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.