Kukoamine B Ameliorate Insulin Resistance, Oxidative Stress, Inflammation and Other Metabolic Abnormalities in High-Fat/High-Fructose-Fed Rats

Quan Zhao,1,* Linhai Li,1,* Yu Zhu,1 Dezhi Hou,1 Yuejin Li,1 Xiaodong Guo,1 Yongzhi Wang,1 Opeyemi Joshua Olatunji,2 Ping Wan,3 Kunmei Gong1 1Department of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan 650032, People’s Republic of China; 2Faculty of Thai Traditional Medicine, Prince of Songkla University, Hat Yai 90112, Thailand; 3Department of Digestive Internal Medicine, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan 650032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kunmei GongDepartment of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan 650032, People’s Republic of ChinaEmail gkmmed@sina.comPing WanDepartment of Digestive Internal Medicine, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan 650032, People’s Republic of ChinaEmail kmwp_66@sina.comBackground: Obesity is characterized by excessive body fat, insulin resistance and dyslipidemia, which increases the chances of developing chronic diseases like type 2 diabetes, cardiovascular diseases, hypertension, nonalcoholic fatty liver diseases, some types of cancers and neurodegenerative diseases. Kukoamine B (Kuk B) is a spermine alkaloid obtained from Lycium chinense, and it has been shown to possess antidiabetic, antioxidant and anti-inflammatory properties. In this study, we evaluated the therapeutic effect of Kuk B on high-fat diet/high-fructose (HFDFr)-induced insulin resistance and obesity in experimental rats.Materials and Methods: Rats were fed with either normal rat diet or HFDFr for 10 consecutive weeks. The groups that were fed with HFDFr received Kuk B (25 and 50 mg/kg) from the beginning of the 6th week to the 10th week. After treatment, the effect of Kuk B on body weight, food, water intake, insulin, blood glucose, serum biochemical parameters, hepatic oxidative stress (malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and proinflammatory cytokine (interleukin (IL)-6, interleukin (IL)-1β and tumor necrosis factor alpha (TNF-α)) levels was determined. Histopathological analysis of the liver tissues was also performed.Results: HFDFr-fed rats showed a significant increase in body weight, fasting blood glucose, insulin, lipid accumulation and liver function enzymes. In addition, HFDFr diet increased hepatic MDA, TNF-α, IL-1β and IL-6 and decreased hepatic SOD, CAT and GSH-Px activities. On the other hand, Kuk B significantly attenuated body weight, insulin resistance, lipid accumulation, oxidative stress and inflammation.Conclusion: These results indicated that Kuk B showed protective effect against HFDFr-induced metabolic disorders by downregulating lipid accumulation, oxidative stress and inflammatory factors.Keywords: kukoamine B, obesity, insulin resistance, high-fat diet, inflammation, oxidative stress