REVIEW Aloe vera as an herbal medicine in the treatment of metabolic syndrome: A review Zahra Shakib 1 | Naghmeh Shahraki 1 | Bibi Marjan Razavi 2,4 | Hossein Hosseinzadeh 3,4 1 School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran 2 Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran 3 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran 4 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran Correspondence Hossein Hosseinzadeh, Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Razavi Khorasan Province, Iran. Email: hosseinzadehh@mums.ac.ir Metabolic syndrome (MS) is a highly prevalent health problem worldwide and is asso- ciated with different risk factors, including hyperglycemia, dyslipidemia, hypertension, and obesity. This condition increases the risk of developing type II diabetes mellitus and cardiovascular problems. The MS is one of the most important health concerns in industrialized countries and mainly results from a sedentary lifestyle, high levels of subjective stress, and unhealthy diets. Nowadays, the identification of appropriate health care approaches, such as herbal medicines, with fewer side effects is more favorable, especially with regard to the adverse effects of chemical drugs. Aloe barbadensis Miller known as Aloe vera is a useful plant with two major parts, including leaves that contain high concentrations of anthraquinone compounds and a clear gel. The gel is used as a food with several beneficial properties, such as antiinflammatory, antioxidant, antiviral, antibacterial, and wound‐healing features. Other effects of A. vera, such as its lipid‐lowering, antihypertensive, antidiabetic, antiobesity, and cardioprotective impacts, have been demonstrated in several studies. The present study was conducted to review the evidence on the pharmacological effects of A. vera on the different components of MS. KEYWORDS Aloe barbadensis, Aloe vera, diabetes mellitus, dyslipidemia, hypertension, metabolic syndrome, obesity 1 | INTRODUCTION Metabolic syndrome is one of the most common health problems in industrialized countries. This condition mainly results from a sedentary lifestyle, high levels of subjective stress, and unhealthy diet. Various definitions and diagnostic approaches have been developed for metabolic syndrome on the basis of different criteria. Hypertension, hyperglycemia, high levels of triglyceride (TG), low levels of high‐ density lipoprotein (HDL), and presence of central obesity are included in almost all definitions (Cramer, Langhorst, Dobos, & Lauche, 2016). According to the National Cholesterol Education Program definition, people that have at least three out of five risk factors are diagnosed with metabolic syndrome (Figure 1; Lakka et al., 2002). The first approach for the management of metabolic syndrome is a healthy lifestyle, and the second solution is pharmacotherapy (Huseini, Kianbakht, Hajiaghaee, & Dabaghian, 2012). However, drugs have Abbreviations: ACC, acetyl‐CoA carboxylase; ACO, acyl‐CoA oxidase; Acox1, acyl‐coenzyme A oxidase 1; AHM, A.vera L. high molecular weight; ALS, aloesin; ALT, alanine aminotransferase; AMP, the adenosine monophosphate; AMPK, AMP‐activated protein kinase; APOIII, apolipoprotein C‐III; AST, aspartate aminotransferase; ATMs, adipose tissue macrophages; CPT1, palmitoyltransferase I; DIO, diet‐induced obesity; FAS, fatty acid synthase; FATP1, fatty acid transport protein 1; FBS, fast blood glucose; FFA, free fatty acid; G6Pase, glucose 6‐phosphatase; GK, glucokinase; HbA1c, hemoglobin A1c; HDL‐C, high‐density lipoprotein‐cholesterol; HFD, high‐fat diet; HIF1α, hypoxia‐inducible factor 1‐alpha; HMGCS2, hydroxymethylglutaryl CoA synthase 2; IL‐1β, interleukin1β; IL6, interleukin6; IR, insulin resistance; LDL‐C, low‐density lipoprotein‐cholesterol; LP625, probiotic Lactobacillus plantarum; MCP‐1, monocyte chemotactic protein‐1; mRNA, messenger RNA; NF‐κB, nuclear factor‐kappa B; PAG, processed Aloe vera gel; PEPCK, phosphoenolpyruvate carboxykinase; PL, phospholipid; PMSF, phenylmethylsulfonyl fluoride; PPAR, peroxisome proliferator activated receptors; PPG, postprandial glucose; SREBF1, sterol regulatory element‐binding transcription factor 1; STZ, streptozotocin; T2DM, type II diabetes mellitus; TC, total cholesterol; TG, triglyceride; UCP‐2, uncoupling protein‐2; WHO, World Health Organization; ZDF, Zucker diabetic fatty Received: 5 January 2019 Revised: 6 July 2019 Accepted: 9 July 2019 DOI: 10.1002/ptr.6465 Phytotherapy Research. 2019;33:2649–2660. © 2019 John Wiley & Sons, Ltd. wileyonlinelibrary.com/journal/ptr 2649