Inhibition of microglial activation by the herbal flavonoid baicalein attenuates inflammation-mediated degeneration of dopaminergic neurons

• Published in: Journal of Neural Transmission Vol. 112; no. 3; pp. 331 - 347
• Main Authors: Li, F-Q, Wang, T, Pei, Z, Liu, B, Hong, J-S
• Format: Journal Article
• Language: English
• Published: Austria Springer Nature B.V 01.03.2005
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Antioxidants - pharmacology; Antioxidants - therapeutic use; Cells, Cultured; Dopamine - metabolism; Dose-Response Relationship, Drug; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; Flavanones - pharmacology; Flavanones - therapeutic use; Flavonoids - pharmacology; Flavonoids - therapeutic use; Mice; Microglia - drug effects; Microglia - metabolism; Nerve Degeneration - metabolism; Nerve Degeneration - pathology; Nerve Degeneration - prevention & control; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Rats; Rats, Inbred F344
• ISSN: 0300-9564; 1435-1463
• DOI: 10.1007/s00702-004-0213-0

Accumulating evidence has suggested that inflammation in the brain participates in the pathogenesis of Parkinson's disease (PD). Therefore, anti-inflammatory therapy has attracted much attention as novel interference to neurodegenerative diseases. Baicalein, a major flavonoid extracted from a traditional Chinese herb Scutellaria baicalensis Georgi (Huangqin), possesses potent anti-inflammatory and antioxidant properties. To test the potential neuroprotective effect of baicalein on dopaminergic neurons, primary midbrain neuron-glia cultures from E-14 rat embryos were used. Cultures were pretreated with baicalein for 30 min prior to stimulation with lipopolysaccharide (LPS, 10 ng/ml). LPS leads to massive activation of microglial cells revealed by OX-42 immunostaining, and produced excessive quantities of NO. Excessive elevation of superoxide level was also observed in enriched-microglia after stimulating with LPS. LPS-induced damage to dopaminergic neurons was evaluated by uptake capacity for [3H]dopamine and tyrosine hydroxylase (TH)-immunocytochemistry. Pretreatment with baicalein concentration-dependently attenuated LPS-induced decrease in [3H]dopamine uptake and loss of TH-immunoreactive (TH-ir) neurons, which the maximum protective effect was observed at the concentration of 5 microM. Post-treatment with baicalein (5 microM) was also shown to be effective even if baicalein administered up to 2 h later than LPS application. Morphological study shows that baicalein (5 microM) almost completely blocked LPS-induced activation of microglia. Excessive production of TNF(alpha) and free radicals such as NO and superoxide by LPS stimulation were also attenuated by baicalein at a concentration-dependent pattern. The present study indicates that baicalein exerts potent neuroprotective effect on LPS-induced injury of dopaminergic neurons. We hypothesize that the inhibition of LPS-induced production of NO and free radicals from microglia may underlie the mechanism of baicalein's neuroprotection.