Zheng Yinghao, Wang Yun, Xia Mengyu, Song Yanan, Gao Ya, Zhang Lan, Zhang Cun
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China.
Ann Transl Med. 2022 Oct;10(20):1093. doi: 10.21037/atm-21-6415.
As documented in the Chinese Pharmacopoeia, fructus Praeparatus (GFP) can cool the blood during hemostasis and treat various internal hemorrhagic diseases. However, the underlying mechanisms are not yet well understood. This work was designed to decipher the possible mechanism by which GFP prevents hemorrhage. The integration of pharmacodynamics-based and bioinformatics-based methods provided evidence to support the clinical effects of GFP in treating bleeding.
Using ultra-performance liquid chromatography (UPLC) analysis, we quantified the main active ingredients for a preliminary quality assessment of GFP. The pharmacology study was conducted to confirm the essential antihemorrhagic effects of GFP. A rat model of ethanol-induced gastric hemorrhage was established and was followed by intervention with GFP in low, middle, and high doses (4.5, 9, 18 g/kg). Gastric tissues were harvested for macroscopic and histological evaluation of lesions. The contents of thromboxane B2 (TXB) and 6-keto-prostaglandin-F1α (6-keto-PGF) in the serum were determined. Additionally, network pharmacology was proposed to illuminate the potential mechanisms. Following the collection of GFP compositions, the compound- and hemorrhage-related targets were retrieved from public databases. The protein-protein interaction (PPI), gene ontology, pathways analysis, and molecular docking were performed for targets of GFP in gastrointestinal bleeding.
The study found ten main active ingredients that could be used for quality control of GFP. Importantly, the middle and high doses of GFP were found to promote the healing of gastric bleeding. The content of 6-keto-PGF was significantly degraded in the middle and high treated groups (P<0.05). The level of TXB was augmented by a middle (P<0.05) and high dose of GFP. Further, we constructed the network of candidate ingredients and hemorrhage-related targets. Pathway analysis predicted the mechanisms associated with interleukin 4 and interleukin 13 signaling and platelet activation. PPI analysis identified subnetworks with biological functions and also sifted hub targets that affected the antihemorrhagic progress. The candidate proteins had a good binding force with major components.
GFP exhibits a promising effect in ameliorating bleeding, with the relevant molecular mechanisms possibly being related to the regulation of the immune system and platelet activation. Therefore, GFP can potentially exert a protective effect on gastrointestinal bleeding in clinic.
如《中国药典》所述，炮姜能止血凉血，治疗各种内出血疾病。然而，其潜在机制尚未完全明确。本研究旨在阐明炮姜止血的可能机制。基于药效学和生物信息学方法的整合为炮姜治疗出血的临床疗效提供了证据支持。
采用超高效液相色谱（UPLC）分析对炮姜的主要活性成分进行定量，以进行初步质量评估。开展药理学研究以确认炮姜的基本止血作用。建立乙醇诱导的大鼠胃出血模型，随后分别用低、中、高剂量（4.5、9、18 g/kg）的炮姜进行干预。采集胃组织进行病变的宏观和组织学评估。测定血清中血栓素B2（TXB）和6-酮-前列腺素F1α（6-酮-PGF）的含量。此外，采用网络药理学阐明潜在机制。收集炮姜成分后，从公共数据库中检索化合物和出血相关靶点。对胃肠道出血中炮姜的靶点进行蛋白质-蛋白质相互作用（PPI）、基因本体、通路分析和分子对接。
研究发现了10种可用于炮姜质量控制的主要活性成分。重要的是，发现中、高剂量的炮姜能促进胃出血的愈合。中、高剂量治疗组的6-酮-PGF含量显著降低（P<0.05）。中剂量（P<0.05）和高剂量的炮姜可使TXB水平升高。此外，构建了候选成分与出血相关靶点的网络。通路分析预测了与白细胞介素4和白细胞介素13信号传导以及血小板活化相关的机制。PPI分析确定了具有生物学功能的子网，并筛选出影响止血进程的枢纽靶点。候选蛋白与主要成分具有良好的结合力。
炮姜在改善出血方面显示出良好的效果，其相关分子机制可能与免疫系统调节和血小板活化有关。因此，炮姜在临床上可能对胃肠道出血发挥保护作用。
