Glioprotective Effects of Ilex paraguariensis Standardized Extract Through Nrf2 Activation and NF-κB Suppression in lipopolysaccharide-treated Astrocytes

Ilex paraguariensis (IP) is a plant native to South America, traditionally consumed as a beverage and holding significant economic and social value. This plant has been associated with a range of pharmacological activities, including anti-inflammatory and antioxidant effects. Although some studies have suggested its neuroprotective properties, the effects of IP on glial cells, particularly astrocytes, remain poorly understood. Astrocytes play a crucial role in the neuroinflammatory response, and dysfunction in these cells can contribute to the development of neurodegenerative diseases. This study aimed to investigate the glioprotective mechanisms of a standardized IP extract against inflammatory and oxidative damage induced by lipopolysaccharide (LPS) in primary astrocyte cultures. Astrocytes were treated with IP extract (10, 30, 100, and 300 µg/mL) for 24 h, followed by a 3-hour exposure to LPS (1 µg/mL). LPS exposure resulted in the up-regulation of mRNA expression of interleukin-1β and nuclear factor-kappa B genes, increased cell proliferation, and acetylcholinesterase activity, elevated levels of reactive oxygen and nitrogen species, and reduced astrocytic viability, Na⁺, K⁺-ATPase activity, and antioxidant defenses. Treatment with IP extract was able to prevent these effects by reducing pro-inflammatory and oxidative mediators, modulating acetylcholinesterase and Na⁺, K⁺-ATPase activity, enhancing antioxidant defenses, and up-regulating mRNA expression of superoxide dismutase 2, glutathione peroxidase, and nuclear factor erythroid-derived 2-like 2 genes. To the best of our knowledge, this is the first study to demonstrate the glioprotective effects of IP extract on astroglial cells, laying the groundwork for future research into the neuroprotective mechanisms of IP related to neuroinflammation.