Eriobotrya japonica leaf triterpenoid acids ameliorate metabolic syndrome in C57BL/6J mice fed with high-fat diet

• Published in: Biomedicine & pharmacotherapy Vol. 132; p. 110866
• Main Authors: Li, Feng, Li, Yijia, Li, Qingxian, Shi, Xianai
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.12.2020; Elsevier
• Subjects: 11-beta-Hydroxysteroid Dehydrogenase Type 1 - metabolism; Animals; Biomarkers - blood; Blood Glucose - drug effects; Blood Glucose - metabolism; Diet, High-Fat; Disease Models, Animal; Dyslipidemia; Energy Metabolism - drug effects; Eriobotrya - chemistry; Eriobotrya japonica leaf triterpenoid acids; Gene Expression Regulation; Glucokinase - metabolism; High-fat diet; Inflammation Mediators - metabolism; Insulin resistance; JNK Mitogen-Activated Protein Kinases - metabolism; Lipids - blood; Male; Metabolic syndrome; Metabolic Syndrome - blood; Metabolic Syndrome - etiology; Metabolic Syndrome - genetics; Metabolic Syndrome - prevention & control; Molecular docking; Oxidative Stress - drug effects; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plant Leaves - chemistry; PPAR gamma - metabolism; Signal Transduction; Triterpenes - isolation & purification; Triterpenes - pharmacology; FFA; FXR; SHIP2; JNK; HFD; Dyslipidemia; ITT; LPO; IRS; UA; Metabolic syndrome; Molecular docking; AUC; OA; MA; PI3K; BW; Nrf2; Pi; GSH; CA; PPAR-γ; GK; LDL-c; Eriobotrya japonica leaf triterpenoid acids; IR; MAPK; IL-6; TC; HDL-c; MetS; PTP1B; TG; ELTA; TNF-α; High-fat diet; Keap1; AMPK; Insulin resistance; 11βHSD-1; OGTT; ERK
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2020.110866

[Display omitted] •HFD consumption induces a series of typical symptoms of MetS.•ELTA administration alleviates typical symptoms of HFD-induced MetS.•ELTA affects the signaling of Nrf2/ARE, MAPKs, IRS-1/PI3K/AKT, or LXR/SREBPs.•ELTA may ameliorates MetS by multiple targeting on 11βHSD-1, GK, PPAR-γ, or JNK. 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. 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. 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. 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.