The potential of baicalin to enhance neuroprotection and mitochondrial function in a human neuronal cell model

• Published in: Molecular psychiatry Vol. 29; no. 8; pp. 2487 - 2495
• Main Authors: Liu, Zoe S. J., Truong, Trang T. T., Bortolasci, Chiara C., Spolding, Briana, Panizzutti, Bruna, Swinton, Courtney, Kim, Jee Hyun, Hernández, Damián, Kidnapillai, Srisaiyini, Gray, Laura, Berk, Michael, Dean, Olivia M., Walder, Ken
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2024; Nature Publishing Group
• Subjects: 13/106; 13/21; 14/34; 38/39; 38/43; 38/91; 631/208; 631/337; Animal models; Animals; Axonogenesis; Baicalin; Behavioral Sciences; Biological Psychology; Brain research; Cell culture; Cell Line; Culture media; Cytokines; Enzyme-linked immunosorbent assay; Flavonoids - pharmacology; Flowering; Gene expression; Gene set enrichment analysis; Genomic analysis; Glycolysis; Glycosides; Humans; Inflammation - drug therapy; Inflammation - metabolism; Ischemia; Kinases; Medical research; Medicine; Medicine & Public Health; Mental disorders; Mice; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Neurogenesis; Neuronal Outgrowth - drug effects; Neurons - drug effects; Neurons - metabolism; Neuroprotection; Neuroprotection - drug effects; Neuroprotective Agents - pharmacology; Neurosciences; Neurotrophin 2; Oxygen consumption; Pharmacotherapy; Psychiatry; Tricarboxylic acid cycle; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α
• ISSN: 1359-4184; 1476-5578; 1476-5578
• DOI: 10.1038/s41380-024-02525-5

Baicalin is a flavone glycoside derived from flowering plants belonging to the Scutellaria genus. Previous studies have reported baicalin’s anti-inflammatory and neuroprotective properties in rodent models, indicating the potential of baicalin in neuropsychiatric disorders where alterations in numerous processes are observed. However, the extent of baicalin’s therapeutic effects remains undetermined in a human cell model, more specifically, neuronal cells to mimic the brain environment in vitro. As a proof of concept, we treated C8-B4 cells (murine cell model) with three different doses of baicalin (0.1, 1 and 5 μM) and vehicle control (DMSO) for 24 h after liposaccharide-induced inflammation and measured the levels of TNF-α in the medium by ELISA. NT2-N cells (human neuronal-like cell model) underwent identical baicalin treatment, followed by RNA extraction, genome-wide mRNA expression profiles and gene set enrichment analysis (GSEA). We also performed neurite outgrowth assays and mitochondrial flux bioanalysis (Seahorse) in NT2-N cells. We found that in C8-B4 cells, baicalin at ≥ 1 μM exhibited anti-inflammatory effects, lowering TNF-α levels in the cell culture media. In NT2-N cells, baicalin positively affected neurite outgrowth and transcriptionally up-regulated genes in the tricarboxylic acid cycle and the glycolysis pathway. Similarly, Seahorse analysis showed increased oxygen consumption rate in baicalin-treated NT2-N cells, an indicator of enhanced mitochondrial function. Together, our findings have confirmed the neuroprotective and mitochondria enhancing effects of baicalin in human-neuronal like cells. Given the increased prominence of mitochondrial mechanisms in diverse neuropsychiatric disorders and the paucity of mitochondrial therapeutics, this suggests the potential therapeutic application of baicalin in human neuropsychiatric disorders where these processes are altered.