Publications by authors named "Lifeng Han"

91 Publications

Configuration of the ion exchange chromatography, hydrophilic interaction chromatography, and reversed-phase chromatography as off-line three-dimensional chromatography coupled with high-resolution quadrupole-Orbitrap mass spectrometry for the multicomponent characterization of Uncaria sessilifructus.

J Chromatogr A 2021 Jul 11;1649:462237. Epub 2021 May 11.

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai, Tianjin 301617, China; Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai, Tianjin 301617, China. Electronic address:

Herbs represent complex chemical systems involving various primary and secondary metabolites that are featured by large spans of acid-base property, polarity, molecular mass, and content, etc., which thus poses great challenges to characterize the metabolites contained. Here, the combination of multiple-mechanism chromatography coupled with improved data-dependent-MS acquisition (DDA-MS) is presented as a strategy to support the deep metabolites characterization. Targeting Uncaria sessilifructus, a reputable medicinal herb containing alkaloids and triterpenic acids (TAs) as the main pharmacologically bioactive ingredients, a three-dimensional liquid chromatography (3D-LC) system was established by integrating ion exchange chromatography, hydrophilic interaction chromatography, and reversed-phase chromatography (IEC-HILIC-RPC). The first-dimensional chromatography, configuring a PhenoSphere SCX column eluted by methanol/20 mM ammonium acetate-0.05% formic acid in water, could well fractionate the total extract into two fractions (unretained ingredients and alkaloids). The subsequent HILIC using an XAmide column and RPC by a CSH Phenyl-Hexyl column achieved the sufficient resolution of the total TAs and total alkaloids, respectively. A polarity-switching precursor ions list-including DDA approach by Q-Orbitrap-MS enabled the high-efficiency, coverage-enhanced identification of alkaloids and TAs. This 3D-LC/Q-Orbitrap-MS system was validated as precise (RSD < 5% for intra-day/inter-day precision), Up to 308 components were separated from U. sessilifructus, and 128 thereof (including 85 alkaloids, 29 TAs, and 14 others) were identified or tentatively characterized, exhibiting superiority over the conventional one-dimensional LC/MS. Conclusively, 3D-LC/MS in an off-line mode can facilitate the flexible configuration of multiple chromatography to accomplish the fit-for-purpose characterization of the metabolites from an herbal extract or a biosample.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chroma.2021.462237DOI Listing
July 2021

Glutaredoxin 1 protects neurons from oxygen-glucose deprivation/reoxygenation (OGD/R)-induced apoptosis and oxidative stress via the modulation of GSK-3β/Nrf2 signaling.

J Bioenerg Biomembr 2021 May 6. Epub 2021 May 6.

Department of Anesthesiology, The First Hospital of Yulin, No. 93 Yuxi Street, Yulin, Shaanxi, 719000, China.

Increasing evidence has indicated that glutaredoxin 1 (GRX1) is a potent antioxidant protein that promotes cell survival under conditions of oxidative stress. Oxidative stress-induced neuronal injury contributes to cerebral ischemia/reperfusion injury. However, the role of GRX1-mediated antioxidant defense against neuronal damage during cerebral ischemia/reperfusion injury has not been thoroughly investigated. Thus, the objective of this study was to evaluate whether GRX1 protects neurons against oxygen-glucose deprivation/reoxygenation (OGD/R)-evoked oxidative stress injury in an in vitro model of cerebral ischemia/reperfusion injury. Our data revealed that GRX1 was induced by OGD/R treatment in neurons. Functional assays indicated that loss of GRX1 exacerbated OGD/R-induced apoptosis and the generation of reactive oxygen species (ROS), while GRX1 up-regulation protected against OGD/R-evoked neuronal injury. Further investigation revealed that GRX1 promoted the nuclear expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and enhanced transcription of the Nrf2/antioxidant response element (ARE) in GOD/R-exposed neurons. Furthermore, GRX1 promoted the activation of Nrf2/ARE associated with the modulation of glycogen synthase kinase-3β (GSK-3β). GSK-3β inhibition blocked GRX1 knockdown-mediated suppression of Nrf2 activation. Notably, the suppression of Nrf2 partially reversed GRX1-mediated anti-oxidative stress injury in OGD/R-exposed neurons. In summary, these findings indicate that GRX1 protects neurons against OGD/R-induced oxidative stress injury by enhancing Nrf2 activation via the modulation of GSK-3β. Our study suggests that GRX1 is a potential neuroprotective protein that protects against cerebral ischemia/reperfusion injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10863-021-09898-0DOI Listing
May 2021

Multiple component-pharmacokinetic studies on 10 bioactive constituents of Peiyuan Tongnao capsule using parallel reaction monitoring mode.

Biomed Chromatogr 2021 Apr 30:e5153. Epub 2021 Apr 30.

State Key Laboratory of Component-Based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Peiyuan Tongnao capsule (PTC) plays an important role in clinical application due to its excellent curative efficacy in the treatment of ischemic stroke and chronic cerebral circulation insufficiency. To standardize and rationalize the clinical application of PTC, a rapid and sensitive method based on ultra-high performance liquid chromatography/quadrupole-Orbitrap mass spectrometry with parallel reaction monitoring (PRM) mode was developed and validated for the pharmacokinetic (PK) study. Ten bioactive compounds (aucubin, salidroside, echinacoside, paeoniflorin, verbascoside, liquiritin, 2,3,5,4'-tetrahydroxy stilbene-2-O-β-d-glucoside, coumarin, glycyrrhizic acid, and emodin) were simultaneously determined in rat plasma. All calibration curves exhibited good linearity (r  > 0.99). The lower limits of quantification were 0.082-13.291 ng mL . The intra- and inter-day precision was 0.54-12.36%, whereas the intra- and inter-day accuracy ranged from 100.45 to 114.00%. The mean extraction recoveries were 81.77-117.66%, and the average matrix effects (MEs) were 86.23-109.96%. The high extraction recoveries and acceptable MEs indicated that the pretreatment method was feasible. And the stability was acceptable under various storage conditions and processing procedures. The validated method was successfully applied to the multiple components-PK studies, which lay the foundation for further pharmacological and clinical research of PTC and may provide a reference for other traditional Chinese medicines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/bmc.5153DOI Listing
April 2021

Structurally diverse triterpenes obtained from the fruits of Ziziphus jujuba Mill. as inflammation inhibitors by NF-κB signaling pathway.

Food Funct 2021 May 22;12(10):4496-4503. Epub 2021 Apr 22.

Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, 301617, Tianjin, China. [email protected] tjutcm.edu.cn

Twenty-nine triterpenes were obtained from the fruits of Ziziphus jujuba Mill. through various chromatography methods, and their stereo-structures were confirmed by spectroscopic methods. Among them, 2α,3β,20-trihydroxylupane-28-oic acid (1) was identified as a new compound, and the H and C NMR data of 7, 8 and 23, as well as the C NMR data of 17 are reported here for the first time. Meanwhile, the nitric oxide (NO) inhibitory activities of all compounds were examined in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. As results, compounds 2, 7, 10-13, 15, 16, 18-21, 26-29 were found to play important roles in suppressing NO production at 5 μM. The structure-activity relationships (SARs) on NO inhibition indicated that the ursolic and oleanolic acid skeletons, p-coumaroyl group substitution, six-membered A ring, and deoxygenation (loss of C[double bond, length as m-dash]O) in the C ring showed a more positive effect on the NO inhibitory activity of triterpenes, while the reduction of the A ring C[double bond, length as m-dash]O to OH was a negative factor. Moreover, it was found that compounds 15 and 19 could suppress the phosphorylation of IκBα and NF-κB/p65 to prevent it from shifting into the nucleus and downregulate the expression of inflammatory factors, such as iNOS, IL-6 and TNF-α. Our investigations revealed that the NO inhibitory effects of the active triterpenes obtained from Z. jujuba were mediated, at least in part, through the NF-κB signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1fo00117eDOI Listing
May 2021

Determination of Trimethylamine -oxide and Betaine in Serum and Food by Targeted Metabonomics.

Molecules 2021 Mar 2;26(5). Epub 2021 Mar 2.

State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

Trimethylamine -oxide (TMAO), as a gut-derived metabolite, has been found to be associated with enhanced risk for atherosclerosis and cardiovascular disease. We presented a method for targeted profiling of TMAO and betaine in serum and food samples based on a combination of one-step sample pretreatment and proton nuclear magnetic resonance spectroscopy. The key step included a processing of sample preparation using a selective solid-phase extraction column for retention of basic metabolites. Proton signals at 3.29 and 3.28 were employed to quantify TMAO and betaine, respectively. The developed method was examined with acceptable linear relationship, precision, stability, repeatability, and accuracy. It was successfully applied to detect serum levels of TMAO and betaine in TMAO-fed mice and high-fructose-fed rats and also used to determine the contents of TMAO and betaine in several kinds of food, such as fish, pork, milk, and egg yolk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules26051334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958608PMC
March 2021

Discovery of natural adenosine monophosphate‑activated protein kinase activators through virtual screening and activity verification studies.

Mol Med Rep 2021 03 26;23(3). Epub 2021 Jan 26.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P.R. China.

The adenosine monophosphate‑activated protein kinase (AMPK) is a promising target in drug development for various metabolic diseases. In the present study, the aim was to discover natural direct AMPK activators from natural sources, thus a virtual screening for direct AMPK activators was conducted by combining ligand‑based and structure‑based screening. A common‑feature pharmacophore model (HipHop1) was generated with two hydrogen bond acceptor lipid features and one hydrophobic region feature. A total of 1,235 natural products were screened using the HipHop1 hypothesis and CDOCKER protocol successively. According to the docking score, seven hit compounds were selected for AMPK activation assays. Ultimately, (‑)‑catechin (compound 522) and licochalcone A (compound 1148) exhibited the highest AMPK activation activity. These findings may contribute to the development of AMPK activators from medicinal plants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2021.11842DOI Listing
March 2021

Polygonum multiflorum: Recent updates on newly isolated compounds, potential hepatotoxic compounds and their mechanisms.

J Ethnopharmacol 2021 May 21;271:113864. Epub 2021 Jan 21.

State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin, 301617, PR China. Electronic address:

Ethnopharmacological Relevance: Polygonum multiflorum Thunb.(PM), (known as Heshouwu () in China) is one of the most important and well mentioned Chinese medicinal herbs in the literature for its use in blackening hair, nourishing liver and kidney, anti-aging, anti-hyperlipidemia, antioxidant, anti-inflammatory, anticancer, hepatoprotection, cardio-protection and improving age-related cognitive dysfunction. The purpose of this review is to give a comprehensive and recent update on PM: new compounds or isolated for the first time, potential hepatotoxic compounds and their mechanisms. Moreover, future perspectives and challenges in the future study of this plant are conversed which will make a new base for further study on PM.

Materials And Methods: A comprehensive review of relevant published literature on PM using the scientific databases SCOPUS, PubMed, and Science Direct was done.

Results: PM is broadly produced in many provinces of China and well known in other Eastern Asian Countries for its ethno-medical uses. Previous phytochemical investigation of PM had led to the isolation of more than 175 compounds including recently isolated 70 new compounds. Most of the new compounds isolated after 2015 are majorly dianthrone glycosides and stilbene glycosides. Processing has also a significant effect on chemical composition, pharmacological activities, and toxicity of PM. PM-induced liver injury is increasing after the first report in Hong Kong in 1996. Hepatotoxicity of PM was constantly reported in Japan, Korea, China, Australia, Britain, Italy, and other countries although its toxicity is related to idiosyncratic hepatotoxicity. More interestingly, although there is indispensable interest to predict idiosyncratic hepatotoxicity of PM and understand its mechanisms, the responsible hepatotoxic compounds and mechanisms of liver damage induced by PM are still not clear. There is a big controversy on the identification of the most responsible constituent. Anthraquinone and stilbene compounds in PM, mainly emodine and TSG are mentioned in the literature to be the main responsible hepatotoxic compounds. However, comparing the two compounds, which one is the more critical toxic agent for PM-induced hepatotoxicity is not well answered. Affecting different physiological and metabolic pathways such as oxidative phosphorylation and TCA cycle pathway, metabolic pathways, bile acid excretion pathway and genetic polymorphisms are among the mechanisms of hepatotoxicity of PM.

Conclusion: Deeper and effective high throughput experimental studies are still research hotspots to know the most responsible constituent and the mechanism of PM-induced hepatotoxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2021.113864DOI Listing
May 2021

The composition differences between small black beans and big black beans from different habitats and its effects on the processing of Polygonum multiflorum.

Phytochem Anal 2020 Dec 17. Epub 2020 Dec 17.

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Introduction: The roots of Polygonum multiflorum (PM) serve as a classical traditional Chinese medicine (TCM), which has multiple biological activities. However, many cases of hepatotoxicity in PM have been reported in recent years. Processing PM with black beans decoction is one of the typical processing methods to reduce the hepatotoxicity of PM since ancient times.

Objectives: To find potential effective constituents, as well as the optimal variety and origin of black beans for the processing of PM.

Methods: Based on ultrahigh-performance liquid chromatography Q-Orbitrap mass spectrometry (UHPLC-Q-Orbitrap-MS) analysis, we measured the contents of the two potential toxic compounds (emodin-8-O-glucoside and torachrysone-O-hexose) in raw PM (R-PM), PM processed with big black beans (B-PM) and PM processed with small black beans (S-PM). The flow cytometry method analysed the effects of different processed products of PM on apoptosis of L02 cells in different drug concentration. Proton nuclear magnetic resonance ( H-NMR) and UHPLC-Q-Orbitrap-MS together with multivariate statistical analysis were used to systematically analyse the different components between small black beans (Small-BB) and big black beans (Big-BB) from 30 different habitats.

Results: The toxicity was ranked from small to large: S-PM < B-PM < R-PM. Processing PM with black beans could significantly decrease the apoptosis rate of L02 cells, especially when the drug concentration is 80 μg/mL. Besides, we find five differential compounds (α-arabinose, α-galactose, proline, isomer of daidzein and isomer of genistein) may be potential active ingredients. In terms of the black beans collected from 30 producing areas, we find that Small-BB from Weifang in Shandong province was optimum to processing PM, followed by Shangqiu in Henan province, Jilin and Liaoning province.

Conclusion: The ingredients that affect the processing of PM may be attributed to α-arabinose, α-galactose, proline, isomer of daidzein and isomer of genistein in black beans. When the drug concentration is higher, the effect of reducing the hepatotoxicity of PM is better. Besides, Small-BB was more effective than Big-BB for reducing the toxicity of PM, especially Small-BB from Weifang in Shandong, Shangqiu in Henan province and northeast China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pca.3022DOI Listing
December 2020

A Proposed Drought Response Equation Added to the Münch-Horwitz Theory of Phloem Transport.

Front Plant Sci 2020 4;11:505153. Epub 2020 Nov 4.

School of Mathematical and Statistical Sciences, Arizona State University, Tempe, AZ, United States.

Theoretical and experimental evidence for an effect of sieve tube turgor pressure on the mechanisms of phloem unloading near the root tips during moderate levels of drought stress is reviewed. An additional, simplified equation is proposed relating decreased turgor pressure to decreased rate kinetics of membrane bound transporters. The effect of such a mechanism would be to decrease phloem transport speed, but increase concentration and pressure, and thus prevent or delay negative pressure in the phloem. Experimental evidence shows this mechanism precedes and exceeds a reduction in stomatal conductance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpls.2020.505153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672028PMC
November 2020

Thirteen bisbenzylisoquinoline alkaloids in five Chinese medicinal plants: Botany, traditional uses, phytochemistry, pharmacokinetic and toxicity studies.

J Ethnopharmacol 2021 Mar 7;268:113566. Epub 2020 Nov 7.

Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin-300250, China. Electronic address:

Relevance: Bisbenzylisoquinoline (BBIQ) alkaloids are generally present in plants of Berberidaceae, Monimiaceae and Ranunculaceae families in tropical and subtropical regions. Some species of these families are used in traditional Chinese medicine, with the effects of clearing away heat and detoxification, promoting dampness and defecation, and eliminating sores and swelling. This article offers essential data focusing on 13 representative BBIQ compounds, which are mainly extracted from five plants. The respective botany, traditional uses, phytochemistry, pharmacokinetics, and toxicity are summarized comprehensively. In addition, the ADME prediction of the 13 BBIQ alkaloids is compared and analyzed with the data obtained.

Materials And Methods: We have conducted a systematic review of the botanical characteristics, traditional uses, phytochemistry, pharmacokinetics and toxicity of BBIQ alkaloids based on literatures collected from PubMed, Web of Science and Elsevier during 1999-2020. ACD/Percepta software was utilized to predict the pharmacokinetic parameters of BBIQ alkaloids and their affinity with enzymes and transporters.

Results: Botany, traditional uses, phytochemistry, pharmacokinetic and toxicity of 13 alkaloids, namely, tetrandrine, dauricine, curine, trilobine, isotrilobine, cepharanthine, daurisoline, thalicarpine, thalidasine, isotetrandrine, liensinine, neferine and isoliensinine, have been summarized in this paper. It can't be denied that these alkaloids are important material basis of pharmacological effects of family Menispermaceae and others, and for traditional and local uses which has been basically reproduced in the current studies. The 13 BBIQ alkaloids in this paper showed strong affinity and inhibitory effect on P-glycoprotein (P-gp), with poor oral absorption and potent binding ability with plasma protein. BBIQ alkaloids represented by tetrandrine play a key role in regulating P-gp or reversing multidrug resistance (MDR) in a variety of tumors. The irrationality of their usage could pose a risk of poisoning in vivo, including renal and liver toxicity, which are related to the formation of quinone methide during metabolism.

Conclusion: Although there is no further clinical evaluation of BBIQ alkaloids as MDR reversal agents, their effects on P-gp should not be ignored. Considering their diverse distribution, pharmacokinetic characteristics and toxicity reported during clinical therapy, the quality standards in different plant species and the drug dosage remain unresolved problems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2020.113566DOI Listing
March 2021

Docking Studies on Potential Mechanisms for Decreasing Insulin Resistance by the Tangzhiqing Herbal Formula.

Evid Based Complement Alternat Med 2020 9;2020:1057648. Epub 2020 Oct 9.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin 301617, China.

Insulin resistance (IR) is considered as one of the principal pathways of type 2 diabetes mellitus pathogenesis and is associated with a series of abnormal signaling pathways. Tangzhiqing (TZQ) herbal formula is a well-known antidiabetic traditional Chinese medicine and has been used to treat type 2 diabetes mellitus and prediabetes for many years in China. We selected 13 natural products as representative compounds of the main active components in TZQ to investigate the interaction of these natural products with key signal proteins associated with IR using two different docking calculations. Salvianolic acids A and C (phenolic acids from ), rutin (a flavonoid from ), paeoniflorin (a saponin from ), and quercitrin (a flavonoid from ) showed great docking abilities towards multiple target proteins. These results have contributed to a clearer understanding regarding the regulation mechanism of TZQ on IR and have provided direction for further pharmacological studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/1057648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568782PMC
October 2020

Multiomics Integrative Analysis for Discovering the Potential Mechanism of Dioscin against Hyperuricemia Mice.

J Proteome Res 2021 01 27;20(1):645-660. Epub 2020 Oct 27.

State Key Laboratory of Component-Based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, 10 Poyanghu Road, Jinghai District, Tianjin 301617, China.

Hyperuricemia is a well-known key risk factor for gout and can cause a variety of metabolic diseases. Several studies have shown that dioscin could improve metabolic symptoms and reduce the uric acid level in blood. However, there is no comprehensive metabolomic study on the anti-hyperuricemia effects of dioscin. A total of 29 adult male Kunming mice were divided into three groups: Normal (blank), PO (potassium oxonate-administrated, 200 mg/kg/day), and Dioscin (potassium oxonate + dioscin, potassium oxonate 200 mg/kg/day, dioscin 50 mg/kg/day). All mice were treated for 42 days via oral gavage. This paper implemented an untargeted metabolomics study based on H NMR and LC-MS to discover the comprehensive mechanism of dioscin. Furthermore, a targeted lipidomics was fulfilled to further analyze the lipid metabolism disorder. Finally, the metabolic pathway mediated by dioscin was verified at the gene level by means of transcriptomics. The results show 53 different metabolites were closely related to the improvement of dioscin in PO-induced hyperuricemia, and 19 of them were lipids. These metabolites are mainly involved in the tricarboxylic acid cycle, lipid metabolism, amino acid metabolism, and pyrimidine metabolism. According to the transcriptomics study, the levels of 89 genes were significantly changed in the PO group compared to the normal control. Among them, six gene levels were restored by the treatment of dioscin. The six changed genes (tx1b, Tsku, Tmem163, Psmc3ip, Tcap, Tbx15) are mainly involved in the cell cycle and energy metabolism. These metabolites and genes might provide useful information for further study of the therapeutic mechanism of dioscin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jproteome.0c00584DOI Listing
January 2021

leaf extract alters gut microbiota composition, enhances short-chain fatty acids production, and ameliorates osteoporosis in the senescence-accelerated mouse P6 (SAMP6) model.

Food Sci Nutr 2020 Sep 19;8(9):4897-4906. Epub 2020 Jul 19.

Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae Ministry of Education Tianjin University of Traditional Chinese Medicine Tianjin China.

The bark and the leaf of Oliv. content similar bioactive components, but the leaf of this medically important plant is mostly abandoned. In this study, we revealed that the aqueous extract of leaf (EUL) can promote the growth of the probiotic (LB) and inhibit the formation of osteoclast in vitro. This extract was next administrated to senescence-accelerated mice P6 to evaluate examine its influence on the composition of gut microbiota (GM), short-chain fatty acids (SCFAs), and osteoporosis (OP). The results showed that supplementation of the EUL aqueous extract to the mouse model: (a) increased bacterial diversity and Firmicutes/Bacteroidetes ratio in the gut, (b) increased SCFAs concentration in the feces and serum, and (c) ameliorated OP based on the results of bone mineral density (BMD), Dual-energy X-ray bone scan, and HE staining of distal femur.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/fsn3.1779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500782PMC
September 2020

3D porous graphene composite film embedded by Ni/NiO nanoparticles as freestanding electrodes for efficient energy storage devices.

Nanotechnology 2020 Nov;31(47):475704

State Laboratory of Surface and Interface, Zhengzhou University of Light Industry, Zhengzhou 450002, People's Republic of China.

A 3D porous graphene composite film containing Ni/NiO hybrid nanoparticles (Ni/NiO NPs) is prepared by combining electrophoresis deposition and thermal H annealing techniques. The Ni/NiO NPs with a mean diameter of 45 nm are uniformly embedded on both the exterior and interior surfaces of reduced graphene, forming a 3D porous reduced graphene oxide composite film (Ni/NiO rGO). The insertion of Ni/NiO NPs into rGO greatly improves the electric conductivity and charge storage capability of the resultant Ni/NiO rGO film. By directly using it as freestanding electrodes, the fabricated lithium-ion battery and supercapacitor respectively exhibited high capacities of 758 mAh [email protected] 0.2 A g and 430.8 F [email protected] A g, an increase of 82.3-fold and 20.2-fold compared to the pure rGO electrode-based counterparts under the same condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1361-6528/abae2dDOI Listing
November 2020

Identification and Structural Analysis of Spirostanol Saponin from by Integrating Silica Gel Column Chromatography and Liquid Chromatography/Mass Spectrometry Analysis.

Molecules 2020 Aug 24;25(17). Epub 2020 Aug 24.

Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin 301617, China.

Roezl (Mojave), a kind of ornamental plant belonging to the genus (Agavaceae), whose extract exhibits important roles in food, beverage, cosmetic and feed additives owing to its rich spirostanol saponins. To provide a comprehensive chemical profiling of the spirostanol saponins in it, this study was performed by using a multi-phase liquid chromatography method combining a reversed phase chromatography T column with a normal phase chromatography silica column for the separation and an ESI-Q-Exactive-Orbitrap MS in positive ion mode as the detector. By comparing the retention time and ion fragments with standards, thirty-one spirostanol saponins were identified. In addition, according to the summary of the chromatographic retention behaviors and the MS/MS cleavage patterns and biosynthetic pathway, another seventy-nine spirostanol saponins were speculatively identified, forty ones of which were potentially new ones. Moreover, ten novel spirostanol saponins (three pairs of (25)-spirostanol saponin isomer mixtures) were targeted for isolation to verify the speculation. Then, the comprehensive chemical profiling of spirostanol saponins from was reported here firstly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules25173848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504267PMC
August 2020

New 12,23-Epoxydammarane Type Saponins Obtained from Leaves and Their Anti-Inflammatory Activity.

Molecules 2020 Aug 20;25(17). Epub 2020 Aug 20.

Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin 301617, China.

Two new 12,23-epoxydammarane-type saponins, notoginsenosides NL-I () and NL-J (), were isolated and identified from leaves through the combination of various chromatographies and extensive spectroscopic methods, as well as chemical reactions. Among them, notoginsenoside NL-J () had a new skeleton. Furthermore, the lipopolysaccharide (LPS)-induced RAW 264.7 macrophage model was used to identify the in vitro anti-inflammatory activity and mechanisms of compounds and . Both of them exerted strong inhibition on nitric oxide (NO) productions in a concentration-dependent manner at 1, 10, and 25 μM. Moreover, these two compounds significantly decreased the secretion of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), cyclooxygenase-2 (COX-2), nuclear factor kappa-B (NF-κB/p65), and nitric-oxide synthase (iNOS) in LPS-activated RAW 264.7 cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules25173784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504330PMC
August 2020

Regulating the electrochemical behaviours of a hierarchically structured Co(PO)/Ni-Co-O for a high-performance all-solid-state supercapacitor.

Dalton Trans 2020 Aug;49(30):10621-10630

School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001, People's Republic of China. and Henan Key Laboratory of Advanced Nylon Materials and Application, Zhengzhou University, Zhengzhou 450001, People's Republic of China.

Battery-type materials (e.g., transition metal phosphates) have been intensely explored in supercapacitors due to their rich electroactive sites and high theoretical capacity. Yet poor rate performance, resulting in a low energy density at high current density, limits their further applications. Herein, an improvement in rate performance resulting from enhanced surface capacitive behaviour contribution has been observed in a hierarchically structured Co3(PO4)2/[email protected] foam (CPNO-12). The optimized CPNO-12 synthesized through a facile hydrothermal treatment also exhibits a striking gravimetric and areal capacity of 1410C g-1 (14 100 mC cm-2) at 5 mA cm-2 and superb cyclability (91% of retention at 50 mA cm-2 after 12 000 cycles), which can be attributed to its unique hierarchical porous structure and high mass loading per area. More importantly, a high-performance all-solid-state asymmetric supercapacitor with CPNO-12 and Fe2P/graphene [email protected] foam as positive and negative electrodes respectively has been assembled; the device delivering a maximum energy density of 95 W h kg-1 (32 mW h cm-3) and maximum power density of 4000 W kg-1 (800 mW cm-3) has the potential to power sophisticated systems. These attractive performances confirm that an enhancement of capacitive behaviour in battery-type materials holds the promise for fabricating high-performance supercapacitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0dt01818jDOI Listing
August 2020

Anti-inflammatory canthin-6-one alkaloids from the roots of Thailand Eurycoma longifolia Jack.

J Nat Med 2020 Sep 8;74(4):804-810. Epub 2020 Jul 8.

Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, China.

Two new canthin-6-one alkaloids, 4,9-dimethoxy-5-hydroxycanthin-6-one (1) and 9-methoxy-(R/S)-5-(1-hydroxyethyl)-canthin-6-one (2), together with fifteen known ones were isolated from the roots of Thailand Eurycoma longifolia Jack. Among the known canthin-6-one alkaloids, compounds 9 and 16 were isolated from the Eurycoma genus for the first time. Meanwhile, the nitric oxide (NO) inhibitory activities of all isolates were examined in lipopolysaccharide (LPS)-stimulated RAW264.7 cells at 50 µM. Moreover, a dose-dependent experiment was conducted for active compounds 1, 2, 4, 6, 7, 10, 12-17 at the concentration of 10, 25, and 50 µM, respectively. Consequently, compounds 1, 4, 6, 7, 12, 14, 15, as well as 17 were found to inhibit NO release from RAW264.7 cells in a dose-dependent manner. Two new canthin-6-one alkaloids, 4,9-dimethoxy-5-hydroxycanthin-6-one (1) and 9-methoxy-(R/S)-5-(1-hydroxyethyl)-canthin-6-one (2), together with fifteen known ones were isolated from the roots of Thailand Eurycoma longifolia Jack. Among them, 1, 4, 6, 7, 12, 14, 15, as well as 17 were found to inhibit NO release from RAW264.7 cells in a dose-dependent manner at the concentration of 10, 25, and 50 µM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11418-020-01433-6DOI Listing
September 2020

Integration of multicomponent characterization, untargeted metabolomics and mass spectrometry imaging to unveil the holistic chemical transformations and key markers associated with wine steaming of Ligustri Lucidi Fructus.

J Chromatogr A 2020 Aug 26;1624:461228. Epub 2020 May 26.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Tianjin 300193, China; Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Tianjin 300193, China. Electronic address:

Processing of traditional Chinese medicine (TCM) can enhance the efficacy and/or reduce the toxicity. Currently available approaches regarding TCM processing generally focus on a few markers, rendering a one-sided strategy that fail to unveil the involved global chemical transformation. We herein present a strategy, by integrating enhanced multicomponent characterization, untargeted metabolomics, and mass spectrometry imaging (MSI), to visualize the chemical transformation and identify the markers associated with the wine steaming of Ligustri Lucidi Fructus (LLF), as a case. An ultra-high-performance liquid chromatography/quadrupole-Orbitrap mass spectrometry-based polarity-switching (between the negative and positive modes), precursor ions list-including data-dependent acquisition approach was developed, which enabled the simultaneous targeted/untargeted characterization of 158 components from LLF via one injection analysis. Holistic, continuous, and time-dependent chemical variation trajectory, among different processing time (0-12 h) for LLF, was depicted by principle component analysis. Pattern recognition chemometrics could unveil 20 markers, among which the peak area ratios of eight components to oleuropein aglycone, used as an internal standard, were diagnostic to identify the processed (both the commercial and in-house prepared) from the raw LLF. Four markers (10-hydroxyoleoside dimethylester, 8-demethyl-7-ketoliganin, elenolic acid, and salidroside) showed an increasing trend, while another four (neonuezhenide/isomer, verbascoside/isomer, luteoline, and nuzhenal A) decreased in LLF after processing. MSI visualized the spatial distribution in the fruit and indicated consistent variation trends for four major markers deduced by the untargeted metabolomics approach. This integral strategy, in contrast to the conventional approaches, gives more convincing data supporting the processing mechanism investigations of TCM from a macroscopic perspective.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chroma.2020.461228DOI Listing
August 2020

Rapid identification of chemical composition and metabolites of Pingxiao Capsule in vivo using molecular networking and untargeted data-dependent tandem mass spectrometry.

Biomed Chromatogr 2020 Sep 6;34(9):e4882. Epub 2020 Jul 6.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Pingxiao capsule (PXC) is a herbal medicine used for adjuvant therapy in breast cancer. However, the constituents and absorbed components of the formula and their related metabolites have not been elucidated to date. PXC is a typical traditional Chinese medicine formula consisting of Strychnos nux-vomica L., Curcuma wenyujin Y. H., Agrimonia pilosa Ledeb., Toxicodendron vernicifluum, Trogopterus dung, alumen, potassium nitrate (saltpeter) and Citrus aurantium L. In this study, a ultra-high performance liquid chromatography system equipped with high resolution Q-Orbitrap mass spectrometry (MS) and comparative Global Natural Product Social molecular networking together with the Compound Discoverer software were used to identify metabolites of PXC in vitro and in vivo. Based on untargeted data-dependent MS and data-mining techniques, 89 peaks of alkaloids, flavonoids, organic acid and phenolic compounds were identified in a PXC 70% methanol extract. Furthermore, 15 absorbed prototype compounds and their metabolites were rapidly confirmed in rat blood. Glucuronidation, oxidation, methylation and hydroxylation were the main metabolic pathways. We fully clarified the chemical constituents of PXC and provided a scientific and efficient strategy for rapid discovery and identification of prototypes and their metabolites in rat plasma using high-resolution MS aided by Global Natural Product Social and Compound Discoverer software.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/bmc.4882DOI Listing
September 2020

Structure-Based Reactivity Profiles of Reactive Metabolites with Glutathione.

Chem Res Toxicol 2020 07 9;33(7):1579-1593. Epub 2020 May 9.

Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China.

Therapeutic agents can be transformed into reactive metabolites under the action of various metabolic enzymes and then covalently combine with biological macromolecules (such as protein or DNA), resulting in increasing toxicity. The screening of reactive metabolites in drug discovery and development stages and monitoring of biotransformation in post-market drugs has become an important research field. Generally, reactive metabolites are electrophilic and can be captured by small nucleophiles. Glutathione (GSH) is a small peptide composed of three amino acids (i.e., glutamic acid, cysteine, and glycine). It has a thiol group which can react with electrophilic groups of reactive metabolic intermediates (such as benzoquinone, -acetyl--benzoquinoneimine, and Michael acceptor) to form a stable binding conjugate. This paper aims to provide a review on structure-based reactivity profiles of reactive metabolites with GSH. Furthermore, this review also reveals the relationship between drugs' molecular structures and reactive metabolic toxicity from the perspective of metabolism, giving a reference for drug design and development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.chemrestox.0c00081DOI Listing
July 2020

Identification of prototypes from Ligustri Lucidi Fructus in rat plasma based on a data-dependent acquisition and multicomponent pharmacokinetic study.

Biomed Chromatogr 2020 Jul 20;34(7):e4833. Epub 2020 Apr 20.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

The identification and quantization of traditional Chinese medicine (TCM) are a challenge for researchers and industry. Using untargeted analytical methods, the in vivo detection and identification of TCM compounds are difficult because of the significant interference of endogenous substances. Fortunately, the ongoing development of new analytical technologies, especially Q-Orbitrap-MS, offers some solutions. Our team developed a holistic MS method, combining untargeted data-dependent MS (dd-MS ) modes to extensively identify TCM prototypes in vivo. The method was successfully applied to the analysis of Ligustri Lucidi Fructus (LLF). LLF is a widely used TCM with a remarkable nourishing effect on the liver and kidney. In the study, we aimed to identify the prototypes in rat plasma after oral administration of LLF extract. Following separation on an HSS T column, LLF extract and rat plasma were performed in untargeted dd-MS mode. Forty-seven compounds were characterized in rats plasma as prototypes of LLF extract. Furthermore, seven major prototypes were chosen as pharmacokinetic markers to investigate LLF's pharmacokinetic properties. The results provides comprehensive determination of compounds in LLF both in vitro and in vivo, which is important for quality control, pharmacology studies and clinical use of LLF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/bmc.4833DOI Listing
July 2020

Potent Inhibitors of Organic Anion Transporters 1 and 3 From Natural Compounds and Their Protective Effect on Aristolochic Acid Nephropathy.

Toxicol Sci 2020 06;175(2):279-291

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, P.R. China.

Organic anion transporters 1 and 3 (OAT1 and OAT3) play a critical role in renal drug-drug interactions and are involved in the nephrotoxicity of many anionic xenobiotics. To date, relatively little is known about the interaction of natural compounds with OAT1 and OAT3. Of the 270 natural compounds screened in the present study, 21 compounds inhibited OAT1 and 45 compounds inhibited OAT3. Further concentration-dependent studies identified 7 OAT1 inhibitors and 10 OAT3 inhibitors with IC50 values of <10 μM, and most of them were flavonoids, the most commonly ingested polyphenolic compounds in the diet and herbal products. Computational modeling of OAT1 and OAT3 revealed the important residues for the recognition of inhibitors. The two strong OAT inhibitors, namely wedelolactone and wogonin, were evaluated for their in vivo interactions with the OAT substrate aristolochic acid I (AAI), a natural compound causing aristolochic acid-induced nephropathy (AAN) in many species. The cytotoxicity of AAI increased in two OAT-overexpressing cell lines, with more cytotoxicity in OAT1-overexpressing cells, suggesting a more important role of OAT1 than OAT3 in AAN. Both wedelolactone and wogonin markedly increased serum AAI concentrations in AAI-treated rats and ameliorated kidney injuries in AAI-treated mice. To conclude, the present findings are of significant value in understanding natural compound-drug interactions and provide a natural source for developing treatments for AAN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/toxsci/kfaa033DOI Listing
June 2020

Hierarchically Porous MoS-Carbon Hollow Rhomboids for Superior Performance of the Anode of Sodium-Ion Batteries.

ACS Appl Mater Interfaces 2020 Mar 21;12(9):10402-10409. Epub 2020 Feb 21.

Institute for Superconducting and Electronic Materials, University of Wollongong, Wollongong, New South Wales 2522, Australia.

It is always challenging to fabricate two-dimensional transition-metal dichalcogenides into multiple hollow micro-/nanostructures with improved properties for various potential applications. Here, hierarchically porous MoS-C hollow rhomboids (MCHRs) have been creatively synthesized via a facile self-templated solvothermal approach. It has been clarified that the obtained MCHRs assembled beneath ultrathin γ-MnS and carbon cohybridized MoS nanosheets under the structural direction of the MnMoO·0.49HO self-template. The prepared MCHR anode of sodium-ion batteries exhibited a reversible capacity of 506 mA h g at 0.1 A g, ultrahigh rate capabilities up to 10 A g with 310 mA h g, and exceptional stability over 3000 cycles. This study provides inspiration for the rational design of hierarchically porous hollow nanostructures with specific geometries as an excellent electrode material for outstanding performance energy storage equipment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.9b21365DOI Listing
March 2020

Cistanche polysaccharides enhance echinacoside absorption in vivo and affect the gut microbiota.

Int J Biol Macromol 2020 Apr 24;149:732-740. Epub 2020 Jan 24.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin 301617, PR China; Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin 301617, PR China. Electronic address:

The polysaccharides and phenylethanoid glycosides from Cistanche deserticola have been demonstrated with various health benefits, however the interactive effect between these two kinds of compounds in vivo are not in detail known. The objective of this study was to investigate the synergistic actions of cistanche polysaccharides with phenylethanoid glycoside and the effects of polysaccharides on gut microbiota. Sprague-Dawley rats were fed with different kinds of cistanche polysaccharides for 20 days, on the last day, all rats were administered the echinacoside at 100 mg/kg. The results were compared mainly on the difference of pharmacokinetic parameters, gut microbiota composition, and short chain fatty acids contents. The results indicated that all the cistanche polysaccharides, including crude polysaccharide, high molecular weight polysaccharide and low molecular weight polysaccharide, could regulate the gut microbiota diversity, increase beneficial bacteria and particularly enhance the growth of Prevotella spp. as well as improve the production of short chain fatty acids and the absorption of echinacoside. By exploring the synergistic actions of polysaccharides with small molecules, these findings suggest that cistanche polysaccharides, particularly low molecular weight polysaccharides, could be used as a gut microbiota manipulator for health promotion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2020.01.216DOI Listing
April 2020

Systematic quality evaluation of Peiyuan Tongnao capsule by offline two-dimensional liquid chromatography/quadrupole-Orbitrap mass spectrometry and adjusted parallel reaction monitoring of quality markers.

Anal Bioanal Chem 2019 Nov 12;411(29):7747-7760. Epub 2019 Nov 12.

Tianjin State Key Laboratory of Modern Chinese Medicine, No. 312 Anshanxi Road, Nankai District, Tianjin, 300193, China.

Peiyuan Tongnao capsule (PTC) is a prescription medicine of traditional Chinese medicine with the effects of "nourishing the kidney," "replenishing essence," "extinguishing wind," and "opening the meridian". PTC is also widely used in clinic for the treatment of stroke and chronic cerebral circulation insufficiency. However, the quality control studies of PTC are hitherto quite limited. Here, we aim to fully utilize an advanced chromatography-mass spectrometry hyphenation technique to qualitatively and quantitatively evaluate the quality of PTC. Firstly, a two-dimensional liquid chromatography/quadrupole-Orbitrap mass spectrometry (2D-LC/Q-Orbitrap-MS) approach was established for multicomponent characterization. An offline 2D-LC system fitted with an Xbridge Amide column and an HSS T column showed an orthogonality of 0.63 and a theoretical peak capacity of 6930. Eleven fractions of PTC, after hydrophilic interaction chromatography (first dimension), were further analyzed by reversed-phase ultrahigh-performance liquid chromatography/Q-Orbitrap-MS (UHPLC/Q-Orbitrap-MS, second dimension) using a rapid negative/positive switching mode. Consequently, 178 compounds were separated, 96 of which were identified or tentatively characterized. Secondly, co-condition fingerprint analysis of seven constituted herbal medicines of PTC was performed to unveil ten active ingredients (citric acid, rehmannioside D, echinacoside, paeoniflorin, verbascoside, liquiritin, 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside, cinnamic aldehyde, glycyrrhizic acid, and emodin) as the quality markers of PTC. Thirdly, a UHPLC/PRM (adjusted parallel reaction monitoring) method was established and validated to quantify the ten marker compounds in 14 batches of PTC. To the best of our knowledge, this is the first study to report comprehensive multicomponent characterization, authentication, and quality evaluation of PTC, which could be used to lay the foundation for quality control, biological efficacy research, and further development. Graphical abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00216-019-02119-zDOI Listing
November 2019

Evaluation of intestinal permeation enhancement with carboxymethyl chitosan-rhein polymeric micelles for oral delivery of paclitaxel.

Int J Pharm 2020 Jan 9;573:118840. Epub 2019 Nov 9.

Pharmacy College, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China. Electronic address:

Polymeric micelles (PMs) are currently under investigation as potential nanocarriers for oral administration of paclitaxel (PTX). Previously, we developed amphiphilic carboxymethyl chitosan-rhein (CR) conjugate for oral delivery of PTX. PTX-loaded CR PMs exhibited a homogeneous and small size (<200 nm) with a drug loading capacity (DL) of 35.46 ± 1.07%. However, The absorption parameters of PTX using CR PMs have not been studied before. Here, we evaluated the intestinal permeation of CR PMs by in situ intestinal absorption experiments. PTX-loaded CR PMs enhanced the absorption of PTX in the intestine without causing significant intestinal villi injury. Compared to the P-glycoprotein (P-gp) inhibition of verapamil, the transport mechanism of CR PMs across intestinal epithelial cells may bypass P-gp efflux. Caco-2 cell uptake assays also confirmed that CR PMs can be taken up into the enterocyte as whole and independent of P-gp. Local biodistribution evaluation showed that fluorescence-labeled CR PMs were absorbed into the intestinal villi. In vivo bioimaging of tumor-bearing mice verified a significant portion of CR PMs were intactly absorbed through the intestine, then distributed and accumulated at the tumor site. For their significant intestinal permeation enhancement, CR PMs might be considered as promising oral delivery carriers for PTX and other water-insoluble drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2019.118840DOI Listing
January 2020

Glucocorticoids Increase Renal Excretion of Urate in Mice by Downregulating Urate Transporter 1.

Drug Metab Dispos 2019 11 13;47(11):1343-1351. Epub 2019 Sep 13.

School of Pharmaceutical Science and Technology, Tianjin University (G.L., R.M., K.S., H.X., Y.Z.), and Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Nankai District (L.H.), Tianjin, China; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington (C.D.K.); and Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China (Y.L.)

Both nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids have been widely used for the treatment of gout, a disease promoted by an excess body burden of uric acid (UA); however, their effects on the homeostasis of UA remain poorly understood. The present study showed that 1-week treatments with three NSAIDs (ibuprofen, diclofenac, and indomethacin) had little effect on UA homeostasis in mice, whereas 1-week low doses (1 and 5 mg/kg) of dexamethasone (DEX) significantly decreased serum UA by about 15%. Additionally, low doses of DEX also resulted in increases in hepatic UA concentration and urinary UA excretion, which were associated with an induction of xanthine oxidoreductase (XOR) in the liver and a downregulation of urate transporter 1 (URAT1) in the kidney, respectively. Neither 75 mg/kg DEX nor 100 mg/kg pregnenolone-16-carbonitrile altered UA concentrations in serum and livers of mice, suggesting that the effect of DEX on UA homeostasis was not due to the pregnane X receptor pathway. Further in vitro studies demonstrated that glucocorticoid receptor (GR) was involved in DEX-mediated downregulation of URAT1. Knockdown of both p65 and c-Jun completely blocked the effect of DEX on URAT1, suggesting that GR regulates URAT1 via its interaction with both nuclear factor κB and activator protein 1 signaling pathways. To conclude, the present study identifies, for the first time, a critical role of glucocorticoids in regulating UA homeostasis and elucidates the mechanism for GR-mediated regulation of URAT1 in mice. SIGNIFICANCE STATEMENT: This study demonstrates, for the first time, a critical role of glucocorticoid receptor in regulating urate transporter 1 in mouse kidney.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1124/dmd.119.087700DOI Listing
November 2019

Enhanced Switching Ratio and Long-Term Stability of Flexible RRAM by Anchoring Polyvinylammonium on Perovskite Grains.

ACS Appl Mater Interfaces 2019 Oct 23;11(39):35914-35923. Epub 2019 Sep 23.

College of Materials and Chemical Engineering , Zhengzhou University of Light Industry , Zhengzhou 450002 , People's Republic of China.

The ON/OFF ratio and long-term stability are two important issues for flexible organic-inorganic hybrid perovskite (OHP) resistive random access memory (RRAM) for practical applications. In this work, polyvinylammonium (PVAm) is applied to partially replace methylamine ions (MA) to fabricate the stable and flexible polymeric OHP RRAM devices, wherein PVAm acts as nucleation sites and the template for crystalline growth of MAPbI to tune the microscopic perovskite structure. Simultaneously, the multiple perovskite grain interfaces are strengthened through the long-carbochain polymeric backbone, hence producing a continuous and compact perovskite film. As a result, the PVAm-modified OHP RRAM device shows remarkable enhancement of the ON/OFF ratio, long-term stability, and flexibility compared with the unmodified OHP device. Specifically, the polymeric OHP device exhibits fast and stable nonvolatile resistive switching (RS) characteristics with an ON/OFF ratio of ∼10 and a set voltage of -0.45 V under ambient conditions. Also, the distinct multilevel RS behavior can be realized in this device by controlling the compliance current in the SET process. Additionally, the unsealed polymeric OHP device manifests the striking long-term stability, which can still maintain the stable memory performance after 1 year exposure to the humid and thermal ambient environment. Furthermore, the flexible polymeric OHP device was also fabricated and affords the excellent bending endurance behavior by showing a reproducible RS property over 100-cycle bending experiments. This work provides a new perovskite-based material design strategy of polymeric OHP for stable and flexible RRAM devices with the high ON/OFF ratio.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.9b12931DOI Listing
October 2019

Bioactive Constituents from the Roots of .

Molecules 2019 Aug 30;24(17). Epub 2019 Aug 30.

Tianjin State Key Laboratory of Modern Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China.

Four new phenolic components, eurylophenolosides A () and B (), eurylolignanosides A () and B (), along with twelve known compounds were isolated from the roots of Jack. The structure of these components was elucidated by using various spectral techniques and chemical reactions. Among the known isolates, syringaldehyde (), 3-chloro-4-hydroxybenzoic acid (), 3-chloro-4-hydroxyl benzoic acid-4--β-d-glucopyranoside (), and isotachioside () were isolated from the genus for the first time. Further, the NMR data of was reported here firstly. Meanwhile, the nitric oxide (NO) inhibitory activities of all compounds were examined in lipopolysaccharide (LPS)-stimulated RAW264.7 cells at 40 μM. As results, piscidinol A (), 24--piscidinol A (), bourjotinolone A (), and scopoletin () were found to play important role in suppressing NO levels without cytotoxicity. Furthermore, the Western blot method was used to investigate the mechanism of compounds , , , and by analysing the level of inflammation related proteins, such as inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in LPS-stimulated RAW264.7 cells. Consequently, compounds , , , and were found to significantly inhibit LPS-induced protein expression of IL-6, NF-κB and iNOS in NF-κB signaling pathway. Moreover, it was found that the protein expression inhibitory effects of , , and exhibited in a dose-dependent manner. The mechanism may be related to the inhibition of the iNOS expressions through suppressing the IL-6-induced NF-κB pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules24173157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749187PMC
August 2019