Curcumin analogue C66 attenuates obesity-induced renal injury by inhibiting chronic inflammation.

Obesity has been recognized as a major risk factor for the development of chronic kidney disease, which is accompanied by increased renal inflammation, fibrosis, and apoptosis. C66 is a curcumin derivative that exerts anti-inflammatory effects by inhibiting the JNK pathway and prevents diabetic nephropathy. The present study investigates the possible protective effect of C66 on high-fat diet (HFD)-induced obesity-related glomerulopathy. Mice were fed with HFD for 8 weeks while some were treated with C66 every 2 days for 11 weeks. The HFD-fed mice developed renal dysfunction, as well as elevated triglyceride and cholesterol. Kidneys of the HFD-fed mice showed marked glomerular injuries, apoptosis, and inflammation with markedly increased cytokine production. Interestingly, treating HFD-fed mice with C66 remarkably reversed these pathological changes via inhibiting inflammation and NF-κB/JNK activation. In cultured mesangial cells, Palmitic Acid was able to activate the pro-fibrotic mechanisms, apoptosis, inflammatory response, and NF-κB and JNK signaling pathways, all of which could be attenuated by C66 treatment. In all, we demonstrated that curcumin analogue C66 attenuates obesity-induced renal injury by inhibiting chronic inflammation and apoptosis via targeting NF-κB and JNK. Our data suggest that C66 can be potentially used to prevent obesity-associated renal diseases warranting future investigations.

Kaempferol attenuates streptozotocin-induced diabetic nephropathy by downregulating TRAF6 expression: The role of TRAF6 in diabetic nephropathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferia rhizome is a famous traditional herbal medical in tropical and subtropical areas. Kaempferol (KPF) is one of the main bioactive compounds in Kaempferia rhizome, with anti-oxidant/anti-inflammatory effects demonstrated in various disease models, including cancers, obesity and diabetes. AIM OF THE STUDY: Inflammation plays an important role in the pathogenesis of diabetic nephropathy (DN). TRAF6 functions as a signal transducer in toll-like receptor 4 and NF-κB pro-inflammatory signaling pathway. We aimed at investigate whether KPF is able to mitigate inflammatory responses by regulating TRAF6 in DN. MATERIAL AND METHODS: C57BL/6 mice were injected with streptozotocin to induce type 1 DN. NRK-52E, a tubular epithelial cell line, was used for in vitro analysis. TRAF6 was knockdown using siRNA in vitro and AAV2/2-shRNA in vivo. The anti-DN and inflammatory effects of KPF or knockdown of TRAF6 were evaluated by investigating renal filtration index, pathological changes of kidney tissue. Proinflammatory cytokine levels were detected using ELISA. NF-κB pathway and protein levels of related pathways were detected through Western blot. RESULTS: KPF significantly reduced renal inflammation, fibrosis, and kidney dysfunction in diabetic mice. These effects were associated with a downregulation of TRAF6 in diabetic mouse kidneys, indicating the potential role of TRAF6. Knockdown of TRAF6 in mice through AAV2-shTRAF6 confirmed the importance of TRAF6 in DN. In vitro, treatment of KPF in NRK-52E cells attenuated high glucose (HG)-induced inflammatory and fibrogenic responses, associated with downregulated TRAF6 expression. The conclusion was further confirmed in NRK-52E cells by knocking down the expression and by overexpression of TRAF6. CONCLUSION: Our findings provide direct evidence that TRAF6 mediates diabetes-induced inflammation leading to renal dysfunction. We also show that KPF is a potential therapeutic agent to reduce inflammatory responses in DN. Also, TRAF6 may represent an interesting target to combat DN.

Diverse Associations of Plasma Selenium Concentrations and SELENOP Gene Polymorphism with Metabolic Syndrome and Its Components.

The relationship between selenium and metabolic syndrome (MetS) has been discussed controversially, and limited studies have examined the associations of single nucleotide polymorphisms in selenoproteins genes with MetS. Hence, to examine the associations of plasma selenium concentrations and selenoprotein P rs7579 polymorphism with MetS, a case-control study of 1279 MetS cases and 1279 sex- and age- (±2 years) matched controls was conducted based on the baseline data of the Tongji-Ezhou Cohort study. Plasma selenium concentrations were measured by inductively coupled plasma mass spectrometry. MetS was defined using the definition of the Joint Interim Statement, adjusted for the Chinese population. In addition, the rs7579 polymorphism was genotyped by the Agena MassARRAY System. Plasma selenium concentrations in the MetS group were higher than in the control group (93.88 µg/L (83.17-107.41) vs. 92.66 µg/L (82.36-103.53), P < 0.05). Compared with quartile 4 (≥103.53 µg/L), the multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) associated with MetS were 0.79 (0.59-1.06) for quartile 1 (<82.36 µg/L), 0.75 (0.56-1.01) for quartile 2 (82.37-92.66 µg/L), and 0.61 (0.45-0.83) for quartile 3 (92.67-103.52 µg/L). The cubic spline analyses revealed a U-shaped association between plasma selenium and MetS, with the lowest risk at around 93.69 µg/L. Moreover, in cubic spline analyses, plasma selenium showed U-shaped associations with central obesity and high blood pressure, positive associations with hypertriglyceridemia and hyperglycemia, and a negative association with low high-density lipoprotein cholesterol. Additionally, both the GA and GA+AA genotype carriers were associated with increased ORs of MetS comparing with the GG genotype carriers. Our findings suggested a U-shaped association between plasma selenium and MetS and diverse associations between plasma selenium and components of MetS. Furthermore, our study found that the A allele of rs7579 was associated with higher odds of MetS. Further studies are needed to confirm our findings and elucidate the underlying mechanisms.

Biofabrication of nano copper oxide and its aptamer bioconjugate for delivery of mRNA 29b to lung cancer cells.

Copper oxide nanoparticles (CuO NPs) are fabricated using Coleus aromaticus leaf extract with an environmental friendly method and studied using various microscopic and spectroscopic techniques. Also, a new aptamer-conjugated hybrid delivery system using green synthesized CuO NPs is developed to deliver miRNA-29b to A549 cells. This delivery system can effectively deliver miRNAs to cancer cells, with superior performance compared to traditionally available transfection agents, thus acting as an efficient platform for intracellular miRNA delivery and improving therapeutic outcomes for lung cancer.

Procyanidins extracted from the litchi pericarp ameliorate atherosclerosis in ApoE knockout mice: their effects on nitric oxide bioavailability and oxidative stress.

Epidemiological studies strongly support the role of procyanidin-rich beverages and fruit in the prevention of cardiovascular diseases. Procyanidins extracted from the litchi pericarp (LPPC), a new source of procyanidins, were isolated and identified in our laboratory and have been proven to possess strong antioxidant activity in vitro. In the present study, we investigated the anti-atherosclerotic effects of LPPC in apolipoprotein E knockout (ApoE KO) mice fed a high fat diet for 24 weeks. LPPC (100 mg kg-1 body mass daily) significantly reduced the atherosclerotic lesion size (P < 0.01 versus ApoE KO mice), excess NO production and iNOS expression. Moreover, the mRNA and protein expressions of eNOS in the aortas of ApoE KO mice were increased by LPPC which further explains the endothelial protective action of LPPC. LPPC also showed profound antioxidant effects in ApoE KO mice. Plasma TBARS contents and the mRNA expression for NADPH oxidase (p47phox, p67phox, NOX-2/gp91phox and NOX-4) in the aortas of ApoE KO mice were significantly reduced, whereas plasma SOD activity was markedly elevated by LPPC. These results elucidated that LPPC could ameliorate atherosclerosis in ApoE-KO mice by improving NO bioavailability and reducing oxidative stress through NADPH oxidase-dependent mechanisms.

Comparative safety evaluation of Chinese Pu-erh green tea extract and Pu-erh black tea extract in Wistar rats.

Pu-erh teas are believed to be beneficial beverages for health since they possess several pharmacological properties such as antioxidation, hypocholesterolemia, and antiobesity properties, but their potential toxicities when administered at a high dose as concentrated extracts have not been completely investigated. In this study, the chemical components in Pu-erh green tea and Pu-erh black tea were analyzed and compared, and the safety of tea extracts was evaluated in Wistar rats. The polysaccharide, tea pigment, and flavonoid levels were substantially increased in the Pu-erh black tea, while the polyphenol and free amino acid levels were higher in unfermented green tea. Low toxicities of Pu-erh green tea extract (GTE) were observed at doses of 2500 and 5000 mg/kg/day with a 28-day subacute study. Serum biochemical data including alanine aminotransferase increased to 5000 mg/kg/day GTE males, and creatinine (Cr) increased in all 5000 mg/kg/day GTE groups and 2500 mg/kg/day GTE males. Slight bile duct hyperplasia in the liver was also observed. The target organs of GTE were considered to be the liver and kidney. Comparatively, no adverse effects were observed in Pu-erh black tea extract (BTE)-treated rats. In conclusion, a dose of 1250 mg/kg/day for GTE and 5000 mg/kg/day for BTE following oral administration could be considered safe under the conditions of this study.