Buwang Formula Regulates Microglial Metabolic Reprogramming and Modulates the mTOR/HIF-1α Pathway to Reduce...

Area of Science:

• Neuroscience
• Metabolic Research
• Pharmacology

Background:

• Microglial metabolic reprogramming is a key driver of neuroinflammation in diabetes-associated cognitive dysfunction (DACD).
• Understanding the impact of traditional formulas on microglial metabolism is crucial for developing novel therapeutic strategies.

Purpose of the Study:

• To evaluate the effects of Buwang formula (BWF) on neuroinflammation and microglial metabolism in DACD.
• To elucidate the underlying molecular mechanisms, including the mTOR/HIF-1α pathway.

Main Methods:

• Chemical profiling of BWF by UHPLC-MS/MS and network pharmacology for target prediction.
• In vivo studies in diabetic db/db mice and in vitro validation in BV2 microglial cells exposed to high glucose and palmitic acid.
• Assessment of behavioral, biochemical, histopathological, cellular energy metabolism, cell polarization, and protein expression.

Main Results:

• BWF treatment improved cognitive function in diabetic mice by suppressing pro-inflammatory factors and pathological protein accumulation.
• BWF modulated the mTOR/HIF-1α pathway, inhibiting glycolysis and promoting oxidative phosphorylation (OXPHOS) in microglial cells.
• In vitro, BWF promoted an M2 anti-inflammatory microglial phenotype.

Conclusions:

• BWF effectively attenuates neuroinflammation and improves cognitive deficits in DACD.
• The therapeutic effects of BWF are linked to the regulation of microglial metabolic reprogramming via the mTOR/HIF-1α pathway.
• BWF shows potential as a therapeutic agent for DACD, warranting further investigation.