Abstract:Berberine is an important ingredient in a number of traditional Chinese medicines but has been shown to have poor bioavailability in the dog. The aim of this study was to use the P-glycoprotein (P-glycoprotein) inhibitors cyclosporin A, verapamil and the monoclonal antibody C219 in in vivo and in vitro models of intestinal absorption to determine the role of P-glycoprotein in berberine absorption. In the rat recirculating perfusion model, berberine absorption was improved 6-times by P-glycoprotein inhibitors. In the rat everted intestinal sac model, berberine serosal-to-mucosal transport was significantly decreased by cyclosporin A. In Ussing-type chambers, the rate of serosal-to-mucosal transport across rat ileum was 3-times greater than in the reverse direction and was significantly decreased by cyclosporin A. In Caco-2 cells, berberine uptake was significantly increased by P-glycoprotein inhibitors and by monoclonal antibody C219. Pglycoprotein appears to contribute to the poor intestinal absorption of berberine which suggests P-glycoprotein inhibitors could be of therapeutic value by improving its bioavailability.

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BackgroundThe effectiveness of ginseng in preventing and treating various central nervous system (CNS) diseases has been widely confirmed. However, ginsenosides, the principal components of ginseng, are characterized by poor accessibility to the brain, and this pharmacokinetic-pharmacological paradox remains poorly explained. Anti-inflammatory approaches are becoming promising therapeutic strategies for depression and other CNS diseases; however, previous studies have focused largely on anti-inflammatory therapies directed at the central nervous system. It is thus of interest to determine whether ginsenosides, characterized by poor brain distribution, are also effective in treating lipopolysaccharide- (LPS) induced depression-like behavior and neuroinflammation.MethodsIn an LPS-induced depression-like behavior model, the antidepressant effects of ginseng total saponins (GTS) were assessed using a forced swimming test, a tail suspension test, and a sucrose preference test. The anti-inflammatory efficacies of GTS in brain, plasma, and LPS-challenged RAW264.7 cells were validated using ELISA and quantitative real-time PCR. Moreover, indoleamine 2,3-dioxygenase (IDO) activity in the periphery and brain were also determined by measuring levels of kynurenine/tryptophan.ResultsGTS significantly attenuated LPS-induced depression-like behavior. Moreover, LPS-induced increases in 5-HT and tryptophane turnover in the brain were significantly reduced by GTS. IDO activities in brain and periphery were also suppressed after pretreatment with GTS. Furthermore, GTS-associated recovery from LPS-induced depression-like behavior was paralleled with reduced mRNA levels for IL-1β, IL-6, TNF-α, and IDO in hippocampus. Poor brain distribution of ginsenosides was confirmed in LPS-challenged mice. GTS treatment significantly decreased production of various proinflammatory cytokines in both LPS-challenged mice and RAW264.7 cells.ConclusionThis study suggests that the anti-depression efficacy of GTS may be largely attributable to its peripheral anti-inflammatory activity. Our study also strengthens an important notion that peripheral anti-inflammation strategies may be useful in the therapy of inflammation-related depression and possibly other CNS diseases.

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Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Colorectal adenomatous polyps are at high risk for the development of CRC. In this report, we described the metabolic changes in the sera from patients with colorectal polyps and CRC by using the NMR-based metabolomics. 110 serum samples were collected from patients and healthy controls, including 40 CRC patients, 32 colorectal polyp patients, and 38 healthy controls. The metabolic profiles and differential metabolites of sera were analyzed by multivariate statistical analysis (MSA), including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) methods. A total of 23 differential metabolites were identified from MSA. According to the pathway analysis and multivariate ROC curve-based exploratory analysis by using the relative concentrations of differential metabolites, we found abnormal metabolic pathways and potential biomarkers involved with the colorectal polyp and CRC. The results showed that the pyruvate metabolism and glycerolipid metabolism were activated in colorectal polyps. And the glycolysis and glycine, serine, and threonine metabolism were activated in CRC. The changed metabolism may promote cellular proliferation. In addition, we found that the rates of acetate/glycerol and lactate/citrate could be the potential biomarkers in colorectal polyp and CRC, respectively. The application of 1H-NMR metabolomics analysis in serum has interesting potential as a new detection and diagnostic tool for early diagnosis of CRC.

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With the development of photodynamic therapy (PDT), remarkable studies have been conducted to generate photosensitisers (PSs), especially porphyrin PSs. A variety of chemical modifications of the porphyrin skeleton have been introduced to improve cellular delivery, stability, and selectivity for cancerous tissues. This review aims to highlight the developments in porphyrin-based structural modifications, with a specific emphasis on the role of PDT in anticancer treatment and the design of PSs to achieve a synergistic effect on multiple targets.

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