Canagliflozin-loaded chitosan-hyaluronic acid microspheres modulate AMPK/NF-κB/NLRP3 axis: A new paradigm in the rectal therapy of ulcerative colitis
Ulcerative colitis is an idiopathic disease that is widely incident worldwide. Canagliflozin, antidiabetic agent, exhibited significant anti-inflammatory effects in a variety of animal models. Additionally, hyaluronic acid is considered one of the key players in the tissue regeneration process. It h...
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Elsevier
2022-09-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222007983 |
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| author | Mohamed Nasr Simona Cavalu Sameh Saber Mahmoud E. Youssef Amir Mohamed Abdelhamid Heba I. Elagamy Islam Kamal Ahmed Gaafar Ahmed Gaafar Eman El-Ahwany Noha A. Amin Samuel Girgis Rawan El-Sandarosy Fatma Mahmoud Hadeer Rizk Merna Mansour Amal Hasaballah Amira Abd El-Rafi Reem Abd El-Azez Mahy Essam Dina Mohamed Nada Essam Osama A. Mohammed |
| author_facet | Mohamed Nasr Simona Cavalu Sameh Saber Mahmoud E. Youssef Amir Mohamed Abdelhamid Heba I. Elagamy Islam Kamal Ahmed Gaafar Ahmed Gaafar Eman El-Ahwany Noha A. Amin Samuel Girgis Rawan El-Sandarosy Fatma Mahmoud Hadeer Rizk Merna Mansour Amal Hasaballah Amira Abd El-Rafi Reem Abd El-Azez Mahy Essam Dina Mohamed Nada Essam Osama A. Mohammed |
| author_sort | Mohamed Nasr |
| collection | DOAJ |
| description | Ulcerative colitis is an idiopathic disease that is widely incident worldwide. Canagliflozin, antidiabetic agent, exhibited significant anti-inflammatory effects in a variety of animal models. Additionally, hyaluronic acid is considered one of the key players in the tissue regeneration process. It has been proven to modulate inflammation and cellular migration, which are the main phases of wound healing. The combination of hyaluronic acid with chitosan in microsphere fabrication was anticipated to reveal a synergistic muco-adhesiveness potential with additional advantage of the chitosan penetration enhancing effect. The current study aimed to explore the potential of canagliflozin-loaded chitosan-hyaluronic acid microspheres intrarectal administration to mitigate acetic acid-induced colitis in rats. Colon tissues were examined for macroscopic and microscopic pathological changes. ELISA and qRT-PCR techniques were applied for the detection of cytokines involved in the AMPK/NF-κB/NLRP3 axis. Intrarectal administration of this formula alleviated colitis severity, which was reflected by the reduced DAI, MES, colonic weight/length ratio and histopathological scoring values. Interestingly, canagliflozin-loaded chitosan-hyaluronic acid microspheres significantly enhanced AMPK phosphorylation and depressed NF-κB and NLRP3 expression leading to a subsequent reduction in caspase-1 cleavage and the inhibition of several inflammatory cytokines, including IL-1β, and IL-18. Overall, the current study revealed that the protective effects of the formula against acetic acid-induced colitis are primarily mediated via augmenting AMPK phosphorylation and its consequences of NF-κB inactivation. Since canagliflozin is not associated with hypoglycemic effects, clinical application of canagliflozin-loaded chitosan-hyaluronic acid microspheres represent a novel therapeutic option for the treatment of patients with ulcerative colitis. |
| first_indexed | 2024-04-13T17:59:37Z |
| format | Article |
| id | doaj.art-27e58b87bfdf4a14b61043f2fac4a48c |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-13T17:59:37Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
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| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-27e58b87bfdf4a14b61043f2fac4a48c2022-12-22T02:36:17ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-09-01153113409Canagliflozin-loaded chitosan-hyaluronic acid microspheres modulate AMPK/NF-κB/NLRP3 axis: A new paradigm in the rectal therapy of ulcerative colitisMohamed Nasr0Simona Cavalu1Sameh Saber2Mahmoud E. Youssef3Amir Mohamed Abdelhamid4Heba I. Elagamy5Islam Kamal6Ahmed Gaafar Ahmed Gaafar7Eman El-Ahwany8Noha A. Amin9Samuel Girgis10Rawan El-Sandarosy11Fatma Mahmoud12Hadeer Rizk13Merna Mansour14Amal Hasaballah15Amira Abd El-Rafi16Reem Abd El-Azez17Mahy Essam18Dina Mohamed19Nada Essam20Osama A. Mohammed21Department of Pharmaceutics, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Cairo 11790, EgyptFaculty of Medicine and Pharmacy, University of Oradea, P-ta 1 Decembrie 10, 410087 Oradea, Romania; Corresponding authors.Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt; Corresponding authors.Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt; Corresponding authors.Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, Port Said University, Port Said, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Port Said University, Port Said 42511, EgyptDepartment of Immunology, Theodor Bilharz Research Institute, Giza, EgyptDepartment of Haematology, Theodor Bilharz Research Institute, Giza 12411, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, Alsalam University, EgyptDepartment of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, EgyptDepartment of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, EgyptDepartment of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, EgyptDepartment of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, EgyptDepartment of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, EgyptDepartment of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, EgyptDepartment of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, EgyptDepartment of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, EgyptDepartment of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, EgyptDepartment of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, EgyptDepartment of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt; Department of Clinical Pharmacology, Faculty of medicine, Bisha University, Bisha 61922, Saudi ArabiaUlcerative colitis is an idiopathic disease that is widely incident worldwide. Canagliflozin, antidiabetic agent, exhibited significant anti-inflammatory effects in a variety of animal models. Additionally, hyaluronic acid is considered one of the key players in the tissue regeneration process. It has been proven to modulate inflammation and cellular migration, which are the main phases of wound healing. The combination of hyaluronic acid with chitosan in microsphere fabrication was anticipated to reveal a synergistic muco-adhesiveness potential with additional advantage of the chitosan penetration enhancing effect. The current study aimed to explore the potential of canagliflozin-loaded chitosan-hyaluronic acid microspheres intrarectal administration to mitigate acetic acid-induced colitis in rats. Colon tissues were examined for macroscopic and microscopic pathological changes. ELISA and qRT-PCR techniques were applied for the detection of cytokines involved in the AMPK/NF-κB/NLRP3 axis. Intrarectal administration of this formula alleviated colitis severity, which was reflected by the reduced DAI, MES, colonic weight/length ratio and histopathological scoring values. Interestingly, canagliflozin-loaded chitosan-hyaluronic acid microspheres significantly enhanced AMPK phosphorylation and depressed NF-κB and NLRP3 expression leading to a subsequent reduction in caspase-1 cleavage and the inhibition of several inflammatory cytokines, including IL-1β, and IL-18. Overall, the current study revealed that the protective effects of the formula against acetic acid-induced colitis are primarily mediated via augmenting AMPK phosphorylation and its consequences of NF-κB inactivation. Since canagliflozin is not associated with hypoglycemic effects, clinical application of canagliflozin-loaded chitosan-hyaluronic acid microspheres represent a novel therapeutic option for the treatment of patients with ulcerative colitis.http://www.sciencedirect.com/science/article/pii/S0753332222007983CanagliflozinChitosanHyaluronic acidMicrospheresAMPK/NFκB/NLRP3 axisUlcerative colitis |
| spellingShingle | Mohamed Nasr Simona Cavalu Sameh Saber Mahmoud E. Youssef Amir Mohamed Abdelhamid Heba I. Elagamy Islam Kamal Ahmed Gaafar Ahmed Gaafar Eman El-Ahwany Noha A. Amin Samuel Girgis Rawan El-Sandarosy Fatma Mahmoud Hadeer Rizk Merna Mansour Amal Hasaballah Amira Abd El-Rafi Reem Abd El-Azez Mahy Essam Dina Mohamed Nada Essam Osama A. Mohammed Canagliflozin-loaded chitosan-hyaluronic acid microspheres modulate AMPK/NF-κB/NLRP3 axis: A new paradigm in the rectal therapy of ulcerative colitis Biomedicine & Pharmacotherapy Canagliflozin Chitosan Hyaluronic acid Microspheres AMPK/NFκB/NLRP3 axis Ulcerative colitis |
| title | Canagliflozin-loaded chitosan-hyaluronic acid microspheres modulate AMPK/NF-κB/NLRP3 axis: A new paradigm in the rectal therapy of ulcerative colitis |
| title_full | Canagliflozin-loaded chitosan-hyaluronic acid microspheres modulate AMPK/NF-κB/NLRP3 axis: A new paradigm in the rectal therapy of ulcerative colitis |
| title_fullStr | Canagliflozin-loaded chitosan-hyaluronic acid microspheres modulate AMPK/NF-κB/NLRP3 axis: A new paradigm in the rectal therapy of ulcerative colitis |
| title_full_unstemmed | Canagliflozin-loaded chitosan-hyaluronic acid microspheres modulate AMPK/NF-κB/NLRP3 axis: A new paradigm in the rectal therapy of ulcerative colitis |
| title_short | Canagliflozin-loaded chitosan-hyaluronic acid microspheres modulate AMPK/NF-κB/NLRP3 axis: A new paradigm in the rectal therapy of ulcerative colitis |
| title_sort | canagliflozin loaded chitosan hyaluronic acid microspheres modulate ampk nf κb nlrp3 axis a new paradigm in the rectal therapy of ulcerative colitis |
| topic | Canagliflozin Chitosan Hyaluronic acid Microspheres AMPK/NFκB/NLRP3 axis Ulcerative colitis |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222007983 |
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