1. Academic Validation
  2. Protective effect of cynaroside on sepsis-induced multiple organ injury through Nrf2/HO-1-dependent macrophage polarization

Protective effect of cynaroside on sepsis-induced multiple organ injury through Nrf2/HO-1-dependent macrophage polarization

  • Eur J Pharmacol. 2021 Nov 15;911:174522. doi: 10.1016/j.ejphar.2021.174522.
Jiafan Feng 1 Zhijun Liu 1 Hang Chen 1 Mengning Zhang 1 Xiaochun Ma 1 Qiang Han 1 Dezhao Lu 2 Cui Wang 3
Affiliations

Affiliations

  • 1 School of Life Science, Zhejiang Chinese Medical University, 310053, Hangzhou, China.
  • 2 School of Life Science, Zhejiang Chinese Medical University, 310053, Hangzhou, China. Electronic address: [email protected].
  • 3 School of Life Science, Zhejiang Chinese Medical University, 310053, Hangzhou, China. Electronic address: [email protected].
Abstract

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.

Keywords

Cynaroside; Macrophage polarization; Nrf2/HO-1; Sepsis.

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