Anti-Inflammatory Activities of a Chinese Herbal Formula IBS-20 In Vitro and In Vivo

Irritable bowel syndrome (IBS) is a functional bowel disorder and the etiology is not well understood. Currently there is no cure for IBS and no existing medication induces symptom relief in all patients. IBS-20 is a 20-herb Chinese medicinal formula that offers beneficial effects in patients with IBS; however, the underlying mechanisms are largely unknown. This study showed that IBS-20 potently inhibited LPS- or IFNΓ-stimulated expression of pro-inflammatory cytokines, as well as classically activated macrophage marker nitric oxide synthase 2. Similarly, IBS-20 or the component herb Coptis chinensis decreased LPS-stimulated pro-inflammatory cytokine secretion from JAWS II dendritic cells. IBS-20 or the component herbs also blocked or attenuated the IFNΓ-induced drop in transepithelial electric resistance, an index of permeability, in fully differentiated Caco-2 monolayer. Finally, the up-regulation of key inflammatory cytokines in inflamed colon from TNBS-treated mice was suppressed significantly by orally administrated IBS-20, including IFNΓ and IL-12p40. These data indicate that the anti-inflammatory activities of IBS-20 may contribute to the beneficial effects of the herbal extract in patients with IBS, providing a potential mechanism of action for IBS-20. In addition, IBS-20 may be a potential therapeutic agent against other Th1-dominant gut pathologies such as inflammatory bowel disease

Quality assurance for Chinese herbal formulae: standardization of IBS-20, a 20-herb preparation

<p>Abstract</p> <p>Background</p> <p>The employment of well characterized test samples prepared from authenticated, high quality medicinal plant materials is key to reproducible herbal research. The present study aims to demonstrate a quality assurance program covering the acquisition, botanical validation, chemical standardization and good manufacturing practices (GMP) production of IBS-20, a 20-herb Chinese herbal formula under study as a potential agent for the treatment of irritable bowel syndrome.</p> <p>Methods</p> <p>Purity and contaminant tests for the presence of toxic metals, pesticide residues, mycotoxins and microorganisms were performed. Qualitative chemical fingerprint analysis and quantitation of marker compounds of the herbs, as well as that of the IBS-20 formula was carried out with high-performance liquid chromatography (HPLC). Extraction and manufacture of the 20-herb formula were carried out under GMP. Chemical standardization was performed with liquid chromatography-mass spectrometry (LC-MS) analysis. Stability of the formula was monitored with HPLC in real time.</p> <p>Results</p> <p>Quality component herbs, purchased from a GMP supplier were botanically and chemically authenticated and quantitative HPLC profiles (fingerprints) of each component herb and of the composite formula were established. An aqueous extract of the mixture of the 20 herbs was prepared and formulated into IBS-20, which was chemically standardized by LC-MS, with 20 chemical compounds serving as reference markers. The stability of the formula was monitored and shown to be stable at room temperature.</p> <p>Conclusion</p> <p>A quality assurance program has been developed for the preparation of a standardized 20-herb formulation for use in the clinical studies for the treatment of irritable bowel syndrome (IBS). The procedures developed in the present study will serve as a protocol for other poly-herbal Chinese medicine studies.</p

Carotid Body AT4 Receptor Expression and its Upregulation in Chronic Hypoxia

Hypoxia regulates the local expression of angiotensin-generating system in the rat carotid body and the me-tabolite angiotensin IV (Ang IV) may be involved in the modulation of carotid body function. We tested the hypothesis that Ang IV-binding angiotensin AT4 receptors play a role in the adaptive change of the carotid body in hypoxia. The expression and localization of Ang IV-binding sites and AT4 receptors in the rat carotid bodies were studied with histochemistry. Specific fluorescein-labeled Ang IV binding sites and positive staining of AT4 immunoreactivity were mainly found in lobules in the carotid body. Double-labeling study showed the AT4 receptor was localized in glomus cells containing tyrosine hydroxylase, suggesting the expression in the chemosensitive cells. Intriguingly, the Ang IV-binding and AT4 immunoreactivity were more intense in the carotid body of chronically hypoxic (CH) rats (breathing 10% oxygen for 4 weeks) than the normoxic (Nx) control. Also, the protein level of AT4 receptor was doubled in the CH comparing with the Nx group, supporting an upregulation of the expression in hypoxia. To examine if Ang IV induces intracellular Ca2+ response in the carotid body, cytosolic calcium ([Ca2+]i) was measured by spectrofluorimetry in fura-2-loaded glomus cells dissociated from CH and Nx carotid bodies. Exogenous Ang IV elevated [Ca2+]i in the glomus cells and the Ang IV response was significantly greater in the CH than the Nx group. Hence, hypoxia induces an upregulation of the expression of AT4 receptors in the glomus cells of the carotid body with an increase in the Ang IV-induced [Ca2+]i elevation. This may be an additional pathway enhancing the Ang II action for the activation of chemoreflex in the hypoxic response during chronic hypoxia

Impact of the Herbal Medicine Sophora flavescens on the Oral Pharmacokinetics of Indinavir in Rats: The Involvement of CYP3A and P-Glycoprotein

Sophora flavescens is a Chinese medicinal herb used for the treatment of gastrointestinal hemorrhage, skin diseases, pyretic stranguria and viral hepatitis. In this study the herb-drug interactions between S. flavescens and indinavir, a protease inhibitor for HIV treatment, were evaluated in rats. Concomitant oral administration of Sophora extract (0.158 g/kg or 0.63 g/kg, p.o.) and indinavir (40 mg/kg, p.o.) in rats twice a day for 7 days resulted in a dose-dependent decrease of plasma indinavir concentrations, with 55%–83% decrease in AUC0-∞ and 38%–78% reduction in Cmax. The CL (Clearance)/F (fraction of dose available in the systemic circulation) increased up to 7.4-fold in Sophora-treated rats. Oxymatrine treatment (45 mg/kg, p.o.) also decreased indinavir concentrations, while the ethyl acetate fraction of Sophora extract had no effect. Urinary indinavir (24-h) was reduced, while the fraction of indinavir in faeces was increased after Sophora treatment. Compared to the controls, multiple dosing of Sophora extract elevated both mRNA and protein levels of P-gp in the small intestine and liver. In addition, Sophora treatment increased intestinal and hepatic mRNA expression of CYP3A1, but had less effect on CYP3A2 expression. Although protein levels of CYP3A1 and CYP3A2 were not altered by Sophora treatment, hepatic CYP3A activity increased in the Sophora-treated rats. All available data demonstrated that Sophora flavescens reduced plasma indinavir concentration after multiple concomitant doses, possibly through hepatic CYP3A activity and induction of intestinal and hepatic P-gp. The animal study would be useful for predicting potential interactions between natural products and oral pharmaceutics and understanding the mechanisms prior to human studies. Results in the current study suggest that patients using indinavir might be cautioned in the use of S. flavescens extract or Sophora-derived products

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Antioxidant mechanisms of schisandrin B in protecting against carbon tetrachloride hepatotoxicity

Previous studies have demonstrated the hepatoprotective effect of Schisandrin B (Sch B) against carbon tetrachloride (CCl4) toxicity. Recently, many studies have attributed the protective effect of Sch B to its free radical scavenging activity. Preliminary studies in our laboratory showed that the scavenging activity was not sufficient to explain the hepatoprotection produced by Sch B treatment. Therefore, a detailed investigation is necessary in order to define the protective mechanisms of Sch B treatment. Using CCl4-induced toxicity as a model of free radical-mediated hepatocellular damage, our results showed that the hepatoprotection produced by Sch B pretreatment may be due to (1) an increase in reduced glutathione (GSH) levels in hepatic tissue and mitochondria; (2) an increase in hepatic ascorbate concentration; (3) an enhancement in glutathione-S-transferase activity and (4) inhibition of CCl4 metabolism. A comparative study of Sch B with butylated hydroxytoluene, a synthetic phenolic antioxidant, suggested that the increase in hepatic GSH might be a crucial factor in producing the protection. Studies on the hepatoprotective effect of various Schisandrins suggested that both enhancement of hepatic glutathione status and inhibition of CCl4 metabolism were involved in the protective action of Sch B treatment. However, the enhancement of hepatic glutathione status was more important for hepatoprotection. Treating mice with 1,3-bis(2-chloroethyl)- 1 -nitrosourea (BCNU), a specific inhibitor of glutathione reductase, decreased hepatic glutathione reductase activity as well as GSH concentration. However, BCNU treatment could not completely abrogate the hepatoprotective action of Sch B in CCl4-treated mice. A compensatory increase in hepatic ascorbate concentration by BCNU treatment in Sch B-pretreated mice suggested that the hepatoprotective effect of Sch B treatment may be attributed to the enhancement in the functioning of an integrated antioxidant system. This concept was supported by the protection produced by Sch B pretreatment against hepatocellular damage induced by different chemical toxicants

Prooxidant and antioxidant effects of trolox on ferric ion-induced oxidation of erythrocyte membrane lipids

The prooxidant and antioxidant actions of Trolox were examined in an in vitro system measuring ferric ion-induced oxidation of erythrocyte membrane lipids. Trolox was found to produce a concentration-dependent biphasic effect on the ferric ion-stimulated lipid peroxidation, with the mode of action being similar to those produced by reducing-agent antioxidants, such as ascorbic acid and reduced glutathione, and iron chelator, such as desferrioxamine. Phytic acid, a potent iron chelator, could suppress the prooxidant actions of Trolox and desferrioxamine, but not those of ascorbic acid and reduced glutathione. The ability of Trolox to stimulate ferric ion- catalyzed ascorbate oxidation, as similar to the action produced by ethylenediaminetetraacetic acid, indicates the presence of iron-chelating activity. The ensemble of results suggests the possible involvement of iron chelation in the prooxidant action of Trolox in ferric ion-stimulated lipid peroxidation reactions

Application of Complementary and Alternative Medicine on Neurodegenerative Disorders 2013

Editoria