Efficacy and safety of Chinese herbal medicine children's Zibei Xuanfei syrup in treating acute trachea-bronchitis with wind-heat invading lung syndrome: A randomized, double-blind, multicentre, controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Children's Zibei Xuanfei syrup is an herbal preparation from a lifetime professor, famous old Chinese doctor, and postgraduate supervisor of medical doctor of Shandong University of Traditional Chinese Medicine. This herbal preparation promotes lung health, relieves cough, reduces phlegm, and benefits pharynx. AIM OF THE STUDY: To verify the clinical efficacy and safety of Zibei Xuanfei syrup for children in treatment of acute trachea bronchitis with wind-heat invading lung syndrome. MATERIALS AND METHODS: This was an age-stratified, block randomized, double-blind, extremely low dose parallel control, multi-center clinical trial. A total of 453 pediatric patients diagnosed with acute tracheal bronchitis in Western medicine and cough due to exogenous factors with wind-heat invading lung syndrome in Chinese medicine were enrolled. They were divided into three subgroups based on age 1∼3, 4-7, and 8-14 years old, and randomly assigned to children's Zibei Xuanfei syrup and extremely low doses of children's Zibei Xuanfei syrup (control) in a 3:1 ratio. The primary outcome was the decreased values of cough Visual Analogue Scale (VAS) score after 7 days of administration. Secondary outcomes included a decrease in cough VAS score after 3 and 5 days of the administration, and the total score of Traditional Chinese Medicine(TCM) syndrome after 3, 5, and 7 days of treatment. The chest X-ray and blood C-reactive protein were examined during screening. The safety assessment included blood urine, and stool routine, liver and kidney function of laboratory tests, and an electrocardiogram at the screening and the last visit. RESULTS: The subjects of two groups had high administration adherence (completion over 80%) (299/323, 92.6% in children's Zibei Xuanfei syrup group vs 103/107, 96.3% in the control group; p > 0.05). The children's Zibei Xuanfei syrup group was significantly better than the control group in the decreased values of cough VAS score after 7 days of administration(6.35 ± 3.45 vs 3.73 ± 3.98, p < 0.001). The subgroup analysis of the decreased value of cough VAS scores aged 1-3 years old were 5.80 ± 3.43 vs 3.75 ± 4.38 (P = 0.003), 4-7 years old was 6.30 ± 3.69 vs 2.73 ± 3.65 (P < 0.001), and 8-14 years old were 6.91 ± 3.12 vs 4.69 ± 3.75(P = 0.001)respectively. The secondary outcomes decrease values of cough VAS score of children's Zibei Xuanfei syrup group vs control group after 5 days of administration were 5.88 ± 2.90 vs 3.55 ± 3.41(P < 0.001), after 3 days of administration were 3.61 ± 2.53 vs 2.43 ± 2.56 (P < 0.001). The effective rate of the TCM symptom total score of children's Zibei Xuanfei syrup group vs control group was 91.38% vs 54.95%after 7 days of the administration, 86.93% vs 50.94% after 5 days of the administration, and 64.78% vs 40.19% after 3 days administration(each p < 0.001). There was no significant difference in Adverse Event between the two groups (59/331, 17.82% vs 15/111, 13.51%, P > 0.05). The children's Zibei Xuanfei syrup group had 5 Serious Adverse Events (incidence rate 1.21%), all of which were unrelated to the trial drug. CONCLUSION: Children's Zibei Xuanfei syrup appears to be extremely effective and safe in the treatment of acute trachea bronchitis with wind-heat invading lung syndrome. Future studies with large sample sizes will need to collect more safety data use for children.

Kaempferol-3-O-rutinoside exerts cardioprotective effects through NF-κB/NLRP3/Caspase-1 pathway in ventricular remodeling after acute myocardial infarction.

Ventricular remodeling (VR) after acute myocardial infarction (AMI) is the main pathogenesis of chronic heart failure (CHF). Kaempferol-3-O-rutinoside (KR) is the flavonoid glycoside with the highest content in Lu'an GuaPian tea, which has good pharmacological activities. However, the mechanism of KR against VR after AMI remains unclear. Molecular docking was used to predict the targets of KR on the NLRP3/Caspase-1 signaling pathway. Histological changes in the myocardium were visualized using HE staining, Masson staining. Cardiomyocyte apoptosis was detected using TUNEL. Immunohistochemistry was used to examine NLRP3, Caspase-1 p20, and GSDMD. IL-1ß level in serum was detected using ELISA. Finally, the expressions of NF-κB p65, NLRP3, ASC, Caspase-1 p20, GSDMD, and IL-1ß were measured using RT-PCR and Western blotting. Our results showed that KR had a good binding activity with NLRP3, Caspase-1, and GSDMD, significantly improved cardiac function, alleviated cardiac pathological changes, reduced the excessive deposition of myocardial interstitial collagen, and inhibited cardiomyocyte apoptosis in AMI rats. Furthermore, KR could decrease the IL-1ß level and inhibit the expressions of NF-κB p65, NLRP3, ASC, Caspase-1 p20, GSDMD, and IL-1ß. Our study suggests that KR can prevent and treat VR after AMI, and the protective effect is related to its regulatory NF-κB/NLRP3/Caspase-1 signaling pathway. PRACTICAL APPLICATIONS: Kaempferol-3-O-rutinoside is present in Carthamus tinctorius L., Nymphaea candida, Afgekia mahidoliae and green tea, which has good pharmacological activities against liver injury, cerebral ischemia/reperfusion injury, dementia, hyperglycemia, and myocardial infarction. Our previous study found that kaempferol-3-O-rutinoside had an obvious anti-inflammatory effect, and could significantly improve the cell survival rate of H9c2 myocardium inflammatory injury induced by LPS. In this study, kaempferol-3-O-rutinoside significantly improved cardiac function, alleviated cardiac pathological changes, reduced the excessive deposition of myocardial interstitial collagen, and inhibited cardiomyocyte apoptosis in AMI rats. Furthermore, kaempferol-3-O-rutinoside could decrease the IL-1ß level and inhibit the expressions of NF-κB p65, NLRP3, ASC, Caspase-1, GSDMD and IL-1ß, suggesting that kaempferol-3-O-rutinoside could regulate NF-κB/NLRP3/Caspase-1 signaling pathway.

Efficacy and safety of Chinese herbal medicine Qirui Weishu capsule in treating chronic non-atrophic gastritis: A multicentre, double-blind, randomized controlled clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: QiruiWeishu capsule is an herbal preparation from a herbal formula prescribed by an experienced doctor at Guang'anmen Hospital of China Academy of Chinese Medical Sciences. It has been used clinically for more than 30 years. Abdominal pain, distension, and nausea are common symptoms of chronic non-atrophic gastritis with erosion dampness and heat stasis syndrome, and this herbal medicine has been used to treat them. AIM OF THE STUDY: To verify the clinical efficacy and safety of QiruiWeishu capsule in the treatment of chronic non-atrophic gastritis with damp-heat stasis syndrome. MATERIALS AND METHODS: This study was a multicenter randomized double-blind clinical trial with positive herbal drug SanjiuWeitai capsule as control and superiority test of main efficacy. A total of 477 subjects with chronic non-atrophic gastritis with erosion diagnosed by gastroscopy and pathological biopsy were randomly divided into QiruiWeishu capsule and SanjiuWeitai groups respectively in a ratio of 3:1. During the trial, subjects were required to complete medication for 28 days. The primary outcome was the disappearance rate of epigastric pain from baseline to 4weeks. At baseline, treatment at 1, 2, and 4 weeks, and follow-up at 8 and 16 weeks, the epigastric pain and traditional Chinese medicine (TCM) symptom scores were evaluated; gastroscopy, histopathology, and the helicobacter pylori test were evaluated at baseline and after 4 weeks of treatment. The safety assessment included blood routine, liver and kidney function, coagulation of laboratory tests, and electrocardiogram (ECG). RESULTS: Both groups of subjects had a high level of medication adherence (defined as treatment completion for over 80%) (346/357, 96.9% in Qirui Weishu group vs 118/120, 98.3% in Sanjiu Weitai group; p > 0.05). The QiruiWeishu capsule was significantly better than SanjiuWeitai capsule in disappearance rate of epigastric pain (64.2%, 229/357vs 46.7%, 56/120; p < 0.001)，especially subgroupsubjects with moderate epigastric pain (65.0%, 89/137 vs 30.4%, 14/46; p < 0.001), grade1 erythema (67.7%, 149/220 vs 51.9%, 42/81; p = 0.011) and grade 2 erythema (57.6%, 70/121 vs37.1%, 13/35; p = 0.050) of gastroscopy, grade 2 erosion (66.7%, 118/177 vs43.9%, 25/57; p = 0.002) of gastroscopy and Helicobacter pylori negative (65.4%, 155/237 vs 42.7%, 35/82; p < 0.001) at baseline. For the scores of TCM symptoms in QiruiWeishu group were significantly lower than those in SanjiuWeitai group after 28 days of treatment (p = 0.002). The number and incidence of adverse events related to the trial drug were 14/355 (3.9%) in QiruiWeishu group, 6/118 (5.1%) in SanjiuWeitai group (p > 0.05). No serious adverse reactions occurred in the two groups. According to laboratory tests and ECG, there was no discernible effect on heart, liver, kidney, or blood coagulation function. CONCLUSION: Qirui Weishu capsule appears to be more effective in terms of symptoms than the SanjiuWeitai capsule, and its use is both safe and effective for the treatment of chronic non-atrophic gastritis. A further randomized, double-blind, placebo-control trial is warranted to verify its benefit.

Effects of Plant Extracts on Dentin Bonding Strength: A Systematic Review and Meta-Analysis.

Objective: To systematically review in vitro studies that evaluated the effects of plant extracts on dentin bonding strength. Materials and Methods: Six electronic databases (PubMed, Embase, VIP, CNKI, Wanfang and The Cochrane Library) were searched from inception to September 2021 in accordance with the Preferred Reporting Items for Systematic Reviews (PRISMA). In vitro studies that compared the performance of dental adhesives with and without the plant extracts participation were included. The reference lists of the included studies were manually searched. Two researchers carried out study screening, data extraction and risk of bias assessment, independently and in duplicate. Meta-analysis was conducted using Review Manager 5.3. Results: A total of 62 studies were selected for full-text analysis. 25 articles used the plant extracts as primers, while five added the plant extracts into adhesives. The meta-analysis included 14 articles of in vitro studies investigating the effects of different plant extract primers on dentin bonding strength of etch-and-rinse and self-etch adhesives, respectively. The global analysis showed statistically significant difference between dental adhesives with and without plant extract primers. It showed that the immediate bond strength of dental adhesives was improved with the application of plant extract primers. Conclusion: The application of proanthocyanidin (PA) primers have positive effect on the in vitro immediate bonding strength of dental adhesives irrespective of etch-and-rinse or self-etch modes.

Flavonoids in Lu'an GuaPian tea as potential inhibitors of TMA-lyase in acute myocardial infarction.

Current studies have shown that plasma trimethylamine N-oxide (TMAO) level is closely related to the risk of acute myocardial infarction (AMI), that is, the possibility of AMI occurrence is positively correlated with TMAO level. The production of TMAO is mainly due to the transformation of trimethylamine (TMA) through the hepatic flavin-containing monooxygenase. Hence, inhibition of TMA production is essential. Flavonoids are considered to be mainly responsible for the health-promoting effects, and tea is rich in a variety of flavonoids. However, it is not clear that flavonoids from Lu'an GuaPian tea regulate gut microflora by inhibiting TMA-lyase activity to prevent AMI. Sixteen flavonoids from Lu'an GuaPian tea for the treatment of AMI based on the inhibition of TMA-lyase were summarized and screened. Docking results showed kaempferol 3-O-rutinoside had the highest Vina score, which means that it is the most active and can be used as lead compounds for structural modification. PRACTICAL APPLICATIONS: TMAO can be used as a marker of CHD and thus as a potential research object. Lu'an GuaPian tea is one of the top 10 famous teas in China and has the aroma of chestnuts and orchids. The flavonoids in Lu'an GuaPian tea are mainly composed of flavonoid aglycones and flavonoid glycosides. Since flavonoids have cardiovascular protection and can regulate gut microbiota, and gut microbiota is directly related to TMAO, reduction of TMAO level is to inhibit the transformation from TMA to TMAO. Kaempferol 3-O-rutinoside, quercetin 3-O-rhamnosylgalactoside, kaempferol 3-O-rhamnosylgalactoside, and myricetin 3-O-galactoside in Lu'an GuaPian tea have good binding affinities with TMA-lyase.

Preliminary Study on Antifungal Mechanism of Aqueous Extract of Cnidium monnieri Against Trichophyton rubrum.

Trichoderma rubrum (T. rubrum) is one of the important pathogens because it is the cause of most dermatomycosis. The treatment of Trichophyton rubrum infection is time-consuming and very expensive; it is easy for the infections to reoccur, leading to therapeutic failures, persistence, and chronic infection. These issues have inspired researchers to study natural alternative therapies instead. Cnidium monnieri (L.), as a kind of traditional Chinese medicine, has a variety of pharmacological activities and a wide range of applications, so it has a high potential for researching and economic value. We detected the effect of aqueous extract of C. monnieri (L.) on the activity of T. rubrum by Cell Count Kit-8 assay (CCK-8), and we found that 128 and 256 µg/ml of aqueous extracts of C. monnieri (L.) co-cultured with T. rubrum for 24 h showed the inhibitory effect on T. rubrum. The results of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) confirmed that aqueous extract of C. monnieri (L.) damaged the T. rubrum. At the same time, mass spectrometry screening with T. rubrum before and after the treatment of 256 µg/ml of aqueous extracts of C. monnieri (L.) showed that 966 differentially expressed proteins were detected, including 524 upregulated differentially expressed genes (DEGs) and 442 downregulated DEGs. The most significantly downregulated protein was chitin synthase (CHS); and the results of qRT-PCR and Western blotting demonstrated that the expression level of CHS was downregulated in the 256 µg/ml group compared with the control group. The study showed that the aqueous extract of C. monnieri (L.) could destroy the morphology of mycelia and the internal structure of T. rubrum, and it could inhibit the growth of T. rubrum. The antifungal effect of aqueous extract of C. monnieri (L.) may be related to the downregulation of the expression of CHS in T. rubrum, and CHS may be one of the potential targets of its antifungal mechanism. We concluded that aqueous extract from C. monnieri (L.) may be a potential candidate for antifungal agents.

Rat plasma protein binding of kaempferol-3-O-rutinoside from Lu'an GuaPian tea and its anti-inflammatory mechanism for cardiovascular protection.

Previous study found a high content of kaempferol-3-O-rutinoside (KR) in Lu'an GuaPian tea, however, the rat plasma protein binding and mechanism of KR for cardiovascular protection are unclear. Thus, we studied plasma protein binding using ultrafiltration followed by UPLC, and screened its inhibition against LPS-induced inflammation injury in vitro as well as the underlying mechanism by molecular docking and western blot. KR showed over 74% plasma protein binding ratio. Furthermore, KR may act on the toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). In vitro experiments showed that KR decreases the overexpression of TLR4, MyD88, and nuclear factor-κB (NF-κB), which further validates the molecular docking results, suggesting that KR could block TLR4/MyD88/NF-κB signaling. These results indicate that KR could be a potential active agent in the protection of myocardial injury. PRACTICAL APPLICATIONS: Health benefits of tea are largely dependent on the intake of flavonoids. Flavonoids are a group of compounds beneficial to cardiovascular disease and an important part of "functional foods." Lu'an GuaPian tea is mainly produced in Lu'an City, Anhui Province and is one of the top 10 famous teas in China. Kaempferol-3-O-rutinoside in Lu'an GuaPian has good hypoglycemic effect, mainly manifested in a strong inhibition of α-glucosidase and α-amylase activities. Present study showed that kaempferol-3-O-rutinoside could block TLR4/MyD88/NF-κB signaling, suggesting that it could be a potential active agent in the protection of myocardial injury.

Evaluation of the preventive effect of DL0805-2 against monocrotaline induced rat pulmonary arterial hypertension / 药学学报

In the treatment of hypertensive crisis, the novel Rho kinase inhibitor DL0805-2 can rapidly lower systematic blood pressure, reduce pulmonary artery pressure, and has a significant protective effect on lung injury. This experiment intends to evaluate the efficacy of DL0805-2 against pulmonary arterial hypertension (PAH) and preliminarily reveals its underlying mechanism. Animal welfare and experimental procedures are in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. Sprague Dawley (SD) rats were randomly divided into DL0805-2 low, medium, and high dose groups (1, 3, and 10 mg·kg-1), bosentan positive control group, model group, and blank control group. The drug was administered daily on the 7th day after model establishment by monocrotaline injection. On the 25th day of the experiment, relevant indicators were examined to observe the therapeutic effect of DL0805-2 on pulmonary hypertension. DL0805-2 significantly relieved the abnormal changes in the physiological parameters related to PAH induced by monocrotaline, including reducing right ventricular systolic pressure, alleviating cardiac damage caused by pressure overload, and reducing the levels of endothelin-1 and inflammatory factors in lung tissues. DL0805-2 also attenuated pulmonary arteries remodeling. It was preliminarily discovered that DL0805-2 exerts preventive and therapeutic effect on PAH through Rho-kinase pathway. Our results suggested that DL0805-2 had good therapeutic effects on monocrotaline-induced PAH rat model. It intervened early in the disease process, effectively prevented the development of the disease, and reduced the mortality of the diseased animals. The mechanism is related to Rho-kinase pathway.

Puerarin protects against myocardial ischemia/reperfusion injury by suppressing NLRP3 inflammasome activation via TLR4/Myd88/NF-κB pathway in rats / 药学学报

This study was to investigate the protective effects of puerarin on myocardial ischemia/reperfusion (MI/R) injury and the underlying mechanism. The MI/R-model was established by ligating the left anterior descending artery (LAD) for 60 min followed by 24 h reperfusion, puerarin (10, 30, and 100 mg·kg-1) was orally administered 20 min before reperfusion. Cardiac function, myocardial infarct index, cardiac damage markers, inflammatory cytokines, and apoptosis index were measured to evaluate the protective effects of puerarin on MI/R injury. The activation of Nod-like receptor protein 3 (NLRP3) inflammasome and Toll like receptor 4 (TLR4)/myeloid differentiation factor 88 (Myd88)/nuclear factor kappa B (NF-κB) pathway were determined by Western blot. All animal experimental procedures were approved by the ethics committee of the Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences. The results showed that puerarin could significantly improve cardiac function, reduce myocardial infarct size, decease the levels of lactic dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase-MB (CK-MB), and cardiac troponin T (cTnT) and suppress cardiomyocyte apoptosis. Meanwhile, puerarin could notably decrease the levels of inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Western blot analysis revealed that puerarin could downregulate the expression of TLR4, Myd88, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved-caspase 1, cleaved-gasdermin-D (GSDMD), IL-1β, and IL-18, as well as the phosphorylation levels of inhibitor of NF-κB α (IκBα), IκB kinase β (IKKβ), and NF-κB. These findings demonstrated that puerarin could alleviate MI/R injury by suppressing NLRP3 inflammasome activation, possibly via TLR4/Myd88/NF-κB pathway.

Is it necessary for children to receive professional fluoride in addition to regular fluoride toothpaste? Protocol for a systematic review.

INTRODUCTION: Regular toothbrushing with fluoride toothpaste is a fundamental intervention for caries prevention. Professional fluoride application (PFA) is widely considered a beneficial supplement to the routine use of fluoride toothpaste. However, some recent studies have failed to demonstrate the preventive effect of PFA. In addition, an increasing number of studies have highlighted the potential adverse effects of fluoride. However, little information exists on the effectiveness of additional PFA. The objective of this review is to systematically analyse the efficacy of PFA in addition to regular fluoride toothpaste among children under the age of 16. METHOD AND ANALYSIS: We will search the PubMed, Embase, Google Scholar and Cochrane Central Register of Controlled Trials databases for randomised controlled trials without language or publication date restrictions. Additional studies will be identified by manually searching the reference lists of the included studies and relevant reviews. At least two authors will carry out the selection of studies independently and in duplicate. The Cochrane Risk of Bias tool will be used to assess the risk of bias of the included studies. The random effects model will be used for meta-analyses. The data synthesis will be conducted using Review Manager software (RevMan V.5.3). The Grading of Recommendation, Assessment, Development and Evaluation will be used to assess the quality of supporting evidence for each major comparison. ETHICS AND DISSEMINATION: There is no need for ethical approval. The results of this review will be disseminated through peer-reviewed publications and social networks. PROSPERO REGISTRATION NUMBER: CRD42020165270.

Phytochemicals as potential IKK-ß inhibitor for the treatment of cardiovascular diseases in plant preservation: terpenoids, alkaloids, and quinones.

Modulation of inhibitor kappa B kinase-beta (IKK-ß) kinase activity could be useful for preventing inflammation that serves an efficient role in protection against cardiovascular diseases (CVDs). IKK-ß induces inflammation by activating transcription factor NF-kappa B (NF-κB) through phosphorylation of IκB. Therefore, IKK-ß is considered an interesting target for protecting and treating CVDs. The cardioprotective potential of terpenoids, alkaloids and quinines may be related to modulating inflammatory responses. In this study, the interactions between different classes of inhibitors and IKK-ß were investigated, through the application of SystemsDock. Molecular docking results showed that Diosgenin and Ginsenoside Re were the top docking score compounds. Diosgenin and Ginsenoside Re are the most promising IKK-ß inhibitors in terpenoids, alkaloids, and quinones. Diosgenin and Ginsenoside Re could be helpful to find the lead compounds on designing and developing novel cardioprotective agents.

Two Pairs of Isomerically New Phenylpropanoidated Epicatechin Gallates with Neuroprotective Effects on H2O2-Injured SH-SY5Y Cells from Zijuan Green Tea and Their Changes in Fresh Tea Leaves Collected from Different Months and Final Product.

Zijuan tea ( Camellia sinensis var. assamica), an anthocyanin-rich cultivar with purple leaves, is a valuable material for manufacturing tea with unique color and flavor. In this paper, four new phenylpropanoid substituted epicatechin gallates (pECGs), Zijuanins A-D (1-4), were isolated from Zijuan green tea by different column chromatography. Their structures were identified by extensive high resolution mass spectroscopy (HR-MS), nuclear magnetic resonance (NMR), and experimental and calculated circular dichroism (CD) spectroscopic analyses. Detection of the changes in fresh tea leaves collected from April to September and the final processed product by high performance liquid chromatography (HPLC)-HRMS suggested that production of compounds 1 and 2 may be enhanced by the processing procedure of Zijuan green tea. Additionally, 1-4 were proposed to be synthesized through interaction between the abundant secondary metabolite ECG and phenolic acids from tea leaves by two key steps of phenol-dienone tautomerism. 1 and 2 showed impressive activity in protecting SH-SY5Y cells against H2O2-induced damage at the concentration of 1.0 µM.

Effect of Shen-Fu Injection () on Hemodynamics in Early Volume Resuscitation Treated Septic Shock Patients / 中国结合医学杂志

OBJECTIVE@#To investigate the hemodynamic effect of Shen-Fu Injection (, SFI) in early volume resuscitation treated septic shock patients by monitoring pulse indicator continuous cardiac output (PICCO).@*METHODS@#All septic shock patients admitted in the Intensive Care Unit of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 1st, 2014 to December 31th, 2015, were reviewed, and totally 65 were enrolled in this study. They were assigned to SFI group (33 cases) and control group (32 cases). All 65 patients underwent conventional treatment mainly including volume resuscitation, antibiotics and vasoactive drugs therapy. The patients of the SFI group received additional 100 mL of SFI intravenously every 12 h. In all 65 patients, the PICCO arterial catheter and vein catheter were implanted within 1 h after the diagnosis of septic shock. In the course of early volume resuscitation, hemodynamic data of patients were recorded by PICCO monitor at 0, 12, and 24 h after the catheter implantation.@*RESULTS@#The hemodynamic indices of the two groups showed no significant differences at the beginning of 0 h (P>0.05). At 12 and 24 h, the hemodynamic indices of SFI group were significantly improved in comparison with the control group (P0.05).@*CONCLUSION@#SFI significantly improved hemodynamic indices such as CI, GEDI, MAP and HR in early volume resuscitation treated septic shock patients.

Inhibition of α-glucosidase and α-amylase by flavonoid glycosides from Lu'an GuaPian tea: molecular docking and interaction mechanism.

Green tea may favorably modulate blood glucose homeostasis, and regular consumption of green tea can prevent the development of type 2 diabetes mellitus. In this study, α-glucosidase and α-amylase inhibitory effects of the novel acylated flavonol tetraglycoside (camellikaempferoside C, 1) and 14 other flavone and flavone glycosides (FGs) isolated from Lu'an GuaPian (Camellia sinensis L.O. Kuntze) were evaluated. The kaempferol monoglycoside (15) showed inhibitory activity against α-glucosidase with IC50 at 40.02 ± 4.61 µM, and kaempferol diglycoside (13) showed α-amylase inhibition with IC50 at 0.09 ± 0.02 µM. Further, inhibitory mechanisms of FGs 15 and 13 were studied by molecular docking analysis and fluorescence spectrometry. Molecular docking suggested that FG 15 interacted with α-glucosidase mainly by hydrogen bonding, which was the same interaction force between FG 13 and α-amylase. Intrinsic fluorescence of α-glucosidase and α-amylase was quenched by 15 and 13, respectively, through a static quenching mechanism. The spontaneous formation of 15-α-glucosidase and 13-α-amylase complexes was driven by van der Waals forces and hydrogen bonding. The present study provides new insight into the potential application of Lu'an GuaPian green tea as a functional food ingredient to regulate postprandial hyperglycemia through inhibition of α-glucosidase/α-amylase by FGs, particularly the mono- and di- glycosides of kaempferol.

Interaction between Ester-Type Tea Catechins and Neutrophil Gelatinase-Associated Lipocalin: Inhibitory Mechanism.

Tea is thought to alleviate neurotoxicity due to the antioxidative effect of ester-type tea catechins (ETC). Neutrophil gelatinase-associated lipocalin (NGAL) can sensitize ß-amyloid (Aß) induced neurotoxicity, and inhibitors of NGAL may relieve associated symptoms. As such, the interactions of ETC with NGAL were investigated by fluorescence spectrometry and molecular simulation. NGAL fluorescence is quenched regularly when being added with six processing types of tea infusion (SPTT) and ETC. Thermodynamic analyses suggest that ETC with more catechol moieties has a stronger binding capacity with NGAL especially in the presence of Fe3+. (-)-Epicatechin 3-O-caffeoate (ECC), a natural product isolated from Zijuan green tea, shows the strongest binding ability with NGAL (Kd = 15.21 ± 8.68 nM in the presence of Fe3+). All ETC are effective in protecting nerve cells against H2O2 or Aß1-42 induced injury. The inhibitory mechanism of ETC against NGAL supports its potential use in attenuation of neurotoxicity.

Salvianolic acid A attenuates vascular remodeling in pulmonary arterial hypertension rats induced by monocrotaline / 中国药理学与毒理学杂志

OBJECTIVE Salvianolic acid A (SAA) is one of the most bioactive compounds from a traditional Chinese medicine called Dan Shen(Salvia Miltiorrhiza Bunge)and exhibits many pharmaco-logical activities.Previous studies have indicated that SAA may inhibit endothelial dysfunction and vascular remodeling in spontaneously hypertensive rats. However, whether SAA improves vascular remodeling induced by pulmonary arterial hypertension (PAH) remains unknown. In this study we examined whether SAA attenuated vascular remodeling in a PAH rat induced by monocrotaline(MCT),and elucidated the underlying mechanisms.METHODS PAH was induced in rats by injecting a single dose of monocrotaline (MCT 60 mg·kg-1).The rats were orally treated with either SAA(0.3,1,3 mg·kg-1·d-1)or a positive con-trol Bosentan(30 mg·kg-1·d-1)for 4 weeks.Echocardiography and hemodynamic measurements were performed on d 28.Then the hearts and lungs were harvested,the organ indices and pulmonary artery wall thickness were calculated,and biochemical and histochemical analysis were conducted.The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting.RESULTS Treatment with SAA effectively ameliorated MCT-induced pulmonary artery remodeling,pulmonary hemodynamic ab-normalities and the subsequent increases of right ventricular systolic pressure (RVSP). Furthermore, the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium,parenchymal in-jury and collagen deposition in the lungs.Moreover,the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs.The treatments partially restored MCT-induced reductions of bone morphoge-netic protein typeⅡ receptor (BMPRⅡ) and phosphorylated Smad1/5 in the lungs. CONCLUSION SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis.Thus,SAA may have therapeutic potential for the pa-tients at high risk of PAH.

Antimicrobial activity and drug-resistant reverse of 6 traditional Chinese medicines against multidrug resistant bacteria in vitro / 国际检验医学杂志

Objective To filter the traditional Chinese medicine with strong antibacterial activity and effects of reversing drug resistance of bacteria for providing new ideas for the treatment of multi-drug resistant bacteria infection.Methods Six kinds of antibacterial Chinese traditional medicines commonly used in clinic treatment as Radix Paeoniae Rubra,Indigo Naturalis,Galla Chinensis,Flos Chrysanthemi Indici,Herba Hout-tuyniae,and Berberine were used in this study.After preparation of the extract using decocting method,bacte-riostatic effects of these six kinds of Chinese medicine on multiple resistant bacteria were detected by double dilution method.To evaluate the effects of Chinese medicines on reversing drug resistance of multi-drug resist-ant bacteria,minimum inhibitory concentrations for multi-drug resistant bacteria and the original strain were detected by K-B method and calculated the difference of the bacterial inhibition rings.Results T he six kinds of traditional Chinese medicines had different degrees of inhibitory effects on MDR-AB and MDR-PA,and the bacteriostatic effect sequence were Galla Chinensis,Herba Houttuyniae,Flos Chrysanthemi Indici,Radix Pae-oniae Rubra,Indigo Naturalis,and Berberine.The bacteriostatic titer of Galla Chinensis on MDR-AB and MDR-PA was 512-1 024,whose antibacterial activity was the strongest in the six antibacterial Chinese tradi-tional medicines.Galla chinensis and Berberine had significant effects on reversing drug resistance of MDR-AB MDR-PA(P<0.05),but the difference value of inhibition zone diameters before and after reversing were less than 3 mm.Conclusion Radix Paeoniae Rubra,Indigo Naturalis,Galla Chinensis,Flos Chrysanthemi Indici, Herba Houttuyniae,and Berberine could inhibit MDR-AB and MDR-PA in different degrees,in which Galla Chinensis was the most effective antibacterial Chinese Medicine.Ggalla chinensis and Berberine could reverse drug resistance of MDR-AB and MDR-PA to some extent.

Pharmacological interventions for preventing dry mouth and salivary gland dysfunction following radiotherapy.

BACKGROUND: Salivary gland dysfunction is an 'umbrella' term for the presence of either xerostomia (subjective sensation of dryness), or salivary gland hypofunction (reduction in saliva production). It is a predictable side effect of radiotherapy to the head and neck region, and is associated with a significant impairment of quality of life. A wide range of pharmacological interventions, with varying mechanisms of action, have been used for the prevention of radiation-induced salivary gland dysfunction. OBJECTIVES: To assess the effects of pharmacological interventions for the prevention of radiation-induced salivary gland dysfunction. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 14 September 2016); the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8) in the Cochrane Library (searched 14 September 2016); MEDLINE Ovid (1946 to 14 September 2016); Embase Ovid (1980 to 14 September 2016); CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 14 September 2016); LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; 1982 to 14 September 2016); Zetoc Conference Proceedings (1993 to 14 September 2016); and OpenGrey (1997 to 14 September 2016). We searched the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: We included randomised controlled trials, irrespective of their language of publication or publication status. Trials included participants of all ages, ethnic origin and gender, scheduled to receive radiotherapy on its own or in addition to chemotherapy to the head and neck region. Participants could be outpatients or inpatients. We included trials comparing any pharmacological agent regimen, prescribed prophylactically for salivary gland dysfunction prior to or during radiotherapy, with placebo, no intervention or an alternative pharmacological intervention. Comparisons of radiation techniques were excluded. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 39 studies that randomised 3520 participants; the number of participants analysed varied by outcome and time point. The studies were ordered into 14 separate comparisons with meta-analysis only being possible in three of those.We found low-quality evidence to show that amifostine, when compared to a placebo or no treatment control, might reduce the risk of moderate to severe xerostomia (grade 2 or higher on a 0 to 4 scale) at the end of radiotherapy (risk ratio (RR) 0.35, 95% confidence interval (CI) 0.19 to 0.67; P = 0.001, 3 studies, 119 participants), and up to three months after radiotherapy (RR 0.66, 95% CI 0.48 to 0.92; P = 0.01, 5 studies, 687 participants), but there is insufficient evidence that the effect is sustained up to 12 months after radiotherapy (RR 0.70, 95% CI 0.40 to 1.23; P = 0.21, 7 studies, 682 participants). We found very low-quality evidence that amifostine increased unstimulated salivary flow rate up to 12 months after radiotherapy, both in terms of mg of saliva per 5 minutes (mean difference (MD) 0.32, 95% CI 0.09 to 0.55; P = 0.006, 1 study, 27 participants), and incidence of producing greater than 0.1 g of saliva over 5 minutes (RR 1.45, 95% CI 1.13 to 1.86; P = 0.004, 1 study, 175 participants). However, there was insufficient evidence to show a difference when looking at stimulated salivary flow rates. There was insufficient (very low-quality) evidence to show that amifostine compromised the effects of cancer treatment when looking at survival measures. There was some very low-quality evidence of a small benefit for amifostine in terms of quality of life (10-point scale) at 12 months after radiotherapy (MD 0.70, 95% CI 0.20 to 1.20; P = 0.006, 1 study, 180 participants), but insufficient evidence at the end of and up to three months postradiotherapy. A further study showed no evidence of a difference at 6, 12, 18 and 24 months postradiotherapy. There was low-quality evidence that amifostine is associated with increases in: vomiting (RR 4.90, 95% CI 2.87 to 8.38; P < 0.00001, 5 studies, 601 participants); hypotension (RR 9.20, 95% CI 2.84 to 29.83; P = 0.0002, 3 studies, 376 participants); nausea (RR 2.60, 95% CI 1.81 to 3.74; P < 0.00001, 4 studies, 556 participants); and allergic response (RR 7.51, 95% CI 1.40 to 40.39; P = 0.02, 3 studies, 524 participants).We found insufficient evidence (that was of very low quality) to determine whether or not pilocarpine performed better or worse than a placebo or no treatment control for the outcomes: xerostomia, salivary flow rate, survival, and quality of life. There was some low-quality evidence that pilocarpine was associated with an increase in sweating (RR 2.98, 95% CI 1.43 to 6.22; P = 0.004, 5 studies, 389 participants).We found insufficient evidence to determine whether or not palifermin performed better or worse than placebo for: xerostomia (low quality); survival (moderate quality); and any adverse effects.There was also insufficient evidence to determine the effects of the following interventions: biperiden plus pilocarpine, Chinese medicines, bethanechol, artificial saliva, selenium, antiseptic mouthrinse, antimicrobial lozenge, polaprezinc, azulene rinse, and Venalot Depot (coumarin plus troxerutin). AUTHORS' CONCLUSIONS: There is some low-quality evidence to suggest that amifostine prevents the feeling of dry mouth in people receiving radiotherapy to the head and neck (with or without chemotherapy) in the short- (end of radiotherapy) to medium-term (three months postradiotherapy). However, it is less clear whether or not this effect is sustained to 12 months postradiotherapy. The benefits of amifostine should be weighed against its high cost and side effects. There was insufficient evidence to show that any other intervention is beneficial.

Novel acetylcholinesterase inhibitors from Zijuan tea and biosynthetic pathway of caffeoylated catechin in tea plant.

Zijuan tea is a special cultivar of Yunnan broad-leaf tea (Camellia sinensis var. assamica) with purple buds, leaves, and stems. Phytochemical study on this tea led to the discovery of three hydroxycinnamoylated catechins (HCCs) (1-3), seven other catechins (4-10), three proanthocyanidins (11-13), five flavones and flavone glycosides (14-18), two alkaloids (19, 20), one steroid (21), and one phenylpropanoid glycoside (22). The isolation and structural elucidation of the caffeoylated catechin (1) by means of spectroscopic techniques were described. We also provide the first evidence that 1 is synthesized via a two-step pathway in tea plant. The three HCCs (1-3) were investigated on their bioactivity through molecular modeling simulation and biochemical experiments. Our results show that they bind acetylcholinesterase (AChE) tightly and have strong AChE inhibitory activity with IC50 value at 2.49, 11.41, 62.26µM, respectively.

A novel ECG analog 4-(S)-(2,4,6-trimethylthiobenzyl)-epigallocatechin gallate selectively induces apoptosis of B16-F10 melanoma via activation of autophagy and ROS.

Autophagy-induced cancer cell death has become a novel strategy for the development of cancer therapeutic drugs. Numerous studies have indicated that green tea polyphenols induce both autophagy and apoptosis in a variety of cancer cells. Here, we synthesized a series of green tea polyphenol analogues, among which JP8 was shown to potently activate autophagy. JP8 treatment had a stronger effect on apoptosis in B16-F10 melanoma cells than that in normal AML-12 hepatocytes. JP8 selectively resulted in reactive oxygen species (ROS) accumulation in B16-F10 cells, and this effect was associated with corresponding increases in key components of the ER stress-mediated apoptosis pathway. Pharmacological inhibition of ROS by N-acetyl-L-cysteine (NAC) attenuated JP8-induced autophagy and apoptosis, indicating an upstream role of ROS in JP8-induced autophagy. An in vivo study showed that JP8 had significant antitumor effects in a B16-F10 xenograft mouse model. Our results indicate that JP8 is a novel anticancer candidate with both autophagy and ROS induction activities.