Cynaroside is the primary
flavonoid component of honeysuckle which has been widely used as
Chinese traditional medicine given its anti-
inflammation properties. Overactive systemic inflammatory response and multi-organ injury are the leading causes of life-threatening
sepsis. Regulation of macrophage polarization balance may act as a promising strategy for its treatment. In the present study, we aimed to investigate whether
cynaroside exerted protective effects against
sepsis and its potential mechanism. Building upon a
sepsis mouse model, we observed
cynaroside alleviated serum levels of inflammatory factors including IL-1β and TNF-α at 5 and 10 mg/kg. The pathological injury of heart, kidney and lung was remarkedly attenuated as the levels of blood
urea nitrogen,
creatinine,
creatine kinase-MB and
lactate dehydrogenase were reduced nearly 2.8-, 2.7-, 2.4-, and 2.5-fold as compared with the
sepsis mice, respectively. We further demonstrated
cynaroside suppressed the
biomarker of pro-inflammatory macrophage M1 phenotype (iNOS+) and promotes the anti-inflammatory M2 polarization (CD206+) in the injury organs of septic mice. Mechanistic research verified
cynaroside inhibited LPS-induced polarization of macrophage into M1 phenotype, which can be highly blocked by Nrf2 inhibitor. Expectedly, Nrf2 and its downstream (Heme oxygenase-1 (HO-1)) was upregulated in injury organs after treating with
cynaroside, indicating the involvement of Nrf2 signaling. Taken together, the data claims
cynaroside ameliorated systematic
inflammation and multi-organ injury dependent on Nrf2/HO-1 pathway in septic mice.