Медицинская химия

Humulus Scandens has been widely used for a long time in folk medicine, but it has not been systematically researched until now. The aims of this study were to isolate the components and simultaneously determine the contents of luteolin-7-O-β-D-glucoside (LGL) and apigenin-7-O-β-D-glucoside (AGL) in the different parts of H. Scandens. At the same time, our research team verified the anti-cancer activity and the alveolar fluid clearance (AFC) of H. Scandens total flavonoids (HSTF), LGL and AGL. The anti-cancer experiment showed that HSTH and LGL have a significant inhibition effect on the HepG2 cell. The cell viability decreased when drug concentration increased, but AGL has an indistinctive effect on HepG2 cell under the same concentration. The AFC experiment showed that AFCs of HSTF, LGL and AGL, compared to the blank control group, increased, which explained the H. Scandens pharmacological effect of removing edema. This result provides the theoretical basis for H. Scandens clinical application.

The purpose of this 42-day study was to evaluate the risk of oxidative stress in the spleens induced by dietary vanadium through determining changes in antioxidant enzymes and oxidation products. A total of 420 one-day-old avian broilers were divided into six groups. There were 70 broilers in each group. The broilers were fed on a cornsoybean basal diet as a control diet (vanadium 0.073 mg/kg) or the same diet amended to contain 5 mg/kg, 15 mg/kg, 30 mg/kg, 45 mg/kg and 60 mg/kg vanadium supplied as ammonium metavanadate (NH4VO3). When compared with those of the control group, the splenic and serum vanadium contents were increased in the 15 mg/kg, 30 mg/kg, 45 mg/ kg and 60 mg/kg groups. Also, the splenic and serum superoxide dismutase (SOD) activities were greatly depressed in the 45 mg/kg and 60 mg/kg groups; the glutathione peroxidase (GSH-Px) activities and the ability to inhibit hydroxyl radical were markedly depressed in the 30 mg/kg, 45 mg/kg and 60 mg/kg groups; the malondialdehyde (MDA) content was significantly increased in the 30 mg/kg, 45 mg/kg and 60 mg/kg groups. At the same time, the splenic glutathione (GSH) content was significantly decreased in the 30 mg/kg, 45 mg/kg and 60 mg/kg groups, and the serum GSH content was significantly decreased in the 15 mg/kg, 30 mg/kg, 45 mg/kg and 60 mg/kg groups. Also, the splenic and serum glutathione (oxidized form, GSSG) content was significantly higher in the 30 mg/kg, 45 mg/kg and 60 mg/kg groups than that in the control group. These results indicated that dietary vanadium in the range of 30~60 mg/kg caused substantial oxidative stress in the spleen, which then affected the antioxidant function; this may be possible pathway leading to spleen injure. At the same time, it was found that dietary vanadium in the range of 5-15 mg/kg was relatively safe for the spleens of young broilers.

Hochuekkito (TJ-41) is used for the treatment of complaints in patients with general fatigue. However, there is little scientific evidence to demonstrate the liver-protective effects of TJ-41. In the inflamed liver, proinflammatory cytokines stimulate the induction of inducible nitric oxide synthase (iNOS). Over-production of NO by iNOS has been implicated as a factor in liver injury. We examined proinflammatory cytokine-stimulated hepatocytes as a simple in vitro injury model to determine liver-protective effects of TJ-41. The objective was to investigate whether TJ-41 influences iNOS induction and to determine its mechanism. Primary cultured rat hepatocytes were treated with interleukin (IL)-1β in the presence or absence of TJ-41. The induction of iNOS and its signaling pathway were analyzed. IL-1β produced increased levels of NO. This effect was inhibited by TJ-41, which exerted its maximal effects at 6 mg/ml. TJ-41 decreased the levels of iNOS protein and its mRNA expression. Experiments with nuclear extracts revealed that TJ- 41 inhibited the translocation of NF-κB to the nucleus and its DNA binding. TJ-41 also inhibited the activation of Akt, resulting in the reduction of type I IL-1 receptor mRNA and protein expression. Transfection experiments demonstrated that TJ-41 suppressed iNOS induction by the inhibition of promoter transactivation and mRNA stabilization. TJ-41 reduced the expression of an iNOS gene antisense-transcript, which is involved in iNOS mRNA stability. Results indicate that TJ-41 inhibits the induction of iNOS at both transcriptional and post-transcriptional steps, leading to the prevention of NO production. TJ-41 may have therapeutic potential for various liver injuries through the suppression of iNOS induction.

Although dopamine (DA) dysfunction is a well-known hypothesis for etiology of schizophrenia, molecular basis of mesolimbic DA hyperactivity has not yet been clarified. To explain this, modulating function of trace amines on DA neurotransmission and the decreased number of striatal D-neurons, trace amine-producing neurons, were considered. Notably, Trace Amine-Associated Receptor, Type 1 (TAAR1), a subtype of trace amine receptors, has a large number of ligands, including tyramine, β-phenylethylamine and methamphetamine that influence on human mental state, and is now regarded as a target receptor for novel neuroleptics. Reduced stimulation of TAAR1 on DA neurons in the midbrain ventral tegmental area (VTA) has been revealed to increase firing frequency of VTA DA neurons. The author and her colleagues reported the decrease of D-neurons in the striatum and nucleus accumbens of postmortem brains of patients with schizophrenia. This may imply the decrease of trace amine synthesis and consequent reduction of the stimulation of TAAR1 on terminals of midbrain VTA DA neurons, and may lead to mesolimbic DA hyperactivity in schizophrenia. The decrease of striatal D-neurons of postmortem brains of schizophrenia might be due to neural stem cell dysfunction in the subventricular zone of lateral ventricle. The new “D-cell hypothesis”, in which D-neurons and TAAR1 are involved, may explain mesolimbic DA hyperactivity of schizophrenia.