Baicalin as a Multifunctional Candidate for Depression and Related Neuropsychiatric Comorbidities: From...

Depression involves complex mechanisms, including neuroinflammation, impaired neuroplasticity, mitochondrial dysfunction, oxidative stress, HPA-axis dysregulation, and gut-brain axis disturbance. Baicalin, a major flavonoid glycoside from Scutellaria baicalensis Georgi, has shown antidepressant-like and neuroprotective effects in preclinical studies. This review summarizes evidence on baicalin in depression and related CNS comorbidities, including anxiety, epilepsy-associated depression, inflammatory depression, and metabolic comorbidity-associated depressive phenotypes. Literature published between 2000 and 2026 was searched in PubMed, Web of Science, Scopus, ScienceDirect, and Google Scholar, focusing on experimental models, dose regimens, mechanisms, and translational limitations. Compared with previous reviews, this review further emphasizes evidence strength, dose regimens, dose-related safety, and translational limitations. Current evidence suggests that baicalin may regulate inflammatory signaling, microglial activation, neurogenesis, synaptic plasticity, mitochondrial metabolism, glucocorticoid signaling, oxidative stress, apoptosis, and ferroptosis. However, most findings derive from animal or cellular models, and clinical applicability requires further pharmacokinetic, toxicological, and clinical validation.