Scientific publications

AG5 is a potent non-steroidal anti-inflammatory and immune regulator that preserves innate immunity

Nov 18, 2023 | Magazine: Biomed Pharmacotherapy

Pablo Botella-Asunción  1 , Eva M Rivero-Buceta  2 , Carla Vidaurre-Agut  2 , Raquel Lama  3 , Magalí Rey-Campos  3 , Alejandro Moreno  3 , Laura Mendoza  4 , Patricia Mingo-Casas  5 , Estela Escribano-Romero  5 , Alfonso Gutierrez-Adan  6 , Juan Carlos Saiz  5 , Cristian Smerdou  7 , Gloria Gonzalez  7 , Felipe Prosper  8 , Josepmaría Argemí  8 , Jesus San Miguel  8 , Pedro J Sanchez-Cordón  9 , Antonio Figueras  3 , Jose Manuel Quesada-Gomez  10 , Beatriz Novoa  3 , María Montoya  4 , Miguel A Martín-Acebes  5 , Antonio Pineda-Lucena  11 , Jose María Benlloch  12


Abstract

An archetypal anti-inflammatory compound against cytokine storm would inhibit it without suppressing the innate immune response. AG5, an anti-inflammatory compound, has been developed as synthetic derivative of andrographolide, which is highly absorbable and presents low toxicity.

We found that the mechanism of action of AG5 is through the inhibition of caspase-1. Interestingly, we show with in vitro generated human monocyte derived dendritic cells that AG5 preserves innate immune response. AG5 minimizes inflammatory response in a mouse model of lipopolysaccharide (LPS)-induced lung injury and exhibits in vivo anti-inflammatory efficacy in the SARS-CoV-2-infected mouse model.

AG5 opens up a new class of anti-inflammatories, since contrary to NSAIDs, AG5 is able to inhibit the cytokine storm, like dexamethasone, but, unlike corticosteroids, preserves adequately the innate immunity.

This is critical at the early stages of any naïve infection, but particularly in SARS-CoV-2 infections. Furthermore, AG5 showed interesting antiviral activity against SARS-CoV-2 in humanized mice.

CITATION  Biomed Pharmacother. 2023 Dec 31:169:115882. doi: 10.1016/j.biopha.2023.115882

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