Icaritin inhibits the invasion and epithelial-to-mesenchymal transition of glioblastoma cells by targeting EMMPRIN via PTEN/AKt/HIF-1α signalling.

Icaritin, a hydrolytic product of icariin from the Epimedium genus, exerts anti-tumour effects on a variety of tumour cell types, mainly by inhibiting cell proliferation and inducing apoptosis. However, little is known about the role of icaritin in cancer invasion and epithelial-to-mesenchymal transition (EMT). In the present study, the glioblastoma (GBM) cell line U87MG was used as a model to investigate the effects of icaritin on the invasion and EMT of cancer cells. The results showed that icaritin significantly inhibited the invasion and EMT of GBM cells by targeting extracellular matrix metalloproteinase (EMMPRIN). Furthermore, the findings strongly indicate that the modulatory effect of icaritin on EMMPRIN is mediated via the PTEN/Akt/HIF-1α signalling pathway. The data provide the first experimental evidence of the inhibitory effect of icaritin on cancer cell invasion and EMT, thus highlighting the potential of icaritin to be employed as a promising anti-cancer agent in the treatment of GBM.

Corrigendum: Gut microbiota and chronic obstructive pulmonary disease: a Mendelian randomization study.

[This corrects the article DOI: 10.3389/fmicb.2023.1196751.].

Gut microbiota and chronic obstructive pulmonary disease: a Mendelian randomization study.

Background: A growing number of studies implies a strong association between gut microbiota and chronic obstructive pulmonary disease (COPD). However, the causal impact between gut microbiota and COPD remains unclear. As a result, we used a two-sample Mendelian randomization (MR) method to investigate the connection between gut microbiota and COPD in this study. Methods: The largest available genome-wide association study (GWAS) of gut microbiota was obtained from the MiBioGen consortium. Summary-level dataset for COPD were obtained from the FinnGen consortium. The main analysis method for determining the causal link between gut microbiota and COPD was inverse variance weighted (IVW). Subsequently, pleiotropy and heterogeneity tests were performed to determine the reliability of the results. Results: IVW method identified 9 bacterial taxa nominally associated with the risk of COPD. Class Actinobacteria (p = 0.020), genus Allisonella (p = 0.024), genus Coprococcus2 (p = 0.002) and genus Oscillospira (p = 0.018) were protective against COPD. In addition, order Desulfovibrionales (p = 0.011), family Desulfovibrionaceae (p = 0.039), family Peptococcaceae (p = 0.020), family Victivallaceae (p = 0.012) and genus Marvinbryantia (p = 0.017) were associated with a higher risk of COPD. No pleiotropy or heterogeneity were found. Conclusion: According to the findings of this MR analysis, a causal relationship exists between certain gut microbiota and COPD. New insights into the mechanisms of COPD mediated by gut microbiota are provided.

Monomeric compounds from traditional Chinese medicine: New hopes for drug discovery in pulmonary fibrosis.

Pulmonary fibrosis (PF) is a chronic and irreversible pulmonary disease, and can lead to decreased lung function, respiratory failure and even death. The pathogenesis research and treatment strategy of PF significantly lag behind the medical progress and clinical needs. The treatment of this disease remains a thorny clinical problem, and the effective therapeutic drugs are still limited. Monomeric compounds from traditional Chinese medicine own various biological activities and high safety. They play a broad part in treating diseases and is also a candidate drug for preventing and treating PF. In this paper, we reviewed the mechanism of action and potential value of various anti-PF monomeric compounds from traditional Chinese medicine. These monomeric compounds can attenuate inflammatory response, oxidative stress, epithelial mesenchymal transformation and other processes of lung through many signaling pathways, and inhibit the activation and differentiation of fibroblasts, thus contributing to the treatment of PF. This review can provide new ideas for the development of anti-PF drugs in high efficiency with low toxicity.

Mechanistic study of salidroside on ovalbumin-induced asthmatic model mice based on untargeted metabolomics analysis.

Salidroside (SAL) is a natural component derived from Rhodiola rosea and is well known for its wide range of biological activities such as its anti-inflammatory and anti-oxidative properties. However, its effects and mechanisms of action related to asthma have not been well explored yet. Recent studies have found that changes in host metabolism are closely related to the progression of asthma. Many natural components can ameliorate asthma by affecting host metabolism. The use of untargeted metabolomics can allow for a better understanding of the metabolic regulatory mechanisms of herbs on asthma. This study aimed to demonstrate the anti-asthmatic effects and metabolic regulatory mechanisms of SAL. In this study, the therapeutic effects of SAL on asthmatic mice were tested at first. Secondly, the effects of SAL on the airway inflammatory reaction, oxidative stress, and airway remodeling were investigated. Finally, untargeted metabolomics analysis was used to explore the influence of SAL on lung metabolites. The results showed that SAL had a significant therapeutic effect on asthmatic model mice. Moreover, SAL treatment lowered interleukin (IL)-4, IL-5, and IL-13 levels but elevated interferon gamma (IFN-γ) and IL-10 levels in bronchoalveolar lavage fluid (BALF). Additionally, it also increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and decreased methane dicarboxylic aldehyde (MDA) levels in the lungs. Besides, SAL-treated mice showed decreased expression of smooth muscle actin (α-SMA), matrix metallopeptidase 2 (MMP2), matrix metallopeptidase 9 (MMP9), and transforming growth factor-beta 1 (TGF-ß1) in the lung. Untargeted metabolomics analysis showed 31 metabolites in the lungs that were influenced by SAL. These metabolites were related to pyrimidine metabolism, steroid hormone biosynthesis, and tricarboxylic acid (TCA) cycle. In conclusion, SAL treatment can reduce the inflammatory response, oxidative stress, and airway remodeling in asthmatic model mice. The mechanism of SAL in the treatment of asthma may be related to the regulation of pyrimidine metabolism, steroid hormone biosynthesis, and the TCA cycle. Further studies can be carried out using targeted metabolomics and in vitro models to deeply elucidate the anti-inflammatory and anti-oxidative mechanisms of SAL on asthma based on regulating metabolism.

Bu-Fei-Huo-Xue capsule alleviates bleomycin-induced pulmonary fibrosis in mice through modulating gut microbiota.

Introduction: Bu-Fei-Huo-Xue capsule (BFHX) has been used to treat pulmonary fibrosis (PF) in clinic. However, the mechanism of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis remains unclear. Recent studies have shown that the changes in gut microbiota were closely related to the progression of pulmonary fibrosis. Modulating gut microbiota provides new thoughts in the treatment of pulmonary fibrosis. Methods: In this study,a mouse model of pulmonary fibrosis was induced using bleomycin (BLM) and treated with Bu-Fei-Huo-Xue capsule. We firstly evaluated the therapeutic effects of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis model mice. Besides,the anti-inflammatory and anti- oxidative effects of Bu-Fei-Huo-Xue capsule were evaluated. Furthermore, 16S rRNA sequencing was used to observe the changes in gut microbiota in pulmonary fibrosis model mice after Bu-Fei-Huo-Xue capsule treatment. Results: Our results showed that Bu-Fei-Huo-Xue capsule significantly reduced the collagen deposition in pulmonary fibrosis model mice. Bu-Fei-Huo-Xue capsule treatment also reduced the levels and mRNA expression of pro-inflammatory cytokines and inhibited the oxidative stress in lung. 16S rRNA sequencing showed that Bu-Fei-Huo-Xue capsule affected the diversity of gut microbiota and the relative abundances of gut microbiota such as Lactobacillus, Lachnospiraceae_NK4A136_group, and Romboutsia. Conclusion: Our study demonstrated the therapeutic effects of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis. The mechanisms of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis may be associated with regulating gut microbiota.

Study on the Mechanism of Qing-Fei-Shen-Shi Decoction on Asthma Based on Integrated 16S rRNA Sequencing and Untargeted Metabolomics.

Qing-Fei-Shen-Shi decoction (QFSS) consists of Prunus armeniaca L., Gypsum Fibrosum, Smilax glabra Roxb., Coix lacryma-jobi L., Benincasa hispida (Thunb.) Cogn., Plantago asiatica L., Pyrrosia lingua (Thunb.) Farw., Houttuynia cordata Thunb., Fritillaria thunbergii Miq., Cicadae Periostracum, and Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle. QFSS shows significant clinical efficacy in the treatment of asthma. However, the specific mechanism of QFSS on asthma remains unclear. Recently, multiomics techniques are widely used in elucidating the mechanisms of Chinese herbal formulas. The use of multiomics techniques can better illuminate the multicomponents and multitargets of Chinese herbal formulas. In this study, ovalbumin (OVA) was first employed to induce an asthmatic mouse model, followed by a gavage of QFSS. First, we evaluated the therapeutic effects of QFSS on the asthmatic model mice. Second, we investigated the mechanism of QFSS in treating asthma by using an integrated 16S rRNA sequencing technology and untargeted metabolomics. Our results showed that QFSS treatment ameliorated asthma in mice. In addition, QFSS treatment affected the relative abundances of gut microbiota including Lactobacillus, Dubosiella, Lachnospiraceae_NK4A136_group, and Helicobacter. Untargeted metabolomics results showed that QFSS treatment regulated the metabolites such as 2-(acetylamino)-3-[4-(acetylamino) phenyl] acrylic acid, D-raffinose, LysoPC (15 : 1), methyl 10-undecenoate, PE (18 : 1/20 : 4), and D-glucose6-phosphate. These metabolites are associated with arginine and proline metabolism, arginine biosynthesis, pyrimidine metabolism, and glycerophospholipid metabolism. Correlation analysis indicated that arginine and proline metabolism and pyrimidine metabolism metabolic pathways were identified as the common metabolic pathways of 16s rRNA sequencing and untargeted metabolomics. In conclusion, our results showed that QFSS could ameliorate asthma in mice. The possible mechanism of QFSS on asthma may be associated with regulating the gut microbiota and arginine and proline metabolism and pyrimidine metabolism. Our study may be useful for researchers to study the integrative mechanisms of Chinese herbal formulas based on modulating gut microbiota and metabolism.

Efficacy and safety of Jin-shui Huan-xian granule for idiopathic pulmonary fibrosis: study protocol for a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND AND RATIONALE: Idiopathic pulmonary fibrosis is a critical disease with a poor prognosis. Although different studies have been conducted for the treatment of idiopathic pulmonary fibrosis, limited treatments are available. Jin-shui Huan-xian granule (JHG), which is a Chinese medicine herbal compound, has shown promising efficacy in reducing frequencies of acute exacerbations, improving exercise capacity the quality of life of patients with idiopathic pulmonary fibrosis. This study is to evaluate the efficacy and safety of JHG for IPF. SUBJECTS AND METHODS: This is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 312 idiopathic pulmonary fibrosis patients will be enrolled and randomly allocated to one of the two groups with 1:1. After a 2-week washout period, 52-week treatment will also be performed for all the patients. Patients in the experimental group and the control group will be given JHG and JHG placebo, respectively. Outcome measures including acute exacerbations, pulmonary function, dyspnea, exercise capacity, and quality of life will be evaluated in this study. DISCUSSION: Based on our previous study, it is hypothesized that JHG will reduce acute exacerbations; improve exercise capacity, pulmonary function, and quality of life; and delay the disease progression-free. High-level evidence-based support for TCM in IPF will also be obtained in this study. TRIAL REGISTRATION: ClinicalTrials.gov NCT04187690. Register on December 11, 2019.

He-Jie-Shen-Shi Decoction as an Adjuvant Therapy on Severe Coronavirus Disease 2019: A Retrospective Cohort and Potential Mechanistic Study.

Combination therapy using Western and traditional Chinese medicines has shown notable effects on coronavirus disease 2019 (COVID-19). The He-Jie-Shen-Shi decoction (HJSS), composed of Bupleurum chinense DC., Scutellaria baicalensis Georgi, Pinellia ternata (Thunb.) Makino, Glycyrrhiza uralensis Fisch. ex DC., and nine other herbs, has been used to treat severe COVID-19 in clinical practice. The aim of this study was to compare the clinical efficacies of HJSS combination therapy and Western monotherapy against severe COVID-19 and to study the potential action mechanism of HJSS. From February 2020 to March 2020, 81 patients with severe COVID-19 in Wuhan Tongji Hospital were selected for retrospective cohort study. Network pharmacology was conducted to predict the possible mechanism of HJSS on COVID-19-related acute respiratory distress syndrome (ARDS). Targets of active components in HJSS were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and PharmMapper databases. The targets of COVID-19 and ARDS were obtained from GeneCards and Online Mendelian Inheritance in Man databases. The key targets of HJSS in COVID-19 and ARDS were obtained based on the protein-protein interaction network (PPI). Kyoto Encyclopedia of Genes and Genomes analysis (KEGG) was conducted to predict the pathways related to the targets of HJSS in COVID-19 and ARDS. A "herb-ingredient-target-pathway" network was established using Cytoscape 3.2.7. Results showed that the duration of the negative conversion time of nucleic acid was shorter in patients who received HJSS combination therapy. HJSS combination therapy also relieved fever in patients with severe COVID-19. Network pharmacology analysis identified interleukin (IL) 6, tumor necrosis factor (TNF), vascular endothelial growth factor A (VEGFA), catalase (CAT), mitogen-activated protein kinase (MAPK) 1, tumor protein p53 (TP53), CC-chemokine ligand (CCL2), MAPK3, prostaglandin-endoperoxide synthase 2 (PTGS2), and IL1B as the key targets of HJSS in COVID-19-related ARDS. KEGG analysis suggested that HJSS improved COVID-19-related ARDS by regulating hypoxia-inducible factor (HIF)-1, NOD-like receptor, TNF, T cell receptor, sphingolipid, PI3K-Akt, toll-like receptor, VEGF, FoxO, and MAPK signaling pathways. In conclusion, HJSS can be used as an adjuvant therapy on severe COVID-19. The therapeutic mechanisms may be involved in inhibiting viral replication, inflammatory response, and oxidative stress and alleviating lung injury. Further studies are required to confirm its clinical efficacies and action mechanisms.