NEUROPROTECTIVE EFFECT OF ARTOCARPUS LAKOOCHA EXTRACT AND OXYRESVERATROL AGAINST HYDROGEN PEROXIDE-INDUCED TOXICITY IN SH-SY5Y CELLS

Objective: Artocarpus lakoocha Roxb. is a traditional medical plant native to Southeast Asia and used as a dried aqueous extract so-called puag haad. Its role (and its major ingredient, oxyresveratrol) as an antioxidant neuroprotectant were explored. Methods: Differentiated SH-SY5Y neuroblastoma cells in 96-well plates were challenged with 200 µM H 2 O 2 for 4 h and either Trolox (100 µM), oxyresveratrol (5-100 µM), or puag haad (1.2-25 µg/ml) applied 2 h before H 2 O 2 or for 20 h after H 2 O 2 washout. Cell viability, mitochondrial function, intracellular ROS, and lipid peroxidation were assessed. Results: Continuous presence of both H 2 O 2 and antioxidant reduced mitochondrial function by ~50% but only by 30% with antioxidant. Sustained 24 h H 2 O 2 showed no recoveries with antioxidants. Cell viability was modestly restored when antioxidants accompanied H 2 O 2 for 4 h and both washed for another 20 h, but little recovery of mitochondrial function even though antioxidants removed ROS and prevent lipid peroxidation. Antioxidants added for 20 h after H 2 O 2 marginally improve mitochondria and modestly restore cell viability, but lipid peroxidation was completely reversed. Conclusion: These results show that mitochondrial protection was illusive, yet both tested compounds, puag haad and oxyresveratrol, improved cell viability and especially ROS levels and lipid peroxidation. The potency oxyresveratrol on the redox-sensitive expression of antioxidant enzymes and its pharmacokinetics suggests that oral puag haad could provide effective protection in transient neurodegenerative disease.