Critical Reviews TM in Eukaryotic Gene Expression, 25(2):91-112 (2015) 91 1045-4403/15/$35.00 © 2015 Begell House, Inc. www.begellhouse.com Zingiber offcinale and Type 2 Diabetes Mellitus: Evidence from Experimental Studies Muhammad Sajid Hamid Akash, 1,2,* Kanwal Rehman, 1,3 Muhammad Tariq, 1 & Shuqing Chen 1,* 1 Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zheji- ang University, Hangzhou, China; 2 Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan; 3 Institute of Pharmacy, Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan. M.S.H.A. and K.R. acted as joint frst authors. *Address all correspondence to: Muhammad Sajid Hamid Akash; Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan. sajidakash@gmail.com/sajidakash@gcuf.edu.pk, or Shuqing Chen; Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. chenshuqing@zju.edu.cn ABSTRACT: Zingiber offcinale is being used as diet-based therapy because of its wide therapeutic potential in type 2 diabetes mellitus (T2DM) and against diabetic complications by directly interacting with different molecu- lar and cellular pathways that provoke the pathogenesis of T2DM. This article explores the overall benefcial ef- fects of Z. offcinale on T2DM and its associated complications. Along with elucidating the benefcial facts of Z. offcinale, this article may also aid in understanding the molecular basis of its effects in T2DM. The mechanistic rationale for antidiabetic effects of Z. offcinale includes the inhibition of several transcriptional pathways, lipid peroxidation, carbohydrate-metabolizing enzymes, and HMG-CoA reductase and the activation of antioxidant en- zyme capacity and low-density lipoprotein receptors. Consequently, by targeting these pathways, Z. offcinale shows its antidiabetic therapeutic effects by increasing insulin sensitivity/synthesis, protecting β-cells of pancre- atic islets, reducing fat accumulation, decreasing oxidative stress, and increasing glucose uptake by the tissues. In addition to these effects, Z. offcinale also exhibits protective effects against several diabetes-linked complica- tions, notably nephropathy and diabetic cataract, by acting as an antioxidant and antiglycating agent. In conclu- sion, this work suggests that consumption of Z. offcinale can help to treat T2DM and diabetic complications; nevertheless, patient counseling also is required as a guiding force for the success of diet-based therapy in T2DM. KEY WORDS: antidiabetic effects of Zingiber offcinale, diabetes mellitus, antioxidative effects of ginger, hypogly- cemic effects of ginger, hypolipidemic effects of ginger I. INTRODUCTION Type 2 diabetes mellitus (T2DM) is among the most fatal and life-threatening diseases and is becoming a global problem. The use of conventional ant-diabet- ic agents to cure T2DM is declining because of their unwanted side effects. 1–3 T2DM is recognized as an autoinfammatory syndrome involving various com- plex pathophysiological mechanisms. 4–8 Despite having many new therapeutic modalities, 9–14 T2DM is still considered a challenging disease. The use of dietary supplements for the treatment of T2DM was encouraged by ancient medical practi- tioners, 15,16 a practice that has now gained consider- able attention from researchers who wish to discov- er the biopharmaceutical activities of these dietary supplements. Many are naturally rich in various risk-free phytochemical constituents that have been proven to have medicinal properties against various diseases. 17–27 For almost two-thirds of the world’s population, T2DM is usually treated using various medicinal plants. 21 According to the available sci- entifc literature, a large number of plants have been evaluated for their antidiabetic effects. A majority of these plants also are available worldwide in the form of polyherbal formulations and are presently being prescribed by medical practitioners for the treatment of T2DM, especially in developing countries.