Revolutionizing Treatment Strategies for Autoimmune and Inflammatory Disorders: The Impact of Dipeptidyl-Peptidase 4 Inhibitors

Abstract

Kashif Rahim,1 Muhammad Shan,2 Ihtisham Ul Haq,3– 5 Muhammad Naveed Nawaz,2 Sajida Maryam,3,4 Mansour S Alturki,6 Abdulaziz H Al Khzem,6 Kamel Metwally,7 Simona Cavalu,8 Saleh F Alqifari,9 Galal Yahya10 1School of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, People’s Republic of China; 2Department of Microbiology, Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Punjab, Pakistan; 3Department of Physical Chemistry and Technology of Polymers, Silesian University of Technology, Gliwice, Poland; 4Joint Doctoral School, Silesian University of Technology, Gliwice, 44-100, Poland; 5Programa de Pós-graduação em Inovação Tecnológica, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil; 6Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, 34212, Saudi Arabia; 7Department of Medicinal Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, 71491, Saudi Arabia; 8Faculty of Medicine and Pharmacy, University of Oradea, Oradea, 410073, Romania; 9Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk, 71491, Saudi Arabia; 10Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Al Sharqia, 44519, EgyptCorrespondence: Kashif Rahim, School of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, People’s Republic of China, Email [email protected] Saleh F Alqifari, Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk, 71491, Saudi Arabia, Email [email protected]: DPP4 (Dipeptidyl-peptidase 4) a versatile protease, emerges as a prominent player in soluble and membrane-bound forms. Its heightened expression has been intimately linked to the initiation and severity of diverse autoimmune diseases, spanning rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (SSc), inflammatory bowel disease, autoimmune diabetes, and even SARS-CoV-2 infection. Operating as a co-stimulator of T cell activity, DPP4 propels T cell proliferation by binding adenosine deaminase (ADA), thereby augmenting the breakdown of adenosine—an influential inhibitor of T cell proliferation. However, the discovery of a wide range of DPP4 inhibitors has shown promise in alleviating these diseases’ signs, symptoms, and severity. The available DPP4 inhibitors have demonstrated significant effectiveness in blocking DPP4 activity. Based on the characterization of their binding mechanisms, three distinct groups of DPP4 inhibitors have been identified: saxagliptin, alogliptin, and sitagliptin, each representing a different class. Elevated levels of angiotensin-converting enzyme 2 (ACE2) expression are associated with producing various coronavirus peptidases. With its anti-inflammatory properties, Sitagliptin may assist COVID-19 patients in preventing and managing cytokine storms. This comprehensive review delves into the burgeoning realm of DPP4 inhibitors as therapeutic interventions for diverse autoimmune diseases. With a discerning focus on their efficacy, the investigation sheds light on their remarkable capacity to alleviate the burdensome signs and symptoms intricately linked to these conditions.Keywords: autoimmune diseases, DPP4 inhibitors, inflammatory disorders, MERS-CoV, diabetes mellitus, COVID-19

Keywords

• autoimmune diseases
• dpp4 inhibitors
• inflammatory disorders
• mers-cov
• diabetes mellitus
• covid-19