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Honokiol attenuates lipopolysaccharide-induced acute respiratory distress syndrome via activation of mitochondrion-dependent Sirt3/AMPK pathway / 中南大学学报(医学版)
Journal of Central South University(Medical Sciences) ; (12): 1075-1082, 2018.
Article in Chinese | WPRIM | ID: wpr-813151
ABSTRACT
To explore the effects of honokiol (HKL) on pulmonary microvascular endothelial cells in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) and the underlying mechanisms.


Methods:

In animal experiment, a total of 40 C57BL/6J mice were randomly divided into a control group (Con group), a LPS intervention group (LPS group), a LPS+honokiol (HKL) intervention group (HKL group) and a LPS+HKL+nicotinamide (NAM) intervention group (NAM group) (n=10 in each group). In the cell experiment, the experiment cells were divided into a control group (Con group), a LPS intervention group (LPS group), a LPS+HKL intervention group (HKL group), a LPS+HKL+NAM intervention group (NAM group), and a LPS+HKL+compound C (CMC) intervention group (CMC group). The pathological changes of the lung tissues were evaluated by hematoxylin and eosin (HE) staining; the protein concentration, total cells and neutrophils in the bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) activity in the lung tissues were detected; the changes of pulmonary microvascular permeability were determined by Evans blue assay; the effect of HKL on the vitality of human pulmonary microvascular endothelial cells were examined by cell counting kit-8 (CCK-8); the inhibitors including NAM and CMC were applied to explore the molecular mechanism of the protective effects of HKL. The expression levels of Sirt3, caspase-3, cleaved caspase-3, Bcl-2, Bax, p-adenosine monophosphate activated protein kinase (p-AMPK) and AMPK in lung tissues or cells were detected by Western blot.


Results:

In animal models, compared with the Con group, the mice in the LPS group displayed typical ARDS pathological changes, and the ratio of lung wet/dry weight (W/D) and MPO activity in the lung tissues, protein concentration, total cells and neutrophils in BALF, Evans blue leaking index (ELI), expression levels of cleaved caspase-3 were significantly increased (all P<0.05), while the expression levels of Sirt3 was obviously decreased (P<0.05). Compared with the LPS group, the above changes in the LPS group were significantly improved in the HKL group (all P<0.05); Compared with the HKL group, the curative effect of HKL intervention could be partly inhibited in the NAM group (P<0.05). In cell experiments, compared with the LPS group, the HPMECs viability in the HKL group was markedly improved (P<0.05), while the expression levels of Bcl-2 and Sirt3 were significantly upregulated (P<0.05), and the expression levels of Bax and cleaved caspase-3 were significantly downregulated (P<0.05), accompanied by the activation of AMPK pathway (P<0.05) in the HKL group. Compared with the HKL group, the curative effect of HKL intervention was partly inhibited in the CMC group (P<0.05).


Conclusion:

HKL can significantly attenuate LPS-induced lung injury and inhibit the apoptosis of pulmonary microvascular endothelial cells through regulation of Sirt3/AMPK pathway.
Subject(s)
Full text: Available Index: WPRIM (Western Pacific) Main subject: Pharmacology / Biphenyl Compounds / Signal Transduction / Lipopolysaccharides / Lignans / Therapeutic Uses / Drug Therapy / Acute Lung Injury / AMP-Activated Protein Kinases / Sirtuin 3 Limits: Animals / Humans Language: Chinese Journal: Journal of Central South University(Medical Sciences) Year: 2018 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pharmacology / Biphenyl Compounds / Signal Transduction / Lipopolysaccharides / Lignans / Therapeutic Uses / Drug Therapy / Acute Lung Injury / AMP-Activated Protein Kinases / Sirtuin 3 Limits: Animals / Humans Language: Chinese Journal: Journal of Central South University(Medical Sciences) Year: 2018 Type: Article