Romanian Society of Pharmaceutical Sciences
 

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ASSESSMENT OF THE ANTI-ARTHRITIC AND IMMUNOSUPPRESSIVE POTENTIAL OF ENALAPRIL BY USING NETWORK PHARMACOLOGY, MOLECULAR DOCKING AND EXPERIMENTAL PHARMACOLOGY APPROACHES

SUMERA QASIM 1*, YUSRA HABIB KHAN 2, AMBREEN MALIK UTTRA 3, NASSER HADAL ALOTAIBI 2, ABDULLAH SALAH ALANAZI 2, ABDULAZIZ I. ALZAREA 2, AHMED D. ALATAWI 2, NIDA TANVEER 4, GHADA S. ALRUWAILI 5, TAUQEER HUSSAIN MALLHI 2

1Department of Pharmacology, College of Pharmacy, Jouf University, Saudi Arabia
2 Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Saudi Arabia
3 College of Pharmacy, University of Sargodha, Pakistan
4 Institute of molecular cardiology, University of Louisville, Louisville, KY 40202, USA
5 College of pharmacy, Jouf University, Sakaka, Saudi Arabia

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The present study validates the anti-arthritic and immunosuppressive attributes of enalapril, an angiotensin-converting enzyme inhibitor (ACEI) with a potential role in major inflammatory pathways. A network pharmacology-based prediction approach was utilised to reveal the possible target genes that can be targeted by enalapril for managing arthritis. In vitro anti-arthritic efficacy of enalapril was assessed using an assay that measures the denaturation of proteins in bovine serum albumin (BSA), egg albumin and the stability of the human red blood cell (HRBC) membrane at a dosage ranging from 100 to 6400 μg/mL. In vivo anti-arthritic efficacy of enalapril at doses of 2, 4 and 8 mg/kg bw was assessed in formaldehyde-induced arthritis model. Dinitrochlorobenzene (DNCB)-provoked delayed type hypersensitivity (DTH) and cyclophosphamide-provoked myelosuppression were employed to assess the immunosuppressant capacity of enalapril. Network pharmacology outcomes revealed that the anti-arthritic effects of enalapril targets include tumour necrosis factor (TNF), matrix metalloproteinase 9 (MMP-9) and caspase 3 (CASP3). Molecular docking of enalapril with these three targets also validates the strong interaction between them. Enalapril markedly inhibited protein denaturation in egg albumin and bovine serum albumin (BSA) assays and stabilised RBC haemolysis exposed to hypotonic media. Likewise, enalapril demonstrated a dose-dependent inhibition of paw oedema provoked by formaldehyde. In the DTH assay, enalapril significantly reduced skin thickness compared to the negative control group and exhibited potent immunosuppressant potential in cyclophosphamide-induced myelosuppression. Based on the outcomes of the current study, it can be predicted that enalapril has anti-arthritic attributes that might be due to its immunosuppressive potential.