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World J Diabetes. Feb 15, 2023; 14(2): 62-75
Published online Feb 15, 2023. doi: 10.4239/wjd.v14.i2.62
Modulatory effect of caffeic acid in alleviating diabetes and associated complications
Risha Ganguly, Shiv Vardan Singh, Kritika Jaiswal, Ramesh Kumar, Abhay K Pandey
Risha Ganguly, Shiv Vardan Singh, Kritika Jaiswal, Ramesh Kumar, Abhay K Pandey, Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, India
Author contributions: Pandey AK conceptualized the idea; Ganguly R, Singh SV, Jaiswal K, and Kumar R performed the literature search; Ganguly R and Singh SV wrote the first draft of the manuscript and validated the references; Pandey AK critically reviewed and revised the manuscript; all authors have read and approved the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Abhay K Pandey, PhD, Professor, Department of Biochemistry, University of Allahabad, University Road, Allahabad (Prayagraj) 211002, India. akpandey23@rediffmail.com
Received: August 28, 2022
Peer-review started: August 28, 2022
First decision: October 21, 2022
Revised: November 4, 2022
Accepted: December 13, 2022
Article in press: December 13, 2022
Published online: February 15, 2023
Processing time: 169 Days and 17.7 Hours
Abstract

Diabetes mellitus (DM) is one of the most common metabolic disorders characterized by elevated blood glucose levels. Prolonged uncontrolled hyperglycemia often leads to multi-organ damage including diabetic neuropathy, nephropathy, retinopathy, cardiovascular disorders, and diabetic foot ulcers. Excess production of free radicals causing oxidative stress in tissues is often considered to be the primary cause of onset and progression of DM and associated complications. Natural polyphenols can be used to induce or inhibit the expression of antioxidant enzymes such as glutathione peroxidase, heme oxygenase-1, superoxide dismutase, and catalase that are essential in maintaining redox balance, and ameliorate oxidative stress. Caffeic acid (CA) is a polyphenolderived from hydroxycinnamic acid and possesses numerous physiological properties includ-ing antioxidant, anti-inflammatory, anti-atherosclerotic, immune-stimulatory, cardioprotective, antiproliferative, and hepatoprotective activities. CA acts as a regulatory compound affecting numerous biochemical pathways and multiple targets. These include various transcription factors such as nuclear factor-B, tumor necrosis factor-α, interleukin-6, cyclooxygenase-2, and nuclear factor erythroid 2-related factor 2. Therefore, this review summarizes the pharmacological properties, molecular mechanisms, and pharmacokinetic profile of CA in mitigating the adverse effects of DM and associated complications. The bioavailability, drug delivery, and clinical trials of CA have also been discussed.

Keywords: Diabetes mellitus; Caffeic acid; Diabetic foot ulcer; Retinopathy; Nephropathy

Core Tip: Diabetes mellitus has emerged as one of the most common metabolic disorders worldwide which can lead to other complications such as retinopathy, nephropathy, neuropathy, and foot ulcers. Free radical-induced oxidative stress is one of the primary causes of diabetes. Caffeic acid (CA) is a natural polyphenol obtained from various fruits and vegetables. CA and its derivatives act as an antioxidant and regulate the signaling pathways involved in lipid and carbohydrate metabolism. CA also exerts anti-diabetic effects by modulation of inflammatory cytokines and transcription factors.