Emodin and baicalein inhibit sodium taurocholate-induced vacuole formation in pancreatic acinar cells

AIM To investigate the effects of combined use of emodin and baicalein(CEB) at the cellular and organism levelsin severe acute pancreatitis(SAP) and explore the underlying mechanism.METHODS SAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in 48 male SD rats. Pancreatic histopathology score, serum amylase activity, and levels of tumour necrosis factor alpha(TNf-α), interleukin 6(IL-6), and IL-10 were determined to assess the effects of CEB at 12 h after the surgery. The rat pancreatic acinar cells were isolated from healthy male SD rats using collagenase. The cell viability, cell ultrastructure, intracellular free Ca2+ concentration, and inositol(1,4,5)-trisphosphate receptor(IP3 R) expression were investigated to assess the mechanism of CEB.RESULTS Pancreatic histopathology score(2.07 ± 1.20 vs 6.84 ± 1.13, P 0.05) and serum amylase activity(2866.2 ± 617.7 vs 5241.3 ± 1410.0, P 0.05) were significantly decreased in the CEB(three doses) treatment group compared with the SAP group(2.07 ± 1.20 vs 6.84 ± 1.13, P 0.05). CEB dose-dependently reduced the levels of the pro-inflammatory cytokines IL-6(466.82 ± 48.55 vs 603.50 ± 75.53, P 0.05) and TNF-α(108.04 ± 16.10 vs 215.56 ± 74.67, P 0.05) and increased the level of the anti-inflammatory cytokine IL-10(200.96 ± 50.76 vs 54.18 ± 6.07, P 0.05) compared with those in the SAP group. CEB increased cell viability, inhibited cytosolic Ca2+ concentration, and significantly ameliorated intracellular vacuoles and IP3 m RNA expression compared with those in the SAP group(P 0.05). There was a trend towards decreased IP3 R protein in the CEB treatment group; however, it did not reach statistical significance(P 0.05).CONCLUSION These results at the cellular and organism levels reflect a preliminary mechanism of CEB in SAP and indicate that CEB is a suitable approach for SAP treatment.     

黄芩素对人乳腺癌MCF-7细胞内酪氨酸蛋白激酶的抑制作用

目的观察黄芩素对MCF-7细胞内酪氨酸蛋白激酶(TPK)活性的影响。方法采用台盼蓝拒染法,在不同条件下测定细胞增殖的抑制率。TPK活性通过测定转移到TPK底物上[-32P]ATP的32P放射性活度来检测。结果黄芩素能够显著地抑制MCF-7细胞内TPK的活性并呈剂量依赖性关系,其IC50为2·5μmol/L。结论黄芩素作为一种细胞内的TPK抑制剂具有潜在的抗乳腺癌应用价值。     

不同炮制方法对黄芩水煎液总黄酮成分的影响

目的 :探讨不同炮制方法对黄芩水煎液总黄酮成分的影响。方法 :对采用不同方法炮制的黄芩 ,用分光光度法在(4 2 5± 1) nm波长处测定其水煎液中总黄酮成分的含量。结果 :黄芩蒸 1h软化切片 ,色黄鲜艳 ,黄芩素含量较高 ,质量较好 ,与冷浸 2 4h切片比较 ,黄芩素含量平均高 2 2 .9%。经统计学处理 t>0 .0 1,即 P<0 .0 1;与水煎煮 10 min切片比较 ,黄芩素平均高于 9.2 % ,P<0 .0 5 ;酒炒后黄芩素含量平均下降 10 .1% ,P<0 .0 1。结论 :不同炮制方法黄芩中黄芩素含量均有显著性差异     

黄芩素和黄芩苷对四氯化碳所致肝脏损伤大鼠转氨酶的影响

目的 :研究黄芩素和黄芩苷降转氨酶活性 ,以其评价二者的肝保护作用。方法 :复制大鼠 CCl4 肝损伤模型 ,用黄芩素和黄芩苷防治 ,用生化方法测定血清 AL T、AST、AL B和 TP。结果 :与 CCl4 组相比 ,黄芩素组和黄芩苷组 AL T、AST均显著降低 (P <0 .0 1) ,AL B和 TP无显著性差异 (P >0 .0 5 ) ;黄芩素组和黄芩苷组之间各项指标均无显著差异 (P >0 .0 5 )。结论 :黄芩素和黄芩苷均对 CCl4 所致肝损伤具有一定的保护作用 ,二者作用效果无显著差异。     

Effects of baicalein on beta-amyloid peptide-(25-35)-induced amnesia in mice

Baicalein may act on the benzodiazepine binding sites to exert an anxiolytic-like effect in mice. Since many benzodiazepine drugs have amnesic side-effect and baicalein can protect cultured cortical neurons from beta-amyloid peptide-(25-35)-induced toxicity, this study examined the amnesic effect of baicalein and its effects on beta-amyloid peptide-(25-35) (3 nmol/mouse, i.c.v.)-induced amnesia in mice. Using the step-through passive avoidance test, the results showed that baicalein (10-100 mg/kg, i.p.), unlike the benzodiazepine drug chlordiazepoxide (10 mg/kg, i.p.), had no significant amnesic effect. Baicalein (10-50 mg/kg, i.p.) also had no facilitating effect on the learning and memory. However, one dosage pretreatment, but not post-treatment, of baicalein (5 or 10 mg/kg, i.p.) attenuated beta-amyloid peptide-(25-35)-induced amnesia. Interestingly, post-treatment for 7 or 13 days of baicalein (10-15 mg/kg/day, i.p.), like melatonin (10 mg/kg/day, i.p.), also attenuated beta-amyloid peptide-(25-35)-induced amnesia. Therefore, this study demonstrated that baicalein has protective effect on beta-amyloid peptide-(25-35)-induced amnesia.     

Baicalein attenuates intimal hyperplasia after rat carotid balloon injury through arresting cell-cycle progression and inhibiting ERK, Akt, and NF-κB activity in vascular smooth-muscle cells

Baicalein (5,6,7-trioxyflavone-7-O-beta-D-glucuronide) derived from the Chinese herb Scutellaria baicalensis is well known as a lipoxygenase inhibitor. We investigated baicalein-mediated inhibitory effects on vascular smooth-muscle cell (VSMC) proliferation and intimal hyperplasia by balloon angioplasty in the rat. In vascular injury studies, baicalein significantly suppressed intimal hyperplasia by balloon angioplasty. Baicalein significantly inhibited cell proliferation via a lipoxygenase-independent pathway using [³H]thymidine incorporation, 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT), and flow cytometry assays. At the concentrations used, no cytotoxic effect on cell culture was found. Baicalein blocks cell-cycle progression in S/G2/M phase, consistent with the cell-cycle effects, baicalein significant inhibited cyclin D1, p42/44 mitogen-activated protein kinase (MAPK), and Akt phosphorylation without change in the other cell-cycle regulatory proteins. Furthermore, baicalein attenuated serum-induced deoxyribonucleic acid (DNA) binding activity of nuclear factor kappa B (NF-κB). These results show that baicalein blocks cell proliferation via blocking cell-cycle progression and proliferating events, including p42/44 MAPK and Akt activations as well as NF-κB activation. It also inhibits intimal hyperplasia after balloon vascular injury in the rat, indicating the therapeutic potential for treating restenosis after arterial injury. C.-Y. Peng and Y.-W. Huang contributed equally to this work.     

黄芩素对大鼠神经病理痛的镇痛作用及其机制

观察黄芩素对大鼠坐骨神经慢性压迫引起痛行为的抑制作用及初级感觉神经元中胶质细胞源性神经营养因子（GDNF）表达的调控作用,阐明黄芩素对神经病理痛的镇痛机制。     

黄芩素对人胰腺癌细胞增殖与凋亡的影响

摘 要 目的：探讨黄芩素对人胰腺癌细胞增殖与凋亡的影响。方法: 人胰腺癌细胞株BxPC 3和PANC 1经不同浓度（0,50,75,100 μmol·L-1）的黄芩素处理后,通过CCK 8检测、划痕愈合实验、细胞迁移、侵袭实验、显微镜观察、Real time qPCR 检测增殖和凋亡相关基因的影响等方法,观察黄芩素在胰腺癌细胞增殖、迁移、侵袭以及凋亡、基因表达的影响。结果: 与空白对照组比较,黄芩素能够显著抑制胰腺癌细胞BxPC 3和PANC 1的增殖,并且随着浓度的加大,对BxPC 3和PANC 1增殖的抑制作用在加强（P＜0.01）;且黄芩素对两种胰腺癌细胞系的作用效果与临床常用抗癌药吉西他滨（2 μmol·L-1）的作用效果相似。黄芩素能显著抑制胰腺癌细胞的迁移和侵袭,诱导癌细胞的凋亡,诱导胰腺癌细胞自噬;经过黄芩素处理的癌细胞,细胞周期相关基因和抗凋亡基因（cyclinD1、cyclinE、cyclinA和Bcl 2）表达水平下降,而细胞凋亡相关基因（caspase 3和Bax）的表达水平上调明显。结论: 黄芩素能有效抑制胰腺癌细胞BxPC 3和PANC 1的增殖、迁移和侵袭,并且可以通过凋亡和自噬诱导细胞死亡。     

灯盏细辛胶囊治疗缺血性脑卒中的药理机制研究

目的：利用网络药理学研究灯盏细辛胶囊治疗缺血性脑卒中的药理机制。方法：采用TCMSP等检索灯盏细辛胶囊的活性成分,并且得到其灯盏细辛胶囊活性成分对应的靶点;然后通过PharmGKB、Genecards2个数据库检索缺血性脑卒中相关靶点,使用METASCAPE软件对两者取交集的49个靶点进行GO注释分析和KEGG通路分析。采用Cytoscape 3.7.1软件建立活性成分-靶点-通路网络模型。结果：灯盏细辛胶囊可能通过补体和凝血级联通路、HIF-1信号通路、PI3K-Akt信号通路、FoxO信号通路、核因子-κB信号通路、脂肪细胞因子信号通路等多个通路治疗缺血性脑卒中。结论：灯盏细辛胶囊体现了中药多成分、多靶点、多通路的特点,为进一步阐释灯盏细辛胶囊治疗缺血性脑卒中的药理机制提供了理论依据。