Exploring the potential of flavonoids as efflorescing antidiabetic: An updated SAR and mechanistic based approach

Katharigatta N Venugopala; Jasmine Chaudhary; Vishal Sharma; Akash Jain; Manish Kumar; Diksha Sharma; Pottathil Shinu; Bandar E Aldhubiab; PranKishore Deb; Osama I Alwassil; Mahesh Attimarad; Anroop B Nair; Nagaraja Sreeharsha; Rashmi Venugopala; Mahmoud Kandeel; Christophe Tratrat; Wael El-Deeb; Michelyne Haroun; Mohamad Fawzi Mahomoodally; Viresh Mohanlall; Mohamed A Morsy

Articles

Abstract

Pharmacognosy Magazine,2022,18,80,791-807.

DOI:10.4103/pm.pm_372_22

Published:November 2022

Type:Invited Review

Authors:

Author(s) affiliations:

Katharigatta N Venugopala¹, Jasmine Chaudhary², Vishal Sharma², Akash Jain², Manish Kumar², Diksha Sharma³, Pottathil Shinu⁴, Bandar E Aldhubiab⁵, PranKishore Deb⁶, Osama I Alwassil⁷, Mahesh Attimarad⁵, Anroop B Nair⁵, Nagaraja Sreeharsha⁸, Rashmi Venugopala⁹, Mahmoud Kandeel¹⁰, Christophe Tratrat⁵, Wael El-Deeb¹¹, Michelyne Haroun⁵, Mohamad Fawzi Mahomoodally¹², Viresh Mohanlall¹³, Mohamed A Morsy¹⁴

¹Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia; Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, Durban 4001, South Africa
²M. M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana, India
³Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana, India
⁴Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
⁵Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
⁶Department of Pharmaceutical Sciences, Faculty of Pharmacy, Philadelphia University, Amman 19392, Jordan
⁷Department of Pharmaceutical Sciences, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia
⁸Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia; Department of Pharmaceutics, Vidya Siri College of Pharmacy, Off Sarjapura Road, Bangalore, Karnataka, India
⁹ Department of Public Health Medicine, Howard College Campus, University of KwaZulu-Natal, Durban 4001, South Africa
¹⁰ Department of Biomedical Sciences, King Faisal University, Al-Ahsa 31982, Saudi Arabia; Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt
¹¹Department of Clinical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia; Department of Internal Medicine, Infectious Diseases and Fish Diseases, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt
¹²Department of Health Sciences, Faculty of Medicine and Health Sciences, University of Mauritius, Réduit 80837, Mauritius
¹³Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, Durban 4001, South Africa
¹⁴Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia; Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia 61511, Egypt

Abstract:

Diabetes is a metabolic complication distinguished mainly by persistent hyperglycemia and is involved in the formation of reactive oxygen species, thereby causing oxidative stress, which is the major culprit for diabetic complications in different organs, including the vascular system. Controlling blood glucose is the most effective strategy for preventing diabetes and its complications. Currently, the available antidiabetic therapy is associated with several side effects, thus inexhaustible attention has been paid toward the development of natural compounds. The present review highlights the different types of flavonoids as potent antidiabetic agents along with their structure–activity relationship (SAR) studies, which will definitely aid in designing innovative molecules with improved antidiabetic efficacy. The type of substitution in the flavonoid core structure decides their bindings at different biological targets involved in diabetes development such as xanthine oxidase inhibitors, SGLT-II inhibitors, α-glucosidase inhibitors, PPAR-γ agonists, DPP-4 inhibitors, and glycogen phosphorylase inhibitors. Based on SAR investigation, a double bond between C₂ and C₃ positions, hydroxy substitutions at C₅and C₇ positions of ring A, and substitution by the ketonic group at the C₄ position were considered as lead modifications in the bioactivity of flavonoids for potent antidiabetic activity.