Abstract
Oxidative stress inflicts mitochondrial dysfunction, which has been recognized as a key driver of intestinal diseases. Resveratrol (RSV) and its derivative pterostilbene (PTS) are natural antioxidants and exert a protective influence on intestinal health. However, the therapeutic effects and mechanisms of RSV and PTS on oxidative stress-induced mitochondrial dysfunction and intestinal injury remain unclear. The present study used porcine and cellular settings to compare the effects of RSV and PTS on mitochondrial redox homeostasis and function to alleviate oxidative stress-induced intestinal injury. Our results indicated that PTS was more potent than RSV in reducing oxidative stress, maintaining intestinal integrity, and preserving the mitochondrial function of diquat-challenged piglets. In the in vitro study, RSV and PTS protected against hydrogen peroxide (H2O2)-induced mitochondrial dysfunction in intestinal porcine enterocyte cell line (IPEC-J2) by facilitating mitochondrial biogenesis and increasing the activities of mitochondrial complexes. In addition, both RSV and PTS efficiently mitigated mitochondrial oxidative stress by increasing sirtuin 3 protein expression and the deacetylation of superoxide dismutase 2 and peroxiredoxin 3 in H2O2-exposed IPEC-J2 cells. Furthermore, RSV and PTS preserved mitochondrial membrane potential, which restrained the release of cytochrome C from mitochondria to the cytoplasm and caspase-3 activation and further reduced apoptotic rates in H2O2-exposed IPEC-J2 cells. Mechanistically, depletion of sirtuin 1 (SIRT1) abrogated RSV's and PTS's benefits against mitochondrial reactive oxygen species overproduction, mitochondrial dysfunction, and apoptosis in H2O2-exposed IPEC-J2 cells, suggesting that SIRT1 was required for RSV and PTS to protect against oxidative stress-induced intestinal injury. In conclusion, RSV and PTS improve oxidative stress-induced intestinal injury by regulating mitochondrial redox homeostasis and function via SIRT1 signaling pathway. In offering this protection, PTS is superior to RSV.