Ginseng marc-derived low-molecular-weight neutral glucan SN-GOS ameliorates ulcerative colitis via inhibition of apoptosis and activation of autophagy in human intestinal HT-29 cells and DSS-induced inflammatory colitis mice.

Although ginseng marc has been routinely discarded as a waste, it still contains considerable amounts of bioactive compounds, including polysaccharides. This study assessed the protective effects of a low-molecular-weight neutral glucan, SN-GOS, obtained by enzymatic degradation of polysaccharides from Panax ginseng marc, against ulcerative colitis (UC) using human intestinal HT-29 cells and dextran sulphate sodium (DSS)-induced inflammatory colitis mice models. Correlation NMR spectroscopy and methylation analysis confirmed that SN-GOS is a starch-like branched glucan consisting mainly of glucose (92.67 mol%) and having a backbone composed of (1 → 4)(1 → 6)-α-d-glucopyranosyl units, with other minor sugars and variable linkages. SN-GOS (25-500 μg/mL) significantly suppressed TNF-α-induced inflammatory apoptotic death of HT-29 cells by downregulating caspase-9 cleavage, DNA fragmentation, disruption of mitochondrial membrane potential (MMP), and upregulating Bcl-2 expression. SN-GOS also attenuated pro-inflammatory cytokine expression (TNF-α and interleukin-6) and ROS generation caused by TNF-α treatment. In addition, SN-GOS increased LC3-II expression with a concomitant reduction in p62/SQSTM1 accumulation, suggesting activation of autophagy-associated responses. Furthermore, SN-GOS attenuated TNF-α-induced phosphorylation of ERK and p38 MAPK, suggesting modulation of inflammatory stress-related MAPK signaling. Oral administration of SN-GOS (200-400 mg/kg) resulted in significant recovery of colon length, body weight, and damaged crypts and ulcerative tissues in DSS-induced colitis mice. These results suggest that SN-GOS alleviates UC-associated inflammatory injury by inhibiting inflammatory apoptotic cell death, promoting autophagy-associated responses, and suppressing inflammatory MAPK signaling, supporting its potential use as a functional food ingredient for UC management.