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To identify potentially new combined therapeutic strategies, 3,6'\u2010disinapoylsucrose (DISS) and tenuifoliside A (TFSA) have been observed to show antidepressant\u2010like effects and its related 5\u2010HT\u2010BDNF pathway. We have tried to investigate whether combined administration of DISS and TFSA exerted more effective in the treatment of depression, as assessed through tail suspension test (TST) and forced swimming test (FST). In addition, we also analyzed the expression of three important proteins, cyclic adenosine monophosphate (cAMP) response element binding (CREB), brain\u2010derived neurotrophic factor (BDNF), and cAMP\u2010regulated transcriptional coactivators (CRTC1), which have been shown to be involved in the regulation of the neurotrophic factors in the hippocampus. The DISS and TFSA separately, both at a dose of 5\u00a0mg\/kg each, displayed small effect in the immobility time. However, combined treatment of these two in multiple doses exhibited better effect. Moreover, combined treatment of DISS and TFSA also demonstrated enhanced levels of 5\u2010hydroxytryptamine (5\u2010HT), and stronger increase in the phosphorylation levels of CREB, BDNF, and CRTC1 proteins in the hippocampus. Overall, our results indicated that coadministration of these two oligosaccharide esters at low dose may induce more pronounced antidepressant activity, in comparison with individual treatment even at high dosage. Thus, the antidepressant properties of both these compounds can be attributed to their ability to influence 5\u2010HT and BDNF pathway, and thereby suggesting that this combination strategy can definitely act as alternative therapy for depression disorder with very limited side effects.<\/jats:p>","DOI":"10.1002\/fsn3.2098","type":"journal-article","created":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T18:54:58Z","timestamp":1609786498000},"page":"1180-1191","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Involvement of 5\u2010HT\u2010BDNF signaling axis in mediating synergistic antidepressant\u2010like effects after combined administration of two oligosaccharide esters"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1666-4261","authenticated-orcid":false,"given":"Wen Shan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pharmacy Medical Supplier Center Chinese PLA General Hospital Beijing China"},{"name":"Medical School of Chinese PLA Chinese PLA General Hospital Beijing China"},{"name":"Department of Outpatient Group 82 Military Hospital Baoding China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen\u2010Guo","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Medical Supplier Center Chinese PLA General Hospital Beijing China"},{"name":"Medical Affair Pharmacy Office Chinese PLA General Hospital Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xian\u2010Zhe","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Medical Supplier Center Chinese PLA General Hospital Beijing China"},{"name":"Department of Pharmacy Xuanwu Hospital of Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Medical Supplier Center Chinese PLA General Hospital Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng\u2010li","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Medical Supplier Center Chinese PLA General Hospital Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Medical Supplier Center Chinese PLA General Hospital Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,1,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2008.05.005"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300320"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.088005"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.12084su1c.04"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2012.04.011"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2016.10.015"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011\u2010018\u20100280\u20109"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2014.04.022"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2017.03.002"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2012.09.016"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/728342"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2009.12.004"},{"issue":"9","key":"e_1_2_11_14_1","first-page":"605","article-title":"A bioactive compound from Polygala tenuifolia regulates efficiency of chronic stress on hypothalamic\u2010pituitary\u2010adrenal axis","volume":"64","author":"Hu Y.","year":"2009","journal-title":"Die Pharmazie"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3736\/jcim20090712"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031\u2010013\u20100226\u2010y"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042\u20107158.2011.01281.x"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3109\/13880200903280034"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213\u2010017\u20104587\u20108"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201013929\u20105"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.5717\/jenb.2014.18.1.97"},{"issue":"2","key":"e_1_2_11_22_1","first-page":"193","article-title":"Antioxidant properties of fruit and vegetable juices: More to the story than ascorbic acid","volume":"32","author":"Leonard S. 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