gingerol and Inflammation

Natural dietary agents have attracted considerable attention due to their role in promoting health and reducing the risk of diseases including cancer. Ginger, one of the most ancient known spices, contains bioactive compounds with several health benefits. [6]-Gingerol constitutes the most pharmacologically active among such compounds. The aim of the present work was to review the literature pertaining to the use of ginger extract and [6]-gingerol against tumorigenic and oxidative and inflammatory processes associated with cancer, along with the underlying mechanisms of action involved in signaling pathways. This will shed some light on the protective or therapeutic role of ginger derivatives in oxidative and inflammatory regulations during metabolic disturbance and on the antiproliferative and anticancer properties. Data collected from experimental (in vitro or in vivo) and clinical studies discussed in this review indicate that ginger extract and [6]-gingerol exert their action through important mediators and pathways of cell signaling, including Bax/Bcl2, p38/MAPK, Nrf2, p65/NF-κB, TNF-α, ERK1/2, SAPK/JNK, ROS/NF-κB/COX-2, caspases-3, -9, and p53. This suggests that ginger derivatives, in the form of an extract or isolated compounds, exhibit relevant antiproliferative, antitumor, invasive, and anti-inflammatory activities.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Catechols; Cell Line, Tumor; Fatty Alcohols; Humans; Inflammation; Neoplasms; Plant Extracts; Signal Transduction; Zingiber officinale

Sepsis is characterized by an overactive inflammatory response. Acute lung injury (ALI) is the most common type of organ injury in sepsis, with high morbidity and mortality. 6-Gingerol is the main bioactive compound of ginger, and it possesses anti-inflammatory bioactivity in different diseases. This study is aimed to explore the specific function of 6-Gingerol in sepsis-induced ALI.. Lipopolysaccharide (LPS) was intraperitoneally injected into Sprague-Dawley rats for establishing the ALI models in vivo. The ALI rats were intraperitoneally injected with 20 mg/kg 6-Gingerol. The contents of oxidative stress markers malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were detected in the lung tissues of ALI rats. The concentrations of inflammatory factors [Tumor Necrosis Factor alpha (TNF-α), interleukin (IL)-6, and IL-1β] were measured by ELISA. Inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) of rats was tested. Western blot was utilized to test the protein levels of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) in lung tissues. Furthermore, immunohistochemical staining was applied for testing the expression of NLRP3 inflammasome in lung tissues.. The pathological changes in ALI rats were characterized by increased accumulation of inflammatory cells, alveolar hemorrhage, and pulmonary interstitial edema. However, the degree of pathological injury of lung tissues was significantly improved after 6-Gingerol treatment. Additionally, 6-Gingerol significantly attenuated the lung wet/dry ratio and protein permeability index (PPI) of LPS-induced rats. Furthermore, 6-Gingerol repressed oxidative stress and inflammatory reaction in LPS-induced rats by reducing the contents of MDA, GSH, SOD, TNF-α, IL-6, and IL-1β in the lung. LPS-induced infiltration of eosinophils, macrophages, neutrophils, and lymphocytes into lung was suppressed by 6-Gingerol administration. Moreover, 6-Gingerol activated Nrf2/HO-1 signaling and repressed LPS-induced‑NLRP3 inflammasome expression in lung tissues of LPS-induced rats. Intraperitoneal injection of ML385 (Nrf2 inhibitor) treatment into rats reversed the effects of 6-Gingerol on lung injury, inflammation, and oxidative stress in LPS-subjected rats.. 6-Gingerol attenuates sepsis-induced ALI by suppressing NLRP3 inflammasome activation via stimulation of Nrf2.

Topics: Acute Lung Injury; Animals; Inflammasomes; Inflammation; Interleukin-6; Lipopolysaccharides; Lung; NF-E2-Related Factor 2; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Rats, Sprague-Dawley; Sepsis; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Acrolein is the main toxic metabolite of ifosfamide (IFO) that causes urothelial damage by oxidative stress and inflammation. Here, we investigate the molecular mechanism of action of gingerols, Zingiber officinale bioactive molecules, as an alternative treatment for ifosfamide-induced hemorrhagic cystitis. Female Swiss mice were randomly divided into 5 groups: control; IFO; IFO + Mesna; and IFO + [8]- or [10]-gingerol. Mesna (80 mg/kg, i.p.) was given 5 min before, 4 and 8 h after IFO (400mg/kg, i.p.). Gingerols (25 mg/kg, p.o.) were given 1 h before and 4 and 8 h after IFO. Animals were euthanized 12 h after IFO injection. Bladders were submitted to macroscopic and histological evaluation. Oxidative stress and inflammation were assessed by malondialdehyde (MDA) or myeloperoxidase assays, respectively. mRNA gene expression was performed to evaluate mesna and gingerols mechanisms of action. Mesna was able to protect bladder tissue by activating NF-κB and NrF2 pathways. However, we demonstrated that gingerols acted as an antioxidant and anti-inflammatory agent stimulating the expression of IL-10, which intracellularly activates JAK/STAT/FOXO signaling pathway.

Topics: Animals; Cystitis; Female; Hemorrhage; Ifosfamide; Inflammation; Interleukin-10; Mesna; Mice; Signal Transduction

6-Gingerol, one of the major pharmacologically active ingredients extracted from ginger, has been reported experimentally to exert hepatic protection in non-alcoholic fatty liver disease (NAFLD). However, the molecular mechanism remains largely elusive. RNA sequencing indicated the significant involvement of the AMPK signaling pathway in 6-gingerol-induced alleviation of NAFLD in vivo. Given the significance of the LKB1/AMPK pathway in metabolic homeostasis, this study aims to investigate its role in 6-gingerol-induced mitigation on NAFLD. Our study showed that 6-gingerol ameliorated hepatic steatosis, inflammation and oxidative stress in vivo and in vitro. Further experiment validation suggested that 6-gingerol activated an LKB1/AMPK pathway cascade in vivo and in vitro. Co-immunoprecipitation analysis demonstrated that the 6-gingerol-elicited activation of an LKB1/AMPK pathway cascade was related to the enhanced stability of the LKB1/STRAD/MO25 complex. Furthermore, radicicol, an LKB1 destabilizer, inhibited the activating effect of 6-gingerol on an LKB1/AMPK pathway cascade via destabilizing LKB1/STRAD/MO25 complex stability in vitro, thus reversing the 6-gingerol-elicited ameliorative effect. In addition, molecular docking analysis further predicated the binding pockets of LKB1 necessary for binding with 6-gingerol. In conclusion, our results indicate that 6-gingerol plays an important role in regulating the stability of the LKB1/STRAD/MO25 complex and the activation of LKB1, which might weigh heavily in the 6-gingerol alleviation of NAFLD.

Topics: AMP-Activated Protein Kinase Kinases; AMP-Activated Protein Kinases; Animals; Diet, High-Fat; Inflammation; Liver; Mice; Mice, Inbred C57BL; Molecular Docking Simulation; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Protein Serine-Threonine Kinases

Cyclooxygenase (COX) and Lipoxygenase (LOX) are essential enzymes for arachidonic acid (AA) to eicosanoids conversion. These AA-derived eicosanoids are essential for initiating immunological responses, causing inflammation, and resolving inflammation. Dual COX/5-LOX inhibitors are believed to be promising novel anti-inflammatory agents. They inhibit the synthesis of prostaglandins (PGs) and leukotrienes (LTs), but have no effect on lipoxin formation. This mechanism of combined inhibition circumvents certain limitations for selective COX-2 inhibitors and spares the gastrointestinal mucosa. Natural products, i.e. spice chemicals and herbs, offer an excellent opportunity for drug discovery. They have proven anti-inflammatory properties. However, the potential of a molecule to be a lead/ drug candidate can be much more enhanced if it has the property of inhibition in a dual mechanism. Synergistic activity is always a better option than the molecule's normal biological activity. Herein, we have explored the dual COX/5-LOX inhibition property of the three major potent phytoconsituents (curcumin, capsaicin, and gingerol) from Indian spices using in silico tools and biophysical techniques in a quest to identify their probable inhibitory role as anti-inflammatory agents. Results revealed the dual COX/5-LOX inhibitory potential of curcumin. Gingerol and capsaicin also revealed favorable results as dual COX/5-LOX inhibitors. Our results are substantiated by target similarity studies, molecular docking, molecular dynamics, energy calculations, DFT, and QSAR studies. In experimental inhibitory (in vitro) studies, curcumin exhibited the best dual inhibitory activities against COX-1/2 and 5-LOX enzymes. Capsaicin and gingerol also showed inhibitory potential against both COX and LOX enzymes. In view of the anti-inflammatory potential these spice chemicals, this research could pave the way for more scientific exploration in this area for drug discovery.

Topics: Anti-Inflammatory Agents; Arachidonate 5-Lipoxygenase; Capsaicin; Curcumin; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Humans; Inflammation; Lipoxygenase; Lipoxygenase Inhibitors; Molecular Docking Simulation; Spices

Acute lung injury (ALI) and sepsis are complicated syndromes that are often left untreated in critically ill patients. 6-Gingerol is a phenolic phytochemical compound that is found in fresh ginger, has pharmacological effects against inflammation. This study explored the roles of 6-gingerol in a mouse model of acute lung injury caused by lipopolysaccharide (LPS) and RAW-264.7 cells inflammation. The LPS-induced animal model underwent histopathological examinations, and RAW-264.7 cells viability was determined by Cell counting Kit-8 (CCk-8) assay. Additionally, qRT-PCR, Immunofluorescence, Western blot, and ELISA were used in vivo and in vitro to identify inflammatory factors and proteins associated with NF-κB and MAPK signaling pathways. In a histological examination 6-gingerol exhibited protective effects. Moreover, 6-gingerol elevated cell viability and downregulated inflammatory factors Interlukin-1β (IL-1β), Interlukin-6 (IL-6) and Tumor necrosis factor-α (TNF-α) in LPS-treated RAW-264.7 cells. Furthermore, 6-gingerol decreased phosphorylation of P65, P38 and the level of JNK in NF-κB and MAPK pathways. Importantly, 6-gingerol increased transcript abundance of miR-322-5p which suppressed by LPS and miR-322-5p downregulation negated the protective functions of 6-gingerol. The protective activity of 6-gingerol was mediated by miR-322-5p up-regulation.

Topics: Acute Lung Injury; Animals; Humans; Inflammation; Lipopolysaccharides; Mice; MicroRNAs; NF-kappa B; RAW 264.7 Cells; Signal Transduction

We investigated the effects of 6-gingerol on adiposity and obesity-induced inflammation by focusing on the regulation of adipogenesis and adipokines in white adipose tissue (WAT) of diet-induced obese mice. C57BL/6 mice were fed a high-fat diet (HFD) containing 0.05% 6-gingerol for 8 weeks. 6-Gingerol supplementation significantly reduced body weight, WAT mass, serum triglyceride, leptin and insulin levels, and HOMA-IR in HFD-fed mice. Additionally, the size of adipocytes in epididymal fat pads was reduced in HFD-fed mice by 6-gingerol supplementation. 6-Gingerol reduced the mRNA and protein levels of adipogenesis-related transcription factors, such as SREBP-1, PPARγ, and C/EBPα in WAT. Furthermore, 6-gingerol suppressed the expression of lipogenesis-related genes, such as fatty acid synthase and CD36 in WAT. Adiponectin expression was significantly increased, whereas inflammatory adipokines (leptin, resistin, TNF-α, MCP-1, and PAI-1) and the macrophage marker F4/80 were significantly reduced in the WAT of HFD-fed mice by 6-gingerol supplementation. In conclusion, 6-gingerol effectively contributed to the alleviation of adiposity and inflammation in WAT, which is associated with the regulation of adipokines in diet-induced obese mice.

Topics: Adipokines; Adipose Tissue; Adiposity; Animals; Diet, High-Fat; Inflammation; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity

Diabetes mellitus (DM) can induce cardiomyocyte injury and lead to diabetic cardiomyopathy (DCM) which presently has no specific treatments and consequently increase risk of mortality.. To characterize the therapeutic effect of 6-gingerol (6-G) on DCM and identify its potential mechanism.. These findings suggest that 6-G could protect against DCM by the mechanism of ferroptosis inhibition and inflammation reduction via enhancing the Nrf2/HO-1 pathway.

Topics: Animals; Diabetes Mellitus; Diabetic Cardiomyopathies; Glucose; Inflammation; Mice; NF-E2-Related Factor 2; Oxidative Stress; Palmitic Acid; Rats; Superoxide Dismutase

The present study examines the chemopreventive role of [6]-gingerol, an active component of ginger, on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis models. The HBP has been developed with an addition of 0.5% of DMBA to the HBP area three times per week, up to the end of the 16th experimental week. At the end of the experiment, we noticed 100% tumor incidence and precancerous lesions, such as dysplasia, hyperplasia, keratosis, and well-differentiated squamous cell carcinoma, in DMBA-induced HBP. Furthermore, we observed that [6]-gingerol inhibited the increased thiobarbituric acid-reactive substances and decreased antioxidant levels in DMBA-induced hamsters. Moreover, [6]-gingerol inhibits DMBA-exposed over expression of inflammatory markers (inducible nitric oxide synthase, interleukin [IL]-1β, IL-6, cyclooxygenase-2, and tumor necrosis factor-α) and cell proliferation markers (cyclin D1, proliferating cell nuclear antigen); induces proapoptotic markers in HBP. Nuclear factor erythroid-2-related factor-2 (Nrf2) is a major antioxidant transcription factor, which regulates the antioxidant gene-dependent scavenge of tumor proliferation and apoptosis. Overexpression of Nrf2 signaling plays a pivotal role and can be a novel target in preventing carcinogenesis. In this study, [6]-gingerol restores the DMBA-induced depletion of Nrf2 signaling and thereby prevents buccal pouch carcinogenesis in hamsters. These results point out that [6]-gingerol impedes the responses of inflammatory and cell proliferation-associated progression of cancer through the action of Nrf2 signaling.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogenesis; Catechols; Cell Proliferation; Fatty Alcohols; Inflammation; Male; Mesocricetus; Mouth Mucosa; Mouth Neoplasms; Neoplasm Proteins; NF-E2-Related Factor 2; Signal Transduction

6-Gingerol, a pungent ingredient of ginger, has been reported to possess anti-inflammatory and antioxidant activities, but the effect of 6-gingerol on pressure overload-induced cardiac remodeling remains inconclusive. In this study, we investigated the effect of 6-gingerol on cardiac remodeling in in vivo and in vitro models, and to clarify the underlying mechanisms. C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with 6-gingerol (20 mg/kg, ig) three times a week (1 week in advance and continued until the end of the experiment). Four weeks after TAC surgery, the mice were subjected to echocardiography, and then sacrificed to harvest the hearts for analysis. For in vitro study, neonatal rat cardiomyocytes and cardiac fibroblasts were used to validate the protective effects of 6-gingerol in response to phenylephrine (PE) and transforming growth factor-β (TGF-β) challenge. We showed that 6-gingerol administration protected against pressure overload-induced cardiac hypertrophy, fibrosis, inflammation, and dysfunction in TAC mice. In the in vitro study, we showed that treatment with 6-gingerol (20 μM) blocked PE-induced-cardiomyocyte hypertrophy and TGF-β-induced cardiac fibroblast activation. Furthermore, 6-gingerol treatment significantly decreased mitogen-activated protein kinase p38 (p38) phosphorylation in response to pressure overload in vivo and extracellular stimuli in vitro, which was upregulated in the absence of 6-gingerol treatment. Moreover, transfection with mitogen-activated protein kinase kinase 6 expressing adenoviruses (Ad-MKK6), which specifically activated p38, abolished the protective effects of 6-gingerol in both in vitro and in vivo models. In conclusion, 6-gingerol improves cardiac function and alleviates cardiac remodeling induced by pressure overload in a p38-dependent manner. The present study demonstrates that 6-gingerol is a promising agent for the intervention of pathological cardiac remodeling.

Topics: Animals; Anti-Inflammatory Agents; Cardiomegaly; Cardiotonic Agents; Catechols; Fatty Alcohols; Fibroblasts; Fibrosis; Inflammation; Male; MAP Kinase Signaling System; Mice, Inbred C57BL; Myocardium; Myocytes, Cardiac; p38 Mitogen-Activated Protein Kinases; Phenylephrine; Rats, Sprague-Dawley; Transforming Growth Factor beta; Ventricular Remodeling

Diethylnitrosamine (DEN) is a well-known hepatocarcinogen, and its oral administration causes severe liver damage including cancer. DEN induces the pathogenesis of the liver through reactive oxygen species mediated inflammation and modulation of various biological activities. 6-Gingerol, a major component of ginger, is reported to prevent liver diseases by reducing the oxidative stress and proinflammatory mediators. The present study investigated the hepatoprotective effects of 6-gingerol through the measurement of oxidative stress, anti-inflammatory markers, liver function enzyme parameter, and histopathological analysis. The rats were randomly divided into four groups as the control, DEN treated (50 mg/kg b.w.), DEN+6-gingerol (each 50 mg/kg b.w.), and 6-gingerol only. To evaluate the hepatoprotective effects, liver function enzymes (ALT, AST, and ALP), oxidative stress markers (SOD, GSH, GST, and TAC), lipid peroxidation, inflammatory markers (CRP, TNF-

Topics: Albumins; Animals; Anti-Inflammatory Agents; Biphenyl Compounds; Catechols; Chemical and Drug Induced Liver Injury, Chronic; Diethylnitrosamine; Fatty Alcohols; Free Radical Scavengers; Free Radicals; Glutathione; Hydrogen Peroxide; In Vitro Techniques; Inflammation; Lipid Peroxidation; Liver; Male; Mitochondria; Oxidative Stress; Picrates; Rats; Zingiber officinale

This study examined the protective effect of 6-Gingerol (6G) against lipopolysaccharide (LPS)-induced cognitive impairments, oxidative stress, neuroplasticity, amyloidogenesis, and inflammation. Male rats were allocated into six groups in this manner; Group I placed on normal saline only. Group II was treated for 7 days with LPS alone intraperitoneally at 250 µg/kg body weight (bw). Group III received 6G alone at 50 mg/kg bw orally for 14 days. Groups IV and V received 6G at 20 and 50 mg/kg bw for 7 days, respectively, and LPS for another 7 days to induce neurotoxicity. Group VI received 5 mg/kg bw of donepezil for 7 days and LPS for 7 days. Pretreatment with 20 and 50 mg/kg bw of 6G protected against LPS-mediated learning and memory function, and also locomotor and motor deficits. Besides, 20 and 50 mg/kg bw 6G mitigated LPS-induced alteration in markers of oxidative stress. Furthermore, induction of amyloidogenesis associated with disruption of histoarchitecture and high expression of interleukin 1β, inducible nitric oxide synthase, amyloid precursor protein (APP), β-secretase 1, and brain-derived neurotrophic factor by LPS was mitigated by the two doses of 6G in the rat hippocampus and cerebral cortex region of the brain. 6G pretreatment at the two doses mitigated LPS-mediated histopathological changes in the hippocampus and cerebral cortex of rats. Overall, our results demonstrate that the protective effect of 6G is mediated through the reversal of neurobehavioral deficit, oxidative stress, inflammation, and amyloidogenesis, thus making 6G a possible chemoprophylactic agent against brain injury as a result of LPS exposure. PRACTICAL APPLICATIONS: In the search for a holistic prevention of inflammation-associated neurodegeneration, nutraceuticals are becoming prominent. Hence, this study presents 6G, an active constituent of ginger, as a chemoprotective, antioxidant, and anti-inflammatory agent, which is able to ameliorate cognitive impairments, oxidative stress, neuroplasticity, amyloidogenesis, and inflammation in LPS-induced rat model of neuroinflammation.

Topics: Animals; Catechols; Cognition; Cognitive Dysfunction; Fatty Alcohols; Inflammation; Lipopolysaccharides; Male; Neuronal Plasticity; Rats; Zingiber officinale

Toll-like receptor 4 (TLR4) pathway is one of the major pathways that mediate the inflammation in human body. There are different anti-inflammatory drugs available in the market which specifically act on different signaling proteins of TLR4 pathway but they do have few side effects and other limitations for intended use in human body. In this study, Curcumin and its different analogs have been analyzed as the inhibitors of signaling proteins, i.e. Cycloxygenase-2 (COX-2), inhibitor of kappaβ kinase (IKK) and TANK binding kinase-1 (TBK-1) of TLR4 pathway using different computational tools. Initially, three compounds were selected for respective target based on free binding energy among which different compounds were reported to have better binding affinity than commercially available drug (control). Upon continuous computational exploration with induced fit docking (IFD), 6-Gingerol, Yakuchinone A and Yakuchinone B were identified as the best inhibitors of COX-2, IKK, and TBK-1 respectively. Then their drug-like potentialities were analyzed in different experiments where they were also predicted to perform well. Hopefully, this study will uphold the efforts of researchers to identify anti-inflammatory drugs from natural sources.

Topics: Catechols; Computational Chemistry; Curcumin; Cyclooxygenase 2; Diarylheptanoids; Fatty Alcohols; Guaiacol; Humans; I-kappa B Kinase; Inflammation; Lipopolysaccharides; NF-kappa B; Pharmaceutical Preparations; Protein Serine-Threonine Kinases; Signal Transduction; Toll-Like Receptor 4

The natural product 6-gingerol, a major bioactive component of the rhizome of ginger (

Topics: Animals; Biological Products; Catechols; Cell Differentiation; Cells, Cultured; Coculture Techniques; Dinoprostone; Fatty Alcohols; Gene Expression; Inflammation; Interleukin-1; Male; Mice, Inbred ICR; Osteoblasts; Osteoclasts; RANK Ligand

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

Background Acrylonitrile (AN) is a neurotoxin that is widely used to manufacture synthetic fibres, plastics and beverage containers. Recently, we reported the ameliorative role of 6-gingerol-rich fraction from Zingiber officinale (Ginger, GRF) on the chlorpyrifos-induced toxicity in rats. Here, we investigated the protective role of GRF on AN-induced brain damage in male rats. Methods Male rats were orally treated with corn oil (2 mL/kg, control), AN (50 mg/kg, Group B), GRF (200 mg/kg, Group C), AN [50 mg/kg+GRF (100 mg/kg) Group D], AN [(50 mg/kg)+GRF (200 mg/kg) Group E] and AN [(50 mg/kg)+N-acetylcysteine (AC, 50 mg/kg) Group F] for 14 days. Then, we assessed the selected markers of oxidative damage, antioxidant status and inflammation in the brain of rats. Results The results indicated that GRF restored the AN-induced elevations of brain malondialdehyde (MDA), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and Nitric Oxide (NO) levels. GRF also prevented the AN-induced depletion of brain glutathione (GSH) level and the activities of Glutathione S-transferase (GST), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in rats (p<0.05). Furthermore, GRF prevented the AN-induced cerebral cortex lesion and increased brain immunohistochemical expressions of Caspases-9 and -3. Conclusions Our data suggest that GRF may be a potential therapeutic agent in the treatment of AN-induced model of brain damage.

Topics: Acrylonitrile; Animals; Antioxidants; Catalase; Catechols; Cerebral Cortex; Fatty Alcohols; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Inflammation; Interleukin-6; Lipid Peroxidation; Male; Malondialdehyde; Neuroprotection; Nitric Oxide; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; Superoxide Dismutase; Tumor Necrosis Factor-alpha; Zingiber officinale

Chlorpyrifos (CPF) is an organophosphorus pesticide widely used in agricultural applications and household environments. 6-Gingerol-rich fraction from Zingiber officinale (Ginger, 6-GRF) has been reported to possess potent anti-oxidative, anti-inflammatory and anti-apoptotic properties. Here, we investigated the protective properties of 6-GRF on CPF-induced oxidative damage and inflammation in the brain, ovary and uterus of rats. Five groups of rats containing 14 rats/group received corn oil (control), CPF (5 mg/kg), 6-GRF (100 mg/kg), CPF (5 mg/kg) + 6-GRF (50 mg/kg) and CPF (5 mg/kg) + 6-GRF (100 mg/kg) through gavage once per day for 35 days respectively. The results showed that 6-GRF protected against CPF-induced increases in oxidative stress ((hydrogen peroxide (H

Topics: ADAM17 Protein; Animals; Body Weight; Brain; Catechols; Chlorpyrifos; Fatty Alcohols; Female; Inflammation; Ovary; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; Uterus; Zingiber officinale

The present study was performed to investigate the molecular mechanism of 6-gingerol on adipocyte-mediated systemic inflammation

Topics: 3T3-L1 Cells; Acyltransferases; Adipocytes; Adipogenesis; Animals; Catechols; Cytokines; Diacylglycerol O-Acyltransferase; Diet, High-Fat; Down-Regulation; Fatty Acid Synthases; Fatty Acid-Binding Proteins; Fatty Alcohols; I-kappa B Kinase; In Vitro Techniques; Inflammation; JNK Mitogen-Activated Protein Kinases; Macrophages; Mice; Nitric Oxide; Obesity; PPAR gamma; RAW 264.7 Cells; Sterol Regulatory Element Binding Protein 1; Transcription Factor AP-1; Triglycerides; Zebrafish

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

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

A wide array of phytochemicals have been shown to possess potential cancer chemopreventive properties. Ginger contains pungent phenolic substances with pronounced antioxidative and antiinflammatory activities. In the present study, we have determined the antitumor promotional activity of [6]-gingerol, a major pungent principle of ginger, using a two-stage mouse skin carcinogenesis model. Topical application of [6]-gingerol onto shaven backs of female ICR mice prior to each topical dose of 12-O-tetradecanoylphorbol-13-acetate (TPA) significantly inhibited 7,12-dimethylbenz[a]anthracene-induced skin papillomagenesis. The compound also suppressed TPA-induced epidermal ornithine decarboxylase activity and inflammation.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Capillary Permeability; Catechols; Curcumin; Epidermis; Fatty Alcohols; Female; Inflammation; Mice; Mice, Inbred ICR; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; Plants, Medicinal; Skin Neoplasms; Tetradecanoylphorbol Acetate