Feng Li1, Yijia Li2, Qingxian Li2, Xianai Shi3. 1. College of Biological Science and Engineering, Fuzhou University, Fuzhou, 350116, PR China; Institute of Pharmaceutical Biotechnology and Engineering, Fuzhou University, Fuzhou, 350116, PR China; Fujian Key Lab of Medical Instrument and Pharmaceutical Technology, Fuzhou University. Fuzhou, Fujian, 350108, China. Electronic address: lqlchfengli@fzu.edu.cn. 2. College of Biological Science and Engineering, Fuzhou University, Fuzhou, 350116, PR China; Institute of Pharmaceutical Biotechnology and Engineering, Fuzhou University, Fuzhou, 350116, PR China. 3. College of Biological Science and Engineering, Fuzhou University, Fuzhou, 350116, PR China; Institute of Pharmaceutical Biotechnology and Engineering, Fuzhou University, Fuzhou, 350116, PR China; Fujian Key Lab of Medical Instrument and Pharmaceutical Technology, Fuzhou University. Fuzhou, Fujian, 350108, China. Electronic address: shixa@fzu.edu.cn.
Abstract
BACKGROUND: It has been demonstrated in some studies that triterpenoid acid extract fromEriobotrya japonica leaf is beneficial to prevent hyperlipidemia or insulin resistance. However, the effect of triterpenoid acids in Eriobotrya japonica leaf on a series of typical symptoms of metabolic syndrome (MetS) has been rarely studied systematically. Therefore, the present study aims to systematically evaluate the effect of Eriobotrya japonica leaf triterpenoid acids (ELTA) on MetS and explore its potential mechanism. METHODS: ELTA (HPLC purity 95.2 %) was prepared and administered orally (200 mg/kg) to C57BL/6 J mice fed with a high-fat diet (HFD) for 12 weeks. Pioglitazone (30 mg/kg) was used as a positive control drug. Food intake, body weight, total lipid in feces, lipid profiles, inflammatory factors in serum, hepatic glutathione, and lipid peroxide were measured. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed to evaluate insulin sensitivity. RT-qPCR and molecular docking were performed to explore the potential mechanism. RESULTS: ELTA administration reduced body weight gain, relative liver weight, and relative visceral adipose weight. The levels of serum total cholesterol, triglycerides, low-density lipoprotein cholesterol, hepatic total cholesterol, and hepatic triglycerides were also reduced. ELTA reduced the area under curve (AUC) of blood glucose curves in OGTT and ITT. Relative mRNA level analysis of genes related to MetS showed that ELTA can effectively increase the transcriptional levels of Nrf2, HO-1, PPAR-γ, GluT2, GK, FXR, while effectively decrease those of PTP1B, p65, TNF-α, IL-6, SREBP, 11βHSD-1. Molecular docking showed that the ligands in ELTA can bind to 11βHSD-1, GK, PPAR-γ, and JNK, the important targets involved in MetS. CONCLUSIONS: ELTA can effectively alleviate visceral central obesity, insulin resistance, dyslipidemia, oxidative stress, and inflammation of HFD-induced MetS in C57BL/6 J mice. This is possibly achieved by acting on 11βHSD-1, GK, PPAR-γ, and JNK.
BACKGROUND: It has been demonstrated in some studies that triterpenoid acid extract fromEriobotrya japonica leaf is beneficial to prevent hyperlipidemia or insulin resistance. However, the effect of triterpenoid acids in Eriobotrya japonica leaf on a series of typical symptoms of metabolic syndrome (MetS) has been rarely studied systematically. Therefore, the present study aims to systematically evaluate the effect of Eriobotrya japonica leaf triterpenoid acids (ELTA) on MetS and explore its potential mechanism. METHODS:ELTA (HPLC purity 95.2 %) was prepared and administered orally (200 mg/kg) to C57BL/6 J mice fed with a high-fat diet (HFD) for 12 weeks. Pioglitazone (30 mg/kg) was used as a positive control drug. Food intake, body weight, total lipid in feces, lipid profiles, inflammatory factors in serum, hepatic glutathione, and lipid peroxide were measured. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed to evaluate insulin sensitivity. RT-qPCR and molecular docking were performed to explore the potential mechanism. RESULTS:ELTA administration reduced body weight gain, relative liver weight, and relative visceral adipose weight. The levels of serum total cholesterol, triglycerides, low-density lipoprotein cholesterol, hepatic total cholesterol, and hepatic triglycerides were also reduced. ELTA reduced the area under curve (AUC) of blood glucose curves in OGTT and ITT. Relative mRNA level analysis of genes related to MetS showed that ELTA can effectively increase the transcriptional levels of Nrf2, HO-1, PPAR-γ, GluT2, GK, FXR, while effectively decrease those of PTP1B, p65, TNF-α, IL-6, SREBP, 11βHSD-1. Molecular docking showed that the ligands in ELTA can bind to 11βHSD-1, GK, PPAR-γ, and JNK, the important targets involved in MetS. CONCLUSIONS:ELTA can effectively alleviate visceral central obesity, insulin resistance, dyslipidemia, oxidative stress, and inflammation of HFD-induced MetS in C57BL/6 J mice. This is possibly achieved by acting on 11βHSD-1, GK, PPAR-γ, and JNK.
Authors: Valentina Echeverria; Florencia Echeverria; George E Barreto; Javier Echeverría; Cristhian Mendoza Journal: Front Pharmacol Date: 2021-05-20 Impact factor: 5.810