5-Amino Salicylic Acid and Sodium Salicylate Inhibit Activation of Iandkappa;B Kinase and P38 andgamma; MAP Kinase in LPS Induced RAW 264.7 cell

Rama Satyanarayana Raju Kalidhindi; Saurabh Gupta; Gurjeet Thakur; S; eep Arora; Nilesh S Ambhore; Vishakantha Murthy; Ashish D Wadhwani; Md. Afzal Azam; Kannan Elango

Abstract

5-Amino Salicylic Acid and Sodium Salicylate Inhibit Activation of IκB Kinase and P38 γ MAP Kinase in LPS Induced RAW 264.7 cell

Author(s): Rama Satyanarayana Raju Kalidhindi, Saurabh Gupta, Gurjeet Thakur, Sandeep Arora, Nilesh S Ambhore, Vishakantha Murthy, Ashish D Wadhwani, Md. Afzal Azam, Kannan Elango

Allergic asthma is a complicated disorder where multiple stimuli activate various signalling pathways resulting in the synthesis of a wide array of inflammatory proteins. Among the diverse transcription factors in the human genome, Nucleus Factor Kappa B (NFκB) and p38 Mitogen Activated Protein (MAP) kinases play a crucial role in the pathophysiology of allergic asthma. Salicylic acid derivatives, 5-Amino Salicylic Acid (5-ASA) and Sodium Salicylate (SS) have been evidenced to inhibit NFκB in vitro model. 5-ASA has demonstrated significant antiasthmatic activity in preclinical murine models. In the present study, 5-ASA and SS were screened in silico against a definite set of proteins, namely Inhibitor of Kappa Beta (IκB), p38 α, β, γ and δ using Glide and Prime modules of Schrodinger suite. The two drug candidates were attributed to the MTT assay in RAW 264.7 mouse monocyte macrophage cells for their in vitro cytotoxicity. From the hits obtained in silico, IκB and p38γ were further evaluated using western blot analysis followed by evaluation of TNF-alpha, IL-6, IL-13, nitrate and nitrite, Myeloperoxidase (MPO) and Malondialdehyde (MDA) levels in Lipopolysaccharide (LPS) induced RAW 264.7 cells. The results revealed significant reduction in the levels of the aforementioned parameters accompanied by the reduced expression of IκB and p38γ in cells treated with 5 ASA and SS, when compared LPS induced cells indicating the immune suppressive potential of both the drugs that can be used against allergic asthma.

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