zerumbone and Disease-Models--Animal

Neuropathic pain is a chronic pain condition persisting past the presence of any noxious stimulus or inflammation. Zerumbone, of the

Topics: Animals; Disease Models, Animal; Male; Mice; Mice, Inbred ICR; Neuralgia; PPAR alpha; PPAR gamma; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Sesquiterpenes

Hyperlipidaemia and cognitive dysfunction (CD) are the two public health concerns. Though hyperlipidaemia has been comprehensively studied in respect to CVD, its role on CD needs to be explored. Hence, we evaluated hyperlipidaemia as a risk factor for CD and the efficacy of EPA (20 : 5n-3) + DHA (22 : 6n-3) and zerumbone (Z) in modulating CD under hyperlipidaemic conditions. Male Wistar rats (Rattus norvegicus) were fed control, high-fat (HF), high-fat + fish oil (HF + F), high-fat + zerumbone (HF+Z) and high-fat + fish oil + zerumbone (HF+F+Z) containing diets. After a 30 d feeding trial, memory parameters (Morris water maze, elevated plus maze (transfer latency) and T-maze (spontaneous alteration)) and locomotor skills (open field test and rotarod test) were assessed. Hyperlipidaemia significantly (P < 0·05) reduced memory and motor coordination skills compared with control. However, the administration of EPA + DHA and zerumbone significantly (P < 0·05) restored the hyperlipidaemia-induced loss of memory and motor coordination skills. Collectively, our data imply that hyperlipidaemia causes CD by decreasing memory and motor coordination skills, and administration of EPA + DHA and zerumbone prevents hyperlipidaemia-induced CD. The augmented effect of EPA + DHA, together with zerumbone, discloses a promising strategy for lowering the severity of CD in hyperlipidaemic conditions.

Topics: Animals; Cognition; Cognitive Dysfunction; Diet, High-Fat; Disease Models, Animal; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fish Oils; Hyperlipidemias; Male; Morris Water Maze Test; Motor Skills; Nootropic Agents; Rats; Rats, Wistar; Risk Factors; Sesquiterpenes

Topics: Alanine Transaminase; Animals; Anti-Inflammatory Agents; Antioxidants; Aspartate Aminotransferases; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Cyclooxygenase 2; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Injections, Intraperitoneal; Lipopolysaccharides; Male; Mice; Mice, Inbred ICR; NF-kappa B; Oxidative Stress; RAW 264.7 Cells; Sesquiterpenes; Signal Transduction; Toll-Like Receptor 4

Acute lung injury (ALI) is a clinical syndrome with high morbidity and mortality rates mainly caused by Gram-negative bacteria. Nevertheless, an effective treatment strategy for ALI is yet to be developed. Zerumbone, a sesquiterpene isolated from Zingiber zerumbet Smith, possesses several advantageous bioeffects such as antioxidation, anti-inflammation, and antiulcer. Pretreatment of zerumbone inhibited lipopolysaccharide (LPS)-induced arterial blood gas exchange, neutrophils infiltration, and increased pulmonary vascular permeability. LPS-induced expression of intercellular adhesion molecule-1 (ICAM-1) was inhibited by zerumbone at a lower concentration than that of vascular cell adhesion molecule-1 (VCAM-1). In addition, proinflammatory cytokines, such as interleukin (IL)-1β and macrophage inflammatory protein (MIP)-2 were suppressed by zerumbone. The phosphorylation of nuclear factor (NF)-κB, a proinflammatory transcription factor, and degradation of inhibitor of κB (IκB), an inhibitor of NF-κB, were also reduced by zerumbone. Furthermore, we found the inhibitory concentration of zerumbone on phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) was lower than that of extracellular signal-regulated kinase (ERK). In conclusion, zerumbone could be a potential protective agent for ALI, possibly via expression of ICAM-1, IL-1β, and MIP-2. The protective mechanism of zerumbone was by reversing the activation of p38 MAPK/JNK-IκB/NF-κB pathway.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Capillary Permeability; Chemokine CXCL2; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; I-kappa B Proteins; Intercellular Adhesion Molecule-1; Interleukin-1beta; JNK Mitogen-Activated Protein Kinases; Lipopolysaccharides; Lung; Male; Mice, Inbred ICR; Neutrophil Infiltration; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Phytotherapy; Plant Extracts; Plants, Medicinal; Sesquiterpenes; Signal Transduction; Zingiberaceae

Acute lung injury (ALI) is a serious disease with high morbidity and mortality rate. Although there are effective strategies for treatment of ALI; a widely accepted specific pharmacotherapy has not yet established. Zerumbone, the major active phytochemical compound from Zingiber zerumbet Smith, exhibits various beneficial biological and pharmacological activities, such as antioxidation, anti-inflammation, immunomodulation, and anti-cancer. We aimed to study the potential protective effects and mechanisms of zerumbone in mouse model of lipopolysaccharide (LPS)-induced ALI. Pretreatment with zerumbone inhibited the histopatholgical changes such as neutrophils infiltration, increased in alveolar barrier thickness, hemorrhage, and hyaline membrane formation occurred in lungs in LPS-induced ALI. In addition, not only LPS-induced activation of myeloperoxidase (MPO) and metallopeptidase-9 (MMP-9) was suppressed by zerumbone, but also lipid peroxidation in lungs was inhibited as well. Moreover, pretreatment with zerumbone reversed the antioxidative enzymes activities, including superoxide dismutase, catalase, and glutathione peroxidase, decreased by LPS and enhanced the expression of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase (HO-1) induced by LPS. These results from present study suggested that the protective mechanisms of zerumbone on LPS-induced ALI were via up-regulation of antioxidative enzymes and Nrf2/HO-1 pathway.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Antioxidants; Cells, Cultured; Disease Models, Animal; Heme Oxygenase-1; Humans; Lipopolysaccharides; Male; Matrix Metalloproteinase 9; Membrane Proteins; Mice; Mice, Inbred ICR; NF-E2-Related Factor 2; Peroxidase; Sesquiterpenes; Signal Transduction; Zingiberaceae

Zerumbone, a cyclic eleven-membered sesquiterpene, is the major component of the essential oil isolated from the wild ginger, Zingiber zerumbet. There are several beneficial pharmacological activities of zerumbone including anti-inflammatory, antioxidant, and anticancer activities. Acute lung injury (ALI) is an acute pulmonary inflammatory disorder with high morbidity and mortality rate. In present study, we aimed to investigate the protective effects and mechanisms of zerumbone on endotoxin, lipopolysaccharide (LPS)-induced ALI. Mice were pretreated with zerumbone at various concentrations for 30 min followed by intratracheal administration of LPS for 6 h. Pretreatment with zerumbone not only reduced leukocytes infiltration into the alveolar space but also inhibited lung edema in LPS-induced ALI. Decreased secretion of proinflammatory cytokines such as TNFα and IL-6 caused by LPS were reversed by zerumbone. LPS-induced expressions of proinflammatory mediators, iNOS and COX-2, were inhibited by zerumbone. In addition, NFκB activation and Akt phosphorylation were inhibited by zerumbone in LPS-induced ALI. All these results suggested that the protective mechanisms of zerumbone on endotoxin-induced ALI were via inhibition of Akt-NFκB activation.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Disease Models, Animal; Endotoxins; Enzyme Activation; Inflammation; Male; Mice; NF-kappa B; Oncogene Protein v-akt; Sesquiterpenes; Signal Transduction; Zingiber officinale

Neuropathic pain is a chronic condition that is difficult to be treated. Current therapies available are either ineffective or non-specific thus requiring newer treatment approaches. In this study, we investigated the antiallodynic and antihyperalgesic effects of zerumbone, a bioactive sesquiterpene from Zingiber zerumbet in chronic constriction injury (CCI)-induced neuropathic pain animal model. Our findings showed that single and repeated dose of intra-peritoneal administration of zerumbone (5, 10, 50, 100 mg/kg) significantly attenuated the CCI-induced neuropathic pain when evaluated using the electronic von Frey anesthesiometer, cold plate, Randall-Selitto analgesiometer and the Hargreaves plantar test. Zerumbone significantly alleviated tactile and cold allodynia as well as mechanical and thermal hyperalgesia. Our findings are in comparison to the positive control drugs thatused gabapentin (20 mg/kgi.p.) and morphine (1 mg/kgi.p.). Together, these results showed that the systemic administration of zerumbone produced marked antiallodynic and antihyperalgesic effects in the CCI-induced neuropathic pain in mice and may serve as a potential lead compound for further analysis.

Topics: Analgesics; Animals; Constriction; Disease Models, Animal; Hyperalgesia; Mice; Mice, Inbred ICR; Neuralgia; Pain Measurement; Rhizome; Sesquiterpenes; Zingiberaceae

Owing to the high incidence of cholesterol-induced cardiovascular disease, particularly atherosclerosis, the current study was designed to investigate the preventive and therapeutic efficacies of dietary zerumbone (ZER) supplementation on the formation and development of atherosclerosis in rabbits fed with a high cholesterol diet. A total of 72 New Zealand white rabbits were divided randomly on two experimental studies carried out 8 weeks apart. The first experiment was designed to investigate the prophylactic efficacy of ZER in preventing early developed atheromatous lesion. The second experimental trial was aimed at investigating the therapeutic effect of ZER in reducing the atherosclerotic lesion progression and establishment. Sudanophilia, histopathological, and ultrastructural changes showed pronounced reduction in the plaque size in ZER-medicated aortas. On the other hand, dietary supplementation of ZER for almost 10 weeks as a prophylactic measure indicated substantially decreasing lipid profile values, and similarly, plaque size in comparison with high-cholesterol non-supplemented rabbits. Furthermore, the results of oxidative stress and antioxidant biomarker evaluation indicated that ZER is a potent antioxidant in suppressing the generation of free radicals in terms of atherosclerosis prevention and treatment. ZER significantly reduced the value of malondialdehyde and augmented the value of superoxide dismutase. In conclusion, our data indicated that dietary supplementation of ZER at doses of 8, 16, and 20 mg/kg alone as a prophylactic measure, and as a supplementary treatment with simvastatin, significantly reduced early plague formation, development, and establishment via significant reduction in serum lipid profile, together with suppression of oxidative damage, and therefore alleviated atherosclerosis lesions.

Topics: Animals; Anticholesteremic Agents; Antioxidants; Aorta; Aortic Diseases; Atherosclerosis; Biomarkers; Cholesterol, Dietary; Dietary Supplements; Disease Models, Animal; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Malondialdehyde; Oxidative Stress; Plaque, Atherosclerotic; Rabbits; Sesquiterpenes; Simvastatin; Superoxide Dismutase; Time Factors

We investigated the effects of zerumbone, a natural cyclic sesquiterpene of Zingiber zerumbet Smith, on high-fat diet (HFD)-induced hyperlipidemic hamsters. After being fed HFD for 2 weeks, Syrian golden hamsters were dosed orally with zerumbone (25, 50, and 100 mg/kg) once daily for 8 weeks. Decreased plasma levels of TC, TG and LDL-C, as well as the concentrations of hepatic lipids, with a simultaneous increase in fecal lipids were found. The ratios of LDL-C/HDL-C and TC/HDL-C were elevated by zerumbone. Zerumbone exhibited the ability to decreased hepatic mRNA levels of fatty acid synthase, malic enzyme, sterol-regulatory element binding protein and 3-hydroxy-3-methyl-glutaryl-CoA reductase reductase. The hepatic mRNA expression of peroxisome proliferator-activated receptor α, together with its target gene carnitine palmitoyl transferase and acyl-CoA oxidase were also upregulated by zerumbone. Zerumbone is effective to improve dyslipidemia by modulating the genes expression involving in the lipolytic and lipogenic pathways of lipids metabolism.

Topics: Animals; Body Weight; Carnitine O-Palmitoyltransferase; Diet, High-Fat; Disease Models, Animal; Eating; Feces; Gene Expression Regulation; Hyperlipidemias; Lipase; Lipid Metabolism; Lipids; Lipolysis; Liver; Male; Mesocricetus; Sesquiterpenes; Sterol Regulatory Element Binding Protein 1; Zingiberaceae

Rhizome of Zingiber montanum has been extensively used as a folk medicine to ameliorate peptic ulcer at northern part of Bangladesh.. To identify the antiulcer principle of the MeOH extract of the rhizome of Zingiber montanum by an ex vivo bioassay guided chromatographic separation and purification, and structure elucidation of the purified compound by spectroscopic methods.. Dried powder of Zingiber montanum rhizomes was extracted with MeOH. The antiulcer activity of the crude extract and its chromatographic fractions were evaluated by the inhibition of 1N HCl induced gastric lesions in Swiss albino mice. The pure compound was purified from the active fraction by crystallization with hexanes. Structure of the pure compound was elucidated by spectroscopic methods. The antiulcer activity of the pure compound was evaluated by the inhibition of 1N HCl, 95% ethanol and indomethacin induced gastric lesions in mice.. The MeOH extract of Zingiber montanum showed 61.97% and 83.10% inhibition of the 1N HCl induced gastric lesions at doses of 200mg/kg and 400mg/kg, respectively, in mice. Chromatographic separation on silica gel of the extract was yielded seven fractions and the fraction 2 was found to have most potent antiulcer activity in mice. This fraction showed 77.46% inhibition of the 1N HCl induced gastric lesions at a dose of 40mg/kg in mice. Crystallization of the fraction yielded 1 (zerumbone, 180mg). It showed statistically 45.77% and 92.25% inhibition of 1N HCl induced gastric lesions in mice at doses of 20mg/kg and 40mg/kg, respectively. It also showed 29.07% and 45.35% inhibition of 95% ethanol induced gastric mucosal damage, and 64.76% and 72.38% inhibition of indomethacin induced gastric lesions in mice at doses of 20mg/kg and 40mg/kg, respectively.. Zerumbone (1) showed potent cytoprotective effect against necrotizing agent (HCl) and non-steroidal anti-inflammatory drug (indomethacin) induced gastric ulceration. It also exhibited moderate cytoprotective effect against noxious agent (EtOH) induced gastric lesions. It can be considered as a promising new antiulcer natural drug lead.

Topics: Animals; Anti-Ulcer Agents; Chromatography; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Ethanol; Female; Gastric Mucosa; Hydrochloric Acid; Indomethacin; Magnetic Resonance Spectroscopy; Male; Methanol; Mice; Molecular Structure; Phytotherapy; Plants, Medicinal; Rhizome; Sesquiterpenes; Solvents; Stomach Ulcer; Zingiberaceae

This paper investigated the potential effects of zerumbone pretreatment on an acute necrotizing pancreatitis rat model induced by sodium taurocholate. The pancreatitis injury was evaluated by serum AMY, sPLA2, and pancreatic pathological score. Pancreatitis-induced hepatic injury was measured by ALT, AST, and hepatic histopathology. The expression of I-κBα and NF-κB protein was evaluated by western blot and immunohistochemistry assay while ICAM-1 and IL-1β mRNA were examined by RT-PCR. The results showed that AMY, sPLA2, ALT, and AST levels and histopathological assay of pancreatic and hepatic tissues were significantly reduced following administration of zerumbone. Applying zerumbone also has been shown to inhibit NF-κB protein and downregulation of ICAM-1 and IL-1β mRNA. The present paper suggests that treatment of zerumbone on rat attenuates the severity of acute necrotizing pancreatitis and pancreatitis-induced hepatic injury, via inhibiting NF-κB activation and downregulating the expression of ICAM-1 and IL-1β.

Topics: Amylases; Animals; Anti-Inflammatory Agents; Disease Models, Animal; Gene Expression Regulation; I-kappa B Proteins; Intercellular Adhesion Molecule-1; Interleukin-1beta; Liver; Male; NF-kappa B; NF-KappaB Inhibitor alpha; Pancreatitis, Acute Necrotizing; Phospholipases A2; Rats; Rats, Wistar; Sesquiterpenes; Taurocholic Acid

The anti-inflammatory activity of zerumbone (1), a natural cyclic sesquiterpene isolated from Zingiber zerumbet Smith was investigated using carrageenan-induced paw edema and cotton pellet-induced granuloma tissue formation test in mice. It was demonstrated that intraperitoneal administration of 1 at a dose of 5, 10, 50 and 100 mg/kg produced significant dose-dependent inhibition of paw edema induced by carrageenan. It was also demonstrated that 1 at similar doses significantly suppressed granulomatous tissue formation in cotton pellet-induced granuloma test.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Disease Models, Animal; Edema; Gossypium; Granuloma; Inflammation; Male; Mice; Mice, Inbred ICR; Phytotherapy; Plant Extracts; Rhizome; Sesquiterpenes; Zingiberaceae

Recent in vitro and in vivo studies have demonstrated that zerumbone (ZER) possesses anticancer properties. The main objective of this study was to examine the effectiveness of the combination of ZER and cisplatin (CIS) to treat cervical intraepithelial neoplasia (CIN) in vivo. Microculture tetrazolium assay and immunohistochemistry of proliferating cellular nuclear antigen were used to study the antitumor effect of ZER. Prenatally exposed female BALB/c mice were used as a model. The progenies with CIN were injected peritoneally with isotonic sodium chloride solution (positive control), CIS, ZER, and a combination of both compounds. All treated and untreated mice were humanely killed, and serum and cervix were obtained for interleukin 6 analysis and histopathologic studies using hematoxylin and eosin staining, respectively. Zerumbone has revealed an antitumor effect on human cervical cancer cells and downregulates immunoexpression of proliferating cellular nuclear antigen (P < 0.05). In vivo study indicates that ZER at 16 mg/kg and CIS at 10 mg/kg have a regressing effect on CIN. The combination of ZER and CIS also showed similar effectiveness in regressing CIN. Our results indicate that the combination of ZER and CIS has modulated the serum level of interleukin 6 when compared with that in mice treated with isotonic sodium chloride solution (P < 0.05). The effectiveness of combining ZER and CIS could be further explored as a new therapeutic intervention of early precancerous stages of carcinogenesis before the invasive stage begins.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Proliferation; Cell Survival; Cisplatin; Diethylstilbestrol; Disease Models, Animal; Drug Screening Assays, Antitumor; Female; HeLa Cells; Humans; Male; Mice; Mice, Inbred BALB C; Sesquiterpenes; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Ulcerative colitis (UC) and Crohn's disease are inflammatory disorders of unknown cause and difficult to treat, though some synthetic chemicals, including ligands for peroxisome proliferator-activated receptors (PPARs), are anticipated to be useful drugs. In contrast, few food phytochemicals have been reported to suppress colitis in animal models. The present study was undertaken to explore the suppressive efficacy of zerumbone (ZER), a sesquiterpenoid present in the rhizome of Zingiber zerumbet Smith that is used as a condiment in Southeast Asian countries and known to be a potent suppressant of cyclooxygenase (COX)-2 and inducible nitric oxide synthase expression in cell culture systems. Acute colitis was induced by exposing female ICR mice to 5% DSS in drinking water for 1 week. One week prior to DSS administration, the experimental mice were fed ZER alone, nimesulide (NIM, a selective COX-2 inhibitor) alone, or both in combination (1000 ppm each) for a total of 2 weeks. Inflammatory biomarkers, i.e. interleukin (IL)-1alpha and IL-1beta, tumor necrosis factor (TNF)-alpha, and prostaglandin (PG)E(2) and PGF(2alpha) in colonic mucosa were quantified by an enzyme-linked immunosorbent assay in conjunction with histological alterations. Oral feeding of ZER significantly lowered the levels of IL-1beta [inhibitory rate (IR)=34%], TNF-alpha (IR=29%), and PGE(2) (IR=73%) and suppressed DSS-induced colitis, whereas NIM suppressed the histological changes induced by DSS without affecting inflammatory biomarkers. However, their treatment in combination was most effective for suppressing these biomarkers. Our results suggest that ZER is a novel food factor for mitigating experimental UC and that use of a combination of agents, with different modes of actions, may be an effective anti-inflammatory strategy.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Colitis; Dextran Sulfate; Disease Models, Animal; Drug Therapy, Combination; Female; Mice; Sesquiterpenes; Sulfonamides; Zingiber officinale