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 s...
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| Veröffentlicht in: | Phytotherapy research 2024-11, Vol.38 (11), p.5134-5149 |
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| creator | Liu, Xiaoxi Lai, Jia Zhang, Xiaoqin Wu, Anguo Zhou, Ling Li, Yueyue Huang, Qianqian Huang, Xinwu Li, Hua Lan, Cai Liu, Jian Huang, Feihong Wu, Jianming |
| description | 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.
Schematic illustration of HM for MK differentiation and thrombopoiesis. |
| doi_str_mv | 10.1002/ptr.8317 |
| format | Article |
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Schematic illustration of HM for MK differentiation and thrombopoiesis.</description><identifier>ISSN: 0951-418X</identifier><identifier>ISSN: 1099-1573</identifier><identifier>EISSN: 1099-1573</identifier><identifier>DOI: 10.1002/ptr.8317</identifier><identifier>PMID: 39152726</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>5‐HTR2A/Rac1/Cdc42/JNK ; alkaloids ; Animals ; Biological activity ; Blood Platelets - drug effects ; Cdc42 protein ; Cell differentiation ; Cell Differentiation - drug effects ; Differentiation (biology) ; Flow cytometry ; harmine ; Harmine - pharmacology ; Hematological diseases ; Herbal medicine ; Humans ; In vivo methods and tests ; irradiation ; Male ; MAP Kinase Signaling System - drug effects ; Maturation ; Medicinal plants ; megakaryocyte differentiation ; Megakaryocytes - drug effects ; Mice ; Molecular docking ; Molecular Docking Simulation ; Oriental traditional medicine ; Phalloidin ; phalloidine ; Pharmacology ; phytotherapy ; Plant extracts ; Plant layout ; Platelets ; rac1 GTP-Binding Protein - metabolism ; Rac1 protein ; radiation ; Receptor, Serotonin, 5-HT2A - metabolism ; Staining ; Thrombocytopenia ; Thrombocytopenia - drug therapy ; Thrombopoiesis ; Thrombopoiesis - drug effects ; Traditional Chinese medicine</subject><ispartof>Phytotherapy research, 2024-11, Vol.38 (11), p.5134-5149</ispartof><rights>2024 John Wiley & Sons Ltd.</rights><rights>2024 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2737-cca3daaafe5a97518fd1e20e64a1f7af68d606de0b61ce7b4b5ffa89e1d7be083</cites><orcidid>0000-0003-4688-6081 ; 0000-0002-6136-7469</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fptr.8317$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fptr.8317$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39152726$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Xiaoxi</creatorcontrib><creatorcontrib>Lai, Jia</creatorcontrib><creatorcontrib>Zhang, Xiaoqin</creatorcontrib><creatorcontrib>Wu, Anguo</creatorcontrib><creatorcontrib>Zhou, Ling</creatorcontrib><creatorcontrib>Li, Yueyue</creatorcontrib><creatorcontrib>Huang, Qianqian</creatorcontrib><creatorcontrib>Huang, Xinwu</creatorcontrib><creatorcontrib>Li, Hua</creatorcontrib><creatorcontrib>Lan, Cai</creatorcontrib><creatorcontrib>Liu, Jian</creatorcontrib><creatorcontrib>Huang, Feihong</creatorcontrib><creatorcontrib>Wu, Jianming</creatorcontrib><title>Harmine promotes megakaryocyte differentiation and thrombopoiesis by activating the Rac1/Cdc42/JNK pathway through a potential target of 5‐HTR2A</title><title>Phytotherapy research</title><addtitle>Phytother Res</addtitle><description>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.
Schematic illustration of HM for MK differentiation and thrombopoiesis.</description><subject>5‐HTR2A/Rac1/Cdc42/JNK</subject><subject>alkaloids</subject><subject>Animals</subject><subject>Biological activity</subject><subject>Blood Platelets - drug effects</subject><subject>Cdc42 protein</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - drug effects</subject><subject>Differentiation (biology)</subject><subject>Flow cytometry</subject><subject>harmine</subject><subject>Harmine - pharmacology</subject><subject>Hematological diseases</subject><subject>Herbal medicine</subject><subject>Humans</subject><subject>In vivo methods and tests</subject><subject>irradiation</subject><subject>Male</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Maturation</subject><subject>Medicinal plants</subject><subject>megakaryocyte differentiation</subject><subject>Megakaryocytes - drug effects</subject><subject>Mice</subject><subject>Molecular docking</subject><subject>Molecular Docking Simulation</subject><subject>Oriental traditional medicine</subject><subject>Phalloidin</subject><subject>phalloidine</subject><subject>Pharmacology</subject><subject>phytotherapy</subject><subject>Plant extracts</subject><subject>Plant layout</subject><subject>Platelets</subject><subject>rac1 GTP-Binding Protein - metabolism</subject><subject>Rac1 protein</subject><subject>radiation</subject><subject>Receptor, Serotonin, 5-HT2A - metabolism</subject><subject>Staining</subject><subject>Thrombocytopenia</subject><subject>Thrombocytopenia - drug therapy</subject><subject>Thrombopoiesis</subject><subject>Thrombopoiesis - drug effects</subject><subject>Traditional Chinese medicine</subject><issn>0951-418X</issn><issn>1099-1573</issn><issn>1099-1573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAQhi0EoktB4gmQJS5c0rUdJ3GO1QpYoAK0WiRu0cQZ77ps4mA7VLnxCIhH5EnwtgUkJMRpDvPNN5r5CXnM2RlnTCzH6M9Uzqs7ZMFZXWe8qPK7ZMHqgmeSq48n5EEIl4yxWjB5n5zkNS9EJcoF-b4G39sB6ehd7yIG2uMOPoGfnZ4j0s4agx6HaCFaN1AYOhr3iW3d6CwGG2g7U9DRfknAsEtNpBvQfLnqtBTL12_f0BHi_grm67lpt6dAx7TpqDzQCH6HkTpDix9fv623G3H-kNwzcAj46Laekg8vnm9X6-zi3ctXq_OLTIsqrzKtIe8AwGABdVVwZTqOgmEpgZsKTKm6kpUdsrbkGqtWtoUxoGrkXdUiU_kpeXbjTad_njDEprdB4-EAA7opNDkvJC9zwdn_UVZLJqVSMqFP_0Iv3eSHdEgSCsWYkmX9R6i9C8GjaUZv-_T1hrPmGGmTIm2OkSb0ya1wanvsfoO_MkxAdgNc2QPO_xQ177eba-FPXJGtVw</recordid><startdate>202411</startdate><enddate>202411</enddate><creator>Liu, Xiaoxi</creator><creator>Lai, Jia</creator><creator>Zhang, Xiaoqin</creator><creator>Wu, Anguo</creator><creator>Zhou, Ling</creator><creator>Li, Yueyue</creator><creator>Huang, Qianqian</creator><creator>Huang, Xinwu</creator><creator>Li, Hua</creator><creator>Lan, Cai</creator><creator>Liu, Jian</creator><creator>Huang, Feihong</creator><creator>Wu, Jianming</creator><general>John Wiley & Sons, Ltd</general><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0003-4688-6081</orcidid><orcidid>https://orcid.org/0000-0002-6136-7469</orcidid></search><sort><creationdate>202411</creationdate><title>Harmine promotes megakaryocyte differentiation and thrombopoiesis by activating the Rac1/Cdc42/JNK pathway through a potential target of 5‐HTR2A</title><author>Liu, Xiaoxi ; Lai, Jia ; Zhang, Xiaoqin ; Wu, Anguo ; Zhou, Ling ; Li, Yueyue ; Huang, Qianqian ; Huang, Xinwu ; Li, Hua ; Lan, Cai ; Liu, Jian ; Huang, Feihong ; Wu, Jianming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2737-cca3daaafe5a97518fd1e20e64a1f7af68d606de0b61ce7b4b5ffa89e1d7be083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>5‐HTR2A/Rac1/Cdc42/JNK</topic><topic>alkaloids</topic><topic>Animals</topic><topic>Biological activity</topic><topic>Blood Platelets - drug effects</topic><topic>Cdc42 protein</topic><topic>Cell differentiation</topic><topic>Cell Differentiation - drug effects</topic><topic>Differentiation (biology)</topic><topic>Flow cytometry</topic><topic>harmine</topic><topic>Harmine - pharmacology</topic><topic>Hematological diseases</topic><topic>Herbal medicine</topic><topic>Humans</topic><topic>In vivo methods and tests</topic><topic>irradiation</topic><topic>Male</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Maturation</topic><topic>Medicinal plants</topic><topic>megakaryocyte differentiation</topic><topic>Megakaryocytes - drug effects</topic><topic>Mice</topic><topic>Molecular docking</topic><topic>Molecular Docking Simulation</topic><topic>Oriental traditional medicine</topic><topic>Phalloidin</topic><topic>phalloidine</topic><topic>Pharmacology</topic><topic>phytotherapy</topic><topic>Plant extracts</topic><topic>Plant layout</topic><topic>Platelets</topic><topic>rac1 GTP-Binding Protein - metabolism</topic><topic>Rac1 protein</topic><topic>radiation</topic><topic>Receptor, Serotonin, 5-HT2A - metabolism</topic><topic>Staining</topic><topic>Thrombocytopenia</topic><topic>Thrombocytopenia - drug therapy</topic><topic>Thrombopoiesis</topic><topic>Thrombopoiesis - drug effects</topic><topic>Traditional Chinese medicine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Xiaoxi</creatorcontrib><creatorcontrib>Lai, Jia</creatorcontrib><creatorcontrib>Zhang, Xiaoqin</creatorcontrib><creatorcontrib>Wu, Anguo</creatorcontrib><creatorcontrib>Zhou, Ling</creatorcontrib><creatorcontrib>Li, Yueyue</creatorcontrib><creatorcontrib>Huang, Qianqian</creatorcontrib><creatorcontrib>Huang, Xinwu</creatorcontrib><creatorcontrib>Li, Hua</creatorcontrib><creatorcontrib>Lan, Cai</creatorcontrib><creatorcontrib>Liu, Jian</creatorcontrib><creatorcontrib>Huang, Feihong</creatorcontrib><creatorcontrib>Wu, Jianming</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Phytotherapy research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Xiaoxi</au><au>Lai, Jia</au><au>Zhang, Xiaoqin</au><au>Wu, Anguo</au><au>Zhou, Ling</au><au>Li, Yueyue</au><au>Huang, Qianqian</au><au>Huang, Xinwu</au><au>Li, Hua</au><au>Lan, Cai</au><au>Liu, Jian</au><au>Huang, Feihong</au><au>Wu, Jianming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Harmine promotes megakaryocyte differentiation and thrombopoiesis by activating the Rac1/Cdc42/JNK pathway through a potential target of 5‐HTR2A</atitle><jtitle>Phytotherapy research</jtitle><addtitle>Phytother Res</addtitle><date>2024-11</date><risdate>2024</risdate><volume>38</volume><issue>11</issue><spage>5134</spage><epage>5149</epage><pages>5134-5149</pages><issn>0951-418X</issn><issn>1099-1573</issn><eissn>1099-1573</eissn><abstract>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.
Schematic illustration of HM for MK differentiation and thrombopoiesis.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>39152726</pmid><doi>10.1002/ptr.8317</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0003-4688-6081</orcidid><orcidid>https://orcid.org/0000-0002-6136-7469</orcidid></addata></record> |
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| subjects | 5‐HTR2A/Rac1/Cdc42/JNK alkaloids Animals Biological activity Blood Platelets - drug effects Cdc42 protein Cell differentiation Cell Differentiation - drug effects Differentiation (biology) Flow cytometry harmine Harmine - pharmacology Hematological diseases Herbal medicine Humans In vivo methods and tests irradiation Male MAP Kinase Signaling System - drug effects Maturation Medicinal plants megakaryocyte differentiation Megakaryocytes - drug effects Mice Molecular docking Molecular Docking Simulation Oriental traditional medicine Phalloidin phalloidine Pharmacology phytotherapy Plant extracts Plant layout Platelets rac1 GTP-Binding Protein - metabolism Rac1 protein radiation Receptor, Serotonin, 5-HT2A - metabolism Staining Thrombocytopenia Thrombocytopenia - drug therapy Thrombopoiesis Thrombopoiesis - drug effects Traditional Chinese medicine |
| title | Harmine promotes megakaryocyte differentiation and thrombopoiesis by activating the Rac1/Cdc42/JNK pathway through a potential target of 5‐HTR2A |
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