{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:13:43Z","timestamp":1782278023932,"version":"3.54.5"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T00:00:00Z","timestamp":1655424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Rehmanniae Radix (RR, the dried tuberous roots of <jats:italic>Rehmannia glutinosa<\/jats:italic> (Gaertn.) DC.) is an important traditional Chinese medicine distributed in Henan, Hebei, Inner Mongolia, and Northeast in China. RR is frequently used to treat diabetes mellitus, cardiovascular disease, osteoporosis and aging-related diseases in a class of prescriptions. The oligosaccharides and catalpol in RR have been confirmed to have neuroprotective effects. However, there are few studies on the anti-Alzheimer\u2019s disease (AD) effect of oligosaccharides in Rehmanniae Radix (ORR). The chemical components and pharmacological effects of dried Rehmannia Radix (DRR) and prepared Rehmannia Radix (PRR) are different because of the different processing methods. ORR has neuroprotective potential, such as improving learning and memory in rats. Therefore, this study aimed to prove the importance of oligosaccharides in DRR (ODRR) and PRR (OPRR) for AD based on the <jats:italic>Caenorhabditis elegans<\/jats:italic> (<jats:italic>C. elegans<\/jats:italic>) model and the different roles of ODRR and OPRR in the treatment of AD. In this study, we used paralysis assays, lifespan and stress resistance assays, bacterial growth curve, developmental and behavioral parameters, and ability of learning and memory to explore the effects of ODRR and OPRR on anti-AD and anti-aging. Furthermore, the accumulation of reactive oxygen species (ROS); deposition of A\u03b2; and expression of amy-1, sir-2.1, daf-16, sod-3, skn-1, and hsp-16.2 were analyzed to confirm the efficacy of ODRR and OPRR. OPRR was more effective than ODRR in delaying the paralysis, improving learning ability, and prolonging the lifespan of <jats:italic>C. elegans<\/jats:italic>. Further mechanism studies showed that the accumulation of ROS, aggregation, and toxicity of A\u03b2 were reduced, suggesting that ORR alleviated A\u03b2-induced toxicity, in part, through antioxidant activity and A\u03b2 aggregation inhibiting. The expression of amy-1 was downregulated, and sir-2.1, daf-16, sod-3, and hsp-16.2 were upregulated. Thus, ORR could have a possible therapeutic effect on AD by modulating the expression of amy-1, sir-2.1, daf-16, sod-3, and hsp-16.2. Furthermore, ORR promoted the nuclear localization of daf-16 and further increased the expression of sod-3 and hsp-16.2, which significantly contributed to inhibiting the A\u03b2 toxicity and enhancing oxidative stress resistance. In summary, the study provided a new idea for the development of ORR.<\/jats:p>","DOI":"10.3389\/fphar.2022.878631","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T04:29:31Z","timestamp":1655440171000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["Neuroprotective Effects of Oligosaccharides in Rehmanniae Radix on Transgenic Caenorhabditis elegans Models for Alzheimer\u2019s Disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Nianxin","family":"Kang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yage","family":"Luan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijun","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonggang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2857","DOI":"10.1007\/s00221-018-5341-0","article-title":"Dihydrolipoamide Dehydrogenase Suppression Induces Human Tau Phosphorylation by Increasing Whole Body Glucose Levels in a C. elegans Model of Alzheimer's Disease","volume":"236","author":"Ahmad","year":"2018","journal-title":"Exp. 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