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Tumor necrosis factor-alpha, prostaglandin-E2 and interleukin-1β targeted anti-arthritic potential of fluvoxamine: drug repurposing

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Abstract

Fluvoxamine, a selective serotonin re uptake inhibitor, is used to treat depression. The aim of present study was to evaluate fluvoxamine in acute (egg albumin-induced inflammation) and chronic inflammatory rat models (formaldehyde and complete Freund’s adjuvant (CFA)-induced arthritis). Fluvoxamine showed highly significant (p<0.001) protective effect at dose of 50 mg/kg orally with percentage suppression 21.3% as compared to disease control group in acute model. Likewise, formaldehyde-induced arthritic experiment confirmed the significant (p<0.001) anti-arthritic behavior, showed by fluvoxamine (50 mg/kg orally) throughout the study. Moreover, In CFA-induced model, the higher dose (fluvoxamine 50 mg/kg) exhibited highly significant (p<0.001) decrease in paw thickness and arthritic score with significant increase in weight of animals from 123.8± 1.934 g to 130.2± 1.655 g, significantly decreased the level of RF and CRP to level of 12.0±0.707 and 11.40±0.50 respectively and restoration of SOD, CAT (69.8±1.5, 72.0±1.4 respectively). Furthermore, the level of TNF-α, PGE2, and IL-1β (147.0±2.0, 406.8±2.5, and 93.8±1.3 respectively) in arthritic animals was reduced to significant (p<0.001) level (53.8±1.3, 205±3.6, and 42.0±1.4 respectively) after treatment with fluvoxamine. Furthermore, molecular docking of fluvoxamine against TNF-α, PGE2, and IL-1β protein targets showed good binding energies which hereby from computational studies proves our compound anti-inflammatory potential. In addition, absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies reveled that fluvoxamine has very good pharmacokinetic profile with no specific hepatic toxicity and good absorption level. In addition, the skin sensitization test in vitro human cell line activation test (h-CLAT) and KeratinoSens have revealed that isolated flavone is not skin sensitive with confidence score of 59.6% and 91.6%. The current findings validated the anti-arthritic potential of fluvoxamine but it should be recommended for clinical investigation in future research.

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Acknowledgements

The authors would like to acknowledge the Higher Education Commission of Pakistan and University of Sargodha, Pakistan, for providing the facilities to conduct research.

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Authors and Affiliations

  1. Faculty of Pharmacy, University of Sargodha, Sargodha, Pakistan

    Haseeb Ahsan, Mahnoor Ayub & Hafiz Muhammad Irfan

  2. Department of Pharmacology, University College of Pharmacy, University of the Punjab, Lahore, Pakistan

    Muhammad Saleem

  3. Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan

    Irfan Anjum

  4. Nawaz Sharif Medical College, University of Gujrat, Gujrat, Pakistan

    Ihtisham Haider & Awais Asif

  5. Department of Pharmacy, Sarhad University of Science and Technology, Peshawar, Pakistan

    Syed Qamar Abbas

  6. Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China

    Syed Shams ul Hulassan

  7. Department of Natural Product Chemistry, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China

    Syed Shams ul Hulassan

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  1. Haseeb Ahsan
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  2. Mahnoor Ayub
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  3. Hafiz Muhammad Irfan
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  4. Muhammad Saleem
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  5. Irfan Anjum
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  6. Ihtisham Haider
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  7. Awais Asif
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  8. Syed Qamar Abbas
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  9. Syed Shams ul Hulassan
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Contributions

H. Ahsan and M. Ayub have done the experiments and written the original draft. H. M. Irfan and M. Saleem have rechecked the manuscript for any errors. I. Anjum and S. Q. Abbas have analyzed the data. I. Haider and A. Asif have done the in vitro studies. H. A and S. S. U. H have designed and supervised an experiment. I.A revised the manuscript according to reviewer’s comments and prepared the response letter.

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Correspondence to Syed Shams ul Hulassan.

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Ahsan, H., Ayub, M., Irfan, H.M. et al. Tumor necrosis factor-alpha, prostaglandin-E2 and interleukin-1β targeted anti-arthritic potential of fluvoxamine: drug repurposing. Environ Sci Pollut Res 30, 14580–14591 (2023). https://doi.org/10.1007/s11356-022-23142-1

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