title: High-Throughput Screening Platform for the Discovery of New Immunomodulator Molecules from Natural Product Extract Libraries.
abstract: It is widely accepted that central nervous system inflammation and systemic inflammation play a significant role in the progression of chronic neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, neurotropic viral infections, stroke, paraneoplastic disorders, traumatic brain injury, and multiple sclerosis. Therefore, it seems reasonable to propose that the use of anti-inflammatory drugs might diminish the cumulative effects of inflammation. Indeed, some epidemiological studies suggest that sustained use of anti-inflammatory drugs may prevent or slow down the progression of neurodegenerative diseases. However, the anti-inflammatory drugs and biologics used clinically have the disadvantage of causing side effects and a high cost of treatment. Alternatively, natural products offer great potential for the identification and development of bioactive lead compounds into drugs for treating inflammatory diseases with an improved safety profile. In this work, we present a validated high-throughput screening approach in 96-well plate format for the discovery of new molecules with anti-inflammatory/immunomodulatory activity. The in vitro models are based on the quantitation of nitrite levels in RAW264.7 murine macrophages and interleukin-8 in Caco-2 cells. We have used this platform in a pilot project to screen a subset of 5976 noncytotoxic crude microbial extracts from the MEDINA microbial natural product collection. To our knowledge, this is the first report on an high-throughput screening of microbial natural product extracts for the discovery of immunomodulators.
authors.affiliation: Fundación MEDINA, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento 34, 18016, Granada, Spain jose.perezdelpalacio@medinaandalucia.es.
authors.forename: José
authors.initials: J
authors.lastname: Pérez Del Palacio
authors.affiliation: Fundación MEDINA, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento 34, 18016, Granada, Spain.
authors.forename: Caridad
authors.initials: C
authors.lastname: Díaz
authors.affiliation: Fundación MEDINA, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento 34, 18016, Granada, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: de la Cruz
authors.affiliation: Fundación MEDINA, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento 34, 18016, Granada, Spain.
authors.forename: Frederick
authors.initials: F
authors.lastname: Annang
authors.affiliation: Fundación MEDINA, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento 34, 18016, Granada, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Martín
authors.affiliation: Fundación MEDINA, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento 34, 18016, Granada, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Pérez-Victoria
authors.affiliation: Fundación MEDINA, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento 34, 18016, Granada, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: González-Menéndez
authors.affiliation: Fundación MEDINA, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento 34, 18016, Granada, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: de Pedro
authors.affiliation: Fundación MEDINA, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento 34, 18016, Granada, Spain.
authors.forename: José R
authors.initials: JR
authors.lastname: Tormo
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs. Granada, Center for Biomedical Research (CIBM), University of Granada, Granada, Spain.
authors.forename: Francesca
authors.initials: F
authors.lastname: Algieri
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs. Granada, Center for Biomedical Research (CIBM), University of Granada, Granada, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Rodriguez-Nogales
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs. Granada, Center for Biomedical Research (CIBM), University of Granada, Granada, Spain.
authors.forename: M Elena
authors.initials: ME
authors.lastname: Rodríguez-Cabezas
authors.affiliation: Fundación MEDINA, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento 34, 18016, Granada, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Reyes
authors.affiliation: Fundación MEDINA, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento 34, 18016, Granada, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Genilloud
authors.affiliation: Fundación MEDINA, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento 34, 18016, Granada, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Vicente
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs. Granada, Center for Biomedical Research (CIBM), University of Granada, Granada, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Gálvez
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology*; D018938:Caco-2 Cells; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology; D045424:Complex Mixtures / Q000494:pharmacology; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D016209:Interleukin-8 / Q000378:metabolism; D051379:Mice; D009410:Nerve Degeneration / Q000188:drug therapy; D019636:Neurodegenerative Diseases; D009573:Nitrites / Q000378:metabolism; D000067996:RAW 264.7 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D001688:Biological Products; D045424:Complex Mixtures; D007155:Immunologic Factors; D016209:Interleukin-8; D009573:Nitrites
keywords: high-throughput screening; immune response; inflammation; natural products; neurodegenerative diseases