title: Anti-inflammatory properties of mutolide isolated from the fungus Lepidosphaeria species (PM0651419).
abstract: Mutolide an anti-inflammatory compound was isolated from the coprophilous fungus Lepidosphaeria sp. (PM0651419). The compound mitigated LPS-induced secretion of pro-inflammatory cytokines TNF-α and IL-6 from THP-1 cells as well as human peripheral blood mononuclear cells (hPBMCs). Mutolide also inhibited secretion of another pro-inflammatory cytokine IL-17 from anti-hCD3/anti-hCD28 stimulated hPBMCs. NF-κB is the major transcription factor involved in the secretion of pro-inflammatory cytokines including IL-17. Mechanistic evaluations revealed that mutolide inhibited induced NF-κB activation and translocation from cytoplasm into the nucleus. However, mutolide did not significantly affect activity of p38 MAPK enzyme, a serine/threonine kinase involved in cell cycle proliferation and cytokine secretion. These results indicate that mutolide may exert its anti-inflammatory effect via NF-κB inhibition. Oral administration of mutolide at 100 mg/kg showed significant inhibition of LPS-induced release of TNF-α from Balb/c mice in an acute model of inflammation. Our results highlight the anti-inflammatory properties of mutolide and suggest that further evaluation in a chronic model of inflammation is required to confirm the potential of mutolide as a druggable candidate for the treatment of inflammatory diseases.
authors.affiliation: NCE Research Division, Piramal Enterprises Ltd., Mumbai, India ; Vellore Institute of Technology, Vellore, India.
authors.forename: Meet
authors.initials: M
authors.lastname: Shah
authors.affiliation: NCE Research Division, Piramal Enterprises Ltd., Mumbai, India.
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Deshmukh
authors.affiliation: NCE Research Division, Piramal Enterprises Ltd., Mumbai, India.
authors.forename: Shilpa A
authors.initials: SA
authors.lastname: Verekar
authors.affiliation: NCE Research Division, Piramal Enterprises Ltd., Mumbai, India.
authors.forename: Akash
authors.initials: A
authors.lastname: Gohil
authors.affiliation: NCE Research Division, Piramal Enterprises Ltd., Mumbai, India.
authors.forename: Abhijeet S
authors.initials: AS
authors.lastname: Kate
authors.affiliation: Vellore Institute of Technology, Vellore, India.
authors.forename: V
authors.initials: V
authors.lastname: Rekha
authors.affiliation: NCE Research Division, Piramal Enterprises Ltd., Mumbai, India.
authors.forename: Asha
authors.initials: A
authors.lastname: Kulkarni-Almeida
keywords: Inflammation; Lepidosphaeria species; Mutolide; NF-κB