A herbal extract with acetyl-coenzyme A carboxylase inhibitory activity and its potential for treating metabolic syndrome.

Metabolism. 2009 Jun 4; Chen CH, Chang MY, Lin YS, Lin DG, Chen SW, Chao PMAcetyl-coenzyme A carboxylase (ACC) plays a crucial role in fatty acid metabolism, and its inhibition is an effective approach for treating metabolic syndrome. Partially purified ACC from rat liver was used to screen herbs commonly used in Taiwanese folk medicine for ACC inhibitory effects. An ethanol extract of Polygonum hypoleucum Ohwi (EP), the Taiwan tuber fleece flower, was found to have the highest inhibitory activity (half-maximal inhibitory concentration = 30 mug/mL). We then tested the physiologic effects of EP using high-fat (HF) diet-fed C57BL/6J mice. After 4 weeks, body weight and levels of blood glucose, insulin, triacylglycerol, total cholesterol, and leptin were significantly reduced (P < .05) in mice fed a 3% EP-containing HF diet. The EP also improved the glucose tolerance and insulin sensitivity of HF diet-fed mice. In addition, EP at concentrations of 0.0725 and 0.145 mg/mL (2.5- and 5-fold higher than the half-maximal inhibitory concentration) was also effective in decreasing ACC and fatty acid synthase activity and the triacylglycerol content of HepG2 cells incubated in high-glucose (30 mmol/L) medium. These results show that EP, acting by inhibiting ACC activity, is effective in alleviating the symptoms associated with metabolic disease.

Analysis of the constituents in rat plasma after oral administration of Shexiang Baoxin pill by HPLC-ESI-MS/MS.

Biomed Chromatogr. 2009 Jun 10; Jiang P, Liu R, Dou S, Liu L, Zhang W, Chen Z, Xu R, Ding JA valid method using liquid chromatography coupled with electrospray ionization (ESI) and ion trap mass spectrometry was established for the study of the absorbed components in rat plasma after oral administration of a traditional Chinese medicine (TCM) Shexiang Baoxin pill. The plasma was deproteinated by adding methanol prior to liquid chromatography, in which separation was carried out on a Symmetry C(18 )column (5 microm, 250 x 4.6 mm). A linear gradient with 0.5% formic acid-water-acetonitrile was used as mobile phase. Mass spectra were acquired in both negative and positive modes. Twenty-one components including 17 components from Shexiang Baoxin pill and four metabolites were observed from a comprehensive analysis of the chromatography of Shexiang Baoxin pill, controlled plasma and dosed plasma. All of the 17 prototype compounds and three of the metabolites were identified by comparing their retention behaviors and MS and MS/MS spectra with reference compounds and literature data. This study developed an integrated method for screening the bioactive constituents in plasma after oral adminstration of Chinese herbal medicine and provided helpful chemical information for further pharmacology and active mechanism research on TCM. Copyright (c) 2009 John Wiley & Sons, Ltd.

Experimental study on the effect of Kang-Lai-Te induced apoptosis of human hepatoma carcinoma cell HepG2.

Hepatobiliary Pancreat Dis Int. 2009 Jun; 8(3): 267-72Lu Y, Wu LQ, Dong Q, Li CSBACKGROUND: Kang-Lai-Te (KLT) is extracted from the traditional Chinese herbal medicine Semen Coicis, which has been used in China as an effective clinical drug for over a thousand years. It contains numerous ingredients with anti-tumor effects. In our previous studies on transplanted hepatomas in rats, KLT could stop the cells in the G2+M stage of cell cycle and then reduce the number of cells entering the stage G0 and G1, but the mechanism of the anti-proliferative effect was unknown. In this experiment, we examined whether KLT inhibits HepG2 cell growth, if so, tried to explore its mechanism. METHODS: KLT at different concentrations was used for the treatment of hepatocellular carcinoma cells in vitro, respectively. The proliferation inhibitory rate was evaluated by MTT assay, induction of cell apoptosis rate and the protein levels of Fas and Fas ligand (FasL) were determined by flow cytometry (FCM), and the expression of Fas and FasL mRNA was detected by real-time fluorescent quantitative RT-PCR. RESULTS: KLT produced an obvious time and dose-dependent inhibitory effect on HepG2 cells, and marked apoptosis was detected by FCM. The protein of Fas increased by 11.01%, 18.71%, 28.71% and 37.15%; the protein of FasL increased by 1.49%, 1.91%, 3.27% and 3.38% in comparison with the control (P

Paving roads for new drugs in oncology.

Recent Pat Anticancer Drug Discov. 2009 Jun; 4(2): 137-45Zaenker KS, Entschladen FLow productivity and the escalating costs of drug development have been well documented over the past years. A fraction of new pre-clinical compounds successfully pass experimental test batteries, and less than 10% of these compounds that enter clinical trials ultimately make it to the market. These challenges in the "critical path" of drug development will be discussed for drugs in the field of oncology, regarding the i) the impact of FDA and EMEA guidelines, and ii) microdosing studies/phase 0 trials before a drug enters phase I to III, to inform drug development, compressing drug development timelines and decision-making for continuation into clinical trials. Moreover, this review should embark on i) how to find new key molecules involved in life-and-death decision of a cell, how ii) old drugs will have a revival for new indications, because of novel information for their mode of action, and iii) how the revolutionary advances - high-throughput technologies, gene therapy and the deciphering of the human genome - do have their potential to develop personalized therapy. Therapy has progressed from an age of administering herbal remedies and organ extracts to an era of meticulously planned drug discovery, when pharmaceutical industry was born in a Western understanding. The relevant patents are discussed.

Neuroprotective role of Convolvulus pluricaulis on aluminium induced neurotoxicity in rat brain.

J Ethnopharmacol. 2009 Jun 5; Bihaqi SW, Sharma M, Singh AP, Tiwari MAIM OF THE STUDY: Convolvulus pluricaulis (Convolvulaceae) has long been used as traditional herbal medicine in India as nerve tonic. We investigated neuroprotective effects of aqueous extract from Convolvulus pluricaulis (CP) against aluminium chloride induced neurotoxicity in rat cerebral cortex. MATERIAL, METHOD AND RESULT: Daily administration of CP (150mg/kg) for three months along with aluminium chloride (50mg/kg) decreased the elevated enzymatic activity of acetylcholine esterase and also inhibited the decline in Na(+)/K(+)ATPase activity which resulted from aluminium intake. Beside, preventing accumulation of lipid and protein damage, changes in the levels of endogenous antioxidant enzymes associated with aluminium administration were also rectified. Oral administration of CP preserved the mRNA levels of Muscarinic receptor 1 (M1 receptor), Choline acetyl transferase (ChAT) and Nerve Growth Factor-Tyrosine kinase A receptor (NGF-TrkA). It also ameliorated the upregulated protein expression of Cycline dependent kinase5 (Cdk5) induced by aluminium. The potential of CPE to inhibit aluminium induced toxicity was compared with rivastigmine tartrate (1mg/kg), which was taken as standard. The potential of the extract to prevent aluminium induced neurotoxicity was also reflected at the microscopic level, indicative of its neuroprotective effects. CONCLUSION: Convolvulus pluricaulis possesses neuroprotective potential, thus validating its use in alleviating toxic effects of aluminium.