Biochanin A, a soy isoflavone, diminishes insulin resistance by modulating insulin-signalling pathway in high-fat diet-induced diabetic mice.

AIM: The objective of this study was to evaluate the probable mechanism of action of Biochanin A (BCA) on high-fat diet-induced insulin resistance mice. METHODS: Twenty-four male C57/BL/6J mice were divided into two and fed either control diet or a high fat-high diet (HFD). After 6 weeks, mice were grouped into: Control, Control + BCA, HFD and HFD + BCA (n = 6). Mice were made diabetic by feeding them an HFD. RESULTS: Body weight, plasma glucose, insulin, leptin levels and HOMA values were significantly lower in the BCA supplemented HFD group when related to the HFD group. Furthermore, BCA supplementation significantly increased Insulin receptor substrate 1 (IRS 1), PI3K, Akt and Glucose transporter type 4 (GLUT-4) protein abundance in skeletal muscle when equated with HFD. CONCLUSION: This study demonstrates that BCA can improve insulin sensitivity by activating insulin signalling, suggesting that it may possess antidiabetic activities.

Anti-inflammatory and anti-apoptotic effect of zingiberene on isoproterenol-induced myocardial infarction in experimental animals.

This study aimed to investigate the antihyperlipidemic and anti-inflammatory effect of zingiberene (ZBN) on isoproterenol-(ISO) induced myocardial infarction in rats. ZBN (10 mg/kg b.wt.) was orally administered to rats for 21 days and ISO (85 mg/kg b.wt.) was subcutaneously injected into the rats at 24 h intervals for the last 2 consecutive days. We observed increased serum creatine kinase, creatine kinase-MB, cardiac troponin T, and I levels in ISO-treated MI rats. Conversely, ZBN oral administration significantly prevented in cardiac marker enzyme activities in ISO-mediated rats. We also noticed that ZBN oral administration prevented ISO-induced expression of lipid peroxidative markers, total cholesterol, triglycerides, phospholipids, free fatty acids, very-low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C) to the normal basal level. Furthermore, ZBN restored ISO-mediated antioxidant status, increased level of high-density lipoprotein cholesterol (HDL-C), and tissue phospholipids to the near-normal levels. Besides, ZBN pre-treatment significantly reduced the level of inflammatory markers (TNF-α, IL-6, NF-κB, and IL-1ß) in ISO-induced MI in rats. We noticed that ZBN pretreatment inhibited the pro-apoptotic proteins Bax and cytochrome c and increased the Bcl-2 expression in ISO induced rats. The gene expression profiling by qRT-PCR array illustrates that ZBN treatment prevents the ISO mediated activation of cardiac markers, inflammatory, and fibrosis-related genes in the heart tissue. Taken together, pre-treatment with ZBN attenuated ISO-induced MI resolved exhibits the anti-inflammatory and antiapoptotic effect.

Galangin Attenuates Isoproterenol-Induced Inflammation and Fibrosis in the Cardiac Tissue of Albino Wistar Rats.

Galangin (GA) is an active flavonoid of the rhizome of Alpinia galanga that belongs to the ginger family. GA exhibit potent anti-inflammatory properties. Therefore, we evaluated the preventive effects of GA against isoproterenol (ISO)-induced inflammation and myocardial fibrosis in male albino Wistar rats. We found that GA (1 mg/kg b.wt.) pretreatment attenuated the ISO-mediated (5 mg/kg b.wt. for 14 consecutive days) elevation of heart rate, activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase-MB (CKMB) in the rat serum. We also noticed that GA prevented the ISO-mediated cardiac markers i.e. cardiac troponin T and I (cTnT and cTnI) expression in the serum of rats. Further, GA pretreatment prevented ISO-mediated lipid peroxidation and diminished blood pressure and loss of antioxidants status in the heart tissue of ISO treated rats. In addition, GA treatment modulates ISO-induced alterations the expressions of tissue inhibitor of metalloproteinases-1 (TIMP-1), p-AKT, glycogen synthase kinase-3ß (p-GSK-3ß) and peroxisome proliferators-activated receptor-γ (PPAR-γ) in the heart tissue. Furthermore, molecular analysis (PCR array and western blot) revealed that GA pretreatment prevented inflammation and fibrosis related gene expression pattern in ISO-induced rats. Taken together, the results indicate the cardioprotective effect of GA against ISO-induced inflammation and fibrosis. The antioxidant and anti-inflammatory potential of GA could be considered for its cardioprotective effect in the ISO-treated rats.

Predicting Tumor Sensitivity to Chemotherapeutic Drugs in Oral Squamous Cell Carcinoma Patients.

Oral Squamous Cell Carcinoma (OSCC) patients respond poorly to chemotherapy. We analyzed the expression of 11 drug response-related genes in 31 OSCC biopsies, collected prior to any treatment, using custom-designed PCR array. Further, we investigated the drug response pattern of selected anticancer drugs by BH3 (Bcl2 Homology-3) profiling in the primary cells isolated from OSCC tissues. Then, we correlated the results of drug-response gene expression pattern with apoptotic priming to predict tumor response to chemotherapy. The best performing drug (BPD) and response differences (RD) between the drugs were identified using statistical methods to select the best choice of drug in a personalized manner. Based on the correlation, we classified OSCC tumors as sensitive (13 tumors), moderately responsive (16 tumors) or resistant (2 tumors) to chemotherapy. We found that up-regulation of genes linked with drug resistance facilitates survival of tumor samples, which was revealed by the percentage of apoptotic priming. Moreover, we found that paclitaxel-induced 40-45% apoptotic priming compared to other drugs. Average response difference (RD) analysis showed that 80% of tumors responded well to paclitaxel as compared to other drugs studied. Therefore, gene expression analysis with BH3 profiling reveals drug sensitivity that could be translated for drug selection before treatment.

Preventive effect of apigenin against isoproterenol-induced apoptosis in cardiomyoblasts.

We investigated the effect of apigenin, a dietary flavonoid, on isoproterenol hydrochloride (ISO)-induced apoptotic signaling in cardiomyoblast H9C2 cells. The results showed that apigenin treatment (10 µM) prevented ISO (31.25 µM)-induced lipid peroxidative levels and antioxidants status in H9C2 cells. Furthermore, apigenin inhibited expression of inflammatory markers in ISO-treated cells. In addition, apigenin prevented ISO-induced DNA damage and apoptotic signaling through modulating the expression of Bax, caspase-3, -8 and -9, cytochrome c, and Fas proteins in H9C2 cells. It is concluded that apigenin prevents ISO-induced antioxidants depletion, oxidative DNA damage, inflammatory, and apoptotic signaling in H9C2 cells. Thus, the present results demonstrated that apigenin has a cardioprotective effect on cardiomyoblasts cells.

Linalool prevents oxidative stress activated protein kinases in single UVB-exposed human skin cells.

Ultraviolet-B radiation (285-320 nm) elicits a number of cellular signaling elements. We investigated the preventive effect of linalool, a natural monoterpene, against UVB-induced oxidative imbalance, activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling in HDFa cells. We observed that linalool treatment (30 µM) prevented acute UVB-irradiation (20 mJ/cm2) mediated loss of activities of antioxidant enzymes in HDFa cells. The comet assay results illustrate that linalool significantly prevents UVB-mediated 8-deoxy guanosine formation (oxidative DNA damage) rather than UVB-induced cyclobutane pyrimidine (CPD) formation. This might be due to its ability to prevent UVB-induced ROS formation and to restore the oxidative imbalance of cells. This has been reflected in UVB-induced overexpression of MAPK and NF-κB signaling. We observed that linalool inhibited UVB-induced phosphorylation of ERK1, JNK and p38 proteins of MAPK family. Linalool inhibited UVB-induced activation of NF-κB/p65 by activating IκBa. We further observed that UVB-induced expression of TNF-α, IL6, IL-10, MMP-2 and MMP-9 was modulated by linalool treatment in HDFa cells. Thus, linalool protects the human skin cells from the oxidative damages of UVB radiation and modulates MAPK and NF-κB signaling in HDFa cells. The present findings substantiate that linalool may act as a photoprotective agent against UVB-induced skin damages.