Cytoprotective effect of eupatilin against indomethacin-induced damage in feline esophageal epithelial cells: relevance of HSP27 and HSP70

Abstract

Indomethacin is a non-steroidal anti-inflammatory drug with clearly known side effects on the gastrointestinal tract. The purpose of the present study was to investigate whether eupatilin inhibit cell injury induced by indomethacin in cultured feline esophageal epithelial cells (EECs). EECs were used to investigate the ability of eupatilin to induce the expression of heat shock proteins (HSP27 and HSP70) and analyze its cytoprotective effect against indomethacin-induced damage. The treatment of EECs with indomethacin for 8 h decreased cell viability. Western blot analysis showed that the levels of HSPs gradually decreased in cells treated with indomethacin, while eupatilin treatment increased the levels of HSPs. When treated with both indomethacin and eupatilin, the levels of HSPs increased rapidly, and were maintained at 130-140%. In addition, treatment with the specific inhibitors of PTK, PKC, PLC, p38 MAPK, JNKs, and PI3K attenuated the eupatilin-induced expression of HSPs. Pretreatment of EECs with the inhibitors of protein synthesis, actinomycin D or cycloheximide, attenuated the cytoprotective effect of eupatilin on indomethacin-induced cell damage. Reactive oxygen species production was upregulated by indomethacin, but downregulated by eupatilin. Taken together, it was suggested that HSPs were partly responsible for the eupatilin-mediated cytoprotective activity against the indomethacin-induced damage in EECs.

The hepato-protective effect of eupatilin on an alcoholic liver disease model of rats

“…Although the causes of ALD are not well established, some studies have revealed that alcohol-induced oxidative stress, hepatotoxicity, and the complex interactions involving alcohol metabolism, liver cells, and multiple cytokines can affect the progression of ALD [26]. The antioxidant and anti-inflammatory effects of eupatilin were examined in several studies [15,17,27,28]. Recently, pharmacokinetic study also performed to demonstrate its potential benefit for diverse applications.…”

“…5,7-Dihydroxy-3΄,4΄,6-trimethoxyflavone (eupatilin) is a pharmacologically active flavone extracted from an Artemisia species [ 15 ]. Eupatilin is known to have several pharmacological properties, such as anti-oxidative, anti-apoptosis, and anti-inflammatory [ 16 , 17 ]. Additionally, it exhibits therapeutic effects on gastritis and peptic ulcers associated with different cytokines and neuropeptides that can affect gastrointestinal motility [ 18 ], gastric mucosal damage [ 19 ], cerulein-induced pancreatitis [ 20 ], dextran sulfate sodium-induced colitis [ 21 ], and reflux esophagitis [ 22 ].…”