Journal
ACS CHEMICAL NEUROSCIENCE
Volume 12, Issue 13, Pages 2320-2335Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.1c00024
Keywords
Baicalein; astrocytes senescence; SASP; NF-kappa B; JAK2/STAT1; leucine
Funding
- National Natural Science Foundation of China [81603319]
- Youth Science and Technology Research Fund of Shanxi Province [201801D221374]
- Shanxi Key Research and Development Plan Project [201903D321216]
- Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province [202105D121009]
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Baicalein, extracted from Scutellaria baicalensis, has shown protective effects against astrocyte senescence through regulation of leucine metabolism, suppression of SASP secretion, and inhibition of NF-kappa B and JAK2/STAT1 pathways. Experiment results in T98G cells and primary astrocytes of newborn SD rats support its potential in delaying senescence and enhancing cell viabilities.
Baicalein is an active ingredient extracted from the dried roots of the Scutellaria baicalensis Georgi. It has been demonstrated to improve memory impairment in multiple animal models; however, the underlying mechanisms remain ambiguous. The accumulation of senescent astrocytes and senescence-associated secretory phenotype (SASP) secreted by senescent astrocytes has been deemed as potential contributors to neurodegenerative diseases. Therefore, this study explored the protective effects of baicalein against astrocyte senescence and investigated the molecular mechanisms and metabolic mechanisms of baicalein against astrocyte senescence. Our results demonstrated that treatment with baicalein protects T98G cells from H2O2-induced damage, delays cell senescence, inhibits the secretion of SASP (IL-6, IL-8, TNF-alpha, CXCL1, and MMP-1), and inhibits SASP-related pathways NF-kappa B and JAK2/STAT1. H-1 NMR metabolomics analysis and correlation analysis revealed that leucine was significantly correlated with SASP factors. Further study demonstrated that supplement with leucine could restrain SASP secretion, and baicalein could significantly increase leucine level through down-regulation of BCAT1 and up-regulation of SLC7A5 expression. The above results revealed that baicalein exerted protective and antisenescence effects in H2O2-induced T98G cells possibly through inhibition of SASP, suppression of JAK2/STAT1/NF-kappa B pathway, and regulation of leucine metabolism. Consistent results were obtained in primary astrocytes of newborn SD rats, which suggests that baicalein significantly increases viabilities, delays senescence, inhibits IL-6 secretion, and increases leucine level in H2O2-induced primary astrocytes.
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