Deep-Sea Coral Garden Invertebrates and Their Associated Fungi Are Genetic Resources for Chronic Disease Drug Discovery
| Autor: | Sam Afoullouss, Pietro Marchese, A. Louise Allcock, Ryan M. Young, J. Mary Murphy, Enda O'Connell, Bill J. Baker, Frank Barry |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Aquatic Organisms
natural products QH301-705.5 Cellular differentiation Pharmaceutical Science regenerative medicine Inflammation Biology 01 natural sciences Regenerative medicine Article Microbiology 03 medical and health sciences Drug Discovery medicine Animals Progenitor cell Biology (General) Pharmacology Toxicology and Pharmaceutics (miscellaneous) Marine fungi 030304 developmental biology anti-inflammatory 0303 health sciences 010405 organic chemistry Drug discovery marine fungi Mesenchymal stem cell Fungi High-throughput screening Anthozoa osteoporosis 0104 chemical sciences osteoarthritis Drug development Chronic Disease medicine.symptom hMSC |
| Zdroj: | Marine Drugs, Vol 19, Iss 390, p 390 (2021) Marine Drugs Volume 19 Issue 7 |
| ISSN: | 1660-3397 |
| Popis: | Chronic diseases characterized by bone and cartilage loss are associated with a reduced ability of progenitor cells to regenerate new tissues in an inflammatory environment. A promising strategy to treat such diseases is based on tissue repair mediated by human mesenchymal stem cells (hMSCs), but therapeutic outcomes are hindered by the absence of small molecules to efficiently modulate cell behaviour. Here, we applied a high-throughput drug screening technology to bioprospect a large library of extracts from Irish deep-sea organisms to induce hMSC differentiation toward musculoskeletal lineages and reduce inflammation of activated macrophages. The library included extracts from deep-sea corals, sponges and filamentous fungi representing a novel source of compounds for the targeted bioactivity. A validated hit rate of 3.4% was recorded from the invertebrate library, with cold water sea pens (octocoral order Pennatulacea), such as Kophobelemnon sp. and Anthoptilum sp., showing the most promising results in influencing stem cell differentiation toward osteogenic and chondrogenic lineages. Extracts obtained from deep-sea fungi showed no effects on stem cell differentiation, but a 6.8% hit rate in reducing the inflammation of activated macrophages. Our results demonstrate the potential of deep-sea organisms to synthetize pro-differentiation and immunomodulatory compounds that may represent potential drug development candidates to treat chronic musculoskeletal diseases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|