{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:49:40Z","timestamp":1791859780137,"version":"4.3.4"},"reference-count":80,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006261","name":"Taif University","doi-asserted-by":"publisher","award":["TU-DSPP-2024-116"],"award-info":[{"award-number":["TU-DSPP-2024-116"]}],"id":[{"id":"10.13039\/501100006261","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Parkinson\u2019s disease (PD) is a pathological state characterized by a combined set of abnormal movements including slow motion, resting tremors, profound stiffness of skeletal muscles, or obvious abnormalities in posture and gait, together with significant behavioral changes. Until now, no single therapeutic modality was able to provide a complete cure for PD. This work was a trial to assess the immunomodulatory effects of canagliflozin with or without levodopa\/carbidopa on rotenone-induced parkinsonism in Balb\/c mice. Materials and Methods: In a mouse model of PD, the effect of canagliflozin with or without levodopa\/carbidopa was assessed at the behavioral, biochemical, and histopathological levels. Results: The combination of levodopa\/carbidopa and canagliflozin significantly mitigated the changes induced by rotenone administration regarding the behavioral tests, striatal dopamine, antioxidant status, Nrf2 content, SIRT\u20131\/PPAR\u2013gamma axis, RAGE\/HMGB1\/NF-\u03baB signaling, and mitochondrial dysfunction; abrogated the neuroinflammatory responses, and alleviated the histomorphologic changes induced by rotenone administration relative to the groups that received either levodopa\/carbidopa or canagliflozin alone. Conclusions: Canagliflozin may represent a new adjuvant therapeutic agent that may add value to the combatting effects of levodopa\/carbidopa against the pathological effects of PD.<\/jats:p>","DOI":"10.3390\/medicina60101682","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T05:47:58Z","timestamp":1728884878000},"page":"1682","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Targeting the Sirtuin\u20131\/PPAR\u2013Gamma Axis, RAGE\/HMGB1\/NF-\u03baB Signaling, and the Mitochondrial Functions by Canagliflozin Augments the Protective Effects of Levodopa\/Carbidopa in Rotenone-Induced Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"60","author":[{"given":"Mennatallah A.","family":"Elkady","sequence":"first","affiliation":[{"name":"Pharmacology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5101-8011","authenticated-orcid":false,"given":"Ahmed M.","family":"Kabel","sequence":"additional","affiliation":[{"name":"Pharmacology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamees M.","family":"Dawood","sequence":"additional","affiliation":[{"name":"Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta 31511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azza I.","family":"Helal","sequence":"additional","affiliation":[{"name":"Department of Histology and Cell Biology, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hany M.","family":"Borg","sequence":"additional","affiliation":[{"name":"Physiology Department, Faculty of Medicine, Kafrelsheikh University, Kafr El-Shaikh 33516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan Abdelmawgoud","family":"Atia","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, University of Hail, Hail 2440, Saudi Arabia"},{"name":"Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Al-Azhar University, Cairo 35527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nesreen M.","family":"Sabry","sequence":"additional","affiliation":[{"name":"Clinical Oncology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nouran M.","family":"Moustafa","sequence":"additional","affiliation":[{"name":"Medical Microbiology & Immunology Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt"},{"name":"Basic Medical Science Department, College of Medicine, Dar Al Uloom University, Riyadh 13314, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9034-6624","authenticated-orcid":false,"given":"El-Shaimaa A.","family":"Arafa","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Health Sciences, Ajman University, Ajman 346, United Arab Emirates"},{"name":"Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman 346, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5567-6169","authenticated-orcid":false,"given":"Shuruq E.","family":"Alsufyani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hany H.","family":"Arab","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S30","DOI":"10.1016\/j.parkreldis.2017.07.033","article-title":"Neuropathology of Parkinson disease","volume":"46","author":"Dickson","year":"2018","journal-title":"Park. 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