ThesisPDF Available

Effect of ginger on some biochemical parameters in obese male rats

Authors:

Abstract and Figures

The obesity epidemic is a growing health, social and economic problem worldwide. Aside from being a social stigma, obesity is frequently associated with insulin resistance, in turn linked to development of type II diabetes, hypertension, hyperlipidemia, and atherosclerosis – the so-called metabolic syndrome (Alberti et al., 2006). Obesity and metabolic syndrome have earned the name “the silent disease” because their adverse effects are insidious (Abraham et al., 2016). According to World Health Organization (WHO), Obesity is defined as a profuse accumulation of fat caused by an imbalance in intake and consumption of energy accompanied by insufficient physical activity (WHO, 2017). Obesity is considered as a complex neuroendocrine disorder in which genetic predisposition and environmental factors act in concern (Walley et al., 2009, and Hebebrand et al, 2009). The brain plays a relevant role in the regulation of appetite, body weight, and physical activity. The hypothalamus [via regulatory neuropeptides such as cholecystokinin, ghrelin, neuropeptide Y] is a brain region that chiefly regulates hemostasis food intake (Dietrich et al, 2009) and is implicated in obesity (Belgardt et al., 2009). Also, Adipocytes secrete a variety of bioactive peptide hormones called adipokines [e.g. leptin, adiponectin, resistin, visfatin, tumor necrosis factor-α (TNF-α) and interleukin (IL)-6], which play a role in energy regulation (Garg, 2006). A unifying mechanism behind the pathogenesis of obesity-associated diseases has given birth of the concept of "meta-inflammation" which describes the chronic low grade inflammatory response to obesity (Lumeng et al, 2011).WNT-inducible signaling pathway protein-1(WISP1), also known as CCN4, is a novel adipokine which is a member of secreted extracellular matrix-associated proteins of the CCN family and a target gene of Wingless type (WNT) signaling pathway. Growing evidence links the WNT signaling pathway to the regulation of adipogenesis and meta-inflammation in obesity (Murahovschi et al., 2015). WNT signaling family members are secreted glycoproteins that act in both autocrine and paracrine fashions to regulate cell proliferation, cell fate and differentiation (Logan et al, 2004). The WNT signaling network comprises multiple so-called "canonical' and "non-canonical" pathways that lead to tightly controlled cell remodeling. WISP1 is a downstream target gene of the non-canonical WNT signaling pathway (Katoh et al, 2007) and acts anti-apoptotically through the phosphatidyl-inositol 3-kinase (PIK) and Akt pathways (Maiese et al., 2012). Heme oxygenase-1 (HO1), the rate-limiting enzyme (EC 1.14.99.3) in heme degradation, catalyzes the oxidation of heme to generate several biologically active molecules: carbon monoxide, biliverdin, and ferrous ion (Maines, 1988). Li et al. (2007) reported that induction of HO1 enhances cell survival and moderates diabetes and obesity. Furthermore, Vanella et al. (2013) showed that increased HO1 expression and activity decreased adipocyte hypertrophy and TNF-α level, and increased adiponectin level and expression of the genes central to the canonical WNT signaling cascade. HO1 acted as upstream regulator of canonical WNT signaling cascade decreasing lipogenesis and adipocyte differentiation.The medicinal properties of ginger have been used since ancient times in India for various biomedical applications especially obesity. Ginger (Zingiber officinale) is the rhizome of the plant, which belongs to the family Zingiberaceae, and is consumed as a medicine or spice (Ali et al., 2008). The major chemical constituents of the ginger rhizome include a volatile oil and non-volatile pungent compounds e.g. gingerols, shagols and zingerones (Tapsell et al., 2006). Various well-reported pharmacological activities of ginger and its constituents include anti-ulcer, antiplatelet, hypotensive and hypolipidemic actions (González-Castejón et al, 2011).
Content may be subject to copyright.
A preview of the PDF is not available
ResearchGate has not been able to resolve any citations for this publication.
Article
Full-text available
Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. The pathogenesis of this disease is closely associated with obesity and insulin resistance. Ginger can have hypolipidemic and antioxidant effects, and act as an insulinsensitizer. Objectives: The aim of this study was to evaluate the effects of ginger supplementation in NAFLD management. Patients and methods: In a randomized, double-blind, placebo-controlled clinical trial, 44 patients with NAFLD were assigned to take either two grams per day of a ginger supplement or the identical placebo, for 12 weeks. In both groups, patients were advised to follow a modified diet and physical activity program. The metabolic parameters and indicators of liver damage were measured at study baseline and after the 12 week intervention. Results: Ginger supplementation resulted in a significant reduction in alanine aminotransferase, γ-glutamyl transferase, inflammatory cytokines, as well as the insulin resistance index and hepatic steatosis grade in comparison to the placebo. We did not find any significant effect of taking ginger supplements on hepatic fibrosis and aspartate aminotransferase. Conclusions: Twelve weeks of two grams of ginger supplementation showed beneficial effects on some NAFLD characteristics. Further studies are recommended to assess the long-term supplementation effects.
Article
Full-text available
Mechanical ventilation may cause ventilator-induced lung injury (VILI). Canonical Wnt signaling has been reported to serve an important role in the pathogenesis of VILI. Bioinformatics analysis revealed that canonical and non-canonical Wnt signaling pathways were activated in VILI. However, the role of non-canonical Wnt signaling in the pathogenesis of VILI remains unclear. The present study aimed to analyze the potential role of non-canonical Wnt signaling in VILI pathogenesis. Lung injury was assessed via Evans blue albumin permeability and histological scoring, as well as by inflammatory cytokine expression and total protein concentration in bronchoalveolar lavage fluid. The relative protein expression of canonical and non-canonical Wnt signaling pathway components were examined via western blotting and immunohistochemistry. The results demonstrated that 6 h of mechanical ventilation at low tidal volume (LTV; 6 ml/kg) or moderate tidal volume (MTV; 12 ml/kg) induced lung injury in sensitive A/J mice. Ventilation with MTV increased the protein levels of Wnt-induced secreted protein 1 (WISP1), Rho-associated protein kinase 1 (ROCK1), phosphorylated (p)-Ras homolog gene family, member A and p-C-Jun N-terminal kinase (JNK). Inhibition of ROCK1 by Y27632 and JNK by SP600125 attenuated MTV-induced lung injury and decreased the expression of proteins involved in non-canonical Wnt signaling, including WISP1. In conclusion, non-canonical Wnt signaling participates in VILI by modulating WISP1 expression, which has been previously noted as critical for VILI development. Therefore, the non-canonical Wnt signaling pathway may provide a preventive and therapeutic target in VILI.
Article
Full-text available
Ginger, one of worldwide consumed dietary spice, in fact, it is not only famous as food supplements, and also believed to exert a variety of remarkable pharmacological activity as herbal remedies. In this study, a ginger constituent, 12-dehydrogingerdione (DHGD) was proven that has comparable anti-inflammatory activity with positive control 6-shogaol in inhibiting LPS-induce dinterleukin (IL)-6, tumor necrosis factor (TNF)-α, prostaglandin (PG) E2, nitric oxide (NO), inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, without interfering with COX-1 in cultured microglial cells. Subsequent mechanistic studies indicate that 12-DHGD may inhibit neuro-inflammation through suppressing the LPS-activated Akt/IKK/NF-κB pathway. Furthermore, 12-DHGD markedly promoted the activation of NF-E2-related factor (Nrf)-2 and heme oxygenase (HO)-1, and we demonstrated that the involvement of HO-1 on the production of pro-inflammatory mediators such as NO and TNF-α by using a HO-1 inhibitor, Zinc protoporphyrin (Znpp). These results indicate that 12-DHGD may protect against neuro-inflammation by inhibiting Akt/IKK/IκB/NF-κB pathway and promoting Nrf-2/HO-1 pathway.
Article
Full-text available
Ginger is a plant whose rhizome is used as a spice or folk medicine. We aimed to investigate the effect of ginger root extract on obesity and inflammation in rats fed a high-fat diet. Sprague-Dawley rats were divided into three groups and fed either a 45% high-fat diet (HF), HF + hot-water extract of ginger (WEG; 8 g/kg diet), or HF + high-hydrostatic pressure extract of ginger (HPG; 8 g/kg diet) for 10 weeks. The HPG group had lower body weight and white adipose tissue (WAT) mass compared to the HF group. Serum and hepatic lipid levels of HPG group were lower, while fecal lipid excretion of the HPG group was higher than that of the HF group. In the WAT of the WEG and HPG groups, mRNA levels of adipogenic genes were lower than those of the HF group. Moreover, HPG group had lower mRNA levels of pro-inflammatory cytokines than did the HF group. MicroRNA (miR)-21 expression was down-regulated by both WEG and HPG. Additionally, miR-132 expression was down-regulated by HPG. The adenosine monophosphate-activated protein kinase (AMPK) activity of HPG group was greater than that of the HF group. HPG may have beneficial effects on obesity and inflammation, partially mediated by regulation of miR-21/132 expression and AMPK activation in WAT.
Article
Full-text available
Aims/hypothesis: Wingless-type (Wnt) inducible signalling pathway protein-1 (WISP1) has been recently identified as a proinflammatory adipokine. We examined whether WISP1 expression and circulating levels are altered in type 2 diabetes and whether WISP1 affects insulin signalling in muscle cells and hepatocytes. Methods: Serum and visceral adipose tissue (VAT) biopsies, for analysis of circulating WISP1 levels by ELISA and WISP1 mRNA expression by real-time quantitative RT-PCR, were collected from normal-weight men (control group, n = 33) and obese men with (n = 46) and without type 2 diabetes (n = 56) undergoing surgery. Following incubation of primary human skeletal muscle cells (hSkMCs) and murine AML12 hepatocytes with WISP1 and insulin, insulin signalling was analysed by western blotting. The effect of WISP1 on insulin-stimulated glycogen synthesis and gluconeogenesis was investigated in hSkMCs and murine hepatocytes, respectively. Results: Circulating WISP1 levels were higher in obese men (independent of diabetes status) than in normal-weight men (mean [95% CI]: 70.8 [55.2, 86.4] ng/l vs 42.6 [28.5, 56.6] ng/l, respectively; p < 0.05). VAT WISP1 expression was 1.9-fold higher in obese men vs normal-weight men (p < 0.05). Circulating WISP1 levels were positively associated with blood glucose in the OGTT and circulating haem oxygenase-1 and negatively associated with adiponectin levels. In hSkMCs and AML12 hepatocytes, recombinant WISP1 impaired insulin action by inhibiting phosphorylation of insulin receptor, Akt and its substrates glycogen synthase kinase 3β, FOXO1 and p70S6 kinase, and inhibiting insulin-stimulated glycogen synthesis and suppression of gluconeogenic genes. Conclusions/interpretation: Circulating WISP1 levels and WISP1 expression in VAT are increased in obesity independent of glycaemic status. Furthermore, WISP1 impaired insulin signalling in muscle and liver cells.
Article
Full-text available
Heme oxygenase-1 (HO-1) is considered to be the main protein in diseases arising as a result of oxidative and inflammatory insults. Tremendous research has been carried out on HO-1 since years, pertaining its cytoprotective effect against oxidative injury and other cellular stresses. HO-1, by regulating intracellular levels of pro-oxidant heme, or by other benefits of its by-products such as carbon monoxide (CO) and biliverdin (BV) had become an important candidate protein to be up-regulated to combat diverse stressful events. Although the beneficial effects of HO-1 induction have been reported in a number of cells and tissues, a growing body of evidence indicates that this increased HO-1 expression may lead to the progression of several diseases such as neurodegeneration, carcinogenesis. But it is not clear, what accounts for the increased expression of HO-1 in cells and tissues. The observed friendly role of HO-1 in a wide range of stress conditions since times is now doubtful. Therefore, more studies are needed to elucidate the exact role of HO-1 in various stressful events. Being more concise, elucidating the effect of HO-1 up-regulation on critical genes involved in particular diseases such as cancer will help to a larger extent to comprehend the exact role of HO-1. This review will assist in understanding the dual role (protective and detrimental) of HO-1 and the signaling pathway involved and will help in unraveling the doubtful role of HO-1 induction.
Article
Full-text available
The canonical Wnt/β-catenin pathway is a highly conserved signaling cascade that plays critical roles during embryogenesis. Wnt ligands regulate axonal extension, growth cone guidance and synaptogenesis throughout the developing central nervous system (CNS). Recently, studies in mammalian and fish model systems have demonstrated that Wnt/β-catenin signaling also promotes axonal regeneration in the adult optic nerve and spinal cord after injury, raising the possibility that Wnt could be developed as a therapeutic strategy. In this review, we summarize experimental evidence that reveals novel roles for Wnt signaling in the injured CNS, and discuss possible mechanisms by which Wnt ligands could overcome molecular barriers inhibiting axonal growth to promote regeneration. A central challenge in the neuroscience field is developing therapeutic strategies that induce robust axonal regeneration. Although adult axons have the capacity to respond to axonal guidance molecules after injury, there are several major obstacles for axonal growth, including extensive neuronal death, glial scars at the injury site, and lack of axonal guidance signals. Research in rodents demonstrated that activation of Wnt/β-catenin signaling in retinal neurons and radial glia induced neuronal survival and axonal growth, but that activation within reactive glia at the injury site promoted proliferation and glial scar formation. Studies in zebrafish spinal cord injury models confirm an axonal regenerative role for Wnt/β-catenin signaling and identified the cell types responsible. Additionally, in vitro and in vivo studies demonstrated that Wnt induces axonal and neurite growth through transcription-dependent effects of its central mediator β-catenin, potentially by inducing regeneration-promoting genes. Canonical Wnt signaling may also function through transcription-independent interactions of β-catenin with cytoskeletal elements, which could stabilize growing axons and control growth cone movement. Therefore, these studies suggest that Wnt-induced pathways responsible for regulating axonal growth during embryogenesis could be repurposed to promote axonal growth after injury.
Article
SCI-45 Clinical and epidemiological studies have long established a connection between obesity and thrombosis leading to increased cardiovascular complications, in part attributed to elevated expression of the prothrombotic molecules plasminogen activator inhibitor 1 and circulating tissue factor (TF). Obesity also increases the risk for metabolic dysfunction, and emerging evidence indicates that coagulation proteases offer a range of signaling pathways that control multiple aspects of the metabolic syndrome, including weight gain, insulin resistance, type 2 diabetes, and hepatic steatosis. While adipose inflammation due to recruitment and activation of macrophages and secretion of inflammatory cytokines promotes systemic hypercoagulability and insulin resistance, pathways that sustain adipose macrophage inflammation in obesity are unclear. Our studies suggest that TF signaling via the G-protein-coupled receptor, protease activated receptor 2 (PAR2), represents a novel link between obesity, coagulation, and associated adipose inflammation and insulin resistance. Mice lacking the cytoplasmic domain of TF or PAR2 were protected from high fat diet-induced weight gain, adipose inflammation, and insulin resistance. Genetic loss of TF cytoplasmic domain and PAR2 in myeloid cells attenuated adipose macrophage inflammation and increased insulin sensitivity, an effect that was also achieved by acute pharmacologic inhibition of TF-PAR2 signaling in macrophages. In contrast, TF signaling in nonhematopoietic cells specifically promoted obesity via its effects on energy metabolism. In adipocytes, TF-VIIa signaling suppressed basal and insulin-mediated AKT phosphorylation, with concordant transcriptional changes in genes regulating lipid and glucose metabolism. Thus, the procoagulant state induced by obesity can in fact contribute to the metabolic syndrome, and adipose TF signaling may be at the intersection between obesity, inflammation, and thrombosis. Disclosures No relevant conflicts of interest to declare.
Article
Obesity is associated with low-grade chronic inflammation of adipose tissue, which leads to the development of metabolic disorders such as insulin resistance, type 2 diabetes, cardio vascular disease (CVD), and cancer. Obesity and a high calorie diet are associated with altered endocrine and metabolic functions of adipose tissue contributing to systemic inflammation as a result of the release of pro-inflammatory cytokines/adipokines into the circulation and metabolic endotoxemia. Furthermore, the accumulation of proinflammatory macrophages within the visceral adipose tissue also may be a major cause of chronic inflammation of adipocytes. Thus, it is important to understand factors that regulate the function of both adipocytes and macrophages to find attractive strategies that counteract the burden of obesity-induced health problems. Although the vast range of activities of dietary bioactive compounds on obesity and inflammation has been widely investigated, the mechanism underlying their beneficial effects on obesity-associated inflammatory response are still poorly understood. This review focuses on the molecular biological mechanism of obesity-induced inflammation and the reciprocal interactions between the major molecular mechanisms and a range of dietary bioactive compounds.
Article
Obesity is a health concern related with many metabolic disorders. In the prevention and treatment of overweight, medicines and bariatric surgeries are major strategies but with side effects. A variety of naturally occurring bioactive ingredients derived from common spices, including cinnamon, rosemary, ginger, pepper, saffron, garlic, onion and turmeric, have been proved to have weight-loss effects. In this work, the molecular mechanisms of anti-obesity effect of eight common spices are reviewed and evaluated in cell models, animal models and human subjects. Bioactive compounds from these spices are able to reduce lipid accumulation in fat cells and adipose tissues through regulating the expressions of related transcriptional factors, such as CCAAT/enhancer-binding proteins (C/EBPs) and peroxisome proliferator-activated receptor gamma (PPAR); modulating activities of certain enzymes related with lipogenesis, such as acyl-CoA carboxylase (ACC), fatty acid synthase (FAS), glycerol-3-phosphate dehydrogenase (GPDH) and others. The induced apoptosis in 3T3-L1 cells, promoted thermogenesis in adipose tissues, decreased body weight gain in obese animal models and human participants have also been reported after the oral treatment of spice extracts, providing theoretical basis for these functional food compounds to be developed into dietary supplements against obesity.