青藤碱对SSNI模型大鼠镇痛效应和纹状体细胞外液单胺类递质的影响

目的:观察青藤碱对部分坐骨神经损伤(SSNI)诱导的神经病理性疼痛大鼠模型镇痛效应,并探讨其对纹状体细胞外液中单胺类神经递质及其代谢产物的影响.方法:雄性SD大鼠,随机分为假手术组、SSNI模型组、加巴喷丁组(100mg·kg-1)、青藤碱高、低剂量组(40,20mg·kg-1),采用Von Frey hairs和Cold Spray法评价机械痛敏和冷痛敏的程度.纹状体微透析采样,高效液相色谱-电化学法检测细胞外液中去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)等神经递质及其代谢产物二羟苯乙酸(DOPAC)和5-羟吲哚乙酸(5-HIAA)的含量.结果:SSNI模型大鼠的机械痛阈、冷痛敏显著改变,脑内NE显著降低,DA,5-HT及其代谢产物明显升高.与模型组相比,青藤碱高剂量组在腹腔给药30～120min时机械痛阈显著提高(P＜0.01),在30～240min冷痛敏分值明显降低(P＜0.05);在45～135 min内明显上调纹状体细胞外液NE含量(P＜0.05),45,75,135 min明显降低DA的含量(P＜0.05),45～135 min显著减少5-HT的含量(P＜0.01),并在45～135m in显著降低DOPAC(P＜0.01),45～75 min明显降低5-HIAA的含量(P＜0.05).结论:青藤碱对SSNI模型大鼠神经源性疼痛有干预作用,其机制可能与调节纹状体细胞外液单胺类神经递质紊乱相关.     

青藤碱抗肿瘤作用机制的研究进展

青藤碱是青风藤中主要的生物碱类成分。近年来,青藤碱的抗肿瘤活性受到广泛关注。实验研究表明,青藤碱可通过诱导肿瘤细胞凋亡、抑制肿瘤细胞侵袭和迁移、影响肿瘤新生血管、逆转肿瘤细胞多药耐药等多途径发挥抗肿瘤作用,并能与化疗药物协同生效。通过查阅国内外相关文献报道,综述了青藤碱抗肿瘤机制的研究进展,希望为青藤碱的深入研究提供参考。     

乌藤镇痛片质量标准初步研究

目的 :建立乌藤镇痛片的质量标准。方法 :采用薄层色谱(TLC)法对制剂中的青风藤、独活、红花进行定性鉴别,并对制剂中双酯型生物碱进行限量检查,用高效液相色谱(HPLC)法测定制剂中青藤碱的含量。结果:TLC可以检测出青风藤、独活、红花的特征性斑点,制剂中双酯型生物碱含量在限量范围内。青藤碱在0.0126~0.1255 mg/m L内线性关系良好,Y=1626.58256X-9.20930,r=0.99998(n=6),平均回收率98.14%,RSD=1.41%。结论:建立了乌藤镇痛片的质量标准,方法简便、准确,能够有效控制制剂的质量。     

Therapeutic effect of an injectable sustained-release sinomenine hydrochloride and sodium hyaluronate compound in a rabbit model of osteoarthritis

Background  While intra-articular injection of sinomenine hydrochloride has a therapeutic effect on osteoarthritis, it has a short half-life, and is thermolabile and photolabile. The aim of this research was to evaluate the sustained-release of sinomenine hydrochloride from an injectable sinomenine hydrochloride and sodium hyaluronate compound (CSSSI) and its therapeutic effect in a rabbit model of osteoarthritis following intra-articular injection.

Methods  An injectable compound consisting of 1% sodium hyaluronate and 2.5% sinomenine hydrochloride was prepared and kept as the experiment group, and 2.5% sinomenine hydrochloride was prepared and kept as the control group. The cumulative mass release was measured at different time points in each group in vitro. Sixty-five male Zelanian rabbits were randomly divided into five groups: 15 (30 knees) each for the control, sodium hyaluronate, sinomenine hydrochloride, and CSSSI groups respectively, and five (10 knees) for the modeling group. Papain was injected into both knees of each rabbit for model establishment. Subsequently, 0.2 ml of the corresponding drugs was injected into the articular cavities of the remaining experiment groups, while the control group was treated with 0.2 ml normal saline. All groups were treated once a week for 4 weeks. Seven days after the last treatment, knees were anatomized to perform pathological observations and Mankin’s evaluation of the synovium. Four groups were compared using the SPSS 13.0 software package.

Results  In the in vitro sustained-release experiments, 90% of the drug was released in the experiment group 360 minutes following the injection. Comparison of the Mankin’s evaluations of the four groups illustrated statistical discrepancies (P <0.05). In further paired comparisons of the CSSSI group vs. modeling control/sodium hyaluronate/sinomenine hydrochloride groups, statistical significance was uniformly obtained. Moreover, sodium hyaluronate and sinomenine hydrochloride treatments showed significant improvement over the modeling control (P <0.05), whereas sodium hyaluronate vs. sinomenine hydrochloride comparison failed to reach significance (P >0.05).

Conclusions  CSSSI has a sustained-release effect on sinomenine hydrochloride. Intra-articular injection of CSSSI was significantly better than the sole sodium hyaluronate or sinomenine hydrochloride for the treatment of osteoarthritis in a rabbit model.

     

Clinical observations on the therapeutic effect of compound sinomenine hydrochloride and sodium hyaluronate sustained-release injection in treatment of rabbit osteoarthritis synovial disease

Objective: To discuss the sustained-release effect of compound sinomenine hydrochloride and sodium hyaluronate sustained-release injection (CSSSI) on sinomenine hydrochloride and its therapeutic effect on rabbit osteoarthritis synovial disease after injected into the articular cavity. Methods: Compound injection consists of 1% sodium hyaluronate and 2.5% sinomenine hydrochloride was prepared as an experimental group, and 2.5% sinomenine hydrochloride was prepared as a control group. The cumulative mass release was measured at different time points for each group in vitro. 65 male Zelanian rabbits were randomly divided into five groups: 15 (30 knees) for the control, sodium hyaluronate, sinomenine hydrochloride and CSSSI groups, and five (10 knees) for the modeling group. Papain articular cavity was modeled with both knees of rabbits. Seven days later the rabbits of the modeling group were sacrificed, thus the modeling succeeded. Then, 0.2 ml corresponding drugs were injected into articular cavities of the remaining experimental groups, while the control group was treated with 0.2 ml normal saline, once a week for 4 weeks. Seven days after the last treatment, the rabbits were sacrificed by air injection into the auricular vein, and anatomized at knees to perform pathological observations and Mankin’s evaluation of synovium. Four groups were better evaluated, and a=0.05 was used as cutoff for variance analysis; LSD tests were carried out on every two groups; the SPSS13.0 software package was used. Results: In the in vitro sustained-release experiments, 90% of drugs was released in the control group of sinomenine hydrochloride sustained-release injection after 360 minutes. Comparisons of Mankin’s evaluations of four groups, P<0.05, indicates the statistical discrepancies in osteoarthritis therapy among the four groups. In further pairwise comparisons of CSSSI group vs. modeling control/sodium hyaluronate/sinomenine hydrochloride groups, P<0.05 was always obtained. Moreover, P<0.05 was for sodium hyaluronate vs. modeling control and sinomenine hydrochloride vs. modeling control, whereas P>0.05 for sodium hyaluronate vs. sinomenine hydrochloride. Conclusion: CSSSI has sustained-release effect on sinomenine hydrochloride. Articular cavity injection of CSSSI treats the rabbit osteoarthritis synovial disease better than sole sodium hyaluronate or sinomenine hydrochloride.     

青藤碱抗肿瘤作用与分子机制研究进展

肿瘤为机体在多重致瘤因子的影响下,导致局部组织细胞增生产生的病因未明的新生物,严重威胁人类生命和健康.肿瘤根据其病理性质分为良性肿瘤、交界性肿瘤、恶性肿瘤;其中恶性肿瘤统称为癌症,目前尚无特效药及可靠的治愈手段,为当前医学界研究的一大热点和难点.文献古籍中多有中草药治疗肿瘤屡建良效的记载,且现代药理研究表明,越来越多的...     

青藤碱对类风湿关节炎患者外周血单核源性树突状细胞趋化因子分泌和受体表达的影响

目的 观察中药单体青藤碱对类风湿关节炎患者外周血单核源性树突状细胞趋化因子分泌和受体表达的影响.方法 分离8例类风湿关节炎患者的单核细胞,采用细胞因子刺激分化为树突状细胞.分别采用青藤碱高(5 mmol/L)、中(2 mmol/L)、低(1 mmol/L)剂量和空白对照干预.流式细胞仪检测各组树突状细胞趋化因子受体CCR5和CCR7的表达,半定量RT-PCR检测树突状细胞CCR5和CCR7mRNA的表达,酶联免疫吸附试验(ELISA)检测培养上清中趋化因子CXCL9(MIG1、CXCL10(IP-10)、CXCL11(ITAC)的表达.结果 与对照组相比,经青藤碱高干预后的树突状细胞趋化因子受体CCR5、CCR7的蛋白和mRNA表达明显降低(P<0.05或P<0.01).青藤碱干预后的DC分泌CXCL9(MIG)、CXCL10(IP-10)降低(P<0.05或P<0.01).但对CXCL11(ITAC)的表达没有影响.结论 青藤碱可能通过抑制趋化因子对树突状细胞的趋化作用,减少其趋化因子的分泌,而产生治疗类风湿关节炎的作用.     

通光素等15种药物抗约氏鼠疟的实验观察

本工作在整体实验条件下,观察了通光素(Tenacissigenin)等15种药物(包括植物药的提取物及化学合成药),对小鼠约氏疟原虫(P.yoclli)红细胞内期的杀灭作用,并以生理盐水为阴性对照,氯喹为阳性对照。实验结果通光素、利胆素(Nikoform)、青藤碱(Sinomenine)、6、7-二甲氧基香豆素(6、7-Dimxhoxcoumarin)、甲硝哒唑五种药物和氯喹,均可使感染约氏疟的小鼠存活期延长,存活比率增加,血中疟原虫减少,与生理盐水对照组比较,经统计学处理,差别显著(P<0.01)。     

Effect of sinomenine on the in vitro intestinal epithelial transport of selected compounds

Herbal products can interfere with allopathic medicinal treatment through pharmacokinetic and pharmacodynamic interactions. Although pharmacokinetic interactions that alter drug absorption may cause variable and unsatisfactory drug bioavailability, a drug absorption enhancement effect of a herb may be used to ensure sufficient absorption of poorly absorbable drugs. The effect of the hydrochloride salt of sinomenine, an alkaloid obtained from the plant Sinomenium acutum, on the transepithelial electrical resistance and transport of different compounds (including cimetidine, vitamin C, rutin, luteolin and insulin) across Caco‐2 epithelial cell monolayers was investigated in this study. Sinomenine HCl induced a concentration dependent lowering effect on the transepithelial electrical resistance of Caco‐2 cell monolayers, which was completely reversible. Sinomenine HCl significantly increased the transport of all the test compounds in the apical‐to‐basolateral direction compared with the control group and decreased the transport of cimetidine, a P‐glycoprotein substrate, in the basolateral‐to‐apical direction. From these results it can be concluded that sinomenine HCl increases drug absorption across the intestinal epithelium by means of one or more mechanisms including a transient opening of the tight junctions (as indicated by a reduction in transepithelial electrical resistance) to allow for paracellular transport and/or inhibition of active drug efflux transport (as indicated by inhibition of basolateral‐to‐apical transport of cimetidine). Copyright © 2009 John Wiley & Sons, Ltd.     

Vasodilatation induced by sinomenine lowers blood pressure in spontaneously hypertensive rats

1. Sinomenine is an alkaloid with a wide range of pharmacological actions. In the present study, we investigated the effect of sinomenine on blood pressure and its possible mechanisms of action. 2. Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were given intraperitoneal injections of sinomenine. At 30 min, 2.5-10 mg/kg sinomenine decreased systolic blood pressure (SBP) in a dose-dependent manner in SHR, but had no effect on the SBP in WKY rats. 3. The vascular effect of sinomenine was then examined in aortic rings isolated from Wistar rats. Sinomenine (0.1-10 micromol/L) produced concentration-dependent relaxation in aortic rings precontracted with phenylephrine (10 nmol/L) or KCl (40 mmol/L). Glibenclamide (1-100 micromol/L), a specific inhibitor of ATP-sensitive K(+) channels attenuated the sinomenine-induced relaxation, but this effect was not observed when inhibitors of other types of K(+) channels were used. 4. We further investigated the effects of sinomenine on changes in intracellular Ca(2+) concentrations ([Ca(2+)](i)) in cultured aortic smooth muscle (A7r5) cells by using the Ca(2+)-sensitive dye fura-2 as an indicator. Sinomenine, over the concentration range 0.1-10 micromol/L, decreased the increases in [Ca(2+)](i) elicited by phenylephrine (1 micromol/L) or KCl (40 mmol/L) in a concentration-dependent manner. Glibenclamide (1-100 micromol/L) abolished the effects of sinomenine. 5. In conclusion, sinomenine causes vascular relaxation by opening ATP-sensitive K(+) channels, thus decreasing [Ca(2+)](i).