Exploring the Effectiveness and Potential Pharmacological Mechanism of Minocycline for Spinal Cord Injury through Meta-Analysis and Network Pharmacology.

Abstract

Spinal cord injury (SCI) has a catastrophic impact and lifelong functional incapacity on patients. Recent research has demonstrated the anti-inflammation and neuroprotection of minocycline, which were advantageous for treating disorders having an inflammatory foundation, including SCI. This study summarized the antioxidant, anti-inflammation, and neuro-restoration of minocycline. PubMed, Web of Science, Embase, and Chinese database were explored from their origin date to July 2022. Data extraction, methodological quality assessment, and study selection were conducted by 2 reviewers. Twenty-four studies were ultimately included. Overall, minocycline improved motor recovery after SCI, with Basso Beattie Bresnahan (BBB) scores in the treated group from the first week (15 studies, n = 378; MD = 2.34; 95% Confidence interval (CI), 1.31-3.36; p < 0.00001) to the fourth week (14 studies, n = 346; MD = 3.15; 95% Confidence Interval (CI), 2.07-4.23; p < 0.00001). Subgroup analysis showed function recovery was related to the mode of drug dose, animal race, and article quality. Network pharmacology identified 100 minocycline-related targets and 6720 SCI-related targets. Heat Shock Protein 90 Alpha Family Class A Member 1(HSP90AA1), Serine/Threonine kinase 1(Akt1), Steroid Receptor Coactivator (SRC), Epidermal growth factor receptor (EGFR) and Catenin (Cadherin-Associated Protein)-Beta 1 (CTNNB1) were key targets. 20 pathways were identified, including PI3K/Akt, MAPK and chemokine signaling pathway. Finally, molecular docking results showed B-cell CLL/lymphoma 2 (BCL2-6), CTNNB1, HSP90AA1, plasminogen activator urokinase (PLAU), and α protein kinase C alpha (PRCAKA) bound to minocycline better. This article concluded that minocycline was effective in treating SCI by improving neurological recovery and inhibiting oxidative stress, apoptosis, and inflammation.