Berberine enhances antidiabetic effects and attenuates untoward effects of canagliflozin in streptozotocin-induced diabetic mice.

The present study aimed at determining whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus. Streptozotocin-induced diabetic mice were introduced, and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated. Our results showed that berberine combined with canagliflozin (BC) increased reduction of fasting and postprandial blood glucose, diet, and water intake compared with berberine or canagliflozin alone. Interestingly, BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone. In addition, BC showed increased phosphorylated 5' AMP-activated protein kinase (pAMPK) expression and decreased tumor necrosis factor alpha (TNFα) levels in kidneys, compared with berberine or canagliflozin alone. These results indicated that BC was a stronger antidiabetic than berberine or canagliflozin alone with less negative side effects on the kidneys in the diabetic mice. The antidiabetic effect was likely to be mediated by synergically promoting the expression of pAMPK and reducing the expression of TNFα in kidneys. The present study represented the first report that canagliflozin combined with berberine was a promising treatment for diabetes mellitus. The exact underlying mechanisms of action should be investigated in future studies.

Suppressive effects of quercetin-3-O-(6″-Feruloyl)-ß-D-galactopyranoside on adipogenesis in 3T3-L1 preadipocytes through down-regulation of PPARγ and C/EBPα expression.

Obesity is a chronic, costly disease, and flavonoids such as quercetin have been proven to play protective roles against it. This study investigated the suppressive effect of quercetin-3-O-(6″-feruloyl)-ß-D-galactopyranoside (QFG) on adipogenesis of 3T3-L1 preadipocytes. Quercetin-3-O-(6″-feruloyl)-ß-D-galactopyranoside and quercetin were both extracted from Psidium guajava (Myrtaceae, commonly known as guava) leaves and were evaluated for their suppressive effect on adipogenesis by means of oil red O staining and triglyceride assay. It was shown that QFG inhibited adipogenesis in a dose- and time-dependent manner, and it exerted a stronger effect than did quercetin at the same concentration. Quantitative real-time polymerase chain reaction and western blotting were conducted to further examine the differentiation expression of marker genes and transcriptional factors. Both mRNA and protein expression of the key adipogenic transcriptional factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT (cytidine-cytidine-adenosine-adenosine-thymidine)/enhancer-binding protein alpha (C/EBPα), were inhibited by QFG. Moreover, the mRNA expression patterns of key participants in the Wnt-ß-catenin pathway were not altered during the QFG-induced adipogenesis inhibition. These results suggest that QFG effectively suppresses adipogenesis and that it exerts its role mainly through the significant down-regulation of PPARγ and C/EBPα and, probably, via a Wnt-ß-catenin independent pathway.

Aqueous extracts of Fructus Ligustri Lucidi enhance the sensitivity of human colorectal carcinoma DLD-1 cells to doxorubicin-induced apoptosis via Tbx3 suppression.

Chemoresistance has imposed a great challenge for cancer therapy. Fructus Ligustri Lucidi (FLL) is one of the commonest Chinese herbs that has been used for thousand years. This study shows that the aqueous extract of FLL (AFLL) enhanced the sensitivity of DLD-1 colon cancer cells to doxorubicin-induced apoptosis. Furthermore, Tbx3 expression was found to be suppressed by AFLL when the expression of tumor suppressor genes p14 and p53 were activated. Therefore, reduction of Tbx3 rescued the dysregulated P14(ARF)-P53 signaling, which in turn contributed to the sensitivity of DLD-1 cells to doxorubicin-induced apoptosis. As a conclusion, the findings suggest that FLL has a potential of being an appealing agent for auxiliary chemotherapy in treatment of human colorectal carcinoma.

Total flavonoids of Herba Epimedii improves osteogenesis and inhibits osteoclastogenesis of human mesenchymal stem cells.

INTRODUCTION: In China Herba Epimedii is one of the most common herbs that could be prescribed for treating osteoporosis. It is known to increase the overall mineral content, therefore, to promote bone formation and to increase lumbar bone mineral density (BMD). The present study was aimed at investigating the effect of flavonoids of Herba Epimedii (HEF) on osteogenesis in human MSCs. METHODS: The human bone marrow-derived MSCs (BM-MSCs) were isolated and their osteogenic differentiation was evaluated by their alkaline phosphatase (ALP) activities and level of mineralization. After treating with total flavonoids during osteogenic differentiation process, differential mRNA expression was examined by RT-PCR. RESULTS: The total time needed for osteogenic differentiation of BM-MSCs was significantly shortened by adding HEF. Up-regulation of mRNA expression by HEF was observed for several marker genes and osteogenic regulators. HEF was also found to inhibit osteoclastogenesis of MSCs by enhancing the ratio OPG/RANKL. CONCLUSIONS: Our study demonstrated that the HEF could improve osteogenic differentiation and inhibit the osteoclast differentiation of BM-MSCs concurrently.