Phloroglucinol Derivatives Exert Anti-Inflammatory Effects and Attenuate Cognitive Impairment in LPS-Induced Mouse Model.

Neuroinflammation is an inflammatory immune response that arises in the central nervous system. It is one of the primary causes of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Phloroglucinol (PG) is a natural product contained in extracts of plant, algae and microbe and has been reported to have antioxidant and anti-inflammatory properties. In this study, we synthesized PG derivatives to enhance antioxidant and anti-inflammatory activity. Among PG derivatives, 6 a suppressed pro-oxidative and inflammatory molecule nitric oxide (NO) production more effectively than PG. Moreover, 6 a dose-dependently reduced the expression of proinflammatory cytokines such as IL-6, IL-1ß, TNF-α, and NO producing enzyme iNOS in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Additionally, we confirmed that 6 a alleviated cognitive impairment and glial activation in mouse model of LPS-induced neuroinflammation. These findings suggest that novel PG derivative, 6 a, is a potential treatment for neurodegenerative diseases.

AMPK-induced mitochondrial biogenesis decelerates retinal pigment epithelial cell degeneration under nutrient starvation.

The implications of nutrient starvation due to aging on the degeneration of the retinal pigment epithelium (RPE) is yet to be fully explored. We examined the involvement of AMPK activation in mitochondrial homeostasis and its relationship with the maintenance of a healthy mitochondrial population and epithelial characteristics of RPE cells under nutrient starvation. Nutrient starvation induced mitochondrial senescence, which led to the accumulation of reactive oxygen species (ROS) in RPE cells. As nutrient starvation persisted, RPE cells underwent pathological epithelial-mesenchymal transition (EMT) via the upregulation of TWIST1, a transcription regulator which is activated by ROS-induced NF-κB signaling. Enhanced activation of AMPK with metformin decelerated mitochondrial senescence and EMT progression through mitochondrial biogenesis, primed by activation of PGC1-α. Thus, by facilitating mitochondrial biogenesis, AMPK protects RPE cells from the loss of epithelial integrity due to the accumulation of ROS in senescent mitochondria under nutrient starvation. [BMB Reports 2023; 56(2): 84-89].