Network Pharmacology, Molecular Docking and Experimental Validation on Potential Application of Diabetic Wound Healing of Cinnamomum zeylanicum Through Matrix Metalloproteinases-8 And 9 (MMP-8 And MMP-9)

Sharmin Akter,1 Shihab Uddin Ahmad,1 Mohiuddin Ahmed Bhuiyan,1 Irin Dewan,1 Rumman Reza,2 Niaz Morshed,2 Md Nazmus Samdani,2 Md Selim Reza,2 Ajoy Kumer,3,4 Isa Naina Mohamed5 1Department of Pharmacy, School of Medicine, University of Asia Pacific, Dhaka, 1215, Bangladesh; 2Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh; 3Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, TN, 602105, India; 4Department of Chemistry, College of Arts and Sciences, International University of Business Agriculture and Technology, Dhaka, 1230, Bangladesh; 5Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, 56000, MalaysiaCorrespondence: Shihab Uddin Ahmad, Department of Pharmacy, School of Medicine, University of Asia Pacific, 74/A, Green Road, Dhaka, 1205, Bangladesh, Email [email protected] Isa Naina Mohamed, Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur, 56000, Malaysia, Email [email protected]: Diabetic wounds are a significant clinical challenge due to impaired healing processes often exacerbated by elevated matrix metalloproteinases (MMPs). Cinnamomum zeylanicum, known for its anti-inflammatory and antioxidant properties, has shown potential in promoting wound healing. This study investigates the molecular docking and experimental validation of Cinnamomum zeylanicum’s effects on diabetic wound healing, focusing on its interaction with matrix metalloproteinases-8 (MMP-8) and 9 (MMP-9).Methods: Molecular docking studies were performed to predict the binding affinity of Cinnamomum zeylanicum compounds to MMP-8 and MMP-9. Diabetic wound healing was evaluated using in vivo models where wounds were induced and treated with Cinnamomum zeylanicum extract. Various parameters were measured, including wound contraction, hydroxyproline content, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels. Biochemical analyses included glucose levels, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and histomorphological examination of skin tissues.Results: Molecular docking results indicated a high binding affinity of Cinnamomum zeylanicum’s bioactive compounds with MMP-8 and MMP-9, suggesting potential inhibition. Experimental validation showed significant improvement in wound contraction and increased hydroxyproline content, indicating enhanced collagen synthesis. Antioxidant enzyme activities (SOD, GPx, CAT) were significantly elevated, while MDA levels were reduced, reflecting decreased oxidative stress. Biochemical analysis demonstrated improved glucose homeostasis with reduced FBG and enhanced OGTT responses. Histomorphological studies revealed improved tissue architecture and re-epithelialization in treated wounds.Conclusion: Cinnamomum zeylanicum exhibits promising potential in diabetic wound healing by modulating MMP-8 and MMP-9 activities, enhancing antioxidant defenses, and improving glucose regulation. These findings support its therapeutic application for diabetic wounds, providing a foundation for further clinical investigations.Keywords: Cinnamomum zeylanicum, xanthosine, methylquinoline, matrix metalloproteinase, wound healing