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Front. Immunol. | doi: 10.3389/fimmu.2019.00581

Anti-nociceptive and anti-inflammatory activities of Asparacosin A involve selective cyclooxygenase 2 and inflammatory cytokines inhibition: an in-vitro, in-vivo and in-silico approach

 Nasiara Karim1, Waheed Khan1,  Ajmal Khan2, 3*, Imran Khan4,  Inamullah Khan5, Sobia A. Halim6 and  Ahmed Al-Harrasi3
  • 1University of Malakand, Pakistan
  • 2COMSATS Institute of Information Technology Abbottabad, Pakistan
  • 3University of Nizwa, Oman
  • 4University of Swabi, Pakistan
  • 5University of Peshawar, Pakistan
  • 6Kinnaird College for Women University, Pakistan

Triterpenes possess anti-inflammatory and anti-nociceptive effects. In this study anti-inflammatory activities of Asparacosin A were evaluated` using in-vitro cyclooxygenases 1 and 2 (COX-1/2) inhibition assays. Moreover anti-nociceptive activities were assessed in-vivo by carrageenan-induced paw edema test, xylene-induced ear edema tests, and acetic acid-induced writhing and formalin tests. Additionally molecular docking was conducted to elucidate the binding mechanism of the compound and to correlate the in-vitro findings with the in-silico data. Oral administration of Asparacosin A at the doses of 10, 20 and 40mg/kg induced significant anti-inflammatory effects (*p<0.05, **p<0.01 and ***p<0.001) in a dose-dependent manner in both models. Asparacosin A also inhibited the human recombinant COX-2 enzyme and caused a dose-dependent decrease in the levels of TNF-α, IL-1β, and PGE2 in the carrageenan-induced paws. Moreover Asparacosin A displayed significant anti-nociceptive effects (*p< 0.05, **p< 0.01, ***p< 0.001) at the doses of 10, 20 and 40 mg/kg in acetic-acid induced writhing test. However in formalin test, Asparacosin A (10-40 mg/kg, p.o) produced anti-nociceptive effects only in the late phase, similar to the effect observed with the reference drug celecoxib (50 mg/kg, p.o). Molecular docking was carried out on both COX-1 and COX-2 structures which revealed that Asparacosin A targets allosteric binding site similar to the binding mode of the selective COX inhibitor. In conclusion, Asparacosin A exhibits anti-inflammatory and peripheral antinociceptive activities which are likely mediated via inhibition of COX-2 enzyme and inflammatory cytokines. Furthermore, Asparacosin A can serve as a model to obtain new and more selective potent anti-inflammatory and antinociceptive drugs.

Keywords: Asparacosin A, Acetic acid-induced writhing test,, Formalin test,, Carrageenan-induced paw edema, Xylene-induced ear edema, docking studies

Received: 11 Sep 2018; Accepted: 04 Mar 2019.

Edited by:

Silvano Sozzani, University of Brescia, Italy

Reviewed by:

Giovanna Montana, Istituto di biomedicina e di immunologia molecolare Alberto Monroy (IBIM), Italy
Annunciata Vecchi, University of Brescia, Italy  

Copyright: © 2019 Karim, Khan, Khan, Khan, Khan, Halim and Al-Harrasi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Ajmal Khan, COMSATS Institute of Information Technology Abbottabad, Abbottabad, Pakistan,