Danggui Jixueteng decoction for the treatment of myelosuppression after chemotherapy: A combined metabolomics and network pharmacology analysis
Objective: This study aimed to explore the mechanism of the Danggui Jixueteng decoction (DJD) in treating Myelosuppression after chemotherapy (MAC) through network pharmacology and metabolomics. Methods: We obtained the chemical structures of DJD compounds from TCMSP and PubMed. SwissTargetPredictio...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024007266 |
| _version_ | 1797304590549385216 |
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| author | Mingxin Guo Jiaqi Zeng Wenjing Li Zhiqiang Hu Ying Shen |
| author_facet | Mingxin Guo Jiaqi Zeng Wenjing Li Zhiqiang Hu Ying Shen |
| author_sort | Mingxin Guo |
| collection | DOAJ |
| description | Objective: This study aimed to explore the mechanism of the Danggui Jixueteng decoction (DJD) in treating Myelosuppression after chemotherapy (MAC) through network pharmacology and metabolomics. Methods: We obtained the chemical structures of DJD compounds from TCMSP and PubMed. SwissTargetPrediction, STITCH, CTD, GeneCards, and OMIM were utilized to acquire component targets and MAC-related targets. We identified the key compounds, core targets, main biological processes, and signaling pathways related to DJD by constructing and analyzing related networks. The main active compounds and key proteins of DJD in treating AA were confirmed by molecular docking. A MAC rat model was established through intraperitoneal injection of cyclophosphamide to confirm DJD's effect on the bone marrow hematopoietic system. Untargeted metabolomics analyzed serum metabolite differences between MAC rats and the control group, and before and after DJD treatment, to explore DJD's mechanism in treating MAC. Results: Of the 93 active compounds identified under screening conditions, 275 compound targets and 3113 MAC-related targets were obtained, including 95 intersecting targets; AKT1, STAT3, CASP3, and JUN were key proteins in MAC treatment. The phosphatidylinositol-3-kinase/RAC-alpha serine/threonine-protein kinase (PI3K/AKT) signaling pathway may play a crucial role in MAC treatment with DJD. Molecular docking results showed good docking effects of key protein AKT1 with luteolin, β-sitosterol, kaempferol, and glycyrrhizal chalcone A. In vivo experiments indicated that, compared to the model group, in the DJD group, levels of WBCs, RBCs, HGB, and PLTs in peripheral blood cells, thymus index increased, spleen index decreased, serum IL-3, GM-CSF levels increased, and IL-6, TNF-α, and VEGF levels decreased (p < 0.01); the pathological morphology of femoral bone marrow improved. Eleven differential metabolites were identified as differential serum metabolites, mainly concentrated in phenylalanine, tyrosine, and tryptophan biosynthesis pathways, phenylalanine metabolism, and arachidonic acid metabolism. Conclusion: This study revealed that DJD's therapeutic effects are due to multiple ingredients, targets, and pathways. DJD may activate the PI3K/AKT signaling pathway, promote hematopoietic-related cytokine production, regulate related metabolic pathways, and effectively alleviate cyclophosphamide-induced myelosuppression after chemotherapy in rats. |
| first_indexed | 2024-03-08T00:12:37Z |
| format | Article |
| id | doaj.art-e6cda515af7240d3b1b0182476e5bccd |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-08T00:12:37Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-e6cda515af7240d3b1b0182476e5bccd2024-02-17T06:38:27ZengElsevierHeliyon2405-84402024-02-01103e24695Danggui Jixueteng decoction for the treatment of myelosuppression after chemotherapy: A combined metabolomics and network pharmacology analysisMingxin Guo0Jiaqi Zeng1Wenjing Li2Zhiqiang Hu3Ying Shen4Department of Pharmacy, The Affiliated Yixing Hospital of Jiangsu University, Yixing, 214200, ChinaDepartment of Pharmacy, The Affiliated Yixing Hospital of Jiangsu University, Yixing, 214200, ChinaSchool of Pharmacy, Qiqihar Medical University, Qiqihaer, 161006, ChinaDepartment of Pharmacy, The Affiliated Yixing Hospital of Jiangsu University, Yixing, 214200, ChinaDepartment of Pharmacy, The Affiliated Yixing Hospital of Jiangsu University, Yixing, 214200, China; Corresponding author.Objective: This study aimed to explore the mechanism of the Danggui Jixueteng decoction (DJD) in treating Myelosuppression after chemotherapy (MAC) through network pharmacology and metabolomics. Methods: We obtained the chemical structures of DJD compounds from TCMSP and PubMed. SwissTargetPrediction, STITCH, CTD, GeneCards, and OMIM were utilized to acquire component targets and MAC-related targets. We identified the key compounds, core targets, main biological processes, and signaling pathways related to DJD by constructing and analyzing related networks. The main active compounds and key proteins of DJD in treating AA were confirmed by molecular docking. A MAC rat model was established through intraperitoneal injection of cyclophosphamide to confirm DJD's effect on the bone marrow hematopoietic system. Untargeted metabolomics analyzed serum metabolite differences between MAC rats and the control group, and before and after DJD treatment, to explore DJD's mechanism in treating MAC. Results: Of the 93 active compounds identified under screening conditions, 275 compound targets and 3113 MAC-related targets were obtained, including 95 intersecting targets; AKT1, STAT3, CASP3, and JUN were key proteins in MAC treatment. The phosphatidylinositol-3-kinase/RAC-alpha serine/threonine-protein kinase (PI3K/AKT) signaling pathway may play a crucial role in MAC treatment with DJD. Molecular docking results showed good docking effects of key protein AKT1 with luteolin, β-sitosterol, kaempferol, and glycyrrhizal chalcone A. In vivo experiments indicated that, compared to the model group, in the DJD group, levels of WBCs, RBCs, HGB, and PLTs in peripheral blood cells, thymus index increased, spleen index decreased, serum IL-3, GM-CSF levels increased, and IL-6, TNF-α, and VEGF levels decreased (p < 0.01); the pathological morphology of femoral bone marrow improved. Eleven differential metabolites were identified as differential serum metabolites, mainly concentrated in phenylalanine, tyrosine, and tryptophan biosynthesis pathways, phenylalanine metabolism, and arachidonic acid metabolism. Conclusion: This study revealed that DJD's therapeutic effects are due to multiple ingredients, targets, and pathways. DJD may activate the PI3K/AKT signaling pathway, promote hematopoietic-related cytokine production, regulate related metabolic pathways, and effectively alleviate cyclophosphamide-induced myelosuppression after chemotherapy in rats.http://www.sciencedirect.com/science/article/pii/S2405844024007266Danggui Jixueteng decoctionMyelosuppression after chemotherapyNetwork pharmacologyMolecular dockingHematopoietic microenvironment |
| spellingShingle | Mingxin Guo Jiaqi Zeng Wenjing Li Zhiqiang Hu Ying Shen Danggui Jixueteng decoction for the treatment of myelosuppression after chemotherapy: A combined metabolomics and network pharmacology analysis Heliyon Danggui Jixueteng decoction Myelosuppression after chemotherapy Network pharmacology Molecular docking Hematopoietic microenvironment |
| title | Danggui Jixueteng decoction for the treatment of myelosuppression after chemotherapy: A combined metabolomics and network pharmacology analysis |
| title_full | Danggui Jixueteng decoction for the treatment of myelosuppression after chemotherapy: A combined metabolomics and network pharmacology analysis |
| title_fullStr | Danggui Jixueteng decoction for the treatment of myelosuppression after chemotherapy: A combined metabolomics and network pharmacology analysis |
| title_full_unstemmed | Danggui Jixueteng decoction for the treatment of myelosuppression after chemotherapy: A combined metabolomics and network pharmacology analysis |
| title_short | Danggui Jixueteng decoction for the treatment of myelosuppression after chemotherapy: A combined metabolomics and network pharmacology analysis |
| title_sort | danggui jixueteng decoction for the treatment of myelosuppression after chemotherapy a combined metabolomics and network pharmacology analysis |
| topic | Danggui Jixueteng decoction Myelosuppression after chemotherapy Network pharmacology Molecular docking Hematopoietic microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024007266 |
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