Effects of Ginkgo biloba leaf extract, shenmai and matrine on a human embryonic lung fibroblast fibrosis model

Zhang,Xingcai; Cai,Yuli

doi:10.3892/etm.2018.6698

Effects of Ginkgo biloba leaf extract, shenmai and matrine on a human embryonic lung fibroblast fibrosis model

Authors:
- Xingcai Zhang
- Yuli Cai
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Affiliations: Department of Lung Diseases, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250011, P.R. China, Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250011, P.R. China
Published online on: September 5, 2018 https://doi.org/10.3892/etm.2018.6698
Pages: 4289-4295

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Abstract

The aim of the present study was to investigate the effects of Ginkgo biloba leaf extract (GBLE), shenmai (S), and matrine (M) on human embryonic lung fibroblasts (HELFs). HELFs were allocated into the following groups: Group A (control group), group B [transforming growth factor β1 (TGF‑β1) model group], groups C1‑3 (TGF‑β1 + low‑, moderate‑ and high‑dose GBLE), groups D1‑3 (TGF‑β1 + low‑, moderate‑ and high‑dose S) and groups E1‑3 (TGF‑β1 + low‑, moderate‑ and high‑dose oM). Cell proliferation was assessed with an MTT assay and apoptosis was measured by annexin V/propidium iodide double staining and flow cytometry analysis. Collagen type I (COL‑I), collagen type III (COL‑III), α‑smooth muscle actin (α‑SMA) and extracellular superoxide dismutase (ECSOD) mRNA expression levels were measured using semi‑quantitative reverse transcription‑polymerase chain reaction, and protein content was measured using ELISA. The cell growth inhibition rates of the S groups were significantly higher than those of the other treatment groups (P<0.05). The rate of apoptosis was significantly increased in the treatment groups compared with the model group (P<0.05), and S induced a significant increase in HELF apoptosis compared with the other treatment groups (P<0.05). The mRNA and protein expressions of COL‑III, COL‑I and α‑SMA in the GBLE, S and M groups were significantly decreased, while the expression of ECSOD was significantly increased when compared with the model group (P<0.05). In conclusion, GBLE, S and M inhibited the pro‑fibrotic role of TGF‑β1 by targeting different steps in TGF‑β1‑mediated fibrosis.

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1	Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, et al: An official ATS/ERS/JRS/ALAT statement: Idiopathic pulmonary fibrosis: Evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 183:788–824. 2011. View Article : Google Scholar : PubMed/NCBI
2	King TE Jr, Albera C, Bradford WZ, Costabel U, Hormel P, Lancaster L, Noble PW, Sahn SA, Szwarcberg J, Thomeer M, et al: Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): A multicentre, randomized, placebo-controlled trial. Lancet. 374:222–228. 2009. View Article : Google Scholar : PubMed/NCBI
3	Raghu G, Rochwerg B, Zhang Y, Garcia CA, Azuma A, Behr J, Brozek JL, Collard HR, Cunningham W, Homma S, et al: An official ATS/ERS/JRS/ALAT clinical practice guideline: Treatment of idiopathic pulmonary fibrosis An update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 192:e3–e19. 2015. View Article : Google Scholar : PubMed/NCBI
4	Merrill WW and Reynoldss HY: Bronchial lavage in inflammatory lung disease. Clin Chest Med. 4:71–84. 1983.PubMed/NCBI
5	Katzenstein AL and Myers JL: Idopathic pulmonary fibrosis: Clinical relevance of pathologic classification. Am J Respir Crit Care Med. 157:1301–1315. 1998. View Article : Google Scholar : PubMed/NCBI
6	Munger JS, Huang X, Kawakatsu H, Griffiths MJ, Dalton SL, Wu J, Pittet JF, Kaminski N, Garat C, Matthay MA, et al: The integrin alpha v beta 6 binds and activates latent TGF beta 1: A mechanism for regulating pulmonary inflammation and fibrosis. Cell. 96:319–328. 1999. View Article : Google Scholar : PubMed/NCBI
7	Remy-Jardin M, Giraud F, Remy J, Copin MC, Gosselin B and Duhamel A: Importance of groundglass attenuation in chronic diffuse infiltrative lung disease: Pathologic-CT correlation. Radiology. 189:693–698. 1993. View Article : Google Scholar : PubMed/NCBI
8	Baroke E, Gauldie J and Kolb M: New treatment and markers of prognosis for idiopathic pulmonary fibrosis: Lessons learned from translational research. Expert Rev Respir Med. 7:465–478. 2013. View Article : Google Scholar : PubMed/NCBI
9	Selman M, King TE and Pardo A: American Thoracic Society; European Respiratory Society and American College of Chest Physicians: Idiopathic pulmonary fibrosis: Prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann Intern Med. 134:136–151. 2001. View Article : Google Scholar : PubMed/NCBI
10	Noble PW, Barkauskas CE and Jiang D: Pulmonary fibrosis: Patterns and perpetrators. J Clin Invest. 122:2756–2762. 2012. View Article : Google Scholar : PubMed/NCBI
11	Lawson WE, Cheng DS, Degryse AL, Tanjore H, Polosukhin VV, Xu XC, Newcomb DC, Jones BR, Roldan J, Lane KB, et al: Endoplasmic reticulum stress enhances fibrotic remodeling in the lungs. Pro Natl Acad Sci USA. 108:10562–10567. 2011. View Article : Google Scholar
12	Lawson WE, Crossno PF, Polosukhin VV, Roldan J, Cheng DS, Lane KB, Blackwell TR, Xu C, Markin C, Ware LB, et al: Endoplasmic reticulum stress in alveolar epithelial cells is prominent in IPF: Association with altered surfactant protein processing and herpesvirus infection. Am J Physiol Lung Cell Mol Physiol. 294:L1119–L1126. 2008. View Article : Google Scholar : PubMed/NCBI
13	Chen CY, Peng WH, Wu LC, Wu CC and Hsu SL: Luteolin ameliorates experimental lung fibrosis both in vivo and in vitro: Implications for therapy of lung fibrosis. J Agric Food Chem. 58:11653–11661. 2010. View Article : Google Scholar : PubMed/NCBI
14	Broekelmann TJ, Limper AH, Colby TV and McDonald JA: Transforming growth factor beta-1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. Proc Natl Acad Sci USA. 88:6642–6646. 1991. View Article : Google Scholar : PubMed/NCBI
15	Ho YY, Lagares D, Tager AM and Kapoor M: Fibrosis-a lethal component of systemic sclerosis. Nat Rev Rheumatol. 10:390–402. 2014. View Article : Google Scholar : PubMed/NCBI
16	Park S and Lee EJ: Recent advances in idiopathic pulmonary fibrosis. Tuber Respir Dis (Seoul). 74:1–6. 2013. View Article : Google Scholar
17	Chen J, He B and Liu X: Experimental study on effect of folium Ginkgo biloba in treating pulmonary interstitial fibrosis in rats. Zhongguo Zhong Xi Yi Jie He Za Zhi. 20:441–443. 2000.(In Chinese). PubMed/NCBI
18	Xiao-Jiao LI, Guo G, Cheng ZX, Hui-Yun LI, Zhang HS and Zhong QC: Effect of Shenmai Kaifei San on the level of IL-6, TNF-α and TGF-β1 in patients with systemic sclerosis complicated by pulmonary fibrosis. Rheumatism and Arthritis. 5:10–12. 2016.(In Chinese).
19	Ma X, Chen R, Liu X, Xie J, Si K and Duan L: Effects of matrine on JAK-STAT signaling transduction pathways in bleomycin-induced pulmonary fibrosis. Afr J Tradit Complement Altern Med. 10:442–448. 2013.PubMed/NCBI
20	He WW, Zhang DP and Xie N: Effect of curcumin on proliferation, apoptosis and the extracellular matrix of human embryonic lung fibroblast. Pharm Clin Res. 21:322–325. 2013.
21	Thannickal VJ and Horowitz JC: Evolving concepts of apoptosis in idiopathic pulmonary fibrosis. Proc Am Thorc Soc. 3:350–356. 2006. View Article : Google Scholar
22	Nkyimbeng T, Ruppert C, Shiomi T, Dahal B, Lang G, Seeger W, Okada Y, D'Armiento J and Günther A: Pivotal role of matrix metalloproteinase 13 in extracellular matrix turnover in idiopathic pulmonary fibrosis. PLoS One. 8:e732792013. View Article : Google Scholar : PubMed/NCBI
23	Tsukui T, Ueha S, Abe J, Hashimoto S, Shichino S, Shimaoka T, Shand FH, Arakawa Y, Oshima K, Hattori M, et al: Qualitative rather than quantitative changes are hallmarks of fibroblasts in bleomycin-induced pulmonary fibrosis. Am J Pathol. 183:758–773. 2013. View Article : Google Scholar : PubMed/NCBI
24	Kliment CR and Oury TD: Oxidative stress, extracellular matrix targets, and idiopathic pulmonary fibrosis. Free Radic Biol Med. 49:707–717. 2010. View Article : Google Scholar : PubMed/NCBI
25	Meltzer EB and Noble PW: Idiopathic pulmonary fibrosis. Orphanet J Rare Dis. 3:82008. View Article : Google Scholar : PubMed/NCBI
26	Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat ML and Gabbiani G: The myofibroblast: One function, multiple origins. Am J Pathol. 170:1807–1816. 2007. View Article : Google Scholar : PubMed/NCBI
27	Zheng L, Zhou Z, Lin L, Alber S, Watkins S, Kaminski N, Choi AM and Morse D: Carbon monoxide modulates alpha-smooth muscle actin and small proline rich-1a expression in fibrosis. Am J Respir Cell Mol Biol. 41:85–92. 2009. View Article : Google Scholar : PubMed/NCBI
28	Daniil ZD, Papageorgiou E, Koutsokera A, Kostikas K, Kiropoulos T, Papaioannou AI and Gourgoulianis KI: Serum levels of oxidative stress as a marker of disease severity in idiopathic pulmonary fibrosis. Pulm Pharmacol Ther. 21:26–31. 2008. View Article : Google Scholar : PubMed/NCBI
29	Bowler RP and Crapo JD: Oxidative stress in airways: Is there a role for extracellular superoxide dismutase. Am J Respir Crit Care Med. 166:S38–S43. 2002. View Article : Google Scholar : PubMed/NCBI
30	Serra V, von Zglinicki T, Lorenz M and Saretzki G: Extracellular superoxide dismutase is a major antioxidant in human fibroblasts and slows telomere shortening. J BiolChem. 278:6824–6830. 2003.
31	Chen X and Chen WZ: Recent phremacological progress of Ginkgobiloba extract for cardiovascular and neuronal disease. Chin J Integ Trad West Med. 2:3001996.(In Chinese).
32	Isah T: Rethinking Ginkgo biloba L: Medicinal uses and conservation. Pharmacogn Rev. 9:140–148. 2015. View Article : Google Scholar : PubMed/NCBI
33	Wang CG, Dai Y, Li DL and Ma KY: Ginkgo biloba leaf extract action in scavenging free radicals and reducing mutagenicity and toxicity of cigarette smoke in vivo. J Environ Sci Health A Tox Hazard Subst Environ Eng. 45:498–505. 2010. View Article : Google Scholar : PubMed/NCBI
34	Akiba S, Chiba M, Mukaida Y, Tamura A and Sato T: The leaf extract of Ginkgo Biloba L. suppresses oxidized LDL-stimulated fibronectin production through an antioxidant action in rat mesangial cells. Br J Pharmacol. 142:419–424. 2004. View Article : Google Scholar : PubMed/NCBI
35	Su X, Ma Y, Huang R, Wang X and Wang Y: Effects of shenmai injection on blood SOD activity and MDA level in senile patients with coronary heart disease. J Tradit Chin Med. 25:50–53. 2005.PubMed/NCBI
36	Zhao LM, Ma LJ, Zhang LX and Wu JZ: Shenmai injection inhibiting the extracellular signal regulated kinase-lnduced human airway smooth muscle proliferation in asthma. Chin J Integr Med. 16:331–336. 2010. View Article : Google Scholar : PubMed/NCBI
37	Yu YH, Cui NQ, Fu Q and Li J: Change of TH1/TH2 cytokine equilibrium in rats with severe sepsis and therapeutic effect of recombinant interleukin-12 and shenmai injection. Chin J Integr Med. 11:136–141. 2005. View Article : Google Scholar : PubMed/NCBI
38	Li Y, Wang B, Zhou C and Bi Y: Matrine induces apoptosis in angiotensin II-stimulated hyperplasia of cardiac fibroblasts: Effects on Bcl-2/Bax expression and caspase-3 activation. Basic Clin Pharmacol Toxicol. 101:1–8. 2007. View Article : Google Scholar : PubMed/NCBI
39	Jung E, Lee J, Huh S, Lee J, Hwang H, Kim Y, Kim YW, Byun SY and Park D: Matrine inhibits PMA-induced MMP-1 expression in human dermal fibroblasts. Biofactors. 33:121–128. 2008. View Article : Google Scholar : PubMed/NCBI