Inhibitory effects of collismycin C and pyrisulfoxin A on particulate matter-induced pulmonary injury.
Phytomedicine. 2019 Sep ;62:152939. Epub 2019 Apr 23. PMID: 31100678
BACKGROUND: Inhalation of fine particulate matter (PM) is associated with elevated pulmonary injury caused by the loss of vascular barrier integrity. Marine microbial natural products isolated from microbial culture broths were screened for pulmonary protective effects against PM. Two 2,2'-bipyridine compounds isolated from a red alga-associated Streptomyces sp. MC025-collismycin C (2) and pyrisulfoxin A (5)-were found to inhibit PM-mediated vascular barrier disruption.
PURPOSE: To confirm the inhibitory effects of collismycin C and pyrisulfoxin A on PM-induced pulmonary injury STUDY DESIGN: In this study, we investigated the beneficial effects of collismycin C and pyrisulfoxin A on PM-induced lung endothelial cell (EC) barrier disruption and pulmonary inflammation.
METHODS: Permeability, leukocyte migration, proinflammatory protein activation, reactive oxygen species (ROS) generation, and histology were evaluated in PM-treated ECs and mice.
RESULTS: Collismycin C and pyrisulfoxin A significantly scavenged PM-induced ROS and inhibited the ROS-induced activation of p38 mitogen-activated protein kinase as well as activated Akt, which helped in maintaining endothelial integrity, in purified pulmonary endothelial cells. Furthermore, collismycin C and pyrisulfoxin A reduced vascular protein leakage, leukocyte infiltration, and proinflammatory cytokine release in the bronchoalveolar lavage fluid of PM-treated mice.
CONCLUSION: These data suggested that collismycin C and pyrisulfoxin A might exert protective effects on PM-induced inflammatory lung injury and vascular hyperpermeability.