Induction and Stabilization of Columnar Mesophases in Fluorinated Polycyclic Aromatic Hydrocarbons by Arene-Perfluoroarene Interactions.

The straightforward synthesis of several Fluorinated Polycyclic Aromatic Hydrocarbons by the efficient, transition-metal-free, arene fluorine nucleophilic substitution reaction is described, and the full investigation of their liquid crystalline and optical properties reported. The key precursors for this study, i. e. 2,2'-dilithio-4,4',5,5'-tetraalkoxy-1,1'-biphenyl derivatives, were obtained in two steps from the highly selective Scholl oxidative homo-coupling of 3,4-dialkoxy-1-bromobenzene, followed by quantitative double-lithiation. In situ room temperature nucleophilic annulation with either perfluorobenzene or perfluoronaphthalene leads to 1,2,3,4-tetrafluoro-6,7,10,11-tetraalkxoytriphenylenes and 9,10,11,12,13,14-hexafluoro-2,3,6,7-tetraalkoxybenzo[f]tetraphenes, respectively, in good yields. Exploiting the same strategy, subsequent double annulations resulted in the formation of 9,18-difluoro-2,3,6,7,11,12,15,16-octa(alkoxy)tribenzo[f,k,m]tetraphenes and 9,10,19,20-tetrafluoro-2,3,6,7,12,13,16,17-octakis(hexyloxy)tetrabenzo[a,c,j,l]tetracenes, respectively. Despite the presence of only four alkoxy chains, the polar "Janus" mesogens display a columnar hexagonal mesophase over broad temperature ranges, with higher mesophase stability than the archetypical 2,3,6,7,10,11-hexa(alkoxy)triphenylenes and their hydrogenated counterparts. The improvement or induction of mesomorphism is attributed to efficient antiparallel face-to-face π-stacking driven by the establishment of non-covalent perfluoroarene-arene intermolecular interactions. The larger lipophilic discotic π-extended compounds also exhibit columnar mesomorphism, over similar temperature ranges and stability than their hydrogenated homologs. Finally, these fluorinated molecules form stringy gels in various solvents, and show interesting solvatochromic emission properties in solution as well as strong emission in thin films and gels.

Urinary Metabolomic Study of Chlorogenic Acid in a Rat Model of Chronic Sleep Deprivation Using Gas Chromatography-Mass Spectrometry.

The urinary metabolomic study based on gas chromatography-mass spectrometry (GC-MS) had been developed to investigate the possible antidepressant mechanism of chlorogenic acid (CGA) in a rat model of sleep deprivation (SD). According to pattern recognition analysis, there was a clear separation among big platform group (BP), sleep deprivation group (SD), and the CGA (model + CGA), and CGA group was much closer to the BP group by showing a tendency of recovering towards BP group. Thirty-six significantly changed metabolites related to antidepressant by CGA were identified and used to explore the potential mechanism. Combined with the result of the classic behavioral tests and biochemical indices, CGA has significant antidepressant effects in a rat model of SD, suggesting that the mechanism of action of CGA might be involved in regulating the abnormal pathway of nicotinate and nicotinamide metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and arginine and proline metabolism. Our results also show that metabolomics analysis based on GC-MS is a useful tool for exploring biomarkers involved in depression and elucidating the potential therapeutic mechanisms of Chinese medicine.

Combination treatment with quercetin and resveratrol attenuates high fat diet-induced obesity and associated inflammation in rats via the AMPKα1/SIRT1 signaling pathway.

Diet-induced obesity is associated with systemic inflammation, which is considered to originate predominantly from the adipose tissue. Quercetin and resveratrol are two dietary polyphenols that exhibit anti-inflammatory properties and anti-insulin resistance when administered in isolation or combination (CQR). It remains unknown whether CQR reduces high fat diet (HFD)-induced obesity and inflammation in rats. In the current study, 46 male Wistar rats were divided into two groups, one of which was fed a normal diet (ND, 5.4% fat, w/w) and one of which was fed a HFD (45% fat, w/w) for 3 weeks. Following removal of the 12 most obesity-resistant rats from the HFD group, the remaining rats were divided into two sub-groups: A HFD group and a HFD+CQR group (administered 120 mg/kg/day resveratrol and 240 mg/kg/day quercetin). The results revealed that the HFD+CQR group had significantly lower body weights at 11 weeks compared with the HFD group and had significantly reduced visceral adipose tissue weights and adipocyte sizes. Serum lipid profiles were also significantly ameliorated in the HFD+CQR group. CQR attenuated the expression of systemic proinflammatory adipokines, including leptin, tumor necrosis factor-α, monocyte chemoattractant protein-1 and interleukin-6. It also reduced the recruitment of mast cells to the epididyotic adipose tissue (EAT). Furthermore, CQR reversed the HFD-induced suppression of 5'-adenosine monophosphate-activated protein kinase α1 (AMPKα1) phosphorylation and sirtuin 1 (SIRT1) expression in EAT. In conclusion, CQR may suppress obesity and associated inflammation via the AMPKα1/SIRT1 signaling pathway in rats fed a HFD.

Serum and Brain Metabolomic Variations Reveal Perturbation of Sleep Deprivation on Rats and Ameliorate Effect of Total Ginsenoside Treatment.

Sleep loss or sleep deprivation (SD) refers to shorter sleep than average baseline need, and SD has been a serious problem of modern societies which affects health and well-being. Panax ginseng is a well-known traditional Chinese medicine (TCM). Our previous study has demonstrated that total ginsenosides (GS), the extracts from Panax ginseng, could effectively improve cognition and behavior on SD rats. However, little is known about its metabolomic study. In this study, serum and brain metabolomic method based on gas chromatography coupled with mass spectrometry (GC/MS) was employed to evaluate the efficacy and study the mechanism of GS on a rat model of SD. With pattern recognition analysis of serum and brain tissue metabolite profile, a clear separation of the model group and control group was acquired for serum and brain tissue samples; the MGS (model + GS) group showed a tendency of recovering when compared to control group, which was consistent with behavioral and biochemical parameters. 39 and 40 potential biomarkers of brain tissues and serum samples, respectively, were identified and employed to explore the possible mechanism. Our work revealed that GS has significant protective effects on SD, and metabolomics is a useful tool for evaluating efficacy and elucidating mechanism in TCM.

[Recent progress of potential effects and mechanisms of chlorogenic acid and its intestinal metabolites on central nervous system diseases].

Chlorogenic acid displays several important roles in the therapeutic properties of many herbs, such as antioxidant activity, antibacterial, antiviral, scavenging free radicals and exciting central nervous system. Only about one-third of chlorogenic acid was absorbed in its prototype, therefore, its gut metabolites play a more important role in the therapeutic properties of chlorogenic acid. It is necessary to consider not only the bioactivities of chlorogenic acid but also its gut metabolites. This review focuses on the potential activities and mechanisms of chlorogenic acid and its gut metabolites on central nervous system diseases.

[Study on effects of baicalin, berberine and Astragalus polysaccharides and their combinative effects on aldose reductase in vitro].

OBJECTIVE: To observe the activities of baicalin, berberine and Astragalus polysaccharides and their combinative effects on aldose reductase (AR) by a screening model of aldose reductase inhibitor (ARI) in vitro. METHODS: The inhibition of AR by baicalin, berberine and Astragalus polysaccharides and positive drug (Epalrestat) in different concentrations were evaluated, and their combinative effects were studied according to orthogonal t design. RESULTS: Baicalin and berberine had remarkable inhibitory effects on AR, the inhibitory rates were (88.4 +/- 7.4)% and (69.0 +/- 9.4)% at the concentration of 300 microg/mL. However, the combinative effect of the inhibition on AR by the two compounds was antagonistic action. Astragalus polysaccharides had no activity of inhibition on AR. CONCLUSION: Baicalin and berberine are the potential AR inhibitors as they can inhibit the activity of AR in vitro.

[Study on extraction and purification of polysaccharides from Astragalus membranaceus].

OBJECTIVE: To optimize the extraction and purification procedure for polysaccharides from Astragalus membranaceus. METHODS: The orthogonal test was used to determine the optimal extraction technology in terms of the extraction rate of crude polysaccharides and the concentration of polysaccharides. The efficiency of deproteinization and decoloration with different methods were evaluated with the ration of protein and colorant removing as the indices. Their influence on the content of Astragalus polysaccharides was calculated as well. RESULTS: The optimum extraction procedure was as follows: 8 times of water extracting three times at 100 degrees C, 90 minutes per time. Deproteinization using pepsase combined with Sevage solvent and depigmenting with DEAE fibrin achieved a high purification rate. CONCLUSION: The optimized extraction and purification procedure is simple, quick and efficient. The result establishes the foundation for the further study of the polysaccharides from Astragalus membranaceus.

[Systemic biologic study on traditional Chinese medicine--a short-lived fad or a long-term policy?].

The research of traditional Chinese medicine (TCM) has failed to achieve major breakthrough, especially on some important and fundamental medical problems and concepts. One of the reasons for such failure is that the methodology used in the TCM research follows basically the path of partitioned reductive analysis, which is unable to capture practically the characteristics of TCM scientific system, such as the holistic and dynamic nature of diseases, and the interaction among various biological components. The systemic thinking and strategy of the systematic biology and its aim at grasping integral function have provided unprecedented enlightenment for the modem TCM research. To conduct a systemic strategic reductive analysis on human body and diseases under the guidance of holistic view will be an utmost important way for developing TCM towards the future of healthcare. The modernization of TCM does not have to follow the partitioned reductive approach, which has been practiced in the development of modern science in recent centuries. Instead, it should proceed in a "top down" way of systemic research by firstly investigating and understanding the systemic information, followed by a layered excavation on local information, so as to stride over the gap between the traditional medicine and the future medicine.

[Anti-inflammatory and anti-allergic effects of acidic fraction of Pheratima extract in asthma mice induced by ovalbumin].

OBJECTIVE: To explore the effects of acidic fraction of Pheratima extract in an ovalbumin (OVA) induced asthma mouse model, and to provide the experimental evidences for the anti-asthmatic application of Pheratima extract with further purification and development. METHOD: Mice model of allergic asthma was established through the OVA challenge. To investigate the inflammatory cell level and Th1/Th2 levels as well as the therapeutic effects of acidic fraction from Pheratima extract, cell count of bronchoalveolar lavage fluid (BALF) was performed to evaluate the secretion of eosinophils (EOS) cells, and IgE, IL-4, IL-5, IL-13, IFN-y levels were detected by ELISA. RESULT: Compared with control group, the EOS count of BALF in the model group was remarkably increased (P<0.01), and IgE, IL-4, IL-5, IL-13 levels were also increased (P<0.01), while IFN-gamma decreased (P<0.01). Acidic fraction from Pheratima (S) extract and its 30% ethanol washed fraction (S30) significantly inhibited the increase of EOS count (P<0.01), decreased the IgE, IL-4, IL-5, IL-13 levels (P<0.05), and inhibited the decrease of IFN-gamma level (P<0.01). CONCLUSION: The results indicate that inhibition of the EOS secretion and balancing of the altered Th1/Th2 levels may be important mechanisms of Pheratima's therapeutic effect in asthmatic mice model, and S30 is pharmacologically effective as evaluated with the above mentioned parameters, as a representative fraction of the Pheratima extract.

[Metabonomics, pharmaco-metabonomics, and the modernization of traditional Chinese medicine].

Facing the complicated life phenomemon, both metabonomics and pharmaco-metabonomics take an organic conception of the human body, which conforms to the way of thinking of traditional Chinese medicine (TCM). The application of metabonomics and pharmaco-metabonomics in the modernization of TCM will deepen the evaluation of the therapeutic effects of TCM, the study of intrinsic quality of TCM syndrome and the treatment by differentiation of syndrome, facilitate the integration of TCM with modern biological science and technology, promote the modernization of TCM, and provide a new space for the development of TCM.

[Application of metabonomics in complicated theory system research of traditional Chinese medicine].

Metabonomics, a new and rapid-developing technology, will be powerful means to the research of complexed theory system and modernization of traditional Chinese medicine (TCM). Discovery of biomarkers and analysis of common properties from the metabolome of a specific TCM syndrome will facilitate the modernized study of TCM system, promote the quantitative and scientific elucidation of TCM syndrome differentiation, provide an in-depth understanding of the TCM theory of Zang-xiang, help predict the disease on-set, and achieve a comprehensive evaluation of systemic clinical efficacy, safety and mechanism of action of the TCM combination formulas along with a better understanding of intestinal microflora ecology. The new approach with combined metabonomics and TCM methodologies will provide a new pathway and methodology for the study of complicated theory system of TCM and its modernization.