作者机构:
湖南中医药大学分子病理实验室,中西医结合心脑疾病防治湖南省重点实验室,细胞生物学与分子技术湖南省高校重点实验室,湖南长沙410208;[黄小平; 欧阳波; 丁煌; DENG Chang-qing; 杨筱倩; 刘晓丹] 湖南中医药大学
通讯机构:
[Huang, X.-P.; Deng, C.-Q.] H;Hunan Key Laboratory of Prevention and Treatment of Integrated Traditional Chinese and Western Medicine on Cardio-cerebral Diseases, China
摘要:
<jats:p>Although the compatibility of Astragali Radix (AR) and Angelicae Sinensis Radix (ASR) has favorable effect on promoting hematopoiesis in traditional Chinese medicine (TCM), the main active components and pharmacological mechanism are unknown. We investigated the five active components and its mechanisms <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic>. Five active components of Astragalus glycosides (AST), Formononetin (FRM), Ferulic acid (FRA), Calycosin (CAL), and Calycosin-7-glucoside (CLG), which could be absorbed in intestinal tract, were detected in this study. The peripheral blood, hematopoietic growth factors (HGFs), and hematopoietic progenitor cells (HPCs) colony were observed to evaluate the effect of these five active components promoting hematopoiesis. Furthermore, hematopoietic stem cell (HSC) proliferation, aging, cycle, and related proteins were detected to explore the mechanism of these five components promoting HSC proliferation. <jats:bold>i)</jats:bold> The <jats:italic>in vivo</jats:italic> experiments showed that the combination of the five active components could remarkably increase the number of RBCs, WBCs, PLTs, and content of Hb in peripheral blood and the area of bone marrow hematopoietic tissue, as well as thrombopoietin (TPO), erythropoietin (EPO), granulocyte-macrophage colony stimulating factor (GM-CSF), and colony of CFU-GM, CFU-MK, CFU-E, and BFU-E in serum. Each of these five components promoted the recovery of RBCs and Hb, and increased TPO, CFU-MK, and CFU-E. All components except for AST increased the CFU-GM. FRA increased the number of WBCs, the area of bone marrow hematopoietic tissue, and BFU-E. FRA and AST promoted PLT recovery. FRA and CAL improved the content of GM-CSF. FRA, CAL, and CLG improved the content of EPO. <jats:bold>ii)</jats:bold> The <jats:italic>in vitro</jats:italic> experiments showed that FRA, FRM, and AST significantly promoted cell proliferation, reduced the positive rate and G0/G1 cells, and increased G2/M + S cells and the expression of cyclin D1 and CDK4 proteins in aging HSCs. Furthermore, the combination of five components had the best effect. Taken together, the five active components of AST, FRM, FRA, CAL, and CLG were the main pharmacodynamic substances of the AR-ASR compatibility, which promoted hematopoiesis. The combination of them had a synergistic effect. The mechanism of promoting hematopoiesis may be relevant to regulating cyclin-related proteins, promoting cell cycle transformation, and promoting HSC proliferation.</jats:p>
通讯机构:
[Huang, X.-P.] K;Key Laboratory of Hunan Province for Prevention and Treatment of Integrated Traditional Chinese and Western Medicine on Cardio-Cerebral Diseases, China
摘要:
目的:探讨冰片、黄芪甲苷(ASTⅣ)和三七总皂苷(PNS)配伍促进脑缺血再灌注后神经修复的作用和Wnt/β-catenin信号机制。方法:采用大鼠局灶性脑缺血再灌注模型,灌胃给药冰片、ASTⅣ、PNS及其配伍药物,神经功能评分和病理形态评价药物对脑组织损伤的影响,免疫组织化学方法检测脑组织巢蛋白(Nestin)、神经元核抗原(NeuN)反映神经发生,Western blot法检测Wnt/β-catenin信号通路相关蛋白表达。结果:与模型组比较,ASTⅣ+PNS配伍组、冰片+ASTⅣ+PNS配伍高、低剂量组可显著降低神经功能评分(P<0.01),冰片+ A S TⅣ+P N S配伍低剂量组降低的效应均强于各药物单用(P<0.01)。病理学检测表明,各用药组细胞损伤明显减轻,A S TⅣ+P N S配伍组效应显著优于单用A S TⅣ组、单用P N S组,冰片+A S TⅣ+P N S配伍低剂量组效应优于各药物单用及AS TⅣ+P NS配伍组(P<0.01,P<0.05)。A S TⅣ+P N S配伍组、冰片+A S TⅣ+P N S配伍低剂量组使Ne s t i n表达增加,冰片+A S TⅣ+P NS配伍低剂量组的作用显著强于各药物单用及AS TⅣ+P N S配伍组(P<0.01,P< 0.0 5)。A S T Ⅳ+ P N S配伍组、冰片+A S T Ⅳ+ P N S配伍低剂量组使N e u N阳性细胞表达增多,药物配伍的作用显著强于单用A S TⅣ与单用冰片组。A S TⅣ+ P N S配伍组、冰片+ A S TⅣ+ P N S配伍低剂量组使Wnt3a、Wnt7b、β-catenin蛋白表达显著增加,糖原合成酶激酶3β(GSK3β)表达下调,冰片+ ASTⅣ+PNS配伍低剂量组升高Wnt3a、Wnt7b蛋白表达的效应强于各药物单用及ASTⅣ+PNS配伍组(P<0.01, P<0.05),ASTⅣ+PNS配伍组和冰片+ASTⅣ+PNS配伍低剂量组降低GSK3β表达和增强β-catenin蛋白表达的作用强于各药物单用(P<0.01)。结论:冰片、ASTⅣ、PNS配伍能够通过促进脑内神经细胞的增殖,修复受损的神经细胞,增强抗脑缺血再灌注损伤的作用,其作用与调控Wnt/β-catenin信号通路有关。
作者机构:
[Chen X.-L.; Ding H.; Tang S.; Huang X.-P.; Deng C.-Q.; Yang X.-Q.] Molecular Pathology Laboratory, Key Laboratory of Hunan Province for Prevention and Treatment of Integrated Traditional Chinese and Western Medicine on Cardio-Cerebral Diseases, Key Laboratory of Hunan Universities for Cell Biology and Molecular Techniques, Hunan University of Chinese Medicine, Changsha, 410208, China
通讯机构:
[Huang, X.-P.] M;Molecular Pathology Laboratory, China
摘要:
Danggui Buxue Tang (DBT), a combination of Astragalus and Angelica at a 5 : 1 ratio, mainly promotes hematopoiesis. However, in the clinic, the combination ratio of Astragalus and Angelica to treat low hematopoietic function is not an absolute 5 : 1 ratio, suggesting that the herbs may promote hematopoiesis better after being combined at a certain range of ratios. The objective of this study is to investigate the effect of different ratio combinations of Astragalus and Angelica on bone marrow hematopoiesis suppression induced by cyclophosphamide (CTX) and to probe the interaction and mechanism of Astragalus combined with Angelica in promoting hematopoiesis. Following establishment of the model, mice were administered with Astragalus (6.00 g.kg(-1)), Angelica (3.00 g.kg(-1)), and combinations of Astragalus and Angelica at different ratios, including 10 : 1 (Astragalus 9.81 g.kg(-1)+Angelica 0.98 g.kg(-1)), 5 : 1 (Astragalus 9.00 g.kg(-1)+Angelica 1.80 g.kg(-1)), 2 : 1 (Astragalus 7.71 g.kg(-1)+Angelica 3.08 g.kg(-1)), 1 : 1 (Astragalus 5.40 g.kg(-1)+Angelica 5.40 g.kg(-1)), 1 : 2.5 (Astragalus 3.08 g.kg(-1)+Angelica 7.71 g.kg(-1)), 1 : 5 (Astragalus 1.80 g.kg(-1)+Angelica 9.00 g.kg(-1)), and 1 : 10 (Astragalus 0.98 g.kg(-1)+Angelica 9.81 g.kg(-1)). Our results suggested that Astragalus mixed with Angelica synergistically promoted hematopoiesis best when the combination ratio of Astragalus and Angelica was 1 : 1, 1 : 2.5 or 1 : 5; moreover, the effect of Angelica was greater than that of Astragalus. The potential mechanisms of the combinations of Astragalus and Angelica that promote hematopoiesis include the dissolution of the effective components, promoting the synthesis and secretion of hematopoietic growth factor (HGF) and the proliferation of hematopoietic progenitor cells (HPCs).
作者机构:
[YANG Xiao-qian; TANG Ying-hong; 李静娴; LIU Xiao-dan; 邓常清; TANG Biao; HUANG Xiao-ping] Key Laboratory of Hunan Province for Prevention and Treatment of Integrated Traditional Chinese and Western Medicine on Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, China