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1.
Pharmacol Res ; 207: 107323, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39053865

ABSTRACT

The natural aging process is accompanied by changes in exosomes, gut microbiota, and metabolites. This study aimed to reveal the anti-aging effect and mechanisms of fecal microbiota transplantation (FMT) from young donors on the natural aging process in mice by analyzing exosomes, gut microbiota, and metabolomics. Aging-relevant telomeric length, oxidative stress indexes in brain tissue, and serum cytokine levels were measured. Flow analysis of T-regulatory (Treg), CD4+, and CD8+ cells was performed, and the expression levels of aging-related proteins were quantified. High-throughput sequencing technology was used to identify differentially expressed serum exosomal miRNAs. Fecal microbiota was tested by 16 S rDNA sequencing. Changes in fecal metabolites were analyzed by UPLC-Q-TOF/MS. The results indicated that the expression of mmu-miR-7010-5p, mmu-miR-376b-5p, mmu-miR-135a-5p, and mmu-miR-3100-5p by serum exosomes was down-regulated and the abundance of opportunistic bacteria (Turicibacter, Allobaculum, Morganella.) was decreased, whereas the levels of protective bacteria (Akkermansia, Muribaculaceae, Helicobacter.) were increased after FMT. Metabolic analysis identified 25 potential biomarkers. Correlation analysis between the gut microbiota and metabolites suggested that the relative abundance of protective bacteria was positively correlated with the levels of spermidine and S-adenosylmethionine. The study indicated that FMT corrected brain injury due to aging via lipid metabolism, the metabolism of cofactors and vitamins, and amino acid metabolism.


Subject(s)
Aging , Brain , Exosomes , Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Metabolomics , Mice, Inbred C57BL , MicroRNAs , Animals , Brain/metabolism , MicroRNAs/metabolism , Exosomes/metabolism , Male , Mice , Oxidative Stress , Cytokines/metabolism , Cytokines/blood
2.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2117-2127, 2024 Apr.
Article in Zh | MEDLINE | ID: mdl-38812227

ABSTRACT

Piperlongumine(PL), a natural alkaloid extracted from Piperis Longi Fructus, has attracted much attention in recent years because of its strong anti-tumor activity, little toxicity to normal cells, and excellent sensitizing effect combined with chemotherapy and radiotherapy, which endow PL with unique advantages as an anti-tumor drug. However, similar to other alkaloids, PL has low water solubility and poor bioavailability. To improve the application of PL in the clinical treatment of tumors, researchers have constructed various nano-drug delivery systems to increase the efficiency of PL delivery. This paper reviewed the physicochemical properties, anti-tumor mechanism, combined therapies, and nano-drug delivery systems of PL in recent years. The review aimed to provide a reference for further research on the anti-tumor effect and nano-drug delivery system of PL. Moreover, this review is expected to provide a reference for the development and application of PL in the anti-tumor therapies.


Subject(s)
Dioxolanes , Neoplasms , Dioxolanes/chemistry , Humans , Animals , Neoplasms/drug therapy , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Drug Delivery Systems , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/administration & dosage , Nanoparticle Drug Delivery System/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/pharmacology , Piperidones
3.
Zhongguo Zhong Yao Za Zhi ; 49(17): 4658-4671, 2024 Sep.
Article in Zh | MEDLINE | ID: mdl-39307804

ABSTRACT

The preparation processes of iron-based organic framework(FeMOF) MIL-100(Fe) and MIL-101(Fe) with two different ligands were optimized and screened, and the optimized FeMOF was loaded with piperlongumine(PL) to enhance the biocompatibility and antitumor efficacy of PL. The MIL-100(Fe) and MIL-101(Fe) were prepared by solvent thermal method using the optimized reaction solvent. With particle size, polymer dispersity index(PDI), and yield as indexes, the optimal preparation processes of the two were obtained by using the definitive screening design(DSD) experiment and establishing a mathematical model, combined with the Derringer expectation function. After characterization, the best FeMOF was selected to load PL by solvent diffusion method, and the process of loading PL was optimized by a single factor combined with an orthogonal experiment. The CCK-8 method was used to preliminarily evaluate the biological safety of blank FeMOF and the antitumor effect of the drug-loaded nano preparations. The experimental results showed that the optimal preparation process of MIL-100(Fe) was as follows: temperature at 127.8 ℃, reaction time of 14.796 h, total solvent volume of 11.157 mL, and feed ratio of 1.365. The particle size of obtained MIL-100(Fe) nanoparticles was(108.84±2.79)nm; PDI was 0.100±0.023, and yield was 36.93%±0.79%. The optimal preparation process of MIL-101(Fe) was as follows: temperature at 128.1 ℃, reaction time of 6 h, total solvent volume of 10.005 mL, and feed ratio of 0.500. The particle size of obtained MIL-101(Fe) nanoparticles was(254.04±22.03)nm; PDI was 0.289±0.052, and yield was 44.95%±0.45%. The optimal loading process of MIL-100(Fe) loaded with PL was as follows: the feed ratio of MIL-100(Fe) to PL was 1∶2; the concentration of PL solution was 7 mg·mL~(-1), and the ratio of DMF to water was 1∶5. The drug loading capacity of obtained MIL-100(Fe)/PL nanoparticles was 68.86%±1.82%; MIL-100(Fe) was nontoxic to HepG2 cells at a dose of 0-120 µg·mL~(-1), and the half-inhibitory concentration(IC_(50)) of free PL for 24 h treatment of HepG2 cells was 1.542 µg·mL~(-1). The IC_(50) value of MIL-100(Fe)/PL was 1.092 µg·mL~(-1)(measured by PL). In this study, the optimal synthesis process of MIL-100(Fe) and MIL-101(Fe) was optimized by innovatively using the DSD to construct a mathematical model combined with the Derringer expectation function. The optimized preparation process of MIL-100(Fe) nanoparticles and the PL loading process were stable and feasible. The size and shape of MIL-100(Fe) particles were uniform, and the crystal shape was good, with a high drug loading capacity, which could significantly enhance the antitumor effect of PL. This study provides a new method for the optimization of the nano preparation process and lays a foundation for the further development and research of antitumor nano preparations of PL.


Subject(s)
Antineoplastic Agents , Dioxolanes , Iron , Metal-Organic Frameworks , Humans , Dioxolanes/chemistry , Metal-Organic Frameworks/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Iron/chemistry , Cell Line, Tumor , Particle Size , Nanoparticles/chemistry , Drug Carriers/chemistry , Cell Survival/drug effects , Drug Compounding/methods , Cell Proliferation/drug effects , Piperidones
4.
Zhongguo Zhong Yao Za Zhi ; 48(21): 5790-5797, 2023 Nov.
Article in Zh | MEDLINE | ID: mdl-38114174

ABSTRACT

Scutellariae Radix-Coptidis Rhizoma(SR-CR) herbal pair is commonly used in many compound prescriptions for their synergistic heat-clearing and dampness-drying properties. During the decoction process, a substantial amount of precipitate is generated. However, there have been no explicit reports on the composition, morphology, and potential effects of this precipitate on the in vivo behavior of SR-CR decoction. This study employed high-performance liquid chromatography(HPLC), high-resolution mass spectrometry, and other techniques to analyze the composition of the co-precipitate in the decoction of SR-CR. Scanning electron microscopy and mass spectrometry imaging were used to analyze its appearance and morphology. Additionally, rats were used to investigate the effects of the co-precipitate on the in vivo behavior of the main components in the SR-CR decoction. The research findings indicated that eight components, including coptisine, berberine, epiberberine, palmatine, baicalin, oroxylin A-7-O-ß-D-glucuronide, wogonoside and baicalein, constituted the primary composition of the co-precipitate. Among these, baicalin and berberine hydrochloride were the most abundant, accounting for about 60% of the total weight. Moreover, the co-precipitate contained 18% tannins. Morphological analysis revealed that the particles in the SR-CR decoction precipitate were spherical microparticles with an average diameter of around 600 nm. Pharmacokinetic research demonstrated that there were significant differences in the AUC, C_(max), t_(1/2), and T_(max) of baicalin, a major component, in rats administered with lyophilized powders of the combined decoction and single decoctions of SR-CR orally, suggesting that the precipitate generated during the decoction process can affect the in vivo behavior of the main components of the SR-CR decoction. It can reduce the absorption of baicalin in the body, decrease the extent of rapid drug release, and to a certain extent, prevent adverse reactions or side effects.


Subject(s)
Berberine , Drugs, Chinese Herbal , Rats , Animals , Drugs, Chinese Herbal/pharmacology , Scutellaria baicalensis/chemistry , Chromatography, High Pressure Liquid , Mass Spectrometry
5.
Chem Soc Rev ; 50(20): 11270-11292, 2021 Oct 18.
Article in English | MEDLINE | ID: mdl-34632985

ABSTRACT

The development of efficient catalysts to break down and convert woody biomass will be a paradigm shift in delivering the global target of sustainable economy and environment via the use of cheap, highly abundant, and renewable carbon resources. However, such development is extremely challenging due to the complexity of lignocellulose, and today most biomass is treated simply as waste. The solution lies in the design of multifunctional catalysts that can place effective control on substrate activation and product selectivity. This is, however, severely hindered by the lack of fundamental understanding of (i) the precise role of active sites, and (ii) the catalyst-substrate chemistry that underpins the catalytic activity. Moreover, active sites alone often cannot deliver the desired selectivity of products, and full understanding of the microenvironment of the active sites is urgently needed. Here, we review key recent advances in the study of reaction mechanisms of biomass conversion over emerging heterogeneous catalysts. These insights will inform the design of future catalytic systems showing improved activity and selectivity.

6.
Zhongguo Zhong Yao Za Zhi ; 47(14): 3701-3708, 2022 Jul.
Article in Zh | MEDLINE | ID: mdl-35850826

ABSTRACT

The production of solid preparations is a multi-unit and multi-step system and is a whole process chain. Its quality is affected by many factors such as material properties and process parameters. As an important analysis tool, multivariate models play an important role in pharmaceutical monitoring. Besides, multivariate models can comprehensively understand the multi-factor relationship between material properties, process parameters, and quality attributes of products, thereby promoting the whole process optimization and controlling the drug production quality. This paper summarized the application of commonly used multivariate models in the process of solid preparations, which provides a certain reference for the process modeling of Chinese medicinal preparations.


Subject(s)
Technology, Pharmaceutical , Pharmaceutical Preparations , Quality Control
7.
Angew Chem Int Ed Engl ; 61(6): e202115585, 2022 02 01.
Article in English | MEDLINE | ID: mdl-34843165

ABSTRACT

Air pollution by SO2 and NO2 has caused significant risks on the environment and human health. Understanding the mechanism of active sites within capture materials is of fundamental importance to the development of new clean-up technologies. Here we report the crystallographic observation of reversible coordinative binding of SO2 and NO2 on open NiII sites in a metal-organic framework (NKU-100) incorporating unprecedented {Ni12 }-wheels; each wheel exhibits six open NiII sites on desolvation. Immobilised gas molecules are further stabilised by cooperative host-guest interactions comprised of hydrogen bonds, π⋅⋅⋅π interactions and dipole interactions. At 298 K and 1.0 bar, NKU-100 shows adsorption uptakes of 6.21 and 5.80 mmol g-1 for SO2 and NO2 , respectively. Dynamic breakthrough experiments have confirmed the selective retention of SO2 and NO2 at low concentrations under dry conditions. This work will inspire the future design of efficient sorbents for the capture of SO2 and NO2 .

8.
Angew Chem Int Ed Engl ; 61(51): e202212164, 2022 12 19.
Article in English | MEDLINE | ID: mdl-36240785

ABSTRACT

The production of conjugated C4-C5 dienes from biomass can enable the sustainable synthesis of many important polymers and liquid fuels. Here, we report the first example of bimetallic (Nb, Al)-atomically doped mesoporous silica, denoted as AlNb-MCM-41, which affords quantitative conversion of 2-methyltetrahydrofuran (2-MTHF) to pentadienes with a high selectivity of 91 %. The incorporation of AlIII and NbV sites into the framework of AlNb-MCM-41 has effectively tuned the nature and distribution of Lewis and Brønsted acid sites within the structure. Operando X-ray absorption, diffuse reflectance infrared and solid-state NMR spectroscopy collectively reveal the molecular mechanism of the conversion of adsorbed 2-MTHF over AlNb-MCM-41. Specifically, the atomically-dispersed NbV sites play an important role in binding 2-MTHF to drive the conversion. Overall, this study highlights the potential of hetero-atomic mesoporous solids for the manufacture of renewable materials.


Subject(s)
Alkadienes , Niobium , Niobium/chemistry , Aluminum , Catalysis
9.
J Am Chem Soc ; 143(8): 3153-3161, 2021 Mar 03.
Article in English | MEDLINE | ID: mdl-33606937

ABSTRACT

Ammonia (NH3) is a promising energy resource owing to its high hydrogen density. However, its widespread application is restricted by the lack of efficient and corrosion-resistant storage materials. Here, we report high NH3 adsorption in a series of robust metal-organic framework (MOF) materials, MFM-300(M) (M = Fe, V, Cr, In). MFM-300(M) (M = Fe, VIII, Cr) show fully reversible capacity for >20 cycles, reaching capacities of 16.1, 15.6, and 14.0 mmol g-1, respectively, at 273 K and 1 bar. Under the same conditions, MFM-300(VIV) exhibits the highest uptake among this series of MOFs of 17.3 mmol g-1. In situ neutron powder diffraction, single-crystal X-ray diffraction, and electron paramagnetic resonance spectroscopy confirm that the redox-active V center enables host-guest charge transfer, with VIV being reduced to VIII and NH3 being oxidized to hydrazine (N2H4). A combination of in situ inelastic neutron scattering and DFT modeling has revealed the binding dynamics of adsorbed NH3 within these MOFs to afford a comprehensive insight into the application of MOF materials to the adsorption and conversion of NH3.

10.
Nat Mater ; 19(1): 86-93, 2020 01.
Article in English | MEDLINE | ID: mdl-31844281

ABSTRACT

The efficient production of light olefins from renewable biomass is a vital and challenging target to achieve future sustainable chemical processes. Here we report a hetero-atomic MFI-type zeolite (NbAlS-1), over which aqueous solutions of γ-valerolactone (GVL), obtained from biomass-derived carbohydrates, can be quantitatively converted into butenes with a yield of >99% at ambient pressure under continuous flow conditions. NbAlS-1 incorporates simultaneously niobium(V) and aluminium(III) centres into the framework and thus has a desirable distribution of Lewis and Brønsted acid sites with optimal strength. Synchrotron X-ray diffraction and absorption spectroscopy show that there is cooperativity between Nb(V) and the Brønsted acid sites on the confined adsorption of GVL, whereas the catalytic mechanism for the conversion of the confined GVL into butenes is revealed by in situ inelastic neutron scattering, coupled with modelling. This study offers a prospect for the sustainable production of butene as a platform chemical for the manufacture of renewable materials.


Subject(s)
Alkenes/chemistry , Lactones/chemistry , Zeolites/chemistry , Adsorption , Biomass , Carbohydrates/chemistry , Catalysis , Hydrogen Bonding , Materials Testing , Neutrons , Scattering, Radiation , Spectroscopy, Fourier Transform Infrared , Synchrotrons
11.
Molecules ; 26(11)2021 May 26.
Article in English | MEDLINE | ID: mdl-34073180

ABSTRACT

In this work, microwave-assisted ionic liquids treatment, followed by hydro-distillation (MILT-HD), as an efficient extraction technology, was used to extract essential oil. The purpose for this was to use multivariate analysis (MVA) models to investigate the effects of potential critical process parameters on the extraction efficiency of essential oil, and explore the mechanism of ionic liquids (ILs). According to the design of experiment (DoE), under optimal process conditions, the extraction efficiency of essential oil was dramatically enhanced, and had low energy demands. Since little is known regarding those mechanisms, according to the non-covalent interaction analysis, the underlying mechanism for ILs improving extraction efficiency was explored based on the density functional theory (DFT). The results showed that ILs could form intense non-covalent bond interaction with cellulose. It helped destroy the network hydrogen bond structure of cellulose in plant cells and caused the essential oils in the cells to be more easily exposed to the extraction solution, thereby accelerating extraction efficiency. Based on this work, it is conducive to understand the MILT-HD process better and gain knowledge of the mechanism of ILs.


Subject(s)
Foeniculum/chemistry , Ionic Liquids/chemistry , Oils, Volatile/analysis , Carbon Dioxide/chemistry , Cellulose/chemistry , Chemistry Techniques, Analytical , Distillation/methods , Gas Chromatography-Mass Spectrometry , Hydrogen Bonding , Imidazoles/chemistry , Kinetics , Microscopy, Electron, Scanning , Microwaves , Multivariate Analysis , Oils, Volatile/isolation & purification , Polysaccharides/chemistry , Spectroscopy, Fourier Transform Infrared
12.
Zhongguo Zhong Yao Za Zhi ; 46(5): 1141-1147, 2021 Mar.
Article in Zh | MEDLINE | ID: mdl-33787108

ABSTRACT

The volatile oil from Mastiche and Olibanum medicinal materials was extracted by steam distillation, and the chemical components of the volatile oil were analyzed by GC-MS technology. The differences of the volatile oil components were compared and study on the Helicobacter pylori in vitro antimicrobial activitiy was conducted. The results showed that the yields of the volatile oil from Mastiche and Olibanum were 11.93% and 2.40%, respectively. A total of 46 compounds(91.31%) were identified from the volatile oil from Mastiche annd 35 compounds(92.49%) from Olibanum. The classification and comparison study of the components showed that the content of monoterpenes in the volatile oil from Mastiche was the highest(40.69%), followed by alcohols(28.48%); while the content of alcohols in the volatile oil from Olibanum was the highest(35.81%), followed by esters(24.92%). There were significant differences in the components of volatile oil from Mastiche and Olibanum, which might be one of the reasons for the difference in efficacy and application. In vitro bacteriostatic experiments showed that the minimum inhibitory concentration(MIC) of the volatile oil from Mastiche against H. pylori was 1 mg·mL~(-1), and the MIC of the volatile oil from Olibanum against H. pylori was more than 1 mg·mL~(-1). In combination with the results of the oil yield experiment, Mastiche had the advantage of inhibiting H. pylori activity. The research results provide scientific basis for the rational application of Mastiche and Olibanum.


Subject(s)
Frankincense , Helicobacter pylori , Oils, Volatile , Anti-Bacterial Agents/pharmacology , Gas Chromatography-Mass Spectrometry , Monoterpenes/analysis , Oils, Volatile/pharmacology
13.
J Am Chem Soc ; 142(36): 15235-15239, 2020 09 09.
Article in English | MEDLINE | ID: mdl-32786806

ABSTRACT

Nitrogen dioxide (NO2) is a toxic air pollutant, and efficient abatement technologies are important to mitigate the many associated health and environmental problems. Here, we report the reactive adsorption of NO2 in a redox-active metal-organic framework (MOF), MFM-300(V). Adsorption of NO2 induces the oxidation of V(III) to V(IV) centers in MFM-300(V), and this is accompanied by the reduction of adsorbed NO2 to NO and the release of water via deprotonation of the framework hydroxyl groups, as confirmed by synchrotron X-ray diffraction and various experimental techniques. The efficient packing of {NO2·N2O4}∞ chains in the pores of MFM-300(VIV) results in a high isothermal NO2 uptake of 13.0 mmol g-1 at 298 K and 1.0 bar and is retained for multiple adsorption-desorption cycles. This work will inspire the design of redox-active sorbents that exhibit reductive adsorption of NO2 for the elimination of air pollutants.

14.
Zhongguo Zhong Yao Za Zhi ; 45(23): 5753-5761, 2020 Dec.
Article in Zh | MEDLINE | ID: mdl-33496116

ABSTRACT

The aim of this paper was to explore the potential molecular mechanism of Banxia Xiexin Decoction in the treatment of colon cancer through pharmacology network and molecular docking methods. The chemical constituents and action targets of 7 herbs from Banxia Xiexin Decoction were collected by using TCMSP database,Chinese Pharmacopoeia and literatures consultation. GeneCards database was used to predict the potential targets of colon cancer. GO biological process analysis and KEGG pathway enrichment analysis of the disease and drug intersection targets were carried out through DAVID database. "Component-target-pathway" network and protein-protein interaction(PPI) network were construction by using Cytoscape and STRING database,and then the core components and targets of Banxia Xiexin Decoction in the treatment of colon cancer were selected according to the topological parameters. Finally, Autodock Vina was used to realize the molecular docking of core components and key targets. The prediction results showed that there were 190 active compounds and 324 corresponding targets for Banxia Xiexin Decoction,involving 74 potential targets for colon cancer. Cytoscape topology analysis revealed 11 key targets such as STAT3,TP53,AKT1,TNF,IL6 and SRC, as well as 10 core components such as quercetin,ß-sitosterol,baicalein,berberine,and 6-gingerol.In bioinformatics enrichment analysis, 679 GO terms and 106 KEGG pathways were obtained, mainly involving PI3 K-AKT signaling pathway,TNF signaling pathway and TP53 signaling pathway. The results of molecular docking showed that baicalein,berberine,licochalcone A and 6-gingerol had a high affinity with SRC,STAT3,TNF and IL6. The results suggested that Banxia Xiexin Decoction could play an anti-colon cancer effect by inhibiting cell proliferation, regulating cell cycle, inducing apoptosis and anti-inflammatory function. The study revealed the multi-components,multi-targets and multi-pathways molecular mechanism of Banxia Xiexin Decoction,which could provide scientific basis and research ideas for the clinical application of Banxia Xiexin Decoction and the treatment of colon cancer with compound Chinese medicines.


Subject(s)
Colonic Neoplasms , Drugs, Chinese Herbal , Humans , Molecular Docking Simulation , Technology
15.
Zhongguo Zhong Yao Za Zhi ; 45(3): 539-547, 2020 Feb.
Article in Zh | MEDLINE | ID: mdl-32237511

ABSTRACT

To evaluate the traits and rheological properties of thermosensitive in situ gel of Yihuang Decoction and its common gel for vaginal use, and predict the release behavior of Yihuang Decoction in situ gel in vitro. Poloxamer was used as thermosensitive material to prepare Yihuang Decoction vaginal in situ gel, and Yihuang Decoction common gel was prepared with carbopol. Then the differences of the two gels before and after diluting with vaginal fluid were compared. The rheological parameters of Yihuang Decoction in situ gel and its common gel were determined with Anton Paar MCR102 rheometer. In addition, berberine hydrochloride was selected as an index component to evaluate the in vitro release properties of Yihuang Decoction vaginal thermosensitive in situ gel. Yihuang Decoction vaginal thermosensitive in situ gel was Newtonian fluid under low-temperature conditions, which was yellow and transparent. After reaching the gelling temperature of 24.5 ℃, it became semi-solid, pseudoplastic fluid. The gelling temperature was predicted to be 37 ℃, and the phase transition time was 30 s after diluting with simulated vaginal fluid. However, the rheological properties of Yihuang Decoction common gel had no significant changes with temperature. Compared with in situ gel, the color of common gel was darker and more translucent. Besides, its mobility was stronger after diluting with simulated vaginal fluid. The in vitro release study showed that the kinetic behavior of berberine hydrochloride in Yihuang Decoction vaginal thermosensitive in situ gel was matched with the Higuchi equation. Through simulation of vaginal administration, physical properties and dynamic rheological parameters were used to intuitively and scientifically evaluate the two gels. Compared with the common gel, the thermosensitive in situ gel could quickly attached to the vaginal mucosa and release drug, and thus was more suitable for developing vaginal administration of Yihuang Decoction, which also provides references for studying new vaginal preparation of Yihuang Decoction.


Subject(s)
Administration, Intravaginal , Drugs, Chinese Herbal/chemistry , Gels/chemistry , Female , Humans , Poloxamer , Rheology , Temperature , Viscosity
16.
Pak J Pharm Sci ; 31(6): 2329-2332, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30473500

ABSTRACT

Isopropylidene shikimic acid (ISA), a new drug derviatived from Shikimic Acid, had been proved to be effective in the cerebral protection after cerebral ischemia and reperfusion. But there was little research on the physical pharmacy and biopharmaceutical properties about the drug. In order to provide some useful data for the pharmaceutical development of ISA, the solubility, stability and Oil/Water partition coefficient (LogP) were determined by the classic preformulation study method, and the transmembrane performance of ISA was studied by Franz -diffusion cell method in vitro. The results showed that ISA was water-soluble with a solubility 32.52mg/ml, which could be improved to 44.32 mg/ml by 1% (w/v) sodium dodecylsulfate; the LogP was -0.63; ISA was less stable in water but it was stable when pH greater than 6.0 and unstable when pH less than 6.0; the accumulated permeation rates at 1h were about 50% and more than 80% at 6h. Data obtained by the study indicated that the medium selection and pH control were important for liquid preparation of ISA, and avoiding dissolution and absorption in stomach was critical for the oral solid dosage forms. Mucosal drug delivery systems would be considered, according to the certain hydrophilic-lipophilic characters and good transmembrane capability.


Subject(s)
Neuroprotective Agents/chemistry , Shikimic Acid/chemistry , Drug Compounding , Drug Liberation , Drug Stability , Excipients/chemistry , Hydrogen-Ion Concentration , Hydrophobic and Hydrophilic Interactions , Neuroprotective Agents/pharmacology , Permeability , Shikimic Acid/analogs & derivatives , Shikimic Acid/pharmacology , Sodium Dodecyl Sulfate/chemistry , Solubility , Solvents/chemistry , Water/chemistry
17.
Cell Physiol Biochem ; 43(5): 2102-2116, 2017.
Article in English | MEDLINE | ID: mdl-29065401

ABSTRACT

BACKGROUND/AIMS: Clinical reports on adverse reactions that result from Polygonum multiflorum (PM) and its preparations, especially regarding liver injury, have recently received widespread attention. This study aimed to investigate the mechanism of hepatotoxicity induced by different PM extracts through iTRAQ quantitative proteomics. METHODS: The different PM extracts were orally administrated for 90 days to rats, and the hepatotoxicity effect was evaluated through measurement of biochemical indexes, oxidative damage indexes and hematoxylin-eosin (HE) staining. Then, the hepatotoxicity mechanism was investigated by iTRAQ quantitative proteomics. RESULTS: The results of biochemical and histopathological analyses showed that liver injury occurred in all groups of rats given by various PM extracts, which proved all of the PM extracts could induce hepatotoxicity. The hepatotoxicity mechanism may differ between the total extract group and the other groups through the results of biochemical indicators. The iTRAQ proteomics study showed that hepatotoxicity resulting from PM was mainly related to the abnormal activity of mitochondrion function-related oxidative phosphorylation pathways. CONCLUSION: This iTRAQ proteomics study revealed that the hepatotoxicity induced by PM is primarily related to the oxidative phosphorylation pathways. NADH dehydrogenase family proteins and Slc16a2 could be potential biomarkers of hepatotoxicity resulting from PM.


Subject(s)
Chemical and Drug Induced Liver Injury/metabolism , Fallopia multiflora/chemistry , Liver/drug effects , Liver/metabolism , Plant Extracts/chemistry , Plant Extracts/toxicity , Proteomics/methods , Animals , Blotting, Western , Male , Rats , Rats, Sprague-Dawley
18.
Zhongguo Zhong Yao Za Zhi ; 42(10): 1964-1970, 2017 May.
Article in Zh | MEDLINE | ID: mdl-29090558

ABSTRACT

To establish HPLC-MS/MS method for simultaneous determination of daphnetin, daphnoretin, and daphneticin in rat plasma after oral and intravenous administration of Daphne giraldii extract, and then use them in the calculation of pharmacokinetic parameters. Six sprague-dawley rats received intragastric administration of D. giraldii extract (daphnetin, daphnoretin and daphneticin were 88.40, 3.24 and 4.28 mg•kg⁻¹, respectively). Their drug plasma concentration was determined by LC-MS/MS with schisandrin as an internal standard to draw plasma concentration-time curve. The pharmacokinetic parameters were calculated by Kinetica 4.4. The results showed that the linear range was 5-1 000 µg•L⁻¹ for daphnetin, daphnoretin and daphneticin, and the method ological test showed conformance to the requirements.The intraday and inter-day variable coefficients (RSD) were both less than 15.0%, indicating that both of legitimate precise and accuracy were consistent with the analysis requirements of biological samples. For daphnetin, the pharmacokinetic parameters Tmax, Cmax, AUC0-t, T1/2 and MRT were 4 h, 858.96 µg•L⁻¹, 10 566.4 µg•L⁻¹â€¢h, 5.19 h and 9.43 h, respectively. For daphnoretin, the pharmacokinetic parameters Tmax, Cmax, AUC0-t, T1/2 and MRT were 2.92 h, 178.00 µg•L⁻¹, 905.89 µg•L⁻¹â€¢h, 3.50 h and 6.95 h, respectively. For daphneticin, the pharmacokinetic parameters Tmax, Cmax, AUC0-t, T1/2 and MRT were 2 h, 36.67 µg•L⁻¹, 355.11 µg•L⁻¹â€¢h, 4.95 h and 8.27 h, respectively. The LC-MS/MS analysis method established in this study was proved to be so accurate and sensitive that it can be applied to the pharmacokinetic study of daphnetin, daphnoretin and daphneticin.


Subject(s)
Coumarins/blood , Daphne/chemistry , Plant Extracts/pharmacokinetics , Umbelliferones/blood , Animals , Chromatography, Liquid , Coumarins/pharmacokinetics , Rats , Rats, Sprague-Dawley , Tandem Mass Spectrometry , Umbelliferones/pharmacokinetics
19.
Phytother Res ; 30(8): 1207-18, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27188216

ABSTRACT

Emodin is a natural anthraquinone derivative that occurs in many widely used Chinese medicinal herbs, such as Rheum palmatum, Polygonum cuspidatum and Polygonum multiflorum. Emodin has been used as a traditional Chinese medicine for over 2000 years and is still present in various herbal preparations. Emerging evidence indicates that emodin possesses a wide spectrum of pharmacological properties, including anticancer, hepatoprotective, antiinflammatory, antioxidant and antimicrobial activities. However, emodin could also lead to hepatotoxicity, kidney toxicity and reproductive toxicity, particularly in high doses and with long-term use. Pharmacokinetic studies have demonstrated that emodin has poor oral bioavailability in rats because of its extensive glucuronidation. This review aims to comprehensively summarize the pharmacology, toxicity and pharmacokinetics of emodin reported to date with an emphasis on its biological properties and mechanisms of action. Copyright © 2016 John Wiley & Sons, Ltd.


Subject(s)
Emodin/pharmacology , Emodin/pharmacokinetics , Medicine, Chinese Traditional/methods , Plant Extracts/pharmacology , Plant Extracts/pharmacokinetics , Humans
20.
Biomed Chromatogr ; 29(7): 1048-55, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25450501

ABSTRACT

Radix polygoni multiflori (RPM) has antioxidative, anti-aging, liver-protective and antihuman cytomegalovirus activity. It has been proved to be hepatotoxic. Considering multiple ingredients to control RPM quality is essential. The aim of this study was to establish a simple, rapid method using resolution liquid chromatography coupled with a triple quadruple mass spectrometry to identify and quantify the major bioactive constituents in RPM. The method was applied to analyze 14 marker batches from manufacturers from the same province. The ultrasonic extracts of all samples were determined by LC-MS/MS, and assessed by hierarchical cluster analysis. The proposed method was applied to analyze 21 batches of samples with acceptable linearity (R(2) , 0.9930-0.9998), precision (relative standard deviation, RSD, 0.45-4.73%) repeatability (RSD, 1.14-9.41%), stability (RSD, 1.29-12.88%) and recovery (RSD, 1.80-12.15%) of the 14 compounds. Furthermore, the hierarchical cluster analysis was applied to classify 21 samples on the basis of characteristics of the 14 compound markers. The developed method was demonstrated to be simple, sensitive and reproducible, and has significant importance and comprehensive evaluation for quality control of RPM and related preparations. Hierarchical cluster analysis clearly indicated that the RPM from the same province was similar, whereas samples of RPM from different provinces were significantly different.


Subject(s)
Chromatography, Liquid/methods , Drugs, Chinese Herbal/chemistry , Tandem Mass Spectrometry/methods , Cluster Analysis , Drugs, Chinese Herbal/standards , Flavonoids/analysis , Gallic Acid/analysis , Limit of Detection , Linear Models , Phenols/analysis , Plant Roots/chemistry , Reproducibility of Results
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