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Maslinic acid is a pentacyclic triterpenoid that is distributed in the peel of olives. Previous studies found that maslinic acid inhibited inflammatory response and antioxidant effects. We investigated whether maslinic acid ameliorates nonalcoholic fatty liver disease in mice with high-fat-diet (HFD)–induced obesity and evaluated the regulation of lipogenesis in hepatocytes. Male C57BL/6 mice fed a normal diet or HFD (60% fat, w/w) were tested for 16 wk. After the fourth week, mice were injected intraperitoneally with maslinic acid for 12 wk. In another experiment, HepG2 cells were treated with oleic acid to induce lipid accumulation or maslinic acid to evaluate lipogenesis. Maslinic acid significantly reduced body weight compared with HFD-fed mice. Maslinic acid reduced liver weight and liver lipid accumulation and improved hepatocyte steatosis. Furthermore, serum glucose, leptin, and free fatty acid concentrations significantly reduced, but the serum adiponectin concentration was higher, in the maslinic acid group than in the HFD group. In liver tissue, maslinic acid suppressed transcription factors involved in lipogenesis and increased adipose triglyceride lipase. In vitro, maslinic acid decreased lipogenesis by activating AMPK. These findings suggest that maslinic acid acts against hepatic steatosis by regulating enzyme activity involved in lipogenesis, lipolysis, and fatty acid oxidation in the liver.—Liou, C.-J., Dai, Y.-W., Wang, C.-L., Fang, L.-W., Huang, W.-C. Maslinic acid protects against obesity-induced nonalcoholic fatty liver disease in mice through regulation of the Sirt1/AMPK signaling pathway.

Lactone monomers with different chain lengths are copolymerized with poly(ethylene glycol) or methoxypoly(ethylene glycol) to form triblock and diblock pegylated polyester copolymers. The pegylated polyester copolymers have an amphiphilic character because they are comprised of both hydrophobic and hydrophilic domains, which spontaneously assemble in aqueous media to form nano-sized micelles at concentrations above the critical micelle concentration. The type of lactone monomer, the chain lengths of the hydrophobic as well as the hydrophilic blocks, the molecular weight of poly(ethylene glycol), and the formation of triblock or diblock polymeric micelles all play important roles in micelle performance. The triblock and diblock pegylated poly(d-valerolactone) copolymers show higher in vitro cytotoxicity than the others. Triblock PCL-PEG 10,000 -PCL micelles possess high drug loading, low in vitro cytotoxicity, proper in vitro sustained release performance and prolonged mean residence time of drug in blood circulation. Diblock PCLMPEG micelles have lower critical micelle concentration, higher biocompatibility, and higher drug loading than PVL-MPEG micelles. The enzyme-catalyzed chain cleavage of labile ester linkages of pegylated polyester copolymer occurs in rat plasma, and the changes in mass, molecular weight and morphology of the copolymers are associated with changes in its composition.

Cyphomandra betacea Sendt. (tamarillo) is a subtropical fruit containing rich contents of anthocyanins and carotenoids. The antioxidant activity was investigated using a crude ethanol extract of C. betacea fruit and its partitioned fractions, i.e. the ethyl acetate, butanol and water fractions. The ethyl acetate fraction exhibited the highest DPPH scavenging activity, Trolox equivalent antioxidant capacity (TEAC) and total phenol content. C. betacea phenolics in ethyl acetate fraction inhibited copper-induced LDL oxidation equally to or more effectively than dl -α-tocopherol, as measured by decreased formation of thiobarbituric acid-reactive substances (TBARS), conjugated diene and relative electrophoretic mobility (REM). Furthermore, 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) reduction assay showed that C. betacea phenolics in ethyl acetate fraction prevent oxidative stress-induced cell death in neuronal PC12 cells in a dose-dependent manner via attenuation of ROS production. In conclusion, C. betacea phenolics are potent antioxidants which can inhibit LDL oxidation in vitro and ROS production in PC12 cells.

Ginkgolide C, isolated from Ginkgo biloba leaves, is a flavone reported to have multiple biological functions, from decreased platelet aggregation to ameliorating Alzheimer disease. The study aim was to evaluate the antiadipogenic effect of ginkgolide C in 3T3-L1 adipocytes. Ginkgolide C was used to treat differentiated 3T3-L1 cells. Cell supernatant was collected to assay glycerol release, and cells were lysed to measure protein and gene expression related to adipogenesis and lipolysis by western blot and real-time PCR, respectively. Ginkgolide C significantly suppressed lipid accumulation in differentiated adipocytes. It also decreased adipogenesis-related transcription factor expression, including peroxisome proliferator-activated receptor and CCAAT/enhancer-binding protein. Furthermore, ginkgolide C enhanced adipose triglyceride lipase and hormone-sensitive lipase production for lipolysis and increased phosphorylation of AMP-activated protein kinase (AMPK), resulting in decreased activity of acetyl-CoA carboxylase for fatty acid synthesis. In coculture with an AMPK inhibitor (compound C), ginkgolide C also improved activation of sirtuin 1 and phosphorylation of AMPK in differentiated 3T3-L1 cells. The results suggest that ginkgolide C is an effective flavone for increasing lipolysis and inhibiting adipogenesis in adipocytes through the activated AMPK pathway.

Three types of pegylated amphiphilic copolymers of poly(δ-valerolactone) (PVL) were copolymerized with methoxy poly(ethylene glycol) (MePEG) and poly(ethylene glycol) (PEG4000 and PEG10,000), respectively. Pegylation of PVL allowed copolymers possessing amphiphilic property and efficiently self-assembled to form micelles with a low critical micelle concentration (CMC) in the range of 10−7–10−8M. The average molecular weight of copolymers was in the range of 10,000–20,000 Da, and the polydispersity of copolymers was about 1.7–1.8. Higher mobility of low molecular weight PEG (i.e., MePEG and PEG4000) than high molecular weight PEG10,000 allowed valerolactone ring opening more efficient in terms of PVL/MePEG and PVL/PEG4000 copolymers possessing longer chain length in hydrophobic domain. Pegylated PVL with low CMC and triblock structure was preferred to encapsulate drug during micelle formation. Although all of these amphiphilic copolymers exhibited controlled release character, the micelles formed by triblock copolymer possessed a more stable core-shell conformation than that by diblock copolymer, and resulted in the release of drug from triblock micelles slower than that from diblock micelles. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 1836–1841, 2006

The aim of this study was to evaluate the ability of forming micelles from two types of synthesized diblock pegylated amphiphilic copolymers and their potential as a drug carrier. Two lactone monomers, epsilon-caprolactone (CL) and delta-valerolactone (VL), were copolymerized with methoxy poly(ethylene glycol) (MePEG), respectively. The properties of copolymers were investigated and their biocompatibility was tested through an in vitro cytotoxicity study. The influences of the type of lactone monomer (CL and VL) and the feed molar ratios of lactone/MePEG (50/1, 80/1, 160/1) on the performance and release behavior of drug-loaded micelles were investigated. The opening of CL and VL rings by MePEG was efficient, and the pegylation of poly(lactone)s allowed copolymers possessing amphiphilic property and efficiently self-assembled to form micelles with a low critical micelle concentration (CMC) in the range of 10(-7)-10(-8) M. The nano-sized micelles were able to incorporate hydrophobic drug and regulate drug release, and the release of drug was dominated by the hydrophobic poly(lactone) chain length. Although both amphiphilic copolymers exhibited similar controlled release character, the PCL/MePEG micelles possessed lower CMC, higher biocompatibility, and higher drug loading than PVL/MePEG micelles. These suggested that results choosing pegylated PCL as a drug carrier could be better than PVL/MePEG.

We present a method whereby the excited triplet state of diphenylmethylene can be populated in a spin‐polarized manner. The method features sensitization by benzophenone triplet excitons. We ascertain the spin‐polarized nature of the excited triplet by observing magnetic field effects on the fluorescence. The observed effects provide information concerning the spin dipolar and intersystem crossing nature of excited diphenylmethylene.

We present a method whereby the excited triplet state of diphenylmethylene can be populated in a spin‐polarized manner. The method features sensitization by benzophenone triplet excitons. We ascertain the spin‐polarized nature of the excited triplet by observing magnetic field effects on the fluorescence. The observed effects provide information concerning the spin dipolar and intersystem crossing nature of excited diphenylmethylene.