Protective effects of corni fructus extract in mice with potassium oxonate-induced hyperuricemia.

Corni fructus is consumed as food and herbal medicine in Chinese culture. Studies have revealed that corni fructus exhibits potent antioxidant activity; however, few studies have investigated the ability of corni fructus to lower uric acid concentrations. In this study, the xanthine oxidase (XO) inhibition and uric acid-lowering effect of corni fructus extract (CFE) were evaluated in mice with potassium oxonate-induced hyperuricemia. Hyperuricemia is a chronic disease prevalent worldwide and is associated with high recurrence rates. In addition, drugs used to treat hyperuricemia induce side effects that discourage patient compliance. Hyperuricemia induces metabolic imbalances resulting in accumulative uric acid deposition in the joints and soft tissues. Hyperuricemia not only induces gout but also interrupts hepatic and renal function, thereby trigging severe inflammation and various complications, including obesity, nonalcoholic fatty liver disease, diabetes, and metabolic diseases. In this study, the ethyl acetate fraction (EAF) of CFE resulted in yields of antioxidant photochemical components significantly higher than those of CFEs formed using other substances. The EAF of CFE exhibited high free radical scavenging activity and XO inhibition and effectively lowered uric acid concentrations in the animal model of chemically induced hyperuricemia. The results of this study can serve as a reference for the prevention of preclinical gout as well as for functional food research.

A Rapid and Feasible 1H-NMR Quantification Method of Ephedrine Alkaloids in Ephedra Herbal Preparations.

A highly specific and sensitive proton nuclear magnetic resonance (1H-NMR) method has been developed for the quantification of ephedrine alkaloid derivatives in Ephedra herbal commercial prescriptions. At the region of δ 4.0 to 5.0 ppm in the 1H NMR spectrum, the characteristic signals are separated well from each other, and six analogues in total, methylephedrine (ME), ephedrine (EP), norephedrine (NE), norpseudoephedrine (NP), pseudoephedrine (PE), and methylpseudoephedrine (MP) could be identified. The quantities of these compounds are calculated by the relative ratio of the integral values of the target peak for each compound to the known concentrations of the internal standard anthracene. The present method allows for a rapid and simple quantification of ephedrine alkaloid derivatives in Ephedra-related commercial prescriptions without any preliminary purification steps and standard compounds, and accordingly it can be a powerful tool to verify different Ephedra species. In comparison to conventional chromatographic methods, the advantages of this method include the fact that no standard compounds are required, the quantification can be directly performed on the crude extracts, a better selectivity for various ephedrine alkaloid derivatives, and the fact that a very significant time-gain may be achieved.

Intraocular pressure-lowering effect of Cordyceps cicadae mycelia extract in a glaucoma rat model.

Glaucoma is a leading cause of irreversible blindness worldwide. This study evaluates the reduction of intraocular pressure (IOP) induced by C. cicadae mycelia extract in a steroid-induced rat model of glaucoma. Cordyceps cicadae mycelia is a well-known and valued traditional Chinese herbal medicine. C. cicadae mycelia were cultured using a liquid fermentation technique. The harvested C. cicadae mycelia were then lyophilized and extracted with two solvents, water and ethanol. The aqueous extract (CCM-DW) and ethanolic extract (CCM-EtOH) of the mycelia were obtained through lyophilization. Sprague Dawley rats were randomly divided into four groups (n = 6 in each group): a normal group, a control group, and experimental groups treated with CCM-DW, or CCM-EtOH (both at 50 mg/kg/body weight). Except for those in the normal group, all rats received a subconjunctival injection of betamethasone to induce high IOP. The rats in the experimental groups received a daily administration of CCM by oral gavage for four consecutive weeks. IOP reduction is the known treatment for glaucoma. The results revealed that steroid treatment caused a significant increase in the animals' IOP (control group). Elevated IOP decreased significantly after treatment with CCM-DW and CCM-EtOH (p < 0.01), and CCM-DW was more effective than CCM-EtOH. CCM-DW and CCM-EtOH were capable of causing significant decreases in high IOP-induced lesions in pathological studies in which it was shown that the efficacy of CCM-DW surpassed that of CCM-EtOH. After CCM-DW administration for 28 days, there were significant decreases in malondialdehyde and lactate dehydrogenase levels and significant increases in catalase, superoxide dismutase, and glutathione peroxidase levels. In summary, C. cicadae mycelia may be beneficial for preventing or treating glaucoma due to its significant IOP-lowering and antioxidant activities.

Protective effect of Corchorus capsularis L. leaves on ethanol-induced acute gastric mucosal lesion in rats.

In Taiwan, Corchorus capsularis L. has long been cultivated and the leaves are consumed as edible vegetable. This study is to investigate the protection effect of extract of C. capsularis leaves (ECC) on ethanol-induced acute gastric mucosal lesion (AGML) in rats. The results of phytochemical determination in ECC for total polyphenol, flavonoid and polysaccharide were 59.88 ± 0.61 mg/g, 86.39 ± 18.0 mg/g and 320.89 ± 6.99 mg/g, respectively. ECC showed significant activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging with IC50 of 0.25 mg/ml. In vivo studies, Sprague-Dawley (SD) rats were randomly divided into five groups: sham, vehicle (control) and low-, medium-, and high-dose ECC (LECC, MECC, HECC; 200, 400, and 1,000 mg/kg/day, respectively). ECC was able to decrease significantly the ulcer index (UI) caused by 80% ethanol in a dose dependent manner. There was no significant effect on growth trend and food intake rate after the administration of ECC in the experimental period. The serum lipid parameters in ECC groups revealed significant increase in glutathione peroxidase (GPx), superoxide dilmutase (SOD) and catalase (CAT), and a decrease in malondialdehyde (MDA). Significant amelioration on pathological lesion score was found in ECC groups compared with the control group (P<0.05). The overall results indicate that ECC has protective effects on ethanol-induced AGML in rats, which could be associated with its antioxidant activity.

Autophagy and apoptotic machinery caused by Polygonum cuspidatum extract in cisplatin­resistant human oral cancer CAR cells.

Polygonum cuspidatum (Hu Zhang) is a traditional Chinese medicine (TCM) and has been revealed to exert anticancer, anti­angiogenesis, anti­human immunodeficiency virus (HIV), anti­hepatitis B virus, anti­microbial, anti­inflammatory, and neuro­protective bio­activities. However, the effect of P. cuspidatum extract (PCE) on drug­resistant human oral cancer cells regarding cell death is not fully understood yet. The present study was undertaken to explore the induction of autophagic and apoptotic cell death and to investigate their underlying molecular mechanisms in PCE­treated cisplatin­resistant human oral cancer CAR cells. Our results revealed that PCE was determined via HPLC analytic method, and it was revealed that resveratrol may be a major compound in PCE. The data also demonstrated that PCE reduced CAR cell viability in a concentration­ and time­dependent response via an MTT assay. PCE had an extremely low toxicity in human normal gingival fibroblasts (HGF). Autophagic and apoptotic cell death was found after PCE treatment by morphological determination. PCE was revealed to induce autophagy as determined using acridine orange (AO), LC3­GFP, monodansylcadaverine (MDC) and LysoTracker Red staining in CAR cells. In addition, PCE was revealed to induce apoptosis in CAR cells via 4',6­diamidino­2­phenylindole (DAPI)/terminal deoxynucleotidyl transferase dUTP nick­end labeling (TUNEL) double staining. PCE significantly stimulated caspase­9 and ­3 activities as revealed using caspase activity assays. PCE markedly increased the protein levels of Atg5, Atg7, Atg12, Beclin­1, LC3, Bax and cleaved caspase­3, while it decreased the protein expression of Bcl­2 in CAR cells as determined by western blotting. In conclusion, our findings are the first to suggest that PCE may be potentially efficacious for the treatment of cisplatin­resistant human oral cancer.

Effects of Lycium barbarum (goji berry) on dry eye disease in rats.

Lycium barbarum (goji berry) has long been used as a food and traditional herbal medicine. This study aimed to investigate the beneficial effect of the goji berry on dry eye disease in rats. Male Sprague­Dawley rats with induced dry eye disease were randomly assigned to four groups: Vehicle (control), low­dose goji berry extract [GBE; 250 mg/kg/body weight (bw)], median­dose GBE (350 mg/kg/bw), and high­dose GBE (500 mg/kg/bw). Three methods, Schirmer's test, tear break­up time (BUT) measurement and keratoconjunctival fluorescein staining, were used to evaluate the effect of GBE on symptoms of dry eye disease experienced by the rats. The results of the present study revealed that both the Schirmer's test score and tear BUT significantly increased following 1 week of GBE administration. Furthermore, the severity of the keratoconjunctival staining decreased significantly. In addition, the results suggested that administration of GBE may ameliorate dry eye disease symptoms in a dose­dependent manner. There were no mortalities and no apparent abnormal histopathology changes in the liver or kidney tissues of rats administered GBE for 21 consecutive days. Polysaccharides and betaine present in GBE may have important effects in alleviating dry eye disease induced by oxidative stress and inflammation. In conclusion, the goji berry is a safe, functional food with beneficial effects in alleviating dry eye disease.

Effect of burdock extract on physical performance and physiological fatigue in mice.

Burdock (BD) is a common vegetable with many pharmacological properties. However, few studies have examined the effect of BD on exercise performance and physical fatigue. We aimed to evaluate the potential beneficial effects of BD on fatigue and ergogenic functions following physical challenge in mice. METHODS: Male ICR mice were divided into four groups to receive either vehicle, or BD at 348.5, 697 or 1,742.5 mg/kg/day, by daily oral gavage for 4 weeks. Exercise performance and fatigue were evaluated from forelimb grip strength, exhaustive swimming time, and post-exercise levels of physical fatigue-related biomarkers serum lactate, ammonia, glucose, and creatine kinase (CK). RESULTS: BD supplementation elevated endurance and grip strength in a dose-dependent manner. It also significantly decreased lactate, ammonia, and CK levels after physical challenge. In addition, BD supplementation had few subchronic toxic effects. CONCLUSIONS: Supplementation with BD has a wide spectrum of bioactive effects, including health promotion, performance improvement, and fatigue reduction.

Anti-inflammatory Flavan-3-ol-dihydroretrochalcones from Daemonorops draco.

Four A-type flavan-3-ol-dihydroretrochalcone dimers, dragonins A-D (1-4), were characterized from the traditional Chinese medicine Sanguis Draconis. The structures of 1-4 were elucidated by spectroscopic and spectrometric analyses. Compounds 1 and 2 exhibited significant inhibition of fMLP/CB-induced superoxide anion and elastase. The signaling pathways accounting for the inhibitory effects of compound 2 were also elucidated. These purified A-type flavan-3-ol-dihydroretrochalcones are new potential leads for the development of anti-inflammatory drugs.

Ionone Derivatives from the Mycelium of Phellinus linteus and the Inhibitory Effect on Activated Rat Hepatic Stellate Cells.

Three new γ-ionylideneacetic acid derivatives, phellinulins A-C (1-3), were characterized from the mycelium extract of Phellinus linteus. The chemical structures were established based on the spectroscopic analysis. In addition, phellinulin A (1) was subjected to the examination of effects on activated rat hepatic stellate cells and exhibited significant inhibition of hepatic fibrosis.

Effect of NPC-14686 (Fmoc-l-Homophenylalanine) on Ca²âº Homeostasis and Viability in OC2 Human Oral Cancer Cells.

The effect of the anti-inflammatory compound NPC-14686 on intracellular Ca²âº concentration ([Ca²âº](i)) and viability in OC2 human oral cancer cells was investigated. The Ca²âº-sensitive fluorescent probe fura-2 was used to examine [Ca²âº](i). NPC-14686 induced [Ca²âº](i) rises in a concentration-dependent fashion. The effect was reduced approximately by 10% by removing extracellular Ca²âº. NPC-14686- elicited Ca²âº signal was decreased by nifedipine, econazole, SKF96365, and GF109203X. In Ca²âº-free medium, incubation with the endoplasmic reticulum Ca²âº pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) abolished NPC-14686-induced [Ca²âº](i) rises. Conversely, pretreatment with NPC-14686 abolished thapsigargin or BHQ-induced [Ca²âº](i) rises. Inhibition of phospholipase C with U73122 abolished NPC-14686-induced [Ca²âº](i) rises. At 20-100 µM, NPC-14686 inhibited cell viability, which was not reversed by chelating cytosolic Ca²âº with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'- tetraacetic acid-acetoxymethyl ester (BAPTA/AM). NPC-14686 between 20 µM and 40 µM also induced apoptosis. Collectively, in OC2 cells, NPC-14686 induced [Ca²âº](i) rises by evoking phospholipase C-dependent Ca²âº release from the endoplasmic reticulum and Ca²âº entry via protein kinase C-regulated store-operated Ca²âº channels. NPC-14686 also caused Ca²âº-independent apoptosis.

Effect of curcumin supplementation on physiological fatigue and physical performance in mice.

Curcumin (CCM) is a well-known phytocompound and food component found in the spice turmeric and has multifunctional bioactivities. However, few studies have examined its effects on exercise performance and physical fatigue. We aimed to evaluate the potential beneficial effects of CCM supplementation on fatigue and ergogenic function following physical challenge in mice. Male ICR mice were divided into four groups to receive vehicle or CCM (180 µg/mL) by oral gavage at 0, 12.3, 24.6, or 61.5 mL/kg/day for four weeks. Exercise performance and anti-fatigue function were evaluated after physical challenge by forelimb grip strength, exhaustive swimming time, and levels of physical fatigue-associated biomarkers serum lactate, ammonia, blood urea nitrogen (BUN), and glucose and tissue damage markers such as aspartate transaminase (AST), alanine transaminase (ALT), and creatine kinase (CK). CCM supplementation dose-dependently increased grip strength and endurance performance and significantly decreased lactate, ammonia, BUN, AST, ALT, and CK levels after physical challenge. Muscular glycogen content, an important energy source for exercise, was significantly increased. CCM supplementation had few subchronic toxic effects. CCM supplementation may have a wide spectrum of bioactivities for promoting health, improving exercise performance and preventing fatigue.

Antioxidant and antifatigue activities of Polygonatum Alte-lobatum Hayata rhizomes in rats.

Polygonatum alte-lobatum Hayata, a rhizomatous perennial herb, belongs to the Liliaceae family and is endemic to Taiwan. We investigated the antioxidant and anti-fatigue activities of P. alte-lobatum in exercised rats. Levels of polyphenols, flavonoids and polysaccharides and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging activity were measured in extracts of P. alte-lobatum (EPA). Sprague-Dawley rats were randomly divided into four groups for 8-week treatment with vehicle (control) and low-, medium-, and high-dose EPA (LEPA, MEPA, HEPA; 0, 75, 150, and 375 mg/kg/day, respectively). Exercise performance was evaluated by exhaustive treadmill exercise time and by changes in body composition and biochemical variables at the end of the experiment. EPA contained polyphenols, flavonoids and polysaccharides, with polysaccharide content at least 26 times greater than that of polyphenols and flavonoids. Trend analysis revealed that EPA dose-dependently scavenged DPPH free radicals. EPA treatment dose-dependently increased endurance running time to exhaustion and superoxide dismutase activity and total antioxidant ability of blood. EPA dose-dependently decreased serum urea nitrogen and malondialdehyde levels after exercise. Hepatic glycogen content, an important energy source for exercise, was significantly increased with EPA treatment. EPA could be a potential agent with an anti-fatigue pharmacological function.

Hypolipidemic activity of Taraxacum mongolicum associated with the activation of AMP-activated protein kinase in human HepG2 cells.

This study investigated the hypolipidemic effect and potential mechanisms of T. mongolicum extracts. T. mongolicum was extracted by refluxing three times with water (TM-1), 50% ethanol (TM-2) and 95% ethanol (TM-3). TM-2 contained components with the most effective hypolipidemic potentials in HepG2 cells. Extended administration of TM-2 stimulated a significant reduction in body weight and levels of serum triglyceride LDL-C and total cholesterol in rats. To evaluate the bioactive compounds, we successively fractionated TM-2 with n-hexane (TM-4), dichloromethane (TM-5), ethyl acetate (TM-6), and water (TM-7). TM-4 fraction had the most effective hypolipidemic potential in HepG2 cells, and it decreased the expression of fatty acid synthase (FASN) and inhibited the activity of acetyl-coenzyme A carboxylase (ACC) through the phosphorylation of AMP-activated protein kinase (AMPK). Linoleic acid, phytol and tetracosanol are bioactive compounds identified from TM-4. These results suggest that T. mongolicum is expected to be useful for hypolipidemic effects.

The activity of lowering intraocular pressure of cassiae seed extract in a DBA/2J mouse glaucoma model.

PURPOSE: To evaluate the activity of lowering intraocular pressure (IOP) by Cassiae seed in the DBA/2J mouse glaucoma model. METHODS: Young male (mean age: 3 months) inherited glaucoma mice (BDA/2J) were enrolled in this study. To evaluate the potential of Cassiae seed in the treatment of glaucoma, all subjects were divided into 6 groups. There were 1 sham group, positive control identified as group 2 topical brimonidine and group 3 oral acetazolamide, and groups 4-6 Cassiae seed extract (CSE) groups. The lactate dehydrogenase (LDH) level in the anterior aqueous humor and the changes of IOP were investigated. Contents of total polyphenol glycosides in the CSE were measured using a high-performance liquid chromatography (HPLC) method. Chromatographic separation was performed on a Cosmosil 5C(18)-MS reverse-phase HPLC column (4.6×250-mm i.d., 5 µm) with methanol/0.1% H(3)PO(4) as the mobile phases in a gradient elution mode at a flow rate of 1.0 mL/min and an injection volume of 10 µL. The wavelength of UV detector was set at 254 nm. RESULTS: The LDH level in the anterior aqueous humor and IOP significantly decreased after treatment with CSE. The IOP-lowering effect of CSE was comparable to those of oral acetazolamide and brimonidine instillation. There were no abnormal findings in the external appearance, and body weight change after treatment with CSE for 5 weeks. Chrysophanol and physcion were measured by an HPLC method to obtain total polyphenol glycosides of the CSE, and were involved in the IOP-lowering function. CONCLUSION: Cassiae seed may be safe and beneficial for treating glaucoma due to its significant IOP- and LDH-lowering activities.

Body weight management effect of burdock (Arctium lappa L.) root is associated with the activation of AMP-activated protein kinase in human HepG2 cells.

Burdock (Arcticum lappa L.) root is used in folk medicine and also as a vegetable in Asian countries. In the present study, burdock root treatment significantly reduced body weight in rats. To evaluate the bioactive compounds, we successively extracted the burdock root with ethanol (AL-1), and fractionated it with n-hexane (AL-2), ethyl acetate (AL-3), n-butanol (AL-4), and water (AL-5). Among these fractions, AL-2 contained components with the most effective hypolipidemic potential in human hepatoma HepG2 cells. AL-2 decreased the expression of fatty acid synthase (FASN) and inhibited the activity of acetyl-coenzyme A carboxylase (ACC) by stimulating AMP-activated protein kinase (AMPK) through the LKB1 pathway. Three active compounds were identified from the AL-2, namely α-linolenic acid, methyl α-linolenate, and methyl oleate. These results suggest that burdock root is expected to be useful for body weight management.

Induction of apoptosis by [8]-shogaol via reactive oxygen species generation, glutathione depletion, and caspase activation in human leukemia cells.

Ginger, the rhizome of Zingiber officinale , is a traditional medicine with a carminative effect and antinausea, anti-inflammatory, and anticarcinogenic properties. This study examined the growth inhibitory effects of [8]-shogaol, one of the pungent phenolic compounds in ginger, on human leukemia HL-60 cells. It demonstrated that [8]-shogaol was able to induce apoptosis in a time- and concentration-dependent manner. Treatment with [8]-shogaol caused a rapid loss of mitochondrial transmembrane potential, stimulation of reactive oxygen species (ROS) production, release of mitochondrial cytochrome c into cytosol, and subsequent induction of procaspase-9 and procaspase-3 processing. Taken together, these results suggest for the first time that ROS production and depletion of glutathione that contributed to [8]-shogaol-induced apoptosis in HL-60 cells.

Effect of shanzha, a Chinese herbal product, on obesity and dyslipidemia in hamsters receiving high-fat diet.

AIM: The present study is designed to investigate the effect of shanzha (Crataegus pinnatifida) on obesity or dyslipidemia induced by high-fat diet in hamsters and characterize the role of PPARalpha in this action of shanzha. MATERIALS AND METHODS: We induced dyslipidemia and obesity in hamsters using high-fat diet and treated hamsters with shanzha or vehicle for 7 days. We measured the body weight, adipose tissue weights, and food intake of hamsters. Plasma total cholesterol (TC), triglyceride (TG), LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) were determined at the beginning and end of this treatment. Effect of shanzha on adipogenesis was examined in vitro and change of PPARalpha was analyzed using Western blot. RESULTS: The food intake, body weights, and weights of both brown and white adipose tissues were markedly reduced in hamsters receiving shanzha as compared with the vehicle-treated control. Plasma levels of TC, TG and LDL-C were decreased by this shanzha treatment while HDL-C was elevated. The effects of shanzha were reversed by the combined treatment with PPARalpha antagonist, MK886. Shanzha inhibited the fat droplet accumulation in 3T3-L1 adipocytes in a dose-dependent manner and this effect was abolished by MK886. Western blot results showed activation of PPARalpha by shanzha in hamster adipose tissue. CONCLUSION: We suggest that shanzha could activate PPARalpha to improve dyslipidemia or obesity.

The inhibition effect of 2,3,7,8-tetrachlorinated dibenzo-p-dioxin-induced aryl hydrocarbon receptor activation in human hepatoma cells with the treatment of cadmium chloride.

Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), considered as endocrine disruptors, tend to accumulate in fatty tissues. Dioxin-responsive element chemical activated luciferase gene expression assay (DRE-luciferase assay) has been recognized as a semi-quantitative method for screening dioxins for its fast and low-cost as compared with HRGC/HRMS. However, some problems with the bioassay, including specificity, detection variation resulted from different cleanup strategies, and uncertainty of false-negative or false-positive results, remain to be overcome. Cadmium is a prevalent environmental contaminant around the world. This study was aimed to examine the effects of cadmium on the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced activation of aryl hydrocarbon receptor (AhR)-mediated gene expression in human hepatoma cells (Huh7-DRE-Luc cells and Huh7 cells). Ethoxyresorufin-O-deethylase (EROD) and DRE-luciferase assay were employed to determine the enzyme activity of cytochrome P450 1A1 (CYP1A1) and activation of AhR, respectively. The results showed that Cd(2+) levels significantly inhibited the induction of TCDD-induced CYP1A1 and DRE luciferase activation in hepatoma cells. The 50% inhibited concentrations (IC(50)) of CdCl(2) were 0.414 microM (95% confidence interval (C.I.): 0.230-0.602 microM) in Huh7-DRE-Luc cells and 23.2 microM (95% C.I.: 21.7-25.4 microM) in Huh7 cells. Accordingly, prevention of interference with non-dioxin-like compounds in a DRE-luciferase assay is of great importance in an extensive cleanup procedure.

Elimination of ephedrines in urine following administration of a Sho-seiryu-to preparation.

Sho-seiryu-to is one of the most common Traditional Chinese Medicine preparations for the attenuation of colds. Ephedrae Herba is one of the prescriptions of Sho-seiryu-to. The major ingredients of Ephedrae Herba, ephedrines, are banned substances on the World Anti-Doping Agency (WADA) list. The purpose of this study was to investigate the elimination of urinary ephedrines after administering Sho-seiryu-to preparation and to determine the possibility of positive ephedrines test results in urine. Six healthy volunteers took a single 2.5-g dose of concentrated Sho-seiryu-to preparation. All urine was collected for 48 h. The concentrations of urinary ephedrines were analyzed by high-performance liquid chromatography and the elimination half-life of the ephedrines was estimated. The results show that ephedrine and cathine (norpseudoephedrine), the prohibited substances of the WADA, were excreted in the urine after taking a single dose of Sho-seiryuto preparation. The peak concentration of ephedrine was 3.88 +/- 1.87 mg/mL (mean +/- SD), which was lower than the WADA permitted value (10 mg/mL). The estimated elimination half-lives of ephedrine, norephedrine, pseudoephedrine, and norpseudoephedrine following administration of this preparation were 5.3 +/- 1.2, 4.9 +/- 0.9, 4.4 +/- 1.0, and 5.4 +/- 1.8 h, respectively. This study concluded that the urine would not violate the antidoping rules after administering a single dose of Sho-seiryu-to preparation. Nevertheless, an applied multiple-dose study upon administering the preparation for three times per day for three days showed a positive urine ephedrine result (13.7 mg/mL). Athletes should be careful when taking more than a single dose of Sho-seiryu-to preparation.

Autonomic nervous system mediates the cardiovascular effects of Rhodiola sacra radix in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola sacra (Crassulaceae) exhibits cardiovascular bioactivities and is used in Tibetan medicine for promoting circulation and preventing hypertension. However, the underlying mechanisms of its cardiovascular effects are poorly understood. AIM OF THE STUDY: The aim of this study was therefore to evaluate the cardiovascular activity of water-soluble fraction (WtF) and n-butanol-soluble fraction (BtF) of Rhodiola sacra radix and to explore its mechanism of action in propofol anesthetized Sprague-Dawley rats. MATERIALS AND METHODS: The changes of blood pressure, heart rate and cardiac contractility after systemic administration of the extracts (10-75 mg/kg) were examined for at least 40 min. Different antagonists were used to evaluate the mechanisms of cardiovascular effects of the extracts. RESULTS: Intravenous injection of the WtF (10, 25, 35, 50 or 75 mg/kg) exhibited dose-dependent hypotension and increases in heart rate and cardiac contractility. In contrast, mild alterations in the same cardiovascular parameters were detected only at high dose (75 mg/kg) BtF. The WtF-induced hypotensive, positive inotropic and chronotropic effects were significantly abolished by pretreatment with hexamethonium (30 mg/kg, i.v.) or reserpine (5 mg/kg, i.v.), whereas the hypotensive, but not the positive inotropic or chronotropic effect was potentiated by captopril (2.5 mg/kg, i.v.). Pretreatment with methylatropine (1 mg/kg, i.v.), on the other hand, reversed the positive inotropic and chronotropic but not the hypotensive effects of WtF. The WtF-induced cardiovascular responses were not affected in rats pretreated with N(G)-nitro-l-arginine methyl ester (20 mg/kg, i.v.). CONCLUSIONS: We conclude that systemic administration of the WtF of Rhodiola sacra radix elicited a potent hypotensive effect that was mediated by the withdrawal of sympathetic vasomotor tone and interaction with the circulatory angiotensin system. The positive inotropic and chronotropic effects of WtF may result from a direct vagal inhibition on the heart.