Pharmacokinetic alterations in poloxamer 407-induced hyperlipidemic rats

1. Plasma lipid profile abnormalities in hyperlipidemia can potentially alter the pharmacokinetics of a drug in a complex manner. To evaluate these pharmacokinetic alterations in hyperlipidemia and to determine the underlying mechanism(s), poloxamer 407-induced hyperlipidemic rats (HL rats), a well-established animal model of hyperlipidemia have been used.

2. In this review, we summarize findings on the pathophysiological and gene expression changes in drug-metabolizing enzymes and transporters in HL rats. We discuss pharmacokinetic changes in drugs metabolized primarily via hepatic cytochrome P450 (CYPs) in terms of alterations in hepatic intrinsic clearance (CL^′_int), free fraction in plasma (f_u) and hepatic blood flow rate (Q_H), depending on the hepatic excretion ratio, as well as drugs eliminated primarily by mechanisms other than hepatic CYPs.

3. For lipoprotein-bound drugs, increased binding to lipoproteins resulted in lower f_u values and volumes of distribution, with some exceptions. Generally, slower non-renal clearance (or total body clearance) of drugs that are substrates of hepatic CYP3A and CYP2C is well explained by the following factors: alterations in CL^′_int (due to down-regulation of hepatic CYPs), decreased f_u and/or possible decreased Q_H.

4. These consistent findings across studies in HL rats suggest more studies are needed at the clinical level for optimal pharmacotherapies for hyperlipidemia.     

Anti-hyperlipidemic effect of an edible brown algae, Ecklonia stolonifera, and its constituents on poloxamer 407-induced hyperlipidemic and cholesterol-fed rats

We conducted this study to isolate novel anti-hyperlipidemic agents derived from natural marine products. To accomplish this, we investigated the effects of ethanolic (EtOH) extracts of Ecklonia stolonifera and its phlorotannin constituents, eckol and dieckol, on serum lipid levels in rats with hyperlipidemia that was induced by a high-cholesterol diet or poloxamer 407. Treatment with the EtOH extracts of E. stolonifera and its phlorotannin-rich ethyl acetate (EtOAc) and n-butanol (n-BuOH) fractions induced a significant reduction in triglycerides (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) levels, as well as a significant increase in the high-density lipoprotein-cholesterol (HDLC) level in hyperlipidemic rats. However, treatment with the water (H₂O) fraction did not exert any significant effects on the serum levels of hyperlipidemic rats. In addition, eckol and dieckol isolated from the active EtOAc fraction induced a significant reduction in serum TG, TC, and LDL-C levels, as well as in the atherogenic index (A.I.). Furthermore, treatment with dieckol induced a greater decrease in the serum TG, TC, and LDL-C levels of hyperlipidemic rats than eckol or lovastatin, as well as an increase in the serum HDL-C levels. Taken together, these results suggest that phlorotannins such as eckol and dieckol have the potential for use for the prevention of hyperlipidemic atherosclerosis.     

Assessment of glibenclamide pharmacokinetics in poloxamer 407-induced hyperlipidemic rats

The aim of the present research was to describe the consequences of hyperlipidemia (HL) on the pharmacokinetics of glibenclamide (Gb) in poloxamer 407-induced hyperlipidemic rats. Rats were given intraperitoneal dose of poloxamer 407 to cause hyperlipidemia. A single oral dose of Gb (10 mg/Kg) was given to normal and HL rats. The C_max and t_max after oral dose of Gb in normal rats were 340.10 µg/ml and 3.67 h, respectively. Whereas, the C_max and t_max after oral dose of Gb in HL rats were noted as 773.39 µg/ml and 2.50 h respectively. The AUC value of Gb was found considerably higher in the HL rats. While the plasma clearance (CL) after oral dose of Gb was 2.53 ml/h and 1.39 ml/h in normal and HL rats respectively. The improved plasma concentration of Gb following oral dosing in rats with HL seems to be due to a direct influence on hepatic clearance or metabolizing enzymes. In conclusion, the Gb pharmacokinetics was considerably affected by the HL in rats. Such findings play an important role for predicting the alterations in the pharmacokinetics of drugs including GB, in cases having hyperlipidemia.     

Evaluation of antihyperlipidemic effect of Polygonum minus,a South East Asian salad plant in poloxamer 407-induced acute hyperlipidemic rats

OBJECTIVE To investigate the antihyperlipidemic effect of methanol and aqueous extracts of the leaves of Polygonum minus in acute hyperlipidemic rat model.METHODS Acute hyperlipidemia was chemically induced in Sprague Dawley rats by using poloxamer 407(500mg·kg-1 of body weight;intraperitoneal).Increase in total cholesterol was confirmed after six hours of induction.The normal and hyperlipidemic control groups were administered with 1mL carboxymethylcellulose(CMC),the two test groups received aqueous and methanol extract of leaves of P.minus respectively(1000mg·kg-1;orally;suspended in 1% CMC)whereas reference standard treated group received atorvastatin(60mg·kg-1;orally;suspended in 1% CMC)once daily for 3consecutive days.Blood samples were collected at 10 th and 24 th hour of the study for total cholesterol and triglycerides determination,while terminal blood samples were collected at58 th hour for full lipids profile analysis.RESULTS In the present study,both methanol and aqueous extracts lowered the serum total cholesterol and triglycerides significantly(P<0.001 and P<0.05,respectively)when compared with the hyperlipidemic control,similar to the standard drug atorvastatin.Varying effects were observed for both extracts on the other lipid parameter studied.Methanol extract showed significant reduction in LDL(P<0.05),VLDL(P<0.01)and atherogenic index(AI;P<0.001)and it showed a significant elevation in HDL levels(P<0.05).On the other hand,the aqueous extract showed significant reduction only in VLDL and AI(P<0.05)but no increase in HDL levels.CONCLUSION Present study confirmed the antihyperlipidemic effect of leaves of P.minus in acute hyperlipidemic rat model.The study also suggested that the methanol extract possess higher antihyperlipidemic effect than aqueous extract.Currently a study is ongoing to evaluate the antihyperlipidemic effect of the methanol extract in high-fat diet-induced chronic hyperlipidemic rat model.     

Pharmacokinetics of clomipramine, an antidepressant, in poloxamer 407-induced hyperlipidaemic model rats

Objective This study was undertaken to investigate the effects of hyperlipidaemia on the pharmacokinetics of clomipramine, an antidepressant, particularly addressing the change of clomipramine distribution to plasma components in poloxamer 407‐induced hyperlipidaemia model rats. Methods Clomipramine pharmacokinetic studies in hyperlipidaemic rats were performed with clomipramine continuous infusion. Furthermore, clomipramine protein binding and distribution to the brain and plasma components such as lipoproteins were investigated. Key findings Mean plasma concentration of clomipramine at steady state during continuous infusion (17.5 µg/min/kg) in hyperlipidaemic rats (0.45 ± 0.01 µg/ml) was significantly higher than that in the control rats (0.30 ± 0.02 µg/ml). However, the amount of clomipramine in the brain in hyperlipidaemic rats (0.31 ± 0.06 µg/g) was dramatically lower than in the control rats (1.89 ± 0.13 µg/g). However, the plasma unbound fraction in hyperlipidaemic rats (0.98 ± 0.05%) was significantly lower than that of the control rats (6.51 ± 0.62%). Conclusions Lower distribution to the brain and lower plasma clearance of clomipramine in hyperlipidaemic rats resulted from lower plasma unbound fraction because of higher lipid‐rich protein contents in blood. Results of this study provide useful information for dosage adjustment of clomipramine in hyperlipidaemia.     

Pharmacokinetics of tolbutamide and its metabolite 4‐hydroxy tolbutamide in poloxamer 407‐induced hyperlipidemic rats

Under hyperlipidemic conditions, there are likely to be alterations in the pharmacokinetics of CYP2C11 substrates following decreased expression of CYP2C11, which is homologous to human CYP2C9. The pharmacokinetics of tolbutamide (TB) and its metabolite 4‐hydroxy tolbutamide (4‐OHTB) were evaluated as a CYP2C11 probe after intravenous and oral administration of 10 mg/kg tolbutamide to poloxamer 407‐induced hyperlipidemic rats (HL rats). Changes in the expression and metabolic activity of hepatic CYP2C11 and the plasma protein binding of tolbutamide in HL rats were also evaluated. The total area under the plasma concentration–time curve (AUC) of tolbutamide in HL rats after intravenous administration was comparable to that in controls due to their comparable non‐renal clearance (CL_NR). The free fractions of tolbutamide in plasma were comparable between the control and HL rats. The 4‐hydroxylated metabolite formation ratio (AUC_4‐OHTB/AUC_TB) in HL rats was significantly smaller than that in the control rats as a result of the reduced expression of hepatic CYP2C11 (by 15.0%) and decreased hepatic CL_int (by 28.8%) for metabolism of tolbutamide to 4‐OHTB via CYP2C11. Similar pharmacokinetic changes were observed in HL rats after oral administration of tolbutamide. These findings have potential therapeutic implications, assuming that the HL rat model qualitatively reflects similar changes in patients with hyperlipidemia. Since other sulfonylureas in clinical use are substrates of CYP2C9, their hepatic CL_int changes have the potential to cause clinically relevant pharmacokinetic changes in a hyperlipidemic state. Copyright © 2014 John Wiley & Sons, Ltd.     

Hypolipidemic effects of Solidago chilensis hydroalcoholic extract and its major isolated constituent quercetrin in cholesterol-fed rats

Abstract

Context: Despite several studies on the effects of Solidago chilensis Meyen (Asteraceae), the phytochemical and hypolipidemic properties remain underappreciated.

Objective: This study evaluates the hypolipidemic and antioxidant effects of hydroalcoholic extract (HE) and quercetrin from S. chilensis aerial parts in cholesterol-fed rats.

Materials and methods: The HE was analyzed by high-performance liquid chromatography, followed by quercetrin isolation. Hypercholesterolemic rats (1% cholesterol and 0.5% cholic acid for 15?d) were treated with HE (150, 300, and 600?mg/kg p.o.; n?=?6), simvastatin (4?mg/kg p.o.; n?=?6), or quercetrin (10?mg/kg p.o.; n?=?6) once a day for 30?d. During this period, a high-cholesterol diet was maintained until the 30th day of treatment.

Results: Rats treated with HE (150, 300, and 600?mg/kg) and quercetrin showed decreased serum levels of total cholesterol (?19.9, ?27.5, ?31.0, and ?39.4%), lipoprotein-cholesterol (?36.0, ?37.5, ?43.3, and ?59.4%), and triacylglycerides (?15.6, ?23.5, ?29.8, and ?27.2%) when compared with the control group similar to simvastatin. Moreover, treatment with HE and quercetrin decreased hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity (35.1% on average) and increased fecal cholesterol levels (38.2% on average).

Discussion and conclusions: Our results suggest that hypolipidemic effects of HE are associated with it modulating the activity of HMG-CoA reductase and its interference in the reabsorption and/or excretion of intestinal lipids. Solidago chilensis and its main constituent, quercetrin, may thus be effective as cholesterol-lowering agents and in preventing atherosclerosis.     

瑞舒伐他汀对poloxamer407诱导的小鼠高血脂模型血脂水平的影响

目的观察瑞舒伐他汀对poloxamer 407(P-407)诱导的小鼠高血脂模型血脂水平的影响。方法小鼠于腹腔注射P-407前先以瑞舒伐他汀(2或10 mg/kg)连续灌胃,并于腹腔注射P-407(0.3 g/kg)后3 h再次灌胃瑞舒伐他汀。以注射P-407前及注射后第3、4、24及48 h血甘油三酯和胆固醇水平评价瑞舒伐他汀的疗效,同时观察造模后24 h高密度脂蛋白-胆固醇水平。结果瑞舒伐他汀组血清甘油三酯和胆固醇水平减低,具有显著的量效关系,且作用可持续至造模后的48 h。瑞舒伐他汀组小鼠造模后24 h血清高密度脂蛋白-胆固醇水平显著升高(P<0.05)。结论瑞舒伐他汀可有效降低P-407诱导的高血脂模型小鼠的血脂水平。     

Pharmacokinetics of verapamil and its metabolite norverapamil in rats with hyperlipidaemia induced by poloxamer 407

In this study, the pharmacokinetics of verapamil and its active metabolite norverapamil were evaluated following intravenous and oral administration of 10 mg/kg verapamil to rats with hyperlipidaemia (HL) induced by poloxamer 407 (HL rats). The total area under the plasma concentration time curve (AUC) of verapamil in HL rats following intravenous administration was significantly greater (by 11.2%) than in control rats due to their slower (by 11%) non-renal clearance. The oral AUC of verapamil in HL rats was also significantly greater (by 116%) compared with controls, with a larger magnitude than the data observed following intravenous administration. This may have been a result of the decreased intestinal metabolism of verapamil in HL rats. The AUC of norverapamil and AUC(norverapamil)/AUC(verapamil) ratios following intravenous and oral administration of verapamil were unchanged in HL rats. Assuming that the HL rat model qualitatively reflects similar changes in patients with HL, the findings of this study have potential therapeutic implications. Further studies in humans are required to determine whether modification of the oral verapamil dosage regimen in HL states is necessary.     

Pharmacokinetics of verapamil and its metabolite norverapamil in rats with hyperlipidaemia induced by poloxamer 407

1. In this study, the pharmacokinetics of verapamil and its active metabolite norverapamil were evaluated following intravenous and oral administration of 10?mg/kg verapamil to rats with hyperlipidaemia (HL) induced by poloxamer 407 (HL rats).

2. The total area under the plasma concentration time curve (AUC) of verapamil in HL rats following intravenous administration was significantly greater (by 11.2%) than in control rats due to their slower (by 11%) non-renal clearance. The oral AUC of verapamil in HL rats was also significantly greater (by 116%) compared with controls, with a larger magnitude than the data observed following intravenous administration. This may have been a result of the decreased intestinal metabolism of verapamil in HL rats.

3. The AUC of norverapamil and AUC_norverapamil/AUC_verapamil ratios following intravenous and oral administration of verapamil were unchanged in HL rats.

4. Assuming that the HL rat model qualitatively reflects similar changes in patients with HL, the findings of this study have potential therapeutic implications. Further studies in humans are required to determine whether modification of the oral verapamil dosage regimen in HL states is necessary.

     

苦参的化学成分

目的研究中药苦参 (SophoraflavescensAit)的化学成分。 方法采用硅胶柱色谱的手段 ,利用理化和波谱分析方法 ,对苦参中的化合物进行分离、分析、鉴定。结果从苦参根中分离得到 2个紫檀素类化合物、一个异黄酮类化合物、一个酚酸类化合物和 β 谷甾醇。确定其结构 ,分别为高丽槐素 (maackiain ,Ⅰ )、三叶豆紫檀苷 6′ 单乙酸酯 (trifolirhizin 6′ monoacetate ,Ⅱ )、芒柄花黄素 (for mononetin ,Ⅲ )、2 ,4 二羟基苯甲酸 (2 ,4 dihydroxybenzoicacid ,Ⅳ )、β 谷甾醇 (β sitosterol,Ⅴ )。 结论三叶豆紫檀苷 6′ 单乙酰酯 (trifolirhizin 6′ monoacetate)为首次从苦参中分离得到     

Hypolipidemic effect of fucoidan from Laminaria japonica in hyperlipidemic rats

In this study, we investigated the effect of fucoidan polysaccharide sulfuric acid ester (FPS) from Laminaria japonica Aresch (Laminariaceae) on hyperlipidemic rats. FPS notably reduced the concentration of serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) of hyperlipidemic rats and increased the concentration of high-density lipoprotein cholesterol (HDL-C) and the activities of lipoprotein lipase (LPL), hepatic lipoprotein (HL), and lecithin cholesterol acyltransferase (LCAT).     

Hypolipidemic activity of Anthocephalus indicus (kadam) in hyperlipidemic rats

The hypolipidemic action of Anthocephalus indicus (family, Rubiaceae: Hindi name, Kadam) fruit extract has been studied in hyperlipidemic rats fed a triton- and cholesterol-rich high-fat diet. In triton WR-1339-induced hyperlipidemic rats, feeding with the fruit extract (500 mg/kg b.w.) exerted a lipid-lowering effect as assessed by reversal of plasma levels of total cholesterol, phospholipids, and triglyceride following reactivation of the post-heparin lipolytic activity. In another model, chronic feeding of this natural product (500 mg/kg, b.w.) to animals simultaneously fed a high-fat diet for 30 days caused lowering of lipid levels in plasma and liver accompanied with stimulation of hepatic lipolytic activity. The hypolipidemic activity of Anthocephalus indicus fruit extract iscompared with guggulipid, a known lipid-lowering drug, in both models.     

苦参系列生物碱体外抗CVB_3病毒活性

目的研究苦参系列生物碱(Sophora flavescens alkaloids)对柯萨奇B3病毒(CVB3)所致的Vero细胞和大鼠原代心肌细胞病变抑制作用、病毒繁殖抑制反应,并测定其对大鼠原代心肌细胞培养上清液中心肌酶(LDH、CK MB)活性的影响。方法在Vero细胞、大鼠原代心肌细胞中加入不同稀释度苦参系列生物碱后,感染CVB3病毒,观察细胞病变,MTT染色比较各组间活细胞数的变化,病毒繁殖抑制实验比较半数组织感染量(TCID50)的差别;紫外分光光度法测定心肌细胞培养液上清中LDH和CK MB活性。结果槐果碱、苦参碱、槐啶碱在Vero细胞和原代乳鼠心肌细胞试验中可有效抑制CVB3病毒引起的细胞病变(P<0.05,P<0.01);槐果碱对病毒的繁殖有抑制作用(对数值升高一个单位),并可降低心肌细胞释放心肌酶(P<0.05,P<0.01)。结论槐果碱、苦参碱、槐啶碱对CVB3病毒感染的Vero细胞和原代乳鼠心肌细胞具有一定保护作用。对细胞病变(CPE)的抑制作用强弱顺序为:槐果碱>苦参碱>槐定碱>氧化槐果碱、苦豆碱、槐胺碱、槐醇碱。槐果碱对CVB3病毒的繁殖有抑制作用,在一定浓度下可降低心肌酶的释放,其作用机制尚需做进一步探讨。     

Genistein-loaded poloxamer 403/407 mixed micelles: preparation and pharmacokinetic study in rats

In the present study, we aimed to prepare poloxamer 403/407 mixed micelles in order to improve the solubility and oral bioavailability of genistein.Genistein was incorporated in the mixed poloxamer micelles by thin-film hydration method, and its physicochemical properties, including particle size, zeta potential, entrapment efficiency and drug loading, were investigated.In vitro release of genistein from the mixed micelles was monitored by dialysis method, and pharmacokinetic study of genistein loaded mixed micelles was carried out in rats. We found that the particle size and zeta potential of mixed micelles were (20.31±0.43) nm and (–8.94±0.35) mV, with encapsulation efficiency 90.59%±0.67% and drug loading 7.74%±0.05%. Solubility of genistein in mixed micelles reached 3.80 mg/mL, which was about 130 times higher than that in water.Genistein-loaded mixed micelles showed sustained release characteristics in vitro with no burst release phenomenon, but it was faster than suspension.The AUC_0–t andAUC_0–∞ of mixed micelles were 196.74% and 204.62% greater than that of genisein suspension, respectively.Consequently,poloxamer 403/407 mixed micelles significantly improved the solubility and oral bioavailability of genistein, which could be used as an effective drug delivery system for oral administration of poorly soluble drugs.     

Determination of poloxamer 188 and poloxamer 407 using high-performance thin-layer chromatography in pharmaceutical formulations

Poloxamers (PXMs) are amphiphilic non-ionic block polymers commonly used in the cosmetic and pharmaceutical industries. In spite of the wide use of PXMs, few studies have dealt with the analysis of these polymers in pharmaceutical preparations. In this work, high-performance thin-layer chromatography (HPTLC) has been used to quantify both PXM-188 and PXM-407 in pharmaceutical preparations. The separation of these compounds was carried out using reverse phase HPTLC plates with a chloroform-methanol mixture as the mobile phase. Detection was performed densitometrically using the Dragendorff's reagent for the visualization of PXMs. Quality parameters were established, and the detection limits ranged from 24 to 47ng/spot. A good precision (day to day and run to run), with relative standard deviations <11.18%, was obtained. The proposed method was satisfactorily applied to the analysis of laboratory-made and commercial pharmaceutical products.     

Antipruritic effects of Sophora flavescens on acute and chronic itch-related responses in mice

To find new antipruritic herbal medicines for pruritus, we screened the methanol extracts of seven herbal medicines which have been used to treat dermatologic diseases, testing them on mouse models of acute and chronic itch. When administrated perorally (p.o.) at a dose of 200 mg/kg, methanol extracts of Sophora flavescens and Cnidium monnieri, but not the others, significantly inhibited a serotonin (5-HT)-induced itch-related response (scratching) and the spontaneous scratching of NC mice, a mouse model of atopic dermatitis. The inhibitory effect of Sophora flavescens was stronger than that of Cnidium monnieri. The methanol extract from Sophora flavescens (50-200 mg/kg) inhibited 5-HT-induced scratching in a dose-dependent manner, without any effects on the locomotor activity. These results suggest that Sophora flavescens and its constituents widely affect acute and chronic pruritus, and are possible as new antipruritic agents.     

Hypolipidemic and antioxidant effects of ethanol extract of Cassia fistula fruit in hyperlipidemic mice

Context: The plant Cassia fistula L. (Caesalpiniaceae) fruit was widely used by traditional practitioners to treat cardiovascular diseases (CVDs) in India. Hyperlipidemia is a lipid metabolism disorder and the major risk factor for the development of CVDs. Although most of the current hypolipidemic drugs are expensive and have potential side effects, the research focusing on natural alternative medicines is relevant.

Objective: To investigate the hypolipidemic and antioxidant effects of ethanol extract of C. fistula fruit (CFE) in high-fat diet (HFD) induced hyperlipidemia in mice.

Materials and methods: Oral administration of CFE at 100, 300 and 500?mg/kg body weight on HFD induced hyperlipidemia mice for 30 days. The standard drug atorvastatin (20?mg/kg) was used to compare the efficacy of CFE. Hypolipidemic effect was evidenced by the measurement of serum lipid profile and further confirmed by Oil Red O staining of adipose tissue. The hepatic and cardiac melondialdehyde (MDA) level and antioxidant enzyme activities including superoxide dismutase, catalase and glutathione peroxidase were determined.

Results: Treatment with CFE at different doses has significantly restored the levels of serum lipid, MDA and enzymes activities in the liver and heart of hyperlipidemia mice. Oil Red O staining of visceral adipose tissue has shown marked reduction of lipid accumulation in adipocytes; whereas, administration of CFE at 500?mg/kg showed remarkable (p?<?0.001) hypolipidemic and antioxidant effects in HFD fed mice.

Conclusion: C. fistula fruit demonstrated hypolipidemic and antioxidant properties in vivo and the results corroborate the use of this plant in traditional medicine for cardiac ailments.     

Antitumor effects of concanavalin A and Sophora flavescens lectin in vitro and in vivo

Aim： Proteins with legume lectin domains are known to possess a wide range of biological functions. Here, the antitumor effects of two representative legume lectins, concanavalin A （ConA） and Sophora flavescens lectin （SFL）, on human breast carcinoma cells were investigated in vitro and in vivo. Methods： Human breast carcinoma MCF-7 cells and human normal mammary epithelial MCF-IOA cells were examined. Cell viability was detected using WST-1 and CCK-8 assays. Cell apoptosis was analyzed with Hoechst 33258 staining. Cell cycle was investigated using flow cytometry. The expression of relevant proteins was measured using Western blotting. Breast carcinoma MCF-7 bearing nude mice were used to study the antitumor effects in vivo. The mice were injected with ConA （40 mg/kg, ip） and SFL （55 mg/kg, ip） daily for 14 d. Results： ConA and SFL inhibited the growth of MCF-7 cells in dose- and time-dependent manners （ICso values were 15 and 20 pg/mL, respectively）. Both ConA and SFL induced apoptotic morphology in MCF-7 cells without affecting MCF-IOA cells. ConA and SFL dose- dependently increased the sub-G1 proportion in MCF-7 cells, while SFL also trip=~ered the G2/M phase cell cycle arrest. Both ConA and SFL dose-dependently increased the activities of caspase-3 and caspase-9 and release of cytochrome c from mitochondria into cytoplasm, up-regulated Bax and Bid, and down-regulated Bcl-2 and BcI-XL in MCF-7 cells. ConA reduced NF-KB, ERK, and JNK levels, and increased p53 and p21 levels, while SFL caused similar changes in NF-KB, ERK, p53, and p21 levels, but did not affect JNK expression. Administration of ConA and SFL significantly decreased the subcutaneous tumor mass volume and weight in MCF-7 bearing nude mice. Conclusion： ConA and SFL exert anti-tumor actions against human breast carcinoma MCF-7 cells both in vitro and in vivo.     

苦参、山豆根植物中主要生物碱药学研究进展

该文综述了药用植物苦参、山豆根主要生物碱分离纯化及含量测定研究进展.对近年来国内外发表的相关文献进行收集、分析整理及归纳.现有文献多为苦参总碱的纯化,而涉及单体生物碱的分离较少;在含量测定方面多以苦参碱、氧化苦参碱等为质控指标,不尽合理.应加强对苦参、山豆根中生物碱的结构多样性、毒理及构效关系等研究,以扩大这类植物活性...