{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T06:58:35Z","timestamp":1774594715928,"version":"3.50.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T00:00:00Z","timestamp":1618876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Our previous study revealed that Shuanghuang Shengbai granule could cure the myelosuppression induced by cyclophosphamide (CTX) in lung cancer. However, its hematopoietic effects and molecular mechanisms remain not fully understood. Therefore, this study was intended to investigate the effects and the underlying mechanisms of Astragaloside IV (AS) and saponins of rhizoma polygonati (SRP), the two main bioactive ingredients of Shuanghuang Shengbai granule, on CTX-induced myelosuppression. CTX inhibited the proliferation and promoted apoptosis in bone marrow hematopoietic stem cells (BMHSCs), accompanied by the increased expression of miR-142-3p. AS and\/or SRP treatment could alleviate CTX-induced cell injury and suppress the expression of miR-142-3p. Over-expression of miR-142-3p partially reversed the therapeutic effect of AS and\/or SRP on CTX-induced cell injury in BMHSCs. Further mechanism exploration discovered that <jats:italic>HMGB1<\/jats:italic> was the target gene of miR-142-3p, and miR-142-3p negatively regulated the expression of HMGB1. To further explore the function of AS and\/or SRP <jats:italic>in vivo<\/jats:italic>, we constructed a lung cancer xenograft combined with CTX-induced myelosuppression mouse model, and we found that AS and SRP remarkably reversed the CTX-induced reduction of white blood cells, bone marrow nucleated cells, and thymus index <jats:italic>in vivo<\/jats:italic> and did not affect the chemotherapy effect of lung cancer. Collectively, our results strongly suggested that AS and SRP could improve the hematopoietic function of myelosuppressed lung cancer mice, and their effects may be related to the inhibition of miR-142-3p expression in BMHSCs.<\/jats:p>","DOI":"10.3389\/fonc.2021.630921","type":"journal-article","created":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T04:30:33Z","timestamp":1618893033000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Astragaloside IV and Saponins of Rhizoma Polygonati Cure Cyclophosphamide-Induced Myelosuppression in Lung Adenocarcinoma via Down-Regulating miR-142-3p"],"prefix":"10.3389","volume":"11","author":[{"given":"Xian","family":"Gu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling-yu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen-ye","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke-ping","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"725","DOI":"10.17219\/acem\/68631","article-title":"Multiple primary lung cancer: a literature review","volume":"27","author":"Romaszko","year":"2018","journal-title":"Adv Clin Exp Med."},{"key":"B2","first-page":"1079","article-title":"Small-cell lung cancer: management and novelties","volume":"16","author":"Abdelhamid","year":"2020","journal-title":"Rev Med Suisse."},{"key":"B3","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1080\/14737140.2018.1453361","article-title":"Current and future therapeutic approaches for the treatment of small cell lung cancer","volume":"18","author":"Rossi","year":"2018","journal-title":"Expert Rev Anticancer Ther."},{"key":"B4","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1007\/s00520-019-04875-1","article-title":"Relative dose intensity of first-line chemotherapy and overall survival in patients with advanced non-small-cell lung cancer","volume":"28","author":"Crawford","year":"2020","journal-title":"Support Care Cancer."},{"key":"B5","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1097\/CCO.0000000000000268","article-title":"Hematopoietic growth factors in lung cancer","volume":"28","author":"Genova","year":"2016","journal-title":"Curr Opin Oncol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3606","DOI":"10.1007\/s12325-020-01419-6","article-title":"Patient burden and real-world management of chemotherapy-induced myelosuppression: Results from an online survey of patients with solid tumors","volume":"37","author":"Epstein","year":"2020","journal-title":"Adv Ther."},{"key":"B7","first-page":"486","article-title":"The long-term social value of granulocyte colony-stimulating factors","volume":"25","author":"Sexton Ward","year":"2019","journal-title":"Am J Manag Care."},{"key":"B8","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1177\/1078155212466123","article-title":"Propensity score matched assessment of treatment patterns and cost of erythropoiesis stimulating agent treatment in patients with cancer receiving myelosuppressive chemotherapy","volume":"19","author":"Tunceli","year":"2013","journal-title":"J Oncol Pharm Pract."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.12659\/msm.909128","article-title":"Highly expressed granulocyte colony-stimulating factor (G-CSF) and franulocyte colony-stimulating factor receptor (G-CSFR) in human gastric cancer leads to poor survival","volume":"24","author":"Fan","year":"2018","journal-title":"Med Sci Monit."},{"key":"B10","doi-asserted-by":"publisher","first-page":"38","DOI":"10.4103\/wjtcm.wjtcm_6_17","article-title":"Interactions between Traditional Chinese Medicine and anticancer drugs in chemotherapy","volume":"3","author":"Ding","year":"2017","journal-title":"World J Tradit Chin Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"199","DOI":"10.2147\/OTT.S37407","article-title":"Dual control of Shuanghuang Shengbai granule on upstream and downstream signal modulators of CyclinD-CDK4\/6 signaling pathway of cell cycle in Lewis-bearing mice with cyclophosphamide-induced myelosuppression","volume":"6","author":"Gu","year":"2013","journal-title":"Onco Targets Ther."},{"key":"B12","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s11655-016-2503-4","article-title":"Clinical observation of Shuanghuang Shengbai Granule on prevention and treatment of myelosuppression caused by chemotherapy in cancer patients","volume":"23","author":"Wang","year":"2017","journal-title":"Chin J Integr Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"62154","DOI":"10.18632\/oncotarget.19129","article-title":"Shuanghuang Shengbai granule cures myelosuppression and suppresses lung cancer progression: mechanism and therapeutic targets from the aspect of microRNAs","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget."},{"key":"B14","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1007\/s12011-018-1264-7","article-title":"Autophagy protects MC3T3-E1 cells upon aluminum-induced apoptosis","volume":"185","author":"Yang","year":"2018","journal-title":"Biol Trace Elem Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1097\/CAD.0000000000000815","article-title":"Oral metronomic cyclophosphamide in advanced ovarian cancer: long-lasting clinical response in an elderly frailty patient","volume":"30","author":"Villa","year":"2019","journal-title":"Anticancer Drugs."},{"key":"B16","first-page":"14693","article-title":"Pemetrexed and cyclophosphamide combination therapy for the treatment of non-small cell lung cancer","volume":"8","author":"Li","year":"2015","journal-title":"Int J Clin Exp Pathol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"3432750","DOI":"10.1155\/2017\/3432750","article-title":"Oral Chinese Herbal medicine as an adjuvant treatment for chemotherapy, or radiotherapy, induced myelosuppression: a systematic review and meta-analysis of randomized controlled trials","volume":"2017","author":"Hou","year":"2017","journal-title":"Evid Based Complement Alternat Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.lfs.2018.07.025","article-title":"The regulation of ginsenoside Rg1 upon aging of bone marrow stromal cell contribute to delaying senescence of bone marrow mononuclear cells (BMNCs)","volume":"209","author":"Zeng","year":"2018","journal-title":"Life Sci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1182\/blood-2018-03-791517","article-title":"Differentiation-based model of hematopoietic stem cell functions and lineage pathways","volume":"132","author":"H\u00f6fer","year":"2018","journal-title":"Blood."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2643","DOI":"10.1002\/lary.28441","article-title":"Apoptosis signaling molecules as treatment targets in head and neck squamous cell carcinoma","volume":"130","author":"Ow","year":"2020","journal-title":"Laryngoscope."},{"key":"B21","doi-asserted-by":"publisher","first-page":"5","DOI":"10.4103\/2277-9175.148285","article-title":"Myeloprotective activity of crude methanolic leaf extract of Cassia occidentalis in cyclophosphamide-induced bone marrow suppression in Wistar rats","volume":"4","author":"Neboh","year":"2015","journal-title":"Adv Biomed Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1038\/cr.2013.145","article-title":"miR-142-3p regulates the formation and differentiation of hematopoietic stem cells in vertebrates","volume":"23","author":"Lu","year":"2013","journal-title":"Cell Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","article-title":"MicroRNAs: target recognition and regulatory functions","volume":"136","author":"Bartel","year":"2009","journal-title":"Cell."},{"key":"B24","doi-asserted-by":"publisher","first-page":"5299","DOI":"10.1038\/onc.2010.261","article-title":"HMGB1 release and redox regulates autophagy and apoptosis in cancer cells","volume":"29","author":"Tang","year":"2010","journal-title":"Oncogene."},{"key":"B25","doi-asserted-by":"publisher","first-page":"102701","DOI":"10.1016\/j.dnarep.2019.102701","article-title":"Interactions of high mobility group box protein 1 (HMGB1) with nucleic acids: Implications in DNA repair and immune responses","volume":"83","author":"Mandke","year":"2019","journal-title":"DNA Repair."},{"key":"B26","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1186\/s13046-018-0883-3","article-title":"HMGB1 knockdown increases MM cell vulnerability by regulating autophagy and DNA damage repair","volume":"37","author":"Guo","year":"2018","journal-title":"J Exp Clin Cancer Res."},{"key":"B27","first-page":"10800","article-title":"MiR-142-3p functions as a potential tumor suppressor directly targeting HMGB1 in non-small-cell lung carcinoma","volume":"8","author":"Xiao","year":"2015","journal-title":"Int J Clin Exp Pathol."}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.630921\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T04:30:36Z","timestamp":1618893036000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.630921\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,20]]},"references-count":27,"alternative-id":["10.3389\/fonc.2021.630921"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2021.630921","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,20]]},"article-number":"630921"}}