Abstract
Zanthoxylum bungeanum is a traditional Chinese medicine (TCM) used to relieve pain, dispel dampness, stop diarrhea, and prevent itching. The aim of this study was to investigate the antiobesity and hypolipidemic effects of hydroxy-α-sanshool (HAS) isolated from Z. bungeanum on hyperlipidemic rats. Wistar rats (n = 48) were randomly divided into six groups: (1) normal diet rats (ND), (2) high-fat diet- (HFD-) treated rats, (3) HFD+fenofibrate-treated rats (HFD+FNB), (4) HFD+low dose of HAS-treated rats (HFD+LD, 9 mg/kg), (5) HFD+middle dose of HAS-treated rats (HFD+MD, 18 mg/kg), and (6) HFD+high dose of HAS-treated rats (HFD+HD, 36 mg/kg). The body weight and food intake of the rats were recorded during the treatment period. After 4 weeks of HAS treatment, abdominal adipose tissues were observed and total cholesterol (T-CHO), triglycerides (TG), high-density lipoprotein (HDL) cholesterol (HDL-C), and low-density lipoprotein (LDL) cholesterol (LDL-C) of serum and liver tissues were determined. Furthermore, histochemical examinations using oil red O and hematoxylin-eosin staining (H&E) were carried out and levels of malondialdehyde (MDA) and glutathione (GSH) and activities of superoxide dismutase (SOD) in the liver were determined. After HFD feeding, the body weight gain and food efficiency ratio of HFD rats were significantly enhanced (p < 0.05vs. ND rats) and HAS treatment (18 and 36 mg/kg) significantly decreased the body weight gain and food efficiency ratio (p < 0.05vs. HFD rats). In addition, HAS treatment could decrease the abdominal adipose tissues and liver adipocytes. Furthermore, HAS treatment significantly decreased the T-CHO, TG, and LDL-C, whereas it increased HDL-C (p < 0.05vs. HFD rats) in serum and the liver. HAS treatment increased the GSH level and SOD activity in the liver (p < 0.05vs. HFD rats), whereas it decreased the levels of MDA (p < 0.05vs. HFD rats). mRNA analyses suggested that HAS treatment increases the expression of Pparg (proliferator-activated receptor γ) and Apoe (peroxisome apolipoprotein E). Immunohistochemistry and Western blotting indicated that HAS stimulation increased the levels of PPARγ and APOE in the liver, as a stress response of the body defense system. These results revealed that HAS exerts antiobesity and hypolipidemic activities in HFD rats by reducing liver oxidative stress and thus could be considered as a potential candidate drug to cure or prevent obesity and hyperlipidemia.
Highlights
Cardiovascular diseases (CVDs), such as atherosclerosis (AS) and coronary heart disease (CHD), have become a global epidemic with high morbidity and mortality
The total cholesterol (T-CHO), triglycerides (TG), high-density lipoprotein (HDL) cholesterol (HDL-C), low-density lipoprotein (LDL) cholesterol (LDL-C), superoxide dismutase (SOD), malondialdehyde (MDA), tripeptide glutathione (GSH), and coomassie bright blue (CBB) kits were purchased from Nanjing Jiancheng Bioengineering Institute (Nanjing, China); rabbit anti-PPARγ and rabbit anti-APOE antibodies were products of Bioss Antibodies (Beijing, China); GAPDH antibodies, radioimmunoprecipitation assay (RIPA) lysate buffer, bicinchoninic acid (BCA) protein quantitative kit, and SDS-polyacrylamide gel electrophoresis (SDS-PAGE) preparation kit were purchased from Multi Sciences (Hangzhou, China); RNA TRIzol Reagent was purchased from Servicebio Company (Wuhan, China); the RevertAid First Strand cDNA Synthesis Kit was purchased from Thermo Fisher (MO, USA); and the all other chemicals used in this study were of analytical reagent grade
After 2 weeks of high-fat diet (HFD) feeding, the body weights of the HFD rats were significantly higher than those of the normal diet rats (ND) rats (p < 0 05) (Figure 5(a)) and were similar to the positive drug-treated rats
Summary
Cardiovascular diseases (CVDs), such as atherosclerosis (AS) and coronary heart disease (CHD), have become a global epidemic with high morbidity and mortality. Previous studies have shown that obesity and hyperlipidemia are positive risk factors for the initiation of atherosclerosis, which lead to a series of cardiovascular complications. Hyperlipidemia is a metabolic disorder disease that involves abnormally high levels of blood lipids and lipoproteins [1,2,3]. With the globalization of Western diet, a high-fat and high-cholesterol diet is believed to be one of the most important causes of the high incidence of obesity and hyperlipidemia worldwide [4]. The present study would be beneficial for the development of HAS as a candidate drug to treat obesity and hyperlipidemia in the clinic
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