Tanshinone IIA attenuates bleomycin-induced pulmonary fibrosis in rats

Abstract

Idiopathic pulmonary fibrosis is a chronic and progressive fibrotic lung disorder with unknown etiology and a high mortality rate. Tanshinone IIA (Tan IIA) is a lipophilic diterpene extracted from the Chinese herb Salvia miltiorrhiza Bunge with diverse biological functions. The present study was conducted to evaluate the effects of Tan IIA on bleomycin (BLM)-induced pulmonary fibrosis in rats. Rats received an intraperitoneal injection of Tan IIA and normal rats were used as controls. Severe pulmonary edema, inflammation and fibrosis were observed in the BLM-treated rats and the counts of total cells, neutrophils and lymphocytes were significantly increased in the bronchoalveolar lavage fluids of those rats. These pathological changes were markedly attenuated by subsequent treatment with Tan IIA. In addition, BLM-induced increased expression of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, cyclooxygenase-2, prostaglandin E2, malondialdehyde, inducible nitric oxide synthase and nitric oxide in rats, which was also suppressed by Tan IIA injection. The present findings suggest therapeutic potential of Tan IIA for pulmonary fibrosis.

Modeling alveolar injury using microfluidic co-cultures for monitoring bleomycin-induced epithelial/fibroblastic cross-talk disorder

“…To further study this pathological process, we performed ELISA to measure TGF-b1, a key driver of cell differentiation, apoptosis, and ECM production in pulmonary brosis. 29 In agreement with our data related to broblast activation, TGF-b1 levels signicantly increased level in the BLM-treated cocultures with or without inammatory cells compared to healthy co-cultures. However, the level of TGF-b1 in BLMtreated co-cultures without epithelial cells was similar to that of healthy co-cultures ( Fig.…”

“…Bleomycin (BLM) can cause fatal pulmonary toxicity leading to lung brosis, and thus is extensively used to induce brogenesis for purposes of studying human pulmonary brosis. [27][28][29] We used BLM to induce epithelial injury and then examined the changes of epithelial cells in phenotype expression, viability and properties. We also assess the activation of interstitial cells under pathological conditions by quantifying the number of cell migration and the expression of activation-relative biomarkers (a-SMA and collagen I).…”

Induced Pluripotent Stem Cells Inhibit Bleomycin-Induced Pulmonary Fibrosis in Mice through Suppressing TGF-β1/Smad-Mediated Epithelial to Mesenchymal Transition

“…Several studies have reported that exogenously supplying PEG 2 protected mice against BLM-induced pulmonary fibrosis (Wilborn et al, 1995; Failla et al, 2009; Dackor et al, 2011), whereas some other reports showed the detrimental effects of PEG 2 in BLM-induced fibrotic process (McCann et al, 2011; Zhao et al, 2014; He et al, 2015). Consistent with the latter view, we found that PEG 2 level and COX-2 expression were up-regulated after BLM induction.…”

Tanshinone IIA treatment alleviated the rat gingival connective tissue overgrowth induced by cyclosporine A

“…Tanshinone IIA (Tan IIA, C 19 H 18 O 3 ) is one of the main lipophilic abietane diterpene compounds isolated from the dried root of Salvia miltiorrhiza Bunge, which has diverse biological functions and is widely used for the treatment of cardiovascular diseases (21). In addition to its well-studied therapeutic efficacy in managing cardiovascular problems, accumulating data from in vitro and in vivo studies indicated that Tan IIA could effectively attenuate a variety of fibrotic conditions including cardiac fibrosis (22)(23)(24)(25), pulmonary fibrosis (26,27), hepatic fibrosis (28,29), renal fibrosis (30), bladder fibrosis (31) and peritoneal fibrosis (32). Although the precise antifibrotic mechanisms of Tan IIA remain unclear, a number of reports suggest that Tan IIA is likely to exert its antifibrotic effect through inhibiting the activities of the TGF-b1/Smad signaling pathway (22,23,26,28,(30)(31)(32), reducing endoplasmic reticulum stress (22), changing the balance between MMPs and TIMPs (23,25), limiting the apoptosis of cardiomyocytes (23) and inducing the apoptosis of hepatic stellate cells (29).…”

“…Although the precise antifibrotic mechanisms of Tan IIA remain unclear, a number of reports suggest that Tan IIA is likely to exert its antifibrotic effect through inhibiting the activities of the TGF-b1/Smad signaling pathway (22,23,26,28,(30)(31)(32), reducing endoplasmic reticulum stress (22), changing the balance between MMPs and TIMPs (23,25), limiting the apoptosis of cardiomyocytes (23) and inducing the apoptosis of hepatic stellate cells (29). The antioxidant (22)(23)(24) and anti-inflammatory (27,30) effects of Tan IIA may also contribute to the prevention of tissue fibrosis.…”