Combination of Salvia miltiorrhiza and ligustrazine attenuates bleomycin-induced pulmonary fibrosis in rats via modulating TNF-α and TGF-β

Abstract

BackgroundIdiopathic pulmonary fibrosis (IPF), a chronic, progressive, fibrosing interstitial lung disease, is associated with extremely poor prognosis, and lacks effective treatment. The frequently used immunosuppressive therapies such as dexamethasone (DEX) are often associated with side effects. Recently, combination of two Chinese herbal medicine preparations, Salvia miltiorrhiza and ligustrazine (SML), serves as an alternative medicine for treatment of IPF in clinical practices in China. The aim of this study is to compare the anti-fibrotic effect of SML with that of DEX and to investigate the underlying mechanisms.MethodsA rat model of bleomycin (BLM) induced pulmonary fibrosis was used in this study. Ninety rats were assigned to six groups: control group; BLM-group; BLM and dexamethasone group (BLM + DEX); BLM + low-dose SML; BLM + medium-dose SML and BLM + high-dose SML. Rats were sacrificed on day 7, 14 and 28 after treatment. The extent of alveolitis and fibrosis was observed by H&E and Masson’s trichrome staining. The expressions of TNF-α, TGF-β1 and SMAD4 were determined and quantified by immunohistochemical analysis. The serum levels of TNF-α and TGF-β1 were further quantified by ELISA kits.ResultsBoth DEX and SML treatment attenuated BLM-induced lung injury and pathological collagen deposition in rats, showing improved alveolitis and fibrosis scores on day 7, 14, 28, compared to the BLM group (p < 0.05). The anti-fibrotic effect of SML was in a dose-dependent manner, and the medium- and high-dose SML showed comparable effect with DEX on day 14 and 28. Expressions of TNF-α, TGF-β1 and SMAD4 were significantly decreased in the DEX- and SML-treated groups compared with BLM groups (p < 0.05). Medium- and high-dose SML showed better repression of TNF-α, TGF-β1 and SMAD4 expression compared to DEX at all time points (p < 0.05). Notably, SML at different dosages did not affect serum levels of alanine aminotransferase, aspartate aminotransferase and creatinine.ConclusionsSML is safe and effective in repressing BLM-induced pulmonary fibrosis, which might be through modulating the expression of TNF-α and TGF-β1. Our findings advocate the use of SML for IPF, which might serve as a better treatment option over DEX.Electronic supplementary materialThe online version of this article (10.1186/s13020-018-0194-9) contains supplementary material, which is available to authorized users.

Schisandra Inhibit Bleomycin-Induced Idiopathic Pulmonary Fibrosis in Rats via Suppressing M2 Macrophage Polarization

“…This phenomenon suggests that M2 is a potential therapeutic target for IPF. As a potent and long-acting glucocorticoid, dexamethasone (Dex) can suppress the expressions of inflammatory cytokines, such as TNF- α , TGF- β 1, and platelet-derived growth factor (PDGF) in AMs, and downregulate the mRNA of monocyte chemotactic protein-1 (MCP-1) [ 16 – 19 ].…”

Pharmacokinetics of salvianolic acid B, rosmarinic acid and Danshensu in rat after pulmonary administration of Salvia miltiorrhiza polyphenolic acid solution

“…Salvia miltiorrhiza polyphenolic acid (SMPA) is the main active component of Salvia miltiorrhiza , including salvianolic acid B (Sal B), rosmarinic acid (Ros A) and Danshensu (DA) (Sun et al, ). In addition to its protective effect on the cardiovascular system (Ho & Hong, ), it also plays an important role in the treatment of lung diseases such as idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease (Huang et al, ).…”

Tetramethylpyrazine Nitrone Improved Motor Deficits and Alleviated Dystrophic Muscle Pathology in the &lt;i&gt;mdx&lt;/i&gt; Mouse Model of Duchenne Muscular Dystrophy

“…xiong), demonstrated activity to reduce liver fibrosis in a previous study [9]. TMP attenuated gastrocnemius (GAS) muscle atrophy by increasing the suppression of Ca 2+ /reactive oxygen species [10].…”