Biomedicine & Pharmacotherapy (Dec 2023)
AG5 is a potent non-steroidal anti-inflammatory and immune regulator that preserves innate immunity
- Pablo Botella-Asunción,
- Eva M. Rivero-Buceta,
- Carla Vidaurre-Agut,
- Raquel Lama,
- Magalí Rey-Campos,
- Alejandro Moreno,
- Laura Mendoza,
- Patricia Mingo-Casas,
- Estela Escribano-Romero,
- Alfonso Gutierrez-Adan,
- Juan Carlos Saiz,
- Cristian Smerdou,
- Gloria Gonzalez,
- Felipe Prosper,
- Josepmaría Argemí,
- Jesus San Miguel,
- Pedro J. Sanchez-Cordón,
- Antonio Figueras,
- Jose Manuel Quesada-Gomez,
- Beatriz Novoa,
- María Montoya,
- Miguel A. Martín-Acebes,
- Antonio Pineda-Lucena,
- Jose María Benlloch
Affiliations
- Pablo Botella-Asunción
- Institute of Chemical Technology (ITQ), Universitat Politècnica de Valencia-Spanish National Research Council (CSIC), 46022 Valencia, Spain; Corresponding authors.
- Eva M. Rivero-Buceta
- Institute of Chemical Technology (ITQ), Universitat Politècnica de Valencia-Spanish National Research Council (CSIC), 46022 Valencia, Spain
- Carla Vidaurre-Agut
- Institute of Chemical Technology (ITQ), Universitat Politècnica de Valencia-Spanish National Research Council (CSIC), 46022 Valencia, Spain
- Raquel Lama
- Institute of Marine Research (IIM), Spanish National Research Council (CSIC), 36208 Vigo, Spain
- Magalí Rey-Campos
- Institute of Marine Research (IIM), Spanish National Research Council (CSIC), 36208 Vigo, Spain
- Alejandro Moreno
- Institute of Marine Research (IIM), Spanish National Research Council (CSIC), 36208 Vigo, Spain
- Laura Mendoza
- Molecular Biomedicine Department, BICS Unit, Centro de Investigaciones Biológicas Margarita Salas (CIB), Spanish National Research Council (CSIC), 28040 Madrid, Spain
- Patricia Mingo-Casas
- Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Spanish National Research Council (CSIC), 28040 Madrid, Spain
- Estela Escribano-Romero
- Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Spanish National Research Council (CSIC), 28040 Madrid, Spain
- Alfonso Gutierrez-Adan
- Animal Reproduction Department, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Spanish National Research Council (CSIC), 28040 Madrid, Spain
- Juan Carlos Saiz
- Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Spanish National Research Council (CSIC), 28040 Madrid, Spain
- Cristian Smerdou
- DNA & RNA Medicine Division, Centro de Investigación Medica Aplicada (CIMA), Universidad de Navarra, 31008 Pamplona, Spain
- Gloria Gonzalez
- DNA & RNA Medicine Division, Centro de Investigación Medica Aplicada (CIMA), Universidad de Navarra, 31008 Pamplona, Spain
- Felipe Prosper
- Hematology Service and Cell Therapy Unit and Program of Hematology-Oncology CIMA-Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN) and Instituto de Investigación Sanitaria de Navarra (IdISNA), Pamplona, Spain. Centro de Investigación Biomedica en Red Cancer (CIBERONC) and RICORS TERAV, Madrid, Spain
- Josepmaría Argemí
- Hematology Service and Cell Therapy Unit and Program of Hematology-Oncology CIMA-Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN) and Instituto de Investigación Sanitaria de Navarra (IdISNA), Pamplona, Spain. Centro de Investigación Biomedica en Red Cancer (CIBERONC) and RICORS TERAV, Madrid, Spain
- Jesus San Miguel
- Hematology Service and Cell Therapy Unit and Program of Hematology-Oncology CIMA-Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN) and Instituto de Investigación Sanitaria de Navarra (IdISNA), Pamplona, Spain. Centro de Investigación Biomedica en Red Cancer (CIBERONC) and RICORS TERAV, Madrid, Spain
- Pedro J. Sanchez-Cordón
- Veterinary Pathology Unit, Animal Health Research Center (CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Spanish National Research Council (CSIC), 28130 Madrid, Spain
- Antonio Figueras
- Institute of Marine Research (IIM), Spanish National Research Council (CSIC), 36208 Vigo, Spain
- Jose Manuel Quesada-Gomez
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Hospital Universitario Reina Sofía, 14004 Córdoba, Spain
- Beatriz Novoa
- Institute of Marine Research (IIM), Spanish National Research Council (CSIC), 36208 Vigo, Spain
- María Montoya
- Molecular Biomedicine Department, BICS Unit, Centro de Investigaciones Biológicas Margarita Salas (CIB), Spanish National Research Council (CSIC), 28040 Madrid, Spain
- Miguel A. Martín-Acebes
- Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Spanish National Research Council (CSIC), 28040 Madrid, Spain
- Antonio Pineda-Lucena
- Enabling Technologies Division, Centro de Investigación Medica Aplicada (CIMA), Universidad de Navarra, 31008 Pamplona Spain
- Jose María Benlloch
- Institute of Instrumentation for Molecular Imaging (I3M), Universitat Politècnica de Valencia-Spanish National Research Council (CSIC), 46011 Valencia, Spain; Corresponding authors.
- Journal volume & issue
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Vol. 169
p. 115882
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.