{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T05:26:50Z","timestamp":1786598810397,"version":"build-2736575974"},"reference-count":41,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011789","name":"Jilin Province Science and Technology Department","doi-asserted-by":"crossref","award":["20240602079RC"],"award-info":[{"award-number":["20240602079RC"]}],"id":[{"id":"10.13039\/501100011789","id-type":"DOI","asserted-by":"crossref"}]},{"award":["20240602079RC"],"award-info":[{"award-number":["20240602079RC"]}],"id":[{"id":"https:\/\/ror.org\/049x38272","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004032","name":"Jilin University","doi-asserted-by":"crossref","award":["2026B32"],"award-info":[{"award-number":["2026B32"]}],"id":[{"id":"10.13039\/501100004032","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2026B32"],"award-info":[{"award-number":["2026B32"]}],"id":[{"id":"https:\/\/ror.org\/00js3aw79","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Disruption of neuronal excitation\u2013inhibition balance and mitochondrial quality control may contribute importantly to lead (Pb)-induced neurotoxicity, but nutritional modulators targeting these processes remain poorly characterized. This study investigated the protective effects and underlying mechanisms of ginsenoside Rh1, a ginseng-derived bioactive compound, in Pb-exposed mice and Pb-treated HT22 hippocampal cells. Chronic Pb exposure caused spatial recognition deficits, reduced exploratory activity, anxiety-like behaviors, and marked neuronal injury, accompanied by Pb accumulation in blood and brain tissues, elevated IL-1\u03b2, TNF-\u03b1, and IL-6 levels, oxidative stress, reduced Gama-aminobutyric acid (GABA) content, and dysregulated NKCC1\/KCC2 expression. In HT22 cells, Pb increased intracellular ROS generation and disrupted mitophagy-related signaling, as indicated by alterations in PINK1, Parkin, LC3, P62, and GABARAP. Rh1 treatment alleviated Pb-induced behavioral abnormalities and neuronal pathology, reduced Pb burden, suppressed neuroinflammatory responses, enhanced antioxidant defenses, improved Pb-associated alterations in GABAergic regulation, and modulated mitochondrial quality-control signaling in vivo and in vitro. These findings suggest that Rh1 may represent a promising nutritional intervention strategy for mitigating Pb-associated neurotoxicity.<\/jats:p>","DOI":"10.3390\/molecules31162801","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:30:32Z","timestamp":1786465832000},"page":"2801","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ginsenoside Rh1 Modulates GABAergic Inhibitory Homeostasis and Mitochondrial Quality Control During Lead (Pb)-Associated Neuronal Dysfunction"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7026-3795","authenticated-orcid":false,"given":"Xiang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacology, College of Basic Medical Sciences, The Medical Basic Research Innovation Center of Airway Disease in North China, Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China"},{"name":"Ginseng Research Institute, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linfeng","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Basic Medical Sciences, The Medical Basic Research Innovation Center of Airway Disease in North China, Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China"},{"name":"Ginseng Research Institute, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixin","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Basic Medical Sciences, The Medical Basic Research Innovation Center of Airway Disease in North China, Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China"},{"name":"Ginseng Research Institute, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongting","family":"Lv","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yantong","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianli","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun 130000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.jmb.2019.06.031","article-title":"Quality Control in Neurons: Mitophagy and Other Selective Autophagy Mechanisms","volume":"432","author":"Evans","year":"2020","journal-title":"J. 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