哈明通过 5-HTR2A 的潜在靶点激活 Rac1/Cdc42/JNK 通路,从而促进巨核细胞分化和血栓形成。

IF 6.1 2区 医学 Q1 CHEMISTRY, MEDICINAL
Phytotherapy Research Pub Date : 2024-11-01 Epub Date: 2024-08-17 DOI:10.1002/ptr.8317
Xiaoxi Liu, Jia Lai, Xiaoqin Zhang, Anguo Wu, Ling Zhou, Yueyue Li, Qianqian Huang, Xinwu Huang, Hua Li, Cai Lan, Jian Liu, Feihong Huang, Jianming Wu
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引用次数: 0

摘要

哈明(HM)是从植物中提取的一种 β-咔啉生物碱,是传统中药(TCM)的重要成分,以其多样的药理活性而闻名。血小板减少症是一种常见且具有挑战性的血液病,常常与严重疾病并存。以往的研究表明,HM 与血小板减少之间存在相关性,但其机制有待进一步阐明。本研究旨在阐明 HM 对血小板减少的影响机制,并开发新的治疗策略。本研究采用流式细胞术、Giemsa 染色法和类黄酮染色法评估 HM 对体外 Meg-01 和 HEL 细胞分化和成熟的影响。采用辐射诱导的血小板减少小鼠模型来评估 HM 对体内血小板生成的影响。利用网络药理学、分子对接和蛋白质印迹技术研究了 HM 的靶点和机制。结果表明,HM 能在体外促进 Meg-01 和 HEL 细胞的分化和成熟,并在体内恢复辐照小鼠的血小板水平。随后研究发现,HM 通过上调 Rac1、Cdc42、JNK 和 5-HTR2A 的表达参与了血小板生成的生物学过程。此外,还证实了 HM 对 5-HTR2A 的靶向作用及其与下游 Rac1/Cdc42/JNK 的相关性。总之,HM 通过 5-HTR2A 和 Rac1/Cdc42/JNK 途径调节巨核细胞分化和血栓形成,为血小板减少症提供了一种潜在的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Harmine promotes megakaryocyte differentiation and thrombopoiesis by activating the Rac1/Cdc42/JNK pathway through a potential target of 5-HTR2A.

Harmine (HM), a β-carboline alkaloid extracted from plants, is a crucial component of traditional Chinese medicine (TCM) known for its diverse pharmacological activities. Thrombocytopenia, a common and challenging hematological disorder, often coexists with serious illnesses. Previous research has shown a correlation between HM and thrombocytopenia, but the mechanism needs further elucidation. The aim of this study was to clarify the mechanisms underlying the effects of HM on thrombocytopenia and to develop new therapeutic strategies. Flow cytometry, Giemsa staining, and Phalloidin staining were used to assess HM's impact on Meg-01 and HEL cell differentiation and maturation in vitro. A radiation-induced thrombocytopenic mouse model was employed to evaluate HM's effect on platelet production in vivo. Network pharmacology, molecular docking, and protein blotting were utilized to investigate HM's targets and mechanisms. The results demonstrated that HM dose-dependently promoted Meg-01 and HEL cell differentiation and maturation in vitro and restored platelet levels in irradiated mice in vivo. Subsequently, HM was found to be involved in the biological process of platelet production by upregulating the expressions of Rac1, Cdc42, JNK, and 5-HTR2A. Furthermore, the targeting of HM to 5-HTR2A and its correlation with downstream Rac1/Cdc42/JNK were also confirmed. In conclusion, HM regulates megakaryocyte differentiation and thrombopoiesis through the 5-HTR2A and Rac1/Cdc42/JNK pathways, providing a potential treatment strategy for thrombocytopenia.

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来源期刊
Phytotherapy Research
Phytotherapy Research 医学-药学
CiteScore
12.80
自引率
5.60%
发文量
325
审稿时长
2.6 months
期刊介绍: Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field. Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters. By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.
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