Effective-components combination alleviates PM2.5-induced inflammation by evoking macrophage autophagy in COPD.

ETHNOPHARMACOLOGICAL RELEVANCE: Bufei Yishen formula (BYF) is clinically used to treat chronic obstructive pulmonary disease (COPD). Effective-component compatibility (ECC) is a combination of five active components derived from BYF, which has an equal effect on COPD to BYF. Our previous study has also demonstrated that ECC can protect COPD rats against PM2.5 exposure. However, the precise mechanisms remain to be elucidated. AIM OF THE STUDY: To explore the mechanism underlying the anti-inflammatory effects of ECC-BYF against PM2.5-accelerated COPD. MATERIALS AND METHODS: MH-S macrophages were stimulated by PM2.5 suspension to establish an in vitro model. Western blotting and immunofluorescent staining were used to measure the protein levels of autophagy markers. ELISA and quantitative PCR were used to detect the levels of inflammatory cytokines. In vivo, an established PM2.5-accelerated COPD rat model was used to determine the protective effect of ECC-BYF. Lung function, pathology, autophagy, and inflammatory mediators were detected. RESULTS: Firstly, we observed a significantly increased number of macrophages in the lungs upon PM2.5 exposure. Then, decreased autophagy flux while elevated inflammation was detected in PM2.5-exposed rats and MH-S cells. In MH-S cells, ECC-BYF significantly suppressed the PM2.5-increased inflammatory cytokines production, which was accompanied by the enhancement of autophagy flux. An autophagy inhibitor counteracted the anti-inflammatory effect elicited by ECC-BYF. In addition, ECC-BYF stimulated Foxo3 nuclear translocation and upregulated Foxo3 expression, whereas Foxo3 knockdown abrogated the inhibitory effect of ECC-BYF on inflammation. In PM2.5-accelerated COPD rats, ECC-BYF also attenuated the autophagy disruption and increased Foxo3 in the lungs, finally resulting in a suppression of pulmonary inflammation and an enhancement of lung function. CONCLUSION: ECC-BYF can ameliorate PM2.5-aggravated inflammation in COPD, which might be associated with the enhancement of autophagy flux in alveolar macrophages through the activation of Foxo3 signals.

The Effects of Nine Compounds on Aldehyde-Oxidase-Related Genes in Bactrocera dorsalis (Hendel).

Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) (B. dorsalis) is an important agricultural, major invasive, and quarantine pest that can cause significant damage to the economic value of the fruit and vegetable industry. Male bait is one of the most effective methods of surveying, monitoring, and controlling B. dorsalis. In our study, we constructed cDNA libraries using total RNA extracted independently from the antennae, mouthparts, and thoracic legs of male and female adults and the ovipositors of female adults and screened out four aldehyde-oxidase-related genes (AOX-related), C58800, C66700, C67485, and C67698. Molecular docking predictions showed that eight compounds, including 3,4-dimethoxycinnamyl alcohol, 3,4-dimethoxy-cinnamaldehyde, deet, ethyl N-acetyl-N-butyl-ß-alaninate, n-butyl butyrate, n-butyl butyrate, ethyl butyrate, methyl eugenol, and ethyl acetate, could combine with proteins encoded by the four B. dorsalis AOX-related genes. Furthermore, QPCR was performed to confirm that four compounds, including 3,4-dimethoxy cinnamic aldehyde, butyl levulinic acid ethyl ester (mosquito repellent), butyl butyrate, and methyl eugenol, induced significant changes in the AOX-related genes of B. dorsalis. These results provide useful information and guidance for the batch screening of potentially useful compounds and the search for effective attractants of B. dorsalis.

Xiaoxuming Decoction: A Traditional Herbal Recipe for Stroke With Emerging Therapeutic Mechanisms.

Xiaoxuming decoction (XXMD) has been traditionally used to manage stroke though debates on its clinical efficacy were present in the history. Till nowadays, it is still one of the most commonly used herbal recipes for stroke. One of the reasons is that a decent proportion of ischemic stroke patients still have residue symptoms even after thrombolysis with rt-PA or endovascular thrombectomy. Numerous clinical studies have shown that XXMD is an effective alternative therapy not only at the acute stage, but also at the chronic sequelae stage of ischemic stroke. Modern techniques have isolated groups of compounds from XXMD which have shown therapeutic effects, such as dilating blood vessels, inhibiting thrombosis, suppressing oxidative stress, attenuating nitric oxide induced damage, protecting the blood brain barrier and the neurovascular unit. However, which of the active compounds is responsible for its therapeutic effects is still unknown. Emerging studies have screened and tested these active compounds aiming to find individual compounds that can be used as drugs to treat stroke. The present study summarized both clinical evidence of XXMD in managing stroke and experimental evidence on its molecular mechanisms that have been reported recently using advanced techniques. A new perspective has also been discussed with an aim to provide new targets that can be used for screening active compounds from XXMD.

The Anti-Inflammatory Effect of a Combination of Five Compounds From Five Chinese Herbal Medicines Used in the Treatment of COPD.

Effective compound combination (ECC; i.e, 20-S-ginsenoside Rh1, astragaloside, icariin, nobiletin, and paeonol), derived from Chinese herbal medicine, significantly ameliorates chronic obstructive pulmonary disease (COPD) in rats; however, the underlying mechanisms of ECC remain largely unclear. In this study, network pharmacology analysis integrated with experimental validation was used to explore the therapeutic mechanisms of ECC against COPD. ECC targets and COPD genes and targets were identified from multiple databases, and then used for an analysis of protein-protein interaction (PPI) networks, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and biological functioning. BisoGenet was used to comprehensively analyze the hub-network. We validated the therapeutic effect and mechanisms of ECC both in vivo and in vitro. We identified 45 ECC targets, which were mainly related to inflammatory processes, such as the NOD-like and NF-kappa B signaling pathways, hematopoietic cell lineage, Th17 cell differentiation, cellular response to lipopolysaccharide, and interleukin-8 secretion. In addition, 1180 COPD genes and 70 COPD targets were identified as being involved in the biological functions associated with COPD development, such as cytokine-cytokine receptor interaction, the TNF signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, regulation of lymphocyte proliferation, and positive regulation of leukocyte migration. Integrative analysis of COPD genes and targets and ECC target networks revealed that 54 genes were mainly involved in the inflammatory process, such as IL-17 signaling, NF-kappa B signaling, innate immune response-activating signal transduction, and macrophage cell differentiation. Six targets (AR, ESR1, HNRNPA1, PAPR1, TP53, and VCAM1) contained in the hub-network and their four related compounds were obtained and recognized as the key molecules associated with the effects of ECC. Molecular docking validation demonstrated that four compounds could bind to six targets that interact with COPD genes. Finally, in vivo and in vitro experiments verified that ECC treatment ameliorated the symptoms of COPD in rats by improving their lung function, reducing pathological changes, and suppressing oxidative responses and pro-inflammatory cytokine secretion, while inhibiting inflammation in LPS-induced macrophages, which may be associated with NF-kappa B and MAPK signaling regulation. This study demonstrates the therapeutic mechanisms and effects of ECC on COPD via regulation of the underlying inflammatory process.

Effective-compound combination inhibits the M2-like polarization of macrophages and attenuates the development of pulmonary fibrosis by increasing autophagy through mTOR signaling.

BACKGROUND AND PURPOSE: The M2 polarization of macrophages substantially contributes to the progression of pulmonary fibrosis (PF). Effective-compound combination (ECC), which is composed of isoliquiritigenin, icariin, nobiletin, peimine, and paeoniflorin, ameliorated bleomycin-induced PF in rats. Hence, we investigated the anti-PF mechanism of ECC with a focus on the suppression of M2 polarization in macrophages in vivo and in vitro. METHODS: The PF rat model was generated via the intratracheal instillation of bleomycin. Histological changes, M2 macrophages, and profibrotic mediators were detected. The M2 polarization model was generated by incubating macrophages with IL-4. Quantitative PCR and Western blotting were used to measure mRNA and protein levels, respectively. RESULTS: ECC attenuated bleomycin-induced PF in rats, which might be associated with reduced macrophage infiltration, M2 polarization, and profibrotic mediator expression. Furthermore, ECC significantly suppressed M2 polarization in IL-4-treated macrophages, which was accompanied by the upregulation of autophagy. An autophagy inhibitor abrogated the inhibitory effect of ECC on M2 polarization. In addition, ECC decreased the levels of p-p70S6K/p-4EBP and p-AKT473/p-GSK3ß, which are critical regulators of autophagy. CONCLUSION: ECC can ameliorate PF, which might be associated with the inhibition of M2 polarization through the promotion of autophagy via mTOR signaling suppression.

Anxiolytic Effect of Essential Oils and Their Constituents: A Review.

Essential oils are usually used in aromatherapy to alleviate anxiety symptoms. In comparison to traditional drugs, essential oils have fewer side effects and more diversified application ways, including inhalation. This review provides a comprehensive overview of studies on anxiolytic effects of essential oils in preclinical and clinical trials. Most of the essential oils used in clinical studies have been proven to be anxiolytic in animal models. Inhalation and oral administration were two common methods for essential oil administration in preclinical and clinical trials. Massage was only used in the clinical trials, while intraperitoneal injection was only used in the preclinical trails. In addition to essential oils that are commonly used in aromatherapy, essential oils from many folk medicinal plants have also been reported to be anxiolytic. More than 20 compounds derived from essential oils have shown an anxiolytic effect in rodents, while two-thirds of them are alcohols and terpenes. Monoamine neurotransmitters, amino acid neurotransmitters, and the hypothalamic-pituitary-adrenal axis are thought to play important roles in the anxiolytic effects of essential oils.

Study on the Mechanism of Artemisia capillaries Based on Systems Pharmacology / 中国药房

OBJECTIVE:To investigate the possible mechanism of Artemisia capillaries,and to provide reference for further development and utilization of it. METHODS:The effective components and related target protein of A. capillaries were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) analysis platform database. The effective compound-target protein visual network of A. capillaries was established by using Cytoscape 3.5.1 software,topology analysis was also performed. The protein-protein interaction (PPI) network was constructed and analyzed by STRING database. KEGG pathway enrichment of target protein coding gene was analyzed by DAVID bioinformatics resource database. RESULTS:A total of 13 kinds of effective compounds,189 target proteins and 34 enrichment pathways were selected. Quercetin,β-glutamol,isorhamnetin and artepillin C were main effective compounds. Prostaglandin G/H sythase 2(PTGS 2),heat shock protein 90(HSP 90),dipeptidyl peptidase Ⅳ, protein kinase A catalytic subunit Cα were main target proteins. Transcription factor AP-1 and cell tumor antigen p53 played a key role in PPI network. The target protein coding gene was rich in TNF-α signaling pathway,HIF-1 signaling pathway,Toll-like receptor signaling pathway,PI3K/Akt signaling pathway,T cell receptor signaling pathway,thyroid hormone signaling pathway, apoptotic signaling pathway,etc. CONCLUSIONS:Quercetin,β-glutamol and isorhamnetin of A. capillaries play an effect on PTGS2,HSP90,transcription factor AP-1 and other target proteins through TNF-α signaling pathway,HIF-1 signaling pathway and PI3K/Akt signaling pathway,so as to play anti-inflammatory and antitumor effect.

Varietal classification and antioxidant activity prediction of Osmanthus fragrans Lour. flowers using UPLC-PDA/QTOF-MS and multivariable analysis.

This study was aimed to classify the varieties and predict the antioxidant activity of Osmanthus fragrans flowers by UPLC-PDA/QTOF-MS and multivariable analysis. The PLS-DA model successfully classified the four varieties based on both the 21 identified compounds and the effective compounds. For the antioxidant activity prediction, PLS performed well to predict the antioxidant activity of O. fragrans flowers. Furthermore, acteoside, suspensaside A, ligustroside, forsythoside A, phillygenin and caffeic acid were selected as effective compounds by UVE-SPA for prediction. On the basis of effective compounds, PLS, MLR and PCR were applied to establish the calibration models. The UVE-SPA-MLR model was the optimal method to predict the antioxidant activity values with Rp of 0.9200, 0.9010 and 0.8905 for DPPH, ABTS and FRAP assays, respectively. The results revealed that the UPLC-PDA/QTOF-MS combined with chemometrics could be a new method to classify the varieties and predict the antioxidant activity of O. fragrans flowers.