Preventive effect of baicalein on methamphetamine-induced amnesia in the passive avoidance test in mice.

BACKGROUND/AIMS: Methamphetamine abuse may produce cognitive impairment. Baicalein, a bioactive flavonoid, has antioxidative, anti-inflammatory and neuroprotective effects. This study examined the effects of baicalein pretreatment on memory performance in the passive avoidance test after either one dose or an acute binge of methamphetamine in Institute of Cancer Research (ICR) mice. METHODS: Methamphetamine was administered by intraperitoneal (i.p.) injection of either one dose (3 mg/kg) or an acute binge (3 mg/kg, 4 i.p. injections at 2-hour intervals). The effects of baicalein pretreatment (1 mg/kg, i.p.) on methamphetamine-induced changes of locomotor activity and memory performance were compared with those of eticlopride, a selective dopamine D2 receptor antagonist. The effects of baicalein on acute binge methamphetamine-induced oxidative stress (malondialdehyde- and nitrotyrosine-modified protein production) in the mouse hippocampus were also examined. RESULTS: One-dose methamphetamine treatment (i.p., 30 min before or immediately after the training trial) induced hyperlocomotion and amnesia in mice, which were blocked by eticlopride but not by baicalein pretreatment. The memory performance in mice was impaired 5 days after acute binge methamphetamine, which was significantly attenuated by baicalein but not by eticlopride pretreatment. Baicalein pretreatment also attenuated acute binge methamphetamine-induced oxidative stress in the mouse hippocampus. CONCLUSIONS: Baicalein exhibits antioxidative and neuroprotective effects in attenuating acute binge methamphetamine-induced memory deficits and oxidative hippocampal damage.

Recent research and development of Antrodia cinnamomea.

Medicinal mushrooms have attracted much attention recently owing to their potent therapeutic activity, especially as chemopreventive and immunomodulatory agents. Antrodia cinnamomea is a treasured Taiwanese mushroom that has been used by aboriginal tribes for centuries to treat food intoxication and to enhance liver functions. It was included in Asian folk medicine in the last few decades with remarkable results in treating inflammatory disorders, cancers, hypertension and hepatitis. This myriad of therapeutic activities encouraged several research groups to subject A. cinnamomea to intensive biological and phytochemical investigation, leading to the isolation of different classes of pharmacologically active secondary metabolites. The in vitro and in vivo biological results of the mushroom extracts and its active components revealed their potent cytotoxic, anti-inflammatory and hepatoprotective activities. The aim of this study is to review recent reports on the biological activities of A. cinnamomea extracts and its active components; quality control protocols; synthetic methodologies for the preparation of active components; developed culture techniques; phylogenetic analysis and gene cloning. This study also tackles major challenges facing future expansion of A. cinnamomea production.

Antileukemia component, dehydroeburicoic acid from Antrodia camphorata induces DNA damage and apoptosis in vitro and in vivo models.

Antrodia camphorata (AC) is a native Taiwanese mushroom which is used in Asian folk medicine as a chemopreventive agent. The triterpenoid-rich fraction (FEA) was obtained from the ethanolic extract of AC and characterized by high performance liquid chromatography (HPLC). FEA caused DNA damage in leukemia HL 60 cells which was characterized by phosphorylation of H2A.X and Chk2. It also exhibited apoptotic effect which was correlated to the enhancement of PARP cleavage and to the activation of caspase 3. Five major triterpenoids, antcin K (1), antcin C (2), zhankuic acid C (3), zhankuic acid A (4), and dehydroeburicoic acid (5) were isolated from FEA. The cytotoxicity of FEA major components (1-5) was investigated showing that dehydroeburicoic acid (DeEA) was the most potent cytotoxic component. DeEA activated DNA damage and apoptosis biomarkers similar to FEA and also inhibited topoisomerase II. In HL 60 cells xenograft animal model, DeEA treatment resulted in a marked decrease of tumor weight and size without any significant decrease in mice body weights. Taken together, our results provided the first evidence that pure AC component inhibited tumor growth in vivo model backing the traditional anticancer use of AC in Asian countries.

Anti-inflammatory and anti-infectious effects of Evodia rutaecarpa (Wuzhuyu) and its major bioactive components.

This article reviews the anti-inflammatory relative and anti-infectious effects of Evodia rutaecarpa and its major bioactive components and the involvement of the nitric oxide synthases, cyclooxygenase, NADPH oxidase, nuclear factor kappa B, hypoxia-inducible factor 1 alpha, reactive oxygen species, prostaglandins, tumor necrosis factor, LIGHT, amyloid protein and orexigenic neuropeptides. Their potential applications for the treatment of endotoxaemia, obesity, diabetes, Alzheimer's disease and their uses as cardiovascular and gastrointestinal protective agents, analgesics, anti-oxidant, anti-atherosclerosis agents, dermatological agents and anti-infectious agents are highlighted. Stimulation of calcitonin gene-related peptide release may partially explain the analgesic, cardiovascular and gastrointestinal protective, anti-obese activities of Evodia rutaecarpa and its major bioactive components.

[Chemical principles and bioactivities of blueberry].

The bioactive principles contained in blueberries (Vaccinium) are various kind of anthocyanins (anthocyanidins, or phenolic aglycone, conjugated with sugar), chlorogenic acid, flavonids, alpha-linolenic acid, pterostilbene, resveratrol, and vitamins. After oral administration, anthocyanins can pass through blood-brain barrier and thus appear in various organs and brain. Improve visual function by increasing rhodopsin regeneration and ocular health is the earliest reported bioactivities of anthocyanin. Recent studies demonstrated the benefit of blueberries to prevent the age-related chronic diseases such as cancer, diabeties, hyperlipidemia, hypertension, neurodegeneration, obesity, and osteoporosis through its apoptosis, antioxidant, antiinflammation, and antiangiogenesis effects. Blueberries can eradicate microorganisms for the prevention of symptomatic urinary tract infections in women. Thus, blueberries are recognized as one of the most nutritious foods and cultivated worldwide. However, how to prolong the shelving time of fresh fruit, well utilize the leaf and stem to isolate the bioactive chemicals, improve quality consistency of juicy and dry products, all should be further concerned.

Comparison of the pharmacological effects of Panax ginseng and Panax quinquefolium.

Medical application of Panax ginseng was first found in "Shen-Nong Herbal Classic"around 200 AD Panax quinquefolium was first introduced in "Essential of Materia Medica" in 1694 in China. The most important bioactive components contained in P ginseng and P quinquefolium are ginseng saponins (GS). The contents of ginsenoside Rb1, Re, and Rd in P quinquefolium are higher than they are in P ginseng. In P ginseng, the contents of Rg1,Rb2, and Rc are higher than they are in P quinquefolium. P ginseng had a higher ratio of Rg1: Rb1, and which was lower in P quinquefolium. After steaming for several hours, the total GS will decrease. However, some ginsenosides (Rg2, 20R-Rg2, Rg3, Rh1 and Rh2) increase, while others (Rb1, Rb2, Rb3, Rc, Rd, Re, and Rg1) decrease. However, variation, especially in P quinquefolium, is high. P ginseng and P quinquefolium are general tonics and adaptogens. Rg1 and Rb1 enhance central nervous system (CNS) activities, but the effect of the latter is weaker. Thus, for the higher contents of Rg1, P ginseng is a stimulant, whereas the Rb1 contents of P quinquefolium are mainly calming to the CNS. Re, Rg1, panaxan A and B from P ginseng are good for diabetes. Re and Rg1 enhance angiogenesis, whereas Rb1, Rg3 and Rh2 inhibit it. Rh2, an antitumor agent, can be obtained from Rb1 by steaming. The content of Re in P quinquefolium are higher than in P ginseng by 3-4 times. The vasorelax, antioxidant, antihyperlipidemic, and angiogenic effects of Re are reported. Thus, for the CNS "hot," wound healing and hypoglycemic effects, P ginseng is better than P quinquefolium. For anticancer effects, P quinquefolium is better.

Tournefolic acid B attenuates amyloid beta protein-mediated toxicity by abrogating the calcium overload in mitochondria and retarding the caspase 8-truncated Bid-cytochrome c pathway in rat cortical neurons.

The effect of tournefolic acid B (TAB) on amyloid beta protein-mediated neurotoxicity and the underlying mechanisms were investigated. Amyloid beta protein 25-35 elicited neuronal death as determined by calcein/ethidium homodimer-1 staining. 10 microM amyloid beta protein 25-35 caused cell death at a level of 41.5+/-3.8% by MTT reduction. 50 microM TAB attenuated the amyloid beta protein 25-35-induced cell death by 49.7+/-11.1%. TAB also abrogated amyloid beta protein-induced activation of caspases 8 and 9 by about 50-60%. Furthermore, TAB significantly diminished the amyloid beta protein 25-35-induced elevation of calcium level in mitochondria, whereas it did not affect the calcium level in cytosol or endoplasmic reticulum. TAB markedly retarded the amyloid beta protein-mediated release of cytochrome c from mitochondria. Amyloid beta protein 25-35 elevated mitochondrial truncated BH3 interacting domain death agonist (tBid) and decreased the level of B-cell leukemia/lymphoma-2alpha (Bcl-2alpha) in mitochondria. Moreover, amyloid beta protein induced a slight up-regulation of Bcl-2 agonist killer 1 (Bak) in cytosol. 50 microM TAB decreased the amyloid beta protein-induced elevation of mitochondrial tBid and the level of Bak, whereas it did not affect the amyloid beta protein-mediated decrease in mitochondrial Bcl-2alpha. Caspase 8 inhibitor significantly inhibited the amyloid beta protein-mediated increase in mitochondrial tBid and the release of cytochrome c. Therefore, TAB blocked the overload of calcium in mitochondria and impaired the amyloid beta protein-mediated activation of the caspase 8-tBid-cytochrome c pathway, thereby conferring its neuroprotective effects on amyloid beta protein-mediated neurotoxicity.

Chinese herb Radix Polygoni Multiflori as a therapeutic drug for liver cirrhosis in mice.

Liver regeneration not only plays a functional role in directing the restoration of liver mass after resection or injury, but also may have participated in effective therapy of liver cirrhosis. Additionally, hepatocyte growth factor (HGF) appears to be a factor of great importance in liver regeneration and attenuated progression of experimental liver cirrhosis. The aim of this study is to use Radix Polygoni Multiflori (POMU) extract, a Chinese herb traditionally used for liver-protective therapy, as a reagent for the evaluation of its potential medicinal use in liver cirrhosis. We used in vitro coculture system to show that POMU could promote the expression of HGF by hepatic nonparenchymal cells, consequently the proliferation of primary liver cells and phagocytic activity of Kupffer cells using fluorescein-labeled Escherichia coli as the target, and inhibit the proliferation of stellate cells. Using dimethylnitrosamine-induced liver cirrhosis animal, POMU even at 20 mg/(kg day) dosage, was illustrated to reverse the pathogenic progression of the disease, decrease the hydroxyproline content and increases the expression of HGF messenger RNA in liver tissue. The survival rate was significantly increased in the POMU-treated animal. In conclusion, our study showed the promise of POMU in the medicinal use for the treatment of liver cirrhosis.

(S)-armepavine inhibits human peripheral blood mononuclear cell activation by regulating Itk and PLCgamma activation in a PI-3K-dependent manner.

Chinese herbs are useful edible and medicinal plants for their immune modulatory functions. We have proven that (S)-armepavine (C19H23O3N; MW313) from Nelumbo nucifera inhibits the proliferation of human PBMCs activated with PHA and improves autoimmune diseases in MRL/MpJ-lpr/lpr mice. In the present study, the pharmacological activities of (S)-armepavine were evaluated in PHA-activated PBMCs. The results showed that (S)-armepavine suppressed PHA-induced PBMC proliferation and genes expression of IL-2 and IFN-gamma without direct cytotoxicity. Inhibition of NF-AT and NF-kappaB activation suggested phospholipase Cgamma (PLCgamma)-mediated Ca2+ mobilization and protein kinase C activation were blocked by (S)-armepavine. Phosphorylation of PLCgamma is regulated by lymphocyte-specific kinase (Lck), ZAP-70, and IL-2-inducible T cell kinase (Itk). We found (S)-armepavine inhibited PHA-induced phosphorylation of Itk and PLCgamma efficiently but did not influence Lck or ZAP-70 phosphorylation. In addition, ZAP-70-mediated pathways, such as the association of linker for activation of T cells with PLCgamma and activation of ERK, were also intact in the presence of (S)-armepavine. Finally, reduction of phosphoinositide 3,4,5-trisphosphate formation and Akt phosphorylation suggested that (S)-armepavine inhibited Itk, and PLCgamma phosphorylation might be a result of the influence of PI-3K activation. Addition of exogenous IL-2 or PMA/A23187 rescued PBMC proliferation in the presence of (S)-armepavine. Therefore, we concluded that (S)-armepavine inhibited PHA-induced cell proliferation and cytokine production in a major way by blocking membrane-proximal effectors such as Itk and PLCgamma in a PI-3K-dependent manner.

Anti-inflammatory effects and mechanisms of the ethanol extract of Evodia rutaecarpa and its bioactive components on neutrophils and microglial cells.

Evodia rutaecarpa is commonly used as an anti-inflammatory drug in traditional Chinese medicine. We previously identified four bioactive compounds (dehydroevodiamine (I), evodiamine (II), rutaecarpine (III), and synephrine (IV)) from the ethanol extract of E. rutaecarpa, but their effects and mechanism(s) of action remain unclear. To study the anti-inflammatory potential and the possible underlying mechanism(s), their effects on phorbol-12-myristate-13-acetate (PMA)- and N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced reactive oxygen species production in neutrophils was studied, as well as lipopolysaccharide (LPS)-induced nitric oxide (NO) production and inducible NO synthetase (iNOS) expression in microglial cells. The ethanol extract of E. rutaecarpa displayed potent antioxidative effects against both PMA- and fMLP-induced reactive oxygen species production in neutrophils (with IC50 values of around 2.7-3.3 microg/ml). Although less potent than the ethanol extract of E. rutaecarpa, compounds I-IV all concentration-dependently inhibited PMA- and fMLP-induced reactive oxygen species production, with compound IV consistently being the most potent agent among these active components. The antioxidative effects of the ethanol extract of E. rutaecarpa and these compounds were partially due to inhibition (10%-33%) of NADPH oxidase activity, a predominant reactive oxygen species-producing enzyme in neutrophils, and to a minor extent to their direct radical-scavenging properties. The ethanol extract of E. rutaecarpa also inhibited LPS-induced NO production (with an IC50 of around 0.8 microg/ml) and iNOS upregulation in microglial cells that was partially mimicked by compounds I, II, and III, but not compound IV. Our results suggest that the ethanol extract of E. rutaecarpa and its four bioactive components all exhibited anti-inflammatory activities which could be partially explained by their different potentials for inhibiting NADPH oxidase-dependent reactive oxygen species and/or iNOS-dependent NO production in activated inflammatory cells.

Lipopolysaccharide-stimulated responses in rat aortic endothelial cells by a systems biology approach.

The vascular endothelium plays an important role in regulating immune and inflammatory responses to resist pathogens infection. Although it has been known that lipopolysaccharide (LPS) is a critical inducer of sepsis or endotoxemia, the systematic responses of LPS-stimulation in endothelial cells (ECs) are still unclear. The present study aims to analyze the late-phase responses of LPS-induced rat aortic ECs by using systematic biology approaches, including rat cDNA microarray, 2-DE and MALDI-TOF MS/MS, and cytokine protein array. Furthermore, to improve the efficiency of analysis of the bulk systematic data of rat, we designed a set of bioinformatic tools to convert and integrate these rat data into the corresponding human genes or proteins IDs based on BioCarta, KEGG, and Gene Ontology databases. Using the systematic analysis, it was shown that LPS could promote some signaling or metabolic pathways as well as pathophysiologic phenomena of proliferation, atherogenesis, inflammation, and apoptosis through activated nuclear factor-kappaB pathway in ECs. Interestingly, ECs also activated the mediators of anti-inflammation, antiapoptosis, and antioxidation to protect themselves. Moreover, the expressions of altered genes, proteins, and their involvement in the hypothetical signaling pathway can provide further understanding of inflammation associated responses in ECs.

Chemical and biological comparisons on Evodia with two related species of different locations and conditions.

Evodia rutaecarpa (ER) and Tetradium glabrifolium (TG) are closely related species collected from different locations, with processed versus unprocessed and fresh versus 1-year-old samples. The purpose of this study is to determine the variability of their bioactive constituents; evodiamine, dehydroevodiamine, rutaecarpine and synephrine--as well as their relaxing effects on an isolated rat aortas and uterus using the extracts of the test specimens. The vasorelaxation was greater in ER from Taiwan than from China in spite of lower levels of the relaxing alkaloids evodiamine, dehydroevodiamine and rutaecarpine. On the other hand, the uterine relaxation of ER from China was better than the one from Taiwan, even though constricting synephrine was only contained in Chinese ER. After processing, the relaxation of ER from China in the uterus was increased while the vasorelaxation remained unchanged. Conversely, TG from Wu-ling contained more relaxing alkaloids than that from Lee Mountain. However, the relaxation in both the uterus and the aorta was less in TG from Wu-ling. After 1 year of storage, the vasorelaxation of TG from Lee Mountain was not changed. Taken together, a significant finding in the present study is the lack of correction between chemical composition and relaxing activities. This strongly supports our assumption that biological function evaluations, instead of chemical standardization, is the more adequate way of showing meaningful consistency of natural preparations.

Elimination of rutaecarpine and its metabolites in rat feces and urine measured by liquid chromatography.

Rutaecarpine is an alkaloid isolated from the medicinal herb Evodia rutaecarpa. This study was to evaluate the elimination pathway of rutaecarpine in rat feces and urine. Rutaecarpine and its metabolites (3-, 10-, 11- and 12-hydroxyrutaecarpine) in urine were measured after incubation with beta-glucuronidase. After the rutaecarpine was administered (25 and 100 mg/kg) orally to rats, the urine and fecal samples were collected using a metabolic cage for five consecutive days. For determining rutaecarpine, the mobile phase consisted of acetontrile-10 mM NaH(2)PO(4) (60:40, v/v, pH 4.2 adjusted with orthophosphoric acid) with a flow rate of 1 mL/min. The calibration curve was linear in concentrations of 0.05-50 microg/mL in fecal and urine sample. The results indicated that more than 42% of the rutaecarpine was excreted by feces after oral administration (25 and 100 mg/kg), but only a small amount of rutaecarpine was detected in urine at a higher dose of rutaecarpine (100 mg/kg). After incubation with beta-glucuronidase, the hydroxyrutaecarpine in urine was eluted using methanol-acetonitrile-0.04% formic acid (6:30:64, v/v) with a flow rate of 1.2 mL/min. We conclude that the metabolic pathway of rutaecarpine went through phase I hydroxylation and phase II conjugation, and the major metabolite is 10-hydroxyrutaecarpine eliminated from urine of the rat.

Comparative evaluation of FET and FDG for differentiating lung carcinoma from inflammation in mice.

BACKGROUND: Clinical FDG/PET (2-deoxy-2-18F-fluoro-D-glucose/positron emission tomography) studies encounter difficulties in detecting early stage lung cancers. The aim of this study was to evaluate the ability of O-2-18F-fluoroethyl-L-tyrosine (FET) and FDG to differentiate between inflammation and lung carcinoma in mice. MATERIALS AND METHODS: Sixty-four C57BL/6 mice were inoculated with 2x10(6) LLC1 lung carcinoma cells in the right hind flank on day 0 and were then injected with 0.1 mL turpentine in the left thigh muscle on day 3. The progress of inflammation and tumor in mice was longitudinally monitored by FDG/microPET. The biodistribution study, pharmacokinetic evaluation and whole-body autoradiography of FET and FDG were performed on day 8 after tumor inoculation. RESULTS: The FDG uptakes in tumor and inflammatory lesions were 4.42-fold and 3.53-fold (n = 4) higher, respectively, than that in muscle at 90 min post-injection and the tumor-to-inflammation ratio was 1.25. For FET/microPET, the tumor uptake was 2.07-fold and 2.07-fold (n = 4) higher than those in muscle and inflammatory lesions at 90 min post-injection, respectively. The distribution half-life (t1/2,alpha) and the elimination half-life (t1/2,beta) of FET were 39 min and 205 min, respectively, in mice. CONCLUSION: FDG delineated both tumor and inflammation, while FET accumulated in tumor to a significantly higher extent. Our results demonstrated the potential of FET to distinguish epidermoid lung carcinoma from inflammatory lesions in mice.

Oxidative metabolism of the alkaloid rutaecarpine by human cytochrome P450.

Rutaecarpine is the main active alkaloid of the herbal medicine, Evodia rutaecarpa. To identify the major human cytochrome P450 (P450) participating in rutaecarpine oxidative metabolism, human liver microsomes and bacteria-expressed recombinant human P450 were studied. In liver microsomes, rutaecarpine was oxidized to 10-, 11-, 12-, and 3-hydroxyrutaecarpine. Microsomal 10- and 3-hydroxylation activities were strongly inhibited by ketoconazole. The 11- and 12-hydroxylation activities were inhibited by alpha-naphthoflavone, quinidine, and ketoconazole. These results indicated that multiple hepatic P450s including CYP1A2, CYP2D6, and CYP3A4 participate in rutaecarpine hydroxylations. Among recombinant P450s, CYP1A1 had the highest rutaecarpine hydroxylation activity. Decreased metabolite formation at high substrate concentration indicated that there was substrate inhibition of CYP1A1- and CYP1A2-catalyzed hydroxylations. CYP1A1-catalyzed rutaecarpine hydroxylations had V(max) values of 1,388 to approximately 1,893 pmol/min/nmol P450, K(m) values of 4.1 to approximately 9.5 microM, and K(i) values of 45 to approximately 103 microM. These results indicated that more than one molecule of rutaecarpine is accessible to the CYP1A active site. The major metabolite 10-hydroxyrutaecarpine decreased CYP1A1, CYP1A2, and CYP1B1 activities with respective IC(50) values of 2.56 +/- 0.04, 2.57 +/- 0.11, and 0.09 +/- 0.01 microM, suggesting that product inhibition might occur during rutaecarpine hydroxylation. The metabolite profile and kinetic properties of rutaecarpine hydroxylation by human P450s provide important information relevant to the clinical application of rutaecarpine and E. rutaecarpa.

Longitudinal evaluation of tumor metastasis by an FDG-microPet/microCT dual-imaging modality in a lung carcinoma-bearing mouse model.

BACKGROUND: Histological methods are used to define the growth and response to various treatments of lung carcinoma in mice. The aim of the study was to evaluate a quantitative and 3D-tomographic microPET/microCT dual-image modality using 18F-fluorodeoxyglucose (FDG) to monitor the tumor progression in an experimental metastasis mouse model. MATERIALS AND METHODS: Six normal mice were subjected to FDG-microPET/microCT image scan to present the normal thorax morphology. Twenty-one 8-week-old male C57BL/6 mice were inoculated with 1 x 10(6) Lewis lung carcinoma cells (LLC1) through the lateral tail vein. FDG-microPET/microCT scans were performed on days 0, 5, 9, 13 and 18 (n=6) to monitor the growth of the tumor. MicroPET and microCT images were further used to monitor the metastasis of the lung carcinoma to the liver. Fifteen mice were sacrificed for biodistribution on days 0, 5, 9, 13 and 18 after the inoculation of lung carcinoma cells. RESULTS: The FDG-microPET/microCT dual-image modality showed that the growth of the tumor could be monitored longitudinally. The standard uptake value (SUV) of FDG increased from 0.63 +/- 0.05 on day 0 to 1.03 +/- 0.15 on day 18, reflecting the growth of the tumor in mice. The tumors located in the lung and liver could be clearly visualized by the fusion of microPET and microCT images, and further confirmed by whole-body autoradiography or H&E stain. CONCLUSION: By FDG-microPET, the increase in SUV provided an alternative for assessing the growth of a tumor in vivo. Our results suggest that the growth progression of lung carcinoma can be identified using the FDG-microPET/microCT dual-image modality longitudinally in mice.

Inhibition of (S)-armepavine from Nelumbo nucifera on autoimmune disease of MRL/MpJ-lpr/lpr mice.

T cell immune responses play important roles in the pathogenesis of systemic lupus erythematosus (SLE). (S)-Armepavine (C19H23O3N; MW313) from Nelumbo nucifera suppresses T cells proliferation. To study its potential benefit on SLE, we examined effects of (S)-armepavine on MRL/MpJ-lpr/lpr mice, which have similar disease features to human SLE. MRL/MpJ-lpr/lpr mice were treated orally with (S)-armepavine for 6 weeks and their SLE characteristics were evaluated. The results revealed that (S)-armepavine prevented lymphadenopathy and elongated life span of MRL/MpJ-lpr/lpr mice. It seemed to be mediated by inhibition of splenocytes proliferation, suppression of interleukin-2 (IL-2), interleukin-4, interleukin-10, and interferon-gamma (IFN-gamma) gene expressions, reduction of glomerular hypercellularity and immune complexes deposition, and decrease of urinary protein and anti-double stranded DNA autoantibody production. Furthermore, the data demonstrated (S)-armepavine impaired IL-2 and IFN-gamma transcripts in human peripheral blood mononuclear cells. We suggest that (S)-armepavine may be an immunomodulator for the management of autoimmune diseases like SLE.

Taxifolin ameliorates cerebral ischemia-reperfusion injury in rats through its anti-oxidative effect and modulation of NF-kappa B activation.

Infarction in adult rat brain was induced by middle cerebral arterial occlusion (MCAO) followed by reperfusion to examine whether taxifolin could reduce cerebral ischemic reperfusion (CI/R) injury. Taxifolin administration (0.1 and 1.0 microg/kg, i.v.) 60 min after MCAO ameliorated infarction (by 42%+/-7% and 62%+/-6%, respectively), which was accompanied by a dramatic reduction in malondialdehyde and nitrotyrosine adduct formation, two markers for oxidative tissue damage. Overproduction of reactive oxygen species (ROS) and nitric oxide (NO) via oxidative enzymes (e.g., COX-2 and iNOS) was responsible for this oxidative damage. Taxifolin inhibited leukocyte infiltration, and COX-2 and iNOS expressions in CI/R-injured brain. Taxifolin also prevented Mac-1 and ICAM-1 expression, two key counter-receptors involved in firm adhesion/transmigration of leukocytes to the endothelium, which partially accounted for the limited leukocyte infiltration. ROS, generated by leukocytes and microglial cells, activated nuclear factor-kappa B (NF-kappaB) that in turn signaled up-regulation of inflammatory proteins. NF-kappaB activity in CI/R was enhanced 2.5-fold over that of sham group and was inhibited by taxifolin. Production of both ROS and NO by leukocytes and microglial cells was significantly antagonized by taxifolin. These data suggest that amelioration of CI/R injury by taxifolin may be attributed to its anti-oxidative effect, which in turn modulates NF-kappaB activation that mediates CI/R injury.

Identification of the microsomal oxidation metabolites of rutaecarpine, a main active alkaloid of the medicinal herb Evodia rutaecarpa.

Rutaecarpine is a quinazolinocarboline alkaloid of the medicinal herb Evodia rutaecarpa and shows a variety of pharmacological effects. Four oxidation metabolites of rutaecarpine were prepared from 3-methylcholanthrene-treated rat liver microsomes. These metabolites had an [M + H]+ ion at m/z 304. The structures of metabolites were identified by comparison of their liquid chromatograms and mass, absorbance, and 1H NMR spectra with those of synthetic standards. Rutaecarpine was metabolized by microsomal enzymes to form 3-, 10-, 11-, and 12-hydroxyrutaecarpine. The formation of 10-hydroxyrutaecarpine was highly induced by a cytochrome P450 1A inducer, 3-methylcholanthrene.