Ginsenosides from Panax ginseng modulate lipid mediator profiles in human leukocytes by interference with cellular...

Lipid mediators are a superfamily of bioactive molecules that are crucially involved in immune responses, regulating all stages of inflammation. Panax (P.) ginseng has pleiotropic pharmacological effects, including anti-cancer, anti-diabetic, and anti-inflammatory properties. Ginsenosides, unique triterpenoid glycosides from the plant's root, are proposed as active ingredients responsible for the immunomodulating potential of P.ginseng. Here, we comprehensively screened 23 ginsenosides for manipulating the lipid mediator network in various primary human innate immune cells. Several ginsenosides selectively inhibited 5-lipoxygenase (5-LOX)-mediated formation of pro-inflammatory leukotriene B₄, but not of prostaglandins, in monocyte-derived macrophages and polymorphonuclear leukocytes by a unique irreversible mechanism. Structure-activity relationships revealed (i) higher anti-5-LOX activity of PPD-type ginsenosides, (ii) correlation with lipophilicity (R² = 0.91), and (iii) eudysmic ratios favoring the 20S-epimers. Our findings highlight ginsenosides as immunomodulatory principles of P. ginseng and reveal abrogation of leukotriene formation rather than interference with prostaglandins as immediate anti-inflammatory mechanism.