Abstract
We have explored the method of extraction and purification of cyclic-peptide extract (CPE) from Pseudostellaria heterophylla (Miq.) Pax. (Taizishen, TZS), characterized the structure about cyclic-peptide compounds and investigated the biological activity of CPE attenuating chronic obstructive pulmonary disease (COPD) in rats. The CPE from TZS was obtained by ethyl acetate, petroleum ether, hot water extraction, and alcohol-precipitation. Cyclic-peptide structures were distinguished using ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Rats were induced by solid combustibles smoke (SCS) for the COPD model, and the anti-COPD activity of CPE was detected using lung airway resistance and dynamic lung compliance, as well as pulmonary tissue hematoxylin and eosin (HE) staining. The relevant inflammatory cytokines were assayed by enzyme-linked immunosorbent assay (ELISA). CPE obtained from TZS contained 12 cyclic-peptide constituents; the purity was up to 92.94%. CPE (200, 400, or 500 mg/kg/day) was given to SCS-induced COPD model rats orally for 15 days. The results showed that in rats given CPE (400 mg/kg/day) there was a sharp fall in lung airway resistance but a rise in dynamic lung compliance. The image analysis of lung tissue sections suggested that CPE could decrease the degree of alveolar destruction (p <0.05), alleviate lung inflammation, increase alveolar space, and improve the infiltration of inflammatory cells. CPE was found to reduce the levels of TNF-α, but increase IL-10, adjusting multiple cytokines in rat serum; the TLR4 mRNA, MyD88 mRNA and AP-1 mRNA levels, the expressing levels of p-JNK, p-p38 and p-TAK1 protein were significantly down regulated in rat alveolar macrophages. CPE intervention could improve the pulmonary ventilation function on COPD rats, which may be related to its effect in inhibiting the abnormal activation of the TLR4-MyD88-JNK/p38 pathway. This is the first report that the CPE of TZS lessens the severity of COPD episodes. The new preparation process of CPEs implements the anticipated goal, which is to refine CPE and actualize quality control.
Highlights
Chronic obstructive pulmonary disease (COPD) is a noteworthy public health problem due to its morbidity and mortality (Lindberg et al, 2012)
Analytical grade reagents including petroleum ether, ethyl acetate, ethanol, n-butanol, ammonia, and chloroform were bought from Xilong Scientific Co., Ltd. (Shantou, China)
Freeze-Dried Powder Identification by ultra-high performance liquid chromatography (UPLC)-MS/MS Analysis. Both positive and negative electrospray ionization (ESI) modes were applied, and the positive ESI response was much better than the negative ESI response
Summary
Chronic obstructive pulmonary disease (COPD) is a noteworthy public health problem due to its morbidity and mortality (Lindberg et al, 2012). COPD exhibits symptoms of airflow blockage and breathlessness and includes emphysema, chronic bronchitis, or even asthma. Diagnosis of COPD can be best addressed by a combination of morphology and function. The morphological imaging of the lung parenchyma and airways can be detected using the three-dimensional high-resolution computed tomography (CT) technique. The image information obtained by functional imaging is perfusion, lung mechanics, and ventilation by magnetic resonance imaging (MRI). The development of COPD is mainly attributable to smoking, but genetic factors and respiratory infections are some of the most common causes of asthma; air pollution can aggravate asthma. Air quality is thought to have a larger role in the progression of COPD (David and Victor, 2006)
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