Piscroside C inhibits TNF-α/NF-κB pathway by the suppression of PKCδ activity for TNF-RSC formation in human airway epithelial cells

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology
Su Ui LeeSei-Ryang Oh

Abstract

Piscroside C, isolated from Pseudolysimachion rotundum var. subintegrum, is a novel iridoid glycoside with therapeutic efficacy in a mouse model of chronic obstructive pulmonary disease (COPD). Piscroside C has been reported as a constituent of YPL-001 (under Phase 2a study, ClinicalTrials.gov identifier NCT02272634). To investigate the mechanisms behind piscroside C therapeutic effects on COPD in human airway epithelial NCI-H292 cells. We tested if piscroside C effectively suppresses MUC5AC gene expression and TNF-RSC/IKK/NF-κB cascades in TNF-α-stimulated NCI-H292 cells by employing, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, luciferase reporter assays, chromatin immunoprecipitation assays and immunoprecipitation. Piscroside C markedly suppressed the expression of TNF-α-induced MUC5AC mucus protein by inhibiting the transcriptional activity of NF-κB in NCI-H292 cells. Indeed, piscroside C negatively regulated the function of TNF receptor 1 signaling complex (TNF-RSC, an upstream regulator of the NF-κB pathway) without affecting its extracellular interaction with the TNF-α ligand. This inhibitory effect by piscroside C is mediated by the inactivation of protein kinase C (PKC), an essent...Continue Reading

Citations

Aug 25, 2020·Journal of Biochemical and Molecular Toxicology·Fatemeh YarmohammadiGholamreza Karimi
Oct 1, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jingyuan Li, Zuguang Ye
Jan 7, 2019·European Journal of Medicinal Chemistry·Priscila Baltazar Gonçalves, Nelilma Correia Romeiro

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