ABSTRACT
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.
Subject(s)
Drugs, Chinese Herbal , Pulmonary Disease, Chronic Obstructive , Humans , Lung/metabolism , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Bronchodilator Agents/pharmacology , Bronchodilator Agents/metabolism , Bronchodilator Agents/therapeutic use , Molecular Docking Simulation , Pulmonary Disease, Chronic Obstructive/drug therapy , Receptor, Muscarinic M3/metabolism , Receptor, Muscarinic M3/therapeutic useABSTRACT
OBJECTIVE: To observe the effect of Yangxue Qingnao Granule (YQG) on the expression of CD11b in CA1 region of hippocampus of vascular dementia rats, and to explore its regulation on microglias. METHODS: Totally 144 SD rats were randomly divided into the sham-operation group, the vascular dementia model group (model), and the YQG treated group (treated). The vascular dementia rat model was prepared by modified Pulsinelli's four-vessel occlusion. Rats in the sham-operation group and the model group were administered with normal saline -(at the daily dose of 10 mL/kg) by gastrogavage, while those in the treated group were administered with YQG (0.32 g/mL, at the daily dose of 10 mL/kg) by gastrogavage. All administration was performed once per day for 8 successive weeks. The expression of CD11b in CA1 region of hippocampus of vascular dementia rats was detected at week 1, 2, 4, and 8, respectively. RESULTS: Compared with the sham-operation group, the expression of CD11b in CA1 region of hippocampus of vascular dementia rats were significantly enhanced in the model group at each time point (P < 0.01). Compared with the model group, the expression of CD11b in CA1 region of hippocampus of vascular dementia rats significantly decreased in the treated group at each time point (P < 0.01), especially at week 2. CONCLUSION: Obvious activation and proliferation of microglias could be seen in CA1 region of hippocampus of vascular dementia rats, and YQG could inhibit activation and proliferation of microglias.