Optimization of antioxidant, anti-diabetic, and anti-inflammatory activities and ganoderic acid content of differentially dried Ganoderma lucidum using response surface methodology

•Ganoderma lucidum extraction was optimized using ultrasonic assisted response surface methodology.•Time was the most critical factor for the optimized extraction procedure.•Antioxidant activity and ganoderic acid content were optimized at 64.2–70 °C for 1.2 h.•Anti-diabetic activity and polysaccharide content were optimized at 66.8–70 °C for > 2.8 h.•Heat-dried samples extracted at 50 °C for 3 h showed high anti-inflammatory potential. The dried Ganoderma lucidum (GL) has been widely used for its pharmacological properties and bioactive ganoderic acids (GAs). Herein, extraction procedures combining ultra-sonication and heating were optimized using response surface methodology based on four variables (antioxidant activity, anti-diabetic activity, total GAs content, and total polysaccharide content) and principal component analysis. The extraction of freeze-dried GL at temperatures between 64.2 and 70 °C for 1.2 h maximized the antioxidant activity and GA content, whereas the polysaccharide content and anti-diabetic activity were maximized by extraction between 66.8 and 70 °C for more than 2.8 h. Heat-dried GL extracted at 50 °C for 3 h provided the greatest anti-inflammatory activity against HaCaT cells by suppressing the response to inflammation related cytokines at mRNA levels. These results suggest that extraction conditions might be a limiting factor for target-oriented investigations, and optimized extraction methods may improve the potential effect and quality of harvested GL products.