ReferenceID 5910

Oridonin attenuates LPS-induced early pulmonary fibrosis by regulating impaired autophagy, oxidative stress, inflammation and EMT

Eur J Pharmacol

Context: Oridonin (Ori) possesses anti-inflammatory, antioxidant and antitumor properties. However, the effects of Ori on Lipopolysaccharide (LPS)-induced early pulmonary fibrosis remain unclear. Objective: We evaluated

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Reference Id
5910
Evidence Id
22500
Core Evidence Id
22500
Source Reference Id
5078
Herb2 Reference Id
HBREF005875
Subject Paper Key
HBIN038254_35398392
Pubmed Id
35398392
Doi
10.1016/j.ejphar.2022.174931
Paper Title
Oridonin attenuates LPS-induced early pulmonary fibrosis by regulating impaired autophagy, oxidative stress, inflammation and EMT
Paper Abstract
Context: Oridonin (Ori) possesses anti-inflammatory, antioxidant and antitumor properties. However, the effects of Ori on Lipopolysaccharide (LPS)-induced early pulmonary fibrosis remain unclear. Objective: We evaluated the protective effects of Ori on the mice model of pulmonary fibrosis. Materials and methods: The BALB/C mice were given LPS (1 mg/kg) or Ori (20 mg/kg) according to experimental grouping. Then the left lung tissues were used for HE, immunohistochemical and Masson staining, and the right lung tissues were used for hydroxyproline measurement and western blot experiments. Bronchoalveolar lavage fluid was collected for Giemsa staining. Results: The high levels of hydroxyproline induced by LPS were reduced by Ori treatment. Immunohistochemical staining and western blot analysis showed that Ori inhibited the increased levels of fibrosis-related proteins (α-smooth muscle actin, transforming growth factor-β, Collagen Ⅰ and phosphorylated-smad). Additionally, Ori treatment increased E-cadherin levels and decreased in Snail and Slug levels. Besides, Ori could suppress LPS-induced the infiltration of neutrophils and activation of the NLRP3 inflammasome. In addition, LPS caused the upregulation of NADPH oxidase 4 and exacerbated lung fibrosis. As the activator of NF-E2 related factor-2, Ori exerted protective effects in this animal model. Moreover, Ori reversed the LPS-triggered increases in Beclin-1, P62/sequestosome 1, autophagy related 3 and LC3. Conclusions: These findings suggested that Ori protected against LPS-induced early pulmonary fibrosis by inhibiting NLRP3-dependent inflammation, NADPH oxidase 4-dependent oxidative stress, the impaired autophagy and epithelial mesenchymal transformation.
Journal
Eur J Pharmacol
Publish Year
2022
Experiment Subject
mouse
Experiment Type
Animal Experiment
Phenotype Related
Pulmonary Fibrosis; Lung Fibrosis
Paper Title Cn
Paper Title En
Oridonin attenuates LPS-induced early pulmonary fibrosis by regulating impaired autophagy, oxidative stress, inflammation and EMT
Bilingual Status
semi_complete