Development of Quasi-Two-Dimensional Perovskites and Their Application in Light-Emitting Diodes.

Quasi-two-dimensional (quasi-2D) perovskites have attracted much attention due to their outstanding properties, such as inherent quantum-well structure, strong dielectric and quantum confinement, large exciton binding energy, and high photoluminescence quantum yield. By virtue of these superior merits, quasi-2D perovskites have shown great potential for next-generation light-emitting diodes (LEDs). Herein, this review presents an overview of the basic properties of quasi-2D perovskites and their photoluminescence modulations by large organic cation engineering, monovalent cation engineering, halogen engineering, defect passivation engineering, and dimensionality engineering. Furthermore, the strategies of charge-transport layer optimization, interfacial engineering, light-outcoupling efficiency improvement, and operating stability improvement are summarized for fabricating high-performance quasi-2D perovskite LEDs (PeLEDs). Finally, the challenges and outlook for the future development of quasi-2D PeLEDs are unambiguously proposed.

[Study on preparation method of reference substance of aristolactam â -deoxyriboside adducts].

A two-step synthetic process of bromination and cross-coupling with aristololactam Ⅰ as raw material was successfully developed. Three aristolactam Ⅰ-deoxyriboside adducts, namely AAⅠ-dA, AAⅠ-dG, and AAⅠ-dC were obtained after a sequential procedure of impurity removal and purification in four different solvents. The yield of the two-step reaction can reach 90%, and the purity of the product is more than 98%, which can meet the requirements of qualitative and quantitative analyses as traditional Chinese medicine chemical reference products. The process has been proven to have good repeatability and scalability, and it features a concise preparation procedure, efficient purification, and high yield and purity, requiring no chromatographic separation. Compared with pre-vious methods, the newly developed process has significant advantages and is suitable for the preparation of chemical reference products of aristolactam Ⅰ-deoxyriboside adducts. This process provides technical support for the preparation of reference products of aristolactam Ⅰ-deoxyriboside adducts and a solid material basis for the related toxicological research.

Unraveling the dynamic behaviors of BF4-based ionic liquids at the SnO2/FAPbI3 interface using ab initio molecular dynamics simulations.

Ab initio molecular dynamics simulations are performed to unravel the complex dynamic behaviors of BF4-based ionic liquids (ILs) at the SnO2/FAPbI3 interface. Specifically, the BMIM+BF4- IL not only eliminates the density of states induced by oxygen vacancies in SnO2, but also significantly increases the iodine ion migration energy barrier in FAPbI3.

A Network-Pharmacology-Combined Integrated Pharmacokinetic Strategy to Investigate the Mechanism of Potential Liver Injury due to Polygonum multiflorum.

Polygonum multiflorum (PM) has been used as a tonic and anti-aging remedy for centuries in Asian countries. However, its application in the clinic has been hindered by its potential to cause liver injury and the lack of investigations into this mechanism. Here, we established a strategy using a network pharmacological technique combined with integrated pharmacokinetics to provide an applicable approach for addressing this issue. A fast and sensitive HPLC-QQQ-MS method was developed for the simultaneous quantification of five effective compounds (trans-2,3,5,4'-tetrahydroxystilbene-2-O-ß-d-glucoside, emodin-8-O-ß-d-glucoside, physcion-8-O-ß-d-glucoside, aloe-emodin and emodin). The method was fully validated in terms of specificity, linearity, accuracy, precision, extraction recovery, matrix effects, and stability. The lower limits of quantification were 0.125-0.500 ng/mL. This well-validated method was successfully applied to an integrated pharmacokinetic study of PM extract in rats. The network pharmacological technique was used to evaluate the potential liver injury due to the five absorbed components. Through pathway enrichment analysis, it was found that potential liver injury is primarily associated with PI3K-Akt, MAPK, Rap1, and Ras signaling pathways. In brief, the combined strategy might be valuable in revealing the mechanism of potential liver injury due to PM.

Discovery of Hepatotoxic Equivalent Markers and Mechanism of Polygonum multiflorum Thunb. by Metabolomics Coupled with Molecular Docking.

Polygonum multiflorum Thunb. (PMT), a commonly used Chinese herbal medicine for treating diseases such as poisoning and white hair, has attracted constant attention due to the frequent occurrence of liver injury incidents. To date, its hepatotoxic equivalent markers (HEMs) and potential hepatotoxic mechanisms are still unclear. In order to clarify the HEMs of PMT and further explore the potential mechanisms of hepatotoxicity, firstly, the chemical constituents in PMT extract were globally characterized, and the fingerprints of PMT extracts were established along with the detection of their hepatotoxicity in vivo. Then, the correlations between hepatotoxic features and component contents were modeled by chemometrics to screen HEMs of PMT, which were then further evaluated. Finally, the hepatotoxic mechanisms of PMT were investigated using liver metabolomics and molecular docking. The results show that the chemical combination of 2,3,5,4-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) and emodin-8-O-glucoside (EG) was discovered as the HEMs of PMT through pre-screening and verifying process. Liver metabolomics revealed that PMT caused liver injury by interfering with purine metabolism, which might be related to mitochondrial function disorder and oxidative injury via the up-regulations of xanthosine and xanthine, and the down-regulation of 5' nucleotidase (NT5E) and adenylate kinase 2 (AK2). This study not only found that the HEMs of PMT were TSG and EG, but also clarified that PMT might affect purine metabolism to induce liver injury, which contributed to our understanding of the underlying mechanisms of PMT hepatotoxicity.

Assessing potential liver injury induced by Polygonum multiflorum using potential biomarkers via targeted sphingolipidomics.

CONTEXT: Polygonum multiflorum Thunb. (Polygonaceae) (PM) can cause potential liver injury which is typical in traditional Chinese medicines (TCMs)-induced hepatotoxicity. The mechanism involved are unclear and there are no sensitive evaluation indicators. OBJECTIVE: To assess PM-induced liver injury, identify sensitive assessment indicators, and screen for new biomarkers using sphingolipidomics. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats were randomly divided into four groups (control, model with low-, middle- and high-dose groups, n = 6 each). Rats in the three model groups were given different doses of PM (i.g., low/middle/high dose, 2.7/8.1/16.2 g/kg) for four months. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the plasma and liver were quantitatively analyzed. Fixed liver tissue sections were stained with haematoxylin and eosin and examined under a light microscope. The targeted sphingolipidomic analysis of plasma was performed using high-performance liquid chromatography tandem mass spectrometry. RESULTS: The maximal tolerable dose (MTD) of PM administered intragastrically to mice was 51 g/kg. Sphingolipid profiling of normal and PM-induced liver injury SD rats revealed three potential biomarkers: ceramide (Cer) (d18:1/24:1), dihydroceramide (d18:1/18:0)-1-phosphate (dhCer (d18:1/18:0)-1P) and Cer (d18:1/26:1), at 867.3-1349, 383.4-1527, and 540.5-658.7 ng/mL, respectively. A criterion for the ratio of Cer (d18:1/24:1) and Cer (d18:1/26:1) was suggested and verified, with a normal range of 1.343-2.368 (with 95% confidence interval) in plasma. CONCLUSIONS: Three potential biomarkers and one criterion for potential liver injury caused by PM that may be more sensitive than ALT and AST were found.

Rapid identification of chemical constituents of Rhodiola crenulata using liquid chromatography-mass spectrometry pseudotargeted analysis.

Rhodiola crenulata (R. crenulata), is a famous traditional Chinese medicine, with observable effects such as anti-high-altitude illness and fatigue resistance. Nevertheless, comprehensive and systematic structural identification of its components remains a challenge. In this study, a pseudotargeted analytical method, involving key fragment filtering by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and ultra-high performance liquid chromatography-linear ion trap-Orbitrap mass spectrometry, was developed for rapid detection and identification of the chemical constituents of R. crenulata. The process consists of three steps: (i) acquiring sufficient mass spectral data, (ii) constructing a key fragments schedule and discovering the substructures rapidly by pseudotargeted key fragment filtering, and (iii) further identification of the compound structures based on accurate masses, fragment ions, related literatures, and authentic standards. As a result, 104 compounds were identified and divided into five categories, among which three potentially new and 59 ones were reported for the first time in R. crenulata. These results indicated that the major types of components are flavanols and gallic acid derivatives, organic acids, alcohols and their glycosides, flavonoids and their glycosides. This study enhances the understanding of R. crenulata and provides a reference for rapid and comprehensive identification of constituents in other herbal medicines.

The evaluation of anti-breast cancer activity and safety pharmacology of the ethanol extract of Aralia elata Seem. leaves.

Aralia elata Seem. is a traditional folk Chinese medicinal plant and its leaves have been used to treat many diseases. We aimed to evaluate the anti-breast cancer activity and safety pharmacology of the ethanol extract of A. elata Seem. leaves (ELE). Cytotoxicity was evaluated on human tumor cell lines by MTT assay in vitro. A tumor bearing-nude mice model was used to assess antitumor activity in vivo. Cell apoptosis was determined by Hoechst 33258 staining, flow cytometry and TUNEL staining. The protein levels were determined by western-blotting and immunohistochemical staining. In safety evaluation, ICR mice and beagle dogs were orally administered ELE at different doses to determine its adverse effects on the central nervous system and cardiorespiratory system. ELE significantly inhibited tumor growth and induced cell apoptosis in MCF-7 cells in vitro and in vivo. The protein levels including caspase-3, caspase-9, bax, bcl-2, PARP, and cytochrome c were significantly changed. For the central nervous system, no treatment-related changes in behavior, motor activity or coordination were observed in mice. For the cardiorespiratory system, no significant differences in cardiorespiratory parameters including heart rate, PR interval, RR interval, P wave duration, QRS duration, QTcF interval, respiratory frequency, tidal volume, body temperature, and blood pressure were observed in beagle dogs between the ELE treatment and control group. In conclusion, ELE possessed anti-breast cancer activity by activating a mitochondrial-mediated apoptotic pathway with high biological safety in animals, which indicates it could be a potential therapeutic agent for treating human breast cancer in the future.

Salidroside orchestrates metabolic reprogramming by regulating the Hif-1α signalling pathway in acute mountain sickness.

CONTEXT: Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba (Crassulaceae) is used to prevent and treat acute mountain sickness. However, the mechanisms underlying its effects on the central nervous system remain unclear. OBJECTIVE: To investigate the effect of Rhodiola crenulata on cellular metabolism in the central nervous system. MATERIALS AND METHODS: The viability and Hif-1α levels of microglia and neurons at 5% O2 for 1, 3, 5 and 24 h were examined. We performed the binding of salidroside (Sal), rhodiosin, tyrosol and p-hydroxybenzyl alcohol to Hif-1α, Hif-1α, lactate, oxidative phosphorylation and glycolysis assays. Forty male C57BL/6J mice were divided into control and Sal (25, 50 and 100 mg/kg) groups to measure the levels of Hif-1α and lactate. RESULTS: Microglia sensed low oxygen levels earlier than neurons, accompanied by elevated expression of Hif-1α protein. Salidroside, rhodiosin, tyrosol, and p-hydroxybenzyl alcohol decreased BV-2 (IC50=1.93 ± 0.34 mM, 959.74 ± 10.24 µM, 7.47 ± 1.03 and 8.42 ± 1.63 mM) and PC-12 (IC50=6.89 ± 0.57 mM, 159.28 ± 8.89 µM, 8.65 ± 1.20 and 8.64 ± 1.42 mM) viability. They (10 µM) reduced Hif-1α degradation in BV-2 (3.7-, 2.5-, 2.9- and 2.5-fold) and PC-12 cells (2.8-, 2.8-, 2.3- and 2.0-fold) under normoxia. Salidroside increased glycolytic capacity but attenuated oxidative phosphorylation. Salidroside (50 and 100 mg/kg) treatment increased the protein expression of Hif-1α and the release of lactate in the brain tissue of mice. CONCLUSIONS: These results suggest that Sal induces metabolic reprogramming by regulating the Hif-1α signalling pathway to activate compensatory responses, which may be the core mechanism underlying the effect of Rhodiola crenulata on the central nervous system.

Pseudotargeted screening and determination of constituents in Qishen granule based on compound biosynthetic correlation using UHPLC coupled with high-resolution MS.

Detection and determination of many known/unknown compounds in traditional Chinese medicines have always been challenging. To comprehensively identify compounds in Qishen granule, which is a widely prescribed herbal formula for treating chronic heart failure, a pseudotargeted screening method was proposed based on compound biosynthetic correlation using ultra high-performance liquid chromatography coupled with high-resolution mass spectrometry. Firstly, all possible compounds of Qishen granule were classified into nine types according to their core skeletons, and potential analogue molecular formulas were predicted according to core compound-related biosynthetic correlations, such as methylation, hydroxylation, and glucosidation. Secondly, nine pseudocompound databases consisting of core compounds, deduced biosynthetic correlations, and predicted analogue molecular formulas were established. Then, compounds of interest were directly located by pseudotargeted screening of high resolution mass spectrometry data and further verified by target tandem mass spectrometry. As a result, 213 constituents were identified and 21 of them were determined as potential new compounds. This demonstrated that pseudotargeted screening based on compound biosynthetic correlations significantly facilitated the processing of extremely large information data and improved the efficiency of compound identification. This research provided essential data for exploration of effective substances in Qishen granule and enriched the methodology for comprehensive characterization of constituents in complex traditional Chinese medicines.

[Quantification of aristolochic acids and their DNA adducts in mice kidney and liver by HPLC-MS/MS].

This study aims to establish a quantitative method of 4 aristolochic acids-DNA adducts in mice kidney and liver based on high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) for monitoring the content changes of aristolochic acids-DNA adducts. A Shiseido Capcellpak AQ C_(18) column(3 mm×100 mm, 3 µm) was used, with a mixture of 0.2% acetic acid-5 mmol·L~(-1) ammonium acetate as the aqueous phase and methanol as the organic phase for gradient elution. The multiple reaction monitoring(MRM) scanning method under positive mode by electrospray ionization(ESI) was performed for the detection of the aristolochic acids-DNA adducts which formed by combining aristolochic acid Ⅰ/Ⅱ with deoxyadenosine, deoxyguanosine, and deoxycytidine, respectively. Balb/c mice were given Guanmutong extract by gavage, and the relative content of aristolochic acids-DNA adducts in liver and kidney samples were analyzed within 60 days. It was found that the concentration of 4 aristolochic acids-DNA adducts in the kidney was significantly higher than that in the liver, and there were about 15.87 adducts in per 1×10~6 normal deoxynucleosides, which was 4.5-7.5 times than that of the liver. What's more, some adducts can still be detected on the 30 th day after administration. The concentration of the adducts in the liver was highest on the first day after administration, and a second peak appeared during the 7 th to 14 th days. The results indicated that aristolochic acids-DNA adducts are difficult to eliminate in vivo, and it is of great significance to study the mechanism of liver and kidney injury of aristolochic acid.

Hyaluronic acid-coated nanostructured lipid carriers for loading multiple traditional Chinese medicine components for liver cancer treatment.

This study aimed to develop hyaluronic acid (HA)-coated nanostructured lipid carriers (NLC) loaded simultaneously with oleanolic acid (OA), ursolic acid (UA) and Ginsenoside Rg3 (Rg3), prepared by electrostatic attraction for delivering OA, UA and Rg3 (OUR), termed HA-OUR-NLC, to tumors over expressing cluster determinant 44(CD44). The dialysis method was used to assess the in vitro release of OUR. Parameters such as pharmacokinetics, biodistribution, fluorescence in vivo endo-microscopy (FIVE), optical in vivo imaging (OIVI) data, and in vivo antitumor effects were evaluated. The results showed a total drug loading rate of 8.76±0.95% for the optimized HA-OUR-NLC; total encapsulation efficiency was 45.67±1.14%; particle size was 165.15±3.84%; polydispersity index was 0.227±0.01; zeta potential was -22.87±0.97 mV. Drug release followed the Higuchi kinetics. Pharmacokinetics and tissue distribution, as well as antitumor effects were evaluated in nude mice in vivo. HA-OUR-NLC were better tolerated, with increased antitumor activity compared with 5-Fu. In in vivo optical imaging, we use 1,1'-dioctadecyl-3,3,3',3'-tetramethy(DiR) as a fluorescent dye to label the NLC. The DiR-OUR-NLC group showed bright systemic signals, while the tumor site was weak. The present findings indicated that HA-OUR-NLC accumulated in the tumor site, prolonging OUR duration in the circulation and enhancing tumoral concentrations. Therefore, NLC prepared by electrostatic attraction constitute a good system for delivering OUR to tumors.

Profiling the constituents of Dachuanxiong decoction by liquid chromatography with high-resolution tandem mass spectrometry using target and nontarget data mining.

Comprehensive characterization of the large number of compounds existing in traditional Chinese medicines is still a great challenge. In this study, a strategy of precursor ion selected acquisition coupled with target and nontarget data mining was established to systematically characterize the chemical constituents of traditional Chinese medicines. This strategy consisted of four steps: (1) precursor ion selected acquisition was developed to trigger additional tandem mass spectrometry fragmentation reactions, especially for trace constituents; (2) in-house database of compounds was established and diagnostic characteristics were summarized; (3) compounds were identified by target and nontarget data mining; and (4) compound structures were elucidated based on accurate mass matching and comparison of fragment ions, and isomers were discriminated by the intensity of fragment ions, fragmentation pattern analysis, and calculated log P values. This strategy was successfully applied to comprehensively identify the constituents in Dachuanxiong decoction. Finally, a total of 218 compounds assigned to six categories were characterized, and 107 compounds were characterized by nontarget analysis for the first time. In addition, three new diagnostic characteristics of esters of citric acids were elucidated. This research enriched the material basis of Dachuanxiong decoction and provided a new strategy for identifying the chemical constituents of other traditional Chinese medicines.

Network Pharmacology-Based Investigation of Protective Mechanism of Aster tataricus on Lipopolysaccharide-Induced Acute Lung Injury.

Acute lung injury (ALI) is a common clinical condition that badly influences people's health. Recent studies indicated that Aster tataricus (RA) had potential effects on ALI, but the effective components and their mechanism is not clear. In this study, we found that the Fraction-75 eluted from RA extract could significantly protect the lipopolysaccharide (LPS)-induced ALI in mice, including alleviating the severity of lung pathology, attenuating the pulmonary edema, and reducing the release of inflammatory cells. Further ingredient analyses demonstrated that there were mainly 16 components in it, among which 10 components were collected according to their relative peak area and oral bioavailability. Next, the components-disease targets network suggested that the candidate components had extensive associations with 49 known therapeutic targets of ALI, among which 31 targets could be regulated by more than one component. Herein, GO functional and pathway analysis revealed that the common targets were associated with four biological processes, including the inflammatory response to stimulus, cellular process, chemokine biosynthetic process and immune system process. Furthermore, the ELISA validation indicated that the candidate components in RA extract may protect the LPS-induced ALI mainly through inhibiting the release of inflammatory cytokines and promoting the repair of vascular endothelial.

[Effects of emodin on lipid accumulation and inflammation in hepatocytes].

The aim of this study was to explore the effect of emodin on lipid accumulation and inflammation in hepatocytes. The cell morphology was observed by microscopy. LDH release was detected by the kit. Levels of intracellular lipid droplets were observed by oil red O staining. The contents of TC and TG in cells were detected by the kit. Western blot was used to determine protein expressions of FASN,SREBF2,APOB,IL-6 and p-NF-κB in hepatocytes. The results showed that the levels of L02 cell LDH were significantly increased after being treated with emodin,and the cells showed shrinkage,volume reduction,decrease in quantity with the increase of dose. Red lipid droplets were observed in L02 hepatocytes. Intracellular TC and TG contents of L02 cell increased in a concentrationdependent manner,with significant differences between medium and high-dose groups( P < 0. 05). Protein expressions of FASN,SREBF2,IL-6 and p-NF-κB were significantly higher than those of the control group,and the expression level of APOB was significantly lower than that of the control group( P<0. 05). In conclusion,emodin could induce lipid accumulation and inflammatory damage in hepatocytes in a dose-dependent manner,which in turn could damage liver cells. This process was related to the up-regulation of FASN,SREBF2,IL-6,p-NF-κB,as well as the down-regulation of the protein expression of APOB.

[Simultaneous quantification and consistency analysis of 19 representative components in Longshengzhi Capsules by HPLC-QQQ/MS].

Longshengzhi capsule consisting of 12 herbs is widely used in clinically treating cerebral ischemia during recovery period.In this study,in order to investigate the consistency of different batches of Longshengzhi capsules,a high performance liquid chromatography coupled to triple quadrupole mass spectrometry method(HPLC-QQQ/MS) was developed for the determination of 19 representative components in Longshengzhi Capsules within 9 min. Methodology validation indicated this method was simple,rapid,accurate,highly sensitive and reproducible,and it could be used for the content determination of components in Longshengzhi Capsules. The consistency analysis results showed that paeoniflorin and calycosin-7-glucoside in Longshengzhi Capsules had the highest content; RSD value of total content of 19 compounds was 5. 2% and the RSD value of main compounds such as astragaloside and calycosin-7-glucoside was all less than 15%,reflecting good consistency among different batches. This study has provided a scientific method and basis for the quality control and consistency evaluation of Longshengzhi Capsules.

Dose-dependent target diversion of Danhong injection on the Glu-GLT-1/Gly-GlyRα dynamic balance module of cerebral ischemia.

Function-oriented modular structure analysis is a great challenge in module-based pharmacological studies. A strategy to uncover target-target interaction (TTI) and dynamic balance regularity (DBR) was established to discover the structural factors influencing modular functions and explore the mechanism of Danhong injection (DHI) in treating cerebral ischemia. The dose-related metabolic features of DHI intervention were investigated using metabolomics and modular pharmacology. The findings indicated that Glu/Gly was a biomarker and Glu-GLT-1/Gly-GlyRα was the core unit regulated by DHI. Gly and Glu displayed opposite patterns and functional roles, representing intra-modular balance. GlyRα was identified as the upstream target and GLT-1 as the downstream target by inhibiting or activating GlyRα, indicating that DHI has two dose-dependent regulatory modes. GlyRα was the major target at low doses, while GLT-1 was activated as the dominant target as doses accumulated. Our study reveals that target-target interaction and dynamic balance regularity are the key factors influencing modular functions, which is a promising breakthrough for module-based pharmacological studies.

Preparing the key metabolite of Z-ligustilide in vivo by a specific electrochemical reaction.

The key in vivo metabolites of a drug play an important role in its efficacy and toxicity. However, due to the low content and instability of these metabolites, they are hard to obtain through in vivo methods. Electrochemical reactions can be an efficient alternative to biotransformation in vivo for the preparation of metabolites. Accordingly, in this study, the metabolism of Z-ligustilide was investigated in vitro by electrochemistry coupled online to mass spectrometry. This work showed that five oxidation products of the electrochemical reaction were detected and that two of the oxidation products (senkyunolide I and senkyunolide H) were identified from liver microsomal incubation as well. Furthermore, after intragastric administration of Z-ligustilide in rats, senkyunolide I and senkyunolide H were detected in the rat plasma and liver, while 6,7-epoxyligustilide, a key intermediate metabolite of Z-ligustilide, was difficult to detect in vivo. By contrast, 6,7-epoxyligustilide was obtained from the electrochemical reaction. In addition, for the first time, 6 mg of 6,7-epoxyligustilide was prepared from 120 mg of Z-ligustilide. Therefore, electrochemical reactions represent an efficient laboratory method for preparing key drug metabolites.

[Studies on constituents of Polygonum multiflorum extract in vivo and in vitro based on UPLC-Q-TOF-MS].

To explore the drug-induced constituents in vivo of Polygonum multiflorum extract (PM). This study was the first to study the drug-induced constituents in target organ liver. Agilent MassHunter qualitative analysis software and Metabolite ID software were applied for the analysis of retention time, exact relative molecular mass, primary and secondary mass spectrum information based on ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and targeted-MS/MS. By comparison with literature and standards, a total of 5 prototypes and 6 metabolites were identified or tentatively elucidated from the liver samples. In addition, the drug-induced constituents in plasma and PM were also analyzed in this study and 8 prototypes and 19 metabolites were detected from the plasma samples, while 30 compounds were detected from the extract of PM. Emodin oxidative acetylation metabolites, hydroxyl methylation metabolites, carboxylation glucuronidation metabolites and ketone glucuronidation metabolites in this study were first reported. Through the comparative analysis between the in vivo and in vitro constituents of PM, the study preliminarily revealed the drug-induced constituents (prototypes and metabolites) in liver and clarified the transfer process and transmutation rules of constituents in PM, blood and liver, which would further deepen our understanding on constituents of PM in vivo.

The Anti-hyperlipidemia Effects of Raw Polygonum multiflorum Extract in Vivo.

Polygonum multiflorum is widely used in the prevention and treatment of hyperlipidemia in traditional Chinese Medicine. In this study, the effects and relevant mechanisms of lipid-regulation by raw Polygonum multiflorum (RPM) were investigated. The results indicated that the basal plasma lipids, such as low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG), were significantly decreased in RPM treatment groups compared with the model group, especially in the RPM high dose group. The key enzymes involved in lipid metabolism, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) in plasma were generally reduced after oral administration, which was consistent with the transcription levels of their target genes. In addition, the hepatotoxicity of RPM was investigated, and RPM showed slightly less liver injury than that induced by simvastatin. Histological analysis indicated that the fat vacuoles and steatosis in hepatocytes were relieved after oral administration of RPM extract at a high dose of 16.2 g/kg, which was more obvious than that induced by simvastatin. These results revealed that RPM exerted its lipid-lowering effect by regulating the expression of related genes, and performed better than simvastatin in the treatment of hyperlipidemia.