The effect of diabetes mellitus on lipid metabolism is well established. The association of hyperglycaemia with an alteration of lipid parameters presents a major risk for cardiovascular complications in diabetes. Many secondary plant metabolites have been reported to possess lipid-lowering properties. The present study was designed to examine the potential anti-hyperlipidaemic efficacy of the ethanolic extract from Aloe vera leaf gel in streptozotocin (STZ)-induced diabetic rats. 2. Oral administration of Aloe vera gel extract at a dose of 300 mg/kg bodyweight per day to STZ-induced diabetic rats for a period of 21 days resulted in a significant reduction in fasting blood glucose, hepatic transaminases (aspartate aminotransferase and alanine aminotransferase), plasma and tissue (liver and kidney) cholesterol, triglycerides, free fatty acids and phospholipids and a significant improvement in plasma insulin. 3. In addition, the decreased plasma levels of high-density lipoprotein-cholesterol and increased plasma levels of low-density lipoprotein-and very low-density lipoprotein-cholesterol in diabetic rats were restored to near normal levels following treatment with the extract. 4. The fatty acid composition of the liver and kidney was analysed by gas chromatography. The altered fatty acid composition in the liver and kidney of diabetic rats was restored following treatment with the extract. 5. Thus, the results of the present study provide a scientific rationale for the use of Aloe vera as an antidiabetic agent.

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Edible nanoparticles (ENPs) are nano-sized vesicles derived from edible plants. These ENPs are loaded with plant derived microRNAs, protein, lipids and phytochemicals. Recently, ginger derived ENPs was shown to prevent inflammatory bowel diseases and colon cancer, in vivo, highlighting their therapeutic potential. Conventionally, differential centrifugation with an ultra-centrifugation step is employed to purify these ENPs which imposes limitation on the cost-effectiveness of their purification. Herein, we developed polyethylene glycol-6000 (PEG6000) based ginger ENP purification (PEG-ENPs) method, which eliminates the need for expensive ultracentrifugation. Using different PEG6000 concentrations, we could recover between 60% to 90% of ENPs compared to ultracentrifugation method. PEG-ENPs exhibit near identical size and zeta potential similar to ultra-ENPs. The biochemical composition of PEG-ENPs, such as proteins, lipids, small RNAs and bioactive content is comparable to that of ultra-ENPs. In addition, similar to ultra-ENPs, PEG-ENPs are efficiently taken up by the murine macrophages and protects cells from hydrogen peroxide induced oxidative stress. Since PEG has been approved as food additive, the PEG method described here will provide a cost-effective alternative to purify ENPs, which can be directly used as a dietary supplement in therapeutic formulations.

Background:Telomerase is essential for cancer cell growth. Results: MiR-498 is a novel 1,25(OH) 2 D 3 target gene that decreases telomerase, induces cell death, and suppresses tumor growth. Conclusion: MiR-498 is an important mediator of the anti-tumor activity of 1,25(OH) 2 D 3 . Significance: The studies define a new mechanism of telomerase regulation by small non-coding RNAs in response to 1,25(OH) 2 D 3 .

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Piperlongumine is a natural product found in the plant species , and this compound exhibits potent anticancer activity in multiple tumor types and has been characterized as an inducer of reactive oxygen species (ROS). Treatment of Panc1 and L3.6pL pancreatic, A549 lung, 786-O kidney, and SKBR3 breast cancer cell lines with 5 to 15 μmol/L piperlongumine inhibited cell proliferation and induced apoptosis and ROS, and these responses were attenuated after cotreatment with the antioxidant glutathione. Piperlongumine also downregulated expression of Sp1, Sp3, Sp4, and several pro-oncogenic Sp-regulated genes, including cyclin D1, survivin, cMyc, EGFR and hepatocyte growth factor receptor (cMet), and these responses were also attenuated after cotreatment with glutathione. Mechanistic studies in Panc1 cells showed that piperlongumine-induced ROS decreased expression of cMyc via an epigenetic pathway, and this resulted in downregulation of cMyc-regulated miRNAs miR-27a, miR-20a, and miR-17 and induction of the transcriptional repressors ZBTB10 and ZBTB4. These repressors target GC-rich Sp-binding sites to decrease transactivation. This pathway observed for piperlongumine in Panc1 cells has previously been reported for other ROS-inducing anticancer agents and shows that an important underlying mechanism of action of piperlongumine is due to downregulation of Sp1, Sp3, Sp4, and pro-oncogenic Sp-regulated genes..

Naturally occurring anticancer agents and their derivatives act on multiple pathways to inhibit carcinogenesis and their inhibition of migration, invasion, growth, survival, and metastasis is associated with downregulation of genes associated with these responses. Several phytochemical-derived anticancer drugs including curcumin, betulinic acid, phenethylisothiocyanate and celastrol, and many others induce reactive oxygen species, and their effects on gene regulation show some overlap in various cancer cell lines. We hypothesize that reactive oxygen species-inducing anticancer agents and many other natural products target a common pathway in cancer cells, which initially involves downregulation of specificity protein 1 (Sp1), Sp3, and Sp4, which are highly expressed in tumors/cell lines derived from solid tumors. This hypothesis is supported by several published reports showing that a large number of phytochemical-derived anticancer agents downregulate Sp1, Sp3, Sp4, and pro-oncogenic Sp-regulated genes involved in cell growth (cyclin D1 and growth factor receptors), survival (bcl-2 and survivin), angiogenesis and migration (MMP-9, vascular endothelial growth factor and its receptors), and inflammation (NF-kB). The contribution of this pathway to the anticancer activity of drugs such as curcumin, celastrol, betulinic acid, and phenethylisothiocyanate must be determined in order to optimize clinical applications of drug combinations containing these compounds. Copyright © 2016 John Wiley & Sons, Ltd.

Edited by Eric R. FearonThe antineoplastic agent benzyl isothiocyanate (BITC) acts by targeting multiple pro-oncogenic pathways/genes, including signal transducer and activator of transcription 3 (STAT3); however, the mechanism of action is not well known. As reported previously, BITC induced reactive oxygen species (ROS) in Panc1, MiaPaCa2, and L3.6pL pancreatic cancer cells. This was accompanied by induction of apoptosis and inhibition of cell growth and migration, and these responses were attenuated in cells cotreated with BITC plus glutathione (GSH). BITC also decreased expression of specificity proteins (Sp) Sp1, Sp3, and Sp4 transcription factors (TFs) and several pro-oncogenic Sp-regulated genes, including STAT3 and phospho-STAT3 (pSTAT3), and GSH attenuated these responses. Knockdown of Sp TFs by RNA interference also decreased STAT3/pSTAT3 expression. BITC-induced ROS activated a cascade of events that included down-regulation of c-Myc, and it was also demonstrated that c-Myc knockdown decreased expression of Sp TFs and STAT3. These results demonstrate that in pancreatic cancer cells, STAT3 is an Sp-regulated gene that can be targeted by BITC and other ROS inducers, thereby identifying a novel therapeutic approach for targeting STAT3. Isothiocyanates (ITCs)3 are a family of structurally related natural products that are found in cruciferous vegetables such as glucosinolates, which are hydrolyzed by the enzyme myrosinase to give the unconjugated ITCs. Cruciferous vegetables in the diet have been associated with decreased risks for human cancers and exhibit both chemoprevention and chemotherapeutic activities in animal models, and this has primarily been associated with ITCs (1-5). Sulforaphane, allyl isothiocyanate, phenethyl isothiocyanate (PEITC), and benzyl isothiocyanate (BITC) have been extensively investigated as anticancer agents, and a recent review summarizes the multiple genes and associated pathways activated by ITCs (4). Treatment of cancer cells or animal models that develop tumors with ITCs decreases cell growth, induces apoptosis, and inhibits epithelial-to-mesenchymal transition, angiogenesis, and cell cycle progression (6 -16). ITCs, including BITC, exhibit a broad spectrum of activities that include induction of ROS and ROS-regulated genes, direct inhibition of genes, and formation of peptide and protein adducts (4,5,(15)(16)(17). ITCs form adducts with both thiol and amino groups, and the formation of amino adducts forms the basis of the Edman procedure used in protein sequencing (15, 18 -20). Many of these ITC-induced effects contribute to their anticancer activities; however, a recent study suggests that the alkylation of peptides by ITCs may also be responsible for allergic skin reactions to these compounds (20).Studies in this laboratory have focused on specificity protein (Sp) transcription factors (TFs) Sp1, Sp3, and Sp4 as non-oncogene addiction genes in cancer cells, and knockdown of Sp1, Sp3, and Sp4 individually and combined inhibits cell growth, induces apoptosis, and inhibi...