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ABSTRACT: This study was aimed to investigate the effects of ginsenoside Rg1 (Rg1) on hematopoietic function of bone marrow in cyclophosphamide-induced bone marrow depression mice. Mice were given cyclophosphamide (150mg/kg, i.p. for three days) to produce bone marrow depression. Rg1 was then administrated at 7.5 and 15mg/kg by i.p. for seven days. Bone marrow cells number was counted, and the percentage of hematopoietic stem cells (Lin(-)Sca-1(+)c-kit(+)) was quantified by flow cytometry. The histology of femoral bone was examined by H&E staining. The expression of calcium-sensing receptor mRNA was determined by the real time RT-PCR. Rg1 (7.5 and 15mg/kg) protected against cyclophosphamide-induced bone marrow depression, as evidenced by increased bone marrow cell numbers and improved femoral bone morphology. The percentage of Lin(-)Sca-1(+)c-kit(+) cells and lymphoid lineage CD3(+) cells were lower in cyclophosphamide group, but returned towards normal after Rg1 treatment in both bone marrow and peripheral blood cells. Expression of calcium-sensing receptor mRNA was increased in bone marrow cells on the 10th day after cyclophosphamide, but it was returned to normal level after Rg1 treatment. Rg1 alone did not produce these changes in normal mice. These results demonstrated that Rg1 improved hematopoietic function of bone marrow in cyclophosphamide-induced myelosuppression.
European journal of pharmacology 08/2012; 695(1-3):7-12. · 2.59 Impact Factor
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ABSTRACT: Neurotrophic factors such as glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) are considered to contribute to the development, maintenance and survival of neurons, glia and oligodendrocytes. Astroglia are a major source of various neurotrophic factors. Thus, enhancement of astroglia-mediated neurotrophic factor release might hold promising potential for neurological diseases. Resveratrol, a natural non-flavonoid polyphenol found in grapes and red wine, has been recognized to be beneficial for health. Here, rat primary astroglia-enriched cultures were used to investigate the effects of resveratrol-mediated neurotrophic factor release and the related mechanisms. The cultures were treated with 25-100 μmmol/L resveratrol for 12-48 h. Results showed resveratrol increased BDNF and GDNF production in the culture medium. In addition, the production of BDNF in the supernatant of cultures was increased five-fold over control cultures 24 h after resveratrol treatment and then remained high 36 h later. Meanwhile, the production of GDNF was initially increased by up to four-fold 24 h after resveratrol treatment and continued to increase to six-fold at 36 h and remained at a high level till 48 h. Western blot analysis of BDNF and GDNF protein in astroglia at different time points after resveratrol treatment indicated similar increases. Furthermore, resveratrol significantly induced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP responsive element-binding protein (CREB) in astroglia. Overall, resveratrol is effective in promoting astroglia-derived neurotrophic factor release, and this effect is mediated, at least in part, by the activation of ERK1/2 and CREB.
Experimental Biology and Medicine 08/2012; 237(8):943-8. · 2.64 Impact Factor
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ABSTRACT: To compare sub-acute toxic effects of cinnabar and Wansheng Huafeng Dan with mercury chloride and methyl-mercury.
Healthy SD rats were orally administered with Wansheng Huafeng Dan (0.42 g x kg(-1)), cinnabar (0.15 g x kg(-1)), HgS (0.15 g x kg(-1)), HgCl2 (0.02 g x kg(-1)), MeHg (0.001 g x kg(-1)) and saline for 21 days under observed and their weights were monitored. After the final administration, they were decapitated and their blood, liver, kidney and brain tissues were collected for calculating hepatic and renal indexes and detecting the contents of serum glutamic pyruvic transaminase, urea nitrogen and creatinine and the mercury accumulation in liver, kidney and brain tissues. Besides, relative expressions of liver metallothionein-1 (MT-1) and cytochrome P450 gene subtypes (Cyp1a1, Cyp2b1, Cyp2e1, Cyp3a2, Cyp4a10) mRNA.
HgCl2 caused obvious weight lose in rats. Mercury contents in liver and kidney were markedly increased by HgCl2 and MeHg, and MeHg markedly increased mercury contents of brain either, but these advent effects were not notable in Wansheng Huafeng Dan and cinnabar groups. However, blood biochemistry and histopathology did not show significant changes in all groups. The expression of rat hepatic MT-1 mRNA was remarkably induced by both HgCl2 and MeHg. The expression of hepatic Cyp3a2 was increased by Wansheng Huafeng Dan and cinnabar, while the expression of Cyp2e1 was inhibited by HgCl2 and MeHg.
The administration of Wansheng Huafeng Dan with equivalent dose for three weeks shows a much low sub-acute toxicity than HgCl2 and MeHg in rats.
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 04/2012; 37(7):1017-22.
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ABSTRACT: Increasing evidence indicated astroglia-derived neurotrophic factors generation might hold a promising therapy for Parkinson's disease (PD). Resveratrol, naturally present in red wine and grapes with potential benefit for health, is well known to possess a number of pharmacological activities. Besides the antineuroinflammatory properties, we hypothesized the neuroprotective potency of resveratrol is partially due to its additional neurotrophic effects. Here, primary rat midbrain neuron-glia cultures were applied to investigate the neurotrophic effects mediated by resveratrol on dopamine (DA) neurons and further explore the role of neurotrophic factors in its actions. Results showed resveratrol produced neurotrophic effects on cultured DA neurons. Additionally, astroglia-derived neurotrophic factors release was responsible for resveratrol-mediated neurotrophic properties as evidenced by the following observations: (1) resveratrol failed to exert neurotrophic effects on DA neurons in the cultures without astroglia; (2) the astroglia-conditioned medium prepared from astroglia-enriched cultures treated with resveratrol produced neurotrophic effects in neuron-enriched cultures; (3) resveratrol increased neurotrophic factors release in the concentration- and time-dependent manners; (4) resveratrol-mediated neurotrophic effects were suppressed by blocking the action of the neurotrophic factors. Together, resveratrol could produce neurotrophic effects on DA neurons through prompting neurotrophic factors release, and these effects might open new alternative avenues for neurotrophic factor-based therapy targeting PD.
Evidence-based Complementary and Alternative Medicine 01/2012; 2012:937605. · 4.77 Impact Factor
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ABSTRACT: An improved tracheal intubation method was used in preparation of myocardial infarction model in the mouse for increasing the success rate.
The mice were intubated by an improved trachea cannula through oral cavity. The left anterior thoracotomy performed. The myocardial infarction model was made by legating the left anterior descending coronary artery in mouse. The color of heart was observed, and electrocardiogram was recorded. The survival rate and pathologic change were observed after two weeks of operation.
40 myocardial infarction model mice were made by improved trachea cannula. The color of ventricles anterior wall had got madder red, and ST stages were raised on II leads of electrocardiogram in all of model mice. After two weeks, 27 mice were survival. The survival rate was 87.1% except for accidental death during operation. The heart chamber expanded and ventricular wall became thin in myocardial infarction mice by eyes. After pathological sections were stained, by HE cardiac muscle fibers ruptured or lysed. There were some of necrosis of myocardiac cells and many of infiltration of inflammatory cells.
Application of an improved tracheal intubation method simplified operation of tracheal intubation during preparation of myocardial infarction model in the mouse. The trauma was tinier than the other one, and achievement ratio of the model preparation was improved.
Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 08/2011; 27(3):380-3.
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ABSTRACT: An-Gong-Niu-Huang Wan (AGNH) is a patent traditional Chinese medicine for brain disorders. It contains 10% cinnabar (HgS). Hg is known to produce toxicity to the kidney, brain and liver. Is AGNH safe? Liver is a major organ for drug metabolism, whether the long-term use of AGNH would affect hepatic P450 enzymes is unknown. To address these concerns, mice were given orally cinnabar (300mg/kg), cinnabar-containing AGNH daily for 44days, and liver toxicity was examined and compared with that of methylmercury (MeHg, 2.6mg/kg) and mercuric chloride (HgCl(2), 32mg/kg). Serum aminotransferases were increased by MeHg and HgCl(2) only. Histopathology showed more severe liver damage in MeHg- and HgCl(2)-treated mice than in the cinnabar and AGNH groups. Accumulation of Hg in MeHg- and HgCl(2)-treated mice was 96- and 71-fold higher than controls, respectively, but was only 2-fold after cinnabar and AGNH administration. Expressions of metallothionein-1 and heme oxygenase-1, biomarkers for Hg toxicity, were increased by MeHg and HgCl(2,) but were not altered in cinnabar- and AGNH-treated mice. Expression of hepatic cytochrome P450 genes, such as Cyp1a1, Cyp1b1 and Cyp4a10 was increased only after MeHg and HgCl(2), and the expressions of Cyp3a11and Cyp3a25 were increased by all treatments, indicating the potential Hg-drug interactions after long-term use of cinnabar-containing traditional medicines. Taken together, the results demonstrate that AGNH is much less hepatotoxic than common mercurials, and that the use of total Hg content to evaluate the toxicity of cinnabar-containing traditional Chinese medicines appears to be inappropriate.
Regulatory Toxicology and Pharmacology 03/2011; 60(2):206-11. · 2.43 Impact Factor
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ABSTRACT: Cinnabar (HgS) is used in traditional medicines, and total Hg content is used for risk assessment of cinnabar-containing traditional medicines such as Zhu-Sha-An-Shen-Wan (ZSASW). Is ZSASW or cinnabar toxicologically similar to common mercurials? Adult Sprague-Dawley rats were gavaged with ZSASW (1.4 g/kg), cinnabar (0.2g/kg), HgCl(2) (0.02 g/kg), MeHg (0.001 g/kg), or saline daily for 60 days, and toxicity was determined. Animal body-weight gain was decreased by HgCl(2) and MeHg. Blood urea nitrogen (BUN) was increased by MeHg. Histology showed severe kidney injury following MeHg and HgCl(2) treatments, but mild after ZSASW and cinnabar. Renal Hg contents were markedly increased in the HgCl(2) and MeHg groups but were not elevated in the ZSASW and cinnabar groups. The expression of kidney injury molecule-1 was increased 50-fold by MeHg, 4-fold by HgCl(2), but was unaltered by ZSASW and cinnabar; the expression of matrilysin was increased 3-fold by MeHg. In contrast, the expression of N-cadherin was decreased by HgCl(2). Thus, ZSASW and cinnabar are much less nephrotoxic than HgCl(2) and MeHg, indicating that chemical forms of mercury underlie their disposition and toxicity.
Toxicology Letters 02/2011; 200(3):194-200. · 3.23 Impact Factor
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ABSTRACT: Mercury (Hg) and arsenic (As) are frequently found in traditional medicines as sulfides, such as cinnabar (HgS) and realgar (As(4)S(4)). There is a general perception that any medicinal use of such metal-containing remedies is unacceptable. An opposing opinion is that different chemical forms of arsenic and mercury have different toxic potentials.
To clarify this question, cinnabar, realgar, and cinnabar- and realgar-containing traditional medicine An-Gong-Niu-HuangWan (AGNH), were compared to well-known mercurials (HgS, HgCl(2) and MeHg) and arsenicals (As(2)S(2), As(2)O(3), NaAsO(2), and Na(2)HAsO(4)) for their cytotoxicity in human and rodent cell lines.
Cultured cells derived from target organs such as brain (HAPI) and liver (Hep3B, HepG2 and TRL1215) were treated with chemicals for 48 h and cytotoxicity was determined by the MTS assay.
MeHg was most toxic with LC(50) of 4-20μM, followed by NaAsO(2) (LC(50), 25-250 μM) and HgCl(2) (LC(50,) 50-100 μM), Na(2)HAsO(4)(LC(50), 60-400μM), As(2)O(3)(LC(50), 30-900 μM), and As(2)S(2) (LC(50), 100-500 μM). In comparison, the LC(50) of realgar ranged from 250 to1500 μM; whereas cinnabar or HgS were approximately 20,000 μM and the toxicity of AGNH was in the range of 1500-8000 μM. Approximately 5000-fold differences exist between MeHg and HgS, and over 10-fold differences exist between NaAsO(2) and As(4)S(4).
Chemical forms of metals are important factor in determining their toxicity in traditional medicines, both cinnabar and realgar are much less toxic than well-known mercurial and arsenicals.
Journal of ethnopharmacology 02/2011; 134(3):839-43. · 2.32 Impact Factor
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ABSTRACT: Realgar (As(4)S(4)) and cinnabar (HgS) are frequently included in traditional Chinese medicines and Indian Ayurvedic medicines. Both As and Hg are well known for toxic effects, and their safety is of concern. The aim of this study was to compare chronic nephrotoxicity of An-Gong-Niu-Huang Wan (AGNH), realgar and cinnabar with common arsenicals and mercurials. Mice were orally administrated with AGNH (3 g/kg, 6-fold of clinical dose), cinnabar (0.3 g/kg, amount in AGNH) and realgar (0.3 g/kg, amount in AGNH), HgCl(2) (0.118 mmol/kg, 1/10 of cinnabar), MeHg (0.012 mmol/kg, 1/100 of cinnabar), NaAsO(2) (As(3+) 0.028 mmol/kg, 1/100 of realgar) or Na(2)HAsO(4) (As(5+) 0.056 mmol/kg, 1/50 of realgar), daily for six weeks, and nephrotoxicity was examined. Animal body weights were decreased by MeHg and HgCl(2). Blood urea nitrogen and creatinine levels were elevated by MeHg. Renal pathology was severe in the MeHg and HgCl(2) groups, moderate in the arsenite, arsenate and realgar groups and mild in the cinnabar and AGNH groups. Renal Hg accumulation in the MeHg and HgCl(2) groups was 50-200 folds higher than the cinnabar group. Expressions of metallothionein-1 and heme oxygenase-1, biomarkers for metal toxicity, were increased 2-5 folds by arsenite, arsenate, MeHg and HgCl(2), but not by realgar, cinnabar and AGNH. The chemokine and glutathione-S transferase-α4, markers for inflammation, were also increased by MeHg and HgCl(2). Expressions of cell adhesion gene S100a9 and E-cadherin were altered by HgCl(2), arsenite and realgar. Taken together, chemical forms of mercury and arsenic are major determinants in their disposition and toxicity.
Experimental Biology and Medicine 02/2011; 236(2):233-9. · 2.64 Impact Factor
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ABSTRACT: An-gong-niu-huang wan (AGNH) is a famous traditional Chinese medicine used for brain trauma, hemorrhage, and coma. AGNH contains 10% realgar (As₄S₄) and 10% cinnabar (HgS). Both As and Hg are well-known for their toxic effects, and the safety of AGNH is of concern. To address this question, the acute toxicity of AGNH, realgar and cinnabar were compared to sodium arsenite (NaAsO₂) and mercuric chloride (HgCl₂). Mice were administrated orally AGNH at 1, 3 and 6g/kg. AGNH at 3g/kg contains 2.8mmol As/kg as realgar and 1.18mmol Hg/kg as cinnabar. Realgar, cinnabar, arsenite (0.28 mmol/kg, 10% of realgar) and HgCl₂ (0.256 mmol/kg, 20% of cinnabar) were orally given to mice for comparison. Blood and tissues were collected 8h later for toxicity evaluation. Serum alanine aminotransferase was increased by arsenite and blood urea nitrogen was increased by HgCl₂. Total As accumulation after arsenite in liver (100-fold) and kidney (13-fold) was much higher than that after realgar. The accumulation of Hg after HgCl₂ in liver was 400-fold higher and kidney 30-fold higher than after cinnabar. Histopathology showed moderate liver and kidney injuries after arsenite and HgCl₂, but injuries were mild or absent after AGNH, realgar, and cinnabar. The expression of metallothionein-1, a biomarker of metal exposure, was increased 4-10-fold by arsenite and HgCl₂, but was unchanged by AGNH, realgar and cinnabar. Thus, AGNH, realgar and cinnabar are much less toxic acutely than arsenite and HgCl₂. The chemical forms of As and Hg are extremely important factors in determining their disposition and toxicity.
Chemico-biological interactions 01/2011; 189(1-2):134-40. · 2.46 Impact Factor
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ABSTRACT: Liu-Shen-Wan (LSW) is a widely-used traditional Chinese medicine containing realgar (As(4)S(4)).
Realgar has been included in many traditional medicines, and is often taken as arsenite for risk assessment in realgar-containing traditional remedies. Is realgar toxicologically similar to arsenite?
Mice were orally given LSW (60 and 200mg/kg; 200mg LSW contains 27 mg realgar), realgar (30 mg/kg, equivalent to 21 mg As/kg), and the equivalent As dose as sodium arsenite (NaAsO(2)), or as arsenate (Na(2)HAsO(4)). Acute toxicity and tissue As accumulation were determined 8h later.
Arsenite and arsenate increased serum alanine aminotransferase (ALT) levels, indicative of liver injury; blood urea nitrogen (BUN) was also increased by arsenite and arsenate, indicative of nephrotoxicity. No elevations of ALT and BUN were observed in LSW and realgar groups. Histopathology showed more damage in arsenite- and arsenate-treated liver and kidneys, while in realgar- and LSW- treated animals, only mild alterations were seen. Hepatic and renal As contents were dramatically increased to 6200 and 3350ng/g, respectively, after arsenite, but only increased to 260 and 180 ng/g after LSW. The expressions of arsenic-sensitive stress genes, namely metallothionein-1 and heme oxygenase-1, were increased after arsenite or arsenate by 3-10-folds, but were unaltered after LWS and realgar.
Realgar and LSW are much less toxic than arsenite and arenate. The use of total As content to evaluate the safety of realgar-containing traditional medicines is not scientifically sound.
Journal of ethnopharmacology 12/2010; 134(1):26-31. · 2.32 Impact Factor
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ABSTRACT: The effects of icariin (ICA), a major constituent of flavonoids from the Chinese medical herb Epimedium brevicornum Maxim, on spatial memory performances and expressions of hippocampus brain-derived neurotrophic factor (BDNF) and tyrosine kinase TrkB (tropomyosin receptor kinase B) were investigated in d-galactose (d-gal)-treated rats. Subcutaneous injection of d-gal (500mg/kg/d) for four months caused memory loss as detected by the Morris water maze, morphologic abnormalities of neurons in hippocampus region and the reduced expression of BDNF and TrkB were observed. ICA (60mg/kg/d) given orally 1h after subcutaneous injection of d-gal daily for 4months markedly attenuated d-gal-induced rats behavioral dysfunction and neurodegeneration, as evidenced by shortened escape latency and searching distance and rescued morphologic abnormalities, and also elevated the mRNA levels and the protein expressions of BDNF and TrkB in hippocampus, as evidenced by quantitative real-time RT-PCR and Western blotting analysis. But ICA had no significant influence on normal rats which were not injected d-gal. These results clearly demonstrated that d-gal produced learning and memory deficits after chronic administration, and ICA can protect neuron from d-gal insults and improve the memory loss.
Pharmacology Biochemistry and Behavior 09/2010; 96(3):301-5. · 2.53 Impact Factor
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ABSTRACT: To study the toxicity of Cinnabar and Cinnabar-containing traditional medicines (Zhusha Anshenwan) comparable to common mercurials.
The toxicity of methylmercury (MeHg), mercuric chloride (HgCl2), Cinnabar and Zhusha Anshenwan was studied in cultured human liver HL-7702 cells and in mice following acute and subacute exposures.
The 50% lethal concentrations (LC50) of MeHg, HgCl2, Cinnabar and Zhusha Anshenwan in human liver HL-7702 cells were 4.4, 9.2, 2460, 4050 mg x L(-1), respectively . Oral cinnabar at a dose of 20 g x kg(-1) (clinical dosage 250 times) did not kill mouse, but no mouse could survive MeHg at a dose of 0.1 g x kg(-1) or HgCl2 at a dose of 0. 15 g x kg(-1). Subacute toxicity experiment indicated that HgCl2 retarded body weight gain with significant accumulation of Hg in the liver and kidney. In comparison, mercury accumulation after Cinnabar and Zhusha Anshenwan was insignificant. No apparent hepatic and renal dysfunctions were evident under the experimental conditions, but the metallothionein-2 mRNA levels were much higher in HgCl2 group than in other groups.
Cinnabar and Zhusha Anshenwan are much less toxic than MeHg and HgCl2.
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 02/2010; 35(4):499-503.
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ABSTRACT: Ginsenoside Rg(1) (Rg(1)), one of the active components of Panax ginseng, has been reported to promote endogenous nitric oxide (NO) production in some tissues, and to inhibit left ventricular (LV) hypertrophy in rats. This study aimed to investigate whether Rg(1)-induced inhibition of rat LV hypertrophy is mediated by NO-production. Rat LV hypertrophy was induced by abdominal aorta coarctation. Rg(1) 15 mg/kg/d, L-arginine 200 mg/kg/d, and the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine-methyl ester (L-NAME) 100 mg/kg/d used with the same dose of L-arginine or Rg(1) were given starting from 1 d after surgery for 21 consecutive days. LV hypertrophy was evidenced by determining LV weight and mRNA expression of atrial natriuretic peptide, a marker of cardiac hypertrophic response, as well as by histopathology. Rg(1) and L-arginine administration significantly reduced the elevated LV hypertrophic parameters independent of LV systolic pressure changing, and ameliorated the histopathology of LV myocardium and LV diastolic function. All the beneficial effects of Rg(1) and L-arginine were abolished or blunted by L-NAME. Further to examine the role of NO in Rg(1) inhibition on LV hypertrophy, expression of endothelial NOS was determined at the transcript levels. In our experimental conditions endothelial NOS mRNA expression in LV tissue was lowered by abdominal aorta coarctation, and upregulated by Rg(1) administration. These results demonstrate that Rg(1)-induced protection against LV hypertrophy elicited by abdominal aorta coarctation in rats is mediated, at least in part, via endogenous NO production and release.
Biological & Pharmaceutical Bulletin 01/2010; 33(4):631-5. · 1.66 Impact Factor
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ABSTRACT: The present study was undertaken to investigate the protective effects of icariin on the learning and memory abilities in Alzheimer's disease model rats and explore its protection mechanisms. Beta-amyloid peptide (Abeta) is a key etiology in Alzheimer's disease and targeting on Abeta production and assembly is a new therapeutic strategy. Six-month (400-600 g) Wistar rats were unilaterally injected with amyloid beta-protein fragment 25-35 (Abeta(25-35)) 10 microg (5 g/l, 2 microl) into the right hippocampus. The day following Abeta injection, icariin 30, 60 or 120 mg/kg was administered by gavage for 14 days. The ability of spatial learning and memory of the animals was tested by the Morris water maze. In place navigation test, icariin significantly decreased the mean escape latency and searching distance. In the space probing test, icariin increased remarkably the searching time and searching distance in the quadrant where the platform was originally located. All tests indicated icariin improved the ability of spatial learning and memory in Alzheimer's disease model rats. Furthermore, immunohistochemistry and real time RT-PCR analysis showed that icariin significantly reduced the contents of Abeta(1-40) and the mRNA levels of beta-secretase in the hippocampus and increased the mRNA level of superoxide dismutase-2, but it had no apparent effects on the immunostain and mRNA level of amyloid protein precursor. These results demonstrate that icariin can improve the learning and memory abilities in Abeta(25-35)-induced Alzheimer's disease rats. The mechanisms appear to be due to the decreased production of insoluble fragments of Abeta through suppression of beta-secretase expression.
European journal of pharmacology 09/2009; 626(2-3):213-8. · 2.59 Impact Factor
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ABSTRACT: 1. Icariin is a major constituent of flavonoids derived from the Chinese medicinal herb Epimedium revicornum Maxim. The aim of the present study was to investigate whether icariin has protective effects on learning ability and memory in a rat model of chronic cerebral hypoperfusion. 2. Chronic cerebral hypoperfusion was induced by permanent ligation of the common carotid artery in Wistar rats for 4 months. One month after permanent artery occlusion, rats were adminitered icariin at doses of 0, 30, 60 or 120 mg/kg per day, p.o., for 3 months. Neurobehavioural and neurobiochemical parameters were examined to evaluate the effects of icariin on cognitive deficits induced by chronic cerebral hypoperfusion. 3. The Morris water maze test revealed that learning ability and memory were severely impaired in untreated rats, but were significantly improved in icariin-treated rats. Icariin treatment also ameliorated chronic cerebral hypoperfusion-induced oxidative stress in the brain, as evidenced by reduced malondialdehyde formation and maintained superoxide dismutase activity. In addition, the decreased hippocampal levels of acetylcholine, acetylcholinesterase and choline acetyltransferase associated with chronic cerebral hypoperfusion were significantly prevented by icariin treatment. 4. In conclusion, icariin protects against cognitive deficits induced by chronic cerebral hypoperfusion in rats. These effects appear to be mediated through its anti-oxidant effects, as well as its effects on the circulatory and cholinergic systems.
Clinical and Experimental Pharmacology and Physiology 03/2009; 36(8):810-5. · 1.85 Impact Factor
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ABSTRACT: Ginsenoside Rg(1) (Rg(1)), one of the active components of Panax ginseng, has been reported to inhibit proliferation of vascular smooth musle cells induced by tumor necrosis factor-a. This study aims to investigate whether Rg(1) has protective effect on rat left ventricular hypertrophy and to probe its protective mechanisms. The rat left ventricular hypertrophy was induced by abdominal aorta coarctation and Rg(1) (3.75, 7.5 and 15 mg/kg/day) was given the day after surgery for 21 consecutive days. The left ventricular hypertrophy induced by abdominal aorta coarctation was evidenced by histopathology, electromicroscopy, and by determining the elevated left ventricular weight and the expression of aterial natriuretic peptide. Rg(1) significantly ameliorated left ventricular hypertrophy induced by abdominal aorta coarctation in a dose-dependent manner. To examine the mechanism of protection, the expressions of calcineurin, CnA (the catalytic subunit of calcineurin), extracellular signal-regulated kinase-1, and mitogen-activated protein (MAP) kinase phosphatase-1 were determined at the transcript and protein levels. The abdominal aorta coarctation induced increases in calcineurin, CnA, and extracellular signal-regulated kinase-1 expressions were suppressed , but the expression of MAP kinase phosphatase-1 was increased by Rg(1). These results demonstrate that Rg(1) alleviates left ventricular hypertrophy induced by abdominal aorta coarctation, and the protection appears to be due, at least in part, to its inhibitory effects on calcineurin and MAP kinase signaling pathways.
European journal of pharmacology 03/2009; · 2.59 Impact Factor
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ABSTRACT: Proliferation of vascular smooth muscle cells (VSMCs) is a crucial event in cardiovascular diseases. Isorhynchophylline, an alkaloid from a traditional Chinese medicine Gambirplant, has been used to treat cardiovascular diseases. The aim of this study was to investigate the effects of isorhynchophylline on angiotensin II (Ang II)-induced proliferation of rat VSMCs. VSMCs were isolated from rat artery and cultured for 14 days before experimentation. The effect of isorhynchophylline on Ang II-induced proliferation was evaluated by cell number, MTT assay and flow cytometry, and nitric oxide (NO) content and activity of NO synthase (NOS) were measured. The expression of proto-oncogene c-fos, osteopontin (OPN) and proliferating cell nuclear antigen (PCNA) mRNAs was measured by real-time RT-PCR. VSMC cultures were verified by morphology and immunostaining with alpha-smooth muscle actin. Isorhynchophylline (0.1-10.0 microM) was not toxic to VSMCs, but markedly decreased Ang II (1.0 microM)-enhanced cell number and MTT intensity, and blocked cell transition from G(0)/G(1) to S phase. Furthermore, isorhynchophylline increased the NO content and NOS activity, and suppressed Ang II-induced over-expression of c-fos, OPN and PCNA. Thus, isorhynchophylline was effective against Ang-II induced cell proliferation, an effect that appears to be due, at least in part, to increased NO production, regulation of the cell cycle, and depressed expression of c-fos, OPN and PCNA related to VMSC proliferation.
Journal of Pharmacy and Pharmacology 01/2009; 60(12):1673-8. · 2.17 Impact Factor
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ABSTRACT: The present study was undertaken to investigate the neuroprotective effects of resveratrol on 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease in rats. 6-OHDA-induced Parkinson's disease rat model involves chronic inflammation, mitochondrial dysfunction, and oxidative stress, and the loss of the dopaminergic neurons in the substantia nigra is the predominant lesion. Resveratrol has been shown to have anti-inflammatory actions, and thus was tested for its beneficial effects using 6-OHDA-induced Parkinson's disease rat model. Adult Sprague-Dawley (SD) rats were unilaterally injected with 6-OHDA (5 microg/2 microl) into the right striatum, and the striatum damage was assessed by rotational test, ultrahistopathology, and molecular alterations. Resveratrol (10, 20 and 40 mg/kg) was then given orally to Parkinson's disease rats, daily for 10 weeks to examine the protective effects. Rotational test (turns of rats) showed that resveratrol significantly attenuated apomorphine-induced turns of rats in 6-OHDA-injuried Parkinson's disease rat model as early as two weeks of administration. Ultrastructural analysis showed that resveratrol alleviated 6-OHDA-induced chromatin condensation, mitochondrial tumefaction and vacuolization of dopaminergic neurons in rat substantia nigra. Furthermore, resveratrol treatment also significantly decreased the levels of COX-2 and TNF-alpha mRNA in the substantia nigra as detected by real-time RT-PCR. COX-2 protein expression in the substantia nigra was also decreased as evidenced by Western blotting. These results demonstrate that resveratrol exerts a neuroprotective effect on 6-OHDA-induced Parkinson's disease rat model, and this protection is related to the reduced inflammatory reaction.
European journal of pharmacology 11/2008; 600(1-3):78-82. · 2.59 Impact Factor
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ABSTRACT: Ginsenosides have been reported to release nitric oxide (NO) and decrease intracellular free Ca(2+) in cardiovascular system, which play important roles in antihypertrophic effect. This study investigated the potential inhibitory effect of total ginsenosides (TG) on right ventricular hypertrophy induced by monocrotaline (MCT, 60 mg/kg/d) and examined the possible antihypertrophic mechanism in male Sprague Dawley rats. MCT-intoxicated animals were treated with TG (20, 40, 60 mg/kg/d) for 18 d. TG treatment ameliorated MCT-induced elevations in right ventricular peak systolic pressure, right ventricular hypertrophy and the expression of atrial natriuretic peptide; N(G)-nitro-L-arginine-methyl ester (L-NAME), an NO synthase (NOS) inhibitor, had no influence on these inhibitory effects of TG 40 mg/kg/d, and TG at this dose had no any effect on the eNOS mRNA expression, suggesting the limited rule of NO in TG's effects. To further examine the mechanisms of the protection, the expression of calcineurin and its catalytic subunit CnA, as well as extracellular signal-regulated kinase-1 (ERK-1) and mitogen-activated protein kinase (MAPK) Phosphatase-1 (MKP-1) was examined. TG treatment significantly suppressed MCT-induced elevations of these signaling pathways in a dose-dependent manner. In summary, TG is effective in protecting against MCT-induced right ventricle hypertrophy, possibly through lowering pulmonary hypertension. Multiple molecular mechanisms appeared to be involved in this protection, such as the suppression of MCT-activated calcineurin and ERK signaling pathways.
Biological & Pharmaceutical Bulletin 09/2008; 31(8):1530-5. · 1.66 Impact Factor
