Dioscin prevents LPS‑induced acute lung injury through inhibiting the TLR4/MyD88 signaling pathway via upregulation of HSP70

Zeng,Huiqing; Yang,Lijuan; Zhang,Xiaobin; Chen,Yan; Cai,Jianghang

doi:10.3892/mmr.2018.8667

Dioscin prevents LPS‑induced acute lung injury through inhibiting the TLR4/MyD88 signaling pathway via upregulation of HSP70

Authors:
- Huiqing Zeng
- Lijuan Yang
- Xiaobin Zhang
- Yan Chen
- Jianghang Cai
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Affiliations: Department of Respiration Medicine, Zhongshan Hospital of Xiamen University, P.R. China, Basic Medical College, Fujian Medical University, Xiamen, Fujian 361004, P.R. China
Published online on: March 1, 2018 https://doi.org/10.3892/mmr.2018.8667
Pages: 6752-6758

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Abstract

Dioscin, as a type of important natural steroidal saponin, has widespread sources, primarily from the fenugreek plant, which is an important raw material in the production of synthetic steroid hormone drugs. Dioscin has anti‑tumor, anti‑inflammatory, antioxidant and other significant pharmacological effects with high medicinal value. The present work aimed to research the protective effect and underlying mechanisms by which dioscin prevents acute lung injury (ALI). Mice were injected with 5 mg/kg LPS to induce lung injury. Mice were treated with dioscin (20, 40 and 60 mg/kg) following LPS‑induced lung injury. Treatment with dioscin significantly decreased total number of alveolar macrophages, water content of lung and total protein concentration in ALI mice. Dioscin treatment significantly suppressed the ALI‑induced interleukin (IL)‑1B, IL‑6, tumor necrosis factor‑α, nuclear factor (NF)‑κB, myeloperoxidase, interferon‑γ and intercellular adhesion molecule‑1 activities in ALI rats. Following this, the authors identified that dioscin significantly also suppressed cyclooxygenase‑2, heat shock protein 70, Toll‑like receptor 4, MyD88 and NF‑κB protein expression in ALI rats. The results suggested that dioscin prevents LPS‑induced ALI through inhibiting the TLR4/MyD88 signaling pathway via upregulation of HSP70.

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1	Krupa A, Fol M, Rahman M, Stokes KY, Florence JM, Leskov IL, Khoretonenko MV, Matthay MA, Liu KD, Calfee CS, et al: Silencing Bruton's tyrosine kinase in alveolar neutrophils protects mice from LPS/immune complex-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol. 307:L435–L448. 2014. View Article : Google Scholar : PubMed/NCBI
2	Wang Q, Wang J, Hu M, Yang Y, Guo L and Xu J, Lei C, Jiao Y and Xu J: Uncoupling protein 2 increases susceptibility to lipopolysaccharide-induced acute lung injury in mice. Mediators Inflamm. 2016:91542302016. View Article : Google Scholar : PubMed/NCBI
3	Bohman JK, Vogt MN and Hyder JA: Retrospective report of contraindications to extracorporeal membrane oxygenation (ECMO) among adults with acute respiratory distress syndrome (ARDS). Heart Lung. 45:227–231. 2016. View Article : Google Scholar : PubMed/NCBI
4	Xu X, Liu N, Zhang YX, Cao J, Wu D, Peng Q, Wang HB and Sun WC: The protective effects of HJB-1, a derivative of 17-Hydroxy-Jolkinolide B, on LPS-Induced acute distress respiratory syndrome mice. Molecules. 21:772016. View Article : Google Scholar : PubMed/NCBI
5	Rafat N, Dacho C, Kowanetz G, Betzen C, Tönshoff B, Yard B and Beck G: Bone marrow-derived progenitor cells attenuate inflammation in lipopolysaccharide-induced acute respiratory distress syndrome. BMC Res Notes. 7:6132014. View Article : Google Scholar : PubMed/NCBI
6	Petroni RC, Biselli PJ, de Lima TM, Theobaldo MC, Caldini ET, Pimentel RN, Barbeiro HV, Kubo SA, Velasco IT and Soriano FG: Hypertonic saline (NaCl 7.5%) reduces LPS-Induced acute lung Injury in rats. Inflammation. 38:2026–2035. 2015. View Article : Google Scholar : PubMed/NCBI
7	McKallip RJ, Ban H and Uchakina ON: Treatment with the hyaluronic Acid synthesis inhibitor 4-methylumbelliferone suppresses LPS-induced lung inflammation. Inflammation. 38:1250–1259. 2015. View Article : Google Scholar : PubMed/NCBI
8	Krupa A, Fudala R, Florence JM, Tucker T, Allen TC, Standiford TJ, Luchowski R, Fol M, Rahman M, Gryczynski Z, et al: Bruton's tyrosine kinase mediates FcγRIIa/Toll-like receptor-4 receptor crosstalk in human neutrophils. Am J Respir Cell Mol Biol. 48:240–249. 2013. View Article : Google Scholar : PubMed/NCBI
9	Han LP, Li CJ, Sun B, Xie Y, Guan Y, Ma ZJ and Chen LM: Protective effects of celastrol on diabetic liver injury via TLR4/MyD88/NF-κB signaling pathway in Type 2 diabetic rats. J Diabetes Res. 2016:26412482016. View Article : Google Scholar : PubMed/NCBI
10	Chen S, Yuan J, Yao S, Jin Y, Chen G, Tian W, Xi J, Xu Z, Weng D and Chen J: Lipopolysaccharides may aggravate apoptosis through accumulation of autophagosomes in alveolar macrophages of human silicosis. Autophagy. 11:2346–2357. 2015. View Article : Google Scholar : PubMed/NCBI
11	Zhang Y, Shan P, Srivastava A, Jiang G, Zhang X and Lee PJ: An endothelial Hsp70-TLR4 axis limits Nox3 expression and protects against oxidant injury in lungs. Antioxid Redox Signal. 24:991–1012. 2016. View Article : Google Scholar : PubMed/NCBI
12	Lunova M, Zizer E, Kucukoglu O, Schwarz C, Dillmann WH, Wagner M and Strnad P: Hsp72 overexpression accelerates the recovery from caerulein-induced pancreatitis. PLoS One. 7:e399722012. View Article : Google Scholar : PubMed/NCBI
13	Aschkenasy G, Bromberg Z, Raj N, Deutschman CS and Weiss YG: Enhanced Hsp70 expression protects against acute lung injury by modulating apoptotic pathways. PLoS One. 6:e269562011. View Article : Google Scholar : PubMed/NCBI
14	Tao X, Wan X, Xu Y, Xu L, Qi Y, Yin L, Han X, Lin Y and Peng J: Dioscin attenuates hepatic ischemia-reperfusion injury in rats through inhibition of oxidative-nitrative stress, inflammation and apoptosis. Transplantation. 98:604–611. 2014. View Article : Google Scholar : PubMed/NCBI
15	Zhao X, Xu L, Zheng L, Yin L, Qi Y, Han X, Xu Y and Peng J: Potent effects of dioscin against gastric cancer in vitro and in vivo. Phytomedicine. 23:274–282. 2016. View Article : Google Scholar : PubMed/NCBI
16	Qu X, Zhai Z, Liu X, Li H, Ouyang Z, Wu C, Liu G, Fan Q, Tang T, Qin A and Dai K: Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the Akt signaling cascades. Biochem Biophys Res Commun. 443:658–665. 2014. View Article : Google Scholar : PubMed/NCBI
17	Wu DD, Pan PH, Liu B, Su XL, Zhang LM, Tan HY, Cao Z, Zhou ZR, Li HT, Li HS, et al: Inhibition of alveolar macrophage pyroptosis reduces Lipopolysaccharide-induced acute lung injury in mice. Chin Med J (Engl). 128:2638–2645. 2015. View Article : Google Scholar : PubMed/NCBI
18	Jones HD, Crother TR, Gonzalez-Villalobos RA, Jupelli M, Chen S, Dagvadorj J, Arditi M and Shimada K: The NLRP3 inflammasome is required for the development of hypoxemia in LPS/mechanical ventilation acute lung injury. Am J Respir Cell Mol Biol. 50:270–280. 2014.PubMed/NCBI
19	Haitsma JJ, Lachmann B and Papadakos PJ: Additives in intravenous anesthesia modulate pulmonary inflammation in a model of LPS-induced respiratory distress. Acta Anaesthesiol Scand. 53:176–182. 2009. View Article : Google Scholar : PubMed/NCBI
20	Takahashi M, Chen-Yoshikawa TF, Menju T, Ohata K, Kondo T, Motoyama H, Hijiya K, Aoyama A and Date H: Inhibition of Toll-like receptor 4 signaling ameliorates lung ischemia-reperfusion injury in acute hyperglycemic conditions. J Heart Lung Transplant. 35:815–822. 2016. View Article : Google Scholar : PubMed/NCBI
21	Wu S, Xu H, Peng J, Wang C, Jin Y, Liu K, Sun H and Qin J: Potent anti-inflammatory effect of dioscin mediated by suppression of TNF-α-induced VCAM-1, ICAM-1and EL expression via the NF-κB pathway. Biochimie. 110:62–72. 2015. View Article : Google Scholar : PubMed/NCBI
22	Zhang Z, Chen N, Liu JB, Wu JB, Zhang J, Zhang Y and Jiang X: Protective effect of resveratrol against acute lung injury induced by lipopolysaccharide via inhibiting the myd88-dependent Toll-like receptor 4 signaling pathway. Mol Med Rep. 10:101–106. 2014. View Article : Google Scholar : PubMed/NCBI
23	Wan Q, Wang H, Han X, Lin Y and Yang Y, Gu L, Zhao J, Wang L, Huang L, Li Y and Yang Y: Baicalin inhibits TLR7/MYD88 signaling pathway activation to suppress lung inflammation in mice infected with influenza A virus. Biomed Rep. 2:437–441. 2014. View Article : Google Scholar : PubMed/NCBI
24	Jiang Q, Yi M, Guo Q, Wang C, Wang H, Meng S, Liu C, Fu Y, Ji H and Chen T: Protective effects of polydatin on lipopolysaccharide-induced acute lung injury through TLR4-MyD88-NF-κB pathway. Int Immunopharmacol. 29:370–376. 2015. View Article : Google Scholar : PubMed/NCBI
25	Liu M, Xu Y, Han X, Yin L, Xu L, Qi Y, Zhao Y, Liu K and Peng J: Dioscin alleviates alcoholic liver fibrosis by attenuating hepatic stellate cell activation via the TLR4/MyD88/NF-κB signaling pathway. Sci Rep. 5:180382015. View Article : Google Scholar : PubMed/NCBI
26	Lyons MM, Raj NN, Chittams JL, Kilpatrick L and Deutschman CS: TAT-HSP70 attenuates experimental lung injury. Shock. 43:582–588. 2015. View Article : Google Scholar : PubMed/NCBI
27	Zhang ZJ, Zhou CY, Luo YJ and Xiong HW: Expression of heat shock protein 70 in lung tissues of acute paraquat poisoned rats and intervention of ulinastatin. World J Emerg Med. 1:229–233. 2010.PubMed/NCBI
28	Lin HJ, Wang CT, Niu KC, Gao C, Li Z, Lin MT and Chang CP: Hypobaric hypoxia preconditioning attenuates acute lung injury during high-altitude exposure in rats via up-regulating heat-shock protein 70. Clin Sci (Lond). 121:223–231. 2011. View Article : Google Scholar : PubMed/NCBI
29	Qi M, Zheng L, Qi Y, Han X, Xu Y, Xu L, Yin L, Wang C, Zhao Y, Sun H, et al: Dioscin attenuates renal ischemia/reperfusion injury by inhibiting the TLR4/MyD88 signaling pathway via up-regulation of HSP70. Pharmacol Res. 100:341–352. 2015. View Article : Google Scholar : PubMed/NCBI