Neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, are associated with cognitive impairment and impaired brain glucose metabolism, posing significant challenges for the public health. We previously demonstrated that cyanidin 3-O-β-galactoside (Cy3Gal) from black chokeberry alleviated cognitive impairment in aging mice through regulating brain energy metabolism in a direct way. However, the indirect mechanisms in mitigating brain glucose hypometabolism remain underexplored. Here, we utilized a bilaterally intracerebroventricular injection of streptozotocin (ICV/STZ, 3 mg/kg bw)-induced brain glucose hypometabolism model to investigate the effects of Cy3Gal on cognitive impairment alleviation. Our findings revealed that Cy3Gal administration significantly improved memory deficit and cognitive impairment in ICV/STZ-administrated mice. Subsequently, Cy3Gal showed excellent abilities in inhibiting astrocyte overactivation, regulating neurotransmitters metabolism, and promoting synaptic plasticity. Furthermore, Cy3Gal enhanced brain glucose metabolism by improving glycolysis and the TCA cycle. Additionally, Cy3Gal modulated levels of gut microbiota-derived metabolites, including acetate, butyrate, histidine, glutamine, serine, valine and isoleucine, which were closely linked to brain glucose metabolism. The in vitro results further demonstrated that these metabolites played an important role in the neuron-astrocyte energy metabolism, which accounted for the alleviation of glucose hypometabolism. Overall, our findings suggest that Cy3Gal mitigates ICV/STZ-induced cognitive impairment by modulating gut microbiota-derived short-chain fatty acids and amino acids, which in turn improves brain glucose metabolism.

Unhealthy diets are associated with various diseases that can disrupt brain energy metabolism, which significantly increased the risk of cognitive impairment and chronic neurodegenerative diseases. Early intervention with nutritional supplements may have long-lasting positive effects on diet-related glucose metabolism and potentially mediate the progression of neurodegeneration in middle-aged and elderly people. We previously reported that cyanidin 3-O-β-galactoside (Cy3Gal), an anthocyanin from black chokeberry (Aronia melanocarpa (Michx.) Elliott), alleviated cognitive impairment in aging mice through regulating brain energy metabolism. However, it remains unclear whether Cy3Gal can also exert beneficial effects in mice fed with a high-fat/high-sugar diet. Here we revealed that Cy3Gal treatment conserved the health of neurons and synapses, as well as cognitive function of mice. Furthermore, we observed that Cy3Gal effectively improved glucose uptake and metabolism of skeletal muscle by enhancing glycolysis both in vivo and in vitro models, which is essential for maintaining a stable glucose supply to the brain. Additionally, Cy3Gal significantly increased the levels of glucose-derived tricarboxylic acid cycle intermediates in the mice brain (P < 0.05), and regulated the activities of mitochondrial respiratory chain complexes (P < 0.01). The positive influence on peripheral and brain bioenergetics explained how the Cy3Gal exerted neuroprotective effect. In conclusion, our study illustrated that early dietary intervention of Cy3Gal had significant advantages in terms of neuroprotection and cognition under the challenge of HFHS diet-induced glucose metabolism disorder.

This study employed gas chromatography-mass spectrometry (GC-MS) in conjunction with gas chromatographyion mobility spectrometry (GC-IMS) to identify the characteristic volatile organic compounds (VOCs) in white peppers from global major production regions. Furthermore, the antioxidant activity of white pepper essential oil was evaluated, and the key volatile components were analyzed. The results revealed a total of 40 VOCs were identified, the predominant ones being terpenes and acids, which altogether accounted for over 80% of the identified compounds. Significant variations in the composition and concentrations of VOCs were observed among white pepper samples from different regions, which was the key factor contributing to the differences in their aroma profiles. Furthermore, the characteristic aroma of white peppers from different regions was primarily concentrated on fruity, floral, and other pleasant aromas, as well as undesirable odors such as fecal and sweaty notes. Additionally, a significant correlation was found between the antioxidant activity and volatile terpenes of white pepper essential oils. These findings provide a theoretical foundation for further exploration of the suitability of white peppers from different geographical origins for various processing applications.