Fresh ginseng was fermented with Ganoderma lucidum mycelium (GL) in solid-state culture to enhance its immunomodulatory activity. When crude polysaccharide (FG-GL-CP) was fractionated from lyophilized fermented ginseng (FG-GL), FG-GL-CP showed significantly higher mitogenic, macrophage stimulating, and intestinal immune system modulating activity (1.52-, 1.52- and 1.46-fold, respectively) than those of crude polysaccharide from nonfermented ginseng (NG-CP, 1.36-, 1.37- and 1.32-fold) and G. lucidum mycelium alone (GL-CP, 1.48-, 1.40- and 1.31-fold). After FG-GL-CP was further fractionated into two active carbohydrate-rich fractions (FG-GL-CP-II and III) on DEAE-Sepharose CL-6B (Cl⁻ form), the most active polysaccharide (FG-GL-CP-III-1) was purified as a single peak with a molecular weight of 71 kDa. FG-GL-CP-III-1 mainly consists of Ara, Man, Gal, and Glc (molar ratio: 0.85:1.00:0.81:0.76) in addition to a small amount of uronic acid. Methylation analysis indicates that FG-GL-CP-III-1 is composed mainly of terminal/4- or 5-linked Ara(f), terminal/4-linked Man, terminal/3,6-branched Gal, and terminal/4-linked Glc. NaIO₄ oxidation of FG-GL-CP-III significantly decreased its activity (64.0-79.2%). These results suggest that solid-state culture of ginseng with G. lucidum may enhance the immunomodulatory activity and that neutral polysaccharides containing Ara, Man, Gal, and Glc may be important for the activity of fermented ginseng.

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