Impact of Annual Exposure to Polycyclic Aromatic Hydrocarbons on Acute Exacerbation Frequency in Asthmatic Patients.

PURPOSE: Exposure to polycyclic aromatic hydrocarbons (PAHs) associated with ambient air particulate matter (PM) poses significant health concerns. Increased acute exacerbation (AE) frequency in asthmatic patients has been associated with ambient PAHs, but which subgroup of patients are particularly susceptible to ambient PAHs is uncertain. We developed a new model to simulate grid-scale PM2.5-PAH levels in order to evaluate whether the severity of asthma as measured by the Global Initiative of Asthma (GINA) levels of treatment is related to cumulative exposure of ambient PAHs. METHODS: Patients with asthma residing in the northern Taiwan were reviewed retrospectively from 2014 to 2017. PM2.5 were sampled and analysed for PAHs twice a month over a 72-hour period, in addition to collecting the routinely monitored air pollutant data from an established air quality monitoring network. In combination with correlation analysis and principal component analysis, multivariate linear regression models were performed to simulate hourly grid-scale PM2.5-PAH concentrations (ng/m3). A geographic information system mapping approach with ordinary kriging interpolation method was used to calculate the annual exposure of PAHs (ng/m). RESULTS: Among the 387 patients with asthma aged 18 to 93 (median 62), 97 subjects were treated as GINA step 5 (24%). Asthmatics in GINA 5 subgroup with high annual PAHs exposure were likely to have a higher annual frequency of any AE (1 (0-12), p<0.0001). Annual PAHs exposure was correlated with the annual frequency of any exacerbation (r=0.11, p=0.02). This was more significant in the GINA 5 subgroup (r=0.29, p=0.005) and in the GINA 5 subgroup with severe acute exacerbations (r=0.51, p=0.002). Annual PAHs exposure, severe acute exacerbation and GINA steps were independent variables that predict annual frequency of any exacerbation. CONCLUSION: Asthmatic patients in the GINA 5 subgroup with acute exacerbations were more susceptible to the effect of environmental PAHs on their exacerbation frequency. Reducing environmental levels of PAHs will have the greatest impact on the more severe asthma patients.

Temporal and vertical variations of polycyclic aromatic hydrocarbon at low elevations in an industrial city of southern Taiwan.

Considered that human activities mostly occur below building heights, the objective of this study was to investigate the temporal variations of fine particular matter (PM2.5)-associated polycyclic aromatic hydrocarbons (PAHs) and benzo[a]pyrene-equivalent (BaPeq) concentrations at four different elevations (6.1, 12.4, 18.4, and 27.1 m) in Kaohsiung City, the largest industrial city of southern Taiwan. Temperature variation was critical for the PM2.5-associated PAH concentrations, which were dominated by benzo[g,h,i]perylene (0.27 ± 0.04 ng m-3 and 24.43% of the total concentration) and other high molecular weight (HMW) species. The PM2.5-associated BaPeq was dominated by 5-ring PAH (36.09%). The PM2.5-associated PAH and BaPeq concentrations at all elevations were significantly increased in winter. In the night, the correlations between the PM2.5-associated PAH concentrations and atmospheric temperatures became negatively stronger, notably at lower elevations (r = - 0.73 ~ - 0.86), whereas the BaPeq during daytime and nighttime were not changed significantly in most months. The PAHs analysis with different PM sizes demonstrated the importance of smaller particles such as PM2.5. The meteorological variation was more important than elevation to influence the low-elevation PM2.5-associated PAH and BaPeq concentrations in an urban area like Kaohsiung City, as the two concentrations were dominated by the PAHs with HMWs and those 5-ring species, respectively.

Simulating the spatiotemporal distribution of BTEX with an hourly grid-scale model.

Modeling approaches have been utilized to simulate ambient pollutant concentrations, but very limited efforts have been made to estimate volatile organic compounds in the atmosphere. For this reason, an hourly grid-scale simulation model was developed to determine ambient air concentrations of benzene, toluene, ethylbenzene, and xylene (BTEX). BTEX data were collected over a one-year time frame from the database of the Taiwan Environmental Protection Administration's photochemical assessment monitoring stations. Multivariate linear regression models were used along with correlation analysis to simulate hourly grid-scale BTEX concentrations, using criteria pollutants and selected meteorological variables as predictors. The simulation model was validated in the southern Taiwan area via a portable micro gas chromatography system (n = 121) with significant correlation (r = 0.566**, ** indicated p < 0.01). Moreover, the grid-scale model was applied to areas covering about 72% of the population in Taiwan. A geographic information system (GIS) was used to visualize the spatial distribution of BTEX concentrations from the modeling results. This new grid-scale modeling strategy, which incorporated the GIS output of the simulated data, provides a useful alternative tool for personal exposure analysis and health risk assessment of ambient air BTEX.

Hepatoprotective effect of Coreopsis tinctoria flowers against carbon tetrachloride-induced liver damage in mice.

BACKGROUND: Coreopsis tinctoria is a traditional remedy for the management of various diseases including hepatitis. The hepatoprotective role of the plant is not scientifically explored till now. This study was designed to investigate the hepatoprotective potentials of the ethanol extract from C. tinctoria (CTEtOH) using an animal model of carbon tetrachloride (CCl4)-induced acute liver injury. METHODS: CTEtOH (0.5 and 1.0 g/kg) and silymarin (200 mg/kg) were administered to the experimental mice for 7 days followed by 0.2% CCl4 (10 mL/kg of body weight (bw), ip), then all mice were sacrificed after 24 h. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. Histological analysis of liver was performed. The tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), nitric oxide (NO), malondialdehyde (MDA), and antioxidant enzymatic activities were also measured.. RESULTS: The results revealed that the serum ALT and AST levels significantly decreased after treatment with CTEtOH. Moreover, histological analyses indicated that CTEtOH (0.5 and 1.0 g/kg) and silymarin reduced the extent of CCl4-induced liver lesions. CTEtOH (0.5 and 1.0 g/kg) reduced the levels of malondialdehyde, nitric oxide, and proinflammatory cytokines (TNF-α and IL-1ß). Furthermore, CTEtOH (1.0 g/kg) reduced the level of IL-6. The activities of antioxidant enzymes, namely superoxide dismutase and glutathione reductase, significantly increased after treatment with CTEtOH (0.5 and 1.0 g/kg) and that of glutathione peroxidase increased after treatment with 1.0 g/kg of CTEtOH. CONCLUSIONS: These results demonstrate the hepatoprotective effect of CTEtOH against CCl4-induced acute liver injury in mice, and the underlying hepatoprotective mechanisms are associated with antioxidant and antiproinflammatory activities.

Improving the Concentrations of the Active Components in the Herbal Tea Ingredient, Uraria crinita: The Effect of Post-harvest Oven-drying Processing.

Uraria crinita is widely used as a popular folk drink; however, little is known about how the post-harvest operations affect the chemical composition and bioactivity of UC. We assessed three drying methods (Oven-drying, Air-drying, Sun-drying), as well as the Oven-drying temperature using metabolomics approaches and bioactivity assays. The samples processed at 40 degree show a greater effect on the levels of estrogen receptor-alpha activity and nuclear factor erythroid 2-related factor 2 activity, anti-oxidative activity, and cyclooxygenase-2 inhibition compared with the other samples. A multivariate analysis showed a clear separation between the 40 degree Oven-dried samples and the other samples, which is consistent with the results of bioactivity assay. These results are ascribed to at least two-fold increase in the concentrations of flavonoids, spatholosineside A and triterpenoids in the oven-dried samples compared with the other groups. The proposed Oven-drying method at 40 degree results in an improved quality of UC.

Gallic acid ameliorated impaired glucose and lipid homeostasis in high fat diet-induced NAFLD mice.

Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and fruits, has been shown to have potent anti-oxidative and anti-obesity activity. However, the effects of GA on nonalcoholic fatty liver disease (NAFLD) are poorly understood. In this study, we investigated the beneficial effects of GA administration on nutritional hepatosteatosis model by a more "holistic view" approach, namely 1H NMR-based metabolomics, in order to prove efficacy and to obtain information that might lead to a better understanding of the mode of action of GA. Male C57BL/6 mice were placed for 16 weeks on either a normal chow diet, a high fat diet (HFD, 60%), or a high fat diet supplemented with GA (50 and 100 mg/kg/day, orally). Liver histopathology and serum biochemical examinations indicated that the daily administration of GA protects against hepatic steatosis, obesity, hypercholesterolemia, and insulin resistance among the HFD-induced NAFLD mice. In addition, partial least squares discriminant analysis scores plots demonstrated that the cluster of HFD fed mice is clearly separated from the normal group mice plots, indicating that the metabolic characteristics of these two groups are distinctively different. Specifically, the GA-treated mice are located closer to the normal group of mice, indicating that the HFD-induced disturbances to the metabolic profile were partially reversed by GA treatment. Our results show that the hepatoprotective effect of GA occurs in part through a reversing of the HFD caused disturbances to a range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), amino acids metabolism, choline metabolism and gut-microbiota-associated metabolism. Taken together, this study suggested that a 1H NMR-based metabolomics approach is a useful platform for natural product functional evaluation. The selected metabolites are potentially useful as preventive action biomarkers and could also be used to help our further understanding of the effect of GA in hepatosteatosis mice.

Osthole Improves Spatial Memory Deficits in Rats via Hippocampal α 1-Adrenergic and D 1 /D 2 Receptors.

The present study evaluated the effect of osthole, an active ingredient isolated from Cnidium monnieri L. Cusson, on spatial memory deficits caused by central neurotoxins using the Morris water maze in rats. The involvement of catecholaminergic receptors on the memory-enhancing effect of osthole in rat hippocampus was further investigated by intrahippocampal injection of catecholaminergic receptor antagonists. Intracisternal injection of osthole (10 µ g/brain) improved the spatial performance and working memory impairments caused by the catecholaminergic neurotoxin 6-hydroxydopamine. No significant differences in swimming speeds were observed among sham, neurotoxin-induced, and osthole-treated groups. Intracisternal osthole injection also attenuated the spatial performance and working memory impairments caused by the α 1 receptor antagonist phenoxybenzamine, the D1 receptor antagonist SCH 23390, and the D2 receptor antagonist sulpiride. Therefore, we demonstrated that the effect of osthole on improving spatial memory deficits may be related to the activation of hippocampal α 1 and D1/D2 receptors.

Schizandrin protects primary rat cortical cell cultures from glutamate-induced apoptosis by inhibiting activation of the MAPK family and the mitochondria dependent pathway.

Glutamate-induced excitotoxicity has been implicated in a variety of neuronal degenerative disorders. In the present study, we investigated the possible neuroprotective effects of schizandrin against apoptosis of primary cultured rat cortical cells induced by glutamate. Glutamate (10 µM) administered for 24 h decreased the expression of Bcl-2 and Bcl-X(L) protein, whereas increased the expression of Bax, Bak, apoptosis inducing factor (AIF), endonuclease G (Nodo G) and endoplasmic reticulum (ER) stress of caspase-12. Pretreatment with schizandrin (100 µM) before glutamate treatment increased the Bcl-X(L) and Bcl-2 expression and decreased Bax, Bak, AIF, Nodo G and caspase-12 compared with those only treated with glutamate. Furthermore, glutamate-induced phosphorylation of JNK, p38 and ERK mitogen-activated protein kinases (MAPK), and these effects were attenuated by schizandrin (100 µM) treatment. These results suggest that schizandrin possesses the neuroprotective effects. The molecular mechanisms of schizandrin against glutamate-induced apoptosis may involve the regulation of Bcl-2 family proteins expression, and ER stress through blocking the activation of JNK, ERK and p38 MAPK.

Analgesic and Anti-Inflammatory Activities of Methanol Extract of Cissus repens in Mice.

The aim of this study was to investigate possible analgesic and anti-inflammatory mechanisms of the CR(MeOH). Analgesic effect was evaluated in two models including acetic acid-induced writhing response and formalin-induced paw licking. The anti-inflammatory effect was evaluated by λ-carrageenan-induced mouse paw edema and histopathologic analyses. The results showed that CR(MeOH) (500 mg/kg) decreased writhing response in the acetic acid assay and licking time in the formalin test. CR(MeOH) (100 and 500 mg/kg) significantly decreased edema paw volume at 4th to 5th hours after λ-carrageenan had been injected. Histopathologically, CR(MeOH) abated the level of tissue destruction and swelling of the edema paws. These results were indicated that anti-inflammatory mechanism of CR(MeOH) may be due to declined levels of NO and MDA in the edema paw through increasing the activities of SOD, GPx, and GRd in the liver. Additionally, CR(MeOH) also decreased IL-1ß, IL-6, NFκB, TNF-α, COX-2, and iNOS levels. The contents of two active ingredients, ursolic acid and lupeol, were quantitatively determined. This paper demonstrated possible mechanisms for the analgesic and anti-inflammatory effects of CR(MeOH) and provided evidence for the classical treatment of Cissus repens in inflammatory diseases.

Green Tea Extract Ameliorates Learning and Memory Deficits in Ischemic Rats via Its Active Component Polyphenol Epigallocatechin-3-gallate by Modulation of Oxidative Stress and Neuroinflammation.

Ischemic stroke results in brain damage and behavioral deficits including memory impairment. Protective effects of green tea extract (GTex) and its major functional polyphenol (-)-epigallocatechin gallate (EGCG) on memory were examined in cerebral ischemic rats. GTex and EGCG were administered 1 hr before middle cerebral artery ligation in rats. GTex, EGCG, and pentoxifylline (PTX) significantly improved ishemic-induced memory impairment in a Morris water maze test. Malondialdehyde (MDA) levels, glutathione (GSH), and superoxide dismutase (SOD) activity in the cerebral cortex and hippocampus were increased by long-term treatment with GTex and EGCG. Both compounds were also associated with reduced cerebral infraction breakdown of MDA and GSH in the hippocampus. In in vitro experiments, EGCG had anti-inflammatory effects in BV-2 microglia cells. EGCG inhibited lipopolysaccharide- (LPS-) induced nitric oxide production and reduced cyclooxygenase-2 and inducible nitric oxide synthase expression in BV-2 cells. GTex and its active polyphenol EGCG improved learning and memory deficits in a cerebral ischemia animal model and such protection may be due to the reduction of oxidative stress and neuroinflammation.

Therapeutic Effect of Yi-Chi-Tsung-Ming-Tang on Amyloid ß-Induced Alzheimer's Disease-Like Phenotype via an Increase of Acetylcholine and Decrease of Amyloid ß.

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder characterized by amyloid accumulation, neuronal death, and cognitive impairments. Yi-Chi-Tsung-Ming-Tang (YCTMT) is a traditional Chinese medicine and has never been used to enhance cognitive function and treat neurodegenerative disorders such as senile dementia. Whether YCTMT has a beneficial role in improving learning and memory in AD patients remains unclear. The present study showed that oral administration of YCTMT ameliorated amyloid-ß- (Aß(1-40)) injection-induced learning and memory impairments in rats, examined using passive avoidance and Morris water-maze tests. Immunostaining and Western Blot results showed that continuous Aß(1-40) infusion caused amyloid accumulation and decreased acetylcholine level in hippocampus. Oral administration of medium and high dose of YCTMT 7 days after the Aß(1-40) infusion decreased amyloid accumulation area and reversed acetylcholine decline in the Aß(1-40)-injected hippocampus, suggesting that YCTMT might inhibit Aß plague accumulation and rescue reduced acetylcholine expression. This study has provided evidence on the beneficial role of YCTMT in ameliorating amyloid-induced AD-like symptom, indicating that YCTMT may offer an alternative strategy for treating AD.

Antidepressant-Like Activity of the Ethanolic Extract from Uncaria lanosa Wallich var. appendiculata Ridsd in the Forced Swimming Test and in the Tail Suspension Test in Mice.

This study investigated the antidepressant activity of ethanolic extract of U. lanosa Wallich var. appendiculata Ridsd (UL(EtOH)) for two-weeks administrations by using FST and TST on mice. In order to understand the probable mechanism of antidepressant-like activity of UL(EtOH) in FST and TST, the researchers measured the levels of monoamines and monoamine oxidase activities in mice brain, and combined the antidepressant drugs (fluoxetine, imipramine, maprotiline, clorgyline, bupropion and ketanserin). Lastly, the researchers analyzed the content of RHY in the UL(EtOH). The results showed that UL(EtOH) exhibited antidepressant-like activity in FST and TST in mice. UL(EtOH) increased the levels of 5-HT and 5-HIAA in cortex, striatum, hippocampus, and hypothalamus, the levels of NE and MHPG in cortex and hippocampus, the level of NE in striatum, and the level of DOPAC in striatum. Two-week injection of IMI, CLO, FLU and KET enhanced the antidepressant-like activity of UL(EtOH). UL(EtOH) inhibited the activity of MAO-A. The amount of RHY in UL(EtOH) was 17.12 mg/g extract. Our findings support the view that UL(EtOH) exerts antidepressant-like activity. The antidepressant-like mechanism of UL(EtOH) may be related to the increase in monoamines levels in the hippocampus, cortex, striatum, and hypothalamus of mice.

Diosgenin ameliorates cognition deficit and attenuates oxidative damage in senescent mice induced by D-galactose.

This study attempted to access the neuroprotective effect of diosgenin on the senescent mice induced by d-galactose (D-gal). The mice in the experiments were orally administered with diosgenin (1, 5, 25 and 125 mg/kg), for four weeks from the sixth week. The learning and memory abilities of the mice in Morris water maze test and the mechanism involved in the neuroprotective effect of diosgenin on the mice brain tissue were investigated. Diosgenin (5, 25 and 125 mg/kg, p.o.) showed significantly improved learning and memory abilities in Morris water maze test compared to D-gal treated mice (200 mg/kg, ten weeks). Diosgenin also increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and decreased the malondialdehyde (MDA) level in the brain of D-gal treated mice. These results indicated that diosgenin has the potential to be a useful treatment for cognitive impairment. In addition, the memory enhancing effect of diosgenin may be partly mediated via enhancing endogenous antioxidant enzymatic activities.

The ameliorating effects of luteolin on beta-amyloid-induced impairment of water maze performance and passive avoidance in rats.

The present study investigated the effects of luteolin on Abeta (1-40)-induced impairment of Morris water maze (MWM) spatial performance, reference memory, and passive avoidance (PA) behavior in rats. Luteolin treatment was started 4 days before the initiation of behavioral testing (passive avoidance on treatment day of 4-5; MWM spatial performance memory testing on treatment day of 5-7 and MWM reference memory testing on treatment day of 7) and continued until the end of the study. We also measured the activity of Mn-SOD, copper/zinc (Cu/Zn)-SOD and glutathione (GSH) levels in rat cortex and hippocampus to understand the ameliorating effect of luteolin on Abeta (1-40) induced memory impairment. The present results showed that luteolin (5, 10 mg/kg) has a protective effect on Abeta (1-40)-induced memory dysfunction in spatial performance, reference memory, and inhibitory avoidance response impairment. Finally, luteolin also increases the level of Mn-SOD, (Cu/Zn)-SOD and glutathione (GSH) in the cortex and hippocampus to reduce the oxidative stress by Abeta (1-40). Taken together, the results in this study suggest that luteolin (5, 10 mg/kg) treatment improves the learning and memory in Abeta (1-40)-induced cognition deficit in rats. The ameliorating mechanisms of luteolin on Abeta (1-40)-induced amnesia may be related to activating the anti-oxidation system.

Neuroprotective effect of luteolin on amyloid beta protein (25-35)-induced toxicity in cultured rat cortical neurons.

The present study was carried out to investigate the neuroprotective effect of luteolin on amyloid beta (Abeta) (25-35)-induced neurotoxicity using cultured rat cortical neurons. After exposure of primary cultures of rat cortical cells to 10 muM Abeta (25-35) for 48 h, cortical cell cultures exhibited marked apoptotic death. Pretreatment with luteolin (1, 10 microM) significantly protected cortical cell cultures against Abeta (25-35)-induced toxicity. Luteolin (1, 10 microM) showed a concentration-dependent inhibition on 10 muM Abeta (25-35)-induced apoptotic neuronal death, as assessed by MTT assay. Furthermore, luteolin reduced apoptotic characteristics by DAPI staining. For Western blot analysis, the results showed that the protective effect of luteolin on Abeta (25-35)-induced neurotoxicity was mediated by preventing of ERK-p, JNK, JNK-p, P38-p and caspase 3 activations in rat primary cortical cultures. Taken together, the results suggest that luteolin prevents Abeta (25-35)-induced apoptotic neuronal death through inhibiting the protein level of JNK, ERK and p38 MAP kinases and caspase 3 activations.

Review on experimental research of herbal medicines with anti-amnesic activity.

Amnesia is characterized by the inability to form memories or total or partial loss of memory secondary to cerebral malfunction following degenerative diseases, cerebral infections, traumatic injuries and emotional events which could be differentiated from dementia. However, no effective treatment for amnesia is currently available. Much research effort has been focused on developing new drugs from herbal medicines which have multifunctional properties. Novel plant extracts and their major or bioactive components including alkaloids, flavonoids, glycosides and saponins with promising antioxidant effects, various effects on cholinergic, GABAergic, glutaminergic, serotonergic, catecholaminergic and histaminergic systems, enhancement of cerebral blood flow and elevation of ribonucleic acid (RNA) as well as protein levels have been studied. In this review, we discuss the research findings on novel plant extracts and their bioactives with anti-amnesic effects on different neurotransmitter systems. Developing new drugs from herbal medicines for the treatment of amnesia is a hopeful attempt to meet the unmet medical needs.

Yam (Dioscorea pseudojaponica Yamamoto) ameliorates cognition deficit and attenuates oxidative damage in senescent mice induced by D-galactose.

This study attempted to access the neuroprotective effect of yam (Dioscorea pseudojaponica Yamamoto) on the senescent mice induced by D-gal. The mice in the experiments were administered orally with yam (20, 100 or 500 mg/kg for 4 weeks, from the sixth week). The learning and memory abilities of the mice in Morris water maze test and the mechanisms involved in the neuroprotective effect of yam on the mice brain tissue were investigated. The content of diosgenin in the yam was also detected by using HPLC. Mice treated with yam were found to significantly improve their learning and memory abilities in Morris water maze test compared to those treated with D-gal (200 mg/kg for 10 weeks). In addition, yam was also found to increase the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and decrease the malondialdehyde (MDA) level on the brains of D-gal treated mice. Finally, the amount of diosgenin in the yam was 5.49 mg/g extract. To sum up, these results indicate that yam had the potential to be a useful treatment for cognitive impairment in TCM. Its beneficial effect may be partly mediated via enhancing endogenous antioxidant enzymatic activities.

Rapid optimization of dual-mode gradient high performance liquid chromatographic separation of Radix et Rhizoma Salviae Miltiorrhizae by response surface methodology.

An approach for rapid optimization of dual-mode gradient high performance liquid chromatography (HPLC) by response surface methodology (RSM) was developed for fast simultaneous separation of hydrophilic and hydrophobic components in Radix et Rhizoma Salviae Miltiorrhizae (Danshen) and its preparations. The aim of this study was to achieve a high throughput RSM optimization using a short ultra-high performance liquid chromatographic (UHPLC) column to simultaneously optimize flow rate and solvent gradient, and then transfer the optimized method to conventional HPLC for routine analytical purposes. The optimization was designed with Box Behnken design (BBD) and the global Derringer's desirability was used for describing the multicriteria response variables. Sixty-two designed experiments were performed by UHPLC with a short sub-2 microm column (2.1 mm x 50 mm, 1.7 microm) and a total running time of only 5h. The predicted gradient profile was further transferred to a long UHPLC column (2.1 mm x 100 mm, 1.7 microm) and a conventional HPLC columns (2.1 mm x 100 mm, 3.5 microm and 4 mm x 100 mm, 5 microm, respectively). Compared to the published methods, the newly developed dual-mode gradient is faster and more efficient at simultaneously separating hydrophilic and hydrophobic components in Danshen and its preparations.

Comparison with various parts of Broussonetia papyrifera as to the antinociceptive and anti-inflammatory activities in rodents.

This study compared the antinociceptive and anti-inflammatory effects of various parts of Broussonetia papyrifera (L.) L'Herit. ex Vent. (BP, Moraceae) by chemical-induced pain and inflammation in rodents. All BP parts (1 and 2 g/kg, p.o.) effectively inhibited writhing responses induced by 1% acetic acid. The BP radix, leaf, and fruit effectively inhibited the late-phase licking responses caused by 1% formalin. But only the BP radix and fruit reduced the edema induced by 1% carrageenan at 1-2 h. Furthermore, the BP radix reduced the abdominal Evan's blue extravasations caused by inflammatory mediators, including serotonin and sodium nitroprusside. Finally, the radix had the highest contents of betulin and betulinic acid among all BP parts. In conclusion, the radix is the better medicinal BP part possessing antinociceptive and antiinflammatory effects, and its anti-inflammatory effects are partially related to the inhibition of vascular permeability via autocrines and nitric oxide.

Schizandrin protects primary cultures of rat cortical cells from glutamate-induced excitotoxicity.

The neuroprotective effect of schizandrin on the glutamate (Glu)-induced neuronal excitotoxicity and its potential mechanisms were investigated using primary cultures of rat cortical cells. After exposure of primary cultures of rat cortical cells to 10 microM Glu for 24 h, cortical cell cultures exhibited remarkable apoptotic death. Pretreatment of the cortical cell cultures with schizandrin (10, 100 microM) for 2 h significantly protected cortical neurons against Glu-induced excitotoxicity. The neuroprotective activity of schizandrin was the most potent at the concentration of 100 microM. Schizandrin reduced apoptotic characteristics by DAPI staining in Glu-injured cortical cell cultures. In addition, schizandrin diminished the intracellular Ca2+ influx, inhibited the subsequent overproduction of nitric oxide (NO), reactive oxygen species (ROS), and cytochrome c, and preserved the mitochondrial membrane potential. Furthermore, schizandrin also increased the cellular level of glutathione (GSH) and inhibited the membrane lipid peroxidation malondialdehyde (MDA). As indicated by Western blotting, schizandrin attenuated the protein level changes of procaspase-9, caspase-9, and caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP). Taken together, these results suggest that schizandrin protected primary cultures of rat cortical cells against Glu-induced apoptosis through a mitochondria-mediated pathway and oxidative stress.