An in silico and in vitro integrated analysis method to reveal the curative mechanisms and pharmacodynamic substances of Bufei granule on chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with high disability and mortality. Clinical studies have shown that the Traditional Chinese Medicine Bufei Granule (BFG) has conspicuous effects on relieving cough and improving lung function in patients with COPD and has a reliable effect on the treatment of COPD, whereas the therapeutic mechanism is vague. In the present study, the latent bronchodilators and mechanism of BFG in the treatment of COPD were discussed through the method of network pharmacology. Then, the molecular docking and molecular dynamics simulation were performed to calculate the binding efficacy of corresponding compounds in BFG to muscarinic receptor. Finally, the effects of BFG on bronchial smooth muscle were validated by in vitro experiments. The network pharmacology results manifested the anti-COPD effect of BFG was mainly realized via restraining airway smooth muscle contraction, activating cAMP pathways and relieving oxidative stress. The results of molecular docking and molecular dynamics simulation showed alpinetin could bind to cholinergic receptor muscarinic 3. The in vitro experiment verified both BFG and alpinetin could inhibit the levels of CHRM3 and acetylcholine and could be potential bronchodilators for treating COPD. This study provides an integrating network pharmacology method for understanding the therapeutic mechanisms of traditional Chinese medicine, as well as a new strategy for developing natural medicines for treating COPD.

Unravelling hidden threats of water disinfection: Toxicity evaluation and toxic products identification during diclofenac degradation.

Diclofenac (DCF) is a widely-used nonsteroidal anti-inflammatory drug that is routinely found in surface water bodies. While ozonation and ultraviolet (UV) radiation are commonly employed as disinfection methods in water treatment processes, the degradation of DCF in these processes occurs due to the strong oxidizing activity of the reactive oxygen species produced during both ozonation and UV radiation. Despite extensive studies reporting the removal and transformation of DCF through ozone and UV treatments, the potential hidden hazards of toxicity arising from these processes as well as the identification of the toxic transformation products have often been overlooked. In this study, various toxicities including microtoxicity, genotoxicity and antiestrogenicity were evaluated using multiple in-vitro bioassays. The transformation products were identified via ultra-performance liquid chromatography equipped with mass spectrometry (UPLC-MS). Correlation analysis was employed to gain deeper insight into the contributions of degradation products to overall toxicity. The results revealed that DCF possessed significant genotoxic and antiestrogenic effects, but displayed minimal microtoxicity. Microtoxic products such as those containing carbazole were generated during DCF degradation with ozone, UVA and UVC. Antiestrogenic products with dichloroaniline structures were observed in DCF ozonation but not in photodegradation by UVA and UVC. These findings highlighted the hidden risks associated with the disinfection of water containing micropollutants such as DCF.