6-gingerol ameliorates metabolic disorders by inhibiting hypertrophy and hyperplasia of adipocytes in high-fat-diet induced obese mice

Cheng, Zhe; Xiong, Xinyu; Zhou, Yi; Wu, Fan; Shao, Qingqing; Dong, Ruolan; Liu, Qiong; Li, Lingli; Chen, Guang

doi:10.1016/j.biopha.2021.112491

Cited by 14 publications

(14 citation statements)

References 49 publications

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“…Ginger was used to treat diseases in ancient China. 6-Gingerol (6-G), a polyphenol extracted from ginger, has been reported to have anti-inflammatory, antiapoptotic, and antioxidant properties [16][17][18], and studies have shown that 6-G can upregulate the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to alleviate liver injury [19,20]. 6-G can also modulate ferroptosis by inhibiting ubiquitin-specific peptidase 14 [21].…”

Section: Introductionmentioning

confidence: 99%

6-Gingerol Alleviates Ferroptosis and Inflammation of Diabetic Cardiomyopathy via the Nrf2/HO-1 Pathway

Zhu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. 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. Objective. To characterize the therapeutic effect of 6-gingerol (6-G) on DCM and identify its potential mechanism. Methods. In vivo streptozotocin- (STZ-) induced DM model was established by using a high-fat diet and STZ, followed by low-dose (25 mg/kg) and high-dose (75 mg/kg) 6-G intervention. For an in vitro DCM model, H9c2 rat cardiomyoblast cells were stimulated with high glucose ( glucose = 33 mM) and palmitic acid (100 μM) and then treated with 6-G (100 μM). Histological and echocardiographic analyses were used to assess the effect of 6-G on cardiac structure and function in DCM. Western blotting, ELISA, and real-time qPCR were used to assess the expression of ferroptosis, inflammation, and the Nrf2/HO-1 pathway-related proteins and RNAs. Protein expression of collagen I and collagen III was assessed by immunohistochemistry, and kits were used to assay SOD, MDA, and iron levels. Results. The results showed that 6-G decreased cardiac injury in both mouse and cell models of DCM. The cardiomyocyte hypertrophy and interstitial fibrosis were attenuated by 6-G treatment in vivo and resulted in an improved heart function. 6-G inhibited the expression of ferroptosis-related protein FACL4 and the content of iron and enhanced the expression of anti-ferroptosis-related protein GPX4. In addition, 6-G also diminished the secretion of inflammatory cytokines, including IL-1β, IL-6, and TNF-α. 6-G treatment activated the Nrf2/HO-1 pathway, enhanced antioxidative stress capacity proved by increased activity of SOD, and decreased MDA production. Compared with in vivo, 6-G treatment of H9c2 cells treated with high glucose and palmitic acid could produce a similar effect. Conclusion. 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.

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Section: Introductionmentioning

confidence: 99%

6-Gingerol Alleviates Ferroptosis and Inflammation of Diabetic Cardiomyopathy via the Nrf2/HO-1 Pathway

Zhu

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Obesity is characterized by the enlargement of white adipocytes. 15 According to the H&E staining results (Fig. 3a and b), the control group had normal adipose tissue with intact morphology and uniformly sized adipocytes with a relatively small volume.…”

Section: Results and Analysismentioning

confidence: 88%

“…12 In particular, phenolic compounds have been reported to be effective in lipid reduction and weight loss, both in vivo and in vitro . 13–15…”

Section: Introductionmentioning

confidence: 99%

“…12 In particular, phenolic compounds have been reported to be effective in lipid reduction and weight loss, both in vivo and in vitro. [13][14][15] Castanea is an edible plant genus within the Fagaceae family. Chinese chestnut (Castanea mollissima Blume) is rich in varieties and accounts for approximately 70% of the total chestnut yield globally.…”

Section: Introductionmentioning

confidence: 99%

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Chinese chestnut shell polyphenol extract regulates the JAK2/STAT3 pathway to alleviate high-fat diet-induced, leptin-resistant obesity in mice

et al. 2023

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“…6-Gingerol (6-G, PubChem CID: 442793), one of the major pharmacologically active ingredients extracted from ginger, has been found to have pleiotropic pharmacological functions, including anti-oxidative [ 17 ], anti-inflammatory [ 18 ], anti-obesity, anti-cancer [ 19 , 20 ], anti-hyperglycemic and immunomodulatory [ 21 , 22 ] effects. Previously, 6-gingerol was reported experimentally to alleviate hepatic steatosis in HFD-fed mice [ 23 , 24 ], as well as to mitigate intracellular lipid accumulation and to activate AMPK in free fatty acid (FFA)-induced Hepa1–6 cells [ 24 ]. It has been reported that 6-gingerol modulates the inflammatory status and the metabolic disorders in HFD-fed rats, which is associated with a 6-gingerol-induced activating effect on hepatic AMPK [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

6-Gingerol Ameliorates Hepatic Steatosis, Inflammation and Oxidative Stress in High-Fat Diet-Fed Mice through Activating LKB1/AMPK Signaling

Liu

Dong

Wang

et al. 2023

IJMS

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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.

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6-gingerol ameliorates metabolic disorders by inhibiting hypertrophy and hyperplasia of adipocytes in high-fat-diet induced obese mice

Cited by 14 publications

References 49 publications

6-Gingerol Alleviates Ferroptosis and Inflammation of Diabetic Cardiomyopathy via the Nrf2/HO-1 Pathway

6-Gingerol Alleviates Ferroptosis and Inflammation of Diabetic Cardiomyopathy via the Nrf2/HO-1 Pathway

Chinese chestnut shell polyphenol extract regulates the JAK2/STAT3 pathway to alleviate high-fat diet-induced, leptin-resistant obesity in mice

6-Gingerol Ameliorates Hepatic Steatosis, Inflammation and Oxidative Stress in High-Fat Diet-Fed Mice through Activating LKB1/AMPK Signaling

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