Flavonoid Extract from Seed Residues of Hippophae rhamnoides ssp. sinensis Protects against Alcohol-Induced Intestinal Barrier Dysfunction by Regulating the Nrf2 Pathway

Alcohol has been demonstrated to disrupt intestinal barrier integrity. Some flavonoid compounds that exert antioxidant activity have a protective effect on intestinal barrier function. As an important medicinal and edible plant, sea buckthorn (Hippophae) seeds are rich in flavonoids, but their protective effect on the intestinal barrier has not been reported. In our research, 76 kinds of flavonoids were identified in Hippophae rhamnoides ssp. sinensis seed residue flavonoids (HRSF) by ultra-performance liquid chromatography–tandem mass spectrometry. Kaempferol-3-O-rutinoside, isorhamnetin-3-O-rutinoside, kaempferol-3-O-robinoside-7-O-rhamnoside, isorhamnetin-3-O-2G-rhamnosylrutinoside, quercetin-3-O-rutinoside, (−)-epigallocatechin, and B type of procyanidin were the most abundant substances, accounting for 15.276%, 15.128%, 18.328%, 10.904%, 4.596%, 5.082%, and 10.079% of all identified flavonoids, respectively. Meanwhile, pre-treatment with HRSF was able to prevent alcohol-induced disruption of intestinal barrier integrity through elevating the transepithelial monolayer resistance value, inhibiting the flux of fluorescein isothiocyanate-dextran, and upregulating the mRNA and protein level of TJs (occludin and ZO-1). Furthermore, it was also able to reverse alcohol-induced oxidative stress through suppressing the accumulation of reactive oxygen species and malondialdehyde, improving the glutathione level and superoxide dismutase activity. Finally, the results showed that HRSF pre-treatment effectively elevated the erythroid-related factor 2 mRNA and protein level compared with the alcohol-alone treatment group. Our research was the first to demonstrate that HRSF could prevent alcohol-induced intestinal barrier dysfunction through regulating the Nrf2-mediated pathway in order to attenuate oxidative stress and enhance TJ expression.