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墨旱莲提取物及其成分墨旱莲皂苷A对博莱霉素诱导的小鼠肺纤维化的预防作用。

Preventive effects of Ecliptae Herba extract and its component, ecliptasaponin A, on bleomycin-induced pulmonary fibrosis in mice.

作者信息

You Xin-Yi, Xue Qian, Fang Yue, Liu Qianyu, Zhang Chao Feng, Zhao Ceng, Zhang Mian, Xu Xiang-Hong

机构信息

Research Department of Pharmacognosy, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, PR China.

Research Department of Pharmacognosy, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, PR China.

出版信息

J Ethnopharmacol. 2015 Dec 4;175:172-80. doi: 10.1016/j.jep.2015.08.034. Epub 2015 Sep 16.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Ecliptae Herba, a nourishing traditional Chinese medicine, is also a folk medicine for the treatment of lung diseases.

AIM OF THE STUDY

To investigate the anti-fibrosis effects and the underlying mechanism of the extract of Ecliptae Herba and its potential active components.

MATERIALS AND METHODS

The resulting extract (EXT) was prepared from the 80% ethanol extract of Ecliptae Herba. After intratracheally administrated with bleomycin (BLM, 5mg/kg), mice were orally treated with EXT at 2.5, 1.25, 0.625 g/kg and eclipta saponin A (ESA) at 80 mg/kg once daily for 28 day. The bodyweight, survival rate, pathological changes of lung and levels of hydroxyproline (HYP) were used to evaluate the anti-fibrotic effects. The malonaldehyde (MDA), superoxidae dismutase (SOD) activity, and the protein expressions of matrix metalloproteinase (MMP)-2, 9, tissue inhibitor of metalloproteinase-1 (TIMP-1), cyclooxygenase-2 (COX-2), α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) in lung tissue were analyzed by kits or western blot.

RESULTS

Compared with BLM group, EXT administration could significantly ameliorated the pathological changes of lung, decreased the HYP content, enhanced the SOD activity, and reduced the MDA content of lung tissues. In mechanism, EXT significantly alleviated the levels of COX-2, TGF-β1, MMP-2 and α-SMA, as well as elevated the ratio value of MMP-9/TIMP-1. Additionally, the anti-fibrosis effects of ESA, a large amount of saponins isolated from Eclipta prostrata , was also evaluated by the BLM-induced model. The results showed that ESA could block BLM-induced histological changes of lung tissue and decrease the high levels of TGF-β1 and α-SMA.

CONCLUSIONS

Ecliptae Herba has protective effects against the pulmonary fibrosis induced by BLM via reducing the oxidative stress, lung tissue inflammation, and the subsequent epithelial-mesenchymal transition. The active chemical constituents may be involved with triterpenoid saponins, such as ESA.

摘要

民族药理学相关性

墨旱莲,一种滋补类传统中药,也是治疗肺部疾病的民间药物。

研究目的

探讨墨旱莲提取物及其潜在活性成分的抗纤维化作用及潜在机制。

材料与方法

墨旱莲80%乙醇提取物制备得到提取物(EXT)。经气管内注射博来霉素(BLM,5mg/kg)后,小鼠分别以2.5、1.25、0.625g/kg的剂量口服EXT,以80mg/kg的剂量口服墨旱莲皂苷A(ESA),每日一次,共28天。通过体重、存活率、肺组织病理变化及羟脯氨酸(HYP)水平评估抗纤维化作用。采用试剂盒或蛋白质印迹法分析肺组织中丙二醛(MDA)、超氧化物歧化酶(SOD)活性,以及基质金属蛋白酶(MMP)-2、9、金属蛋白酶组织抑制剂-1(TIMP-1)、环氧合酶-2(COX-2)、α-平滑肌肌动蛋白(α-SMA)和转化生长因子-β1(TGF-β1)的蛋白表达。

结果

与BLM组相比,给予EXT可显著改善肺组织病理变化,降低HYP含量,增强SOD活性,降低肺组织MDA含量。机制方面,EXT显著降低COX-2、TGF-β1、MMP-2和α-SMA水平,并提高MMP-9/TIMP-1比值。此外,还通过BLM诱导的模型评估了从鳢肠中分离出的大量皂苷ESA的抗纤维化作用。结果表明,ESA可阻止BLM诱导的肺组织组织学变化,并降低TGF-β1和α-SMA的高水平。

结论

墨旱莲通过减轻氧化应激、肺组织炎症及随后的上皮-间质转化,对BLM诱导的肺纤维化具有保护作用。活性化学成分可能与三萜皂苷有关,如ESA。

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