Flavonoid extracts of Citrus aurantium L. var. amara Engl. Promote browning of white adipose tissue in high-fat diet-induced mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Obesity has become a public burden worldwide due to its booming incidence and various complications, and browning of white adipose tissue (WAT) is recognized as a hopeful strategy to combat it. Blossom of Citrus aurantium L. var. amara Engl. (CAVA) is a popular folk medicine and dietary supplement used for relieving dyspepsia, which is recorded in the Chinese Materia Medica. Our previous study showed that blossom of CAVA had anti-obesity potential, while its role in browning of WAT was still unclear. AIM OF THE STUDY: This study aimed to characterize the constituents in flavonoids from blossom of CAVA (CAVAF) and to clarify the anti-obesity capacities especially the effects on browning of WAT. MATERIALS AND METHODS: Gradient ethanol eluents from blossom of CAVA were obtained by AB-8 macroporous resin. 3T3-L1 cells and pancreatic lipase inhibition assay were employed to investigate the potential anti-obesity effects in vitro. HPLC and UPLC/MS assays were performed to characterize the chemical profiles of different eluents. Network pharmacology and molecular docking assays were used to reveal potential anti-obesity targets. Furthermore, high-fat diet (HFD)-induced mice were constructed to explore the anti-obesity actions and mechanisms in vivo. RESULTS: 30% ethanol eluents with high flavonoid content and great inhibition on proliferation of 3T3-L1 preadipocytes and pancreatic lipase activity were regarded as CAVAF. 19 compounds were identified in CAVAF. Network pharmacology analysis demonstrated that AMPK and PPARα were potential targets for CAVAF in alleviating obesity. Animal studies demonstrated that CAVAF intervention significantly decreased the body weight, WAT weight, serum TG, TC and LDL-C levels in HFD-fed obese mice. HFD-induced insulin resistance and morphological changes in WAT and brown adipose tissue were also markedly attenuated by CAVAF treatment. CAVAF supplementation potently inhibited iWAT inflammation by regulating IL-6, IL-1ß, TNF-α and IL-10 mRNA expression in iWAT of mice. Furthermore, the gene expression levels of thermogenic markers including Cyto C, ATP synthesis, Cidea, Cox8b and especially UCP1 in iWAT of mice were significantly up-regulated by CAVAF administration. CAVAF intervention also markedly increased the expression levels of PRDM16, PGC-1α, SIRT1, AMPK-α1, PPARα and PPARγ mRNA in iWAT of mice. CONCLUSION: CAVAF treatment significantly promoted browning of WAT in HFD-fed mice. These results suggested that flavonoid extracts from blossom of CAVA were probably promising candidates for the treatment of obesity.

Effectiveness of Zhibai Dihuang pill (Chinese herbal formula) in combination with western drugs in the treatment of recurrent aphthous stomatitis: A systematic review and meta-analysis.

BACKGROUND: The pain caused by recurrent aphthous stomatitis (RAS) and the recurrent nature of RAS lead to diminished quality of life for RAS patients. An alternative treatment for RAS is the oral administration of the Chinese herbal medicine Zhibai Dihuang pill (ZBDHP). Our study aims to investigate the clinical efficacy of ZBDHP when used in combination with Western medicine (WM) for the treatment of RAS and its effectiveness in preventing the recurrence of RAS. METHODS: Following the PRISMA 2020 guidelines, we conducted a literature search on 7 electronic databases according to predefined criteria. The methodological quality of randomized controlled trials (RCTs) was evaluated based on the Cochrane Handbook, and data analysis was performed using RevMan 5.3 software. RESULTS: A meta-analysis which included 7 studies and 669 participants in total was carried out in this study. The quantitative analysis revealed that the combined treatment of ZBDHP and WM has witnessed significantly improved overall clinical efficacy (RR = 1.20, 95% CI [1.12, 1.28], P < .05), reduced recurrence rate (RR = 0.24, 95% CI [0.13, 0.45], P < .05), decreased ulcer area (MD = -0.75, 95% CI [-0.91, -0.59], P < .05), and reduced pain visual simulation score (MD = -0.42, 95% CI [-0.52, -0.33], P < .05). No significant heterogeneity was observed among the studies. Qualitative analysis showed that the combination therapy significantly reduced serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 and interleukin-10, shortened ulcer healing time and pain disappearance time, with no adverse effects observed. CONCLUSION: It was found that the combination of ZBDHP and WM is more effective in treating RAS than the use of WM alone, which thus provides clinicians with a more optimal treatment option. However, due to limitations in the methodological quality of the included original studies and the small sample size, we hold the opinion that more rigorous and scientific clinical trials are needed to further evaluate the efficacy of ZBDHP in treating RAS.

p-Synephrine ameliorates alloxan-induced diabetes mellitus through inhibiting oxidative stress and inflammation via suppressing the NF-kappa B and MAPK pathways.

Oxidative stress and inflammation play important roles in the development of diabetes mellitus. p-Synephrine, the primary pharmacologically active protoalkaloid in Citrus species, has been popularly consumed as a dietary supplement for weight loss management. However, the effects of p-synephrine on diabetes mellitus and the action mechanisms have not been clearly elucidated. In this study, the in vitro antioxidant effects of p-synephrine were evaluated. The data showed that p-synephrine treatment exhibited significant scavenging effects against DPPH, ABTS and OH radicals and showed high reducing power. Diabetic mice were developed by alloxan injection, followed by p-synephrine administration to investigate its hypoglycemic effects in vivo. The results showed that p-synephrine intervention significantly prevented alloxan-induced alteration in body weight, organ indexes, serum uric acid content and serum creatinine content. Meanwhile, p-synephrine application significantly improved the lipid profiles, superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) contents in the serum and kidneys of diabetic mice and reduced the malondialdehyde (MDA) content in the serum of diabetic mice. Further assays suggested that p-synephrine treatment improved alloxan-induced decreases of glucose tolerance and insulin sensitivity. Also, p-synephrine supplementation altered histopathological changes in the kidneys and interscapular brown adipose tissues in diabetic mice. In addition, p-synephrine administration inhibited renal inflammation through suppressing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) gene expression levels, as well as CD45 expression levels. The anti-inflammatory effects were probably involved in the regulation of nuclear factor-κB (NF-κB) activation and mitogen-activated protein kinase (MAPK) phosphorylation. In conclusion, p-synephrine application significantly ameliorated alloxan-induced diabetes mellitus by inhibiting oxidative stress via suppressing the NF-κB and MAPK pathways.

Exploring the mechanism of action of Xuanfei Baidu granule (XFBD) in the treatment of COVID-19 based on molecular docking and molecular dynamics.

Purpose: The Corona Virus Disease 2019 (COVID-19) pandemic has become a challenge of world. The latest research has proved that Xuanfei Baidu granule (XFBD) significantly improved patient's clinical symptoms, the compound drug improves immunity by increasing the number of white blood cells and lymphocytes, and exerts anti-inflammatory effects. However, the analysis of the effective monomer components of XFBD and its mechanism of action in the treatment of COVID-19 is currently lacking. Therefore, this study used computer simulation to study the effective monomer components of XFBD and its therapeutic mechanism. Methods: We screened out the key active ingredients in XFBD through TCMSP database. Besides GeneCards database was used to search disease gene targets and screen intersection gene targets. The intersection gene targets were analyzed by GO and KEGG. The disease-core gene target-drug network was analyzed and molecular docking was used for verification. Molecular dynamics simulation verification was carried out to combine the active ingredient and the target with a stable combination. The supercomputer platform was used to measure and analyze the number of hydrogen bonds, the binding free energy, the stability of protein target at the residue level, the solvent accessible surface area, and the radius of gyration. Results: XFBD had 1308 gene targets, COVID-19 had 4600 gene targets, the intersection gene targets were 548. GO and KEGG analysis showed that XFBD played a vital role by the signaling pathways of immune response and inflammation. Molecular docking showed that I-SPD, Pachypodol and Vestitol in XFBD played a role in treating COVID-19 by acting on NLRP3, CSF2, and relieve the clinical symptoms of SARS-CoV-2 infection. Molecular dynamics was used to prove the binding stability of active ingredients and protein targets, CSF2/I-SPD combination has the strongest binding energy. Conclusion: For the first time, it was found that the important active chemical components in XFBD, such as I-SPD, Pachypodol and Vestitol, reduce inflammatory response and apoptosis by inhibiting the activation of NLRP3, and reduce the production of inflammatory factors and chemotaxis of inflammatory cells by inhibiting the activation of CSF2. Therefore, XFBD can effectively alleviate the clinical symptoms of COVID-19 through NLRP3 and CSF2.

Natural bioactive constituents from herbs and nutraceuticals promote browning of white adipose tissue.

Obesity is a significant public health problem worldwide that is characterized by abnormal or excessive fat accumulation. Unfortunately, the application of available weight-loss drugs has been restricted because of their serious adverse effects. Browning of white adipose tissue (WAT), which refers to the transformation of white adipocytes to beige adipocytes under certain stimulations, is regarded as a new strategy to solve the obesity problem. Numerous studies have recently evidenced that traditional Chinese medicine (TCM) could promote browning of WAT with multi-component and multi-target characteristics. This article summarizes natural constituents from TCM with stimulatory effects on browning of WAT in the past two decades. The active ingredients can be generally divided into polyphenols, saponins, alkaloids, terpenoids, phenylpropanoids and others, such as resveratrol, quercetin, curcumin, genistein, capsaicin, epigallocatechin gallate (EGCG), berberine, menthol, emodin and ginsenosides. Simultaneously, the chemical structures, source, model, efficacy and mechanism of these monomeric compounds are also described. And the mechanisms of these active ingredients are mainly involved in the regulation of PRDM16, PGC-1α, PPARγ, SIRT1, AMPK, ß3-adrenergic receptors, TRPV1 and TRPM8 channels, FGF21 and miRNAs. The present article opens opportunities for developing novel drugs or supplements from TCM with wide acceptability to prevent obesity progression and its associated metabolic disorders.

Effect of Leifsonia sp. on retardation of uranium in natural soil and its potential mechanisms.

Uranium mining and milling activities for many years resulted in release of uranium into the adjoining soil in varying degrees. Bioremediation approaches (i.e., immobilization via the action of bacteria) resulting in uranium bearing solid is supposed as an economic and clean in-situ approach for the treatment of uranium contaminated sites. This study purposes to determine the immobilization efficiency of uranium in soil by Leifsonia sp. The results demonstrated that cells have a good proliferation ability under the stress of uranium and play a role in retaining uranium in soil. Residual uranium in active Leifsonia-medium group (66%) was higher than that in the controls, which was 31% in the deionised water control, 46% in the Leifsonia group, and 47% in the medium group, respectively. This indicated that Leifsonia sp. facilitates the immobilization efficiency of uranium in soil by converting part of the reducible and oxidizable fraction of uranium into the residual fraction. X-ray photoelectron fitting results showed that tetravalent states uranium existed in the soil samples, which indicated that the hexavalent uranium was converted into tetravalent by cells. This is the first report of effect of Leifsonia sp. on uranium immobilization in soil. The findings implied that Leifsonia sp. could, to some extent, prevent the migration and diffusion of uranium in soil by changing the chemical states into less toxicity and less risky forms.

Influence on Uranium(VI) migration in soil by iron and manganese salts of humic acid: Mechanism and behavior.

Soil contains large amounts of humic acid (HA), iron ions and manganese ions, all of which affect U(VI) migration in the soil. HA interacts with iron and manganese ions to form HA salts (called HA-Fe and HA-Mn in this paper); however, the effects of HA-Fe and HA-Mn on the migration of U(VI) is not fully understood. In this study, HA-Fe and HA-Mn were compounded by HA interactions with ferric chloride hexahydrate and manganese chloride tetrahydrate, respectively. The influence of HA, HA-Fe and HA-Mn on U(VI) immobilization and migration was investigated by bath adsorption experiments and adsorption-desorption experiments using soil columns. The results showed that the presence of HA, HA-Fe and HA-Mn retarded the migration of U(VI) in soil. Supported by X-ray photoelectron spectroscopy (XPS) and BCR sequential extraction analyses, a plausible explanation for the retardation was that HA-Fe and HA-Mn could reduce hexavalent uranium to stable tetravalent uranium and increase the specific gravity of Fe/Mn oxide-bound uranium and organic/sulfide-bound uranium, which made it difficult for them to longitudinally migrate in soil. Scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and surface area and pore size analyses indicated that the complex formed between the hydroxyl, amino and carboxyl groups of HA-Fe and U(VI) increased the crystallinity of HA-Fe. The reaction between U(VI) and the hydroxyl, amino, aldehyde, keto and chlorine-containing groups of HA-Mn had no effect on the crystallinity of HA-Mn. Notably, the column desorption experiment found that the U(VI) immobilized in the soil remigrated under the effect of rain leaching, and acid rain promoted uranium remigration better than neutral rain. The findings provide some guidance for the decommissioning disposal of uranium contaminated site and it's risk assessments.

A novel autophagy inhibitor berbamine blocks SNARE-mediated autophagosome-lysosome fusion through upregulation of BNIP3.

Increasing evidences reveal that autophagy inhibitor could enhance the effect of chemotherapy to cancer. However, few autophagy inhibitors are currently approved for clinical application in humans. Berbamine (BBM) is a natural compound extracted from traditional Chinese medicine that is widely used for treatment of a variety of diseases without any obvious side effects. Here we found that BBM is a novel auophagy inhibitor, which potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human breast cancer cells. Mechanistically, we found that BBM blocked autophagosome-lysosome fusion by inhibiting the interaction of SNAP29 and VAMP8. Furthermore, BBM induced upregulation of BNIP3 and the interaction between SNAP29 and BNIP3. BNIP3 depletion or SNAP29 overexpression abrogated BBM-mediated blockade of autophagosome-lysosome fusion through the interaction between SNAP29 and VAMP8, whereas BNIP3 overexpression blocked autophagosome-lysosome fusion through inhibition of the interaction between SNAP29 and VAMP8. These findings suggest that upregulation of BNIP3 and interaction between BNIP3 and SNAP29 could be involved in BBM-mediated blockade of autophagosome-lysosome fusion through inhibition of the interaction between SNAP29 and VAMP8. Our findings identify the critical role of BNIP3 in blockade of autophagosome-lysosome fusion mediated by BBM, and suggest that BBM could potentially be further developed as a novel autophagy inhibitor, which could enhance the effect of chemotherapy to cancer.

Construction of the Syngonium podophyllum-Pseudomonas sp. XNN8 Symbiotic Purification System and Investigation of Its Capability of Remediating Uranium Wastewater.

The endophyte Pseudomonas sp. XNN8 was separated from Typha orientalis which can secrete indole-3-acetic acid and 1-aminocyclopropane-1-carboxylate deaminase and siderophores and has strong resistance to uranium it was then colonized in the Syngonium podophyllum; and the S. podophyllum-Pseudomonas sp. XNN8 symbiotic purification system (SPPSPS) for uranium-containing wastewater was constructed. Afterwards, the hydroponic experiments to remove uranium from uranium-containing wastewater by the SPPSPS were conducted. After 24 days of treatment, the uranium concentrations of the wastewater samples with uranium concentrations between 0.5 and 5.0 mg/L were lowered to below 0.05 mg/L. Furthermore, the uranium in the plants was assayed using Fourier transform infrared spectroscopy (FTIR) and extended X-ray absorption fine structure (EXAFS) spectroscopy. The Pseudomonas sp. XNN8 was found to generate substantial organic groups in the roots of the Syngonium podophyllum, which could improve the complexing capability of S. podophyllum for uranium. The uranium in the roots of S. podophyllum was found to be the uranyl phosphate (47.4 %) and uranyl acetate (52.6 %).

An artificially constructed Syngonium podophyllum-Aspergillus niger combinate system for removal of uranium from wastewater.

Aspergillus niger was inoculated to the roots of five plants, and the Syngonium podophyllum-A. niger combinate system (SPANCS) was found to be the most effective in removing uranium from hydroponic liquid with initial uranium concentration of 5 mg L(-1). Furthermore, the hydroponic experiments on the removal of uranium from the hydroponic liquids with initial uranium concentrations of 0.5, 1.0, and 3.0 mg L(-1) by the SPANCS were conducted, the inhibitory effect of A. niger on the growth of S. podophyllum in the SPANCS was studied, the accumulation characteristics of uranium by S. podophyllum in the SPANCS were analyzed, and the Fourier transform infrared (FT-IR) and extended X-ray absorption fine structure (EXAFS) spectra were measured. The results show that the removal of uranium by the SPANCS from the hydroponic liquids with initial uranium concentrations of 0.5, 1.0, and 3.0 mg L(-1) reached 98.20, 97.90, and 98.50%, respectively, after 37 days of accumulation of uranium; that the uranium concentrations in the hydroponic liquids decreased to 0.009, 0.021, and 0.045 mg L(-1), respectively, which are lower than the stipulated concentration for discharge of 0.050 mg L(-1) by the People's Republic of China; that A. niger helped to generate more groups in the root of S. podophyllum which can improve the complexing capability of S. podophyllum for uranium; and that the uranium accumulated in the root of S. podophyllum was in the form of phosphate uranyl and carboxylic uranyl.

Tea consumption and risk of type 2 diabetes: a dose-response meta-analysis of cohort studies.

Tea consumption has inconsistently been shown to be associated with the risk of type 2 diabetes (T2D). The aim of the present study was to conduct a dose-response meta-analysis of cohort studies assessing the association between consumption of tea and risk of developing T2D. Pertinent studies were identified by searching PubMed, Web of Science and EMBASE through 31 March 2013. A total of sixteen cohorts from fifteen articles that reported 37,445 cases of diabetes among 545,517 participants were included. A significant linearly inverse association between tea consumption and T2D risk was found (P for linear trend = 0.02). An increase of 2 cups/d in tea consumption was found to be associated with a 4.6 (95% CI 0.9, 8.1) % reduced risk of T2D. On the basis of the dose-response meta-analysis, the predicted relative risks of diabetes for 0, 1, 2, 3, 4, 5 and 6 cups of tea consumed per d were 1.00 (referent), 0.97 (95% CI 0.94, 1.01), 0.95(95% CI 0.92, 0.98), 0.93 (95% CI 0.88, 0.98), 0.90 (95% CI 0.85, 0.96), 0.88 (95 % CI 0.83, 0.93) and 0.85 (95% CI 0.80, 0.91), respectively. There was a statistically significant heterogeneity within the selected studies (Q= 45.32, P< 0.001, I 2= 60.3 %). No evidence of substantial small-study bias was found (P= 0·46). Our findings suggest that tea consumption could be linearly inversely associated with T2D risk. Future well-designed observational studies that account for different characteristics of tea such as tea types, preparation methods and tea strength are needed to fully characterise such an association.

Cocaine detection by structure-switch aptamer-based capillary zone electrophoresis.

Aptamers, which are nucleic acid oligonucleotides that can bind targets with high affinity and specificity, have been widely applied as affinity probes in capillary electrophoresis (CE). Due to relative weak interaction between aptamers and small molecules, the application of aptamer-based CE is still limited in certain compounds. A new strategy that is based on the aptamer structure-switch concept was designed for small molecule detection by a novel CE method. A carboxyfluorescein (fluorescein amidite, FAM) label DNA aptamer was first incubated with partial complementary strand (CS), and then the free aptamer and the aptamer-CS duplex were well separated and determined by metal cation mediated CE/laser-induced fluorescence. When the target was introduced into the incubated sample, the hybridized form was destabilized, resulting in the changes of the fluorescence intensities of the free aptamer and the aptamer-CS duplex. The length of CS was investigated and 12 mer CS showed the best sensitivity for the detection of cocaine. The presented CE-LIF method, which combines the separation power of CE with the specificity of interactions occurring between target, aptamer, and CS, could be a universal detection strategy for other aptamer-specified small molecules.

[Monomers optimization and properties evaluation of quercetin-imprinted polymer and its application to thin layer chromatography stationary phase].

The quercetin-molecularly imprinted polymers with specific affinity and selectivity were prepared by using methacrylic acid (MAA), acrylamide (AM), N,N-(diethylamino) ethyl methacrylate and 2-vinylpyridine as functional monomers, respectively. The adsorption properties for template were studied by equilibrium binding experiments. The results showed 2-VP and DEAEM based on ionic interaction with quercetin possessed better imprinting effects. Using the quercetin-imprinted polymers as thin layer chromatographic stationary could successfully separate the template from the other structurally related compounds. In addition, the influence on adsorption effect about the particle size and repeating times of MIP were investigated.

[Studies on chemical components of Cirsium segestum].

Six chemical components were got from the alcohol extract of Cirsium segestum, their structures were identified by UV, IR, NMR, MS and EA. They were 5,7-dihydroxyflavone, baicalin, oleanolic acid, cholesterol, methyl ursolate and rutin. The first to the fifth of which were got from Cirsium segestum for the first time.

[A new approach for exploring the essence of meridian].

The paper includes a brief review and evaluation of the progress in the research of the essence of meridian in China in the last two decades, in which the author suggests that more effort at all levels involving multiple disciplines needs to be investigated in the pursuit of this issue after the failure of prolonged research in the fields of histological anatomy. Microcosmic investigation, in particular, should be pursued making full use of the available achievement in molecular cell biology, genome research, biophysics and biochemistry and so forth, so as to build a solid plateform for making a breakthrough. The author urges the importance of research in the information carrier that regulates the meridian physiological network of the body. Based on the theories in cellular signal transduction and relevant experimental data, the author points out that the signal amplitude and frequency of intracellular Ca(2+) oscillations and intercellular Ca(2) wave elicited by specific acupuncture may contain information of the meridian routes and physiological function regulations. Through its binding proteins, Ca(2+) participates in almost all the physiological processes such as reproduction, metabolism, muscle contraction to cognition and memory. It is therefore hypothetically believed that Ca(2+) and inositol trisphosphate (IP(3), which is required for the propagation of intercellular Ca(2+) waves) can be the long-quested information carriers of the meridian physiological network, and they in conjunction with the gap-junction protein (connexon) build the material bases of the meridian. The author also specifies some possible directions of further study and experimental methods.