Xingbei antitussive granules ameliorate cough hypersensitivity in post-infectious cough guinea pigs by regulating tryptase/PAR2/TRPV1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Xingbei antitussive granules (XB) is a classic Chinese Medicine prescription for treating post-infectious cough(PIC), based on the Sanao Decoction from Formularies of the Bureau of People's Welfare Pharmacies in the Song Dynasty and Jiegeng decoction from Essentials of the Golden Chamber in the Han Dynasty. However, the therapeutic effects and pharmacological mechanisms are still ambiguous. In the present study, we endeavored to elucidate these underlying mechanisms. AIMS OF THE STUDY: This study aimed to explore the potential impact and mechanism of XB on PIC, and provide a scientific basis for its clinical application. MATERIALS AND METHODS: Cigarette smoking (CS) combined with lipopolysaccharide (LPS) nasal drops were administered to induce the PIC guinea pig with cough hypersensitivity status. Subsequently, the model guinea pigs were treated with XB and the cough frequency was observed by the capsaicin cough provocation test. The pathological changes of lung tissue were assessed by HE staining, and the levels of inflammatory mediators, mast cell degranulating substances, and neuropeptides were detected. The protein and mRNA expression of transient receptor potential vanilloid type 1(TRPV1), proteinase-activated receptor2(PAR2), and protein kinase C (PKC) were measured by Immunohistochemical staining, Western blot, and RT-qPCR. Changes in the abundance and composition of respiratory bacterial microbiota were determined by 16S rRNA sequencing. RESULTS: After XB treatment, the model guinea pigs showed a dose-dependent decrease in cough frequency, along with a significant alleviation in inflammatory infiltration of lung tissue and a reduction in inflammatory mediators. In addition, XB high-dose treatment significantly decreased the levels of mast cell Tryptase as well as ß-hexosaminidase (ß-Hex) and downregulated the expression of TRPV1, PAR2, and p-PKC. Simultaneously, levels of neuropeptides like substance P (SP), calcitonin gene-related peptide (CGRP), neurokinin A (NKA), and nerve growth factor (NGF) were improved. Besides, XB also can modulate the structure of respiratory bacterial microbiota and restore homeostasis. CONCLUSION: XB treatment alleviates cough hypersensitivity and inflammatory responses, inhibits the degranulation of mast cells, and ameliorates neurogenic inflammation in PIC guinea pigs whose mechanism may be associated with the inhibition of Tryptase/PAR2/PKC/TRPV1 and the recovery of respiratory bacterial microbiota.

Artesunate: A review of its therapeutic insights in respiratory diseases.

BACKGROUND: Artesunate, as a semi-synthetic artemisinin derivative of sesquiterpene lactone, is widely used in clinical antimalarial treatment due to its endoperoxide group. Recent studies have found that artesunate may have multiple pharmacological effects, indicating its significant therapeutic potential in multiple respiratory diseases. PURPOSE: This review aims to summarize proven and potential therapeutic effects of artesunate in common respiratory disorders. STUDY DESIGN: This review summarizes the pharmacological properties of artesunate and then interprets the function of artesunate in various respiratory diseases in detail, such as bronchial asthma, chronic obstructive pulmonary disease, lung injury, lung cancer, pulmonary fibrosis, coronavirus disease 2019, etc., on different target cells and receptors according to completed and ongoing in silico, in vitro, and in vivo studies (including clinical trials). METHODS: Literature was searched in electronic databases, including Pubmed, Web of Science and CNKI with the primary keywords of 'artesunate', 'pharmacology', 'pharmacokinetics', 'respiratory disorders', 'lung', 'pulmonary', and secondary search terms of 'Artemisia annua L.', 'artemisinin', 'asthma', 'chronic obstructive lung disease', 'lung injury', 'lung cancer', 'pulmonary fibrosis', 'COVID-19' and 'virus' in English and Chinese. All experiments were included. Reviews and irrelevant studies to the therapeutic effects of artesunate on respiratory diseases were excluded. Information was sort out according to study design, subject, intervention, and outcome. RESULTS: Artesunate is promising to treat multiple common respiratory disorders via various mechanisms, such as anti-inflammation, anti-oxidative stress, anti-hyperresponsiveness, anti-proliferation, airway remodeling reverse, induction of cell death, cell cycle arrest, etc. CONCLUSION: Artesunate has great potential to treat various respiratory diseases.

[Meta-analysis of efficacy and safety of Suhuang Zhike Capsules in treatment of chronic obstructive pulmonary disease].

This study aims to evaluate the effectiveness and safety of Suhuang Zhike Capsules in treating chronic obstructive pulmonary disease. The Chinese and English databases were searched(from the establishment to July 2021) for randomized controlled trials(RCTs) on the treatment of chronic obstructive pulmonary disease with Suhuang Zhike Capsules, yielding 130 articles and finally 12 eligible RCTs. The 12 RCTs enrolled a total of 1 159 patients(579 in experimental group, 580 in control group), with 728 males(62.8%) and 431 females(37.2%). Meta-analysis showed that the conventional western medicine combined with Suhuang Zhike Capsules increased clinical efficacy(OR=4.31, 95%CI[2.88, 6.46], Z=7.08, P<0.000 01), forced expiratory volume in one second(FEV1)(SMD=0.88, 95%CI[0.60, 1.16], Z=6.24, P<0.000 01), forced vital capacity(FVC)(SMD=0.96, 95%CI[0.38, 1.55], Z=3.22, P=0.001), forced vital capacity rate of one second(FEV1/FVC%)(SMD=0.85, 95%CI[0.51, 1.19], Z=4.92, P<0.000 01), and maximum voluntary ventilation(MVV)(SMD=0.61, 95%CI[0.39, 0.83], Z=5.40, P<0.000 01) compared with the conventional western medicine alone. The differences in residual volume/total lung capacity(RV/TLC)(SMD=-0.93, 95%CI[-3.38, 1.53], Z=0.74, P=0.46) and adverse reactions(OR=1.39, 95%CI[0.76, 2.56], Z=1.07, P=0.28) are insignificant. The study showed that the conventional western medicine combined with Suhuang Zhike Capsules could improve clinical efficacy and lung functions in the treatment of chronic obstructive pulmonary disease. In addition, the combination had been verified to be safe. However, in view of the uneven method quality, small sample size, and inconsistent outcome indicators of the included studies, higher-quality, multi-center, and large-sample RCTs are needed for further verification.

A comparison of tiotropium/olodaterol vs tiotropium alone in terms of treatment effect for chronic obstructive pulmonary disease: A meta-analysis.

BACKGROUND: Combinations of long-acting bronchodilators with different mechanisms of action are recommended to improve prognosis and reduce risk of adverse events of chronic obstructive pulmonary disease (COPD). It is unclear whether the new combination therapy with long-acting muscarinic antagonist (LAMA) tiotropium (TIO) and long acting beta-agonists (LABA) olodaterol (OLO) was superior to tiotropium alone. METHODS: We measured the efficacy of the TIO/OLO combination vsTIO alone for COPD patients based on electronic databases up to February 2019. After rigorous quality review, data was extracted from eligible trials. All the main outcomes were pooled analysis using RevMan software. RESULTS: A total of 6 randomized controlled trials (RCTs) were identified. The pooled results of our meta-analysis demonstrated that FEV1 [MD = 0.03, 95% CI (-0.01,0.07), P = .18], FVC [MD = -0.03, 95%CI (-0.06,0.00), P = .09] and FEV1%pred [MD = 0.35, 95%CI (-0.30, 0.99), P = .29] all showed no significant difference between the 2 groups. The overall incidence of adverse effects (AEs) [OR = 1.01,95%CI (0.93,1.09), P = .87] and serious AEs [OR = 1.04,95% CI (0.82, 1.32), P = .72] in the combination group was similar to that of the TIO alone group, without statistical significance. CONCLUSION: These studies reported that the TIO/OLO combination did not show superior effects than tiotropium alone for COPD. Additionally, both therapies were well tolerated.

Analysis of the Mechanism of Zhichuanling Oral Liquid in Treating Bronchial Asthma Based on Network Pharmacology.

Zhichuanling oral liquid (ZOL) as a preparation of traditional Chinese medicine is widely used for the treatment of asthma in China; therefore, it is necessary to systematically clarify bioactive chemical ingredients and the mechanism of action of ZOL. Information on ZOL ingredients and asthma-related targets was collected, and we used the latest systematic pharmacological methods to construct protein-protein interaction network and compound-target network and then visualized them. Finally, GO and KEGG pathway enrichment analysis was conducted through the clusterProfiler package in the R software. The results showed that 58 bioactive ingredients and 42 potential targets of ZOL related to asthma were identified, following six important components and nine hub genes screened. Further cluster and enrichment analysis suggested that NF-κB signaling pathway, PI3K/Akt signaling pathway, IL-17 signaling pathway, Toll-like receptor signaling pathway, and TNF signaling pathway might be core pathways of ZOL for asthma. Our work successfully predicted the active ingredients and potential targets of ZOL and provided the explanation for the mechanism of action of ZOL for asthma through the systematic analysis, which suggested that ZOL played a major role in many ways including reducing airway inflammation and inhibiting airway remodeling and mucus secretion. Moreover, ZOL combined with glucocorticoids may have some effects on severe asthma.

Efficacy and safety of Yu-Ping-Feng powder for asthma in children: a protocol of systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Asthma has become the most common chronic disease in children, which seriously affects children's health and growth. Yu-Ping-Feng powder (YPFP) is widely used for the treatment of asthma in children, but there are few meta-analyses to assess the add-on effects of YPFP in children with asthma. Therefore, it is necessary to conduct a systematic review to evaluate the efficacy and safety of YPFP in the management of asthma in children. METHODS: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science and the Chinese electronic databases including China Network Knowledge Infrastructure (CNKI), Chinese Biomedicine (CBM), Chinese Scientific Journals Database (VIP), and Wan Fang Database were searched for the randomized controlled trials (RCTs) of YPFP in children with asthma based on the eligibility criteria from the date of the database inception to 28 November 2018. Two reviewers assessed the articles and extracted data from the included RCTs independently. Data will be synthesized by either the fixed-effects or random-effects model according to a heterogeneity test. We will assess the risk of bias with the Cochrane Collaboration Tool and overall quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation system (GRADE). Primary outcomes include the improvement of symptoms including breathlessness, coughing, wheezing and the frequency of asthma exacerbations. Lung function, serum IgE level, blood eosinophil count, phlegm eosinophil count and adverse events will be assessed as the secondary outcomes. We will perform the data synthesis, sensitivity analyses, and subgroup analyses in the Rev-Man version 5.3 software. A funnel plot will be established to evaluate reporting bias. RESULTS: This systematic review and meta-analysis will review and synthesis current clinical evidence of YPFP for the treatment of asthma in children. CONCLUSION: This analysis will provide high quality evidence of YPFP for the treatment of asthma in children. PROSPERO REGISTRATION NUMBER: CRD42018111223.

A traditional Chinese patent medicine-Suhuang zhike capsule for cough variant asthma in adults: A protocol of systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Many people with cough variant asthma use Traditional Chinese Patent Medicine-Suhuang anti-tussive capsule to help reduce symptoms. However there is no systematic reviews had promising its efficacy and safety for cough variant asthma. METHODS: Four English databases (PubMed, Web of science, EMBASE, and Springer Cochrane Library) and 4 Chinese databases (Wanfang Database, Chinese Scientific Journal Database, China National Knowledge Infrastructure Database, and Chinese Biomedical Literature Database) were researched for the randomized controlled trials of Suhuang anti-tussive capsule for cough variant asthma. The search was limited to human studies, using the search keywords or free-text terms "cough," "cough variant asthma," "Suhuang Zhike capsul,""Suhuang anti-tussive capsul," and "randomized clinical trials." Two reviewers individually extracted data from the included randomized controlled trials (RCTs). Data will be synthesized by either the fixed-effects or random-effects model according to a heterogeneity test. The primary outcomes include the frequency of asthma exacerbations during follow-up, asthmatic symptoms by validated instruments (including symptom scores, Likert scale, visual analogue scale). Lung function, serum immunoglobulin E, blood eosinophil count, phlegm eosinophil count, tumor necrosis factor-a, interleukin-1b, and adverse effects (numbers of participants experiencing each adverse events) will be assessed as the secondary outcome. Meta-analysis will be performed using RevMan5.3.5 software provided by the Cochrane Collaboration. RESULTS: This study will provide high-quality synthesis based on current evidence of Suhuang anti-tussive capsule treatment for cough variant asthma. CONCLUSION: This analysis will provide updated evidence for whether Suhuang anti-tussive capsule is an effective and safe intervention for cough variant asthma. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019139695.