Sini decoction alleviates E. coli induced acute lung injury in mice via equilibrating ACE-AngII-AT1R and ACE2-Ang-(1-7)-Mas axis.

Acute respiratory distress syndrome (ARDS), one of the serious form of acute lung injury (ALI), is the primary cause of death in patients with ALI. Sini decoction (SND) is a widely used Traditional Chinese Medicine (TCM). However, the application of SND in ALI is rarely reported. Previous studies have found that renin-angiotensin-aldosterone system (RAAS) played vital and bidirectional roles in ALI. Therefore, the aim of the present study was to investigate protective effect of SND on ALI model induced by E. coli, as well as to further explore relations between RAAS and SND. The ALI model was evaluated by morphological observations and biochemical assays. The expression levels of angiotensin converting enzyme (ACE), Angiotensin II type 1 receptor (AT1R) and angiotensin converting enzyme 2 (ACE2) were examined by Western blotting. The expression levels of angiotensinII (AngII) and angiotensin-(1-7) (Ang-(1-7)) were measured through ELISA. MasR, IL-6, IL-1β and TNFα were all measured using qRT-PCR. SND significantly ameliorated E. coli-induced ALI, including reducing inflammatory factors in lung tissue and the activity of MPO in serum. Furthermore, SND could obviously decrease the expression of ACE, AngII and AT1R, which were induced by E. coli. On the other hand, SND could markedly activate ACE2-Ang-(1-7)-Mas pathway. In this paper, we demonstrated that SND alleviates E. coli induced acute lung injury in mice via equilibrating ACE-AngII-AT1R and ACE2-Ang-(1-7)-Mas axis.

Liu J ，Chen Q ，Liu S ，Yang X ，Zhang Y ，Huang F ... -  《-》

Sini decoction ameliorates sepsis-induced acute lung injury via regulating ACE2-Ang (1-7)-Mas axis and inhibiting the MAPK signaling pathway.

Sepsis, as life-threatening organ dysfunction caused by a dysregulated host response to infection, is characterized by the extensive release of cytokines and other mediators. Sini decoction (SND), a traditional Chinese prescription medicine, has been used clinically for the treatment of sepsis. But its explicit mechanism of action is still unclear. The present study aims to evaluate the potential protective effects of SND on sepsis-induced acute lung injury (ALI). After SND intervention, the lung tissues of each experimental group were collected. H&E sections were used to observe the pathological changes of lung tissue, and alveolar lavage fluid was collected to detect the infiltration of inflammatory cells. Level of inflammatory factors in lung tissue were analyzed by qRT-PCR. The change of Renin angiotensin system (RAS), as well as downstream MAPK/NF-κB signaling pathways were measured by Western blot. For in vitro experiments, human umbilical vein endothelial cells (HUVECs) were pretreated with lipopolysaccharide (LPS) and treated with SND. Subsequently, the expression levels of RAS and MAPK/NF-κB signaling pathways were measured by Western blot. In vivo, we found that SND significantly attenuated sepsis-induced pathological injury in the lung. SND also inhibited LPS-mediated inflammatory cell infiltration, the expression of pro-apoptotic proteins and the production of IL-6, IL-1β, TNF-α and MCP-1. In vitro, experiments using a co-culture of HUVECs with SND showed that there was a decrease in pro-apoptotic protein and pro-inflammatory mediator. In this research, we also found that SND protective action could be attributed to the regulation of renin-angiotensin system (RAS). MAPKs and NF-κB pathways. To conclude, our study demonstrated that SND ameliorates sepsis-induced-ALI via regulating ACE2-Ang (1-7)-Mas axis and inhibiting the MAPK signaling pathway.

Chen Q ，Liu J ，Wang W ，Liu S ，Yang X ，Chen M ，Cheng L ，Lu J ，Guo T ，Huang F ... -  《-》

BML-111 equilibrated ACE-AngII-AT1R and ACE2-Ang-(1-7)-Mas axis to protect hepatic fibrosis in rats.

It was recently reported Lipoxins (LXs) had protective effects on fibrous diseases, and renin-angiotensin-aldosterone system (RAAS) had played vital and bidirectional roles in hepatic fibrosis. In this paper, a hepatic fibrosis model, induced by carbon tetrachloride (CCL4) in rats, was used to observe the relations between RAAS and LXs, as well as to further explore the alternative anti-fibrosis mechanisms of LXs. The model was evaluated by morphological observations and biochemical assays. The activities and contents of angiotensin converting enzyme (ACE) and angiotensin converting enzyme 2 (ACE2) were examined through assay kits and ELISA. The expression levels of angiotensinII (AngII), Angiotensin II type 1 receptor (AT1R), angiotensin-(1-7) (Ang-1-7), and Mas were all measured using real time PCR, ELISA, and Western blot. The model was established successfully and BML-111 significantly ameliorated CCL4-induced hepatic fibrosis, including reduction inflammation injury, decrease extracellular matrix deposition, and improvement hepatic functions. Furthermore, BML-111 could obviously decrease not only the activities of ACE but also the expression levels of ACE, AngII,and AT1R, which were induced by CCL4. On the other hand, BML-111 could markedly increase the activities of ACE2, besides the expression levels of ACE2, Ang-(1-7) and Mas. More importantly, BOC-2, a lipoxin A4 receptor blocker, could reverse all these phenomena. Equilibrating ACE-AngII-AT1R axis and ACE2-Ang-(1-7)-Mas axis mediated the protective effect of BML-111 on hepatic fibrosis in rats.

Hu Q ，Hu Z ，Chen Q ，Huang Y ，Mao Z ，Xu F ，Zhou X ... -  《PROSTAGLANDINS & OTHER LIPID MEDIATORS》

[ACE2 agonist DIZE alleviates lung injury induced by limb ischemia-reperfusion in mice].

Li SM ，Wang XY ，Liu F ，Yang XH ... -  《-》

Lipoxin A(4) attenuates LPS-induced acute lung injury via activation of the ACE2-Ang-(1-7)-Mas axis.

Chen QF ，Kuang XD ，Yuan QF ，Hao H ，Zhang T ，Huang YH ，Zhou XY ... -  《-》