桑皮苷的药理作用研究进展

桑皮苷是传统中药桑白皮中一种主要的二苯乙烯苷类活性成分,存在于治疗痛风、关节炎和风湿病的传统中医处方中,其主要作用是利尿和减轻水肿。近年来,国内外学者对桑白皮主要活性成分的药理活性研究较多,尤其是在借助现代药理学的技术和方法后,桑皮苷的各种生物活性和药理作用逐渐被发现。该文从药理作用角度对桑皮苷的相关研究进行综述,以期为桑皮苷的进一步研究开发和应用提供参考。

《人体解剖生理学》实验教学改革与探索

文章根据《人体解剖生理学》课程特点,结合药学院专业教学实际情况,对实验教学内容和方法进行改革探索,增加了虚拟仿真实验及正常人体生理实验。实验教学实践表明,该课程的实验教学改革提高了学生学习的主观能动性,加强学生对理论知识的学习兴趣,培养学生的创新精神和实践能力。

Carnitine palmitoyl transferase 1C regulates tumor cell senescence

OBJECTIVE Passage-dependent cel ular senescence is a complex process limiting the proliferative lifespan of tumor cells but the mechanism of this process is not understood.METHODS Replicative senescenceof pancreatic carcinoma-derived PANC-1 cells wasanalyzed.Metabolomics and transcriptomic analyses were performed to find endogenous metabolites changed andassociated genes.Mitochondrial function,cell survival andtumorigenesis of replicative senescent PANC-1 cellswere analyzed.PANC-1 cells were transfected with RNAi CPT1C to specifically knockdown CPT1C expressions,then mitochondrial function,cellular senescence,cell survival and tumorigenesis were investigated.MDA-MB-231,HCT116,A549,MCF7,and He Lacells werealso transfected with si RNA CPT1C and cellular senescence were monitored.RESULTS Replicative senescenceof PANC-1 cells was confirmed.Metabolomic and transcriptomicanalyses revealed that acylcarnitines and their upstream regulator carnitine palmitoyltransferase 1C(CPT1C),an enzyme that catalyzes the initiating step of fatty acidβ-oxidation,were markedly decreased in senescent PANC-1 cells.Furthermore,low CPT1C expression caused abnormal energy metabolism and mitochondrial dysfunction of PANC-1 cells,resulting in decreased cell survival and a suppressed tumorigenesis.Most importantly,loss of CPT1C triggered mitochondrial dysfunction,leading to senescence-like growth suppression and cellular senescence,suppressed cell survival under metabolic stress,and lower tumorigenesis in a mouse xenograft model.Silencing of CPT1C also induced cellular senescence in five other tumor cell lines.CONCLUSION Low CPT1C expression is a novel biomarker and key regulator of cellular senescence in tumor cell lines.Inhibition of CPT1C may be a new cancer therapeutic target impacting cellular senescence and tumorigenesis through modulation of mitochondrial function.

我国高等药学教育改革十年来的创新与实践

高等药学教育的高质量发展是实现健康中国战略,满足人民日益增长的健康需求,推动我国生物医药产业发展走向世界的重要基石。笔者以教育部高等学校药学类专业教学指导委员会的视角,回顾总结2012~2022年高等药学教育围绕“新药创制人才”和“临床药学服务人才”的培养使命,在药学人才培养模式改革、“四新”教育改革、药学教育教学新基建、高等药学教育质量保障体系等十个方面的创新发展举措,根据党的二十大提出“建设中国式现代化”的命题,对如何建设“中国式高等药学教育现代化”进行展望,提出关键环节创新人才自主培养的改革方向。

Targeted bile acids and gut microbiome profiles reveal the hepatoprotective effect of WZ tablet(Schisandra sphenanthera extract) against LCA-induced cholestasis

Cholestasis is caused by the obstacle of bile formation or secretion and can develop into severe liver diseases. We previously reported the ethanol extract of Schisandra sphenanthera(Wuzhi tablet, WZ) can significantly protect against lithocholic acid(LCA)-induced intrahepatic cholestasis in mice, partially due to the activation of PXR pathway and promotion of liver regeneration.However, the effect of WZ on the bile acids profile and gut microbiome in cholestastic mice remain unknown. In this study, the effect of WZ against LCA-induced liver injury was evaluated and its effect on the bile acids metabolome and gut microbiome profiles in cholestastic mice was further investigated. Targeted metabolomics analysis was performed to examine the change of bile acids in the serum, liver, intestine and feces. The change of intestinal flora were detected by the genomics method. Targeted metabolomics analysis revealed that WZ enhanced the excretion of bile acids from serum and liver to intestine and feces. Genomics analysis of gut microbiome showed that WZ can reverse LCA-induced gut microbiome disorder to the normal level. In conclusion, WZ protects against LCAinduced cholestastic liver injury by reversing abnormal bile acids profiles and alteration of gut microbiome.

2018年中国药物代谢研究进展

本文总结了2018年中国学者在药物代谢领域的研究进展。该年度,中国学者聚焦药物代谢酶和药物转运体,开展活性分子药物代谢/转运机制研究、药物代谢酶和转运体的调节机制及其用于药物和疾病的研究、基于药物代谢/转运的药物毒性机制和临床合理用药研究、肠道菌群药物代谢、中药代谢和DMPK新技术和新模型研究等,取得了一系列国际前沿的创新性成果。近年来,中国的药物代谢研究正由新药研发和合理用药导向研究为主,向创新驱动和机制导向深度研究并重转型,研究方向和水平逐步与国际接轨。

桑皮苷A逆转K562/阿霉素耐药细胞化疗多药耐药的研究

目的研究桑皮苷A对人白血病耐药细胞K562/阿霉素耐药细胞(K562/ADM)化疗耐药的影响。方法实验分为溶媒(DMSO)对照组、阳性对照组(10μmol·L^(-1)维拉帕米处理48 h,再用5μg·mL^(-1)阿霉素孵育1 h或2μg·mL^(-1)罗丹明123孵育1.5 h)、阿霉素单用组(5μg·mL^(-1)阿霉素孵育1 h)、阿霉素合用桑皮苷A组(用5,10,20μmol·L^(-1)桑皮苷A处理48 h,再用5μg·mL^(-1)阿霉素孵育1 h)、罗丹明123合用桑皮苷A组(用5,10,20μmol·L^(-1)桑皮苷A处理48 h,再用2μg·mL^(-1)罗丹明123孵育1.5 h)。用噻唑蓝(MTT)实验初步确定桑皮苷A的逆转耐药作用;再以细胞内阿霉素蓄积实验,罗丹明123(Rho123)蓄积及外排实验进一步研究桑皮苷A的逆转耐药作用;分别用聚合酶链反应(PCR)和蛋白质印迹(Western blot)法检测桑皮苷A对K562/ADM细胞中P-糖蛋白(P-gp)mRNA、蛋白表达及磷脂酰肌醇3-激酶-蛋白激酶B-雷帕霉素靶蛋白(PI3K-Akt-mTOR)通路相关蛋白的影响。结果桑皮苷A能增加K562/ADM细胞对阿霉素的敏感性,桑皮苷A(5~20μmol·L^(-1))与阿霉素(5~160μg·mL^(-1))联合处理可明显降低耐药细胞对阿霉素的半数抑制浓度(IC50),逆转倍数分别为1.59,2.20和5.48倍。阿霉素胞内蓄积实验结果显示桑皮苷A能显著升高K562/ADM细胞中阿霉素浓度,其中10,20μmol·L^(-1)桑皮苷A可使胞内阿霉素平均荧光值升高2.3倍和4.3倍;同时,Rho123胞内蓄积和外排实验发现桑皮苷A不仅能增加细胞内Rho123的蓄积,还能减少Rho123的外排,其中10和20μmol·L^(-1)桑皮苷A可分别使胞内Rho123的平均荧光值增加至2.1倍和2.6倍。与对照组相比,桑皮苷A处理可浓度依赖性地降低细胞内P-gp的mRNA和蛋白表达水平,其中10与20μmol·L^(-1)桑皮苷A可分别使P-gp mRNA水平显著下降36.90%和65.40%。桑皮苷A能显著抑制K562/ADM细胞中p-PI3K、p-Akt、p-mTOR蛋白水平。结论桑皮苷A可通过抑制K562/ADM细胞中PI3K-Akt-mTOR通路,进而下调细胞内P-gp的表达水平,以达到提高肿瘤细胞对阿霉素的化疗敏感性和逆转细胞多药耐药的作用。