Hindawi e Scientific World Journal Volume 2021, Article ID 6641128, 20 pages https://doi.org/10.1155/2021/6641128 Review Article Multitargeted Effects of Vitexin and Isovitexin on Diabetes Mellitus and Its Complications Ibrahim Luru Abdulai,1 Samuel Kojo Kwofie ,1,2 Winfred Seth Gbewonyo ,3 Daniel Boison ,4 Joshua Buer Puplampu ,4 and Michael Buenor Adinortey 4 1West African Centre for Cell Biology of Infectious Pathogens, College of Basic and Applied Sciences, University of Ghana, P.O. Box LG 54, Legon, Accra, Ghana 2Department of Biomedical Engineering, School of Engineering Sciences, College of Basic and Applied Sciences, University of Ghana, P.O. Box LG77, Legon, Accra, Ghana 3Department of Biochemistry, Cell and Molecular Biology, School of Biological Sciences, University of Ghana, Legon, Accra, Ghana 4Department of Biochemistry, School of Biological Sciences, University of Cape Coast, Cape Coast, Ghana Correspondence should be addressed to Michael Buenor Adinortey; [email protected] Received 14 October 2020; Accepted 19 March 2021; Published 12 April 2021 Academic Editor: Ahmad Mansour Copyright © 2021 Ibrahim Luru Abdulai et al. 'is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Till date, there is no known antidote to cure diabetes mellitus despite the discovery and development of diverse pharmacotherapeutic agents many years ago. Technological advancement in natural product chemistry has led to the isolation of analogs of vitexin and isovitexin found in diverse bioresources. 'ese compounds have been extensively studied to explore their pharmacological relevance in diabetes mellitus. Aim of the Study. 'e present review was to compile results from in vitro and in vivo studies performed with vitexin and isovitexin derivatives relating to diabetes mellitus and its complications. A systematic online literature query was executed to collect all relevant articles published up to March 2020. Results. In this piece, we have collected data and presented it in a one-stop document to support the multitargeted mechanistic actions of vitexin and isovitexin in controlling diabetes mellitus and its complications. Conclusion. Data collected hint that vitexin and isovitexin work by targeting diverse pathophysiological and metabolic pathways and molecular drug points involved in the clinical manifestations of diabetes mellitus. 'is is expected to provide a deeper understanding of its actions and also serve as a catapult for clinical trials and application research. 1. Introduction major challenge for healthcare providers. Several attempts to grapple with the disease have been confronted by humun- Diabetes mellitus is a disorder characterized by persistent gous financial expenses. In the U.K, for instance, about 10% hyperglycemia, resulting from partial or complete pancreas of the primary care prescribing budget is spent on treating damage leading to the imbalance in carbohydrate, lipid, and diabetes, with a daily average of £2.2 m spent by the National protein homeostases. A hyperglycemic state is the effect of Health Service (NHS) on prescriptions only [2]. 'e global impaired insulin secretion, insulin resistance, or both [1]. economic cost as at 2014 was an estimated US$612 billion. In Medicinal plants and their isolated compounds have re- urban Ghana, the economic burden of diabetes is high with ceived huge attention due to their reported use in the catastrophic effects on households [3]. Studies conducted by management of diabetes mellitus (DM). 'ough several [4] revealed that the overall total cost estimate for diabetes discoveries have been made concerning pharmacotherapies treatment by individuals in Ghana was USD 10,485.11 with a used for managing diabetes mellitus, its management is still a total mean cost of USD 46.81 on monthly basis. 2 'e Scientific World Journal Till date, there is no known antidote to cure diabetes 3. Results and Discussion mellitus despite the discovery and development of di- verse pharmacotherapeutic agents many years ago. 'e 3.1. Natural Sources and Chemical Structural Properties of high cost of these drugs and the unbearable side effect Vitexin and Isovitexin. Vitexin and isovitexin are mono-C- they come along with heighten the demand for natural glycosylflavones found in diverse natural plant sources. antidiabetic products which may possess minimal to no Rapid technological advancement in natural product side effects. Currently, consideration of two mono-c- chemistry has led to the isolation of vitexin and its analogs. glycosylflavones, vitexin and isovitexin, as drug candi- 'e isomer pair and their derivatives are ubiquitously dates for diabetes mellitus and related complication [5], available in natural sources such as insects [7], honey [8], is a growing research interest amongst many scientists all fungus Dichotomopilus funicola Y3 [9], and even plant tis- over the world. Several reports are dotted on different sues, including Tetrastigma hemsleyanum leaves [10], publishing platforms, thus necessitating the need for a buckwheat sprouts [11], leaves of Echinodorus scaber [12], one-stop document that provides knowledge on past and and others. recent advancement regarding studies on vitexin and its Vitexin (apigenin-8-C-β-glucopyranoside) and iso- analogues (Figure 1) as drug candidates for diabetes vitexin (apigenin-6-C-β-glucopyranoside) analogs are mellitus. 'is review provides an appraisal of experi- mono-C-glycosylflavones with one sugar moiety attached to mental data on vitexin and isovitexin in published works the flavone skeleton. In part of the C-glycoside structure of that could serve as the basis for research consideration in vitexin and isovitexin, the sugar moiety is connected right to other preclinical studies and consequently clinical trials. the C6–C3–C6 aglycone skeleton through a C–C bond, In this piece, we methodically provide a comprehensive which is reported to resist acid hydrolysis [13, 14]. It is summary of the antidiabetic mechanisms involved in confirmed that the sugar ring in a flavone-glucosyl moiety is controlling persistent hyperglycemia to serve as evidence attached through C-C bonds to the 8 position of the flavone and also provide a deeper understanding of its actions. nucleus and is approximately perpendicular to the flavone 'is is expected to act as a reference for further clinical plane [15]. Vitexin and isovitexin appear as yellow crystalline applications and research. chemical substances and are soluble in ethanol and dimethyl sulfoxide (DMSO) and mostly give yellow color solution when dissolved in an alkali medium [16]. Several studies 2. Methodology have reported the biosynthesis of these class of compounds 2.1. Search Strategy. A systematic online literature query in the laboratory [17, 18]. was executed to collect all relevant articles published up to March 2020. 'e systematic search was conducted on 3.2. Impact of Vitexin and Isovitexin on Drug Targets in Di- selected databases such as ScienceDirect, PubMed, and abetes Mellitus and Its Complications. Vitexin and its ana- Google Scholar with the singleword “vitexin” to obtain logs have been studied as an antihyperglycemic agent. published studies to-date. Investigators were not con- Using rodents, oral administration of vitexin or isovitexin tacted, and we did not attempt to identify unpublished was reported to significantly decrease postprandial blood data. 'e review was guided by Preferred Reporting Items glucose content in a dose-dependent manner [19, 20]. for Systematic Reviews and Meta-Analyses (PRISMA) Furthermore, isovitexin, in both normal and diabetic rats, recommendations [6]. demonstrated pronounced antihyperglycemic property and also attenuated a rise in blood glucose [21]. Hyper- glycemia, caused mainly by insulin resistance and insen- 2.2. Articles Selection. 'e study articles were selected on sitive receptors, disturbs the metabolism of lipids and the basis of an inclusion criteria stated as studies pub- carbohydrates as well as proteins which can further lished in only English Language and those articles that progress to several micro and macrovascular complica- have the defined keyword “vitexin” either in the title, tions. Examples of these complications include hyperten- abstract, whole text, or even the keywords. Articles on sion, dyslipidemia, neuropathy, nephropathy, and sexual experimental screening with vitexin and isovitexin de- impairments. Several targets are reported in literature to be rivatives were of paramount importance. Review articles, useful points for antidiabetic drug candidates. 'ese in- abstracts, editorial/letters, conference, and proceedings clude pancreatic β-cell, lipid, and carbohydrate digesting were omitted in this systematic review. Also, articles enzymes, cell signaling molecules present in adipose tissue, unrelated to diabetes, except antioxidant, anti-inflam- angiotensin I-converting enzyme (ACE), free radicals, and mation, safety, and toxicological applications of vitexin glutamate transporters. were excluded. To further filter the articles, search results were screened manually and articles that comprise re- peated data or studies duplicated by the search databases 3.2.1. Pancreatic β-Cell. It is now well noted that pan- and some articles on phytochemical isolation of vitexin creatic β-cell functional deficit is a common feature of and isovitexin derivatives were excluded. 'e remaining both type