Protective effect and mechanism of lycopene on endothelial progenitor cells (EPCs) from type 2 diabetes mellitus rats.

Endothelial progenitor cells (EPCs), widely existing in bone marrow and peripheral blood, are involved in the repair of injured vascular endothelium and angiogenesis which are important to diabetic mellitus (DM) patients with vascular complications. The number and the function of EPCs are related to the advanced glycation end products (AGEs) generated in DM patients. Lycopene (Lyc) is an identified natural antioxidant that protects EPCs under the microenvironment of AGEs from damage. However, the underlying mechanism remains unclear. To investigate the effect of Lyc on EPCs, we isolated EPCs from DM rat bone marrow and determined cell proliferation, cell cycle,apoptosis and autophagy of EPCs. The present study showed that 10µg/mL Lyc improved cell proliferation and had low cytotoxicity in the presence of AGEs. In addition, Lyc rescued S phase of the cell cycle arrest, reduced apoptosis rate and decreased autophagic reaction including ROS and mitochondrial membrane potential (MMP) of EPCs. Moreover, Lyc combined use of autophagy inhibitors, 3-MA, had better protective effects. Taken together, our data suggests that Lyc promotes EPCs survival and protect EPCs from apoptosis and oxidative autophagy induced by AGEs, further remaining the number and function of EPCs. This study provides new insights into Lyc protective mechanism of AGEs-induced oxidative autophagy in EPCs from DM patients and offers a new therapy for DM vascular complications.

Effects of lycopene on number and function of human peripheral blood endothelial progenitor cells cultivated with high glucose.

BACKGROUND/OBJECTIVES: The objectives of this study were to investigate the effects of lycopene on the migration, adhesion, tube formation capacity, and p38 mitogen-activated protein kinase (p38 MAPK) activity of endothelial progenitor cells (EPCs) cultivated with high glucose (HG) and as well as explore the mechanism behind the protective effects of lycopene on peripheral blood EPCs. MATERIALS/METHODS: Mononuclear cells were isolated from human peripheral blood by Ficoll density gradient centrifugation. EPCs were identified after induction of cellular differentiation. Third generation EPCs were incubated with HG (33 mmol/L) or 10, 30, and 50 µg/mL of lycopene plus HG. MTT assay and flow cytometry were performed to assess proliferation and apoptosis of EPCs. EPC migration was assessed by MTT assay with a modified boyden chamber. Adhesion assay was performed by replating EPCs on fibronectin-coated dishes, after which adherent cells were counted. In vitro vasculogenesis activity was assayed by Madrigal network formation assay. Western blotting was performed to analyze protein expression of both phosphorylated and non-phosphorylated p38 MAPK. RESULTS: The proliferation, migration, adhesion, and in vitro vasculogenesis capacity of EPCs treated with 10, 30, and 50 µg/mL of lycopene plus HG were all significantly higher comapred to the HG group (P < 0.05). Rates of apoptosis were also significantly lower than that of the HG group. Moreover, lycopene blocked phosphorylation of p38 MAPK in EPCs (P < 0.05). To confirm the causal relationship between MAPK inhibition and the protective effects of lycopene against HG-induced cellular injury, we treated cells with SB203580, a phosphorylation inhibitor. The inhibitor significantly inhibited HG-induced EPC injury. CONCLUSIONS: Lycopene promotes proliferation, migration, adhesion, and in vitro vasculogenesis capacity as well as reduces apoptosis of EPCs. Further, the underlying molecular mechanism of the protective effects of lycopene against HG-induced EPC injury may involve the p38 MAPK signal transduction pathway. Specifically, lycopene was shown to inhibit HG-induced EPC injury by inhibiting p38 MAPKs.

[Effects of lycopene on blood lipid and red blood cell of rat with hypercholesterolemia].

OBJECTIVE: To study the effect of lycopene on red blood cell and the level of blood lipid. METHODS: According to the level of serum total cholesterol and weight, forty-eight adult male SD rats were divided randomly into six groups: normal control (group A), fed by normal feed; hyperlipidemia group (group B): fed by high fat diet; positive control group (group C): fed by high fat diet plus 10 mg * kg(-1) * d(-1) fluvastatin sodium; lycopene groups: fed by high fat diet plus 11 (group D), 22 (group E), 44 mg * kg(-1) * d(-1) (group F) lycopene through gavage, respectively. For all six groups, the level of serum total cholesterol (TC) and total triglyceride (TG) were measured at the end of 0, 1, 3 weeks of the study by taking samples from tail vein. At the end of the experiment, RBC and HGB were measured. RESULTS: After the rats were fed with high-fat feed for a week, models of hyperlipidemia rats were established. At the end of 3 weeks, TC of group A, B, C, D, E and F were (1.31 +/- 0.05), (19.40 +/- 0.54), (4.66 +/- 0.07), (7.18 +/- 0.06), (5.30 +/- 0.28), (4.49 +/- 0.23) mmol/L (F = 4395.72, P = 0.00), respectively;and TG were (0.42 +/- 0.01), (2.29 +/- 0.42), (0.69 +/- 0.03), (1.10 +/- 0.05), (0.63 +/- 0.02), (0.62 +/- 0.04) mmol/L (F = 127.26, P = 0.00), respectively; HGB were (143.13 +/- 6.33), (112.63 +/- 2.56), (124.75 +/- 3.62), (124.63 +/- 7.78), (132.38 +/- 6.41), (142.13 +/- 5.54) g/L (F = 34.14, P = 0.00), respectively; RBC were (6.75 +/- 0.60) x 10(12)/L, (5.08 +/- 0.75) x 10(12)/L, (7.14 +/- 0.82) x 10(12)/L, (5.94 +/- 1.09) x 10(12)/L, (6.18 +/- 0.36) x 10(12)/L and (7.31 +/- 0.58) x 10(12)/L (F = 10.35, P = 0.00), respectively. CONCLUSION: Lycopene have some protective effects on red blood cells of the hyperlipidemic rats by regulating the blood lipid and antioxidant.