Soybean-Derived Tripeptide Leu-Ser-Trp (LSW) Protects Human Vascular Endothelial Cells from TNF alpha-Induced Oxidative Stress and Inflammation via Modulating TNF alpha Receptors and SIRT1

Soybean is a rich source of high-quality proteins and an excellent food source of bioactive peptides. A tripeptide, Leu-Ser-Trp (LSW), was previously identified from soybean as an angiotensin-converting enzyme inhibitory peptide. In the present work, we further studied its antioxidant and anti-inflammatory activities in human vascular endothelial cells (EA.hy926) and elucidated the mechanisms underlying these biological activities. In tumor necrosis factor alpha (TNF alpha)-stimulated EA.hy926 cells, LSW significantly inhibited oxidative stress, both reduced superoxide and malondialdehyde levels (p < 0.001), owing to its free-radical-scavenging ability. LSW treatment also mitigated the elevated protein expression of vascular adhesion molecule-1 (p < 0.001) and cyclooxygenase 2 (p < 0.01) via inhibition of NF-kappa B and p38/JNK signaling, respectively. Additionally, LSW also inhibited the endogenous formation of TNF alpha and attenuated the expression of its two receptors in EA.hy926 cells. Furthermore, LSW upregulated sirtuin-1 level, which partially contributed to its anti-inflammatory activity. These results demonstrate the multiple roles of LSW in ameliorating vascular endothelial oxidative stress and inflammatory responses, which support its uses as a nutraceutical or functional food ingredient for combating endothelial dysfunction and cardiovascular diseases.