Assessment of Anti-Inflammatory Activity of Quercetin and Rosmarinic Acid Induced by Streptozotocin in C6 Cells: A Comparative Study

Abstract

Inflammation is a key contributor to the pathogenesis of various neurological disorders. Natural compounds with anti-inflammatory properties have gained significant attention as potential therapeutic agents. In this work, quercetin (Q) 10µM and rosmarinic acid (RA) 10 µM individually were found to have anti-inflammatory properties in C6 glioma cells when C6 cells exposed with well-known inflammatory agent Streptozotocin (STZ 10µM). Specific markers of oxidative stress (malondialdehyde, MDA; glutathione, GSH), inflammation (nitric oxide, NO; reactive oxygen species, ROS; tumor necrosis factor-alpha, TNF-α; interleukin-6, IL-6), and immune responses (interleukin-10, IL-10) were examined. Additionally, we examined the modulation of signaling molecules involved in inflammation, oxidative stress, and cell survival, including p53, Akt, pCREB, MDM2, NF-κB, and GFAP. Our results demonstrated significant anti-inflammatory effects of both quercetin and rosmarinic acid on the examined markers. Treatment with quercetin and rosmarinic acid resulted in a reduction of malondialdehyde (MDA) levels, indicating their ability to mitigate oxidative stress.

Furthermore, these compounds increased glutathione (GSH) levels, suggesting their potential to enhance cellular antioxidant defense. Quercetin and rosmarinic acid treatment also attenuated NO and ROS production. Moreover, both compounds downregulated TNF-α and IL-6 levels while upregulating IL-10, indicating their potential individually to modulate the pro-inflammatory and anti-inflammatory cytokine balance. Quercetin and rosmarinic acid treatment led to the upregulation of p53, indicating that they may cause C6 glioma cells to undergo cell cycle arrest or apoptosis. Additionally, these compounds modulated Akt phosphorylation levels, indicating their influence on Akt signaling pathways involved in cell survival and inflammation. Treatment with quercetin and rosmarinic acid also increased pCREB levels, suggesting their ability to promote cell survival and modulate inflammatory responses. Furthermore, both compounds individually downregulated MDM2 expression, potentially enhancing p53-mediated cellular responses. Lastly, quercetin and rosmarinic acid individually inhibited NF-κB activation and downregulated GFAP expression STZ insulted C6 cell, indicating their potential to attenuate inflammation.