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Diabetic nephropathy (DN) is one of the serious complications in diabetes. Cyanidin-3-glucoside (C3G) from black rice was reported to have hypoglycemic effects and an anti-osteoporosis effect in diabetic rats. Whether it has preventive effects on DN has not been reported. In this study, we established a rat model of DN, and C3G at two doses (10 and 20 mg kg-1 day-1) were administered to see its anti-DN effect. A total of 8 weeks of C3G supplementation decreased blood glucose and serum insulin, improved the renal function, and relieved renal glomerular sclerosis and interstitial fibrosis of DN rats. Also, the kidneys of DN rats had improved the oxidative defense system. Pro-inflammatory mediators were markedly reduced in serum and kidneys of the C3G-treated groups. Transforming growth factor β1 (TGF-β1), phosphor-Smad2, and phosphor-Smad3 protein expression levels were significantly decreased in the kidney of the C3G-treated group, whereas the Smad7 expression level was upregulated by C3G. Our results indicate that C3G can ameliorate DN via antioxidative stress and anti-inflammation and regulate the TGF-β1/Smad2/3 pathway. Our results suggest that C3G from black rice might be used as a renal-protective nutrient in DN.

In this study, we successfully synthesized d-α-tocopheryl polyethylene glycol 2000 succinate (TPGS2k) and prepared TPGS2k-modified poly(lactic-co-glycolic acid) nanoparticles (TPGS2k/PLGA NPs) loaded with 7-ethyl-10-hydroxycamptothecin (SN-38), designated TPGS2k/PLGA/SN-38 NPs. Characterization measurements showed that TPGS2k/PLGA/SN-38 NPs displayed flat and spheroidal particles with diameters of 80-104 nm. SN-38 was encapsulated in TPGS2k emulsified PLGA NPs with the entrapment efficiency and loading rates of SN-38 83.6 and 7.85%, respectively. SN-38 could release constantly from TPGS2k/PLGA/SN-38 NPs in vitro. TPGS2k/PLGA/SN-38 NPs induced significantly higher cytotoxicity on A549 cells and the multidrug resistance (MDR) cell line (A549/DDP cells and A549/Taxol cells) compared with free SN-38. Further studies on the mechanism of the NPs in increasing the death of MDR cells showed that following the SN-38 releasing into cytoplasm the remaining TPGS2k/PLGA NPs could reverse the P-gp mediated MDR via interfering with the structure and function of mitochondria and rather than directly inhibiting the enzymatic activity of P-gp ATPase. Therefore, TPGS2k/PLGA NPs can reduce the generation of ATP and the release of energy for the requisite of P-gp efflux transporters. The results indicated that TPGS2k/PLGA NPs could become the nanopharmaceutical materials with the capability to reversal MDR and improve anticancer effects of some chemotherapy drugs as P-gp substrates.