaluation of anti-arthritic effect of this nanoformulation in rats. Animals were divided into six groups for 21 days trial. On 21st day blood samples were collected for evaluation of hematological and lipid profile parameters. The data was subjected to statistical analysis by applying one way ANOVA and tukey test. At the end of study it was concluded that PLGA loaded celecoxib, gingerol and oleanic acid coated with chitosan have excellent effects in minimizing the side effects and increasing the therapeutic efficacy of drugs.

Topics: Administration, Oral; Animals; Antirheumatic Agents; Arthritis, Rheumatoid; Catechols; Celecoxib; Disease Models, Animal; Fatty Alcohols; Nanoparticle Drug Delivery System; Oleanolic Acid; Rats

When Zika virus emerged as a public health emergency there were no drugs or vaccines approved for its prevention or treatment. We used a high-throughput screen for Zika virus protease inhibitors to identify several inhibitors of Zika virus infection. We expressed the NS2B-NS3 Zika virus protease and conducted a biochemical screen for small-molecule inhibitors. A quantitative structure-activity relationship model was employed to virtually screen ∼138,000 compounds, which increased the identification of active compounds, while decreasing screening time and resources. Candidate inhibitors were validated in several viral infection assays. Small molecules with favorable clinical profiles, especially the five-lipoxygenase-activating protein inhibitor, MK-591, inhibited the Zika virus protease and infection in neural stem cells. Members of the tetracycline family of antibiotics were more potent inhibitors of Zika virus infection than the protease, suggesting they may have multiple mechanisms of action. The most potent tetracycline, methacycline, reduced the amount of Zika virus present in the brain and the severity of Zika virus-induced motor deficits in an immunocompetent mouse model. As Food and Drug Administration-approved drugs, the tetracyclines could be quickly translated to the clinic. The compounds identified through our screening paradigm have the potential to be used as prophylactics for patients traveling to endemic regions or for the treatment of the neurological complications of Zika virus infection.

Topics: Animals; Antiviral Agents; Artificial Intelligence; Chlorocebus aethiops; Disease Models, Animal; Drug Evaluation, Preclinical; High-Throughput Screening Assays; Immunocompetence; Inhibitory Concentration 50; Methacycline; Mice, Inbred C57BL; Protease Inhibitors; Quantitative Structure-Activity Relationship; Small Molecule Libraries; Vero Cells; Zika Virus; Zika Virus Infection

Sepsis is a major cause of death for ICU patients. Sepsis development depends heavily on the presence of mature IL-1β cytokine. This study evaluates the potential therapeutic properties of a bioactive compound known as 6-gingerol on sepsis. This compound has previously been demonstrated to possess anti-inflammatory properties both in vivo and in vitro.. C57BL/6 mice was used to establish models of sepsis by means of cecal ligation and puncture (CLP). Upon treatment with 6-gingerol, we assessed the survival rate of mice and measured the levels of key pro-inflammatory cytokines in serum and colon tissues. Sepsis pathogenesis was further explored using the RAW264.7 cell line and bone marrow-derived macrophages (BMDMs) treated with ATP and lipopolysaccharide (LPS). The impact of 6-gingerol on pyroptosis was also examined. In addition, we assessed the role of MAPK signaling in 6-gingerol-induced effects in BMDMs and RAW264.7 cells.. In CLP mice, 6-gingerol significantly ameliorated sepsis development, which was associated with the reduction of serum IL-1β. In BMDMs and RAW264.7 cells, 6-gingerol strongly attenuated pyroptosis as well as the release of caspase-1p20, HMGB1, mature IL-1β, IL-18 in response to ATP and LPS treatment. 6-Gingerol conferred these effects by blocking MAPK activation. Exposure to an ERK agonist (EGF) reversed effects of 6-gingerol, causing pyroptosis, LDH and caspase-1p20 release.. By targeting MAPK signaling, 6-gingerol significantly suppressed secretion of pro-inflammatory cytokines and inhibited macrophage cells pyroptosis resulting in overall inhibition of sepsis development.

Topics: Adenosine Triphosphate; Animals; Caspase 1; Catechols; Cytokines; Disease Models, Animal; Epidermal Growth Factor; Fatty Alcohols; HMGB1 Protein; Interleukin-18; Interleukin-1beta; Lipopolysaccharides; Macrophages; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Prognosis; Pyroptosis; RAW 264.7 Cells; Sepsis

Sepsis-induced liver injury is very common in intensive care units. Here, we investigated the effects of 6-gingerol on sepsis-induced liver injury and the role of the Nrf2 pathway in this process. 6-Gingerol is the principal ingredient of ginger that exerts anti-inflammatory and antioxidant effects. Using cecal ligation and puncture (CLP) to induce polymicrobial sepsis and related liver injury, we found that mice pre-treated with 6-Gingerol showed less incidences of severe liver inflammation and death than untreated CLP groups. 6-Gingerol administration also inhibited the expression of pyroptosis-related proteins, including NOD-like receptor protein 3 (NLRP3), IL-1β, and caspase-1. Consistent with these findings, 6-gingerol reduced the effects of pyroptosis induced by lipopolysaccharide (LPS) and adenosine 5'-triphosphate (ATP) in RAW 264.7 cells, as evidenced by IL-1β and caspase-1 protein levels in the supernatant and propidium iodide (PI) staining. 6-Gingerol was shown to activate the Nrf2 pathway in vivo and in vitro. Notably, Nrf2 siRNA transfection nullified the inhibitory effects of 6-gingerol on pyroptosis in vitro. In summary, these findings suggested that 6-gingerol alleviated sepsis-induced liver injury by inhibiting pyroptosis through the Nrf2 pathway.

Topics: Animals; Catechols; Disease Models, Animal; Fatty Alcohols; Gene Knockdown Techniques; Humans; Liver; Liver Failure, Acute; Male; Mice; NF-E2-Related Factor 2; Pyroptosis; RAW 264.7 Cells; RNA, Small Interfering; Sepsis; Signal Transduction

Higenamine (HG) is a natural benzylisoquinoline alkaloid isolated from Aconitum with positive inotropic and chronotropic effects. This study aimed to investigate the possible cardioprotective effects of HG combined with [6]-gingerol (HG/[6]-GR) against DOX-induced chronic heart failure (CHF) by comprehensive approaches. DOX-induced cardiotoxicity model in rats and H9c2 cells was established. Therapeutic effects of HG/[6]-GR on haemodynamics, serum indices and histopathology of cardiac tissue were analysed. Cell mitochondrial energy phenotype and cell mitochondrial fuel flex were measured by a Seahorse XFp analyser. Moreover, UHPLC-Q-TOF/MS was performed to explore the potential metabolites affecting the therapeutic effects and pathological process of CHF. To further investigate the potential mechanism of HG/[6]-GR, mRNA and protein expression levels of RAAS and LKB1/AMPK/Sirt1-related pathways were detected. The present data demonstrated that the therapeutic effects of HG/[6]-GR combination on CHF were presented in ameliorating heart function, down-regulation serum indices and alleviating histological damage of heart tissue. Besides, HG/[6]-GR has an effect on increasing cell viability of H9c2 cells, ameliorating DOX-induced mitochondrial dysfunction and elevating mitochondrial OCR and ECAR value. Metabolomics analyses showed that the therapeutic effect of HG/[6]-GR combination is mainly associated with the regulation of fatty acid metabolites and energy metabolism pathways. Furthermore, HG/[6]-GR has an effect on down-regulating RAAS pathway-related molecules and up-regulating LKB1/AMPKα/Sirt1-related pathway. The present work demonstrates that HG/[6]-GR prevented DOX-induced cardiotoxicity via the cardiotonic effect and promoting myocardial energy metabolism through the LKB1/AMPKα/Sirt1 signalling pathway, which promotes mitochondrial energy metabolism and protects against CHF.

Topics: Aconitum; Alkaloids; Animals; Cardiotoxicity; Catechols; Chronic Disease; Disease Models, Animal; Doxorubicin; Energy Metabolism; Fatty Alcohols; Heart; Heart Failure; Male; Mitochondrial Diseases; Myocytes, Cardiac; Rats; Tetrahydroisoquinolines

Neuroinflammation is critical for the pathogenesis of ischemia brain damage. Over-activated microglia-mediated inflammation plays a very important role in ischemia cerebral injuries. 6-Gingerol, obtained from edible ginger (Zingiber Officinale) exhibits protective effects against inflammation. In this study, we found that 6-Gingerol could reduce the size of infarction (P = 0.0184) and improve neurological functions (P = 0.04) at the third day after ischemic brain injury in vivo. Since 6-Gingerol has the anti-inflammatory effects, we further investigated its impacts on neuroinflammation mediated by microglia both in vivo and in vitro. We found that the levels of pro-inflammatory cytokines Interleukin-1 beta (IL-1β, P = 0.0213), Interleukin-6 (IL-6, P = 0.0316), and inducible NO synthase (iNOS, P = 0.0229) in the infarct penumbra were lower in 6-Gingerol treated groups. Furthermore, microglia induced pro-inflammatory cytokines, such as IL-6, IL-1β, incremental intercellular nitric oxide (NO), as well as iNOS were blocked by the treatment of 6-Gingerol in lipopolysaccharide (LPS) stimulated microglia. In terms of mechanism, 6-Gingerol potently suppressed phosphorylation of serine-threonine protein kinase (Akt) - mammalian target of rapamycin (mTOR) - signal transducer and activator of transcription 3 (STAT3) in LPS-treated microglia. Taken together, the present study suggested that 6-Gingerol improved cerebral ischemia injury by suppressing microglia-mediated neuroinflammation by down-regulating Akt-mTOR-STAT3 pathway.

Topics: Animals; Anti-Inflammatory Agents; Brain; Catechols; Cells, Cultured; Disease Models, Animal; Fatty Alcohols; Infarction, Middle Cerebral Artery; Inflammation Mediators; Ischemic Stroke; Male; Mice, Inbred C57BL; Microglia; Neuroprotective Agents; Phosphorylation; Proto-Oncogene Proteins c-akt; Signal Transduction; STAT3 Transcription Factor; TOR Serine-Threonine Kinases

The currently available anti-tuberculosis treatment (ATT) comprises exclusively of anti-bacterial drugs, is very lengthy, has adverse side effects on the host and leads to the generation of drug-resistant variants. Therefore, a combination therapy directed against the pathogen and the host is required to counter tuberculosis (TB). Here we demonstrate that [6]-Gingerol, one of the most potent and pharmacologically active ingredients of ginger restricted mycobacterial growth inside the lungs, spleen and liver of mice infected with Mycobacterium tuberculosis (Mtb). The spleen of [6]-Gingerol treated mice displayed increased expression of pro-inflammatory cytokines and enhanced Th1/Th17 responses confirming the immunomodulatory action of [6]-Gingerol. Finally, [6]-Gingerol displayed an excellent potential as an adjunct drug, along with front line anti-TB drug isoniazid. Interestingly, [6]-Gingerol displayed stark anti-tubercular activity against dormant/starved bacilli and drug-resistant variants of Mtb. Taken together, these results indicate strong prospects of [6]-Gingerol as an adjunct anti-mycobacterial and immunomodulatory drug for the treatment of drug-susceptible and drug-resistant strains of TB.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Catechols; Chemotherapy, Adjuvant; Disease Models, Animal; Fatty Alcohols; Female; Humans; Immunomodulation; Isoniazid; Mice; Mice, Inbred C57BL; Mycobacterium tuberculosis; Th1 Cells; Th17 Cells; Tuberculosis; Zingiber officinale

The persistent inflammation and oxidative stress at the local site in ulcerative colitis reportedly extend to the testes via systemic circulation resulting in testicular dysfunction. The influence of 6-gingerol (6G), a phenolic compound isolated from Zingiber officinale, on colitis-mediated testicular dysfunction in mice was investigated in this study. Chronic ulcerative colitis was induced in mice using 2.5% dextran sulfate sodium (DSS) in drinking water for three cycles. Each cycle consisted of 7 consecutive days of exposure to DSS-treated water followed by 14 consecutive days of normal drinking water. 6G (100 mg/kg) or sulfasalazine (SZ; 100 mg/kg) was orally administered alone or in combination with DSS-treated water during the three cycles. SZ served as standard reference drug for colitis in this study. 6G significantly prevented the incidence of rectal bleeding, decrease in the body weight gain and colon mass index in DSS-exposed mice. 6G significantly prevented colitis-mediated decreases in luteinizing hormone, follicle-stimulating hormone and testosterone and decreases oxidative stress indices, pro-inflammatory cytokines and caspase-3 activity with concomitant augmentation of antioxidant enzymes activities, sperm characteristics, marker enzymes of testicular function and histoarchitecture in DSS-exposed mice. 6G exerted protective influence against ulcerative colitis-induced testicular damage via mechanisms involving its antioxidant and anti-inflammatory properties.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Caspase 3; Catechols; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Fatty Alcohols; Follicle Stimulating Hormone; Inflammation Mediators; Luteinizing Hormone; Male; Mice, Inbred BALB C; Oxidative Stress; Spermatozoa; Testicular Diseases; Testis; Testosterone

The deterioration of male reproductive health may represent an outcome of an active disease and environmental factors. The present study investigated the modulatory role of [6]-gingerol in spermatotoxicity resulting from colitis and benzo[a]pyrene (B[a]P), an environmental and food-borne pollutant.. Group I (control) mice received corn oil alone, while group II ([6]-gingerol alone) mice orally received [6]-gingerol alone at 100 mg/kg body weight. Group III [benzo[a]pyrene+dextran sulfate sodium (BDS) alone] mice were orally exposed to B[a]P at 125 mg/kg for 7 days followed by three cycles of 4% dextran sulfate sodium (DSS) in drinking water. A cycle consisted of seven consecutive days of exposure to DSS-treated water followed by 14 consecutive days of normal drinking water. Group IV (BDS+[6]-gingerol) mice were orally treated daily with 100 mg/kg of [6]-gingerol during exposure to B[a]P and DSS in the same manner as those of group III.. [6]-Gingerol significantly abrogated BDS-mediated increase in disease activity index and restored the colon wet weight, colon length and colon mass index to near normal when compared to BDS alone group. Moreover, [6]-gingerol significantly prevented BDS-induced decreases in the daily sperm production (DSP), testicular sperm number (TSN), epididymal sperm number, sperm progressive motility and sperm membrane integrity when compared with the control. [6]-Gingerol markedly increased the sperm antioxidant enzymes activities and decreased the sperm head, mid-piece and tail abnormalities as well as suppressed oxidative stress and inflammatory biomarkers in BDS-exposed mice.. [6]-Gingerol protected against spermatotoxicity in experimental model of interaction of colitis with environmental pollutant B[a]P.

Topics: Animals; Benzo(a)pyrene; Catechols; Colitis, Ulcerative; Dextran Sulfate; Disease Models, Animal; Fatty Alcohols; Male; Mice; Mice, Inbred BALB C; Oxidative Stress; Sperm Motility; Spermatozoa

Acute kidney injury (AKI) and metabolic dysfunction are critical complications in sepsis syndrome; however, their pathophysiological mechanisms remain poorly understood. Therefore, we evaluated whether the pharmacological properties of 6-gingerol (6G) and 10-gingerol (10G) could modulate AKI and metabolic disruption in a rat model of sepsis (faecal peritonitis). Animals from the sham and AKI groups were intraperitoneally injected with 6G or 10G (25 mg/kg). Septic AKI decreased creatinine clearance and renal antioxidant activity, but enhanced oxidative stress and the renal mRNA levels of tumour necrosis factor-α, interleukin-1β, and transforming growth factor-β. Both phenol compounds repaired kidney function through antioxidant activity related to decreased oxidative/nitrosative stress and proinflammatory cytokines. Metabolomics analysis indicated different metabolic profiles for the sham surgery group, caecal ligation and puncture model alone group, and sepsis groups treated with gingerols.

Topics: Acute Kidney Injury; Animals; Catechols; Dimethyl Sulfoxide; Dimethylamines; Disease Models, Animal; Fatty Alcohols; Feces; Humans; Injections, Intraperitoneal; Male; Metabolome; Metabolomics; Oxidative Stress; Peritonitis; Rats; Rats, Wistar; Sepsis; Sulfones; Survival Analysis; Treatment Outcome

Screening active constituents of traditional Chinese medicines (TCMs) is vital for lead compound discovery. Sini decoction (SND) is a well-known TCM formula for relieving myocardial ischemia (MI) in clinic. Due to complex nature, the effective compounds of SND are still unknown. In this study, a novel "system to system" strategy based on the correlation of drug-related and drug-induced ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOFMS) serum metabolomic profiles was developed to discover bioactive compounds of SND against isoproterenol-induced MI. Thirteen SND-induced metabolites and 19 SND-related metabolites were identified by UHPLC-Q-TOFMS coupled with S-plot and SUS-plot of orthogonal projection to latent structure-discriminant analysis (OPLS-DA) models, respectively. Canonical correlation analysis between the SND-induced and SND-related metabolites revealed that 12 compounds had strongly correlated relationship with the protective effect of SND on MI, and these compounds include isotalatizidine, songorine, fuziline, neoline, talatizamine, 14-acetyltalatizamine, liquiritigenin, benzoylmesaconitine, isoliquiritin, benzoylaconitne, benzoylhypaconitine and 6-gingerol. Combination functional enrichment analysis and network topology analysis revealed that the targeted metabolic pathways of these correlated compounds were involved in valine, leucine and isoleucine biosyntheses, tryptophan metabolism, glycerophospholipid metabolism and sphingolipid metabolism. The results demonstrated that the "system to system" strategy may be a high-throughput method to discover potentially effective compounds from TCMs.

Topics: Aconitine; Alkaloids; Animals; Aspartate Aminotransferases; Catechols; Chalcone; Chromatography, High Pressure Liquid; Creatine Kinase; Disease Models, Animal; Drugs, Chinese Herbal; Fatty Alcohols; Flavanones; Glucosides; L-Lactate Dehydrogenase; Lipid Peroxidation; Male; Malondialdehyde; Mass Spectrometry; Metabolome; Myocardial Ischemia; Rats; Rats, Sprague-Dawley; Superoxide Dismutase

6-Gingerol, the major component of gingerols extracted from Zingiber officinale, has been shown to exhibit anti-inflammatory and antioxidant bioactivities. Since neuroinflammation plays an important role in neurodegenerative diseases, such as Alzheimer's disease (AD), and astrocytes have been considered important in the process of neurodegeneration, it was of interest to know whether 6-gingerol reduced astrocytes activation or even attenuated cognitive impairment. Here we examined the neuroprotective effects of 6-gingerol in lipopolysaccharide (LPS)-induced disorder models both in vitro and in vivo. C6 astroglioma cells treated with LPS were found to release excessive pro-inflammatory cytokines, including TNF-α and IL-6, and also increase intercellular ROS, NO, and iNOS (i.e. NOS2). All these were blocked by 6-gingerol in a concentration-dependent manner. The spatial learning and memory of rats challenged with LPS (10 μg, i.c.v.) in the absence or presence of 6-gingerol were evaluated using the Morris water-maze (MWM) test. 6-Gingerol attenuated LPS-induced imapirement of MWM learning and memory in a dose-dependent manner. Besides, 6-gingerol inhibited LPS-induced increases in levels of GFAP and TNF-α in the rat brain. The results suggest that 6-gingerol suppresses astrocyte overactivation, through which it contributes to improvement of cognitive ability.

Topics: Animals; Astrocytes; Catechols; Cognitive Dysfunction; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Fatty Alcohols; Glial Fibrillary Acidic Protein; Inflammation; Inflammation Mediators; Lipopolysaccharides; Male; Maze Learning; Memory; Memory Disorders; Neurodegenerative Diseases; Neuroprotective Agents; Rats; Rats, Sprague-Dawley

Gingerol is a major dietary compound that occurs in several plants belonging to the Zingiberaceae family. In the current study, the protective effect of gingerol on STZ-induced sporadic Alzheimer's disease (SAD) was determined. Gingerol was isolated from the seeds of Aframomum melegueta K. Schum and tested at doses of 10 and 20 mg/kgbwt for its possible effect on the SAD model in mice, using celecoxib (30 mg/kg bwt) as a reference standard. The curative effects of gingerol were assessed through measurement of β-amyloid (Aβ-42), α-, β- secretases, APH1a and COX-2 levels. In addition, improvement in the cognitive deficit in mice after treatment was confirmed using the water maze and Y-maze with intra-maze cues. Gingerol improved the cognitive and behavioral impairment and AD-like pathology in streptozotocin model mice. These beneficial effects occurred with an increase in α-secretase activity and a decrease in cerebral Aβ-42, β- secretase, APH1a activity and COX-2-linked neuro-inflammation.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid Precursor Protein Secretases; Animals; Catechols; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Disease Models, Animal; Enzyme Activation; Fatty Alcohols; Immunohistochemistry; Maze Learning; Mice; Protective Agents; Streptozocin

Ulcerative colitis is one of the most common types of inflammatory bowel disease and is multifactorial and relapsing. 6-Gingerol, a component of gingerols extracted from ginger (Zingiber officinale), has been reported to improve ulcerative colitis. The present study aims to investigate the therapeutic efficacy of two analogous forms of 6-gingerol, 8-gingerol, and 10-gingerol, on ulcerative colitis. Colitis was induced in rats through consumption of 5% (w/v) dextran sulfate sodium drinking water for 7 consecutive days. 6-Gingerol, 8-gingerol, and 10-gingerol were then given intraperitoneally at doses of 30 mg kg

Topics: Animals; Catechols; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Fatty Alcohols; Interleukin-1beta; Intestinal Mucosa; Male; Malondialdehyde; Oxidative Stress; Peroxidase; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Tumor Necrosis Factor-alpha

5-Fluorouracil (5-FU) is widely used as an anti cancer drug and is known to cause severe diarrhea. Recently we suggested that levels of chemokine (C-X-C motif) ligand 1 (CXCL1) and neutrophil recruitment in the colonic mucosa were drastically increased by the 5-FU administration in mice. Hange-shashin-to (HST) is prescribed in Japan for treat gastritis, stomatitis, and inflammatory diarrhea. We therefore examined the effects of HST and its active ingredients on 5-FU-induced CXCL1 upregulation in cultured colon tissue, and also examined the effects of HST on 5-FU-induced diarrhea development in the mouse. The distal colon isolated from the mouse was incubated with 5-FU and HST. Mice were given 5-FU (50 mg/kg, intraperitoneally (i.p.)) daily for four days. HST (300 mg/kg, per os (p.o.)) was administered 30 min before mice received 5-FU. mRNA levels of CXCL1 in the colon were examined using quantitative RT-PCR. 5-FU enhanced CXCL1 mRNA in the colon but the effect by 5-FU was markedly suppressed by application of HST and its active ingredients, baicalein and 6-gingerol. Nuclear factor kappa B (NF-κB) was activated by 5-FU treatment in cultured colon tissue, which was also suppressed by HST and the combination of baicalein and 6-gingerol. Furthermore, HST reduced 5-FU-induced diarrhea development. Under such experimental condition, CXCL1 gene, protein levels of neutrophil elastase and myeloperoxidase upregulation induced by 5-FU in the colon was attenuated by HST. These findings suggest that HST, especially baicalein and 6-gingerol, prevent the development of neutrophil recruitment and diarrhea by the inhibition of NF-κB activity.

Topics: Animals; Antimetabolites, Antineoplastic; Catechols; Chemokine CXCL1; Colon; Diarrhea; Disease Models, Animal; Drugs, Chinese Herbal; Fatty Alcohols; Flavonoids; Fluorouracil; Humans; Intestinal Mucosa; Japan; Male; Mice; Mice, Inbred C57BL; Neoplasms; NF-kappa B; RNA, Messenger; Up-Regulation

Protandim and 6-gingerol, two potent nutraceuticals, have been shown to decrease free radicals production through enhancing endogenous antioxidant enzymes. In this study, we evaluated the effects of these products on the expression of different factors involved in osteoarthritis (OA) process. Human OA chondrocytes were treated with 1 ng/ml IL-1β in the presence or absence of protandim (0-10 μg/ml) or 6-gingerol (0-10 μM). OA was induced surgically in mice by destabilization of the medial meniscus (DMM). The animals were treated weekly with an intraarticular injection of 10 μl of vehicle or protandim (10 μg/ml) for 8 weeks. Sham-operated mice served as controls. In vitro, we demonstrated that protandim and 6-gingerol preserve cell viability and mitochondrial metabolism and prevented 4-hydroxynonenal (HNE)-induced cell mortality. They activated Nrf2 transcription factor, abolished IL-1β-induced NO, PGE

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Catechols; Cell Survival; Cells, Cultured; Chondrocytes; Dietary Supplements; Disease Models, Animal; Drugs, Chinese Herbal; Fatty Alcohols; Glutathione Transferase; Humans; Injections, Intra-Articular; Interleukin-1beta; Mice; NF-E2-Related Factor 2; Osteoarthritis; Signal Transduction

This study was to investigate the mechanism of gingerols antagonizing the inflammatory effect of toxic raphides from Pinella pedatisecta. Mice peritonitis models induced by toxic raphides from P. pedatisecta were applied to observe the effect of gingerols on inflammatory mediators PGE2 in the exudates of abdominal inflammation in mice; rats peritoneal macrophage in vitro culture models were adopted to study the anti-inflammatory effects of gingerol against toxic raphides, with TNF-α and IL-1β in supernatant as indexes. Scanning electron microscopy was used to observe the changes in surface morphology of macrophages treated by raphides and gingerols. Macrophages-neutrophils co-cultured models were used to study the antagonism of gingerols against the effect of toxic raphides' stimulation on neutrophils migration. Results showed that gingerols could significantly inhibit the production of PGE2 in the exudates of abdominal inflammation induced by toxic raphides from P. pedatisecta in mice. Gingerols could significantly inhibit the toxic raphides from P. pedatisecta to induce the release of inflammatory factors, with certain dose dependence. Scanning electron microscopy showed that gingerols could significantly inhibit phagocytosis of macrophages, cytomembrane injury, and neutrophils migration induced by toxic raphides from P. pedatisecta. The results showed that the antagonism mechanism of gingerols against the toxic raphides from P. pedatisecta may be associated with inhibiting the pro-inflammatory toxicity including macrophage activation, inflammatory factors release, and neutrophils migration.

Topics: Animals; Anti-Inflammatory Agents; Catechols; Disease Models, Animal; Drug Antagonism; Drugs, Chinese Herbal; Fatty Alcohols; Humans; Inflammation; Interleukin-1beta; Macrophages; Male; Mice; Mice, Inbred ICR; Neutrophils; Phagocytosis; Pinellia; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

The incidence of allergies has recently been increasing worldwide. Immunoglobulin E (IgE)-mediated hypersensitivity is central to the pathogenesis of asthma, hay fever and other allergic diseases. Ginger (Zingiber officinale Roscoe) and its extracts have been valued for their medical properties including antinausea, antiinflammation, antipyresis and analgesia properties. In this study, we investigated the antiallergic effects of ginger and 6-gingerol, a major compound of ginger, using a mouse allergy model and primary/cell line culture system. In mice with ovalbumin (OVA)-induced allergic rhinitis, oral administration of 2% ginger diet reduced the severity of sneezing and nasal rubbing by nasal sensitization of OVA and suppressed infiltration of mast cells in nasal mucosa and secretion of OVA-specific IgE in serum. 6-Gingerol inhibited the expression of not only Th2 cytokines but also Th1 cytokines in OVA-sensitized spleen cells. Accordingly, 6-gingerol suppressed in vitro differentiation of both Th1 cells and Th2 cells from naïve T cells. In addition, 6-gingerol suppressed both superantigen staphylococcal enterotoxin B (SEB)- and anti-CD3-induced T cell proliferation. 6-Gingerol also abrogated PMA plus ionomycin- and SEB-induced IL-2 production in T cells, suggesting that 6-gingerol affected T cell receptor-mediated signal transduction rather than the antigen-presentation process. Indeed, 6-gingerol inhibited the phosphorylation of MAP kinases, calcium release and nuclear localization of c-fos and NF-κB by PMA and ionomycin stimulation. Thus, our results demonstrate that 6-gingerol suppresses cytokine production for T cell activation and proliferation, thereby not causing B cell and mast cell activation and resulting in prevention or alleviation of allergic rhinitis symptoms.

Topics: Animals; Calcium; Catechols; Cell Nucleus; Cell Proliferation; Cytokines; Disease Models, Animal; Fatty Alcohols; Female; Humans; Jurkat Cells; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases; Phosphorylation; Rhinitis, Allergic; T-Lymphocytes; Zingiber officinale

Both gingerol and capsaicin are agonists of TRPV1, which can negatively control tumor progression. This study observed the long-term effects of oral administration of 6-gingerol alone or in combination with capsaicin for 20 weeks in a urethane-induced lung carcinogenic model. We showed that lung carcinoma incidence and multiplicity were 70% and 21.2 ± 3.6, respectively, in the control versus 100% and 35.6 ± 5.2 in the capsaicin group (P < 0.01) and 50% and 10.8 ± 3.1 in the 6-gingerol group (P < 0.01). The combination of 6-gingerol and capsaicin reversed the cancer-promoting effect of capsaicin (carcinoma incidence of 100% versus 20% and multiplicity of 35.6 ± 5.2 versus 4.7 ± 2.3; P < 0.001). The cancer-promoting effect of capsaicin was due to increased epidermal growth-factor receptor (EGFR) level by decreased transient receptor potential vanilloid type-1 (TRPV1) level (P < 0.01) . The capsaicin-decreased EGFR level subsequently reduced levels of nuclear factor-κB (NF-κB) and cyclin D1 that favored enhanced lung epithelial proliferation and epithelial-mesenchymal transition (EMT) during lung carcinogenesis (P < 0.01). In contrast, 6-gingerol promoted TRPV1 level and drastically decreased the levels of EGFR, NF-κB, and cyclin D1 that favored reduced lung epithelial proliferation and EMT (P < 0.01). This study provides valuable information for the long-term consumption of chili-pepper-rich diets to decrease the risk of cancer development.

Topics: Animals; Capsaicin; Carcinogenesis; Catechols; Disease Models, Animal; ErbB Receptors; Fatty Alcohols; Female; Humans; Lung Neoplasms; Mice; Mice, Inbred ICR; NF-kappa B; TRPV Cation Channels; Urethane

Gingerols are phenolic compounds in ginger (Zingiber officinale), which have been reported to exhibit antiinflammatory, antioxidant, and anticancer properties. The present study aimed at evaluating the possible pharmacologic activity of 6-gingerol in a mouse model of dextran sulphate sodium (DSS)-induced ulcerative colitis. Adult male mice were exposed to DSS in drinking water alone or co-treated with 6-gingerol orally at 50, 100, and 200 mg/kg for 7 days. Disease activity index, inflammatory mediators, oxidative stress indices, and histopathological examination of the colons were evaluated to monitor treatment-related effects of 6-gingerol in DSS-treated mice. Administration of 6-gingerol significantly reversed the DSS-mediated reduction in body weight, diarrhea, rectal bleeding, and colon shrinkage to near normal. Moreover, 6-gingerol significantly suppressed the circulating concentrations of interleukin-1β and tumor necrosis factor alpha and restored the colonic nitric oxide concentration and myeloperoxidase activity to normal in DSS-treated mice. 6-Gingerol efficiently prevented colonic oxidative damage by increasing the activities of antioxidant enzymes and glutathione content, decreasing the hydrogen peroxide and malondialdehyde levels, and ameliorated the colonic atrophy in DSS-treated mice. 6-Gingerol suppressed the induction of ulcerative colitis in mice via antioxidant and antiinflammatory activities, and may thus represent a potential anticolitis drug candidate.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Catechols; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Fatty Alcohols; Glutathione; Interleukin-1beta; Male; Malondialdehyde; Mice; Mice, Inbred BALB C; Nitric Oxide; Oxidative Stress; Tumor Necrosis Factor-alpha

Non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis (NASH), appears to be increasingly common worldwide. The aim of the study was to investigate the effects of 6-gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone), a bioactive ingredient of plants belonging to the Zingiberaceae family, on experimental models of NASH. In HepG2 cells, 6-gingerol (100 μmol/L) treatment inhibited free fatty acids mixture (0.33 mmol/L palmitate and 0.66 mmol/L oleate)-induced triglyceride and inflammatory marker accumulations. Male C57BL/6 mice were fed with a methionine and choline-deficient (MCD) diet to induce steatohepatitis. After four weeks of MCD diet feeding, the mice were dosed orally with 6-gingerol (25, 50 or 100 mg/kg/day) once daily for another four weeks. 6-Gingerol (100 mg/kg/day) attenuated liver steatosis and necro-inflammation in MCD diet-fed mice. The expressions of inflammatory cytokine genes, including those for monocyte chemoattractant protein-1, tumor necrosis factor-α, and interleukin-6, and nuclear transcription factor (NF-κB), which were increased in the livers of MCD diet-fed mice, were attenuated by 6-gingerol. 6-Gingerol possesses a repressive property on hepatic steatosis, which is associated with induction of peroxisome proliferator-activated receptor α. Our study demonstrated the protective role of 6-gingerol in ameliorating nutritional steatohepatitis. The effect was mediated through regulating key genes related to lipid metabolism and inflammation.

Topics: Animals; Catechols; Chemokine CCL2; Choline Deficiency; Disease Models, Animal; Fatty Alcohols; Fatty Liver; Inflammation; Interleukin-6; Lipid Metabolism; Male; Methionine; Mice; Mice, Inbred C57BL; NF-kappa B; Non-alcoholic Fatty Liver Disease; Plant Extracts; Tumor Necrosis Factor-alpha

The aim of the study was to investigate the effects of [6]-gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone) in experimental models of non-alcoholic steatohepatitis. HepG2 cells were exposed to 500 µmol/l oleic acid (OA) for 24 h and preincubated for an additional 24 h with [6]-gingerol (25, 50 or 100 µmol/l). [6]-Gingerol (100 µmol/l) inhibited OA-induced triglyceride and inflammatory marker accumulation in HepG2 cells. After being fed a high-fat diet (HFD) for 2 weeks, male golden hamsters were dosed orally with [6]-gingerol (25, 50 or 100 mg/kg/day) once daily for 8 weeks while maintained on HFD. [6]-Gingerol (100 mg/kg/day) alleviated liver steatosis, inflammation, and reversed plasma markers of metabolic syndrome in HFD-fed hamsters. The expression of inflammatory cytokine genes and nuclear transcription factor-κB (NF-κB) were increased in the HFD group; these effects were attenuated by [6]-gingerol. The hepatic mRNA expression of lipogenic genes such as liver X receptor-α, sterol regulating element binding protein-1c and its target genes including acetyl-CoA carboxylase, fatty acid synthase, stearoyl-CoA desaturase 1, and acyl-CoA:diacylglycerol acyltransferase 2 in HFD-fed hamsters was also blocked by [6]-gingerol. [6]-Gingerol may attenuate HFD-induced steatohepatitis by downregulating NF-κB-mediated inflammatory responses and reducing hepatic lipogenic gene expression.

Topics: Animals; Catechols; Cholesterol; Cricetinae; Cytokines; Diet, High-Fat; Disease Models, Animal; Fatty Alcohols; Hep G2 Cells; Humans; Inflammation; Liver; Male; Non-alcoholic Fatty Liver Disease; Triglycerides

6-gingerol has been reported to have anti-inflammatory effects in different experimental settings. The present study aimed at evaluating the effect of 6-gingerol on dextran sodium sulfate (DSS)-induced barrier impairment and inflammation in vitro and in vivo.. a differentiated Caco-2 monolayer was exposed to DSS and treated with different concentrations of 6-gingerol (0, 1, 5, 10, 50, and 100 μM). Changes in intestinal barrier function were determined using transepithelial electrical resistance (TEER). The anti-inflammatory activity of 6-gingerol was examined as changes in the expression of proinflammatory cytokine using quantitative real-time PCR. Western blotting was employed to determine the activation of adenosine monophosphate-activated protein kinase (AMPK). Mice with DSS-induced colitis were given different oral dosages of 6-gingerol daily for 14 days. Body weight and colon inflammation were evaluated, and level of proinflammatory cytokines in colon tissues was measured.. 6-gingerol treatment was shown to restore impaired intestinal barrier function and to suppress proinflammatory responses in DSS-treated Caco-2 monolayers. We found that AMPK was activated on 6-gingerol treatment in vitro. In animal studies, 6-gingerol significantly ameliorated DSS-induced colitis by restoration of body weight loss, reduction in intestinal bleeding, and prevention of colon length shortening. In addition, 6-gingerol suppressed DSS-elevated production of proinflammatory cytokines (IL-1β, TNFα, and IL-12).. our findings highlight the protective effects of 6-gingerol against DSS-induced colitis. We concluded that 6-gingerol exerts anti-inflammatory effects through AMPK activation. It is suggested that 6-gingerol has a promising role in treatment of IBD.

Topics: AMP-Activated Protein Kinases; Animals; Caco-2 Cells; Catechols; Cell Line, Tumor; Cell Survival; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Fatty Alcohols; Female; Humans; Inflammation; Interleukin-12; Interleukin-1beta; Mice; Mice, Inbred C57BL; Phosphorylation; Tumor Necrosis Factor-alpha

Insulin resistance is a core component of metabolic syndrome and usually precedes the development of type 2 diabetes mellitus. We have examined the preventative effect of an ethanol extract of ginger (Zingiber officinale, Zingiberaceae) on insulin resistance in a high-fat high-carbohydrate (HFHC) diet-fed rat model of metabolic syndrome. The HFHC control rats displayed severe insulin resistance, whilst rats treated with ginger extract (200 mg/kg) during HFHC diet feeding showed a significant improvement of insulin sensitivity using the homeostatic model assessment of insulin resistance (HOMA-IR) after 10 weeks (p < 0.01). An in vitro mechanistic study showed that (S)-[6]-gingerol, the major pungent phenolic principle in ginger, dose-dependently (from 50 to 150 μM) increased AMPK α-subunit phosphorylation in L6 skeletal muscle cells. This was accompanied by a time-dependent marked increment of PGC-1α mRNA expression and mitochondrial content in L6 skeletal muscle cells. These results suggest that the protection from HFHC diet-induced insulin resistance by ginger is likely associated with the increased capacity of energy metabolism by its major active component (S)-[6]-gingerol.

Topics: Animals; Catechols; Diet, High-Fat; Dietary Carbohydrates; Disease Models, Animal; Dose-Response Relationship, Drug; Energy Metabolism; Fatty Alcohols; Insulin Resistance; Male; Metabolic Syndrome; Mitochondria; Muscle, Skeletal; Plant Extracts; Rats; Rats, Sprague-Dawley; Zingiber officinale

Phytochemical complexity of plant foods confers health-promoting benefits including chemopreventive and anticancer effects. Isolating single constituents from complex foods may render them inactive, emphasizing the importance of preserving the natural composition of whole extracts. Recently, we demonstrated in vitro synergy among the most abundant bioactive constituents of ginger extract (GE), viz., 6-gingerol (6G), 8-gingerol (8G), 10-gingerol (10G) and 6-shogaol (6S). However, no study has yet examined the in vivo collaboration among ginger phytochemicals or evaluated the importance, if any, of the natural 'milieu' preserved in whole extract. Here, we comparatively evaluated in vivo efficacy of GE with an artificial quasi-mixture (Mix) formulated by combining four most active ginger constituents at concentrations equivalent to those present in whole extract. Orally fed GE showed 2.4-fold higher tumor growth-inhibitory efficacy than Mix in human prostate tumor xenografts. Pharmacokinetic evaluations and bioavailability measurements addressed the efficacy differences between GE and Mix. Plasma concentration-time profiles revealed multiple peaking phenomenon for ginger constituents when they were fed as GE as opposed to Mix, indicating enterohepatic recirculation. Bioavailability of 6G, 8G, 10G and 6S was 1.6-, 1.1-, 2.5- and 3.4-fold higher, respectively, when dosed with GE compared with Mix. In addition, gingerol glucuronides were detected in feces upon intravenous administration confirming hepatobiliary elimination. These data ascribe the superior in vivo efficacy of GE to higher area under the concentration time curves, greater residence time and enhanced bioavailability, of ginger phytochemicals, when fed as a natural extract compared with artificial Mix, emphasizing the usefulness of consuming whole foods over single agents.

Topics: Administration, Intravenous; Administration, Oral; Animals; Antineoplastic Agents, Phytogenic; Catechols; Cell Line, Tumor; Cell Proliferation; Disease Models, Animal; Enterohepatic Circulation; Fatty Alcohols; Humans; Male; Mice; Phenols; Phytochemicals; Plant Extracts; Prostatic Neoplasms; Tumor Burden; Xenograft Model Antitumor Assays; Zingiber officinale

This study investigated the use of a bioactive phytochemical, namely ginger extract (GE), for its antioxidant and antiulcer effects, and also for supporting probiotic growth and activity. Use of probiotics is limited in therapy because of their transience and inability to survive the adverse physiological conditions of the gastrointestinal tract. Packaging probiotics in a suitably designed pharmaceutical system with GE may facilitate their establishment in the stomach mucosa.. A probiotic (Lactobacillus acidophilus) and GE were simultaneously and individually encapsulated/immobilized in alginate floating beads. The developed system was evaluated for diameter, buoyancy, entrapment, porosity, in-vitro viability/release and pharmacodynamics in a cold restraint stress induced gastric ulcer model in rats.. The developed floating beads stayed in the stomach for more than 10 h and both agents were released slowly and over a prolonged period from these beads. Significant and promising results were obtained for the combination (synbiotic) system in terms of ulcer index, mucus secretion, oxidative stress and histopathological parameters, as compared with the individual agents. The developed system could completely revert the damage induced in ulcerated stomachs at physiological (ulcer index and mucus secretion), biochemical (oxidative stress) and histological levels.. This study establishes that suitable packaging of GE and Lactobacillus acidophilus together in floating beads can help exploit their prospects as therapeutic curative agents rather than potential preventive agents.

Topics: Animals; Anti-Ulcer Agents; Biological Availability; Catechols; Disease Models, Animal; Drug Delivery Systems; Fatty Alcohols; Female; Gastric Mucosa; Lactobacillus acidophilus; Microspheres; Monocyclic Sesquiterpenes; Plant Extracts; Rats; Rats, Wistar; Sesquiterpenes; Stomach; Stomach Ulcer; Synbiotics; Zingiber officinale

Gingerol is the generic term for pungent constituents in ginger, which has been reported to be effective for inhibiting vomiting. We attempted to investigate the antiemetic effect of gingerol and its effective mechanism on substance P and NK(1) receptors in minks.. The antiemetic effect of gingerol was investigated during a 6-hour observation on a vomiting model in minks induced by cisplatin, (7.5 mg/kg, intraperitoneal). The distribution of substance P and NK(1) receptors in the area postrema and ileum were measured by immunohistochemistry, and the expression of NK(1) receptor in the area postrema and ileum were measured by Western blotting.. The frequency of cisplatin induced retching and vomiting was significantly reduced by pretreatment with gingerol in a dose-dependent manner (P < 0.05). Substance P-immunoreactive was mainly situated in the mucosa and submucosa of the ileum as well as in the neurons of the area postrema. The immunoreactive production of NK(1) receptor was mainly situated in the muscular and submucosa of ileum and the neurons of area postrema, gingerol markedly suppressed the increased immunoreactivity of substance P and NK(1)1 receptor induced by cisplatin in a dose-dependent manner (P < 0.05), and exhibited effective inhibition on the increased expression levels of NK(1) receptor in both the ileum and area postrema dose-dependently (P < 0.05).. Gingerol has good activity against cisplatin-induced emesis in minks possibly by inhibiting central or peripheral increase of substance P and NK(1) receptors.

Topics: Animals; Area Postrema; Blotting, Western; Catechols; Disease Models, Animal; Fatty Alcohols; Ileum; Immunohistochemistry; Male; Mink; Receptors, Neurokinin-1; Substance P; Vomiting

To investigate the antiemetic effect of gingerol and its multi-targets effective mechanism on 5-hydroxytryptamine (5-HT), dopamine (DA) and substance P (SP). The antiemetic effect of gingerol was investigated on a vomiting model of mink induced by cisplatin (7.5 mg . kg(-1), i.p.) in 6 h observation. The levels of 5-HT, DA and distribution of substance P in the area postrema and ileum were measured by high performance liquid chromatography (HPLC) and immunohistochemistry respectively. The frequency of cisplatin induced retching and vomiting was significantly reduced by pretreatment with gingerol in a dose-dependent manner (P<0.05). Cisplatin produced a significant increase in 5-HT and DA levels in the area postrema and ileum of minks (P<0.05), and this increase was significantly inhibited by gingerol in a dose-dependent manner (P<0.05). Substance P-immunoreactive was mainly situated in the mucosa and submucosa of ileum as well as in the neurons of area postrema, and gingerol markedly suppressed the increase immunoreactivity of substance P induced by cisplatin in a dose-dependent manner (P<0.05). Gingerol has good activity against cisplatin-induced emesis in minks possibly by inhibiting central or peripheral increase of 5-HT, DA and substance P.

Topics: Animals; Antiemetics; Area Postrema; Catechols; Cisplatin; Disease Models, Animal; Dopamine; Dose-Response Relationship, Drug; Down-Regulation; Fatty Alcohols; Ileum; Intestinal Mucosa; Male; Mink; Serotonin; Substance P; Vomiting