Background. Advanced glycation end products play an important role in diabetic atherosclerosis. The effects of advanced glycation end products (AGEs) on vascular smooth muscle cell- (VSMC-) derived foam cell formation and phenotypic transformation are unknown. Methods. Serological and histological samples were obtained from diabetic amputation patients and accident amputation patients from the Affiliated Hospital of Jiangsu University. CD68/Actin Alpha 2 (ACTA2) coimmunofluorescence sections were used to quantify the number of VSMCs with macrophage-like phenotypes. Western blotting was used to detect the expression of the receptor of advanced glycation end products in vascular samples. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the level of serum Nε-carboxymethyl-lysine (CML). In vitro oil red O staining was used to examine lipid accumulation in VSMCs stimulated by CML. The expression of VSMCs and macrophage markers was measured by western blotting and quantitative real-time PCR. Furthermore, changes in VSMC migration and secretion were detected by the Transwell assay and ELISA. Results. In the arterial plaque sections of diabetic patients, VSMCs transformed to a macrophage-like phenotype. The serum CML and RAGE levels in the plaques were significantly higher in the diabetes group than those in the healthy control group and were significantly related to the number of macrophage-like VSMCs. CML stimulation promoted intracellular lipid accumulation. However, CML stimulation decreased the expression of VSMC markers and increased the expression of macrophage phenotype markers. Finally, CML promoted smooth muscle cell migration and the secretion of proinflammatory-related factors. Conclusions. CML induces VSMC-derived foam cell formation, and VSMCs transdifferentiate to a macrophage-like state, which may be mediated by the activation of RAGE.

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Zeaxanthin (ZA), an important compound found in Lycium barbarum, shows various pharmacodynamic effects. In our present study, a high-fat, high-sucrose diet and streptozotocin (STZ)-induced diabetic rat model was used to investigate the antidiabetic activities of ZA. After a 4-week administration of 200 and 400 mg/kg of ZA and 100 mg/kg of metformin hydrochloride, various blood biochemical indexes were detected. ZA strongly normalized the reduced bodyweight and enhanced fasting blood glucose in diabetic rats. The positive data obtained from the oral glucose tolerance test further confirmed its antidiabetic effects. ZA displayed significant hypolipidemic activities indicated by its modulation of serum levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and total cholesterol. The antidiabetic nephropathy of ZA was confirmed by its regulation of pathological kidney structures, urine levels of n-acetyl-β-d-glucosaminidase and albuminuria, and serum levels of urea nitrogen. ZA inhibited the serum levels of inflammatory factors including interleukin-2 (IL-2), IL-6, tumor necrosis factor-α, and nuclear factor kappa B, further confirming its renal protection. Moreover, the serum imbalances in superoxide dismutase, glutathione peroxidase, methane dicarboxylic aldehyde, and catalase were normalized by ZA, suggesting its antioxidant properties. Altogether, ZA produced hypoglycemic, hypolipidemic, and antidiabetic nephritic effects in a diet-STZ-induced diabetic rat model.

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The present study successfully demonstrated the neuroprotective effects of purified Lycium barbarum polysaccharide (LBPS02) against glutamate (L‑Glu)‑induced differentiated PC12 (DPC12) cell apoptosis. Purified polysaccharide was obtained by using a diethylaminoethyl‑52 cellulose anion exchange column and a Sepharose G‑100 column. During identification and characterization, LBPS02 was validated to be a fraction with 68 kDa molecular weight, and with a structure containing 1→3, 1→4 and 1→6 linkages. Data further revealed that LBPS02 pretreatment effectively improved cell viability, reduced apoptosis rate, and restored the mitochondrial dysfunction in L‑Glu‑exposed cells. LBPS02 suppressed L‑Glu‑induced reactive oxygen species (ROS accumulation in DPC12 cells. N‑acetylcysteine, a ROS inhibitor, strongly enhanced the efficacy of LBPS02. Furthermore, LBPS02 normalized the levels of anti‑apoptotic proteins, and regulated the phosphorylation of extracellular signal‑regulated kinases (ERKs) and protein kinase B (Akt) in L‑Glu‑explored DPC12 cells. In conclusion, LBPS02‑mediated neuroprotective effects are at least partially associated with the modulation of Akt and ERKs, and the subsequent inhibition of the mitochondrial apoptotic pathway. LBPS02 may be a candidate for neurodegenerative disease treatment.