**Woon Yong Choi 1, Jae-Hun Sim 2, Jung-Youl Lee 2, Do Hyung Kang <sup>3</sup> and Hyeon Yong Lee 4,\***


Received: 5 April 2019; Accepted: 22 May 2019; Published: 26 May 2019

**Abstract:** The *Spirulina maxima* exact from a non-thermal ultrasonic process (UE) contains 17.5 mg/g of total chlorophyll, compared to 6.24 mg/g of chlorophyll derived from the conventional 70% ethanol extraction at 80 ◦C for 12 h (EE). The UE also showed relatively low cytotoxicity against murine microglial cells (BV-2) and inhibited the production of the inflammatory mediators, NO and PGE2. The UE also effectively suppresses both mRNA expression and the production of pro-inflammatory cytokines, such as TNF-α, IL-6 and IL-1β, in a concentration-dependent manner. Notably, TNF-α gene and protein production were most strongly down-regulated, while IL-6 was the least affected by all ranges of treatment concentrations. This work first demonstrated a quantitative correlation between mRNA expression and the production of cytokines, showing that suppression of TNF-α gene expression was most significantly correlated with its secretion. These results clearly proved that the anti-inflammatory effects of *Spirulina* extract from a nonthermal ultrasonic process, which yielded high concentrations of intact forms of chlorophylls, were increased two-fold compared to those of conventional extracts processed at high temperature.

**Keywords:** *Spirulina maxima*; anti-inflammatory effects; neuroproective activities; ultrasonic extraction process
