{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T06:52:49Z","timestamp":1781679169768,"version":"3.54.5"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008047","name":"Hebei University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"\n Background<\/jats:title>\n \n Alzheimer\u2019s disease (AD) poses a significant threat to human health, and with the number of patients increasing annually, developing effective prevention and treatment strategies has become an urgent priority. Early intervention is a viable strategy for treating AD, as biomarker changes associated with\n \u03b2<\/jats:italic>\n -amyloid (A\u03b2) can emerge 20 or more years before cognitive impairment becomes apparent. Traditional Chinese medicine (TCM) offers a potential avenue for treatment at this early stage.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n This study investigated the potential therapeutic effects of the Yin Huang Ge compound on cognitive function in a mouse model of AD and evaluated its efficacy in mitigating A\u03b2 accumulation, a key pathological feature of AD.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n APP\/PS1 mice were randomly assigned to the following groups: Controls (C57BL\/6\u202fJ mice) group, the Model group, YHG group, and donepezil (DNP) group. The YHG group and the DNP group were administered their respective drugs through gastric gavage, whereas the normal group and the Model group were supplied with saline. Administration sustained for a period of 30 consecutive days. We assessed mouse learning, memory, and spatial cognition using the Morris water maze, novel object recognition, Y-maze spontaneous alternation, and novel arm tests. Western blotting quantified the protein levels of\n \u03b2<\/jats:italic>\n -amyloid 1\u201342 (A\u03b2\n 1-42<\/jats:sub>\n ), insulin-degrading enzyme (IDE), neprilysin (NEP), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9). ELISA measured IDE and NEP enzymatic activity, while immunohistochemistry evaluated the expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In contrast to the Control group, mice in the Model group exhibited significant impairments in learning, memory, and spatial cognition. The protein expression levels of A\u03b2\n 1-42<\/jats:sub>\n , MMP-2, and MMP-9 were markedly elevated (\n p<\/jats:italic>\n \u202f&lt;\u202f0.01), whereas the expression of IDE and NEP was significantly reduced (\n p<\/jats:italic>\n \u202f&lt;\u202f0.05,\n p<\/jats:italic>\n \u202f&lt;\u202f0.01). ELISA analysis further revealed a substantial decrease in IDE and NEP activity (\n p<\/jats:italic>\n \u202f&lt;\u202f0.01). A concomitant reduction in the expression of NT-3 and BDNF was also observed (\n p<\/jats:italic>\n \u202f&lt;\u202f0.01). Compared to the Model group, mice treated with YHG or DNP exhibited significantly improved learning, memory, and spatial cognition. The protein expression of A\u03b2\n 1-42<\/jats:sub>\n , MMP-2, and MMP-9 was reduced (\n p<\/jats:italic>\n \u202f&lt;\u202f0.05,\n p<\/jats:italic>\n \u202f&lt;\u202f0.01), whereas the expression of IDE and NEP was elevated (\n p<\/jats:italic>\n \u202f&lt;\u202f0.05). ELISA results confirmed the increased activity of IDE and NEP (\n p<\/jats:italic>\n \u202f&lt;\u202f0.05). These assays also revealed a marked upregulation in the expression of NT-3 and BDNF (\n p<\/jats:italic>\n \u202f&lt;\u202f0.01).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n The YHG compound reduces cerebral A\u03b2 deposition via a bidirectional regulatory mechanism, upregulating IDE and NEP to promote clearance while downregulating MMP-2 and MMP-9 to mitigate associated damage. It also elevates the expression of the neurotrophic factors BDNF and NT-3, which enhances endogenous neuroprotection and ameliorates core Alzheimer\u2019s disease pathology. Consequently, this treatment markedly improves cognitive function in APP\/PS1 mice.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1821074","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T05:55:46Z","timestamp":1781675746000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Examining of the mechanism by which Yin Huang Ge compound alleviates cognitive dysfunction in Alzheimer\u2019s disease mice through modulation of A\u03b2 degrading enzymes and neurotrophic factors"],"prefix":"10.3389","volume":"18","author":[{"given":"Yaxuan","family":"Hao","sequence":"first","affiliation":[{"name":"Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyue","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Zhong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianhui","family":"Dong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Hebei University of Chinese Medicine","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"113293","DOI":"10.1016\/j.phytochem.2022.113293","article-title":"Astragalus species: Phytochemistry, biological actions and molecular mechanisms underlying their potential neuroprotective effects on neurological diseases","volume":"202","author":"Abd Elrahim Abd Elkader","year":"2022","journal-title":"Phytochemistry"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"742408","DOI":"10.3389\/fnagi.2022.742408","article-title":"Alzheimer's disease: An update and insights into pathophysiology","volume":"14","author":"Abubakar","year":"2022","journal-title":"Front. 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