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Khan AU, Khan A, Khan A, et al. Inhibition of NF-κB signaling and HSP70/HSP90 proteins by newly synthesized hydrazide derivatives in arthritis model. Naunyn Schmiedebergs Arch Pharmacol. 2021;394(7):1497-1519doi: 10.1007/s00210-021-02075-5.
Khan, A. U., Khan, A., Khan, A., Shal, B., Aziz, A., Ahmed, M. N., Islam, S. U., Ali, H., Shehzad, A., & Khan, S. (2021). Inhibition of NF-κB signaling and HSP70/HSP90 proteins by newly synthesized hydrazide derivatives in arthritis model. Naunyn-Schmiedeberg's archives of pharmacology, 394(7), 1497-1519. https://doi.org/10.1007/s00210-021-02075-5
Khan, Ashraf Ullah, et al. "Inhibition of NF-κB signaling and HSP70/HSP90 proteins by newly synthesized hydrazide derivatives in arthritis model." Naunyn-Schmiedeberg's archives of pharmacology vol. 394,7 (2021): 1497-1519. doi: https://doi.org/10.1007/s00210-021-02075-5
Khan AU, Khan A, Khan A, Shal B, Aziz A, Ahmed MN, Islam SU, Ali H, Shehzad A, Khan S. Inhibition of NF-κB signaling and HSP70/HSP90 proteins by newly synthesized hydrazide derivatives in arthritis model. Naunyn Schmiedebergs Arch Pharmacol. 2021 Jul;394(7):1497-1519. doi: 10.1007/s00210-021-02075-5. Epub 2021 Mar 13. PMID: 33713158.
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Naunyn Schmiedebergs Arch Pharmacol. 2021 Jul;394(7):1497-1519. doi: 10.1007/s00210-021-02075-5. Epub 2021 Mar 13.

Inhibition of NF-κB signaling and HSP70/HSP90 proteins by newly synthesized hydrazide derivatives in arthritis model.

Naunyn-Schmiedeberg's archives of pharmacology

Ashraf Ullah Khan, Amna Khan, Adnan Khan, Bushra Shal, Abdul Aziz, Muhammad Naeem Ahmed, Salman Ul Islam, Hussain Ali, Adeeb Shehzad, Salman Khan

Affiliations

  1. Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
  2. Department of Chemistry, The University of Azad Jammu and Kashmir, Muzaffarabad, 13100, Pakistan.
  3. School of Life Sciences, College of Natural Sciences, Kyungpook National University, Daegu, South Korea.
  4. Department of Biomedical Engineering & Sciences, School of Mechanical and Manufacturing Engineering (SMME), National University of Sciences & Technology (NUST), Islamabad, Pakistan.
  5. Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. [email protected].

PMID: 33713158 DOI: 10.1007/s00210-021-02075-5

Abstract

In the current study, the N-benzylidene-4-((2-hydroxynaphthalene-1-yl) diazenyl) hydrazides (NCHDH and NTHDH) were evaluated against the Carrageenan- and CFA-induced models. During the preliminary investigation, the NCHDH and NTHDH treatment showed marked anti-inflammatory and analgesic activity against the Carrageenan-induced acute model. Once the anti-inflammatory activity was established against acute Carrageenan model, the NCHDH and NTHDH were evaluated against the chronic CFA-induced arthritis model. The NCHDH and NTHDH treatment markedly attenuated the inflammatory and analgesic parameters compared to CFA-treated group. Furthermore, the increase in the oxidative stress and attenuation of antioxidant enzymes has been reported following CFA administration. However, NCHDH and NTHDH treatment significantly induced the antioxidants and attenuated the oxidative stress markers. The CFA administration showed marked tailing of DNA; however, the NCHDH- and NTHDH-treated group preserved DNA integrity. Furthermore, the histological studies showed marked alteration in the CFA-treated group; however, the NCHDH and NTHDH treatment markedly improved the histological features. The Western blot, immunohistology, and ELISA assay revealed marked increase in the Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Jun N-terminal Kinase (JNK), TNF-α, and COX-2 levels; however, the NCHDH and NTHDH attenuated their expressions significantly. Similarly, the NCHDH and NTHDH significantly induced the mRNA expression levels of heat shock proteins. The computational analysis showed significant binding interaction with various protein targets via multiple hydrogens, and hydrophobic bonds. The in vivo pharmacokinetic study was also performed to assess the various pharmacokinetic parameters. In conclusion, the NCHDH and NTHDH treatment showed significant anti-arthritic activity against Carrageenan and CFA models.

Keywords: CFA; Carrageenan; Cytokines; Inflammation; Nitric oxide; Oxidative stress; Pain

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