Ganoderma lucidum polysaccharides (GLP) possess remarkable bioactivity and have been studied widely. However, the application of new technologies in the polysaccharide extraction has not been investigated. Herein, a novel continuous phase transition extraction (CPTE) technology was applied for the extraction of polysaccharides from Ganoderma lucidum. The extraction kinetics, physicochemical properties and immunomodulatory activity of GLP were evaluated. The kinetics results showed that the extraction process could be fitted to a two-site kinetic model due to the high R2 values in the range of 0.9939–0.9999. Polysaccharides extracted by different technologies showed that GLP yield by CPTE could be significantly improved, which was 3.34 times and 2.68 times that of hot water and ultrasonic-assisted extraction, respectively. Molecular weight distribution analysis indicated that high molecular mass polysaccharide proportion by CPTE was the highest among the three extraction methods, which was 2.03 times and 3.41 times as much as that of the hot water and ultrasonic-assisted extraction. Morphology analysis showed that CPTE treatment caused disruption of most of the cells and effective release of intracellular components, implying that CPTE was beneficial to extract polysaccharides. Furthermore, the immunomodulatory assays demonstrated that GLP significantly enhanced the proliferation and production of NO, TNF-α and IL-6 in macrophages. Therefore, CPTE was more effective for extracting polysaccharides from Ganoderma lucidum than the common extraction.
