Abstract:Under the optimal ultrasonification extraction conditions of 20.52 kHz for the frequency, 32.59 • C for the temperature, and 4.91 h for the process time, 17.98 mg/g of chlorophyll a was obtained. It was much higher than 13.81 mg/g from conventional 70% ethanol extraction and even higher than other data from Spirulina. This yield was close to the predicted value of 18.21 mg/g from the second-order polynomial model with a regression coefficient of 0.969. This model showed the greatest significance with the ultrasonic frequency and process time and the least significance with the temperature. The extracts also showed high α,α-diphenyl-β-picrylhydrazyl (DPPH) radical scavenging activities as 69.38%, compared to 58.25% for the extracts from the 70% ethanol extraction. It was first shown that the optimal extraction was effective at enhancing the neuroprotective activities possibly due to the synergistic effects of higher amounts of chlorophyll a and other bioactive substances in the extract, revealing a 90% protection of the growth of mouse neuronal cells and a great reduction in Reactive Oxygen Species (ROS) production.