Basic Clin Pharmacol Toxicol. 2014 Aug;115(2):209-15. doi: 10.1111/bcpt.12196. Epub 2014 Feb 15.

Preventative effect of Zingiber officinale on insulin resistance in a high-fat high-carbohydrate diet-fed rat model and its mechanism of action.

Li Y, Tran VH, Kota BP, Nammi S, Duke CC, Roufogalis BD.

Faculty of Pharmacy, The University of Sydney, Sydney, NSW, Australia.

 

Abstract:

Insulin resistance is a core component of metabolic syndrome and usually precedes the development of type 2 diabetes mellitus. We have examined the preventative effect of an ethanol extract of ginger (Zingiber officinale, Zingiberaceae) on insulin resistance in a high-fat high-carbohydrate (HFHC) diet-fed rat model of metabolic syndrome. The HFHC control rats displayed severe insulin resistance, whilst rats treated with ginger extract (200 mg/kg) during HFHC diet feeding showed a significant improvement of insulin sensitivity using the homeostatic model assessment of insulin resistance (HOMA-IR) after 10 weeks (p < 0.01). An in vitro mechanistic study showed that (S)-[6]-gingerol, the major pungent phenolic principle in ginger, dose-dependently (from 50 to 150 μM) increased AMPK α-subunit phosphorylation in L6 skeletal muscle cells. This was accompanied by a time-dependent marked increment of PGC-1α mRNA expression and mitochondrial content in L6 skeletal muscle cells. These results suggest that the protection from HFHC diet-induced insulin resistance by ginger is likely associated with the increased capacity of energy metabolism by its major active component (S)-[6]-gingerol.

PMID: 24428842

 

Supplement:

Zingiber officinale (ginger) is a widely used spice and medicinal herb. Ginger has been the subject of research in our laboratory since 2001. Over the years we have developed several biological methods to understand and establish the scientific basis for the beneficial effects of ginger in type 2 diabetes and metabolic syndrome and our findings have been published in various international journals. In the present research study, we attempted to explore beneficial effects of ginger in rats that are fed with a modern cafeteria-style high fat and high carbohydrate diet. We designed this research study to investigate the potential role of ginger extract in maintaining healthy blood glucose levels when individuals are regularly exposed to a high fat diet coupled with a high content of simple sugars (sucrose and fructose), as often found in a modern cafeteria diet.

fig 1We have used the high fat and high carbohydrate (HFHC) fed rat model to observe the gross changes such as body weight, blood glucose and insulin levels and employed cell based assays to explore the underlying molecular mechanisms responsible for the changes observed in the rodent model. Please refer to the full article for details of the experimental methods.

The ginger extract used in this study is standardized to contain 15.6% (S)-[6]-gingerol. Ginger extract (200 mg/kg) exhibited a trend towards weight gain reduction in HFHC fed rats over 10 weeks. The effects of ginger on blood glucose levels in HFHC fed rats were more profound and confirmed by three separate experiments: 1. Ginger extract (200 mg/kg) markedly reduced blood glucose levels in HFHC fed rats when compared to the HFHC control group. 2. An oral glucose tolerance test (a good indicator of insulin sensitivity) at the end of the 10 week study revealed that ginger extract (200 mg/kg) protected HFHC fed rats from developing insulin resistance symptoms by maintaining blood glucose levels that are similar to normal rats treated with standard diet. 3. Ginger extract treatment (200 mg/kg) markedly reduced serum insulin levels and improved insulin sensitivity in HFHC fed rats and this effect is comparable to the diabetes prescription drug metformin in the HFHC fed rats.

The encouraging findings from these animal experiments led us to conduct further studies to understand the underlying molecular mechanisms that are involved in reducing blood glucose levels and glucose tolerance by the ginger extract. (S)-[6]-gingerol is the major component of the ginger extract we used in our studies. Therefore, we examined the effects of (S)-[6]-gingerol on AMPKα and PGC-1α (regulators of energy metabolism) and found that (S)-[6]-gingerol significantly increased their phosphorylation and m-RNA expression, respectively, in the cell based assays.

In summary, animal data in a rat model of metabolic syndrome revealed that ginger extract enhanced the metabolic capacity of the rats, thereby negating the adverse effects of a HFHC diet. Cell based assays indicated that (S)-[6]-gingerol increased the expression of proteins that are key regulators of glucose metabolism.

The data from our study indicate the potential health benefits of ginger as a complementary medicine to maintain healthy blood glucose levels in individuals in developed nations who are constantly exposed to a high calorie diet. A clinical study using a similar ginger extract will be required to further cement its role as a complementary or even alternative conventional therapy for metabolic syndrome.

 

References:

  1. Li Y, Tran VH, Kota BP, Nammi S, Duke CC, Roufogalis BD. Preventative effect of Zingiber officinale on insulin resistance in a high-fat high-carbohydrate diet-fed rat model and its mechanism of action. Basic Clin Pharmacol Toxicol. 2014 Aug;115(2):209-15.
  2. Gingerols of Zingiber officinale enhance glucose uptake by increasing cell surface GLUT4 in cultured L6 myotubes. Li Y, Tran VH, Duke CC, Roufogalis BD. Planta Med. 2012 Sep;78(14):1549-55.

 

Contact:

BASIL D ROUFOGALIS | Professor Emeritus

Discipline of Pharmacology, School of Medical Sciences, Sydney Medical School

THE UNIVERSITY OF SYDNEY

Bosch Building, The University of Sydney | NSW | 2006

T +61 2 9351 2360

E basil.roufogalis@sydney.edu.au | W http://sydney.edu.au

 

 

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