The therapeutic effect of wine-processed Corni Fructus on chronic renal failure in rats through the interference with the LPS/IL-1-mediated inhibition of RXR function.

ETHNOPHARMACOLOGICAL RELEVANCE: Corni Fructus, derived from the fruit of Cornus officinalis Sieb. et Zucc, is a widely utilized traditional Chinese medicine (TCM) with established efficacy in the treatment of diverse chronic kidney diseases. Crude Corni Fructus (CCF) and wine-processed Corni Fructus (WCF) are the main processed forms of Corni Fructus. Generally, TCM is often used after processing (paozhi). Despite the extensive use of processed TCM, the underlying mechanisms of processing for most TCMs have been unclear so far. AIM OF THE STUDY: In this study, an integrated strategy combined renal metabolomics with proteomics was established and investigated the potential processing mechanisms of CCF or WCF on chronic renal failure (CRF) models. MATERIALS AND METHODS: Firstly, the differences in biochemical parameters and pathological histology were compared to evaluate the effects of CCF and WCF on CRF model rats. Then, the tissue differential metabolites and proteins between CCF and WCF on CRF model rats were screened based on metabolomics and proteomics technology. Concurrently, a combined approach of metabolomics and proteomics was employed to investigate the underlying mechanisms associated with these marker metabolic products and proteins. RESULTS: Compared to the MG group, there were 27 distinct metabolites and 143 different proteins observed in the CCF-treatment group, while the WCF-treatment group exhibited 24 distinct metabolites and 379 different proteins. Further, the integration interactions analysis of the protein and lipid metabolite revealed that both WCF and CCF improved tryptophan degradation and LPS/IL-1-mediated inhibition of RXR function. WCF inhibited RXR function more than CCF via the modulation of LPS/IL-1 in the CRF model. Experimental results were validated by qRT-PCR and western blotting. Notably, the gene expression amount and protein levels of FMO3 and CYP2E1 among 8 genes influenced by WCF were higher compared to CCF. CONCLUSION: The results of this study provide a theoretical basis for further study of Corni Fructus with different processing techniques in CRF. The findings also offer guidance for investigating the mechanism of action of herbal medicines in diseases employing diverse processing techniques.

The influencing mechanism of phosphorus component on network structure and bioactivity of bioactive glass.

(64-x)SiO2-36CaO-xP2O5 (x = 0, 2, 4, 6, 8 mol%) bioactive glasses are successfully prepared by sol-gel method, and the effect of phosphorus (P) content on the network structure, phase composition and in vitro mineralization performance of bioactive glasses is investigated by the various characterization techniques. Results show that the as-prepared bioactive glass has the amorphous structure. With the increase of P content, it can be found in FT-IR spectra that the characteristic peaks of bending vibration corresponding to the P-O bond in PO43- gradually appear. Among, the typical 60S4P has the highest percentage (73.81%) of bridging oxygen (BO), indicating its highest aggregation degree of silicate network. Besides, the introduction of P2O5 results in the formation of monophosphate, which enable the bioactive glasses to dissolve rapidly in water or simulate body fluids (SBF) and crystallize to form hydroxyapatite (HA), thereby enhancing its biological activity. After soaking in SBF for 3 days, the irregular cauliflower-like HA particles appear on the surface of bioactive glass, and the appropriate amount of P addition in glass could result in its high bioactivity. Therefore, this study could provide a theoretical reference for the relationship between the network structure and bioactivity of bioactive glass.

Revealment study on the regulation of lipid metabolism by Lingguizhugan Decoction in heart failure treatment based on integrated lipidomics and proteomics.

Lingguizhugan Decoction (LGZGD) is a classical traditional Chinese medicine prescription. Our previous studies found that disorders of lipid metabolism were reversed by LGZGD in heart failure (HF) mice. This study aimed to reveal the regulation of lipid metabolism of LGZGD. A mice model of HF was established by intraperitoneal injection of doxorubicin. The components of LGZGD were identified with the UHPLC-QTOF-MS method. The regulation of lipid metabolism by LGZGD was detected by serum lipidomics and heart tissue proteomics. Molecular docking was further performed to screen active components. A total of 78 compounds in LGZGD were identified. Results of lipidomics showed that 37 lipids illustrated a significant recovery trend to normal after the treatment of LGZGD. Results of proteomics demonstrated that 55 proteins were altered by the administration of LGZGD in HF mice. After enrichment analysis, the Prakg2/Ucp2/Plin1 axis on the Apelin pathway plays a vital role in HF treatment by LGZGD. Nine active components exhibited the outstanding ability of binding to the apelin receptor with MM-GBSA value lower than -60 Kcal/mol. In conclusion, all results combined together revealed that multi-component in the LGZGD had beneficial effects on the HF through ameliorating lipid disorders, which provides a novel insight into the cardioprotective effects of LGZGD and its clinical application.

Jujuboside B inhibits febrile seizure by modulating AMPA receptor activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Febrile seizure is a common neurologic disorder with limited treatment occurring in infants and children under the age of five. Jujuboside B (JuB) is a main bioactive saponin component isolated from the Chinese anti-insomnia herbal medicine Ziziphi Spinosae Semen (ZSS), seed of Ziziphus jujuba Mill, which has been proved to exhibit neuroprotective effects recently. AIM OF THE STUDY: In this study, we aimed at elucidating the effect of JuB on suppressing febrile seizure and the potential mechanisms. METHODS: Electroencephalogram (EEG) recording was used to monitor the severity of febrile seizures. The JuB in the brain was identified by mass spectrometry. Neuronal excitability was investigated using patch clamp. RESULTS: JuB (30 mg/kg) significantly prolonged seizure latency and reduced the severity in hyperthermia-induced seizures model mice. Hippocampal neuronal excitability was significantly decreased by JuB. And JuB significantly reduced the excitatory synaptic transmission mediated by α-amino-3-hydroxy-5-methyl-4-iso-xazolepropionic acid receptor (AMPAR), including evoked excitatory postsynaptic currents (eEPSCs), and miniature EPSCs (mEPSCs) in hippocampal neurons. Furthermore, JuB also significantly inhibited recombinant GluA1 and GluA2 mediated AMPA current in HEK293 cell and decreased the upregulation of [Ca2+]i induced by AMPA in primary cultured cortex neurons. CONCLUSIONS: JuB suppressed the excitability of hippocampal neurons by inhibiting the activity of AMPAR and reducing the intracellular free calcium, thereby relieving febrile seizures.

Influence of thermal processing on the quality of hawthorn: Quality markers of heat-processed hawthorn.

Hawthorn and its derived products are used worldwide as foods as well as complementary medicine. During the preparation of hawthorn, heating and thermal processing are frequently reported. The thermal processing will change the medicinal purposes and modify the efficacy of hawthorn. However, details including the chemical profile shifting and quality markers of heat-processed hawthorn have not been well understood. In this study, we analyzed the hawthorn samples processed at different temperatures and different times by ultraviolet visible absorption spectrum and liquid-mass spectrometry technologies combined with multivariate statistical analysis. It was revealed for the first time that thermal processing could greatly change the ultraviolet-visible absorption spectra and chemical profiles of hawthorn even with heat treatment at 130°C for 10 min. And the ultraviolet visible absorption spectrum, especially the ratio value (RA500 nm/400 nm ), was a descriptive and qualitative indicator of heating degree for the thermal processing at the macroscopic level. Several components, such as hyperoside, chlorogenic acid, quercetin, and apigenin, decreased or increased in content during the processing, and they could be utilized as the chemical quality markers. The proposed quality markers for heat-processed hawthorn will be helpful for further optimizing the processing conditions of hawthorn.

Effects of transcutaneous tibial nerve stimulation on females with overactive bladder syndrome in multiple sclerosis a protocol for a systematic review and meta-analysis.

BACKGROUND: Overactive bladder (OAB) is a problem that increasingly affects adults and the elderly, especially women. It may affect quality of life, ability to participate and overall wellbeing. Transcutaneous tibial nerve stimulation (TTNS) is a form of neuromodulation involving the use of electrical impulses to address urinary symptoms. There are many randomized controlled trials that have shown that TTNS is effective at treating overactive bladder. In recent years, TTNS has gained increasing attention for this condition. But its effect in females remains controversial and evidence is lacking. Therefore, the main purpose of this study will be to systematically evaluate the effect of TTNS on females with OAB in Multiple sclerosis (MS) by conducting a systematic review and meta-analysis, and also to provide a reference for the application of TTNS in OAB. METHODS: A systematic review of eligible articles will be conducted using Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. A comprehensive search of the literature will be conducted in PubMed, Web of Science, The Cochrane Library, Chinese National Knowledge Infrastructure Database (CNKI), Wanfang Data, Weipu Electronics, and other databases. We will include randomized controlled trials about TTNS in females with OAB in MS. Two reviewers will screen titles, abstracts, and full texts independently. We will use a hierarchy of recommended assessment, development, and assessment methods to assess the overall certainty of the evidence and report findings accordingly. Endnote X9 will be used to select the studies and Review Manager V.5.4 (Cochrane Collaboration) will be used to conduct the meta-analysis. The mean difference or standard deviation with 95% confidence interval (CI) will be used in the computation of continuous variables to synthesize data. RESULTS: The results will provide evidence for judging whether TTNS is effective in females with OAB and MS. CONCLUSION: This study will provide reliable evidence for the effect of TTNS in female patients with OAB and MS. TRIAL REGISTRATION: Systematic review registration: PROSPERO CRD42021256861.

Screening and identification of potential tyrosinase inhibitors from Semen Oroxyli extract by ultrafiltration LC-MS and in silico molecular docking.

There is an increasing interest in screening and developing natural tyrosinase inhibitors widely applied in medicinal and cosmetic products, as well as in the food industry. In this study, an approach by ultrafiltration LC-MS and molecular docking was used to screen and identify tyrosinase inhibitors from Semen Oroxyli extract. The samples were first incubated with the tyrosinase to select the optimal binding conditions including tyrosinase concentration, incubation time and the molecular weight of ultrafiltration membrane. By comparison of the chromatographic profiles of the extracts after ultrafiltration with activated and inactivated tyrosinase, the potential inhibitors were obtained and then identified by LC-MS. The relative binding affinities of the potential inhibitors were also calculated based on the decrease of peak areas of those. As a result, seven compounds were fished out as tyrosinase inhibitors by this assay. Among them, oroxin A and baicalein showed higher tyrosinase inhibitory than resveratrol as positive drug, and their binding mode with enzyme was further verified via the molecular docking analysis. The test results showed that the proposed method was a simple, rapid, effective, and reliable method for the discovery of natural bioactive compounds, and it can be extended to screen other bioactive compounds from traditional Chinese medicines.

Revealing the Inhibitory Effect of Ginseng on Mitochondrial Respiration through Synaptosomal Proteomics.

Ginseng, the active ingredients of which are ginsenosides, is the most popular herbal medicine and has potential merit in the treatment of cerebral disorders. To better understand the function of Ginseng in the cerebral system, we examined changes in the protein expression profiles of synaptosomes extracted from the cerebral cortical and hippocampal tissues of rats administered a high or low dose of Ginseng for 2 weeks. More than 5000 proteins belonging to synaptosomes were simultaneously identified and quantitated by an approach combining tandem mass tags with 2D liquid chromatography-mass spectrometry (LC-MS). Regarding differentially expressed proteins, downregulated proteins were much more highly induced than upregulators in the cerebral cortical and hippocampal synaptosomes, regardless of the dose of Ginseng. Bioinformatic analysis indicated the majority of the altered proteins to be located in the mitochondria, directly or indirectly affecting mitochondrial oxidative respiration. Further functional experiments using the substrate-uncoupler inhibitor titration approach confirmed that three representative ginsenosides were able to inhibit oxidative phosphorylation in mitochondria. Our results demonstrate that Ginseng can regulate the function of mitochondria and alter the energy metabolism of cells, which may be useful for the treatment of central nervous disorders.

[An overview of effects of traditional medicine on pharmacokinetics of western medicine].

Traditional medicine (herb medicine) began to prevail again over last two decades, and it is about 70% of the world population taking herb medicine as supplement or alternative medicine according to a recent survey. The consumption of herb medicine increased exponentially in Canada, Australia and Europe during last 10 years. Since concomitant administration of herbal and western medicine has become a trend, it requires paying close attention to the problem. Herb-drug interactions have been extensively investigated worldwide, and there is an increasing concern about the clinical herb-drug interaction. In this review we introduced the current progress in the herb-drug interactions including evidence-based clinical studies and establishment of levels of evidence for herb-drug interaction; and in the related mechanisms including the induction and inhibition of metabolic enzymes, inhibition and induction of transport and efflux proteins, alteration of gastrointestinal functions, and alteration in renal elimination. We also analyzed both the achievements and the challenges faced in the concomitant administration of traditional Chinese medicine and western medicine.

LC-MS/MS determination and pharmacokinetic study of five flavone components after solvent extraction/acid hydrolysis in rat plasma after oral administration of Verbena officinalis L. extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has been used in clinical practice for several thousand years. TCM has played an indispensable role in the prevention and treatment of diseases, especially the complicated and chronic ones. Pharmacokinetic study on active constituents in herbal preparations is a good way for us to explain and predict a variety of events related to the efficacy and toxicity of TCM. AIM OF THE STUDY: A selective and sensitive HPLC-MS/MS method was first developed and validated for the determination of luteolin, kaempferol, apigenin, quercetol, and isorhamnetin in rat plasma. MATERIALS AND METHODS: The LC system consisted of an Agilent Technologies Series 1200 system (Agilent, USA) equipped with an automatic degasser, a quaternary pump, and an autosampler. Chromatographic separations were performed on a Waters SunFire™ C(18) column (150 mm × 4.6mm, 5 µm), and the column temperature was maintained at 25°C and the sample injection volume was 20 µL. The current LC-MS/MS assay was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability. RESULTS: The validated method was successfully applied to monitoring the concentrations and pharmacokinetic studies of five flavone compounds in rat plasma after a single oral administration of Verbena officinalis L. extract with a dosage of 8.0 mL/kg. The time to reach the maximum plasma concentration (T(max1)) was 0.48 ± 2.14 h for luteolin, 0.25 ± 0.13 h for kaempferol, 0.97 ± 1.08 h for apigenin, 1.04 ± 4.25 h for quercetol and 0.25 ± 0.16 h for isorhamnetin, and the maximum plasma concentration (T(max2)) was 3.97 ± 1.48 h, 4.05 ± 0.46 h, 4.33 ± 0.58 h, 2.99 ± 0.48 h and 4.02 ± 0.34 h. The elimination half-time (t(1/2)) of luteolin, kaempferol, apigenin, quercetol and isorhamnetin was 4.02 ± 0.81, 7.65 ± 0.71, 3.30 ± 0.83, 4.55 ± 0.49 and 5.56 ± 1.32 h, respectively. CONCLUSIONS: This paper described a simple, sensitive and validated LC-MS/MS method for simultaneous determination of luteolin, kaempferol, apigenin, quercetol and isorhamnetin in rat plasma after oral administration of V. officinalis L. extract, and investigated on their pharmacokinetic studies as well, with a short run time of 5 min.

[HPCE fingerprints of Forsythia suspensa from Hebei province].

OBJECTIVE: To develop a HPCE analysis method for fingerprints of Forsythia suspensa from Hebei province, get reference fingerprint and compare the fingerprints of F. suspensa collected from different producing areas and different parts of the plant. METHOD: Electrophoresis was performed on a fused silica capillary column (75 microm x 60 cm, 30 cm). The running buffer was composed of 50 mmol x L(-1) borax (adjust to pH 9.90 with 0.1 mol x L(-1) NaOH). The applied voltage was 15 kV and the temperature was 20 degrees C. The detection wavelength was 214 nm. The semblances to the crude drugs of different producing areas were compared. RESULT: The mutual mode of HPCE fingerprints was set up with 12 common peaks. The fingerprints of F. suspensa from Hebei province had high similarity, F. suspensa from Shanxi and Henan were also of good quality. The chemical composition in different parts of the herb had big differences. CONCLUSION: The method is simple, quick, accurate and can be used as a new means for the quality control of F. suspensa.

[Determination of five coumarins in radix glehniae by micellar electrokinetic capillary chromatography].

A micellar electrokinetic capillary chromatography method with ultraviolet detection was developed for the simultaneous determination of psoralen, xanthotoxin, isoimpinellin, bergapten and scopoletin in Radix Glehniae. The separation was performed on an uncoated fused silica capillary column (50.2 cm x 75 microm x 40 cm) with 20 mmol x L(-1) borax solution (pH 9.6) containing 16 mmol x L(-1) sodium dodecylsulfate (SDS) and 15% acetonitrile as running buffer at applied voltage of 22 kV. The detection wavelength was 214 nm. The effects of concentrations of borax solution, sodium dodecylsulfate (SDS), and organic modifier, voltage, temperature on the separation and sensitivity were investigated. The five active constituents were completely separated within 7 min. The linear ranges of psoralen, xanthotoxin, isoimpinellin, bergapten and scopoletin were 9.91-82.6, 37.2-162, 2.23-18.6, 2.73-22.3 and 2.89-20.1 mg x L(-1), respectively. And the average recoveries were 98.9%, 98.4%, 101.3%, 99.1% and 98.0%, respectively. This simple and rapid method provided a new basis for assessment on quality of Radix Glehniae.

Pharmacokinetic properties of paeoniflorin, albiflorin and oxypaeoniflorin after oral gavage of extracts of Radix Paeoniae Rubra and Radix Paeoniae Alba in rats.

AIM OF THE STUDY: To establish a HPLC-MS method and investigate the pharmacokinetic properties of paeoniflorin, albiflorin and oxypaeoniflorin and the pharmacokinetics difference of Radix Paeoniae Rubra and Radix Paeoniae Alba. MATERIALS AND METHODS: The extracts of Radix Paeoniae Rubra and Radix Paeoniae Alba were separately administrated to rats. The concentrations of paeoniflorin, albiflorin and oxypaeoniflorin in rat plasma were determined by HPLC-ESI-MS method. The plasma samples were pretreated by protein precipitation with methanol and chromatographic separation was performed on a C(18) column with a mobile phase consisted of 0.1% formic acid and methanol (67:33, v/v). The detection was accomplished by multiple-reaction monitoring (MRM) scanning via electrospray ionization (ESI) source operating in the negative ionization mode. Main pharmacokinetic parameters were estimated and the total AUC of the three components were compared. RESULTS: The pharmacokinetic parameters of paeoniflorin, albiflorin and oxypaeoniflorin were significantly different. There was significant difference between the pharmacokinetic characteristics of Radix Paeoniae Rubra and Radix Paeoniae Alba. CONCLUSIONS: A specific and sensitive HPLC-ESI-MS method was developed for simultaneous determination of paeoniflorin, albiflorin and oxypaeoniflorin in rat plasma and was successfully applied to pharmacokinetic study. The results might be helpful for the investigation of different effects of Radix Paeoniae Rubra and Radix Paeoniae Alba.

A practical strategy for the characterization of coumarins in Radix Glehniae by liquid chromatography coupled with triple quadrupole-linear ion trap mass spectrometry.

The aim of the present study was to develop a practical method for the characterization of coumarins in Radix Glehniae by liquid chromatography-mass spectrometry (LC-MS). First, 10 coumarin standards (including two pairs of isomers) were studied, and mass spectrometry fragmentation patterns and elution time rules for the coumarins were found. Then, an extract of Radix Glehniae was analyzed by the combination of two scan modes, i.e., multiple ion monitoring-information-dependent acquisition-enhanced product ion mode (MIM-IDA-EPI) and precursor scan information-dependent acquisition-enhanced product ion mode (PREC-IDA-EPI) on a hybrid triple quadrupole-linear ion trap mass spectrometer. A total of 41 coumarins were identified on the basis of their mass spectrometry fragmentation patterns. This is the first time that these two scan modes have been combined to characterize chemical constituents in traditional Chinese medicine. This new method allowed the identification of coumarins in Radix Glehniae in trace amounts. The methodology proposed in this study could be valuable for the structural characterization of coumarins from complex natural and synthetic sources.