Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Chinese Medicine
Published in: Chinese Medicine 1/2018

Open Access 01-12-2018 | Research

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

Authors: Chengliang Huang, Xu Wu, Shengpeng Wang, Wenjun Wang, Fang Guo, Yuanyuan Chen, Bi Pan, Ming Zhang, Xianming Fan

Published in: Chinese Medicine | Issue 1/2018

Login to get access

Abstract

Background

Idiopathic 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.

Methods

A 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.

Results

Both 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.

Conclusions

SML 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.
Appendix
Available only for authorised users
Literature
1.
Ahluwalia N, Shea BS, Tager AM. New therapeutic targets in idiopathic pulmonary fibrosis. Aiming to rein in runaway wound-healing responses. Am J Respir Crit Care. 2014;190:867–78.CrossRef
2.
Sgalla G, Biffi A, Richeldi L. Idiopathic pulmonary fibrosis: diagnosis, epidemiology and natural history. Respirology. 2016;21:427–37.CrossRefPubMed
3.
Huang H, Peng X, Zhong C. Idiopathic pulmonary fibrosis: the current status of its epidemiology, diagnosis, and treatment in China. Intractable Rare Dis Res. 2013;2:88–93.PubMedPubMedCentral
4.
5.
Wuyts WA, Agostini C, Antoniou KM, Bouros D, Chambers RC, Cottin V, Egan JJ, Lambrecht BN, Lories R, Parfrey H. The pathogenesis of pulmonary fibrosis: a moving target. Eur Respir J. 2013;41:1207–18.CrossRefPubMed
6.
Coward WR, Saini G, Jenkins G. The pathogenesis of idiopathic pulmonary fibrosis. Ther Adv Respir Dis. 2010;4:367.CrossRefPubMed
7.
Song X, Liu W, Xie S, Wang M, Cao G, Mao C, Lv C. All-transretinoic acid ameliorates bleomycin-induced lung fibrosis by downregulating the TGF-β1/Smad3 signaling pathway in rats. J Wuhan Univ Sci Technol. 2013;93:1219–31.
8.
Zhao Y, Tian B, Sadygov RG, Zhang Y, Brasier AR. Integrative proteomic analysis reveals reprograming tumor necrosis factor signaling in epithelial mesenchymal transition. J Proteomics. 2016;148:126–38.CrossRefPubMedPubMedCentral
9.
Kabel AM, Omar MS, Elmaaboud MAA. Amelioration of bleomycin-induced lung fibrosis in rats by valproic acid and butyrate: role of nuclear factor kappa-B, proinflammatory cytokines and oxidative stress. Int Immunopharmacol. 2016;39:335–42.CrossRefPubMed
10.
Raghu G, Brown KK, Costabel U, Cottin V, Du BR, Lasky JA, Thomeer M, Utz JP, Khandker RK, Mcdermott L. Treatment of idiopathic pulmonary fibrosis with etanercept: an exploratory, placebo-controlled trial. Expert Opin Emerg Drugs. 2008;178:948.
11.
Turgut NH, Haki K, Sahende E, Koksal D, Huseyin G, Emre A. The protective effect of naringin against bleomycin-induced pulmonary fibrosis in Wistar rats. Pulm Med. 2016;2016:1–12.CrossRef
12.
Altintas N, Erboga M, Aktas C, Bilir B, Aydin M, Sengul A, Ates Z, Topcu B, Gurel A. Protective effect of infliximab, a tumor necrosis factor-alfa inhibitor, on bleomycin-induced lung fibrosis in rats. Inflammation. 2016;39:65–78.CrossRefPubMed
13.
Chitra P, Saiprasad G, Manikandan R, Sudhandiran G. Berberine attenuates bleomycin induced pulmonary toxicity and fibrosis via suppressing NF-κB dependant TGF-β activation: a biphasic experimental study. Toxicol Lett. 2013;219:178–93.CrossRefPubMed
14.
Lei L, Wei L, Zhuang M, Zhenhua L. Oxymatrine attenuates bleomycin-induced pulmonary fibrosis in mice via the inhibition of inducible nitric oxide synthase expression and the TGF-β/Smad signaling pathway. Int J Mol Med. 2012;29:815.
15.
Ti DY, Han YL, Yang GY, Yang XL. Clinical observation of efficacy of Danshen and ligustrazine on 86 patients with idiopathic pulmonary fibrosis. Heilongjiang Med J. 2010;23:102–3.
16.
Guo F, Fan XM. Therapeutic effect of Danshen and ligustrazine for fibrosis. Med Recapitulate. 2010;16:2087–90.
17.
Pan Y, Fu H, Kong Q, Xiao Y, Shou Q, Chen H, Ke Y, Chen M. Prevention of pulmonary fibrosis with salvianolic acid a by inducing fibroblast cell cycle arrest and promoting apoptosis. J Ethnopharmacol. 2014;155:1589–96.CrossRefPubMed
18.
Lu SJ, Liu YN. Study of Salvia miltiorrhiza on bleomycin-induced pulmonary fibrosis in mice. Chin J Clin Pharmacol Ther. 2005;10:514–7.
19.
Liu M, Xu H, Zhang L, Zhang C, Yang L, Ma E, Liu L, Li Y. Salvianolic acid B inhibits myofibroblast transdifferentiation in experimental pulmonary fibrosis via the up-regulation of Nrf2. Biochem Biophys Res Commun. 2018;495:325–31.CrossRefPubMed
20.
Li YF, Yu Y. Effect of ligustrazine on pulmonary fibrosis caused by hyperoxia in neonatal rats. J Appl Clin Pediatr. 2009;24:126–8.
21.
Zhao J, Wang HM, Wang HZ. The protective effect of ligustrazine on bleomycin-induced pulmonary fibrosis. J Liaoning Med Univ. 2006;27:11–3.
22.
Wu X, Zhang F, Xiong X, Lu C, Lian N, Lu Y, Zheng S. Tetramethylpyrazine reduces inflammation in liver fibrosis and inhibits inflammatory cytokine expression in hepatic stellate cells by modulating NLRP3 inflammasome pathway. IUBMB Life. 2015;67:312–21.CrossRefPubMed
23.
Mai AZ, Zaki HF, El-Brairy AI, Kenawy SA. Pyrrolidinedithiocarbamate attenuates bleomycin-induced pulmonary fibrosis in rats: modulation of oxidative stress, fibrosis, and inflammatory parameters. Exp Lung Res. 2016;42:408–16.CrossRef
24.
Della LV, Cecchettini A, Del RS, Morales MA. Bleomycin in the setting of lung fibrosis induction: From biological mechanisms to counteractions. Pharmacol Res. 2015;97:122–30.CrossRef
25.
Kandhare AD, Bodhankar SL, Mohan V, Thakurdesai PA. Effect of glycosides based standardized fenugreek seed extract in bleomycin-induced pulmonary fibrosis in rats: decisive role of Bax, Nrf2, NF-κB, Muc5ac, TNF-α and IL-1β. Chem Biol Interact. 2015;237:151–65.CrossRefPubMed
26.
Tian K, Lin L, Jia Z, Guo X, Zhang L. Preventive effect of chrysin on bleomycin-induced lung fibrosis in rats. Inflammation. 2014;37:2116–24.CrossRef
27.
Antoniou KM, Alexandrakis MG, Siafakas NM, Bouros D. Cytokine network in the pathogenesis of idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffuse Lung Dis. 2005;22:91–104.PubMed
28.
Carré P, Léophonte P. Cytokines and pulmonary fibroses. Rev Mal Respir. 1993;10:193–207.PubMed
29.
Jin SF, Ma HL, Liu ZL, Fu ST, Zhang CP, He Y. XL413, a cell division cycle 7 kinase inhibitor enhanced the anti-fibrotic effect of pirfenidone on TGF-β1-stimulated C3H10T1/2 cells via Smad2/4. Exp Cell Res. 2015;339:289–99.CrossRefPubMed
30.
Soumyakrishnan S, Divya T, Kalayarasan S, Sriram N, Sudhandiran G. Daidzein exhibits anti-fibrotic effect by reducing the expressions of proteinase activated receptor 2 and TGFβ1/smad mediated inflammation and apoptosis in bleomycin-induced experimental pulmonary fibrosis. Biochimie. 2014;103:23–36.CrossRefPubMed
31.
Zhan H, Huang F, Ma W, Zhao Z, Zhang H, Zhang C. Protective effect of ginsenoside rg1 on bleomycin-induced pulmonary fibrosis in rats: involvement of caveolin-1 and TGF-β1 signal pathway. Biol Pharm Bull. 2016;39:1284–92.CrossRefPubMed
Metadata
Title
Combination of Salvia miltiorrhiza and ligustrazine attenuates bleomycin-induced pulmonary fibrosis in rats via modulating TNF-α and TGF-β
Authors
Chengliang Huang
Xu Wu
Shengpeng Wang
Wenjun Wang
Fang Guo
Yuanyuan Chen
Bi Pan
Ming Zhang
Xianming Fan
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Chinese Medicine / Issue 1/2018
Electronic ISSN: 1749-8546
DOI
https://doi.org/10.1186/s13020-018-0194-9

Other articles of this Issue 1/2018

Chinese Medicine 1/2018 Go to the issue

Review

Internationalization of traditional Chinese medicine: current international market, internationalization challenges and prospective suggestions

Review

SWOT analysis and revelation in traditional Chinese medicine internationalization

Research

Different modulation of Panax notoginseng on the absorption profiling of triptolide and tripterine from Tripterygium wilfordii in rat intestine

Research

Cost-consequence analysis of salvianolate injection for the treatment of coronary heart disease

Research

Wentong decoction cures allergic bronchial asthma by regulating the apoptosis imbalance of EOS

Research

Effects of different principles of Traditional Chinese Medicine treatment on TLR7/NF-κB signaling pathway in influenza virus infected mice