Rapeseed peptide inhibits HepG2 cell proliferation by regulating the mitochondrial and P53 signaling pathways.

BACKGROUND: Rapeseed peptide, extracted from rapeseed protein, is known to have a variety of biological activities. In this study, the anti-proliferation effect and molecular mechanism of rapeseed peptide on HepG2 cells were investigated. RESULTS: In vitro anticancer experiments showed that the rapeseed peptide NDGNQPL could inhibit HepG2 cell proliferation in a concentration-dependent manner [half maximal inhibitory concentration (IC50 ), 1.56 mmol L-1 ). HepG2 cells were induced by NDGNQPL at a 0.5 mmol L-1 concentration and exhibited a 28.39 ± 0.80% apoptosis rate and a cell cycle arrest in the G0/G1 phase. Meanwhile, rapeseed peptide induced a decrease in mitochondrial membrane potential, an increase in reactive oxygen species (ROS) release, and changes in the nuclear morphology of HepG2 cells, indicating that rapeseed peptide could induce cell apoptosis through the mitochondrial pathway. In addition, rapeseed peptide activated the proliferation-related P53 signaling pathway, in which the expression levels of P53, P21, and cleaved-caspase3 were up-regulated, while the expression levels of murine double minute 2 (MDM2) were down-regulated. In molecular docking simulations, NDGNQPL exhibited a good affinity for the MDM2 molecule, which supported the notion that the rapeseed peptide is able to inhibit MDM2, a negative regulator of P53. CONCLUSION: The current results indicate that the rapeseed-derived NDGNQPL peptide has the potential to inhibit the proliferation of HepG2 cells and promote human health. © 2022 Society of Chemical Industry.

Pentoxifylline Inhibits Pulmonary Fibrosis by Regulating Cellular Senescence in Mice.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease, and its occurrence and development are mediated by cellular senescence. Drugs targeting senescent cells seem like a promising and efficacious strategy for IPF treatment. Previous studies have illustrated that pentoxifylline (PTX) may play a certain role in inhibiting pulmonary fibrosis and combating cellular senescence. In this study, we demonstrated that PTX administration inhibits pulmonary fibrosis development and cellular senescence in the bleomycin (BLM)-induced IPF mice model. Moreover, the expression levels of fibrosis-related genes and senescence-related genes in mice lung tissue and primary pulmonary fibroblasts illustrated lung fibroblasts' vital role in these two processes. And the curative effect of PTX was completed mainly by acting on lung fibroblasts. Besides, during the whole treatment, delayed initiation or advanced halt of PTX administration would influence its effectiveness in reducing fibrotic and senescent traits in various degrees, and the latter influenced more. We further determined that a long period of PTX administration could bring noticeable benefits to mice in recovering BLM-induced lung fibrosis and suppressing age-associated cellular senescence. Moreover, it was still effective when PTX administration was used to treat senescent human fibroblasts. Thus, our findings manifested that PTX therapy is an efficient remedy for pulmonary fibrosis by suppressing cellular senescence.

Antihypertensive activity of the ACE-renin inhibitory peptide derived from Moringa oleifera protein.

Moringa oleifera (MO) leaf is a potential plant protein resource with high nutritional and medicinal value. The study aims to investigate the hypotensive activity and stability of MO leaf peptides. MO leaf protein was extracted and then hydrolyzed with Alcalase to produce the MO leaf protein hydrolysate (MOPH). The MOPH was separated into peptide fractions with different molecular weights by membrane ultrafiltration. The MOPH and ultrafiltration fractions were evaluated for antihypertensive activity. Inhibition of the angiotensin-converting enzyme (84.71 ± 0.07%) and renin (43.72 ± 0.02%) was significantly higher for <1 kDa peptides when compared to other fractions. Oral administration of the <1 kDa component in spontaneously hypertensive rats positively lowers the blood pressure (∼17 mmHg). The <1 kDa component was isolated and purified subsequently; the final active component was identified by mass spectrometry and amino acid sequence analysis. Two highly active ACE (angiotensin-converting enzyme) and renin dual inhibitory peptides Leu-Gly-Phe-Phe (LGF) and Gly-Leu-Phe-Phe (GLFF) were obtained. The two peptides exhibited a good dual inhibitory activity of ACE and renin with IC50 values of LGF (0.29 ± 0.13 mM, 1.88 ± 0.08 mM) and GLFF (0.31 ± 0.04 mM, 2.80 ± 0.08 mM). Furthermore, in vivo models, LGF and GLFF significantly reduced the systolic blood pressure (19.4 mmHg; 18.2 mmHg) and diastolic blood pressure (12 mmHg; 13.8 mmHg) of SHRs (spontaneously hypertensive rats). The peptide transmembrane transport experiments and simulated gastrointestinal digestion experiments with LGF and GLFF showed that they can resist gastrointestinal digestion in a complete form. Thus, bioactive peptides from MO leaf may possess the potential to be used for treating hypertension in humans.