{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:26:05Z","timestamp":1785432365952,"version":"3.56.0"},"reference-count":61,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101127"],"award-info":[{"award-number":["82101127"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82101127"],"award-info":[{"award-number":["82101127"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2024JJ8127"],"award-info":[{"award-number":["2024JJ8127"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Research and Development Program of Hunan Province","award":["2022SK2031"],"award-info":[{"award-number":["2022SK2031"]}]},{"name":"National Clinical Key Specialty of Ophthalmology"},{"DOI":"10.13039\/501100012476","name":"Fundamental Research Funds for the Central Universities of Central South University","doi-asserted-by":"publisher","award":["2024ZZTS0990"],"award-info":[{"award-number":["2024ZZTS0990"]}],"id":[{"id":"10.13039\/501100012476","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012476","name":"Fundamental Research Funds for the Central Universities of Central South University","doi-asserted-by":"publisher","award":["2025ZZTS0913"],"award-info":[{"award-number":["2025ZZTS0913"]}],"id":[{"id":"10.13039\/501100012476","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Context\/Objective: Fungi of the genus Tolypocladium are known for their diverse metabolic capabilities and medicinal potential. Indole diterpenoids (IDTs) represent a structurally unique class of fungal metabolites. Beyond their established roles as mycotoxins, these compounds have recently shown promise for neuroprotective effects. The objective of this study was to isolate and characterize novel IDTs from Tolypocladium album DWS131 and evaluate their neuroprotective activities and underlying mechanisms. Methods: IDTs were isolated through comprehensive chromatographic techniques. Their structures were elucidated using HRESIMS data, 1D\/2D NMR spectra, and quantum chemical calculations. Neuroprotective effects were evaluated using glutamate (Glu)-induced R28 cells in vitro and N-methyl-D-aspartic acid-induced mouse models in vivo. A total of 48 mice were utilized for in vivo evaluations, divided into two separate experimental cohorts. In each cohort, mice were randomly assigned to four groups (n = 6 per group). Post-intravitreal injection, retinal survival and visual function were assessed via Brn3a-stained flat-mounts, H&amp;E staining, f-VEP, f-ERG, and OptoDrum. Mechanisms involving the SLC7A11\/GPX4\/ACSL4 axis were investigated by Western blotting and immunofluorescence. Results: Seven previously undescribed paxilline-type IDTs, tolypindoles A\u2013G (1\u20137), and two known analogues (8\u20139) were identified. Compounds 8 and 9 exhibited significant neuroprotection closely associated with the attenuation of oxidative stress and the modulation of ferroptosis-related pathways in Glu-induced R28 cells. In vivo, they preserved retinal ganglion cells, maintained retinal structure, and protected visual function, with compound 8 demonstrating superior efficacy. Mechanistic investigations revealed that both compounds modulate the SLC7A11\/GPX4\/ACSL4 signaling axis. Conclusions: This study expands the chemical diversity of T. album DWS131. Compounds 8 and 9, characterized by isopentenyl moieties, highlight a promising therapeutic potential for retinal neurodegenerative diseases such as glaucoma.<\/jats:p>","DOI":"10.3390\/ph19060807","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:33:54Z","timestamp":1779687234000},"page":"807","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotective Indole Diterpenoids from the Fungus Tolypocladium\u00a0album DWS131"],"prefix":"10.3390","volume":"19","author":[{"given":"Ai-Lin","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China"},{"name":"Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"Eye Center of Xiangya Hospital, Central South University, Changsha 410083, China"},{"name":"Hunan Key Laboratory of Ophthalmology, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing-Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Eye Center of Xiangya Hospital, Central South University, Changsha 410083, China"},{"name":"Hunan Key Laboratory of Ophthalmology, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Feng","family":"Tan","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Yu","family":"Lu","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng-Ju","family":"Xu","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Ping","family":"Long","sequence":"additional","affiliation":[{"name":"Center for Medical Research and Innovation, The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0576-8698","authenticated-orcid":false,"given":"Shao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8133-507X","authenticated-orcid":false,"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China"},{"name":"Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7391-2954","authenticated-orcid":false,"given":"Wen-Xuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1720-7860","authenticated-orcid":false,"given":"Xiaobo","family":"Xia","sequence":"additional","affiliation":[{"name":"Eye Center of Xiangya Hospital, Central South University, Changsha 410083, China"},{"name":"Hunan Key Laboratory of Ophthalmology, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/s41589-022-01246-6","article-title":"Genome mining for unknown\u2013unknown natural products","volume":"19","author":"Yee","year":"2023","journal-title":"Nat. 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