Endothelia-Targeting Protection by Escin in Decompression Sickness Rats

Zhang, Kun; Jiang, Zucheng; Ning, Xiaowei; Yu, Xin; Xu, Jiajun; Buzzacott, Peter; Xu, Wei

doi:10.1038/srep41288

Cited by 16 publications

(20 citation statements)

References 27 publications

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“…Escin, the main active compound of horse chestnuts, 6 has been widely used to treat swelling, exudation, and inflammation. 7 Recently, accumulated experimental evidence has shown that escin is a potential cancer chemotherapeutic and has elucidated some of the underlying mechanisms.…”

mentioning

confidence: 99%

Escin induces caspase-dependent apoptosis and autophagy through the ROS/p38 MAPK signalling pathway in human osteosarcoma cells in vitro and in vivo

Zhu

Liu

et al. 2017

Cell Death Dis

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Osteosarcoma is one of the most malignant neoplasms in adolescents, and it generally develops multidrug resistance. Escin, a natural mixture of triterpene saponins isolated from Aesculus hippocastanum (horse chestnut), has demonstrated potent anti-tumour potential in vitro and in vivo. In the present study, we found that escin inhibited osteosarcoma proliferation in a dose- and time-dependent manner. Additionally, escin-induced apoptosis was evidenced by the increased expression of caspase-related proteins and the formation of apoptotic bodies. Escin also induced autophagy, with elevated LC3, ATG5, ATG12 and Beclin expression as well as autophagosome formation. Inhibition of escin-induced autophagy promoted apoptosis. Moreover, p38 mitogen-activated protein kinases (MAPKs) and reactive oxygen species (ROS) were activated by escin. A p38 MAPK inhibitor partially attenuated the autophagy and apoptosis triggered by escin, but a ROS scavenger showed a greater inhibitory effect. Finally, the therapeutic efficacy of escin against osteosarcoma was demonstrated in an orthotopic model. Overall, escin counteracted osteosarcoma by inducing autophagy and apoptosis via the activation of the ROS/p38 MAPK signalling pathway; these findings provide evidence for escin as a novel and potent therapeutic for the treatment of osteosarcoma.

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mentioning

confidence: 99%

Escin induces caspase-dependent apoptosis and autophagy through the ROS/p38 MAPK signalling pathway in human osteosarcoma cells in vitro and in vivo

Zhu

Liu

et al. 2017

Cell Death Dis

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“… 22 23 In addition, the improvement of vascular function was also found to be protective on DCS. 24 Our study revealed that bubbles secondary to decompression could induce the production of microparticles 22 which also induced the polarization of macrophages. 25 In addition, microbubbles in the blood vessels may cause ischemia and subsequent alteration of vascular permeability, leading to the leakage of plasma.…”

Section: E Vidence On the R Ole Of mentioning

confidence: 63%

Macrophage polarization is related to the pathogenesis of decompression induced lung injury

Han

Zhang²,

Liu³

2017

Med Gas Res

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Studies have shown that blood bubbles may be detectable and there is ultrasonic evidence of acute interstitial lung edema even after diving without protocol violation. Macrophages play a central role in the inflammation, and macrophage polarization is closely related to the pathogenesis some lung diseases. Available findings indicate that decompression may induce the production of pro-inflammatory cytokines, chemokines, and adhesion molecules in the blood and tissues, which are associated with the macrophage polarization, and hyperbaric treatment may exert therapeutic effects on decompression related diseases via regulating these factors. Thus, we hypothesize that the polarization of circulating and/or resident macrophages is involved in the pathogenesis of decompression induced lung injury.

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“…For regular divers, even if decompression protocols are strictly followed during each dive, bubbles may still form in the body, 35 which may protect endothelial cells against future injuries through moderately up-regulating autophagy. As endothelial targeting protection has been shown to prevent DCS, [5][6][7] we speculate that increased tolerance to DCS in regular divers might be, at least in part, related to moderate up-regulation of endothelial autophagy. Related rat-model experiments are currently F I G U R E 7 Effects of two consecutive bubble contact on endothelial injury.…”

Section: Discussionmentioning

confidence: 99%

“…Decompression sickness (DCS) is a medical concern that threatens the safety of divers and is associated with bubbles that may appear during or after decompression, even after strictly following diving protocols . Endothelial dysfunction occurs following decompression in divers, and endothelial protective agents have proven beneficial to DCS in animal models . It is now widely accepted that endothelial injury triggered by bubbles plays an important role in the pathophysiology of DCS .…”

Section: Introductionmentioning

confidence: 99%

Biphasic effects of autophagy on decompression bubble‐induced endothelial injury

Wang¹,

Zhang²,

Nie³

et al. 2019

J Cellular Molecular Medi

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Endothelial dysfunction induced by bubbles plays an important role in decompression sickness (DCS), but the mechanism of which has not been clear. The present study was to investigate the role of autophagy in bubble‐induced endothelial injury. Human umbilical vein endothelial cells (HUVECs) were treated with bubbles, autophagy markers and endothelial injury indices were determined, and relationship strengths were quantified. Effects of autophagy inhibitor 3‐methyladenine (3‐MA) were observed. Bubble contact for 1, 5, 10, 20 or 30 minutes induced significant autophagy with increases in LC3‐II/I ratio and Beclin‐1, and a decrease in P62, which correlated with bubble contact duration. Apoptosis rate, cytochrome C and cleaved caspase‐3 increased, and cell viability decreased following bubble contact for 10, 20 or 30 minutes, but not for 1 or 5 minutes. Injuries in HUVECs were correlated with LC3‐II/I ratio and partially reversed by 3‐MA in 10, 20 or 30 minutes contact, but worsened in 1 or 5 minutes. Bubble pre‐conditioning for 1 minutes resulted in increased cell viability and decreased apoptosis rate compared with no pre‐conditioning, and 30‐minutes pre‐conditioning induced opposing changes, all of which were inhibited by 3‐MA. In conclusion, autophagy was involved and played a biphasic role in bubble‐induced endothelial injury.

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Endothelia-Targeting Protection by Escin in Decompression Sickness Rats

Cited by 16 publications

References 27 publications

Escin induces caspase-dependent apoptosis and autophagy through the ROS/p38 MAPK signalling pathway in human osteosarcoma cells in vitro and in vivo

Escin induces caspase-dependent apoptosis and autophagy through the ROS/p38 MAPK signalling pathway in human osteosarcoma cells in vitro and in vivo

Macrophage polarization is related to the pathogenesis of decompression induced lung injury

Biphasic effects of autophagy on decompression bubble‐induced endothelial injury

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