A Prescribed Chinese Herbal Medicine Improves Glucose Profile and Ameliorates Oxidative Stress in Goto-Kakisaki Rats Fed with High Fat Diet

Oxidative stress (OS) plays a role in hyperglycemia induced islet β cell dysfunction, however, studies on classic anti-oxidants didn’t show positive results in treating diabetes. We previously demonstrated that the prescribed Chinese herbal medicine preparation “Qing Huo Yi Hao” (QHYH) improved endothelial function in type 2 diabetic patients. QHYH protected endothelial cells from high glucose-induced damages by scavenging superoxide anion and reducing production of reactive oxygen species. Its active component protected C2C12 myotubes against palmitate-induced oxidative damage and mitochondrial dysfunction. In the present study, we investigated whether QHYH protected islet β cell function exacerbated by high fat diet (HFD) in hyperglycemic GK rats. 4-week-old male rats were randomly divided into high HFD feeding group (n = 20) and chow diet feeding group (n = 10). Each gram of HFD contained 4.8 kcal of energy, 52% of which from fat. Rats on HFD were further divided into 2 groups given either QHYH (3 ml/Kg/d) or saline through gastric tube. After intervention, serum glucose concentrations were monitored; IPGTTs were performed without anesthesia on 5 fasting rats randomly chosen from each group on week 4 and 16. Serum malondialdehyde (MDA) concentrations and activities of serum antioxidant enzymes were measured on week 4 and 16. Islet β cell mass and OS marker staining was done by immunohistochemistry on week 16. QHYH prevented the exacerbation of hyperglycemia in HFD feeding GK rats for 12 weeks. On week 16, it improved the exacerbated glucose tolerance and prevented the further loss of islet β cell mass induced by HFD. QHYH markedly decreased serum MDA concentration, increased serum catalase (CAT) and SOD activities on week 4. However, no differences of serum glucose concentration or OS were observed on week 16. We concluded that QHYH decreased hyperglycemia exacerbated by HFD in GK rats by improving β cell function partly via its antioxidant effect.

[1]  G. Kimura,et al.  Effects of ezetimibe on visceral fat in the metabolic syndrome: a randomised controlled study , 2012, European journal of clinical investigation.

[2]  G. Speretta,et al.  The effects of exercise modalities on adiposity in obese rats , 2012, Clinics.

[3]  Xin Gao,et al.  Traditional Chinese medicine formula Qing Huo Yi Hao as superoxide anion scavenger in high glucose-treated endothelial cells , 2012, Acta Pharmacologica Sinica.

[4]  J. Crisóstomo,et al.  Dietary restriction improves systemic and muscular oxidative stress in type 2 diabetic Goto–Kakizaki rats , 2011, Journal of Physiology and Biochemistry.

[5]  R. DeFronzo,et al.  Preservation of β-cell function: the key to diabetes prevention. , 2011, The Journal of clinical endocrinology and metabolism.

[6]  J. Haefliger,et al.  Role for inducible cAMP early repressor in promoting pancreatic beta cell dysfunction evoked by oxidative stress in human and rat islets , 2011, Diabetologia.

[7]  P. Rondó,et al.  The effects of lipoic acid and α-tocopherol supplementation on the lipid profile and insulin sensitivity of patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. , 2011, Diabetes research and clinical practice.

[8]  Ming-Wei Wang,et al.  Tetramethylpyrazine protects palmitate-induced oxidative damage and mitochondrial dysfunction in C2C12 myotubes. , 2011, Life sciences.

[9]  Ya-Wen Chen,et al.  Arsenic induces pancreatic β-cell apoptosis via the oxidative stress-regulated mitochondria-dependent and endoplasmic reticulum stress-triggered signaling pathways. , 2011, Toxicology letters.

[10]  M. Düfer,et al.  Oxidative stress and beta-cell dysfunction , 2010, Pflügers Archiv - European Journal of Physiology.

[11]  B. Niklasson,et al.  Pancreatic islets of bank vole show signs of dysfunction after prolonged exposure to high glucose concentrations in vitro. , 2010, The Journal of endocrinology.

[12]  James D. Johnson,et al.  Role of the TLR signaling molecule TRIF in β-cell function and glucose homeostasis , 2010, Islets.

[13]  H. Çelik,et al.  Non-diabetic metabolic syndrome and obesity do not affect serum paraoxonase and arylesterase activities but do affect oxidative stress and inflammation. , 2010, European journal of endocrinology.

[14]  Å. Sjöholm.  Liraglutide Therapy for Type 2 Diabetes: Overcoming Unmet Needs , 2010, Pharmaceuticals.

[15]  G. Lacraz,et al.  Diabetic GK/Par rat beta-cells are spontaneously protected against H2O2-triggered apoptosis. A cAMP-dependent adaptive response. , 2010, American journal of physiology. Endocrinology and metabolism.

[16]  M. Nagy,et al.  Effect of Carnitine and herbal mixture extract on obesity induced by high fat diet in rats , 2009, Diabetology & metabolic syndrome.

[17]  N. Markovits,et al.  The effect of tomato-derived lycopene on low carotenoids and enhanced systemic inflammation and oxidation in severe obesity. , 2009, The Israel Medical Association journal : IMAJ.

[18]  G. Lacraz,et al.  Diabetic β-Cells Can Achieve Self-Protection against Oxidative Stress through an Adaptive Up-Regulation of Their Antioxidant Defenses , 2009, PloS one.

[19]  J. Chan,et al.  Phycocyanin protects INS-1E pancreatic beta cells against human islet amyloid polypeptide-induced apoptosis through attenuating oxidative stress and modulating JNK and p38 mitogen-activated protein kinase pathways. , 2009, The international journal of biochemistry & cell biology.

[20]  J. Corbett,et al.  Glucose-modulated tyrosine nitration in beta cells: targets and consequences. , 2009, Archives of biochemistry and biophysics.

[21]  Ming-Wei Wang,et al.  Antioxidative effect of the herbal remedy Qin Huo Yi Hao and its active component tetramethylpyrazine on high glucose-treated endothelial cells. , 2009, Life sciences.

[22]  M. Dolz,et al.  The GK rat beta-cell: A prototype for the diseased human beta-cell in type 2 diabetes? , 2009, Molecular and Cellular Endocrinology.

[23]  P. Matafome,et al.  Antioxidant and vascular effects of gliclazide in type 2 diabetic rats fed high-fat diet. , 2009, Physiological research.

[24]  C. Gluud,et al.  Systematic review: primary and secondary prevention of gastrointestinal cancers with antioxidant supplements , 2008, Alimentary pharmacology & therapeutics.

[25]  R. Fernandes,et al.  Effects of α‐lipoic acid on endothelial function in aged diabetic and high‐fat fed rats , 2008 .

[26]  R. Fernandes,et al.  Effects of alpha-lipoic acid on endothelial function in aged diabetic and high-fat fed rats. , 2008, British journal of pharmacology.

[27]  I. Calderon,et al.  Effect of Ginkgo biloba on the reproductive outcome and oxidative stress biomarkers of streptozotocin-induced diabetic rats. , 2007, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[28]  R. Robertson,et al.  Chronic oxidative stress as a mechanism for glucose toxicity of the beta cell in Type 2 diabetes , 2007, Cell Biochemistry and Biophysics.

[29]  J. Louw,et al.  Compromised &bgr;-Cell Development and &bgr;-Cell Dysfunction in Weanling Offspring From Dams Maintained on a High-Fat Diet During Gestation , 2007, Pancreas.

[30]  B. Zinman,et al.  Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. , 2006, The New England journal of medicine.

[31]  T. Sanke,et al.  Extracellular superoxide dismutase gene polymorphism is associated with insulin resistance and the susceptibility to type 2 diabetes. , 2006, Diabetes research and clinical practice.

[32]  S. Cinti.  The adipose organ. , 2005, Prostaglandins, leukotrienes, and essential fatty acids.

[33]  Roberto Pastor-Barriuso,et al.  Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality , 2005, Annals of Internal Medicine.

[34]  Li Xin.  Effect and security of traditional Chinese medicine prescription on urine albumin excreting rate of type 2 diabetes , 2004 .

[35]  E. Benjamin,et al.  Obesity and Systemic Oxidative Stress: Clinical Correlates of Oxidative Stress in The Framingham Study , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[36]  Yuichiro Yamada,et al.  Effect of High Dietary Fat on Insulin Secretion in Genetically Diabetic Goto-Kakizaki Rats , 2002, Pancreas.

[37]  V. Poitout,et al.  Differential effects of hyperlipidemia on insulin secretion in islets of langerhans from hyperglycemic versus normoglycemic rats. , 2002, Diabetes.

[38]  R. Haynes.  Diabetic complications , 2009, Journal of general internal medicine.