{"title":"黄芩煎剂中四种活性成分的最佳组合对伊立替康抗结直肠癌的协同增敏作用。","authors":"Hongyan Zhou, Dingxin Hu, Xian Zhao, Siyuan Qin, Qiyao Nong, Yuan Tian, Zunjian Zhang, Haijuan Dong, Pei Zhang, Fengguo Xu","doi":"10.1186/s13020-024-00967-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study.</p><p><strong>Objective: </strong>This study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism.</p><p><strong>Methods: </strong>The orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics.</p><p><strong>Results: </strong>In vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 μM, 47 μM, 46.5 μM and 9.8 μM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism.</p><p><strong>Conclusion: </strong>The optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"19 1","pages":"94"},"PeriodicalIF":5.3000,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218176/pdf/","citationCount":"0","resultStr":"{\"title\":\"An optimal combination of four active components in Huangqin decoction for the synergistic sensitization of irinotecan against colorectal cancer.\",\"authors\":\"Hongyan Zhou, Dingxin Hu, Xian Zhao, Siyuan Qin, Qiyao Nong, Yuan Tian, Zunjian Zhang, Haijuan Dong, Pei Zhang, Fengguo Xu\",\"doi\":\"10.1186/s13020-024-00967-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study.</p><p><strong>Objective: </strong>This study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism.</p><p><strong>Methods: </strong>The orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics.</p><p><strong>Results: </strong>In vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 μM, 47 μM, 46.5 μM and 9.8 μM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism.</p><p><strong>Conclusion: </strong>The optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.</p>\",\"PeriodicalId\":10266,\"journal\":{\"name\":\"Chinese Medicine\",\"volume\":\"19 1\",\"pages\":\"94\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-07-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218176/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chinese Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13020-024-00967-1\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"INTEGRATIVE & COMPLEMENTARY MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chinese Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13020-024-00967-1","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INTEGRATIVE & COMPLEMENTARY MEDICINE","Score":null,"Total":0}
An optimal combination of four active components in Huangqin decoction for the synergistic sensitization of irinotecan against colorectal cancer.
Background: Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study.
Objective: This study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism.
Methods: The orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics.
Results: In vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 μM, 47 μM, 46.5 μM and 9.8 μM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism.
Conclusion: The optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.
Chinese MedicineINTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY
CiteScore
7.90
自引率
4.10%
发文量
133
审稿时长
31 weeks
期刊介绍：
Chinese Medicine is an open access, online journal publishing evidence-based, scientifically justified, and ethical research into all aspects of Chinese medicine.
Areas of interest include recent advances in herbal medicine, clinical nutrition, clinical diagnosis, acupuncture, pharmaceutics, biomedical sciences, epidemiology, education, informatics, sociology, and psychology that are relevant and significant to Chinese medicine. Examples of research approaches include biomedical experimentation, high-throughput technology, clinical trials, systematic reviews, meta-analysis, sampled surveys, simulation, data curation, statistics, omics, translational medicine, and integrative methodologies.
Chinese Medicine is a credible channel to communicate unbiased scientific data, information, and knowledge in Chinese medicine among researchers, clinicians, academics, and students in Chinese medicine and other scientific disciplines of medicine.
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