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Dl-3- n -butylphthalide enhances collateral circulation by promoting endothelial nitric oxide synthase activity and activates neurotrophic signaling pathways such as brain-derived neurotrophic factor/tropomyosin receptor kinase B (TrkB) and calcitonin gene-related peptide (CGRP), thereby improving synaptic plasticity and cognitive recovery 17 (Fig

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Start with 3g daily rather than 5g, and increase only if tolerated well

Zinc and copper compete for absorption, so formulations should contain both in appropriate ratios (typically 15:1 zinc to copper)

Originally engineered at Washington State University by the Harding lab and later licensed to M3 Biotechnology, Dihexa retains the angiotensin IV pharmacophore for AT4 receptor binding while incorporating N-hexanoyl and aminohexanoic acid modifications that confer metabolic stability and lipophilic BBB penetration