Berberine Induces Cell Apoptosis through Cytochrome C/Apoptotic Protease-Activating Factor 1/Caspase-3 and Apoptosis Inducing Factor Pathway in Mouse Insulinoma Cells

Objective: To investigate apoptotic effects of berberine, a significant alkaloids component existing in Rhizoma coptidis, and its possible acting mechanism in insulinoma cells. Methods: Different concentrations of berberine were used to treat mouse insulinoma(MIN6) cells for various period of time. The viability and apoptosis of the cells were analyzed using methylthiazolyldiphenvl-tetrazolium bromide assay, flow cytometry and enzyme-linked immuno sorbent assay. Changes in the relating pro-and anti-apoptosis proteins were detected by western-blotting. Results: The half-maximal inhibitory concentration(IC50) of berberine was 5.7 μmol/L on MIN6 cells viability for 16 h. Berberine caused a 20% reduction(P0.05) in cell number after only 4-h incubation; which reached 50% after 24 h(P0.01). Berberine treatment for 16 h significantly increased the level of DNA fragmentation. The flow cytometry showed the apoptotic rate increased 2.9-and 4.6-fold after treating with berberine(5 μmol/L) for 8 and 16 h, while 3-and 8.7-fold after 10 μmol/L treatment for 8 and 16 h(P0.01). Berberine treatment dramatically elevated the expression ratio of Bax to Bcl-2. Meanwhile, berberine notably increased the apoptosis-inducing factors and cytochrome C transforming from the mitochondria to the cytoplasm. Apoptotic protease-activating factor 1(Apaf-1) was subsequently activated after cytochrome C release. Furthermore, caspase-3 and poly adenosine diphosphate-ribose polymerase were also activated to trigger apoptosis cascade. Conclusion: High concentration(5 and 10 μmol/L) of berberine could induce the apoptosis of MIN6 cells through cytochrome C/Apaf-1/caspase-3 and apoptosis inducing factor(AIF) pathway.     

盐酸氨溴索治疗小儿支气管肺炎的临床分析

目的分析研究盐酸氨溴索用于小儿支气管肺炎的临床效果。方法将本院2017年12月—2018年12月期间收治的小儿支气管肺炎患儿88例按照随机双盲法均分为对照组和治疗组,予以对照组44例患儿常规治疗,予以治疗组44例患儿常规治疗联合氧气驱动雾化吸入盐酸氨溴索治疗,对两组患儿的临床疗效和临床症状缓解时间进行对比。结果与对照组相比,治疗组患儿咳嗽、咳痰、胸片改善时间及肺部干湿啰音缓解时间均显著短于对照组,组间差异具有统计学意义(P<0.05),治疗组的临床总有效率为95.45%(42/44),明显高于对照组77.27%(34/44),组间差异具有统计学意义(P<0.05)。结论小儿支气管肺炎在临床常规治疗的基础上加用盐酸氨溴索治疗有助于患儿临床症状的缓解,效果明显。     

Berberine ameliorates non-steroidal anti-inflammatory drugs-induced intestinal injury by the repair of enteric nervous system

The study was to detect the role of GDNF, PGP9.5 (a neuronal marker), and GFAP (EGCs’ marker) in the mechanism of non-steroidal anti-inflammatory drugs (NSAIDs) related to intestinal injury and to clarify the protective effect of berberine in the treatment of NSAID-induced small intestinal disease. Forty male SD rats were divided randomly into five groups (A–E): Group A: control group; Group B: model group received diclofenac sodium 7.5 mg/(kg*day) for 5 days; Group C–E: berberine low, medium and high dose groups were treated by 7.5 mg/(kg*day) diclofenac sodium for 5 days then received berberine 25 mg/(kg*day), 50 mg/(kg*day), and 75 mg/(kg*day), respectively, between the sixth and eighth day. Intestinal mucosa was taken on the ninth day to observe the general, histological injuries, and to measure the intestinal epithelial thickness. Then, immunohistochemistry was performed to detect the expression of PGP9.5 and GFAP, and Western blot was performed to detect GDNF expression. The histological score and the general score in the model group were, respectively, 5.75 ± 1.04 and 4.83 ± 0.92. Scores in berberine medium and high berberine group were lower compared with the model group (P < 0.05). The intestinal epithelial thickness in the model group was lower than in the control group and the berberine groups (P < 0.05). PGP9.5, GFAP, and GDNF content in the model group and the three berberine groups were significantly lower than in the control groups (P < 0.05). PGP9.5, GFAP, and GDNF content in the control group and the three berberine groups were higher compared with the model groups (P < 0.05). Berberine can protect the intestinal mucosa of NSAID users, and the mechanism is associated with the reparation of the enteric nervous system via upregulating the expression of PGP9.5, GFAP, and GDNF.     

盐酸氨溴索联合排痰仪与大剂量盐酸氨溴索联合支气管镜对老年重症肺炎疗效的Meta分析

目的比较正常剂量盐酸氨溴索联合排痰仪与大剂量盐酸氨溴索联合支气管镜在治疗老年重症肺炎中的临床疗效。方法通过计算机检索PubMed、The Cochrane Library、Web of Science、CNKI、万方数据库、维普数据库和中国生物医学文献服务系统,搜索国内外公开发表的有关盐酸氨溴索联合排痰仪与大剂量盐酸氨溴索联合支气管镜治疗老年重症肺炎的相关文章,检索时限从建库起到2019年5月。分别由两名作者根据文献纳入和排除标准对文献进行筛选以及数据提取,使用RevMan 5.3软件进行Meta分析。结果经筛选后共有27篇文献最终被纳入分析。Meta分析结果表明,大剂量盐酸氨溴索联合支气管镜治疗能减少患者ICU住院时间(MD=-1.84,95%CI:-2.21～-1.48)、呼吸机使用时间(MD=-3.93,95%CI:-4.17～-3.69)、治疗期间死亡率(O^R=0.42,95%CI:0.33～0.53)、急性生理学与慢性健康状况(APACHEⅡ)评分(MD=-0.67,95%CI:-1.05～-0.29)、多器官功能衰竭(MOF)发生率(O^R=0.41,95%CI:0.32～0.53)、C反应蛋白(CRP)浓度(MD=-10.35,95%CI:-11.29～-9.41)以及血清降钙素原(PCT)浓度(MD=-0.37,95%CI:-0.40～-0.33),增加患者动脉血氧分压(PaO_2)(MD=4.85,95%CI:3.83～5.86)、经皮动脉血氧饱和度(SpO_2)(MD=6.47,95%CI:5.65～7.29)和氧合指数(OI)(PaO_2/FiO_2)(MD=31.88,95%CI:29.21～34.54)。结论大剂量使用盐酸氨溴索联合支气管镜治疗老年重症肺炎是安全可行的,且与常规治疗方法相比,在所测指标中均具有一定的优势,有望成为治疗老年重症肺炎的优先选择。     

Palmatine: A review of pharmacological properties and pharmacokinetics

The aim of this review is to collect together the results of the numerous studies over the last two decades on the pharmacological properties of palmatine published in scientific databases like Scopus and PubMed, which are scattered across different publications. Palmatine, an isoquinoline alkaloid from the class of protoberberines, is a yellow compound present in the extracts from different representatives of Berberidaceae, Papaveraceae, Ranunculaceae, and Menispermaceae. It has been extensively used in traditional medicine of Asia in the treatment of jaundice, liver‐related diseases, hypertension, inflammation, and dysentery. New findings describe its possible applications in the treatment of civilization diseases like central nervous system‐related problems. This review intends to let this alkaloid come out from the shade of a more frequently described alkaloid: berberine. The toxicity, pharmacokinetics, and biological activities of this protoberberine alkaloid will be developed in this work.     

盐酸氨溴索与多索茶碱治疗慢性支气管炎的疗效评价

目的探讨对慢性支气管炎急性发作期患者采用盐酸氨溴索联合多索茶碱治疗的临床疗效。方法选取本院收治的慢性支气管炎急性发作期患者88例为研究对象,收治时间为2018年3月-2019年3月,根据入院时间将患者随机分为两组,对照组(n=44)和观察组(n=44)。观察组患者采用盐酸氨溴索联合多索茶碱治疗,对照组采用多索茶碱治疗,对两组患者治疗后的治疗有效率以及两组患者症状改善情况进行观察比较。结果观察组患者治疗有效率(97.7%)高于对照组(84.1%),P <0.05;观察组患者症状改善情况优于对照组,P <0.05。结论盐酸氨溴索联合多索茶碱治疗慢性支气管炎急性发作期患者,临床疗效较好,改善患者症状情况。     

Berberine diminishes cancer cell PD-L1 expression and facilitates antitumor immunity via inhibiting the deubiquitination activity of CSN5

Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blocking therapy has become a major pillar of cancer immunotherapy. Compared with antibodies targeting, small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed. Here we identified berberine (BBR), a proven anti-inflammation drug, as a negative regulator of PD-L1 from a set of traditional Chinese medicine (TCM) chemical monomers. BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells. In addition, BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumor-infiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs). BBR triggered PD-L1 degradation through ubiquitin (Ub)/proteasome-dependent pathway. Remarkably, BBR selectively bound to the glutamic acid 76 of constitutive photomorphogenic-9 signalosome 5 (CSN5) and inhibited PD-1/PD-L1 axis through its deubiquitination activity, resulting in ubiquitination and degradation of PD-L1. Our data reveals a previously unrecognized antitumor mechanism of BBR, suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.     

复方甘草酸苷联合盐酸左西替利嗪治疗皮炎湿疹的效果及对Th1/Th2型细胞因子的影响

目的 分析复方甘草酸苷联合盐酸左西替利嗪治疗皮炎湿疹的效果及对Th1/Th2 型细胞因子的影响。方法 选取2018 年10 月～2019 年10 月于我院接受治疗的皮炎湿疹患者80 例，分为对照组（40 例）和观察组（40 例）。两组采取不同的方法进行治疗，其中对照组采取盐酸左西替利嗪治疗，观察组采取复方甘草酸苷联合盐酸左西替利嗪治疗。治疗后比较两组患者的Th1/Th2 型细胞因子水平指标及临床疗效。结果 治疗后，观察组的Th1 型细胞因子中的IFN-γ 及IL-2 明显高于对照组，差异有统计学意义（P＜0.05）。观察组的Th2 型细胞因子中的IL-4、IgE 与对照组比较，差异有统计学意义（P＜0.05）。治疗后，观察组的瘙痒症状分数及糜烂症状分数与对照组比较，差异有统计学意义（P＜0.05）。观察组的总有效率明显高于对照组（P＜0.05）。结论 对皮炎湿疹患者进行治疗的过程中，使用复方甘草酸苷联合盐酸左西替利嗪进行治疗能够有效改善患者Th1、Th2 型细胞炎症因子，疗效确切，值得推广和应用。     

注射用盐酸柔红霉素的质量评价

目的 按照国家计划抽验要求，评价国内不同企业生产的注射用盐酸柔红霉素的质量。方法 按国家标准检验与探索性研究相结合，对抽验样品进行检验，对检验结果进行统计分析。结果 共抽取样品17批次，按国家标准检验合格率100.0%。探索性研究对主要杂质的来源与结构进行了研究；建立溶液的澄清度检查方法；对包材相容性及稳定性进行了考察。结论 目前国内注射用盐酸柔红霉素总体质量较好；现行标准有待进一步提高，建议现行标准修订有关物质检查方法，增加特定杂质的控制，增加溶液的澄清度检查；建议企业优化生产工艺，以提高产品质量。     

萸竹定眩丸治疗颈性眩晕短期疗效观察

目的:观察萸竹定眩丸治疗颈性眩晕的短期疗效。方法:将河南省中医院脊柱科门诊收治的80例患者随机分为对照组和观察组,各40例。对照组服用盐酸氟桂利嗪胶囊治疗,治疗组在服用盐酸氟桂利嗪胶囊基础上加服萸竹定眩丸治疗。每组疗程均为4周1个疗程,1个疗程后根据改良Macnab标准评估临床疗效。结果:治疗组40例中优4例,良28例,可6例,差2例,有效率80%(32/40);对照组中优1例,良21例,可8例,差10例,有效率55%(22/40),两组差异有统计学意义(P<0.05)。结论:盐酸氟桂利嗪胶囊治疗颈性眩晕能取得一定临床疗效,但盐酸氟桂利嗪胶囊联合萸竹定眩丸临床疗效更显著。