gingerol and Obesity

Metabolic syndrome is an inflammatory disorder characterized by diabetes, obesity, atherosclerosis, and hypertension. Globally, this disease is increasing, especially in developed countries. Supposedly, herbal treatments for this disease likely have fewer adverse effects than chemical medications. Thus, they can be suitable options among the available chemical treatments. Ginger has been used as a spice and medicinal plant in traditional medicine and cooking. This herbal compound and its derivatives, such as 6-gingerol, have shown promising effects on various molecular aspects of metabolic syndrome. In this study, we reviewed and discussed the significant impacts of gingerol, a derivative of ginger, on metabolic syndrome through various mechanisms. The benefits of 6-gingerol include its effects on AMP-activated protein kinase (AMPK), which prevent diabetes, lipid regulating effect (peroxisome proliferator-activated receptors, PPARs), as well as its effects on enzymes and proteins preventing hyperlipidemia caused by a high-fat diet. In addition, 6-gingerol has anti-atherosclerosis and anti-hypertension effects through several molecular mechanisms. The current review will discuss various effects of 6-gingerol on molecular pathways involved in diabetes, obesity, atherosclerosis, and hypertension as characterizing features of metabolic syndrome and suggests that 6-gingerol can be a potential treatment agent for metabolic syndrome and shed light on a higher requirement for more pre-clinical and clinical investigations.

Topics: AMP-Activated Protein Kinases; Catechols; Fatty Alcohols; Humans; Metabolic Syndrome; Obesity; Peroxisome Proliferator-Activated Receptors; Plant Extracts; Zingiber officinale

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

Accumulating studies revealed that 6-gingerol, a compound extracted mainly from ginger, treats obesity by preventing hyperlipidemia in vivo induced by high-fat-diet (HFD). The present study intends to further evaluate the efficacy of 6-gingerol in the treatment of obesity and investigate its potential mechanism.. Obese mice were established by HFD induction. Bioinformatic analysis was used to predict the possible pathways enrolled by the application of 6-gingerol. Body weight and the levels of blood glucose and lipids were examined and analyzed for the evaluation of the therapeutic effect of 6-gingerol. The size and amounts as well as the status of adipocytes were determined by histological staining. The expression levels of related proteins in adipose tissue were assessed by immunohistochemical staining, immunofluorescent staining, and Western blot analysis. In addition, the expression levels of related mRNA were assessed by RT-qPCR.. HFD induced obesity was significantly curbed by 6-gingerol treatment. Here inhibition mechanism of 6-gingerol is demonstrated on excessive hypertrophy and hyperplasia of adipocytes in white adipose tissue (WAT), which may be related to the regulation of adipocytokines, such as PPARγ, C/EBPα, FABP4 and adiponectin, and the TLR3/IL-6/JAK1/STAT3 axis. Moreover, 6-gingerol treatment suppressed the expressions of IL-1β and CD68 in the liver and AKT/INSR/IRS-1 in epididymal WAT.. The results suggested that 6-gingerol could alleviate metabolic inflammation in the liver and insulin resistance to treat obesity. The mechanism is mainly involved in the inhibition of excessive hypertrophy and hyperplasia of adipocytes.

Topics: Adipocytes; Animals; Anti-Obesity Agents; Catechols; Diet, High-Fat; Fatty Alcohols; Hyperplasia; Hypertrophy; Insulin Resistance; Interleukin-1beta; Liver; Male; Metabolic Diseases; Mice, Inbred C57BL; Obesity; PPAR gamma; STAT3 Transcription Factor

Obesity is one of the major health problems across the world and the leading cause of death. Natural bioactive functional compounds (catechin, Cat and gingerol, Gin) have been reported to control obesity. The application of a nanoparticulate (NPs) delivery system has shown greater efficacy in the treatment of different diseases. The present study was designed to prepare the Cat-Gin silver nanoparticles (AgNPs) using the microwave method. The prepared Cat-Gin-AgNPs were characterized for particle size, zeta potential, encapsulation efficiency and drug release. Further, it was evaluated for anti-obesity activity (body weight, total abdominal fat, lipid profile and liver profile) using a high-fed diet (HFD) induced obesity model. The formulated Cat-Gin-AGNPs showed nano-metric size (110 ± 4.65 nm), polydispersity index (PDI) of 0.27 ± 0.03, and surface charge (-17.6 ± 2.6 mV) with a spherical shape. It also depicted high encapsulation efficiency (<80 %) with prolonged drug release behaviour (Cat - 84.34 ± 4.12 % and Gin - 72.33 ± 3.87 %). The in vivo study parameters revealed a significant (p ≤ 0.001) reduction in body weight, food intake and total abdominal fat. The biochemical results displayed a reversal in altered biochemical parameters to the normal range (Group 4) as compared to HFD control (Group 2). It also helps restored the liver enzymes in obese rats. The results of the study highlighted the applicability of Cat-Gin-AGNPs as a novel delivery system in the treatment of obesity.

Topics: Animals; Body Weight; Catechin; Metal Nanoparticles; Nanomedicine; Obesity; Rats; Silver

Grains of paradise (GP) is the seed of Aframomum melegueta, which is widely distributed throughout West Africa and has been used as a spice and a folk remedy for a long time. Anti-obesity effect of GP intake was demonstrated in a previous report. Aim of the present study was to isolate some compounds in GP and clarify the anti-obesity mechanism.. Ten vanilloid compounds were isolated. Among them, 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-ol and 1-(4'-hydroxy-3'-methoxyphenyl)-3-octen-5-one were determined as novel compounds and 6-gingerol, 6-paradol and 6-shogaol were identified as the major constituents in GP extract. Moreover, the extract and 6-gingerol, which is one of the principal components of GP extract, were orally administered to rats to investigate the effect on sympathetic nerve activity (SNA) in brown adipose tissue (BAT). The injection of GP extract and 6-gingerol decreased BAT-SNA, whereas capsaicin, which is a major component of chili pepper, activates the sympathetic nervous system.. This study suggested that GP extract and 6-gingerol were largely unrelated to the anti-obesity effect by the activation of interscapular BAT-SNA and had a different anti-obesity mechanism to capsaicin. © 2018 Society of Chemical Industry.

Topics: Adipose Tissue, Brown; Animals; Catechols; Fatty Alcohols; Guaiacol; Humans; Ketones; Molecular Structure; Obesity; Plant Extracts; Rats; Seeds; Sympathetic Nervous System; Zingiberaceae

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

Obesity, generally linked to hyperlipidemia, has been occurring of late with distressing alarm and has now become a global phenomenon casting a huge economic burden on the health care system of countries around the world. The present study investigated the effects of gingerol over 30 days on the changes in HFD-induced obese rats in marker enzymes of lipid metabolism such as fatty-acid synthase (FAS), Acetyl CoA Carboxylase (ACC), Carnitine Palmitoyl Transferase-1(CPT-1), HMG co-A Reductase (HMGR), Lecithin Choline Acyl Transferase (LCAT) and Lipoprotein Lipase (LPL) and inflammatory markers (TNF-α and IL-6). The rats were treated orally with gingerol (75 mg kg(-1)) once daily for 30 days with a lorcaserin-treated group (10 mg kg(-1)) included for comparison. Changes in body weight, glucose, insulin resistance and expressions of lipid marker enzymes and inflammatory markers in tissues were observed in experimental rats. The administration of gingerol resulted in a significant reduction in body weight gain, glucose and insulin levels, and insulin resistance, which altered the activity, expressions of lipid marker enzymes and inflammatory markers. It showed that gingerol had significantly altered these parameters when compared with HFD control rats. This study confirms that gingerol prevents HFD-induced hyperlipidemia by modulating the expression of enzymes important to cholesterol metabolism.

Topics: Animals; Benzazepines; Biomarkers; Body Weight; Catechols; Diet, High-Fat; Fatty Alcohols; Gene Expression Regulation, Enzymologic; Insulin Resistance; Interleukin-6; Lipid Metabolism; Male; Obesity; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

We investigated the effects of 6-gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone) on the inhibition of rosiglitazone (RGZ)-induced adipogenesis in 3T3-L1 cells. The morphological changes were photographed based on staining lipid accumulation by Oil-Red O in RGZ (1 µmol/l)-treated 3T3-L1 cells without or with various concentrations of 6-gingerol on differentiation day 8. Quantitation of triglycerides content was performed in cells on day 8 after differentiation induction. Differentiated cells were lysed to detect mRNA and protein levels of adipocyte-specific transcription factors by real-time reverse transcription-polymerase chain reaction and Western blot analysis, respectively. 6-gingerol (50 µmol/l) effectively suppressed oil droplet accumulation and reduced the sizes of the droplets in RGZ-induced adipocyte differentiation in 3T3-L1 cells. The triglyceride accumulation induced by RGZ in differentiated 3T3-L1 cells was also reduced by 6-gingerol (50 µmol/l). Treatment of differentiated 3T3-L1 cells with 6-gingerol (50 µmol/l) antagonized RGZ-induced gene expression of peroxisome proliferator-activated receptor (PPAR)γ and CCAAT/enhancer-binding protein α. Additionally, the increased levels of mRNA and protein in adipocyte-specific fatty acid binding protein 4 and fatty acid synthase induced by RGZ in 3T3-L1 cells were decreased upon treatment with 6-gingerol. Our data suggests that 6-gingerol may be beneficial in obesity, by reducing adipogenesis partly through the down-regulating PPARγ activity.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Catechols; CCAAT-Enhancer-Binding Protein-alpha; Cell Differentiation; Down-Regulation; Fatty Acid Synthases; Fatty Acid-Binding Proteins; Fatty Alcohols; Mice; Obesity; PPAR gamma; RNA, Messenger; Rosiglitazone; Thiazolidinediones; Triglycerides

Obesity represents a rapidly growing threat to the health of populations and diet intervention has been proposed as one of the strategies for weight loss. Ginger and its constituents have been used for their anti-flatulent, expectorant and appetising properties and they are reported to possess gastro-protective and cholesterol-lowering properties. The present study investigated the effects of gingerol on the changes in body weight, serum glucose, insulin, insulin resistance and lipid profile in plasma and liver as well as on the activity of amylase, lipase and leptin in high-fat diet (HFD)-induced obese rats.. HFD-induced obese rats were treated orally with gingerol (25, 50 and 75 mg kg(-1) ) once daily for 30 days. A lorcaserin-treated group (10 mg kg(-1) ) was included for comparison. The levels of body weight, glucose, lipid profile and insulin, insulin resistance, leptin, amylase and lipase were increased significantly (P < 0.05) in HFD rats. Rats treated with gingerol and fed a HFD showed significantly (P < 0.05) decreased glucose level, body weight, leptin, insulin, amylase, lipase plasma and tissue lipids when compared to normal control. The effect at a dose of 75 mg kg(-1) of gingerol was more pronounced than that of the dose 25 mg kg(-1) and 50 mg kg(-1) . The lorcaserin-treated group also manifested similar effects to those of gingerol.. These findings suggested that ginger supplementation suppresses obesity induced by a high fat diet and it might be a promising adjuvant therapy for the treatment of obesity and its complications.

Topics: Amylases; Animals; Anti-Obesity Agents; Blood Glucose; Catechols; Dietary Fats; Fatty Alcohols; Insulin; Leptin; Lipase; Lipids; Male; Molecular Structure; Obesity; Rats; Weight Loss

6-Gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone) is one of the pungent constituents of Zingiber zerumbet (L) Smith (Zingiberaceae family). In this study, we investigated the effects of 6-gingerol on the inhibition of adipogenesis in 3T3-L1 cells. After treatment with 6-gingerol in differentiation medium for 4 or 8 days, the 3T3-L1 cells were lysed for experimental analysis. Cells were stained with Oil-Red-O to detect oil droplets in adipocytes. The 3T3-L1 cells were lysed and measured for triglyceride contents. The protein expression of adipogenesis-related transcription factor was evaluated by Western blot analysis. 6-Gingerol suppressed oil droplet accumulation and reduced the droplet size in a concentration (5-15 μg/ml)- and time-dependent manner. Treatment of 3T3-L1 cells with 6-gingerol reduced the protein levels of peroxisome proliferator-activated receptor (PPAR)γ and CCAAT/enhancer-binding protein (C/EBP)α. Additionally, the protein levels of fatty acid synthase (FAS) and adipocyte-specific fatty acid binding protein (aP2) decreased upon treatment with 6-gingerol. Meanwhile, 6-gingerol diminished the insulin-stimulated serine phosphorylation of Akt (Ser473) and GSK3β (Ser9). These results suggest that 6-gingerol effectively suppresses adipogenesis and that it exerts its role mainly through the significant down-regulation of PPARγ and C/EBPα and subsequently inhibits FAS and aP2 expression. 6-Gingerol also inhibited differentiation in 3T3-L1 cells by attenuating the Akt/GSK3β pathway. Our findings provide important insights into the mechanisms underlying the anti-adipogenic activity of 6-gingerol.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Catechols; CCAAT-Enhancer-Binding Protein-alpha; Cytoplasm; Fatty Acid Synthases; Fatty Acid-Binding Proteins; Fatty Alcohols; Hypolipidemic Agents; Insulin; Lipid Metabolism; Mice; Obesity; Phosphorylation; Phytotherapy; Plant Extracts; PPAR gamma; Zingiberaceae