Eucommia ulmoides flavones (EUF) abrogated enterocyte damage induced by LPS involved in NF-κB signaling pathway

• Published in: Toxicology in vitro Vol. 62; p. 104674
• Main Authors: Hussain, Tarique, Yuan, Diaxiu, Tan, Bie, Murtaza, Ghulam, Rahu, Najma, Kalhoro, Muhammed Saleem, Kalhoro, Dildar Hussain, Yin, Yulong
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-02-2020; Elsevier Science Ltd
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Anti-Inflammatory Agents - pharmacology; Apoptosis; Apoptosis - drug effects; BAX protein; Bioenergetics; Caspase-3; Cell cycle; Cell Cycle - drug effects; Cell Line; Cell Survival - drug effects; Cell viability; Damage assessment; DNA biosynthesis; Enterocytes - drug effects; Enterocytes - metabolism; Enterocytes and LPS; Epithelial cells; Eucommia ulmoides; Eucommia ulmoides flavones; Eucommiaceae; Flavones; Flavones - pharmacology; Inflammation; Inflammatory diseases; Intestine; Lipopolysaccharides; Lipopolysaccharides - toxicity; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial DNA; NF-kappa B - metabolism; NF-κB protein; Parameters; PI3K-NFκB signaling pathway; Proteins; Regulatory mechanisms (biology); Signal transduction; Signaling; Superoxide dismutase; Superoxide Dismutase - metabolism; Swine; GSH-Px; Eucommia ulmoides flavones; HRP; IKKα/β; SOD; Inflammation; Bcl; FCCP; Akt; PVDF; LPS; IκBα; NF-κB; PI3K; PDK; CAT; EUF; ROS; Enterocytes and LPS; PIP3; PI3K-NFκB signaling pathway; ATP; OCR
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2019.104674

This study was conducted to explore the regulatory mechanism of Eucommia ulmoides flavones (EUF) using enterocyte damage model induced by lipopolysaccharide (LPS). Intestinal porcine epithelial cell line (IPEC-J2) cells were cultured in Dulbecco's modified eagle medium with high glucose (DMEM-H) medium containing 0 or 10 μg/mL EUF, 0 or 40 ng/mL LPS. The results showed that LPS impaired DNA synthesis, cell viability, mitochondrial function, arrested cell cycle and induced apoptosis, reduced SOD activity while the EUF treated cells provided beneficial effect on all these parameters (P < 0.05). The addition of EUF increased phosphorylated Akt, IκBα and phosphorylated IKKα/β, but decreased Bax and Caspase-3 protein expressions in LPS-treated cells (P < 0.05). For the second experiment, cells were treated by DMEM-H medium containing 10 μg/mL EUF+ 40 ng/mL LPS or 10 μg/mL EUF+ 40 ng/mL LPS+ 10 μmol/L LY29400. EUF + LPS + LY29400 treatment significantly reduced cell viability, proliferation, mitochondrial bioenergetics parameters, SOD activity, and decreased protein expressions of PI3K, p-Akt, p-IKKα/β, p-NFκB and Bax (P < 0.05). These findings revealed the cytoprotective effects of EUF in enterocyte, which may involve the PI3K-NFκB signaling pathway, and it provides a theoretical basis for exploration of EUF as a potential anti-inflammatory compound to intervene intestinal inflammatory diseases.
•LPS induced mitochondrial dysfunction and enterocyte damage•EUF exhibited the cytoprotective effects by counteracting oxidative stress.•Inhibition of PI3K impaired the antioxidant and anti-inflammatory effects of EUF.•PI3K-NFκB signaling pathway plays an important role in the regulation of EUF on inflammatory response in enterocyte.