{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T05:26:10Z","timestamp":1782537970313,"version":"3.54.5"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"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>Attention-deficit\/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition marked by inattention, hyperactivity, and impulsivity. Although current pharmacotherapies are effective for many patients, their clinical utility is frequently limited by insufficient efficacy, adverse effects, and concerns regarding long-term tolerability or patient acceptance. Accordingly, increasing research attention has been directed toward the therapeutic potential of traditional Chinese medicine (TCM) formulas and other natural products, which are thought to offer multi-target mechanisms and holistic regulatory effects. This review provides a critical synthesis of recent preclinical studies, focusing on the molecular mechanisms by which specific TCM formulas and natural products ameliorate ADHD-like behaviors. We delineate these actions across several biological scales, including the modulation of catecholamine neurotransmission, enhancement of neurodevelopment and synaptic plasticity, attenuation of neuroinflammation, and regulation of the gut\u2013brain axis. In addition, this review highlights current limitations, including the overreliance on single animal models and the insufficient integration of pharmacokinetic and translational data. Finally, we discuss future research directions and aim to provide new perspectives for the development of natural product-derived interventions in ADHD management.<\/jats:p>","DOI":"10.3389\/fphar.2026.1766222","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T06:38:46Z","timestamp":1773988726000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular mechanisms and therapeutic potential of natural products and traditional Chinese medicine formulas in ADHD: a review of preclinical evidence"],"prefix":"10.3389","volume":"17","author":[{"given":"Han","family":"Deng","sequence":"first","affiliation":[{"name":"Shandong Provincial Key Medical and Health Laboratory of Shandong Mental Health Center, Shandong University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Medical and Health Laboratory of Shandong Mental Health Center, Shandong University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuze","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Public Health, The First Affiliated Hospital of Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weili","family":"Xia","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Medical and Health Laboratory of Shandong Mental Health Center, Shandong University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Chinese Medicine, Shandong Mental Health Center, Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"122252","DOI":"10.1016\/j.lfs.2023.122252","article-title":"In silico and in vivo analysis of the relationship between ADHD and social isolation in pups rat model: implication of redox mechanisms, and the neuroprotective impact of punicalagin","volume":"335","author":"Abu-Elfotuh","year":"2023","journal-title":"Life Sciences"},{"key":"B2","doi-asserted-by":"publisher","first-page":"100700","DOI":"10.1016\/j.bbih.2023.100700","article-title":"Memory deficits and hippocampal cytokine expression in a rat model of ADHD","volume":"35","author":"Anderson","year":"2024","journal-title":"Brain, Behavior, & Immunity - Health"},{"key":"B3","doi-asserted-by":"publisher","first-page":"G1288","DOI":"10.1152\/ajpgi.00341.2012","article-title":"Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice","volume":"303","author":"Asano","year":"2012","journal-title":"Am. 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