Molecular mechanism of Jianpiyifei II granules in the treatment of chronic obstructive pulmonary disease: Network pharmacology analysis, molecular docking, and experimental assessment.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is defined by persistent airway and lung inflammation, excessive mucus production, remodeling of the airways, and damage to the alveolar tissue. Based on clinical experience, it has been observed that Jianpiyifei II (JPYF II) granules exhibit a significant therapeutic impact on individuals suffering from stable COPD. Nevertheless, the complete understanding of JPYF II's potential mode of action against COPD remains to be further clarified. PURPOSE: To further investigate the underlying mechanism of JPYF II for treating COPD and clarify the role of the IL-17 pathway in the treatment. METHODS: A variety of databases were utilized to acquire JPYF II's bioactive components, as well as related targets of JPYF II and COPD. Cytoscape was utilized to establish multiple interaction networks for the purpose of topological analyses and core-target screening. The Metascape was utilized to identify the function of target genes and crucial signaling pathways. To evaluate the interactions between bioactive ingredients and central target proteins, molecular docking simulations were conducted. Following that, a sequence of experiments was conducted both in the laboratory and in living organisms, which included analyzing the cell counts in bronchoalveolar lavage fluid (BALF), examining lung tissue for histopathological changes, conducting immunohistochemistry, RT‒qPCR, ELISA, and Western blotting. RESULTS: In JPYF II, 88 bioactive ingredients were predicted to have a total of 342 targets. After conducting Venn analysis, it was discovered that 284 potential targets of JPYF II were linked to the provision of defensive benefits against COPD. The PPI network yielded a total of twenty-four core targets. The findings from the analysis of enrichment and gene‒pathway network suggested that JPYF II targeted Hsp90, MAPKs, ERK, AP-1, TNF-α, IL-6, COX-2, CXCL8, and MMP-9 as crucial elements for COPD treatment through the IL-17 pathway. Additionally, JPYF II might modulate MAPK signaling pathways and the downstream transcription factor AP-1 via IL-17 regulation. According to the findings from molecular docking, it was observed that the 24 core target proteins exhibited robust binding affinities towards the top 10 bioactive compounds. Furthermore, the treatment of COPD through the regulation of MAPKs in the IL-17 pathway was significantly influenced by flavonoids and sterols found in JPYF II. In vitro, these observations were further confirmed. In vivo results demonstrated that JPYF II reduced inflammatory cell infiltration in pulmonary tissues and the quantity of inflammatory cells in BALF obtained from LPS- and CS-stimulated mice. Moreover, the administration of JPYF II resulted in the inhibition of IL-17 mRNA and protein levels, phosphorylation levels of MAPK proteins, and expression of phosphorylated AP-1 proteins. It also suppressed the expression of downstream effector genes and proteins associated with the IL-17/MAPK/AP-1 signaling axis in lung tissues and BALF. CONCLUSION: This research reveals that JPYF II improves COPD by controlling the IL-17/MAPK/AP-1 signaling axis within the IL-17 pathway for the first time. These findings offer potential approaches for the creation of novel medications that specifically target IL-17 and proteins involved in the IL-17 pathway to address COPD.

Echinacoside exerts neuroprotection via suppressing microglial α-synuclein/TLR2/NF-κB/NLRP3 axis in parkinsonian models.

BACKGROUND: Echinacoside (ECH), a natural active compound, was found to exert neuroprotection in Parkinson's disease (PD). However, the underlying molecular mechanisms remain controversial. PURPOSE: This study aimed to explore the roles of ECH in PD and its engaged mechanisms. CONCLUSION: In vivo, MPTP was adapted to construct subacute PD mouse model to explore the regulation of ECH on NLRP3 inflammasome. In vitro, α-synuclein (α-syn)/MPP+ was used to mediate the activation of NLRP3 inflammasome in BV2 cells, and the mechanism of ECH regulation of it was explored with molecular docking, immunofluorescence, Western blotting, and small molecule inhibitors. CONCLUSION: The activation of microglial NLRP3 inflammasome could be evoked by MPTP in vitro, but its toxic metabolite MPP+ alone cannot trigger the activation of NLRP3 inflammasome in vitro, which requires α-synuclein (α-syn) priming. Exogenous α-syn could evoke microglial TLR2/NF-κB/NLRP3 axis, playing the priming role in MPP+ -mediated NLRP3 inflammasome activation. ECH can suppress the upregulation of α-syn in MPTP-treated mice and BV2 microglia. It can also suppress the activation of the TLR2/NF-κB/NLRP3 axis induced by α-syn. CONCLUSION: ECH exerts neuroprotective effects by downregulating the TLR2/NF-κB/NLRP3 axis via reducing the expression of α-syn in the PD models.

Determining the safety and effectiveness of Tai Chi: a critical overview of 210 systematic reviews of controlled clinical trials.

BACKGROUND: This overview summarizes the best available systematic review (SR) evidence on the health effects of Tai Chi. METHODS: Nine databases (PubMed, Cochrane Library, EMBASE, Medline, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Sino-Med, and Wanfang Database) were searched for SRs of controlled clinical trials of Tai Chi interventions published between Jan 2010 and Dec 2020 in any language. Effect estimates were extracted from the most recent, comprehensive, highest-quality SR for each population, condition, and outcome. SR quality was appraised with AMSTAR 2 and overall certainty of effect estimates with the GRADE method. RESULTS: Of the 210 included SRs, 193 only included randomized controlled trials, one only included non-randomized studies of interventions, and 16 included both. Common conditions were neurological (18.6%), falls/balance (14.7%), cardiovascular (14.7%), musculoskeletal (11.0%), cancer (7.1%), and diabetes mellitus (6.7%). Except for stroke, no evidence for disease prevention was found; however, multiple proxy-outcomes/risks factors were evaluated. One hundred and fourteen effect estimates were extracted from 37 SRs (2 high, 6 moderate, 18 low, and 11 critically low quality), representing 59,306 adults. Compared to active and/or inactive controls, 66 of the 114 effect estimates reported clinically important benefits from Tai Chi, 53 reported an equivalent or marginal benefit, and 6 an equivalent risk of adverse events. Eight of the 114 effect estimates (7.0%) were rated as high, 43 (37.7%) moderate, 36 (31.6%) low, and 27 (23.7%) very low certainty evidence due to concerns with risk of bias (92/114, 80.7%), imprecision (43/114, 37.7%), inconsistency (37/114, 32.5%), and publication bias (3/114, 2.6%). SR quality was often limited by the search strategies, language bias, inadequate consideration of clinical, methodological, and statistical heterogeneity, poor reporting standards, and/or no registered SR protocol. CONCLUSIONS: The findings suggest Tai Chi has multidimensional effects, including physical, psychological and quality of life benefits for a wide range of conditions, as well as multimorbidity. Clinically important benefits were most consistently reported for Parkinson's disease, falls risk, knee osteoarthritis, low back pain, cerebrovascular, and cardiovascular diseases including hypertension. For most conditions, higher-quality SRs with rigorous primary studies are required. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021225708.

Chinese herbal injections versus intrapleural cisplatin for lung cancer patients with malignant pleural effusion: A Bayesian network meta-analysis of randomized controlled trials.

Background: Malignant pleural effusion (MPE) is a common complication in patients with advanced lung cancer that can severely compromise the quality of life and limit life expectancy. Randomized controlled trials (RCTs) have shown that Chinese herbal injections (CHIs) may be beneficial in improving quality of life. This network meta-analysis (NMA) aims to explore several CHIs used for lung cancer patients with MPE. Methods: Seven databases were systematically searched for eligible RCTs from inception to November 2021. The primary outcome was the clinical effective rate. Secondary outcomes were the improvement rate of Karnofsky performance status (KPS) score and incidence of adverse events (AEs). The Cochrane risk of bias 2 tool was used to assess the quality of included studies. Data analysis was performed using STATA 16.0 and R software 4.1.0. Both pairwise meta-analysis and Bayesian NMA were conducted. Competing interventions were ranked using the surface under the cumulative ranking (SUCRA) probabilities. Evidence grading was evaluated using the Confidence in Network Meta-Analysis online software (https://cinema.ispm.unibe.ch/). Results: A total of 44 studies involving 2,573 patients were included. The combined Huachansu injection (HCS) with intrapleural cisplatin (cis-diamminedichloro-platinum, DDP) had the highest probability of improving the clinical effective rate (SUCRA, 84.33%). The Kangai injection (KA) combined with DDP had the most improvement rate of KPS score (SUCRA, 80.82%), while the Fufangkushen injection (FFKS) alone was more likely to reduce AEs including gastrointestinal reactions (SUCRA, 89.92%), leukopenia (SUCRA, 91.85%), and chest pain (SUCRA, 98.17%). FFKS combined with DDP ranked the best in reducing the incidence of fever (SUCRA, 75.45%). Conclusions: Our NMA showed that CHIs alone or combined with DDP could improve clinical effectiveness and quality of life and reduce AEs, compared to DDP alone. HSC and KA, combined with DDP, may be the most effective considering clinical effective rate and improvement of KPS score, respectively. FFKS, either used alone or in combination therapy with DDP, may be the best in reducing AEs. However, high-quality RCTs with larger sample sizes are needed to further support the evidence. Systematic review registration: PROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42021285275.

Treatment with JianPiYiFei II granules for patients with moderate to very severe chronic obstructive pulmonary disease: A 52-week randomised, double-blinded, placebo-controlled, multicentre trial.

BACKGROUND: Complementary and alternative therapy is widely used to treat chronic obstructive pulmonary disease (COPD). A Chinese herbal medicine, JianPiYiFei (JPYF) II granules, have been shown to improve COPD patients' quality of life, however long-term effectiveness has not been examined. PURPOSE: To investigate whether long-term treatment with JPYF II granules is effective and safe for patients with stable, moderate to very severe COPD. STUDY DESIGN AND METHODS: A multicentre, randomised, double-blinded, placebo-controlled trial was conducted. Eligible participants from six hospitals were randomly assigned 1:1 to receive either JPYF II granules or placebo for 52 weeks. The primary outcome was the change in St. George's Respiratory Questionnaire (SGRQ) score during treatment. Secondary outcomes included the frequency of acute exacerbations during treatment, COPD Assessment Test (CAT), 6-minute walking test (6MWT), lung function, body mass index, airflow obstruction, dyspnoea, exercise capacity (BODE) index, and peripheral capillary oxygen saturation (SpO2) at the end of treatment. RESULTS: A total of 276 patients (138 in each group) were included in the analysis. JPYF II granules led to a significantly greater reduction in SGRQ score (-7.33 points, 95% CI -10.59 to -4.07; p < 0.0001) which reflects improved quality of life. JPYF II granules improved CAT (-3.49 points, 95% CI -5.12 to -1.86; p < 0.0001) and 6MWT (45.61 metres, 95% CI 20.26 to 70.95; p = 0.0005), compared with placebo. Acute exacerbations were less frequent with JPYF II granules than with placebo (0.87 vs. 1.34 events per patient; p = 0.0043). There were no significant differences between the groups in lung function, BODE index and SpO2. JPYF II granules were well tolerated and no significant adverse effects were noted. CONCLUSIONS: Long-term treatment with JPYF II granules is effective in moderate to very severe COPD, improving quality of life and exercise capacity, decreasing the risk of acute exacerbation, and relieving symptoms.

[Identification of chemical constituents in Zhachong Shisanwei Pills by UPLC-Q-TOF-MS/MS].

Zhachong Shisanwei Pills, composed of 13 Chinese medicinal materials, are used for treating the diseases such as hemiplegia, pain of muscles and bones, rheumatism, and joint pain. The chemical composition and pharmacodynamics of Zhachong Shisanwei Pills have not been reported. Ultra-performance liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to quickly identify the chemical components of Zhachong Shisanwei Pills, which was performed with Shim-pack GIST C_(18) column(4.6 mm×150 mm, 5 µm). The gradient elution was conducted with methanol-0.05% acetic acid as the mobile phase. Electrospray ionization mass spectrometry(ESI-MS) was carried out in both positive and negative ion modes. The compounds were identidied based on accurate relative molecular weight, fragment ion species, and the MS data of reference substances and in literature. In conclusion, a total of 98 compounds were identified, including 19 organic acids, 36 flavonoids, 13 volatile oils, 8 tannins, 5 2-(2-phenylethyl)chromones, 5 amino acids, 3 sesquiterpenoids, 3 alkaloids, and 2 other compounds. This study characte-rized the chemical components of Zhachong Shisanwei Pills rapidly for the first time, laying a foundation for further research on the pharmacodynamic material basis and quality evaluation.

Identification of chemical constituents in Zhachong Shisanwei Pills by UPLC-Q-TOF-MS/MS / 中国中药杂志

Zhachong Shisanwei Pills, composed of 13 Chinese medicinal materials, are used for treating the diseases such as hemiplegia, pain of muscles and bones, rheumatism, and joint pain. The chemical composition and pharmacodynamics of Zhachong Shisanwei Pills have not been reported. Ultra-performance liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to quickly identify the chemical components of Zhachong Shisanwei Pills, which was performed with Shim-pack GIST C_(18) column(4.6 mm×150 mm, 5 μm). The gradient elution was conducted with methanol-0.05% acetic acid as the mobile phase. Electrospray ionization mass spectrometry(ESI-MS) was carried out in both positive and negative ion modes. The compounds were identidied based on accurate relative molecular weight, fragment ion species, and the MS data of reference substances and in literature. In conclusion, a total of 98 compounds were identified, including 19 organic acids, 36 flavonoids, 13 volatile oils, 8 tannins, 5 2-(2-phenylethyl)chromones, 5 amino acids, 3 sesquiterpenoids, 3 alkaloids, and 2 other compounds. This study characte-rized the chemical components of Zhachong Shisanwei Pills rapidly for the first time, laying a foundation for further research on the pharmacodynamic material basis and quality evaluation.

Inhibition of Inflammation and Regulation of AQPs/ENaCs/Na+-K+-ATPase Mediated Alveolar Fluid Transport by Total Flavonoids Extracted From Nervilia fordii in Lipopolysaccharide-induced Acute Lung Injury.

Aims: The occurrence of vascular permeability pulmonary edema in acute lung injury (ALI) is related to the imbalance of alveolar fluid transport. Regulating the active transport of alveolar fluid by aquaporins (AQPs), epithelial sodium channels (ENaCs), and Na+-K+-ATPase can effectively reduce the edema fluid in the alveolar cavity and protect against ALI. We evaluated the therapeutic effects of total flavonoids, extracted from Nervilia fordii (TFENF), and investigated its potential mechanisms of alveolar fluid transport in a rat ALI model. Materials and methods: A model of lipopolysaccharide (LPS, 5 mg/kg)-induced ALI was established in Sprague-Dawley (SD) rats through the arteriae dorsalis penis. SD rats were divided into six groups, including the vehicle, LPS model, TFENF (6 mg/kg, 12 mg/kg, 24 mg/kg), and dexamethasone group (DEX group, 5 mg/kg). The wet-to-dry (W/D) lung weight ratio, oxygenation index, and histopathological observation were used to evaluate the therapeutic effect of TFENF. The mRNA expression of AQPs, ENaCs, and pro-inflammatory cytokines was determined using real-time polymerase chain reaction, whereas protein expression was determined using immunohistochemistry. The Na + -K + -ATPase activity was assessed using enzyme-linked immunosorbent assay. Results: LPS significantly stimulated the production of inflammatory mediators including tumor necrosis factor (TNF)-α and interleukin (IL)-1ß, and disrupted the water transport balance in the alveolar cavity by inhibiting AQPs/ENaCs/Na + -K + -ATPase. Pretreatment with TFENF reduced the pathological damage and W/D ratio of the lungs and ameliorated the arterial blood oxygen partial pressure (PaO2) and oxygenation index. TFENF further decreased the mRNA level of TNF-α and IL-1ß; increased the expression of AQP-1, AQP-5, αENaC, and ßENaC; and increased Na + -K + -ATPase activity. Moreover, the regulation of AQPs, ßENaC, and Na + -K + -ATPase and the inhibition of TNF-α and IL-1ß by TFENF were found to be dose dependent. Conclusion: TFENF protects against LPS-induced ALI, at least in part, through the suppression of inflammatory cytokines and regulation of the active transport capacity of AQPs/ENaCs/Na + -K + -ATPase. These findings suggest the therapeutic potential of TFENF as phytomedicine to treat inflammation and pulmonary edema in ALI.

The traditional herbal formulation, Jianpiyifei II, reduces pulmonary inflammation induced by influenza A virus and cigarette smoke in mice.

Chronic obstructive pulmonary disease (COPD) is a worldwide chronic inflammatory lung disease, and influenza A virus (IAV) infection is a common cause of acute exacerbations of COPD (AECOPD). Therefore, targeting viral infections represents a promising strategy to prevent the occurrence and development of inflammatory flare ups in AECOPD. Jianpiyifei II (JPYFII) is a traditional herbal medicine used in China to treat patients with COPD, and its clinical indications are not well understood. However, investigation of the anti-inflammatory effects and underlying mechanism using an animal model of smoking have been reported in a previous study by our group. In addition, some included herbs, such as Radix astragali and Radix aupleuri, were reported to exhibit antiviral effects. Therefore, the aim of the present study was to investigate whether JPYFII formulation relieved acute inflammation by clearing the IAV in a mouse model that was exposed to cigarette smoke experimentally. JPYFII formulation treatment during smoke exposure and IAV infection significantly reduced the number of cells observed in bronchoalveolar lavage fluid (BALF), expression of proinflammatory cytokines, chemokines, superoxide production, and viral load in IAV-infected and smoke-exposed mice. However, JPYFII formulation treatment during smoke exposure alone did not reduce the number of cells in BALF or the expression of Il-6, Tnf-a, and Il-1ß. The results demonstrated that JPYFII formulation exerted an antiviral effect and reduced the exacerbation of lung inflammation in cigarette smoke (CS)-exposed mice infected with IAV. Our results suggested that JPYFII formulation could potentially be used to treat patients with AECOPD associated with IAV infection.

Tai Chi for health and well-being: A bibliometric analysis of published clinical studies between 2010 and 2020.

The objective of this bibliometric review was to identify the volume, breadth, and characteristics of clinical studies evaluating Tai Chi published between January 2010 and January 2020. Five English and four Chinese language databases were searched. Following independent screening, 1018 eligible publications representing 987 studies were identified, which was a three-fold increase from the previous decade. Most common were randomized controlled trials (548/987, 55.5 %), followed by systematic reviews (157/987, 15.9 %), non-randomized controlled clinical studies (152/987, 15.4 %), case series (127/987, 12.9 %) and case reports (3/987, 0.3 %) that were conducted in China (730/987, 74.0 %), followed by the United States of America (123/987, 12.5 %) and South Korea (20/987, 2.0 %). Study participants were mostly in the adult (55.2 %) and/or older adult (72.0 %) age groups. The top ten diseases/conditions were hypertension, chronic obstructive pulmonary disease, diabetes, knee osteoarthritis, heart failure, depression, osteoporosis/osteopenia, breast cancer, coronary heart disease and insomnia. A quarter of the studies enrolled healthy participants to evaluate the effects of Tai Chi on health promotion/preservation, balance/falls, and physiological/biomechanical outcomes. Yang style Tai Chi was the most popular, followed by Chen and Sun style. Tai Chi was mostly commonly delivered face-to-face by a Tai Chi instructor in group settings for 60 min, three times a week, for 12 weeks. Most studies (93.8 %) reported at least one outcome in favor of Tai Chi. Adverse events were underreported (7.2 %). Over half fell short of expected intervention reporting standards, signalling the need for Tai Chi extensions to existing guidelines.

The ethnopharmacology, phytochemistry, pharmacology and toxicology of the genus Erycibe (Convolvulaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Erycibe belongs to the Convolvulaceae family that contains approximately 70 species mainly distributed from tropical and subtropical Asia to north of Australia. Several Erycibe species are traditionally used in folk medicine for the treatment of various ailments, including rheumatic arthralgia, primary glaucoma, hepatopathies, and infectious and malignant diseases. AIM OF THE REVIEW: This review aims to summarize comprehensive and updated information on traditional medicinal uses, phytochemistry, pharmacology, and toxicology of Erycibe species to provide a reference for the further research and application of the Erycibe genus. MATERIALS AND METHODS: The scientific and extensive literatures between 1975 and 2020 were systematically gathered from scientific databases such as SciFinder Scholar, Science Direct, Web of Science, PubMed, Google Scholar, Scopus, Springer Link and China National Knowledge Infrastructure (CNKI), as well as Chinese herbal classic books, PhD and MSc theses, and several official websites. RESULTS: Erycibe species have been used for the treatment of various rheumatoid diseases, glaucoma, a variety of hepatic diseases, infectious diseases and various malignancies in the traditional and local medicine. Since the 1970s, 153 compounds, including coumarins, quinic acid derivatives, flavonoids, alkaloids, lignans, and others have been isolated from five species of the Erycibe genus. Pharmacological studies have shown that these extracts and compounds from the Erycibe genus have extensive activities consistent with the traditional and local applications, such as anti-glaucoma, anti-arthritic, hepatoprotective and anti-cancer activities, as well as anti-inflammatory, anti-respiratory syncytial virus (RSV), and neuroprotective properties. CONCLUSIONS: Although there are extensive data on the genus Erycibe, certain specific gaps still exist. For herbal preparations containing Erycibe species, clinical toxicological investigation is required for the safety of these herbal preparation therapies, as well as further investigations on pharmacokinetics and bioavailability for guideline for clinical application. Furthermore, more detailed pharmacological, toxicological and clinical researches are needed to assess the alternatives to Erycibe species. Systematic and comprehensive pre-clinical studies are similarly required to estimate the possibility of extracts and compounds from the genus Erycibe with bioactivity developing into new drugs.

A systematic review of Tuina for irritable bowel syndrome: Recommendations for future trials.

OBJECTIVES: This systematic review assessed whether Tuina (therapeutic massage) is more effective and safer than no treatment or routine medical treatment for irritable bowel syndrome (IBS). METHODS: Eleven databases were searched for randomized controlled trials of IBS diagnosed based on Manning or Rome criteria. Tuina with or without routine treatments (RTs) was tested against RTs. The Cochrane risk of bias was evaluated for each trial. RevMan 5.3 was used to conduct a meta-analysis. RESULTS: A total of 8 trials (5 IBS-diarrhea and 3 IBS-constipation) with 545 participants using 8 different manipulations were included. All trials were published in Chinese. For overall symptom improving rate (> 30 % improvement in overall symptom scores), it had not been shown that Tuina was significantly better than RTs (RR 1.23, 95 % CI 0.94-1.60, 197 participants, 3 studies, I2 = 65 %) for IBS-diarrhea, and Tuina combined with RTs showed more benefit than RTs alone (RR 1.29, 95 % CI 1.08-1.54, 115 participants, 3 studies) for IBS-diarrhea. All trials did not report adverse effect in relation to Tuina. Risk of bias was generally unclear across all domains. CONCLUSIONS: Tuina combined with RTs may be superior to RTs for improving overall symptom of IBS-diarrhea. Due to the existing methodological issues and the heterogeneity of Tuina manipulation, current findings need to be confirmed in large scale, multicenter, and robust randomized trials (especially on outcome assessing blinding and allocation concealment).

Is Chinese Medicine Injection Applicable for Treating Acute Lung Injury and Acute Respiratory Distress Syndrome? A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To assess the efficacy and safety of Chinese medicine injection (CMI) for treating acute lung injury/acute respiratory distress syndrome (ALI/ARDS). METHODS: Randomized controlled trials (RCTs) were identified by searching 3 English databases and 4 Chinese databases from their inceptions until February 2019. The Cochrane Handbook was used to evaluate risk of bias in the included studies. Data analysis was conducted using RevMan 5.3.3 software. RESULTS: A total of 19 eligible RCTs involving 1,334 participants was included in this systematic review and meta-analysis. The main meta-analysis showed that CMI combined with conventional therapy (CT) was more effective than CT alone in reducing the acute physiology and chronic health evaluation (APACHE) H score [mean difference (MD): -1.74 points, 95% confidence interval (CI): -2.77 to -0.71, I2=0] and increasing the total effective rate [relative risk (RR): 1.35, 95% CI: 1.17 to 1.56, I2=37%]. Compared with CT, CMI combined with CT showed improvements in the arterial partial pressure of oxygen (PaO2, MD: 9.25 mm Hg, 95% CI: 0.87 to 17.63, I2=98%) and oxygenation index [arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2), MD: 50.75 mm Hg, 95% CI: 35.18 to 66.31, I2=94%]. CMI plus CT was superior to CT in reducing the systemic inflammatory response syndrome (SIRS) score (MD: -0.84 points, 95% CI: -1.26 to -0.42, I2=65%), length of hospital stay (MD: -4.22 days, 95% CI: -6.49 to -1.95, I2=92%), and duration of mechanical ventilation (MD: -2.94 days, 95% CI: -4.68 to -1.21, I2=89%). Only 1 study reported adverse events. CONCLUSIONS: CMI as an adjuvant therapy showed great potential benefits for the treatment of ALI/ARDS. However, we could not make a definite conclusion due to low quality of included studies and uncertain security. Future studies should focus on improving research design, especially in blindness and placebo. The reporting of adverse events was also needed.

The Potential Effects and Use of Chinese Herbal Medicine Pine Pollen (Pinus pollen): A Bibliometric Analysis of Pharmacological and Clinical Studies.

The objectives of this study are to conduct a comprehensive literature search and bibliometric analysis to identify the breadth and volume of pharmacological and clinical studies on pine pollen (Pinus pollen) and to identify the potential effects and the use of pine pollen. Three Chinese electronic databases and two English electronic databases were searched for pharmacological and clinical studies on pine pollen. Data were extracted and analyzed and included publication year, authors, study type, pharmacological research topics or clinical diseases/conditions, usage and type of preparation, authors' conclusions, and adverse effects. Of 239 publications identified, 180 were pharmacological studies, 37 were clinical trials, and 22 were reviews. Numbers of publications increased particularly from 2004 onward. The top 10 most frequent topics in pharmacological studies were immune regulation, antisenility, antioxidation, liver protection, inhibiting prostate hyperplasia, inhibiting tumor cell proliferation, lowering blood glucose, lowering blood lipids, antifatigue, and improving intestinal function. The top 10 most frequent clinical diseases treated or where pine pollen was used as an adjuvant were bedsores, diaper dermatitis, hyperlipidemia, oral mucositis, eczema, hyperplasia of prostate, hypertension, prostatitis, type 2 diabetes mellitus, and radiodermatitis. Eight trials reported no adverse events associated with pine pollen, one reported mild gastrointestinal reactions, but symptoms disappeared without special management. There have been an increasing number of publications on pine pollen during the past 20 years. Pharmacological studies have shown many potential benefits, and clinical studies have indicated some positive effects when it is either used as a single herb or as an adjuvant to treat disease. Its use as a topical agent, especially for skin diseases, was notable.

Protective Effect of Jianpiyifei II Granule against Chronic Obstructive Pulmonary Disease via NF-κB Signaling Pathway.

Jianpiyifei II granule (JPYF II) is an oriental herbal formula used clinically in China to treat chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the anti-inflammatory and antioxidative activities of JPYF II in a mouse model of COPD induced by lipopolysaccharide (LPS) and cigarette smoke (CS) and in RAW264.7 cells stimulated with cigarette smoke extract (CSE). Mice were given LPS via intratracheal instillation on days 1 and 15 and exposed to CS generated from 4 cigarettes/day for 28 days. The mice were treated with 0.75, 1.5, or 3 g/kg/d JPYF II by intragastric administration in low, middle, and high dose groups, respectively, for two weeks. RAW264.7 cells were stimulated by CSE and treated with JPYF II at doses of 12.5, 25, or 50 µg/mL. In the mouse model of LPS and CS-induced COPD, JPYF II decreased inflammatory cell counts in broncho alveolar lavage fluid (BALF), in addition to mRNA expression of proinflammatory cytokines and metalloproteinases (MMPs) in lung tissues. In addition, JPYF II elevated catalase (CAT) and glutathione peroxidase (GSH-Px) activities and reduced the levels of malondialdehyde (MDA) and IκBα and p65 phosphorylation and inflammatory cell infiltration in the lung tissues. In RAW264.7 cells stimulated with CSE, JPYF II inhibited the mRNA levels of inflammatory mediators and the phosphorylation of IκBα and p65. Our results suggest that JPYF II enhanced anti-inflammatory and antioxidative activities in a mouse model of COPD induced by LPS and CS and in RAW264.7 cells stimulated with CSE via inhibition of the NF-κB pathway.

Indole Alkaloids from the Leaves of Nauclea officinalis.

Three new indole alkaloids, named naucleamide G (1), and nauclealomide B and C (5 and 6), were isolated from the n-BuOH-soluble fraction of an EtOH extract of the leaves of Nauclea officinalis, together with three known alkaloids, paratunamide C (2), paratunamide D (3) and paratunamide A (4). The structures with absolute configurations of the new compounds were identified on the basis of 1D and 2D NMR, HRESIMS, acid hydrolysis and quantum chemical circular dichroism (CD) calculation. According to the structures of isolated indole alkaloids, their plausible biosynthetic pathway was deduced.

The antiviral effects of acteoside and the underlying IFN-γ-inducing action.

There are many herbal teas that are found in nature that may be effective at treating the symptoms and also shortening the duration of viral infections. When combating viral infections, T lymphocytes are an indispensable part of human acquired immunity. However, studies on the use of natural products in stimulating lymphocyte-mediated interferon-gamma (IFN-γ) production are very limited. In this study, we found that acteoside, a natural phenylpropanoid glycoside from Kuding Tea, enhanced IFN-γ production in mouse lymphocytes in a dose-dependent manner, particularly in the CD4+ and CD8+ subsets of T lymphocytes. To this end, we suggest that the antiviral activity of acteoside was highly correlated to its inducing ability of IFN-γ production. Mechanistically, the activation of T-bet enhanced the promoter of IFN-γ and subsequently resulted in an increased IFN-γ production in T cells. Collectively, we have found a natural product with the capacity to selectively enhance mouse T cell IFN-γ production. Given the role of IFN-γ in the immune system, further studies to clarify the role of acteoside in inducing IFN-γ and prevention of viral infection are needed.

Gypenoside L inhibits autophagic flux and induces cell death in human esophageal cancer cells through endoplasm reticulum stress-mediated Ca2+ release.

Esophageal cancer is one of the leading cause of cancer mortality in the world. Due to the increased drug and radiation tolerance, it is urgent to develop novel anticancer agent that triggers nonapoptotic cell death to compensate for apoptosis resistance. In this study, we show that treatment with gypenoside L (Gyp-L), a saponin isolated from Gynostemma pentaphyllum, induced nonapoptotic, lysosome-associated cell death in human esophageal cancer cells. Gyp-L-induced cell death was associated with lysosomal swelling and autophagic flux inhibition. Mechanistic investigations revealed that through increasing the levels of intracellular reactive oxygen species (ROS), Gyp-L triggered protein ubiquitination and endoplasm reticulum (ER) stress response, leading to Ca2+ release from ER inositol trisphosphate receptor (IP3R)-operated stores and finally cell death. Interestingly, there existed a reciprocal positive-regulatory loop between Ca2+ release and ER stress in response to Gyp-L. In addition, protein synthesis was critical for Gyp-L-mediated ER stress and cell death. Taken together, this work suggested a novel therapeutic option by Gyp-L through the induction of an unconventional ROS-ER-Ca2+-mediated cell death in human esophageal cancer.

Gypenoside L, Isolated from Gynostemma pentaphyllum, Induces Cytoplasmic Vacuolation Death in Hepatocellular Carcinoma Cells through Reactive-Oxygen-Species-Mediated Unfolded Protein Response.

Exploring novel anticancer agents that can trigger non-apoptotic or non-autophagic cell death is urgent for cancer treatment. In this study, we screened and identified an unexplored anticancer activity of gypenoside L (Gyp-L) isolated from Gynostemma pentaphyllum. We showed that treatment with Gyp-L induces non-apoptotic and non-autophagic cytoplasmic vacuolation death in human hepatocellular carcinoma (HCC) cells. Mechanically, Gyp-L initially increased the intracellular reactive oxygen species (ROS) levels, which, in turn, triggered protein ubiquitination and unfolded protein response (UPR), resulting in Ca(2+) release from endoplasm reticulum (ER) inositol trisphosphate receptor (IP3R)-operated stores and finally cytoplasmic vacuolation and cell death. Interruption of the ROS-ER-Ca(2+) signaling pathway by chemical inhibitors significantly prevented Gyp-L-induced vacuole formation and cell death. In addition, Gyp-L-induced ER stress and vacuolation death required new protein synthesis. Overall, our works provide strong evidence for the anti-HCC activity of Gyp-L and suggest a novel therapeutic option by Gyp-L through the induction of a unconventional ROS-ER-Ca(2+)-mediated cytoplasmic vacuolation death in human HCC.

[Three dimensional fluorescent characteristics of soil dissolved organic matter (DOM) in Jiaozhou Bay coastal wetlands, China]. / èƒ¶å·žæ¹¾æ»¨æµ·æ¹¿åœ°åœŸå£¤æº¶è§£æ€§æœ‰æœºè´¨çš„ä¸‰ç»´è§å ‰ç‰¹æ€§.

In order to elucidate the structure characteristics of soil dissolved organic matter (DOM) and analyze the sources in Jiaozhou Bay coastal wetlands, four typical types of wetlands around Jiaozhou Bay were chosen, including Spartina anglica wetland, the barren wetland, Suaeda glauca wetland and Phragmites australis wetland. The soil samples were collected in January 2014. The contents of soil DOM were determined and the spectral analysis was made by three-dimensional fluorescent technology. The results showed that the contents of soil dissolved organic carbon (DOC) in four types of wetlands all decreased with the increasing soil depth, and S. anglica wetland ranked the first in the contents of soil DOC, followed by the barren wetland, S. glauca wetland and P. australis wetland. Five fluorescence peaks including B, T, A, D and C were found in the three-dimensional fluorescence spectrum (3DEEMs), indicating tyrosine-like, tryptophan-like, phenol-like, soluble microbial byproduct-like and humic acid-like- substances, respectively. Fluorescence integration (FRI) was applied in the qualitative analysis of five components. The results showed that tryptophan-like, phenol-like and tyrosine-like substances ranked in top three in content, followed by soluble microbial byproduct-like and humic acid-like substances which were not significantly different. Pearson correlation analysis demonstrated that a positive correlation existed between any two of the five components of DOM, and they were all positively related to DOC content. In addition, there existed different correlations between the five components of DOM and total phosphorus (TP), available phosphorus (AP) and total nitrogen (TN). The soil DOM in the four types of wetlands was mainly produced by biotic interactions, and the degree of humification was relatively low.