{"title":"用Taxus baccata植物成分对抗HTLV-1感染:分子机制 潜在的抗ATLL药物","authors":"Arezoo Baghban , S.A.Rahim Rezaee , Mohsen Tafaghodi , Mohammadreza Bozorgmehr , Mohammad Momen Heravi","doi":"10.1016/j.prenap.2024.100036","DOIUrl":null,"url":null,"abstract":"<div><p><em>Taxus baccata</em> is recognized as a traditional herb with antiviral and anticancer properties, making it a valuable candidate for anti-proliferative and antiviral agents, particularly in the absence of a cure for HTLV-1 infection and related diseases. The alkaloid extract of <em>Taxus baccata</em> was evaluated for its impact on HTLV-1-MT2 cell proliferation and HTLV-1 protease activity, presenting a promising avenue for therapeutic applications akin to HIV-PR inhibitors. Given the pressing need for effective treatments for HTLV-1-associated conditions, our study delved into the alkaloid extract's effects through immunofluorescence assays on HTLV-1 protease both in vitro and in silico. Confirmation of <em>Taxus baccata</em> extraction was achieved through immunofluorescence, infrared spectroscopy (IR), gas chromatography-mass spectrometry (GC-MS), and high-performance liquid chromatography (HPLC) analysis, with paclitaxel serving as a control. Furthermore, the anticancer properties of the alcoholic and alkaloid extracts were explored through in vitro assays using various cell lines, including HTLV-1-MT2, A549, HT29, and MCF7, alongside flow cytometry assessments. Notably, treatment with the alkaloid extract significantly impacted the survival of HTLV-1-MT2 cells (-2.44±0.012), alcoholic extract (11.17<span><math><mrow><mo>±</mo><mn>0.13</mn></mrow></math></span>) and paclitaxel (0.00<span><math><mrow><mo>±</mo><mn>0.18</mn></mrow></math></span>) were evaluated. GC-MS analysis identified Dimethyl malate, Lichexanthone, and Glycinexylidide as bioactive compounds within the plant, with investigations into their molecular interactions with HTLV-1 protease conducted. Molecular dynamics studies revealed key interaction sites between the compounds and HTLV-1 protease (PDB ID:4YDF), particularly highlighting the binding sequence of the dimethyl malate ligand within the protease A chain (Ala59). Collectively, the alkaloid compounds from <em>Taxus baccata</em> exhibit potential inhibitory effects on HTLV-1 oncovirus proliferation and transmission.</p></div>","PeriodicalId":101014,"journal":{"name":"Pharmacological Research - Natural Products","volume":"4 ","pages":"Article 100036"},"PeriodicalIF":0.0000,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Combating HTLV-1 infections with Taxus baccata phytoconstituents: Molecular mechanisms potential anti-ATLL agents\",\"authors\":\"Arezoo Baghban , S.A.Rahim Rezaee , Mohsen Tafaghodi , Mohammadreza Bozorgmehr , Mohammad Momen Heravi\",\"doi\":\"10.1016/j.prenap.2024.100036\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><em>Taxus baccata</em> is recognized as a traditional herb with antiviral and anticancer properties, making it a valuable candidate for anti-proliferative and antiviral agents, particularly in the absence of a cure for HTLV-1 infection and related diseases. The alkaloid extract of <em>Taxus baccata</em> was evaluated for its impact on HTLV-1-MT2 cell proliferation and HTLV-1 protease activity, presenting a promising avenue for therapeutic applications akin to HIV-PR inhibitors. Given the pressing need for effective treatments for HTLV-1-associated conditions, our study delved into the alkaloid extract's effects through immunofluorescence assays on HTLV-1 protease both in vitro and in silico. Confirmation of <em>Taxus baccata</em> extraction was achieved through immunofluorescence, infrared spectroscopy (IR), gas chromatography-mass spectrometry (GC-MS), and high-performance liquid chromatography (HPLC) analysis, with paclitaxel serving as a control. Furthermore, the anticancer properties of the alcoholic and alkaloid extracts were explored through in vitro assays using various cell lines, including HTLV-1-MT2, A549, HT29, and MCF7, alongside flow cytometry assessments. Notably, treatment with the alkaloid extract significantly impacted the survival of HTLV-1-MT2 cells (-2.44±0.012), alcoholic extract (11.17<span><math><mrow><mo>±</mo><mn>0.13</mn></mrow></math></span>) and paclitaxel (0.00<span><math><mrow><mo>±</mo><mn>0.18</mn></mrow></math></span>) were evaluated. GC-MS analysis identified Dimethyl malate, Lichexanthone, and Glycinexylidide as bioactive compounds within the plant, with investigations into their molecular interactions with HTLV-1 protease conducted. Molecular dynamics studies revealed key interaction sites between the compounds and HTLV-1 protease (PDB ID:4YDF), particularly highlighting the binding sequence of the dimethyl malate ligand within the protease A chain (Ala59). Collectively, the alkaloid compounds from <em>Taxus baccata</em> exhibit potential inhibitory effects on HTLV-1 oncovirus proliferation and transmission.</p></div>\",\"PeriodicalId\":101014,\"journal\":{\"name\":\"Pharmacological Research - Natural Products\",\"volume\":\"4 \",\"pages\":\"Article 100036\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-04-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacological Research - Natural Products\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2950199724000247\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacological Research - Natural Products","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2950199724000247","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Taxus baccata is recognized as a traditional herb with antiviral and anticancer properties, making it a valuable candidate for anti-proliferative and antiviral agents, particularly in the absence of a cure for HTLV-1 infection and related diseases. The alkaloid extract of Taxus baccata was evaluated for its impact on HTLV-1-MT2 cell proliferation and HTLV-1 protease activity, presenting a promising avenue for therapeutic applications akin to HIV-PR inhibitors. Given the pressing need for effective treatments for HTLV-1-associated conditions, our study delved into the alkaloid extract's effects through immunofluorescence assays on HTLV-1 protease both in vitro and in silico. Confirmation of Taxus baccata extraction was achieved through immunofluorescence, infrared spectroscopy (IR), gas chromatography-mass spectrometry (GC-MS), and high-performance liquid chromatography (HPLC) analysis, with paclitaxel serving as a control. Furthermore, the anticancer properties of the alcoholic and alkaloid extracts were explored through in vitro assays using various cell lines, including HTLV-1-MT2, A549, HT29, and MCF7, alongside flow cytometry assessments. Notably, treatment with the alkaloid extract significantly impacted the survival of HTLV-1-MT2 cells (-2.44±0.012), alcoholic extract (11.17) and paclitaxel (0.00) were evaluated. GC-MS analysis identified Dimethyl malate, Lichexanthone, and Glycinexylidide as bioactive compounds within the plant, with investigations into their molecular interactions with HTLV-1 protease conducted. Molecular dynamics studies revealed key interaction sites between the compounds and HTLV-1 protease (PDB ID:4YDF), particularly highlighting the binding sequence of the dimethyl malate ligand within the protease A chain (Ala59). Collectively, the alkaloid compounds from Taxus baccata exhibit potential inhibitory effects on HTLV-1 oncovirus proliferation and transmission.