Protective effects and active ingredients of Salvia miltiorrhiza Bunge extracts on airway responsiveness, inflammation and remodeling in mice with ovalbumin-induced allergic asthma

Background: Salvia miltiorrhiza Bunge (S. miltiorrhiza), a traditional Chinese medicine, has demonstrated antioxidant, anti-inflammatory, and antibacterial activities. However, its effects against asthma that shows chronic inflammation and oxidative damage remain unknown. Purpose: To assess the effects of S. miltiorrhiza extracts on airway responsiveness, inflammation, and remodeling in ovalbumin (OVA)-induced asthmatic mice. Methods: Mice with ovalbumin (OVA)-induced allergic asthma were treated with S. miltiorrhiza extracts, and airway resistance (R-L) to methacholine, inflammatory cell infiltration, Th1/Th2 cytokine levels, and airway remodeling were assessed. TGF-beta 1-induced BEAS-2B and MRC-5 cells were used to evaluate the effects of five S. miltiorrhiza compounds on epithelial-mesenchymal transition and fibrosis. Results: OVA-challenge resulted in remarkably increased R-L, inflammatory cell infiltration, Th1/Th2 cytokine levels in BALF, goblet cell hyperplasia, collagen deposition, and airway wall thickening. Daily treatment with S. miltiorrhiza ethanolic (EE, 246 mg/kg) or water (WE, 156 mg/kg) extract significantly reduced OVA-induced airway inflammatory cell infiltration, Th1/Th2 cytokine amounts, and goblet cells hyperplasia. However, only WE remarkably decreased R-L, collagen deposition, and airway wall thickening. Moreover, Chromatography showed that salvianic acid A and caffeic acid levels were much higher in WE than EE, while rosmarinic acid was slightly lower; salvianolic acid B and tanshinone IIA levels were much higher in EE than WE. Interestingly, caffeic acid and rosmarinic acid were more potent in reducing E-cadherin and vimentin levels in TGF-beta 1-induced BEAS-2B cells, and alpha-SMA and COL1A1 amounts in TGF-beta 1-induced MRC-5 cells. Conclusions: Both S. miltiorrhiza WE and EE alleviate airway inflammation in mice with OVA-sensitized allergic asthma. S. miltiorrhiza WE is more potent in reducing responsiveness and airway remodeling.