A study of the molecular mechanism of quercetin and dasatinib combination as senolytic in alleviating age‐related and kidney diseases

Journal of Food BiochemistryVolume 46, Issue 12 e14471 REVIEW A study of the molecular mechanism of quercetin and dasatinib combination as senolytic in alleviating age-related and kidney diseases Khalid Saad Alharbi, Khalid Saad Alharbi Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Saudi ArabiaSearch for more papers by this authorObaid Afzal, Obaid Afzal Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj, Saudi ArabiaSearch for more papers by this authorAbdulmalik Saleh Alfawaz Altamimi, Abdulmalik Saleh Alfawaz Altamimi Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj, Saudi ArabiaSearch for more papers by this authorWaleed Hassan Almalki, Corresponding Author Waleed Hassan Almalki [email protected] orcid.org/0000-0003-2584-8510 Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia Correspondence Waleed Hassan Almalki, Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. Email: [email protected] Imran Kazmi, Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia. Email: [email protected]Search for more papers by this authorImran Kazmi, Corresponding Author Imran Kazmi [email protected] Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia Correspondence Waleed Hassan Almalki, Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. Email: [email protected] Imran Kazmi, Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia. Email: [email protected]Search for more papers by this authorFahad A. Al-Abbasi, Fahad A. Al-Abbasi Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi ArabiaSearch for more papers by this authorSami I. Alzarea, Sami I. Alzarea Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Saudi ArabiaSearch for more papers by this authorHafiz A. Makeen, Hafiz A. Makeen Pharmacy Practice Research Unit, Clinical Pharmacy Department, College of Pharmacy, Jazan University, Jazan, Saudi ArabiaSearch for more papers by this authorMohammed Albratty, Mohammed Albratty Department of Pharmaceutical Chemistry and Pharmacognosy, College of Pharmacy, Jazan University, Jazan, Saudi ArabiaSearch for more papers by this author Khalid Saad Alharbi, Khalid Saad Alharbi Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Saudi ArabiaSearch for more papers by this authorObaid Afzal, Obaid Afzal Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj, Saudi ArabiaSearch for more papers by this authorAbdulmalik Saleh Alfawaz Altamimi, Abdulmalik Saleh Alfawaz Altamimi Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj, Saudi ArabiaSearch for more papers by this authorWaleed Hassan Almalki, Corresponding Author Waleed Hassan Almalki [email protected] orcid.org/0000-0003-2584-8510 Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia Correspondence Waleed Hassan Almalki, Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. Email: [email protected] Imran Kazmi, Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia. Email: [email protected]Search for more papers by this authorImran Kazmi, Corresponding Author Imran Kazmi [email protected] Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia Correspondence Waleed Hassan Almalki, Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. Email: [email protected] Imran Kazmi, Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia. Email: [email protected]Search for more papers by this authorFahad A. Al-Abbasi, Fahad A. Al-Abbasi Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi ArabiaSearch for more papers by this authorSami I. Alzarea, Sami I. Alzarea Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Saudi ArabiaSearch for more papers by this authorHafiz A. Makeen, Hafiz A. Makeen Pharmacy Practice Research Unit, Clinical Pharmacy Department, College of Pharmacy, Jazan University, Jazan, Saudi ArabiaSearch for more papers by this authorMohammed Albratty, Mohammed Albratty Department of Pharmaceutical Chemistry and Pharmacognosy, College of Pharmacy, Jazan University, Jazan, Saudi ArabiaSearch for more papers by this author First published: 21 October 2022 https://doi.org/10.1111/jfbc.14471Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Aging is a significant risk factor for the majority of prevalent human illnesses. The chance of having severe chronic conditions grows dramatically with advancing age. Indeed, more than 90% of people over 65 get at least one chronic disease, including diabetes, heart disease, malignancy, memory loss, and kidney disease, whereas more than 70% have two or more of these ailments. Mouse and human aging lead to increased senescent cells and decreased klotho concentrations. Mice lacking the protein α-klotho show faster aging, similar to human aging. α-Klotho upregulation extends life and slows or suppresses the onset of many age-related illnesses and kidney diseases. Like the consequences of α-klotho deficiency, senescent cell accumulation is linked to tissue dysfunction in various organs and multiple age-related kidney diseases. In addition, α-klotho and cell senescence are negatively and presumably mechanistically linked. Earlier research has demonstrated that klotho exerts its protective effects in age-related and kidney disease by interacting with Wnt ligands, serving as an endogenous antagonist of Wnt/β-catenin signaling. In addition, decreasing senescent cell burden with senolytics, a class of drugs that remove senescent cells selectively and extend the life span of mice. In this work, we are studying the molecular mechanism of the combination of quercetin and dasatinib as senolytic in easing age-related chronic renal illness by altering the level of klotho/Wnt/β-catenin. Practical applications There is an inverse relationship between the onset and the development of age-related disorders and cellular senescence and Klotho. Earlier attempts to suppress transforming growth factor-beta 1 (TGF-β1) in kidney disease with anti-TGF-β1 antibodies were ineffective, and this should be kept in mind. Senolytic medications may benefit from targeting senescent cells, which enhances the protective factor α-klotho. In addition, our study provides a unique, translationally feasible route for creating orally active small compounds to enhance α-klotho, which may also be a valuable biomarker for age-related kidney disease. Additionally, other aspects of aging can be affected by senolytics, such as limiting age-related mitochondrial dysfunction, lowering inflammation and fibrosis, blunting reactive oxygen species (ROS) generation, decreasing deoxyribonucleic acid (DNA) damage, and reinforcing insulin sensitivity. Senolytic agents have been shown to increase adipose progenitor and cardiac progenitor cell activity in aging animals and animals with cellular senescence-related diseases, such as heart, brain, and kidney disease. CONFLICT OF INTEREST No conflict of interest. Open Research DATA AVAILABILITY STATEMENT Data sharing is not applicable to this article as no new data were created or analyzed in this study. Volume46, Issue12December 2022e14471 RelatedInformation