Noscapine Modulates Neuronal Response to Oxygen-glucose Deprivation/Reperfusion Injury Via Activation of Sigma-1 Receptor in Primary Cortical Cultures.

In the present study, we investigated the effects of noscapine (0.5-2 µM), an alkaloid from the opium poppy (Papaver somniferum), on primary murine cortical neurons exposed to 60 min oxygen-glucose deprivation (OGD) in the presence of 5 µM BD-1047, a selective sigma-1 receptor antagonist. The experiments were performed on cortical neurons after 11-16 days of culture. To initiate oxygen-glucose deprivation, the culture medium was transferred to glucose-free DMEM, and placed in a humidified incubation chamber containing a mixture of 95% N2 and 5% CO2 at 37 °C for 60 min. In order to explore the effect on neurons under oxygen-glucose deprivation in this condition, some cultures were pretreated with noscapine and BD1047 together, 24 h prior to OGD followed by 24 h recovery. Cell viability, nitric oxide (NO) production and intracellular calcium concentration ([Ca2+]i) levels were evaluated by MTT assay, the modified Griess method, and Fura-2, respectively. Pretreatment of the cultures with noscapine in the presence of BD1047 significantly increased cell viability and decreased NO generation in a dose-dependent manner compared to BD1047 alone. Pretreatment with 2 µM noscapine and BD-1047 was shown to decrease the rise in [Ca2+]i induced by sodium azide (NaN3) and glucose deprivation. We concluded that noscapine in the presence of BD1047 could protect primary cortical neurons after oxygen-glucose deprivation-induced cell injury but this effect was not complete. Our results indicate that neuroprotective effects of noscapine could be mediated partially through activation of sigma-1 receptor and by decreasing NO production and [Ca2+]i levels.

The Effect of Voluntary Exercise and Prenatal Exposure to Sodium Valproate on Learning, Memory, and Anxiety of Rats' Offspring.

BACKGROUND: Antiepileptic drugs, such as sodium valproate (SV), are teratogenic as their usage by the pregnant mother has been associated with an increased risk of major congenital abnormalities in the fetus. In this study, the effects of voluntary exercise and prenatal exposure to SV on learning, memory, and anxiety in rats' offspring are investigated. METHODS: In the present study, 70 female albino Wistar rats (200-240g) were used. The rats were categorized in seven groups: 1 and 2, pregnant rats with exposure to SV (10 mg/kg/day i.p) 3 and 4, pregnant rats with exposure to SV (20 mg/kg/day i.p) 5 and 6, pregnant rats with exposure to normal saline (0.4 ml/day i.p) and 7, pregnant rats with exposure to lamotrigine (20 mg/kg/day i.p). The even and odd groups were sedentary and voluntary exercise groups, respectively. Learning and memory were tested in male offspring using shuttle-box; anxiety was tested by elevated plus-maze (each group n=12). Statistical analyses were performed using the one-way ANOVA (the Tukey test) and/or two-way ANOVA on rank. RESULTS: The results showed that voluntary exercise in male rats caused improvement of latency and duration time in the dark box compared to sedentary groups (P=0.004). Moreover, the group administrated with 10 mg/kg SV showed better learning capability than the group administrated with 20 mg/kg SV. Voluntary exercise could also improve anxiety (P=0.001). CONCLUSION: This study indicated that exercise could increase learning capacity and improve memories in rats' offspring whose mothers were exposed to SV. Voluntary exercise could improve anxiety too, and the effect was dose-dependent.

Preparation, characterization, and evaluation of the anticancer activity of artemether-loaded nano-niosomes against breast cancer.

BACKGROUND: The aim of this study was to develop nonionic surfactant vesicles (niosomes) as a promising nanocarrier to enhance the anticancer activity of artemether. METHODS: The niosomes were prepared by thin-film hydration method containing a mixture of Span, Tween and cholesterol (Chol) in different molar ratios. All formulations were characterized in terms of size, entrapment efficiency (%EE), release profile and morphology. The optimized niosomal formulation (F7), artemether and phosphate buffered saline (PBS) were intratumorally administrated to mice as the nano-niosome group, the free drug group and the control group, respectively (n = 4 per group). Tumor volume was measured during the 12-day experiment, then mice were sacrificed to evaluate the necrosis, angiogenesis, and cell proliferation of tumor tissues by H&E, CD34 and Ki-67 immunostaining, respectively. RESULTS: Both artemether and nano-niosome groups could decrease angiogenesis and proliferation of tumor cells. However, in nano-niosome group superior tumor necrosis and smaller tumor volume were observed compared to both artemether and control groups. CONCLUSIONS: The niosomal formulation could be a promising carrier for breast cancer treatment.

A New Potentiometric Sensor for Determination and Screening Phenylalanine in Blood Serum Based on Molecularly Imprinted Polymer.

Methods routinely utilized for detection of phenylalanine in new-born blood consist of enzymatic assays, lacking sensitivity and HPLC assays which are expensive and time-consuming to conduct. We, here, report for the first time, the construction of a phenylalanine sensitive electrode, on the basis of a selective molecularly imprinted polymer, offering sensitivity, economy and ease of use for the measurement of phenylalanine .The sensor was constructed of a graphite-rod electrode which was coated by MIP embedded polymer base made from polyvinyl chloride and plasticizer mixture, dissolved in THF. At optimized conditions the electrode revealed a Nernstian response 29.73 ± 1.0 mV decade-1 in a concentration range of 1 × 10⁻8 to 1 × 10-4 M with detection limit of 5 × 10⁻9 M. The potential response of the electrode was constant in the pH range of 4.0-7.5. The electrode unfolded a response time of ~20 sec. The selectivity coefficient of the sensor towards a number of different amino acids with molecular similarities and some metal ions was evaluated. The sensor was successfully used for determination of phenylalanine in blood serum and the results were in good compatibility with HPLC method.

A 53 KDa Glycan Antigen of Hydatid Cyst Wall May Involve in Evasion from Host Immune System.

BACKGROUND: Recent studies have shown that similar host glycan antigens are expressed by helminths such as Echinococcus granulosus hydatid cysts to evade from host immune system. In this work to investigate these antigens further, immunological cross-reactivity between human sera and hydatid cyst wall antigens has been investigated. MATERIALS AND METHODS: Hydatid cyst wall antigens were used in enzyme-linked immunosorbent assay and Western immunoblotting and probed with pooled sera of hydatidosis patients and healthy controls. Sodium metaperiodate treatment was used to investigate glycan antigens. RESULTS: A band with molecular weight about 53 KDa reacted with both hydatid patients' sera and also normal human sera. It has been shown that this band was a glycan antigen. CONCLUSIONS: A 53 KDa glycan antigen of hydatid cyst wall that reacted with all human sera may have an important role for evasion from host immune system.

Antibody response to glycan antigens of hydatid cyst fluid, laminated layer and protoscolex of Echinococcus granulosus.

Background: Hydatid disease is characterized by long-term growth of hydatid cysts in the human. The glycan antigens have an important role in the immunology of hydatid cyst. In this study immunological reaction of host sera to different glycan antigens of the cyst, has been investigated. Methods: The antibody responses were tested to glycoprotein and glycolipid of the laminated layer (LL), cyst fluid (CF) and protoscolex (PS) antigens of E. Granulosus using ELISA and western immunoblotting tests. Thin-layer chromatography and ß-elimination were used for glycan purification. Results: Both hydatid cyst and normal human sera reacted with hydatid cyst fluid, protoscolices, laminated layer, glycoprotein and glycolipid antigens. The most antigen-antibody reaction was related to CF and PS antigens, and LL antigens had the minimal reaction with the sera. Thin layer chromatography (TLC) of the antigens showed presence of many glycan bands in the laminated layer. Conclusion: The parasite may elaborate different glycan antigens in LL to evade host immune response.

Pharmacokinetics of calycopterin and xanthmicrol, two polymethoxylated hydroxyflavones with anti-angiogenic activities from Dracocephalum kotschyi Bioss.

BACKGROUND: Recently flavonoids have attracted the attention of researchers in the fight against cancer. Calycopterin and xanthomicrol, are two polymethoxylated flavonoids found in the aerial parts of Dracocephalum kotschyi Bioss.. We have recently shown that these compounds possess antiangiogenic activity and may be of value as potential anticancer agents. In order to demonstrate putative in vivo antitumor effect of these compounds we needed preliminary information on both pharmacokinetics and toxicological properties of these two agents. METHOD: A new online SPE HPLC method for measurement of calycopterin and xanthomicrol in rat plasma was developed. Pharmacokinetic parameters of calycopterin and xanthomicrol, after i.v. administration in rats, were determined. RESULTS: The plasma half-life for both agents was around 4 h, however, the volume of distribution of calycopterin appeared to be about 8 times greater than xanthomicrol. This was probably due the greater hydrophobicity of the former which had other consequences such as much smaller maximum plasma concentration of calycopterin compared to its less methoxylated congener. Preliminary toxicological study of xanthomicrol failed to show any behavioral, histological and biochemical adverse effects after repeated administrations of high doses. Pharmacokinetics of xanthomicrol in rats.

Comparative Analytical Performance of Various HbA1c Assays in Iran.

INTRODUCTION: Hemoglobin A1c (HbA1c) measurement devices are widely used to evaluate glycemic control in diabetic patients. The aim of this study was to investigate the comparability of various HbA1c instruments used in Iran. METHODS: In the present study, 154 fresh whole blood samples from diabetic patients, with different HbA1c levels (4.0%-10%) and no types of hemoglobinopathy were analyzed by six HbA1c assays including one high performance liquid chromatography (HPLC) method (D10 HbA1c), two immunoassay methods (COBAS INTEGRA 400 and Pars Azmoon kit), one Boronate affinity method (Nycocard Reader II), and two ion exchange methods (Biosystems and DS5). The two National Glycohemoglobin Standardization Programs (NGSP) certified system, D10 and COBAS INTEGRA 400 which are certified as secondary reference measurement procedures, were considered as reference methods. The CLSI document (EP9-A2) - Method comparison and Bias estimation using patient samples, approved guideline - was used to compare the performance of different HbA1c instruments. RESULTS: The mean of HbA1c in all four types of assays was less than the reference methods (P-value < 0.01).The mean of absolute difference between the reference methods was the least (0.11%). Among the other four tests, Biosystems had the smallest mean of difference (-0.21%), while Pars Azmoon had the highest (-1.18%). Pars Azmoon showed the greatest difference (95% confidence interval) when compared to D10 [-15.5%(-5.7%to -25.3%)] and COBAS INTEGRA [-17% (-9.16% to -24.84%)]. The highest regression slope (B) was found in DS5 method (0.96) in regression model with both reference methods. CONCLUSION: It can be concluded that although HbA1c standardization programs have resulted in great improvements in the comparability of HbA1c assays, unacceptable errors still exist and further national and international projects are required for standardization of HbA1c measurement. In this situation, it is recommended to use the same laboratory for HbA1c measurement to monitor diabetic patients.

Camelid antivenom development and potential in vivo neutralization of Hottentotta saulcyi scorpion venom.

Scorpion envenoming is a serious health problem which can cause a variety of clinical toxic effects. Of the many scorpion species native to Iran, Hottentotta saulcyi is important because its venom can produce toxic effects in man. Nowadays, antivenom derived from hyper immune horses is the only effective treatment for sever scorpion stings. Current limitations of immunotherapy urgently require an efficient alternative with high safety, target affinity and more promising venom neutralizing capability. Recently, heavy chain-only antibodies (HC-Abs) found naturally in camelid serum met the above mentioned advantages. In this study, immuno-reactivities of polyclonal antibodies were tested after successful immunization of camel using H. saulcyi scorpion crude venom. The lethal potency of scorpion venom in C57BL/6 mice injected intraperitoneally was determined to be 2.7 mg/kg. These results were followed by the efficient neutralization of lethal activity of H. saulcyi scorpion venom by injection of antivenom and purified IgG fractions into mice intraperitonelly or intravenously, respectively. HC-Ab camelid antivenom could be considered as a useful serotherapeutics instead of present treatment for scorpion envenomation.

Effect of the different assays of HbA1c on diabetic patients monitoring.

BACKGROUND: HbA1c test is widely used for glycemic monitoring of diabetic patients. This study aimed to evaluate clinical performance of different assays for classification of patients into controlled and uncontrolled group base on ADA recommendations. METHOD: A total of 154 samples from patients with diabetes type 2 with HbA1c concentration covering the whole clinical range were analyzed by four commercially methods; D-10 Hb A1c (Bio-Rad Laboratories), Cobas Integra 400 (Roche Diagnostics), NycoCard Reader II (Axis-Shield) and DS5 (Drew Scientific). For each individual assay, patient's results were classified into controlled and uncontrolled groups (less or more than three decision levels; 6.5 %, 7 % and 8 %) compared to D10 results as reference method. The frequency of each group and also sensitivity, specificity, negative and positive predictive value were estimated. RESULTS: We found a significant correlation between assays (r: 0.937-0.945). Sensitivity, specificity, and positive and negative predictive values of the evaluated method to identify uncontrolled patients were as follows: 49.2-95.7 %, 86.5-100 %, 89.1-100 %, and 52.9-93.3 %; respectively. CONCLUSIONS: Results show that some HbA1c assays capability to classify diabetic patients according to HbA1c level is still unacceptable.

Commentary on prevention a possible drug-drug interaction: is concurrent administration of orlistat and pioglitazone increase the risk of durg-induced hepatotoxicity?

BACKGROUND: Drug-drug interactions (DDIs) are an emerging threat to public health and are difficult to detect. To prevent DDIs and their burden, the possible DDIs should be kept in mind. We know that the obesity predisposes to the development of insulin resistance and type 2 diabetes. Therefore, combinational uses of antiobesity drugs and glucose-lowering drugs are very common. As the hepatotoxicity of both pioglitazone (an antidiabetic drug) and orlistat (an antiobesity drug) has been shown in some cases, the aim of this study was to evaluate the interaction of pioglitazone and orlistat in human hepatocellular cell line human hepatocellular carcinoma (HepG2) cells to determine their effect on liver toxicity. METHODS: Human hepatocellular carcinoma cells were treated with 25 µM Pioglitazon (Pio), 20 µM Orlistat (Orl) pioglitazone, orlistat or combination of them. The MTT assay was used to assess cell viability. RESULTS: Pioglitazone and orlistat combination caused a loss of HepG2 cell viability. While pioglitazone (25 µM) and orliatat (20 µM) alone decreased the cell viability around 91% and 85% respectively (notsignificant, P > 0.05), the combination of these two drugs reduced the amount of viable cells to 55% which was significant when compared with each drug alone (P < 0.001). CONCLUSIONS: Revealing the significant loss of viability of HepG2 cells in the combination use of pioglitazone and orlistat indicates these two drugs should not be administered at the same time to prevent their hepatotoxic effects especially in patients with liver dysfunction.

Neuroprotective effect of noscapine on cerebral oxygen-glucose deprivation injury.

BACKGROUND: The present study aims to investigate the effect of noscapine (0.5-2.5 µM), an alkaloid from the opium poppy, on primary murine fetal cortical neurons exposed to oxygen-glucose deprivation (OGD), an in vitro model of ischemia. METHODS: Cells were transferred to glucose-free DMEM and were exposed to hypoxia in a small anaerobic chamber. Cell viability and nitric oxide production were evaluated by MTT assay and the Griess method, respectively. RESULTS: The neurotoxicities produced by all three hypoxia durations tested were significantly inhibited by 0.5 µM noscapine. Increasing noscapine concentration up to 2.5 µM produced a concentration-dependent inhibition of neurotoxicity. Pretreatment of cells with MK-801 (10 µM), a non-competitive NMDA antagonist, and nimodipine (10nM), an L-type Ca(2+) channel blockers, increased cell viability after 30 min OGD, while the application of NBQX (30 µM), a selective AMPA-kainate receptor antagonist partially attenuated cell injury. Subsequently, cells treated with noscapine in the presence of thapsigargin (1 µM), an inhibitor of endoplasmic reticulum Ca(2+) ATPases. After 60 min OGD, noscapine could inhibit the cell damage induced by thapsigargin. However, noscapine could not reduce cell damage induced by 240 min OGD in the presence of thapsigargin. Noscapine attenuated nitric oxide (NO) production in cortical neurons after 30 min OGD. CONCLUSIONS: We concluded that noscapine had a neuroprotective effect, which could be due to its interference with multiple targets in the excitotoxicity process. These effects could be mediated partially by a decrease in NO production and the modulation of intracellular calcium levels.

Preparation of a selective L-phenylalanine imprinted polymer implicated in patients with phenylketonuria.

BACKGROUND: Molecular imprinting is a method for synthesizing polymers with structure-selective adsorption properties with applications such as, selectivity binding, drug delivery systems and anti-bodies. The present study aims at optimizing the preparation of molecularly imprinted polymer (MIP) against l-phenylalanine, in order to increase phenylalanine-binding in Enzymatic Intestinal Simulated Fluid (ESIF). METHODS: The MIP for l-phenylalanine, as a water-soluble template, was successfully synthesized without derivatization. Synthesization was done by a UV polymerization method in which methacrylic acid (MAA), as a functional monomer, and ethylene glycol dimethacrylate (EGDMA), as a cross-linker, were used in the presence of five different porogenic solvents including; acetonitrile, tetrahydrofuran (THF), chloroform, toluene and dimethyl sulfoxide (DMSO). The selectivity of the MIP was examined using 19 different amino acids in human serum and was evaluated by HPLC. In addition, morphological studies were conducted using SEM. RESULTS: The results showed that the obtained MIP with acetonitrile had the highest capacity and selectivity compared with other solvents. The data indicated that Phe-binding to MIP was significantly more than the former binding to NIP in EISF (P≤0.05). Moreover, in comparison with NIP and control group, MIP showed a better selectivity and binding for Phe. This could be used for the reduction of Phe in human serum samples of Phenylketonuria. CONCLUSION: Our findings suggest that the MIP against Phe prepared with acetonitrile, showed a good selectivity and binding, which caused a reduction of blood Phe concentration in enzymatic simulated intestinal fluid and human serum sample of Phenylketonuria.

Protective Effects of Berberine on Oxygen-Glucose Deprivation/Reperfusion on Oligodendrocyte Cell Line (OLN-93).

BACKGROUND: Oligodendrocytes, the myelinating glial cells of central nervous system, are highly vulnerable to ischemic-induced excitotoxic insult, a phenomenon in which calcium overload triggers cell death. Berberine is an alkaloid extracted from medicinal herbs as Coptidis Rhizoma with several pharmacological effects like inhibition of neuronal apoptosis in cerebral ischemia. METHODS: We examined the effects of berberine (0.5-4 µM) and glutamate receptors antagonists (MK-801 [10 µM] and NBQX [30 µM]) on OLN-93 cell line (a permanent immature rat oligodendrocyte) during (30, 60, 240 min) oxygen-glucose deprivation (OGD)/24 h reperfusion. The cells were cultured in 12-well plates. The cells were exposed to glucose-free medium and hypoxia in a small anaerobic chamber. Cell viability was evaluated by MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay. The intracellular calcium levels also were evaluated by Ca(2+)-sensitive indicator Fura-2/AM in presence or absence of berberine (2 µM) during 30 min chemical OGD by NaN3 (20 mM). Student's t-test and ANOVA were used for statistical analysis. RESULTS: Berberine, MK-801and NBQX significantly increased oligodendrocyte viability in all 3 time-scheduled oxygen-glucose deprivation/reperfusion. Berberine at 2 µM produced peak of protection, and increased cell viability to 83%, 77%, and 79% during 30, 60, 240 min ischemic experiments, respectively (P < 0.001). Berberine significantly attenuated intracellular Ca(2+) rise induced by chemical ischemia, and this effect of berberine was significantly stronger than MK-801 and NBQX (P < 0.001). CONCLUSIONS: We concluded that berberine protected OLN-93 oligodendrocyte against ischemic induced excitotoxic injury. Attenuation of intracellular Ca(2+) overload by berberine may be the key mechanism that saved OLN-93 from excitotoxicity damage.

Antiangiogenic activity of xanthomicrol and calycopterin, two polymethoxylated hydroxyflavones in both in vitro and ex vivo models.

Our previous studies had shown xanthomicrol and calycopterin, two plant-derived flavonoids, to have selective antiproliferative activity against some malignant cell lines. The present study is focused on the investigation of antiangiogenic potential of these two flavonoids, using in vitro and ex vivo models. Xanthomicrol and calycopterin were found to have potent inhibitory effects on microvessel outgrowth in the rat aortic ring assay. Xanthomicrol was able to completely block microvessel sprouting at 10 µg/mL, and calycopterin suppressed microvessel outgrowth by 89% at 5 µg/mL. Suramin and thalidomide, used at 20 µg/mL as positive controls, inhibited microvessel formation by 23% and 64%, respectively. The flavones also inhibited endothelial cell tube formation and human umbilical vein endothelial cell proliferation at 0.5, 5, and 10 µg/mL. In order to delineate the underlying mechanisms of antiangiogenic activity of these flavones, we investigated the influences of xanthomicrol and calycopterin on expression of vascular endothelial growth factor (VEGF) and basic-fibroblast growth factor (b-FGF) in endothelial cells. These flavones were able to inhibit VEGF expression at 0.5, 5, and 10 µg/mL, but they had little or no effect on b-FGF expression. These findings suggest that xanthomicrol and calycopterin possess potent antiangiogenic activities, which may be due to their inhibitory influences on VEGF expression.

Effect of berberine on nitric oxide production during oxygen-glucose deprivation/reperfusion in OLN-93 oligodendrocytes.

In this study, the effect of berberine, an isoquinoline alkaloid isolated from Coptidis rhizoma, on Nitric Oxide (NO) production, as a possible involved factor, during excitotoxic injury in oligodendroglial cells were evaluated. The overactivation of ionotropic glutamate receptors which is known as the excitotoxicity, is an important phenomenon because of the contribution in acute injury to the central nervous system, chronic neurodegenerative disorders, oligodendrocyte loss and demyelinating diseases as Multiple Sclerosis (MS). Intracellular Ca2+ overload, have a key role during excitotoxic injury and such increase in cytoplasmic Ca2+ triggers a series of events such as production of NO that end to cell death. Previous report showed the protective effects of berberine on ischemic-induced excitotoxic insult in oligodendrocytes. Hereby, we intended to know if the NO production could be associated with oxygen-glucose deprivation/reperfusion-induced excitotoxic damage in oligodendrocyte; moreover, the alteration of NO production could be considered as an involved mechanism for protective effect of berberine in such condition. Therefore, the effect of berberine (2 µM) on NO production during oxygen-glucose deprivation/24 h reperfusion in oligodendrocytes were examined. The OLN-93 cell line (a permanent immature rat oligodendrocyte) was used as a model of oligodendrocyte. Thirty minutes-oxygen-glucose deprivation/24 h reperfusion was used to induce excitotoxicity. NO production was evaluated by Griess method. Our results demonstrated that berberine (2 µM) significantly decreased NO production during 30 min oxygen-glucose deprivation/reperfusion. It seems that blockade of NO production by berberine may also participate in oligodendroglial cell protection against oxygen-glucose deprivation/reperfusion-induced insult.

Synthesis of a phenylalanine imprinted polymer for attenuation of phenylalanine absorption via the gut in a murine hyperphenylalaninemia model.

Polymer technology plays an influential role in biomedical sciences. Molecular imprinting is a technique for preparation of polymers with structure-selective adsorptive properties. High selectivities of these materials have nowadays advanced to the point that they are being utilized for several biomedical applications such as drug delivery. Phenylketonuria is a genetic disease characterized by accumulation of phenylalanine (Phe) in blood with toxic consequences. The aim of the present study is to synthesize a phenylalanine imprinted polymer for attenuation of phenylalanine absorption in the gut in a murine hyperphenylalaninemia model. A molecularly imprinted polymer (MIP) against Phe and a non-imprinted polymer (NIP) were synthesized and their Phe binding properties were studied in Simulated Intestinal Fluid (SIF). Two classes of binding sites were then found in the MIP: high affinity (KD = 62.5 µM) and low affinity (KD = 1 mM). Histological toxicity and LD50 of the MIP, after oral administration to murine hyperphenylalaninemia, were examined prior to investigation of the effects of the imprinted polymer on blood Phe concentrations in animal models. Our findings suggest that the MIP against Phe can decrease the blood Phe concentration in an animal model of hyperphenylalaninemia.

Antiproliferative activity of flavonoids: influence of the sequential methoxylation state of the flavonoid structure.

Dracocephalum kotschyi Boiss. has been used as part of an ethnobotanical remedy against many forms of human cancer in Iran. It has been demonstrated that a flavonoid named xanthomicrol from D. kotschyi contributes to its preferential antiproliferative activity against malignant cells. In the present study, the antiproliferative activity of its flavonoid fraction was further characterized. Using liquid-liquid extraction and a semi-preparative reversed-phase HPLC method, eight flavonoid aglycones were isolated from the aerial parts of the plant and their identities were confirmed through MS and NMR analyses as luteolin, naringenin, apigenin, isokaempferide, cirsimaritin, penduletin, xanthomicrol and calycopterin. The in vitro antiproliferative activity of each compound was evaluated against a panel of established normal and malignant cell lines using the MTT assay and some structure-activity relationships were observed. The hydroxyflavones (luteolin, apigenin and isokaempferide) exerted comparable antiproliferative activities against malignant and normal cells, while the methoxylated hydroxyflavones (cirsimaritin, penduletin, xanthomicrol and calycopterin) showed preferential activities against tumor cells. This activity may be of value in treating tumors as it would exert few side effects in normal tissues. Xanthomicrol selectively inhibited the growth of human gastric adenocarcinoma, while calycopterin selectively prevented human acute promyelocytic leukemia and human colon carcinoma cells proliferation.