CONCLUSIONS
Tubeimoside III protects against LPS-induced lung and liver injury by attenuating inflammatory factor secretion and inflammatory cell infiltration, and its mechanism of action involves reprogramming macrophage glucose metabolism and increasing itaconic acid levels.
Keyword: Tubeimoside III; Inflammation; Macrophage; Metabolic reprogramming; Itaconic acid; Lipopolysaccharide
Background
Inflammation is a protective response to irritation; excessive or abnormal inflammatory responses exacerbate many acute and chronic diseases. Lipopolysaccharide (LPS) is a bacterial endotoxin that triggers an inflammatory cascade that leads to systemic inflammatory responses. The conventional view is that macrophages activate Toll-like receptor 4, which then activates nuclear factor-κB (NF-κB) and the mitogen-activated protein kinase (MAPK) signaling pathways to regulate the expression of downstream inflammatory target genes, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6[1, 2].
Bolbostemma paniculatum (Maxim.) Franquet is a member of the Cucurbitaceae family with a long history of medicinal use. The Pharmacopoeia of the People’s Republic of China records that it has detoxifying effects, dispersing knots, stopping bleeding, and reducing swelling; it is used to treat canker sores, scrofula, and phlegm toxin[3] . The compounds extracted from B. paniculatuminclude triterpenoids, sterols, alkaloids, anthraquinones, and organic acids. Triterpenoids are abundant active ingredients in B. paniculatum , including tubeimosides I, Ⅱ, and Ⅲ (Tube)[4]. Tube had anti-inflammatory and anti-swelling effects on ear edema induced by arachidonic acid and 12-O-tetradecanoylphorbol-13-acetate(TPA) in mice, and its effects were more potent than those of tubeimosides I and Ⅱ[5]. Similar results were reported by Yu et al., who observed that the anti-inflammatory effect of Tube was more potent than those of tubeimosides I and II in a mouse ear edema model[6]. However, to date, the anti-inflammatory mechanism remains unclear. Therefore, in this study, we established an inflammation model in LPS-induced mononuclear macrophages RAW264.7 in mice to investigate Tube’s anti-inflammatory effect and molecular mechanisms.