期刊
LIFE SCIENCES
卷 282, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2021.119824
关键词
Alzheimer's disease; Berberine; Metabolic profiling; Mitochondrial respiration; Pioglitazone
资金
- National University Health System, National University of Singapore, Singapore [R184-000-275-511]
The study shows that berberine (BBR) can modulate mitochondrial bioenergetics and attenuate dysfunction of the primary energy and glutathione metabolism pathways in AD cell models, while also suppressing the production of pro-inflammatory cytokines in activated microglial cells. Both experimental and computational observations suggest that BBR and PIO have comparable binding affinities to the PPAR gamma protein, indicating potential overlapping effects for AD treatment.
Aim: Berberine (BBR) is an alkaloid extracted from Coptidis Rhizoma, also known as Huang-Lian. Huang-Lian has been used extensively in traditional Chinese medicine for the treatment of various diseases, including diabetes and dementia. Because Alzheimer's disease (AD) is a complex disease that involves various pathophysiological changes, the diverse neuroprotective effects of BBR may be useful for improving the brain's energy state at an early stage of the disease. Main methods: We performed extracellular flux and 1H NMR-based metabolic profiling analyses to investigate the effects of BBR on metabolic processes in these cells. Pioglitazone (PIO), a peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonist has been studied extensively for the treatment of AD. We explored the combination dosing effects of BBR and PIO in vitro, then leveraged computational methods to explain the experimental finding. Key findings: BBR demonstrates potential in modulating the mitochondrial bioenergetics and attenuating dysfunction of the primary energy and glutathione metabolism pathways in an AD cell model. It also suppresses basal respiration and reduces the production of pro-inflammatory cytokines in activated microglial cells. Both experimental and computational observations indicate that BBR and PIO have comparable binding affinities to the PPAR gamma protein, suggesting both drugs may have some overlapping effects for AD. Significance: BBR exerts beneficial effects on disrupted metabolic processes in amyloidogenic cells and activated microglial cells, which are important for preventing or delaying early-stage disease progression. The choice of BBR or PIO for AD treatment depends on their respective pharmacokinetic profiles, delivery, efficacy and safety, and warrants further study.
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