Quantitative combination of natural anti-oxidants prevents metabolic syndrome by reducing oxidative stress.
Insulin resistance and abdominal obesity are present in the majority of people with the metabolic syndrome. Antioxidant therapy might be a useful strategy for type 2 diabetes and other insulin-resistant states. The combination of vitamin C (Vc) and vitamin E has synthetic scavenging effect on free radicals and inhibition effect on lipid peroxidation. However, there are few studies about how to define the best combination of more than three anti-oxidants as it is difficult or impossible to test the anti-oxidant effect of the combination of every concentration of each ingredient experimentally. Here we present a math model, which is based on the classical Hill equation to determine the best combination, called Fixed Dose Combination (FDC), of several natural anti-oxidants, including Vc, green tea polyphenols (GTP) and grape seed extract proanthocyanidin (GSEP). Then we investigated the effects of FDC on oxidative stress, blood glucose and serum lipid levels in cultured 3T3-L1 adipocytes, high fat diet (HFD)-fed rats which serve as obesity model, and KK-ay mice as diabetic model. The level of serum malondialdehyde (MDA) in the treated rats was studied and Hematoxylin-Eosin (HE) staining or Oil red slices of liver and adipose tissue in the rats were examined as well. FDC shows excellent antioxidant and anti-glycation activity by attenuating lipid peroxidation. FDC determined in this investigation can become a potential solution to reduce obesity, to improve insulin sensitivity and be beneficial for the treatment of fat and diabetic patients. It is the first time to use the math model to determine the best ratio of three anti-oxidants, which can save much more time and chemical materials than traditional experimental method. This quantitative method represents a potentially new and useful strategy to screen all possible combinations of many natural anti-oxidants, therefore may help develop novel therapeutics with the potential to ameliorate the worldwide metabolic abnormalities.
MOE Key Laboratory of Bioinformatics, Bioinformatics Division and Center for Synthetic & Systems Biology, TNLIST, Department of Automation, Tsinghua University, Beijing 100084, People's Republic of China; BaiYao CaoYuan Biotechnology Ltd., XuChang City 461000, People's Republic of China.
Mingjing
M
Gao
MOE Key Laboratory of Bioinformatics, Bioinformatics Division and Center for Synthetic & Systems Biology, TNLIST, Department of Automation, Tsinghua University, Beijing 100084, People's Republic of China.
Zhen
Z
Zhao
MOE Key Laboratory of Bioinformatics, Bioinformatics Division and Center for Synthetic & Systems Biology, TNLIST, Department of Automation, Tsinghua University, Beijing 100084, People's Republic of China.
Pengyu
P
Lv
JiuYuanTang Pharmaceutical Co. Limited, HeNan Province, YuZhou 452570, People's Republic of China.
YuFang
Y
Li
MOE Key Laboratory of Bioinformatics, Bioinformatics Division and Center for Synthetic & Systems Biology, TNLIST, Department of Automation, Tsinghua University, Beijing 100084, People's Republic of China.
Juntao
J
Gao
MOE Key Laboratory of Bioinformatics, Bioinformatics Division and Center for Synthetic & Systems Biology, TNLIST, Department of Automation, Tsinghua University, Beijing 100084, People's Republic of China; Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas at Dallas, Richardson, TX, USA.
Michael
M
Zhang
Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
Baolu
B
Zhao
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001205:Ascorbic Acid / Q000097:blood / Q000493:pharmacokinetics*; D001786:Blood Glucose / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D002454:Cell Differentiation; D059305:Diet, High-Fat / Q000009:adverse effects; D019587:Dietary Supplements; D005163:Factor Analysis, Statistical; D016166:Free Radical Scavengers / Q000378:metabolism; D056604:Grape Seed Extract / Q000097:blood / Q000493:pharmacokinetics*; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D024821:Metabolic Syndrome / Q000097:blood / Q000178:diet therapy* / Q000209:etiology / Q000473:pathology; D051379:Mice; D009765:Obesity / Q000097:blood / Q000178:diet therapy* / Q000209:etiology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D044945:Proanthocyanidins / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D016166:Free Radical Scavengers; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D044945:Proanthocyanidins; C527126:green tea extract polyphenone E; D017665:Hydroxyl Radical; D008315:Malondialdehyde; D002392:Catechin; D001205:Ascorbic Acid
Abdominal obesity; Anti-oxidants; High fat diet-fed rats and KK-ay mice; Hill function; Insulin resistance; Quantitative combination