Rahamouz-Haghighi_2025_J.Ethnopharmacol_354_120504

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria litwinowii Bornm. & Sint., native to Iran, belongs to the Lamiaceae family, Scutellaria species are widely used in traditional medicine for treating inflammation, infections, and Neurological diseases. AIM OF THE STUDY: This research aimed to assess the neuroprotective effects of S. litwinowii fractions, focusing on anti-acetylcholinesterase (anti-AChE), antioxidant, and anti-apoptotic activities. MATERIALS AND METHODS: Oxidative stress and apoptosis were created utilizing aluminum chloride (AlCl(3)) in PC12 cells. The neuroprotective effect was assessed using resazurin assays, while reactive oxygen species (ROS), AChE and glutathione (GSH) were assessed using DCF-DA and Ellman's Reagent, respectively. Apoptotic cells, and lactate dehydrogenase (LDH) release were also evaluated. Western blot analysis detected the expression of beta-Catenin, Survivin, and phosphorylated SAPK JNK/SAPKJNK. A dichloromethane (DCM) root fraction underwent HPLC and LC-ESI-MS profiling to identify active anti-AChE compounds. RESULTS: 48 h treatment with 5 mM AlCl(3) decreased cell viability by 27 %. Pretreatment with the DCM fraction at 6.25 and 12.5 microg/ml significantly improved viability, reduced ROS and LDH release, and prevented GSH depletion, comparable to the antioxidant N-acetylcysteine (p < 0.001). At a 12.5 microg/ml, the DCM fraction inhibited AChE activity by 63.61 %, while 12.5 microM baicalein showed 59.11 % inhibition. The DCM fraction and baicalein significantly reduced AlCl(3)-induced apoptosis (p < 0.001), increased of beta-Catenin, Survivin expression and decreased p-JNK/JNK ratio (p < 0.001). In the active time window, baicalein and wogonin were detected. CONCLUSION: This research suggests that S. litwinowii and baicalein may serve as protective agents against oxidative stress and apoptosis-related cell damage.