Hyperoside relieves particulate matter-induced lung injury by inhibiting AMPK/mTOR-mediated autophagy deregulation

  • Pharmacol Res. 2021 May;167:105561. doi: 10.1016/j.phrs.2021.105561.
Yun Gao  1 ,  Xiaoye Fan  1 ,  Wenjing Gu  2 ,  Xinxin Ci  3 ,  Liping Peng  4
Affiliations
  • 1. Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, China.
  • 2. Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China.
  • 3. Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, China; Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China. Electronic address: [email protected].
  • 4. Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, China. Electronic address: [email protected].
PMID: 33737241 DOI: 10.1016/j.phrs.2021.105561
Abstract

Autophagy-mediated cell death plays a critical role in the pathogenesis of PMs-induced lung injury. Hyperoside (Hyp), a flavonoid glycosides, is known to exert protective effects on many diseases by inhibiting autophagic activity. The current study aimed to explore the protective effect and mechanism of Hyp against PMs-induced lung injury in PM2.5 challenged Beas-2b cells in vitro and BALB/C mice in vivo. In vitro, we found that the organic solvent-extractable fraction of SRM1649b (O-PMs) caused more severe cytotoxicity in Beas-2b cells than the water solvent-extractable fraction of SRM1649b (W-PMs). O-PMs treatment dose-dependently upregulated the expression of Autophagy markers (beclin-1, p62, atg3 and LC3II) and apoptotic proteins. This cytotoxicity of O-PMs was attenuated by Hyp pretreatment in parallel with downregulation of the expression of Autophagy markers, apoptotic proteins, and p-AMPK and upregulation of p-mTOR expression. Notably, the therapeutic effect of Hyp was attenuated by pretreated with AICAR (an AMPK inducer), but enhanced by CC and 3-MA treatment. In vivo, Hyp reduced pathological lung injury and decreased the levels of PMs-induced inflammatory cytokines (TNF-α and IL-6), and the number of total cells in the BALF by inhibiting AMPK/mTOR signaling. Furthermore, cotreatment with AICAR (500 mg/kg) reduced but did not abrogate the pulmonary protective effect of Hyp. These findings indicate that Hyp protects against PMs-induced lung injury by suppressing Autophagy deregulation and Apoptosis through regulation of the AMPK/mTOR pathway.

Keywords
AMPK/mTOR-mediated autophagy; Fine particle pollutants; Hyperoside; Lung injury.
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