Toona Sinensis ameliorates insulin resistance via AMPK and PPARγ pathways.

Toona Sinensis leaf (TSL) extract with a beneficial effect for managing hyperglycemia has been reported, however the underlying mechanism by which TSL extract acts as an insulin sensitizer remains uncertain, especially in peripheral tissues. TSL 95% ethanol extract exhibited the highest transactivity of PPARγ and contained the highest amounts of natural PPARγ ligands including palmitic acid, linoleic acid, and α-linolenic acid among different TSL ethanol extracts (0, 10, 50, 70, and 95%). The efficacy and the mechanism of TSL ethanol extract (95%) mediated anti-diabetic effects were examined by both in vivo and in vitro models in this study. An improved whole-body insulin sensitivity was observed in high-fat diet-fed (HFD) mice after 14 weeks of TSL treatment, as evidenced by a faster rate of plasma glucose clearing. The improved insulin sensitivity was through direct stimulation of PPARγ and adiponectin expression in adipose tissues of HFD mice. In addition to the PPARγ pathway, TSL stimulated glucose uptake via directly inducing AMPKα but not AS160 activation in C2C12 myotubes under palmitate-induced insulin resistance. TSL successfully induced sirtuin 1 and restored PGC1α, but failed to restore mitochondrial electron transport complexes I, III, IV and V in mRNA levels. Loss of the mitochondrial membrane potential coupled with AMPK activation suggests that TSL acts as a mitochondrial inhibitor to stimulate AMPK-mediated glucose uptake. This study demonstrated that TSL stimulated glucose uptake via AMPK activation in skeletal muscles and promoted PPARγ and normalized adiponectin expression in adipose tissues, thereby ameliorating insulin resistance.

Toona sinensis Leaf Aqueous Extract Improves the Functions of Sperm and Testes via Regulating Testicular Proteins in Rats under Oxidative Stress.

Toona sinensis leaf (TSL) is commonly used as a vegetable and in spice in Asia. In this study, feeding with aqueous extract of TSL (TSL-A) alleviated oxidative stress and recovered the motility and functions of sperm in rats under oxidative stress. Protein expressions in testes identified by proteomic analysis and verified by Western blot demonstrated that TSL-A not only downregulated the level of glutathione transferase mu6 (antioxidant system), heat shock protein 90 kDa-ß (protein misfolding repairing system), cofilin 2 (spermatogenesis), and cyclophilin A (apoptosis) but also upregulated crease3-hydroxy-3-methylglutaryl-coenzyme A synthase 2 (steroidogenesis), heat shock glycoprotein 96, and pancreatic trypsin 1 (sperm-oocyte interaction). These results indicate that TSL-A promotes the functions of sperm and testes via regulating multiple testicular proteins in rats under oxidative stress, suggesting that TSL-A is a valuable functional food supplement to improve functions of sperm and testes for males under oxidative stress.

Toona sinensis Roem leaf extracts improve antioxidant activity in the liver of rats under oxidative stress.

Toona sinensis Roem (TS) is an herbal plant widely cultivated in Asia. Recently, several antioxidant compounds in TS leaf (TSL) extracts were chemically identified including quercetin, gallic acid, and others. However, in vivo experiments regarding the antioxidative function of TSL are limited. In this study, Sprague Dawley (SD) rats with oxidative stress were successfully established by intraperitoneal injection of hydrogen peroxide (H(2)O(2)) (1mmol/kg BW) and fed with different TSL extracts for in vivo antioxidation evaluation. Among the TSLs tested in this study, TSL6 exhibited the best antioxidative effects which increased the enzyme activities of catalase, cupper/zinc superoxide dismutase (Cu/Zn SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and Glutathione S transferase (GST) activities in liver compared to those in TSL-2 and TSL-2P groups. In conclusion, we provide the strong in vivo evidences for the first time that TSL extracts ameliorate the antioxidant enzymes (AOEs) activity in liver and is beneficial for the hepatic detoxification.

Antihypertension Induced by Tanshinone IIA Isolated from the Roots of Salvia miltiorrhiza.

Tanshinone IIA is one of the active principles in danshen (Salvia miltiorrhiza Bge) widely used in treatment of cardiovascular disorders. We investigated the effect of danshen or tanshinone IIA on blood pressure and its possible mechanisms. An i.p. injection of danshen at 10 mg kg(-1) significantly lowered systolic blood pressure (SBP) of spontaneously hypertensive rats (SHRs) but failed to modify the SBP in normotensive Wistar-Kyoto rats (WKY). Oral administration of tanshinone IIA also decreased SBP in SHR but not in WKY. Tanshinone IIA produced a concentration-dependent relaxation in isolated SHR aortic rings precontracted with phenylephrine (10 nmol l(-1)) or potassium chloride (KCl) (40 mmol l(-1)). The relaxing effect of tanshinone IIA on tonic contraction of phenylephrine in isolated aortic rings without endothelium remained produced. Glibenclamide at concentration sufficient to block adenosine triphosphatase (ATP)-sensitive potassium (K(+)) channel attenuated this tanshinone IIA-induced relaxation that was not influenced by other inhibitors. We further investigated the effect of tanshinone IIA on the changes of intracellular calcium concentration ([Ca(2+)](i)) in cultured aortic smooth muscle (A7r5) cells using fura-2 as indicator. Tanshinone IIA decreased [Ca(2+)](i) elicited by phenylephrine (10 nmol l(-1)) or KCl (40 mmol l(-1)) in a concentration-dependent manner; glibenclamide, but not other inhibitors for K(+) channel, abated this effect. Our results suggest that tanshinone IIA acts as an active principle of danshen showing vasodilation through ATP-sensitive K(+) channel to lower [Ca(2+)](i).

Autonomic regulation of insulin secretion is changed by pentobarbital in mice.

It has been established that insulin secretion is regulated by autonomic nervous homeostasis. In the screen of plasma glucose level, anesthetized animals were widely used. However, effects of anesthetics on blood glucose remain unclear. In the present study, we compared the hypoglycemic action of ginseng that was induced by insulin secretion in mice between conscious and under anesthesia with pentobarbital. The hypoglycemic effect of ginseng was only produced in anesthetized BALB/c mice but not in the conscious mice. Similar results were also observed in C57BL/6 mice. However, the hypoglycemic action of ginseng failed to produce in anesthetized BALB/c mice received streptozotocin to induce type-1 like diabetes showing an insulin-dependent manner. The plasma insulin level in anesthetized BALB/c mice was markedly raised by ginseng but this effect was not observed in conscious mice. Blockade of muscarinic receptors by atropine inhibited ginseng-induced insulin secretion in anesthetized mice. Otherwise, the hypoglycemic action of ginseng was restored in conscious mice treated guanethidine at a sufficient dose to block sympathetic tone. In conclusion, the obtained results suggest that insulin secretion regulated by autonomic nervous homeostasis can be changed by pentobarbital through decrement in sympathetic tone to increase the insulin secretion induced by agent(s) via higher of parasympathetic tone. This finding is suitable to explain the critical hypoglycemia was not observed in subjects received ginseng.

A synthetic method for peptide-PEG-lipid conjugates: application of octreotide-PEG-DSPE synthesis.

A solid phase synthesis method was established for the synthesis of peptide-poly(ethylene glycol)-lipid (peptide-PEG-lipid) conjugates. Octreotide-PEG(2000)-DSPE (OPD(2000)) was used as an example to demonstrate the synthetic approach. The OPD(2000) obtained had confirmed structure, activity, and purity providing a targeting molecule for preparation of well-defined drug delivery systems, such as targeted liposomes, for further studies.

Regulation of endothelin-1 production in deoxycorticosterone acetate- salt-treated endothelial cells.

The aim of this study was to investigate the direct effect of deoxycorticosterone acetate (DOCA) on the expression of endothelin-1 (ET-1) mRNA and production of ET-1 peptides in cultured bovine carotid endothelial cells (BCEC) and human umbilical vein endothelial cells (HUVEC). The mineralocorticoid, DOCA, was administered to BCEC and HUVEC with or without additional salt (200 mmol/l). The ET-1 mRNA was elevated to 150% and 180% after a 24-hour incubation with DOCA (5 micromol/l) in BCEC and HUVEC, respectively. Intracellular content of ET-1 peptides of BCEC and HUVEC was increased from 21.66 +/- 0.3 to 23.64 +/- 0.19 fmol/10(5) cells and from 8.38 +/- 0.82 to 11.26 +/- 0.91 fmol/10(5) cells, respectively, in the DOCA-conditioned medium. Also, DOCA treatment for 24 h increased the secretion of ET-1 peptide from 1.62 +/- 0.17 to 5.33 +/- 0.67 fmol/10(5) cells in BCEC and from 0.95 +/- 0.08 to 3.56 +/- 0.36 fmol/10(5) cells in HUVEC. In DOCA-salt-treated endothelium, regulation of ET-1 gene was similar to that with DOCA alone. The DOCA-induced increase in expression of ET-1 mRNA and the ET-1 peptide level were both diminished in dexamethasone (DEX, 10 nmol/l)- or mifepristone (RU486, 0.5 micromol/l)-treated endothelium. These results suggest that DOCA directly increased the ET-1 mRNA expression in endothelium and could be mediated in part by a glucocorticoid receptor pathway which was independent of salt and hyperosmolarity.