{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:45:39Z","timestamp":1785732339349,"version":"3.56.0"},"reference-count":59,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82304851"],"award-info":[{"award-number":["82304851"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82174073"],"award-info":[{"award-number":["82174073"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82192913"],"award-info":[{"award-number":["82192913"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82304851"],"award-info":[{"award-number":["82304851"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82174073"],"award-info":[{"award-number":["82174073"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82192913"],"award-info":[{"award-number":["82192913"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005892","name":"China Academy of Chinese Medical Sciences","doi-asserted-by":"crossref","award":["CI2023E002"],"award-info":[{"award-number":["CI2023E002"]}],"id":[{"id":"10.13039\/501100005892","id-type":"DOI","asserted-by":"crossref"}]},{"award":["CI2023E002"],"award-info":[{"award-number":["CI2023E002"]}],"id":[{"id":"https:\/\/ror.org\/042pgcv68","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Fundamental Research Funds for the Central Public Welfare Research Institutes","award":["ZZ13-YQ-055"],"award-info":[{"award-number":["ZZ13-YQ-055"]}]},{"name":"Fundamental Research Funds for the Central Public Welfare Research Institutes","award":["ZXKT22044"],"award-info":[{"award-number":["ZXKT22044"]}]},{"name":"Fundamental Research Funds for the Central Public Welfare Research Institutes","award":["ZXKT25036"],"award-info":[{"award-number":["ZXKT25036"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Dangguibuxue decoction (DD), containing Angelica sinensis (Oliv.) Diels (AS) and Astragalus membranaceus (Fisch.) Bge. (AM) (1:5), is a well-known traditional Chinese medicine (TCM) used for strengthening qi and nourishing the blood. DD has shown therapeutic effects in nephropathy patients. However, the underlying mechanisms based on the traditional efficacy are still not fully elucidated. Methods: The chemical constituents in DD were identified using UPLC-MS\/MS. Network pharmacology analysis was applied to predict the potential target genes and associated signaling pathways. A renal fibrosis mouse model was induced by the intraperitoneal injection of aristolochic acid I (AA I) at 3.0 mg\/kg. Mice were treated with AM, AS, and DD at two dosages by oral gavage for 30 days. Body weights, serum biochemistry, hematology, and histopathology observations were assessed. The key targets predicted were validated using qRT-PCR and Western blotting. The active constituents were screened by molecular docking, and their anti-fibrotic effects were evaluated through in vitro assays. Results: DD effectively improved renal functions and alleviated AA I-induced renal fibrosis. DD alleviated anemia and upregulated the expression of Erythropoietin (EPO). Network pharmacology analysis indicated the involvement of signaling pathways, including the PI3K\/Akt, hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) and transforming growth factor-\u03b2 (TGF-\u03b2) signaling pathways. Experimental validation further demonstrated that DD reduced the protein expression of HIF-1\u03b1, collagen I, and TGF-\u03b2, and the ratios of phosphorylated Smad2\/3 to total Smad2\/3. Molecular docking and in vitro assays suggested that rutin may be a potential bioactive compound in DD. Conclusions: This research indicated that DD ameliorated AA I-induced renal fibrosis in mice, which may be associated with the modulation of HIF-1\u03b1 and TGF-\u03b2\/Smad signaling pathways. Rutin may be a potential bioactive compound in DD with anti-fibrotic activity, but further studies are still needed to clarify the content of rutin in DD, the amount of its exposure in the body, and its contribution to the effects of DD.<\/jats:p>","DOI":"10.3390\/ph19081206","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T01:43:27Z","timestamp":1785721407000},"page":"1206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dangguibuxue Decoction Attenuated AA I-Induced Renal Fibrosis: Integrating Network Pharmacology and Experimental Validation"],"prefix":"10.3390","volume":"19","author":[{"given":"Suyan","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"},{"name":"Beijing Key Laboratory of Psychoactive Substances Discovery and Control in Chinese Herbal Medicines, Beijing 100700, China"},{"name":"Key Laboratory of TCM Safety Risk Assessment and Translation, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Meng","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Psychoactive Substances Discovery and Control in Chinese Herbal Medicines, Beijing 100700, China"},{"name":"Key Laboratory of TCM Safety Risk Assessment and Translation, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Psychoactive Substances Discovery and Control in Chinese Herbal Medicines, Beijing 100700, China"},{"name":"Key Laboratory of TCM Safety Risk Assessment and Translation, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunying","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Psychoactive Substances Discovery and Control in Chinese Herbal Medicines, Beijing 100700, China"},{"name":"Key Laboratory of TCM Safety Risk Assessment and Translation, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yi","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Psychoactive Substances Discovery and Control in Chinese Herbal Medicines, Beijing 100700, China"},{"name":"Key Laboratory of TCM Safety Risk Assessment and Translation, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayin","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"},{"name":"Beijing Key Laboratory of Psychoactive Substances Discovery and Control in Chinese Herbal Medicines, Beijing 100700, China"},{"name":"Key Laboratory of TCM Safety Risk Assessment and Translation, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3268-0421","authenticated-orcid":false,"given":"Yushi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Psychoactive Substances Discovery and Control in Chinese Herbal Medicines, Beijing 100700, China"},{"name":"Key Laboratory of TCM Safety Risk Assessment and Translation, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Pan","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Psychoactive Substances Discovery and Control in Chinese Herbal Medicines, Beijing 100700, China"},{"name":"Key Laboratory of TCM Safety Risk Assessment and Translation, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Psychoactive Substances Discovery and Control in Chinese Herbal Medicines, Beijing 100700, China"},{"name":"Key Laboratory of TCM Safety Risk Assessment and Translation, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Psychoactive Substances Discovery and Control in Chinese Herbal Medicines, Beijing 100700, China"},{"name":"Key Laboratory of TCM Safety Risk Assessment and Translation, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Gao","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Psychoactive Substances Discovery and Control in Chinese Herbal Medicines, Beijing 100700, China"},{"name":"Key Laboratory of TCM Safety Risk Assessment and Translation, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingnan","family":"Yue","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Psychoactive Substances Discovery and Control in Chinese Herbal Medicines, Beijing 100700, China"},{"name":"Key Laboratory of TCM Safety Risk Assessment and Translation, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Wu","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Psychoactive Substances Discovery and Control in Chinese Herbal Medicines, Beijing 100700, China"},{"name":"Key Laboratory of TCM Safety Risk Assessment and Translation, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7739-0196","authenticated-orcid":false,"given":"Hongmei","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"},{"name":"Beijing Key Laboratory of Psychoactive Substances Discovery and Control in Chinese Herbal Medicines, Beijing 100700, China"},{"name":"Key Laboratory of TCM Safety Risk Assessment and Translation, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihua","family":"Liang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"},{"name":"Beijing Key Laboratory of Psychoactive Substances Discovery and Control in Chinese Herbal Medicines, Beijing 100700, China"},{"name":"Key Laboratory of TCM Safety Risk Assessment and Translation, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1093\/ckj\/sfab170","article-title":"RICORS2040: The need for collaborative research in chronic kidney 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