Ginseng fermentation solution affects the gut microbiota in zebrafish with alcoholic liver disease via PI3K/Akt pathway.

BACKGROUND: Ginsenosides have received increased amounts of attention due to their ability to modulate the intestinal flora, which may subsequently alleviate alcoholic liver disease (ALD). The effects of ginseng fermentation solution (GFS) on the gut microbiota and metabolism in ALD patients have not been explored. PURPOSE: This research aimed to explore the regulatory effect of GFS on ALD both in vitro and in vivo. METHOD: This study assessed the anti-ALD efficacy of GFS using an LO2 cell model and a zebrafish model. Untargeted metabolomics was used for differentially abundant metabolite analysis, and high-throughput 16S rRNA sequencing was used to examine the effect of GFS on ALD. RESULTS: The LO2 cell line experiments demonstrated that GFS effectively mitigated alcohol-induced oxidative stress and reduced apoptosis by upregulating PI3K and Bcl-2 expression and decreasing the levels of malondialdehyde, total cholesterol, and triglycerides. In zebrafish, GFS improved morphological and physiological parameters and diminished oxidative stress-induced ALD. Meanwhile, the results from Western blotting indicated that GFS enhanced the expression of PI3K, Akt, and Bcl-2 proteins while reducing Bax protein expression, thereby ameliorating the ALD model in zebrafish. Metabolomics data revealed significant changes in a total of 46 potential biomarkers. Among them, metabolites such as prostaglandin F2 alpha belong to arachidonic acid metabolism. In addition, GFS also partly reversed the imbalance of gut microbiota composition caused by alcohol. At the genus level, alcohol consumption elevated the presence of Flectobacillus, Curvibacter, among others, and diminished Elizabethkingia within the intestinal microbes of zebrafish. Conversely, GFS reversed these effects, notably enhancing the abundance of Proteobacteria and Archaea. Correlation analyses further indicated a significant negative correlation between prostaglandin F2 alpha, 11,14,15-THETA, Taurocholic acid and Curvibacter. CONCLUSION: This study highlights a novel mechanism by which GFS modulates anti-ALD activity through the PI3K/Akt signalling pathway by influencing the intestinal flora-metabolite axis. These results indicate the potential of GFS as a functional food for ALD treatment via modulation of the gut flora.

Regulation of polysaccharide in Wu-tou decoction on intestinal microflora and pharmacokinetics of small molecular compounds in AIA rats.

Wu-tou decoction (WTD), a traditional Chinese medicine prescription, is used to treat rheumatoid arthritis (RA). It works by controlling intestinal flora and its metabolites, which in turn modulates the inflammatory response and intestinal barrier function. Small molecular compounds (SM) and polysaccharides (PS) were the primary constituents of WTD extract. In this work, a model of adjuvant-induced arthritis (AIA) in rats was established and treated with WTD, SM, and PS, respectively. 16S rRNA gene sequencing was used to examine the regulatory impact of the various groups on the disturbance of the gut flora induced by RA. Further, since PS cannot be absorbed into the blood, the influence of PS on the absorption and metabolism of SM was studied by examining their pharmacokinetic (PK) parameters of 23 active components in SM by UPLC-MS/MS. WTD was found to be more effective than PS and SM in alleviating arthritis in AIA rats, which may be related to changes in gut flora. The PK properties of 13 active compounds were altered after PS intervene. Based on the findings, PS may be able to manage the disruption of intestinal microbiota, enhance the intestinal environment of model animals, and hence influence SM absorption and metabolism.

Identifying the active compounds and mechanism of action of TongFu XieXia Decoction for treating intestinal obstruction using network pharmacology combined with ultra-high performance liquid chromatography-quadrupole-orbitrap mass spectrometry.

RATIONALE: TongFu XieXia Decoction (TFXXD), a formulation rooted in traditional Chinese medicine and optimized through clinical practice, serves as an advanced version of the classic Da Cheng Qi decoction used for treating intestinal obstruction (IO), demonstrating significant therapeutic efficacy. However, due to the intricate nature of herbal compositions, the principal constituents and potential mechanisms of TFXXD have yet to be clarified. Accordingly, this study seeks to identify the active compounds and molecular targets of TFXXD, as well as to elucidate its anti-IO mechanisms. METHODS: Qualitative identification of the principal constituents of TFXXD was accomplished using ultra-high preformance liquid chromatography-quadrupole-orbitrap mass spectrometry (UPLC-Q-Orbitrap-MS/MS) analysis. PharmMapper facilitated the prediction of potential molecular targets, whereas protein-protein interaction analysis was conducted using STRING 11.0. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the Metascape database. A "compounds-target-pathway" network was meticulously constructed within Cytoscape 3.8.2. Finally, molecular docking studies were performed to investigate the interactions between the core target and the crucial compound. RESULTS: UPLC-Q-Orbitrap-MS/MS analysis identified 65 components with high precision and sensitivity. Furthermore, 64 potential targets were identified as integral to TFXXD bioactivity in IO treatment. Gene Ontology enrichment analysis revealed 995 distinct biological functions, while the Kyoto Encyclopedia of Genes and Genomes enrichment analysis identified 143 intricate signaling pathways. CONCLUSION: Molecular docking studies substantiated the substantial affinity between the TFXXD bioactive constituents and their corresponding targets in the context of IO. TFXXD exerts its therapeutic efficacy in IO through a multifaceted interplay between multiple compounds, targets, and pathways. The integration of network pharmacology with UPLC-Q-Orbitrap-MS/MS has emerged as a promising strategy to unravel the intricate web of molecular interactions underlying herbal medicine. However, it is imperative to emphasize the necessity for further in vivo and in vitro experiments.

Uncovering the effective substances and mechanism of Ipomoea pes-caprae against rheumatoid arthritis using liquid chromatography-mass spectrometry and targeted network pharmacology.

Ipomoea pes-caprae (L.) R. Br (Convolvulaceae) is a commonly used marine traditional Chinese medicine in the southern coastal areas of China. It has been widely used to treat rheumatoid arthritis, but its effective substances and anti-rheumatoid arthritis mechanism remain ambiguous. Hence, in this study, the chemical profile and absorbed ingredients of Ipomoea pes-caprae were elucidated by ultra-performance liquid chromatography-mass spectrometry. Moreover, targeted network pharmacology was used to clarify the mechanism of action of Ipomoea pes-caprae in treating rheumatoid arthritis. Finally, 23 compounds were identified in the aqueous extracts of Ipomoea pes-caprae and 12 absorbed ingredients were detected in rats' plasma. These 12 absorbed ingredients might be the essential effective substances of Ipomoea pes-caprae. The tissue distributions of 3 absorbed ingredients in rats were successfully analyzed. The targeted network pharmacological analysis results indicated that the regulation of inflammatory reaction, immune response, cell proliferation, and apoptosis were the critical mechanism of Ipomoea pes-caprae against rheumatoid arthritis. This study successfully clarified the effective substances and potential mechanisms of Ipomoea pes-caprae in treating rheumatoid arthritis. The results of this research could provide a valuable reference for further scientific research and clinical application.

Anti-colorectal cancer effects of seaweed-derived bioactive compounds.

Seaweeds are classified as Chlorophyta, Rhodophyta, and Phaeophyta. They constitute a number of the most significant repositories of new therapeutic compounds for human use. Seaweed has been proven to possess diverse bioactive properties, which include anticancer properties. The present review focuses on colorectal cancer, which is a primary cause of cancer-related mortality in humans. In addition, it discusses various compounds derived from a series of seaweeds that have been shown to eradicate or slow the progression of cancer. Therapeutic compounds extracted from seaweed have shown activity against colorectal cancer. Furthermore, the mechanisms through which these compounds can induce apoptosis in vitro and in vivo were reviewed. This review emphasizes the potential utility of seaweeds as anticancer agents through the consideration of the capability of compounds present in seaweeds to fight against colorectal cancer.

Identification and chemical profiling of anti-alcoholic liver disease biomarkers of ginseng Huang jiu using UPLC-Q-Orbitrap-HRMS and network pharmacology-based analyses.

This study investigated the mechanism of characteristic non-volatile organic compounds (NVOCs) from ginseng Huang jiu (GH) in the treatment of alcoholic liver disease through UPLC-Q-Orbitrap-HRMS and network pharmacological analyses. Changes in NVOC contents in ginseng Huang jiu and ginseng-soaked wine fermented by different processing technologies were analyzed through liquid chromatography-mass spectrometry (LC-MS). A total of 96 ginsenosides were identified in ginseng Huang jiu throughout the fermentation process, which included 37 protopanaxadiol-type ginsenosides, 47 protopanaxatriol-type ginsenosides, and 4 oleanolic acid-type ginsenosides. Orthogonal partial least squares-discriminant analysis (OPLS-DA) revealed that 20(R)-Rg2, Gypenoside XVII, 20(S)-Rf3, CK, Rg5, Rh2, and other rare ginsenosides in ginseng Huang jiu could be the potential index for determining ginseng Huang jiu. In addition, ginseng Huang jiu could improve alcoholic liver disease by regulating the GSTP1, HRAS, AKR1B1, GSTA1, Androgen receptor (AR), GSR, and LDHB genes through bioinformatics analysis. This study provides new insights into improving the industrial production of ginseng Huang jiu and treating alcoholic liver disease with medicinal and food products.

The chemical profile of Fubai Chrysanthemum (Fubaiju) and its mechanism in preventing cataract based on ultrahigh-performance liquid chromatography coupled with mass spectrometry and network pharmacology.

Chrysanthemum is a kind of herb that can be used for both medicine and food. Although it has been shown to affect the redox damage of the lens, but the mechanism of action has not been systematically studied. This study identified the chemical profile of Fubai Chrysanthemum. Meanwhile, network pharmacology and the enrichment of the Kyoto Encyclopedia of Genes and Genomes pathway were combined to investigate the substance basis of Fubai Chrysanthemum for preventing cataract. The aqueous extracts of Fubaiju mainly contained 39 compounds. Compared with Gongju, Jinsiju, and wild chrysanthemum, Fubai Chrysanthemum showed a higher scavenging rate of 1,1-diphenyl-2-picrylhydrazyl free radicals and a higher content of total flavonoid. Fourteen chemical differences in four kinds of chrysanthemum were found based on principal component difference analysis. Pathway enrichment analysis showed that the main mechanisms of Fubai Chrysanthemum for preventing cataract were affecting the oxidative stress process and regulating cell growth and metabolism. Eventually, 11 key targets of Fubai Chrysanthemum for cataract prevention were identified. The strategy provided a better understanding of the chemical profile of Fubai Chrysanthemum and elucidated that its higher flavonoid content plays an important role in preventing cataract through antioxidant action and regulating cell growth.

Combined 16S rRNA gene sequencing and metabolomics to investigate the protective effects of Wu-tou decoction on rheumatoid arthritis in rats.

Wu-tou decoction (WTD) is a traditional Chinese medicine (TCM) formula which has been used for treating rheumatoid arthritis (RA) for a thousand years. However, the underlying mechanism of WTD in treating RA is still unclear. In recent years, more and more attention has been paid to the role of gut microbiota and microbiota-derived metabolites in the treatment of RA. Hence, this study aims to investigate the roles of microbiota and microbial metabolites in the treatment of RA with WTD. Firstly, the therapeutic effects of WTD on adjuvant-induced arthritis (AIA) rats were evaluated. Then, the 16S rRNA sequencing analysis was used to clarify the changes of the intestinal microbiota and obtain the key microbiota affected by WTD. The important microbial metabolites were quantitated to explore the metabolic characteristics of WTD against RA by targeted metabolomics method. Finally, correlation analysis was performed to investigate the functional correlation among the gut microbiota, metabolites and RA-related serum indexes. The results indicated that WTD could relieve arthritis and reverse gut microbiota dysbiosis. The variation of short-chain fatty acids, bile acids, tryptophan metabolites and amino acids, which are important microbial metabolites, were reversed by WTD intervention. The correlation studies proved that WTD could regulate inflammation and intestinal barrier function partially by modulating Bacteroides, Prevotella, Akkermansia and their associated acetic acid, butyric acid, cholic acid and indole propionic acid. The anti-RA effects of WTD were partially mediated by gut microbiota and microbial metabolites. This study provides a new insight for treating RA and highlights the importance of gut microbiota in the treatment of diseases.

Multiresidue screening of pesticides in Panax Ginseng C. A. Meyer by ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

In this study, an efficient screening method based on a modified quick, easy, cheap, effective, rugged, and safe extraction method combined with ultra-high-performance liquid chromatography coupled to tandem quadrupole time-of-flight mass spectrometry was established for the determination of 90 pesticides residues in Panax Ginseng. The accuracy of the method was then verified by analyzing the false positive rate and the screening detection limit in Ginseng. The results revealed that the screening detection limit of 33 of 90 pesticide residues were 0.01 mg·kg-1 , 22 species were 0.05 mg·kg-1 , 11 species were 0.10 mg·kg-1 , 8 species were 0.20 mg·kg-1 , and another 16 species were greater than 0.20 mg·kg-1 . A total of 73 pesticides were ultimately suitable to be practically applied for rapid analysis of pesticide residues in Ginseng. Finally, the established method was used to analyze the pesticide residues in 35 Ginseng samples available on the market. And the residual of dimethomorph, azoxystrobin, tebuconazole, and pyraclostrobin was relatively severe in Ginseng samples. This work expanded the range of pesticides detected and provided a rapid, effective method for pesticides screening in Ginseng.

Network Pharmacology Combined with Metabolomics Approach to Investigate the Toxicity Mechanism of Paclobutrazol.

Paclobutrazol (PBZ) is a commonly used plant growth regulator (PGR) with good antibacterial activity. It has widespread applications in agricultural production. However, there is limited research reported on the potential risks of human health resulting from PBZ residues. In this study, using Sprague-Dawley rats, we carried out a systematic study on the hepatotoxicity and nephrotoxicity of PBZ in different doses (0.2, 0.5, and 1.0 g/kg). The metabolic profiles and network pharmacology were combined to construct a PBZ-endogenous substances-gene-hepatorenal diseases network to elucidate the underlying mechanism of PBZ's hepatorenal toxicity. At first, metabolomics analysis was done to investigate the metabolites and the related metabolic pathways associated with PBZ. Secondly, the network pharmacology approach was used in further exploration of the toxic targets. Additionally, molecular docking was carried out to investigate the interactions between PBZ and potential targets. The results indicated that PBZ showed obvious toxicity towards the liver and kidney of rats. The metabolomics analysis showed that PBZ mainly affected 4 metabolic pathways, including tryptophan metabolism, arachidonic acid metabolism, linoleic acid metabolism, and purine metabolism. Network pharmacology and molecular docking revealed that CYP1A2, CYP2A6, CYP2E1, MAOA, PLA2G2A, PTGS1, and XDH were critical targets for PBZ hepatorenal toxicity. This preliminary study revealed PBZ's hepatorenal toxicity and provided a theoretical basis for the rational and safe use of PBZ. Furthermore, it provided possible intervention targets for further research on how to avoid or reduce the damage caused by pesticides to the human body.

Comprehensive physiopathology and serum metabolomics for the evaluation of the influence mechanism of qi deficiency on xenograft mouse models of liver cancer.

Traditional Chinese medicine believes that qi deficiency is important pathogenesis and syndrome of liver cancer and thus is crucial in related research. However, the effect of qi deficiency on the occurrence and development of liver cancer is still unclear. This study aimed to establish a liver cancer model of qi deficiency through the swimming exhaustion and xenograft of human hepatoma HepG2 cells. The effects of qi deficiency on the occurrence and development of liver cancer were investigated by analyzing tumor development, blood routine, histopathology, and serum metabolomics. Results showed that qi deficiency greatly affected the physiology and tumor growth of xenograft mice. Eight potential biomarkers were identified by metabolomics based on ultra-high performance liquid chromatography and tandem quadrupole time-of-flight mass spectrometry. Their main pathways were arachidonic acid metabolism, phenylalanine metabolism, purine metabolism, glycerolipid metabolism, steroid biosynthesis, sphingomyelin metabolism, and fatty acid metabolism pathway. Finally, the effects of qi deficiency on the occurrence and development of liver cancer were comprehensively analyzed, and the mechanism of this process was preliminarily clarified.

Near-infrared target enhanced peripheral clearance of amyloid-ß in Alzheimer's disease model.

Clearance of peripheral amyloid-ß (Aß) has been demonstrated particularly promising for overcoming the blood-brain barrier (BBB) hurdle to remove brain-derived Aß associated with Alzheimer's disease (AD). However, currently used therapeutic agents targeting peripheral Aß cannot simultaneously achieve plasma Aß enrichment and enhanced clearance, which may result in poor bioavailability and rather low efficacy. Moreover, most of therapeutic agents usually promote the unfavorable aggregation of Aß. Herein, we construct a near-infrared (NIR) regulated surface-transformable and target peptide-guided upconversion platform (UCNP/ONA-P/K), serving as a safe and effective way for Aß clearance. Taking advantage of extended blood circulation, high selectivity toward Aß, and surface-transformable property, such UCNP/ONA-P/K can address the challenges of peripheral Aß clearance by a combination of enhancing the enrichment of plasma Aß, preventing the unfavorable aggregation of Aß and simultaneously facilitating the hepatic clearance of the captured Aß. After verified by a series of systematic toxicity evaluation, cell uptake, deep tissue penetration, and hemolytic experiments, in vivo studies demonstrate that UCNP/ONA-P/K can efficiently decrease brain Aß burden and reverse memory deficits in 3xTg-AD mice. Overall, this NIR multi-functional design provides a new biocompatible and efficient way for Aß removal, which will promote the application of peripheral clearance of Aß for AD treatment.

Pharmacokinetic and metabolomics approach based on UHPLC-MS to evaluate therapeutic effect of lignans from S. Chinensis in alzheimer's disease.

Lignans from Schisandra chinensis (Turcz.) Baill (LFS) has been proved to improve impaired cognitive ability thereby show potential in treating Alzheimer's disease (AD). In this study, UHPLC-Q-TOF-MS and UHPLC-QQQ-MS were adopted cooperatively to establish a method synchronously detecting 10 kinds of LFS monomers in rat plasma samples. And this method was further applied for pharmacokinetic study to compare the metabolism of LFS in normal and AD rats. The results indicated that AD rats showed an observably better absorption of LFS compared to normal rats. Based on time-varying plasma concentration of LFS, metabolomics was used to establish a plasma concentration-time-endogenous metabolite connection. In total 54 time-varying endogenous metabolites were screened and most of which were closely associated with AD. And LFS exerted a concentration dependent regulating effect to most of these metabolites. Through biomarker related pathways and biological function analysis, LFS might treat AD through neuroprotection, antioxidant damage and regulating the metabolism of unsaturated fatty acids. This is the first study connecting LFS absorbtion and endogenous metabolite changes with the time lapse. The pharmacokinetics and metabolic profile differences between normal and AD rats were firstly investigated as well. This study provides a novel perspective in exploring the effect and mechanism of LFS in treating AD.

Mass spectrometry-based urinary metabolomics for exploring the treatment effects of Radix ginseng-Schisandra chinensis herb pair on Alzheimer's disease in rats.

Herb pairs are the unique combinations of two relatively fixed herbs, intrinsically convey the basic idea of traditional Chinese medicine prescriptions. The compatibility of Radix ginseng and Schisandra chinensis has been used in traditional Chinese medicine for treating Alzheimer's disease for many years. However, there are few studies on Radix ginseng-Schisandra chinensis herb pair, and the underlying action mechanism is still unclear. In this study, the mechanism of Radix ginseng-Schisandra chinensis herb pair on Alzheimer's disease was investigated by using the mass spectrometry-based urinary metabolomics method. Sixteen urinary endogenous metabolites were identified as potential biomarkers. Meanwhile, 10 biomarkers were quantified with tandem mass spectrometry. The study result showed that the brain pathologic symptoms of model rats were improved and the potential biomarkers were adjusted backward significantly after the herb pair administration. The metabolic pathways linked to the herb pair-regulated endogenous biomarkers included phenylalanine and tyrosine metabolism, tryptophan metabolism, purine metabolism, and so on. The above metabolic pathways reflected that Radix ginseng-Schisandra chinensis herb pair mainly regulates abnormal energy metabolism, reduces inflammation, and regulates gut microbiota and neurotransmitters in the treatment of Alzheimer's disease.

Scale-Up Preparation of Crocins I and II from Gardeniajasminoides by a Two-Step Chromatographic Approach and Their Inhibitory Activity Against ATP Citrate Lyase.

Crocins are highly valuable natural compounds for treating human disorders, and they are also high-end spices and colorants in the food industry. Due to the limitation of obtaining this type of highly polar compound, the commercial prices of crocins I and II are expensive. In this study, macroporous resin column chromatography combined with high-speed counter-current chromatography (HSCCC) was used to purify crocins I and II from natural sources. With only two chromatographic steps, both compounds were simultaneously isolated from the dry fruit of Gardenia jasminoides, which is a cheap herbal medicine distributed in a number of countries. In an effort to shorten the isolation time and reduce solvent usage, forward and reverse rotations were successively utilized in the HSCCC isolation procedure. Crocins I and II were simultaneously obtained from a herbal resource with high recoveries of 0.5% and 0.1%, respectively, and high purities of 98.7% and 99.1%, respectively, by HPLC analysis. The optimized preparation method was proven to be highly efficient, convenient, and cost-effective. Crocins I and II exhibited inhibitory activity against ATP citrate lyase, and their IC50 values were determined to be 36.3 ± 6.24 and 29.7 ± 7.41 µM, respectively.

A comprehensive strategy to clarify the pharmacodynamic constituents and mechanism of Wu-tou decoction based on the constituents migrating to blood and their in vivo process under pathological state.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine (TCM) formula, Wu-tou decoction has been used for treating rheumatoid arthritis (RA) for more than a thousand years. Identifying pharmacodynamic constituents (PCs) of WTD and exploring their in vivo process are very meaningful for promoting the modernization of TCM. However, the pathological state might change this process. AIM OF THE STUDY: Hence, it is necessary and significant to compare the process in vivo of drugs both in normal and disease state and clarify their action mechanism. MATERIALS AND METHODS: Taking Wu-tou decoction (WTD) as the research object, a comprehensive strategy based on liquid chromatography coupled with mass spectrometry (LC-MS) was developed to identify PCs, clarify and compare their absorption and distribution in normal and model rats, and then explore the potential mechanism of TCM. Firstly, the PCs in WTD were identified. Then, the pharmacokinetics (PK) and tissue distribution of these ingredients were studied. Finally, the constituents with the difference between normal and model rats were selected for target network pharmacological analysis to clarify the mechanism. RESULTS: A total of 27 PCs of WTD were identified. The absorption and distribution of 20 PCs were successfully analyzed. In the disease state, the absorption and distribution of all these components were improved to have better treatment effects. The results of target network pharmacological analysis indicated that PTGS1, PTGS2, ABCB1, SLC6A4, CHRM2, ESR1, ESR2, CDK2, TNF and IL-6 are 10 key targets for WTD against RA. The regulatory effects of WTD on the expression of PTGS2 and TNF were further verified. Pathway enrichment analysis showed that the key mechanism of WTD against RA is to reduce inflammation and regulate the immune response. CONCLUSION: These results indicated that this strategy could better understand the in vivo process and mechanism of WTD under the pathological state. Furthermore, this strategy is also appropriate for other TCM.

The effects and mechanisms of aloe-emodin on reversing adriamycin-induced resistance of MCF-7/ADR cells.

Multidrug resistance (MDR) is one of the major obstacles for clinical effective chemotherapy. In this study, the effects and possible mechanisms of aloe-emodin (AE) were investigated on reversing the adriamycin (ADR)-induced resistance of MCF-7/ADR cells. AE could significantly reverse the ADR resistance in MCF-7/ADR cells. The combination of AE (20 µM) and ADR had no effect on the P-glycoprotein (P-gp) level, but notably promoted the accumulation of ADR in drug-resistant cells. The efflux function of P-gp required ATP, but AE reduced the intracellular ATP level. AE played a reversal role might through inhibiting the efflux function of P-gp. The research result of energy metabolism pathways indicated that combination of AE and ADR could inhibit glycolysis, tricarboxylic acid (TCA) cycle, glutamine metabolism, and related amino acid synthesis pathways. Moreover, we found AE not only reversed ADR-induced resistant but also induced autophagy as a defense mechanism. In addition, the combination of AE and ADR arrested G2/M cell cycle and induced apoptosis through DNA damage, ROS generation, caspase-3 activation. Our study indicated that AE could be a potential reversal agent to resensitize ADR resistant in tumor chemotherapy and inhibiting autophagy might be an effective strategy to further enhance the reversal activity of AE.

Boronate Affinity-Based Oriented and Double-Shelled Surface Molecularly Imprinted Polymers on 96-Well Microplates for a High-Throughput Pharmacokinetic Study of Rutin and Its Metabolites.

The boronate affinity-based oriented and double-shelled surface molecularly imprinted polymers on 96-well microplates (BDMIPs) were designed and applied to high-specific and high-throughput pharmacokinetic (PK) study of rutin and its metabolites from rat plasma without concentration and redissolution. It integrated the advantages of covalent effects-based boronate affinity, noncovalent effects of ethylene imine polymer (PEI) dendrimer, multiple cavities-based double-shelled layers, and multiparallel wells-based 96-well microplates. Furthermore, ultrahigh-performance liquid chromatography triple quadrupole tandem mass spectrometry (UHPLC-MS/MS) was used to accurately quantify targets. It showed lower limits of detection (LODs) up to 100-fold than the conventional method. And PKs of rutin and trace isoquercetin (IQC) were first reported at the same time. The platform can provide a fast, simple, low-cost, high-selective, high-effective, and high-throughput methodological reference for analysis of large-scale samples in the fields of agriculture and food.

Pharmacokinetics and tissue distribution study of 18 bioactive components in healthy and chronic heart failure rats after oral administration of Qi-Shen-Ke-Li formula using ultra-high-performance liquid chromatography/triple quadrupole mass spectrometry.

RATIONALE: Qi-Shen-Ke-Li (QSKL) is a traditional Chinese formula used in clinical practice to treat chronic heart failure (CHF) in humans. To rationalize the use of this formula in clinical practice, the pharmacokinetics and tissue distribution in rats after oral administration of QSKL were investigated using ultra-high-performance liquid chromatography/triple quadrupole mass spectrometry (UHPLC/TQ-MS). METHODS: The CHF model was induced by intraperitoneal injection of isoprenaline (ISO; also known as isoproterenol) and evaluated by HE staining and brain natriuretic peptide (BNP) measurement. The UHPLC/TQ-MS method was then applied to determine the concentrations of 18 bioactive components in rat plasma and tissues of heathy and CHF rats after oral administration of QSKL. This was followed by investigating the pharmacokinetics and tissue distribution profiles of these bioactive compounds in the heathy and CHF rats. RESULTS: The pharmacokinetics results showed that the duration time of two compounds was prolonged, the absorption rate of four compounds was accelerated, and the bioavailability of four compounds was increased in the CHF rats compared with the healthy rats. Meanwhile, the tissue distribution results showed that the QSKL formula could be distributed rapidly and widely in different rat tissues. The bioavailability of eight compounds in the liver was enhanced in CHF rats. This suggested that the drug/toxic effects should be considered in clinical practice, as drug-drug interactions might occur in liver metabolism during the drug combination. CONCLUSIONS: The pharmacokinetic profiles and tissue distribution of 18 bioactive compounds in QSKL are altered by the CHF status. This study provides insight for better clinical applications of this formula in the future and lays the foundation for the development of a new drug for chronic heart failure based on the QSKL formula.

Poria cocos could ameliorate cognitive dysfunction in APP/PS1 mice by restoring imbalance of Aß production and clearance and gut microbiota dysbiosis.

Alzheimer's disease (AD) is the most common neurodegenerative disorder. Amyloid beta-protein (Aß) plaques, which are the hallmark of AD, are formed from the imbalance of Aß production and clearance accompanied by neuroinflammation, gut dysbiosis, and metabolite dysfunction. All of these processes give rise to neurochemical deficiencies and synaptic dysfunction, which ultimately contribute to recognition dysfunction. Poria cocos (PC), which contains multiple active ingredients, plays a significant role in the treatment of multiple-pathogenesis senile diseases such as AD. Nevertheless, there are only very few investigations on the intricate action mechanism of PC for the treatment of AD. In this study, we evaluate the multi-target cure effect of PC on APP/PS1 mice by behavioral, immunohistochemical (IHC), targeted metabolomics, and 16S rRNA sequencing experiments. Mice treated with PC showed significant improvements in cognitive function as evaluated by the behavioral experiment. IHC revealed that PC treatment relieved Aß deposition by reducing the formation of Aß and increasing its clearance. Moreover, PC treatment improved gut dysbiosis, which reversed the metabolite dysfunction of bile acid. These findings reveal that PC is a promising therapeutic agent, which might ameliorate the cognitive function of AD by restoring the imbalance of Aß production and clearance and gut microbiota dysbiosis.