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This study aimed to characterize the phytochemistry of ZRP and identify active ingredients related to its therapeutic effects. Multiple chromatographic techniques were employed to investigate the constituents of ZRP. H2O2-induced HUVECs were used to assess the vascular protective effects and elucidate the mechanisms of the representative components. Four new diarylheptanoids were separated and purified from ZRP, and their structures were identified using HR-MS, NMR, and ECD calculations. Furthermore, six representative compounds were selected using integrated PCA and OPLS-DA strategies exhibited cytoprotective effects against oxidative damage and promoted tube formation in vitro. Diarylheptanoids and gingerols are candidate active constituents of ZRP for the treatment of hemorrhagic disorders, potentially via activation of the Nrf-2\/HO-1 signaling pathway and upregulation of VEGF in damaged HUVECs.<\/jats:p>","DOI":"10.1021\/acs.jafc.5c12616","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:16:38Z","timestamp":1785849398000},"page":"24244-24262","source":"Crossref","is-referenced-by-count":0,"title":["Diarylheptanoids\nand Gingerols from\n                    <i>Zingiberis rhizoma<\/i>\n                    Praepratum: Isolation, Identification,\nand Their Protective Effects on H2O2-Induced\nHUVECs"],"prefix":"10.1021","volume":"74","author":[{"given":"Qian","family":"Zhu","sequence":"first","affiliation":[{"name":"Anhui University of Chinese Medicine , , ,","place":["Hefei, China, 230012"]},{"name":"Dancheng County Hospital of Traditional Chinese Medicine , , ,","place":["Zhoukou, Henan, China, 466100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanru","family":"Li","sequence":"additional","affiliation":[{"name":"Anhui University of Chinese Medicine , , ,","place":["Hefei, China, 230012"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuandong","family":"Liu","sequence":"additional","affiliation":[{"name":"Anhui University of Chinese Medicine , , ,","place":["Hefei, China, 230012"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Anhui University of Chinese Medicine , , ,","place":["Hefei, China, 230012"]},{"name":"Anhui Province Key Laboratory of Bioactive Natural Products , ,","place":["Hefei, China, 230012"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongsu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Anhui University of Chinese Medicine , , ,","place":["Hefei, China, 230012"]},{"name":"Anhui Province Key Laboratory of New Manufacturing Technology for Traditional Chinese Medicine Decoction Pieces , ,","place":["Hefei, China, 230012"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuxi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Anhui University of Chinese Medicine , , ,","place":["Hefei, China, 230012"]},{"name":"Anhui Province Key Laboratory of Bioactive Natural Products , ,","place":["Hefei, China, 230012"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yashuo","family":"Ren","sequence":"additional","affiliation":[{"name":"Anhui University of Chinese Medicine , , ,","place":["Hefei, China, 230012"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1559-9824","authenticated-orcid":true,"given":"Shengzhuo","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Agricultural Sciences , , ,","place":["Haikou, China, 571101"]},{"name":"Sanya Research Institute of Chinese Academy of Tropical Agricultural Sciences , ,","place":["Sanya, China, 572025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deling","family":"Wu","sequence":"additional","affiliation":[{"name":"Anhui University of Chinese Medicine , , ,","place":["Hefei, China, 230012"]},{"name":"Anhui Province Key Laboratory of Bioactive Natural Products , ,","place":["Hefei, China, 230012"]},{"name":"Anhui Province Key Laboratory of New Manufacturing Technology for Traditional Chinese Medicine Decoction Pieces , ,","place":["Hefei, China, 230012"]},{"name":"Bozhou University , ,","place":["Bozhou, China, 236800"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5956-1556","authenticated-orcid":true,"given":"Fengqing","family":"Xu","sequence":"additional","affiliation":[{"name":"Anhui University of Chinese Medicine , , ,","place":["Hefei, China, 230012"]},{"name":"Anhui Province Key Laboratory of Bioactive Natural Products , ,","place":["Hefei, China, 230012"]},{"name":"Anhui Province Key Laboratory of New Manufacturing Technology for Traditional Chinese Medicine Decoction Pieces , ,","place":["Hefei, China, 230012"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"2026081208090726700_cit1","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1093\/bja\/85.3.487","article-title":"Management of massive blood loss:\na template guideline","volume":"85","author":"Stainsby","year":"2000","journal-title":"Br. 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Ethnopharmacol"},{"key":"2026081208090726700_cit10","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s13020-025-01100-6","article-title":"The integration\nof spear and shield: a panoramic analysis of the blood circulation-promoting\nand hemostatic effects of Panax notoginseng","volume":"20","author":"Zhang","year":"2025","journal-title":"Chin Med"},{"key":"2026081208090726700_cit11","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1080\/13880209.2019.1645700","article-title":"A review on charred\ntraditional Chinese herbs: carbonization to yield a haemostatic effect","volume":"57","author":"Chen","year":"2019","journal-title":"Pharm. 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Food Prop"},{"key":"2026081208090726700_cit18","first-page":"I: 16","volume-title":"Chinese Pharmacopoeia","author":"Chinese Pharmaceutical Association.","year":"2020"},{"key":"2026081208090726700_cit19","first-page":"2950","article-title":"Application of ginger\ndrugs in FU Qing-zhu Nvke","volume":"38","author":"Shao","year":"2023","journal-title":"China J. Tradit.\nChin. Med. Pharm"},{"key":"2026081208090726700_cit20","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.19540\/j.cnki.cjcmm.20180226.002","article-title":"Pharmacological effects and clinical\napplications of Zingiber officinale and its processed\nproducts","volume":"43","author":"Dong","year":"2018","journal-title":"China J. Chin. Mater. 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Biol"},{"key":"2026081208090726700_cit24","first-page":"116","volume-title":"Science of Processing\nChinese Materia Medica","author":"Gong","year":"2007","edition":"2nd"},{"issue":"3","key":"2026081208090726700_cit25","first-page":"24","article-title":"Optimization of sand scalding process\nof processed ginger based on\nmulti-index evaluation","volume":"13","author":"Li","year":"2022","journal-title":"Pharm. Clin. Chin. Mater.\nMed"},{"key":"2026081208090726700_cit26","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5412","article-title":"UPLC-Q-Exactive\/MS\u2013based\nmetabonomics revealed protective effect of Zingiberis rhizome and\nits processed product on deficiency-cold and hemorrhagic syndrome\nrats","volume":"36","author":"Yang","year":"2022","journal-title":"Biomed. Chromatogr"},{"key":"2026081208090726700_cit27","first-page":"1454","article-title":"Study on the\nrelated substances and channel tropism of baked ginger on warming\nmeridian and hemostasis based on \u2018syndrome-efficacy-analysis\nof biological samples\u2019","volume":"35","author":"Niu","year":"2020","journal-title":"China J. Tradit.\nChin. Med. Pharm"},{"key":"2026081208090726700_cit28","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000039351","article-title":"Shenghua decoction for postpartum\nhemorrhage attributed to uterine atony: An observational study","volume":"103","author":"Yu","year":"2024","journal-title":"Medicine"},{"key":"2026081208090726700_cit29","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.jchromb.2016.01.009","article-title":"Chemical characterization\nand antioxidant activities comparison in fresh, dried, stir-frying\nand carbonized ginger","volume":"1011","author":"Li","year":"2016","journal-title":"J. Chromatography. B"},{"key":"2026081208090726700_cit30","doi-asserted-by":"publisher","first-page":"11690","DOI":"10.1021\/jf202544w","article-title":"Chemical\nconstituents and their bioactivities of \u201cTongling\nWhite Ginger\u201d (Zingiber officinale)","volume":"59","author":"Feng","year":"2011","journal-title":"J. Agric. Food Chem"},{"key":"2026081208090726700_cit31","doi-asserted-by":"publisher","first-page":"113975","DOI":"10.1016\/j.phytochem.2024.113975","article-title":"Dimeric diarylheptanoids with anti-inflammatory\nactivity from Zingiber officinale","volume":"219","author":"Fang","year":"2024","journal-title":"Phytochemistry"},{"key":"2026081208090726700_cit32","doi-asserted-by":"publisher","first-page":"2826","DOI":"10.3390\/molecules27092826","article-title":"Plants of the Genus Zingiber: a review of their ethnomedicine, phytochemistry\nand pharmacology","volume":"27","author":"Deng","year":"2022","journal-title":"Molecules"},{"key":"2026081208090726700_cit33","doi-asserted-by":"publisher","first-page":"887","DOI":"10.2174\/0929867330666230524122318","article-title":"Zingiber officinale Roscoe (ginger) and its bioactive compounds in diabetes: A systematic\nreview of clinical studies and insight of mechanism of action","volume":"31","author":"Van","year":"2024","journal-title":"Curr. Med. Chem"},{"key":"2026081208090726700_cit34","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1142\/S0192415X22500410","article-title":"Zingiber officinale: A systematic review of botany, phytochemistry\nand pharmacology of gut microbiota-related gastrointestinal benefits","volume":"50","author":"Lai","year":"2022","journal-title":"Am. J. Chin Med"},{"key":"2026081208090726700_cit35","doi-asserted-by":"publisher","first-page":"29376","DOI":"10.1039\/D1RA03592D","article-title":"Diarylheptanoid analogues\nfrom the rhizomes of Zingiber officinale and their\nanti-tumour activity","volume":"11","author":"Li","year":"2021","journal-title":"RSC Adv"},{"key":"2026081208090726700_cit36","first-page":"387","article-title":"Study on variation\nof non-volatitle compounds of raw ginger after processing by UHPLC-Orbitrap\/HRMS","volume":"36","author":"Chen","year":"2020","journal-title":"J. Nanjing Univ. Tradit. Chin. 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Asian Nat. Prod. Res"},{"key":"2026081208090726700_cit45","doi-asserted-by":"publisher","first-page":"6608","DOI":"10.1021\/acs.jafc.7b02021","article-title":"Diarylheptanoids\nfrom rhizomes of Alpinia officinarum inhibit aggregation\nof \u03b1-synuclein","volume":"65","author":"Fu","year":"2017","journal-title":"J. Agric.\nFood Chem"},{"key":"2026081208090726700_cit46","doi-asserted-by":"publisher","first-page":"15170","DOI":"10.1021\/acs.jafc.3c05224","article-title":"Renoprotective glycoside derivatives from Zingiber officinale (Ginger) peels","volume":"71","author":"Song","year":"2023","journal-title":"J. Agric.\nFood Chem"},{"key":"2026081208090726700_cit47","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1248\/cpb.55.899","article-title":"Facile discrimination\nof aldose enantiomers by reversed-phase HPLC","volume":"55","author":"Tanaka","year":"2007","journal-title":"Chem. Pharm. Bull"},{"key":"2026081208090726700_cit48","doi-asserted-by":"publisher","first-page":"158","DOI":"10.3390\/i4040158","article-title":"Extension of the Karplus relationship for NMR spin-spin\ncoupling constants to nonplanar ring systems: pseudorotation of tetraphydrofuran","volume":"4","author":"Wu","year":"2003","journal-title":"Int. J. Mol. Sci"},{"key":"2026081208090726700_cit49","doi-asserted-by":"publisher","first-page":"119533","DOI":"10.1016\/j.jep.2025.119533","article-title":"Nauclofffcines A and B, two novel monoterpenoid indole\nalkaloids from the Li folk herb Nauclea offfcinalis with anti-allergic inflammatory effects on RBL-2H3 cells","volume":"344","author":"Li","year":"2025","journal-title":"J. Ethnopharmacol"},{"key":"2026081208090726700_cit50","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1002\/ejoc.200801016","article-title":"NMR quantification of tautomeric populations in biogenic purine bases","volume":"2009","author":"Bartl","year":"2009","journal-title":"Eur. J. Org. Chem"},{"key":"2026081208090726700_cit51","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1248\/cpb.39.120","article-title":"Constituents of Zingiberaceae I.\nDiarylheptanoids from the rhizomes of ginger (Zingiber officinale Roscoe)","volume":"39","author":"Kikuzaki","year":"1991","journal-title":"Chem. Pharm. 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