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bioRxiv · 10.1101/2021.11.04.467383

Salidroside protects lipopolysaccharide-induced acute lung injury by regulating miR-145/ cytosolic phospholipase A2

Gu, L.·Shi, Z.
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Abstract

Salidroside is one of the main active components from the root of Rhodiola rosea. Previous reports showed that salidroside exhibits anti-inflammatory properties, but the underlying mechanisms are not fully understood. Here, we observed the effects of salidroside on lipopolysaccharide (LPS)-induced acute lung injury (ALI) both in vivo and in vitro. As revealed by survival study, salidroside reduced mortality of rats and prolonged their survival time. Meanwhile, salidroside significantly improved LPS-induced lung histopathologic changes, decreased lung wet-to-dry and lung-to-body weight ratios, inhibited lung myeloperoxidase (MPO) activity. Salidroside also suppressed the expression of cytosolic PLA2 (cPLA2), the activity of phospholipase A2 (PLA2) in LPS-treated rats and the metabolites of PLA2 in bronchoalveolar lavage fluid (BALF), which was confirmed by results of prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and thromboxane B2 (TXB2) detection. And the expression of microRNA-145 in LPS-treated rats was up-regulated by salidroside. Besides, salidroside raised the level of miR-145and reduced PLA2 activity in LPS-induced A549 cells in a concentration-dependent manner, which was obviously reversed by miR-145 inhibition. In conclusion, the current study demonstrated that salidroside exhibited a protective effect on LPS-induced ALI by inhibiting of the inflammatory response, which may involve in the up-regulation of miR-145 and the suppression of cPLA2. HighlightsO_LISalidroside reduces acute lung injury by inhibiting the increment and metabolism of phospholipase A2; C_LIO_LISalidroside inhibits LPS-induced PLA2 increase dependent on miR-145; C_LIO_LIThe inhibitory effect of Salidroside on Phospholipases A2 provides a link between the identification of new targets and potential new therapeutic agents for the treatment of acute lung injury. C_LI

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Gu, L., Shi, Z.. 2021-11-05. Salidroside protects lipopolysaccharide-induced acute lung injury by regulating miR-145/ cytosolic phospholipase A2. https://doi.org/10.1101/2021.11.04.467383

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