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虎杖中葡萄糖氧基苄基2 - 异丁基苹果酸提取物(BSCE)抑制肺出血的止血活性及作用机制

The hemostatic activity and Mechanistic roles of glucosyloxybenzyl 2-isobutylmalate extract (BSCE) from (Thunb.) Rchb.f. in Inhibiting pulmonary hemorrhage.

作者信息

Liu Gang, Mu Kai-Lang, Ran Fei, Liu Jin-Mei, Zhou Ling-Li, Peng Le-Qiang, Feng Guo, Liu Yu-Chen, Wei Fu-Dao, Zhu Ling-Li, Zhang Xin-Yue, Zhang Yong-Ping, Sun Qing-Wen

机构信息

Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, Guizhou, China.

出版信息

Heliyon. 2024 Sep 20;10(18):e38203. doi: 10.1016/j.heliyon.2024.e38203. eCollection 2024 Sep 30.

Abstract

BACKGROUND

Hemorrhagic events cause numerous deaths annually worldwide, highlighting the urgent need for effective hemostatic drugs. The glucosyloxybenzyl 2-isobutylmalates Control Extract (BSCE) from the orchid plant (Thunb.) Rchb.f. has demonstrated significant hemostatic activity in both in vitro and in vivo studies. However, the effect and mechanism of BSCE on non-traumatic bleeding remain unclear.

METHODS

Pulmonary hemorrhage was induced in 40 Sprague-Dawley rats by administering Roscoe. for 14 days. These rats were then randomly divided into five groups: model (Mod), positive control (YNBY), and BSCE low, medium, and high-dose groups. An additional 8 rats served as the control group (Con). The BSCE groups received different doses of BSCE for 10 days, while the YNBY group received Yunnan Baiyao suspension. The effects on body weight, food and water intake, red blood cell count (RBC), hemoglobin concentration (HGB), lung tissue pathology, platelet count, coagulation parameters, and fibrinolytic system markers were evaluated. Network pharmacology and molecular docking analyses were also conducted to identify potential targets and pathways involved in BSCE's effects.

RESULTS

BSCE treatment significantly improved body weight, food intake, and water consumption in rats with pulmonary hemorrhage. RBC and HGB levels increased significantly in the BSCE medium and high-dose groups compared to the Mod group (P < 0.05). Pathological examination revealed that BSCE reduced lung tissue hemorrhage and inflammation, with improvements in alveolar structure. BSCE also positively affected platelet count, thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (FIB) levels, and fibrinolytic markers (D-dimer, PAI-1, and t-PA). Network pharmacology and molecular docking identified key targets such as MMPs, CASPs, and pathways including IL-17 and TNF signaling, suggesting BSCE's involvement in hemostasis and anti-inflammatory processes.

CONCLUSIONS

BSCE exhibits significant hemostatic and protective effects on .-induced pulmonary hemorrhage in rats by improving hematological parameters, reducing lung tissue damage, and modulating the coagulation and fibrinolytic systems. The study provides evidence supporting the potential of BSCE as a therapeutic agent for hemorrhagic diseases, with its efficacy linked to multi-target and multi-pathway interactions.

摘要

背景

出血事件每年在全球导致众多人死亡,凸显了对有效止血药物的迫切需求。来自兰花植物白及(Bletilla striata (Thunb.) Rchb.f.)的葡萄糖氧基苄基2-异丁基苹果酸对照提取物(BSCE)在体外和体内研究中均显示出显著的止血活性。然而,BSCE对非创伤性出血的作用及机制仍不清楚。

方法

通过给予脂多糖(LPS)14天诱导40只Sprague-Dawley大鼠发生肺出血。然后将这些大鼠随机分为五组:模型组(Mod)、阳性对照组(云南白药,YNBY)以及BSCE低、中、高剂量组。另外8只大鼠作为对照组(Con)。BSCE组给予不同剂量的BSCE持续10天,而YNBY组给予云南白药混悬液。评估对体重、食物和水摄入量、红细胞计数(RBC)、血红蛋白浓度(HGB)、肺组织病理学、血小板计数、凝血参数以及纤溶系统标志物的影响。还进行了网络药理学和分子对接分析,以确定参与BSCE作用的潜在靶点和途径。

结果

BSCE治疗显著改善了肺出血大鼠的体重、食物摄入量和水消耗量。与模型组相比,BSCE中、高剂量组的RBC和HGB水平显著升高(P < 0.05)。病理检查显示,BSCE减少了肺组织出血和炎症,肺泡结构得到改善。BSCE还对血小板计数、凝血酶时间(TT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)水平以及纤溶标志物(D-二聚体、纤溶酶原激活物抑制剂-1(PAI-1)和组织型纤溶酶原激活物(t-PA))产生了积极影响。网络药理学和分子对接确定了关键靶点,如基质金属蛋白酶(MMPs)、半胱天冬酶(CASPs)以及包括白细胞介素-17(IL-17)和肿瘤坏死因子(TNF)信号通路在内的途径,表明BSCE参与了止血和抗炎过程。

结论

BSCE通过改善血液学参数、减少肺组织损伤以及调节凝血和纤溶系统,对脂多糖诱导的大鼠肺出血表现出显著的止血和保护作用。该研究为BSCE作为出血性疾病治疗药物的潜力提供了证据支持,其疗效与多靶点和多途径相互作用有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aade/11459001/171f16959215/gr1.jpg

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