{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:29:29Z","timestamp":1790126969556,"version":"4.0.1"},"reference-count":134,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"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. Pharmacol."],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and amyloid-\u03b2 (A\u03b2) accumulation. Increasing evidence suggests that dietary bioactive compounds may modulate neurodegenerative processes. Here, we evaluated the neuroprotective potential of NeuproGemp, a traditional Chinese functional food formula composed of <jats:italic>Gastrodia elata<\/jats:italic>, <jats:italic>Paeoniae Radix Rubra<\/jats:italic>, and the immunomodulatory protein GMI from <jats:italic>Ganoderma microsporum<\/jats:italic>, in APP\/PS1 transgenic mice. Oral supplementation (300\u00a0mg\/kg\/day, 6\u20138\u00a0weeks) significantly improved ethological behaviors, including a \u223c150% enhancement in burrowing performance (150 \u00b1 25\u00a0g vs. 60 \u00b1 40\u00a0g in controls), and reduced escape latency in the Morris water maze (Day 4: p &amp;lt; 0.05; Day 6: p &amp;lt; 0.01). Histological analyses demonstrated attenuated plaque-associated gliosis, with microglial\/astroglial clusters reduced from 95 \u00b1 22 to 55 \u00b1 11 per section (p &amp;lt; 0.01), alongside increased hippocampal neurogenesis (DCX + cells: 49 vs. 18 cells\/mm, p &amp;lt; 0.001). ELISA revealed reductions of \u223c30% in soluble A\u03b2<jats:sub>1-42<\/jats:sub> and \u223c50% in pyroglutamate-modified A\u03b2<jats:sub>3-42<\/jats:sub> (pE-A\u03b2<jats:sub>3-42<\/jats:sub>). High-performance liquid chromatography identified pentagalloylglucose (PGG) as the principal polyphenolic constituent of <jats:italic>Paeoniae Radix Rubra<\/jats:italic>, which exhibited potent human glutaminyl cyclase (hQC) inhibition (IC<jats:sub>50<\/jats:sub> = 0.09\u00a0\u03bcM; KD = 63.7\u00a0nM). Molecular modeling and dynamics simulations further supported stable binding interactions of PGG and tannic acid with hQC. Collectively, these findings indicate that NeuproGemp, enriched in neuroactive polyphenols, exerts multi-targeted modulation of amyloidogenic pathways and represents a promising botanical intervention for mitigating AD-related neuropathology.<\/jats:p>","DOI":"10.3389\/fphar.2025.1673532","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T05:38:56Z","timestamp":1761025136000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["NeuproGemp, a polyphenol-rich botanical formula, ameliorates Alzheimer\u2019s-like pathology in APP\/PS1 mice via inhibition of human glutaminyl cyclase"],"prefix":"10.3389","volume":"16","author":[{"given":"Tien-Sheng","family":"Tseng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Ching","family":"Liaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Ji","family":"Shiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-I","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hsiu","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang-Chuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keng-Chang","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cbi.2006.10.003","article-title":"Study of antimutagenic and antioxidant activities of gallic acid and 1,2,3,4,6-pentagalloylglucose from pistacia lentiscus. 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