Browse > Article
http://dx.doi.org/10.4062/biomolther.2017.249

Therapeutic Potential of the Rhizomes of Anemarrhena asphodeloides and Timosaponin A-III in an Animal Model of Lipopolysaccharide-Induced Lung Inflammation  

Park, Byung Kyu (College of Pharmacy, Kangwon National University)
So, Kyung Su (College of Pharmacy, Kangwon National University)
Ko, Hye Jung (College of Pharmacy, Kangwon National University)
Kim, Hyun Joong (College of Pharmacy, Kangwon National University)
Kwon, Ki Sun (College of Pharmacy, Kangwon National University)
Kwon, Yong Soo (College of Pharmacy, Kangwon National University)
Son, Kun Ho (Department of Food and Nutrition, Andong National University)
Kwon, Soon Youl (Gyeongbuk Institute for Bio Industry)
Kim, Hyun Pyo (College of Pharmacy, Kangwon National University)
Publication Information
Biomolecules & Therapeutics / v.26, no.6, 2018 , pp. 553-559 More about this Journal
Abstract
Investigations into the development of new therapeutic agents for lung inflammatory disorders have led to the discovery of plant-based alternatives. The rhizomes of Anemarrhena asphodeloides have a long history of use against lung inflammatory disorders in traditional herbal medicine. However, the therapeutic potential of this plant material in animal models of lung inflammation has yet to be evaluated. In the present study, we prepared the alcoholic extract and derived the saponin-enriched fraction from the rhizomes of A. asphodeloides and isolated timosaponin A-III, a major constituent. Lung inflammation was induced by intranasal administration of lipopolysaccharide (LPS) to mice, representing an animal model of acute lung injury (ALI). The alcoholic extract (50-200 mg/kg) inhibited the development of ALI. Especially, the oral administration of the saponin-enriched fraction (10-50 mg/kg) potently inhibited the lung inflammatory index. It reduced the total number of inflammatory cells in the bronchoalveolar lavage fluid (BALF). Histological changes in alveolar wall thickness and the number of infiltrated cells of the lung tissue also indicated that the saponin-enriched fraction strongly inhibited lung inflammation. Most importantly, the oral administration of timosaponin A-III at 25-50 mg/kg significantly inhibited the inflammatory markers observed in LPS-induced ALI mice. All these findings, for the first time, provide evidence supporting the effectiveness of A. asphodeloides and its major constituent, timosaponin A-III, in alleviating lung inflammation.
Keywords
Anemarrhena asphodeloides; Timosaponin A-III; Lung inflammation; Cytokine;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Aaron, S. D., Vandemheen, K. L., Maltais, F., Field, S. K., Sin, D. D., Bourbeau, J., Marciniuk, D. D., FitzGerald, J. M., Nair, P. and Mallick, R. (2013) $TNF{\alpha}$ antagonists for acute exacerbations of COPD: a randomized double-blind controlled trial. Thorax 68, 142-148.   DOI
2 Agbabiaka, T. B., Guo, R. and Ernst, E. (2008) Pelargonium sidoides for acute bronchitis: a systematic review and meta-analysis. Phytomedicine 15, 378-385.   DOI
3 Al-Kassini, F. A. and Alhamad, E. H. (2013) A challenge to the seven widely believed concepts of COPD. Int. J. Chron. Obstruct. Pulmon. Dis. 8, 21-30.
4 Bae, G., Yu, J. R., Lee, J., Chang, J., and Seo, E. K. (2007) Identification of the nyasol and structurally related compounds as the active principles from Anemarrhena asphodeloides against respiratory syncytial virus (RSV). Chem. Biodiver. 4, 2231-2235.   DOI
5 Bae, K. (2000) The medicinal plants of Korea, pp. 546. Kyo-Hak Pub. Co., Seoul, Korea.
6 Barnes, P. J. (2014) Cellular and molecular mechanisms of chronic obstructive pulmonary disease. Clin. Chest Med. 35, 71-86.   DOI
7 Chai, O. H., Shon, D. H., Han, E. H., Kim, H. T. and Song, C. H. (2013) Effects of Anemarrhena asphodeloides on IgE-mediated passive cutaneous anaphylaxis, compound 48/80-induced systemic anaphylaxis and mast cell activation. Exp. Toxicol. Pathol. 65, 419-426.   DOI
8 Dentener, M. A., Creutzberg, E. C., Pennings, H. J., Rijkers, G. T., Mercken, E. and Wouters, E. F. (2008) Effect of inflimab on local and systemic inflammation in chronic obstructive pulmonary disease: a pilot study. Respiration 76, 275-282.   DOI
9 Garrido, G., Gonzalez, D., Lemus, Y., Delporte, C., and Delqado, R. (2006) Protective effects of a standard extract of Mangifera indica L. (VIMANG) against mouse ear edema and its inhibition of eicosanoid production in J774 murine macrophages. Phytomedicine 13, 412-418.   DOI
10 Jeffery, P. K. (2001) Remodeling in asthma and chronic obstructive lung disease. Am. J. Respir. Crit. Care Med. 164, S28-S38.   DOI
11 Jeong, J. J., Jang, S. E., Hyam, S. R., Han, M. J. and Kim, D. H. (2014) The rhizome mixture of Anemarrhena asphodeloides and Coptidis chinensis ameliorates acute and chronic colitis in mice by inhibiting the binding of lipopolysaccharide to TLR4 and IRAK1 phosphorylation. Evid. Based Complement. Alternat. Med. 2014, 809083.
12 Kawasaki, T. and Yamauchi, T. (1963) Saponins of timo (Anemarrhenae Rhizoma). II. Structure of timosaponin A-III. Chem. Pharm. Bull. 11, 1221-1224.   DOI
13 Kim, C. Y., Ahn, M. J. and Kim, J. (2006) Preparative isolation of mangiferin from Anemarrhena asphodeloides rhizomes by centrifugal partition chromatography. J. Liquid Chromat. Relat. Technol. 29, 869-875.   DOI
14 Lim, H. J., Jin, H.-K., Woo, E.-R., Lee, S. K. and Kim, H. P. (2013) The root barks of Morus alba and the flavonoid constituents inhibit airway inflammation. J. Ethnopharmacol. 149, 169-175.   DOI
15 Kim, H. P., Lim, H. and Kwon, Y. S. (2017) Therapeutic potential of medicinal plants and their constituents on lung inflammatory disorders. Biomol. Ther. (Seoul) 25, 91-104.   DOI
16 Lee, B., Trinh, H. T., Jung, K., Han, S. J. and Kim, D. H. (2010) Inhibitory effects of steroidal timosaponins isolated from the rhizomes of Anemarrhena asphodeloides against passive cutaneouos anaphylaxis reaction and pruritus. Immunopharmacol. Immunotoxicol. 32, 357-363.   DOI
17 Lee, S. H., Ryu, S. Y., Choi, S. U., No, Z., Kim, S. K., Lee, C. O. and Ahn, J. W. (1995) Antitumor agent from the rhizome of Anemarrhena asphodeloides. Saengyak Hakhoechi 26, 47-50.
18 Guo, R., Pittier, M. H. and Ernst, E. (2006) Herbal medicines for the treatment of COPD: a systematic review. Eur. Respir. J. 28, 330-338.   DOI
19 Lv, H., Zhu, C., Liao, Y., Gao, Y., Lu, G., Zhong, W., Zheng, Y., Chen, W. and Ci, X. (2015) Tenuigenin ameliorates acute lung injury by inhibiting $NF-{\kappa}B$ and MAPK signalling pathways. Respir. Physiol. Neurobiol. 216, 43-51.   DOI
20 Lim, S. M., Jeong, J. J., Kang, G. D., Kim, K. A., Choi, H. S. and Kim, D. H. (2015) Timosaponin AIII and its metabolite sarsasapogenin ameliorate colitis in mice by inhibiting $NF-{\kappa}B$ and MAPK activation and restoring Th17/Treg cell balance. Int. Immunopharmacol. 25, 493-503.   DOI
21 Matthys, H. and Funk, P. (2008) EPs 7630 improves acute bronchitic symptoms and shortens time to remission. Results of a randomized, double-blind, placebo-controlled, multicenter trial. Planta Med. 74, 686-692.   DOI
22 Park, H. J., Lee, J. Y., Moon, S. S. and Hwang, B. K. (2003) Isolation and anti-oomycete activity of nyasol from Anemarrhena asphodeloides rhizomes. Phytochem. 64, 997-1001.   DOI
23 Reid, D. J. and Pham, N. T. (2012) Rofumilast: a novel treatment for chronic pulmonary disease. Ann. Pharmacother. 46, 521-529.   DOI
24 Rivera, D. G., Balmaseda, I. H., Leon, A. A., Hernandez, B. C., Montiel, L. M., Garrido, G. G., Cuzzocrea, S. and Hernandez, R. D. (2006) Anti-allergic properties of Mangifera indica L. extract (VIMANG) and contribution of its glucosylxanthone mangiferin. J. Pharm. Pharmacol. 58, 385-395.   DOI
25 Severgnini, M., Takahashi, S., Rozo, L. M., Homer, R. J., Kuhn, C., Jhung, J. W., Perides, G., Steer, M., Hassoun, P. M., Fanburg, B. L., Cochran, B. H. and Simon, A. R. (2004) Activation of the STAT pathway in acute lung injury. Am. J. Physiol. Lung Cell Mol. Physiol. 286, L1282-L1292.   DOI
26 Zhang, T., Wang, J., Wang, S. and Ma, C. (2015) Timosaponin B-II inhibits lipopolysaccharide-induced acute lung toxicity via TLR/NF${\kappa}$B pathway. Toxicol. Mech. Methods 25, 665-671.   DOI
27 Sharma, M., Arnason, J. T., Burt, A. and Hudson, J. B. (2006) Echinacea extracts modulate the pattern of chemokine and cytokine secretion in rhinovirus-infected and uninfected epithelial cells. Phytother. Res. 20, 147-152.   DOI
28 Sy, L. K., Yan, S. C., Lok, C. N., Man, R. Y. and Che, C. M. (2008) Timosaponin A-III induces autophagy preceding mitochondria-mediated apoptosis in HeLa cancer cells. Cancer Res. 68, 10229-10237.   DOI