Tanshinone IIA attenuates paraquat‑induced acute lung injury by modulating angiotensin‑converting enzyme 2/angiotensin‑(1‑7) in rats

Abstract

Tanshinone IIA (TIIA) is an active compound that can be isolated from the Chinese herb, Salvia miltiorrhizae Bunge, also known as danshen. Previous studies have demonstrated that TIIA can effectively attenuate bleomycin‑induced pulmonary fibrosis in rats. However, it has not been determined whether TIIA can attenuate paraquat (PQ)‑induced acute lung injury (ALI). In the present study, the protective effects exhibited by TIIA on PQ‑induced ALI, as well as its underlying mechanisms, were investigated using Sprague‑Dawley (SD) rats. ALI animal models using rats were established via administration of PQ. Adult male SD rats were randomly divided into three groups: A control group, a PQ group and a PQ + TIIA group. Total cell count, total protein levels and lactic dehydrogenase (LDH) levels in bronchoalveolar lavage fluid (BALF), as well as myeloperoxidase (MPO) activity in lung tissues were determined. Lung histological alterations were also investigated. Angiotensin converting enzyme 2 (ACE2) and Angiotensin 1‑7 [Ang‑(1‑7)] expression levels in the lung were also analyzed. The results demonstrated that administration of PQ induced marked histological alterations, and markedly increased neutrophil infiltration, lung wet/dry weight ratio, total cell count, protein content and LDH levels in BALF. In addition, PQ was revealed to significantly decrease ACE2 and Ang‑(1‑7) expression levels in lung tissues. However, it was demonstrated that TIIA attenuated these effects. Therefore, the results of the present study suggest that that TIIA may exhibit a therapeutic effect regarding PQ‑induced ALI in rats, and that ACE2 and Ang‑(1‑7) may be involved in the underlying mechanisms of this effect.

Tanshinone IIA ameliorates acute lung injury by inhibition of the NLRP3 inflammasome

“…The protein levels of NLRP3, caspase-1 and IL-1β in pulmonary tissues were increased in OA-treated rats and attenuated by tanshinone IIA treatment. The protective effect of tanshinone IIA on lung injury has been confirmed in different animal models, including lung injury induced by LPS [17][18][19][20], seawater exposure [21,22] and paraquat [23]. In the OA-induced ALI model in rats, we demonstrated the ameliorative effect of tanshinone IIA on ALI, confirmed by an alleviation of pathological histological indicators, pulmonary edema and gas exchange, and decreased levels of inflammatory cytokines in BAL fluid.…”

“…Tanshinone IIA has various biological effects, such as anti-inflammatory and antioxidant effects. The protective effect of tanshinone IIA against ALI has been verified in animal models of ALI induced by lipopolysaccharide (LPS) [17][18][19][20], seawater exposure [21,22] and paraquat [23]. However, the mechanism of the ameliorative effect of tanshinone IIA on ALI has not been fully investigated.…”

Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms

“…Tanshinone IIA has various activities including cardioprotective, anti-atherosclerotic, anti-cancer, anti-bacterial and anti-viral activities. Moreover, tanshinone IIA increased the survival rate as well as attenuated lung histopathologic changes and lung edema in animals with ALI induced by LPS, paraquat, seawater, bleomycin, pancreatitis or aspiration [ [88] , [89] , [90] , [91] , [92] ]. Interestingly, tanshinone IIA exerted inhibitory effects on lung inflammatory condition via inhibition of expression of pro-inflammatory cytokines TNF-a, IL-1β and IL-6.…”

Could SARS-CoV-2-induced lung injury be attenuated by vitamin D?

“…ARDS and acute lung injury are associated with damaged pulmonary microvascular endothelial cells (PMVECs), which result in increased alveolar permeability and pulmonary oedema ( Su et al, 2004 ). The balance between the expression of ACE1 and ACE2 is closely related to the ratio of Ang Ⅱ:Ang1-7, and an imbalance of Ang Ⅱ:Ang1-7 can lead to acute lung injury ( Gao et al, 2019 , Queiroz-Junior et al, 2019 , Wang et al, 2018 ).…”