{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:38:11Z","timestamp":1792625891760,"version":"4.5.0"},"reference-count":45,"publisher":"Georg Thieme Verlag KG","funder":[{"name":"Innovation Projects for Young Scientific and Technological Talents in Lanzhou City, Gansu Province","award":["2024-QN-195"],"award-info":[{"award-number":["2024-QN-195"]}]},{"name":"Science and Technology Program of Gansu Province","award":["25JRRA901"],"award-info":[{"award-number":["25JRRA901"]}]},{"name":"National Natural Science Foundation of China","award":["22107043,22567023"],"award-info":[{"award-number":["22107043,22567023"]}]},{"name":"Lanzhou University of Technology","award":["LUTXKJC-25002"],"award-info":[{"award-number":["LUTXKJC-25002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Planta Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The urgent need for effective Alzheimer\u2019s disease (AD) therapies has spurred the search for novel bioactive compounds within the vast chemical space of microbial natural products. Here, we integrated nontargeted metabolomics with network pharmacology to explore the neuroprotective potential of Streptomyces flavusporus HC307. Systematic profiling of the HC307 metabolome revealed nearly 3000 features. Subsequent statistical screening and database matching narrowed the focus to 34 potential anti-AD candidates, facilitating the targeted isolation of the bioactive cyclodipeptide, cyclo(Gly-L-Pro) (307-1). Network pharmacology analysis predicted that cyclo(Gly-L-Pro) may modulate a network of 86 AD-related targets, with EGFR, CTSB, GSK3B, PARP1, and SIRT1 serving as core nodes. Molecular docking showed favorable binding affinities, particularly toward GSK3B and PARP1 (\u22126.6 kcal mol\u22121 for both), suggesting a multifaceted mechanism spanning tau protein regulation, anti-inflammation, and oxidative stress mitigation. This study establishes S. flavusporus HC307 as a promising source of neuroactive leads and elucidates the multitarget profile of cyclo(Gly-L-Pro), providing a basis for its further development as an anti-AD lead.<\/jats:p>","DOI":"10.1055\/a-2978-1740","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:47:21Z","timestamp":1792622841000},"source":"Crossref","is-referenced-by-count":0,"title":["Integrative Metabolomics and Molecular Docking as a Drug Discovery Approach: A Case Study of Microbial Cyclo(Gly-L-Pro) Targeting Alzheimer\u2019s Disease"],"prefix":"10.1055","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0484-7666","authenticated-orcid":false,"given":"Dan","family":"Tang","sequence":"additional","affiliation":[{"name":"Lanzhou University of Technology, Gansu, China","place":["Lanzhou"],"department":["School of Life Science and Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Luo","sequence":"additional","affiliation":[{"name":"Lanzhou University of Technology, Gansu, China","place":["Lanzhou"],"department":["School of Life Science and Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Ming","family":"He","sequence":"additional","affiliation":[{"name":"Lanzhou University of Technology, Gansu, China","place":["Lanzhou"],"department":["School of Life Science and Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Lin","family":"Qian","sequence":"additional","affiliation":[{"name":"Lanzhou University of Technology, Gansu, China","place":["Lanzhou"],"department":["School of Life Science and Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Xia","family":"Zhou","sequence":"additional","affiliation":[{"name":"Lanzhou University of Technology, Gansu, China","place":["Lanzhou"],"department":["School of Life Science and Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Gang","family":"Wang","sequence":"additional","affiliation":[{"name":"Lanzhou University of Technology, Gansu, China","place":["Lanzhou"],"department":["School of Life Science and Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/ene.13439","article-title":"Alzheimer\u2019s disease","volume":"25","author":"C A Lane","year":"2018","journal-title":"Eur J Neurol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"6518","DOI":"10.3390\/ijms24076518","article-title":"Inflammatory processes in Alzheimer\u2019s disease-Pathomechanism, diagnosis and treatment: a review","volume":"24","author":"B Twarowski","year":"2023","journal-title":"Int J Mol 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