Quality Evaluation of Shexiang Tongxin Dropping Pill Based on HPLC Fingerprints Combined with HPLC-Q-TOF-MS/MS Method.

Shexiang Tongxin Dropping Pill (STP) is a composite formula of traditional Chinese medicine that is widely used for the treatment of cardiovascular diseases. It consists of seven medicinal extracts thereof or materials, including Bufonis venenum, synthetic Moschus, Panax ginseng, Bovis calculus artifactus, Bear bile powder, Salvia miltiorrhiza Bge and synthetic borneol. However, it is considerably difficult to evaluate the quality of STP due to its complex chemical compositions. This paper was designed to explore a comprehensive and systematic method combining fingerprints and chemical identification for quality assessment of STP samples. Twenty batches of STP samples were analyzed by high-performance liquid chromatography (HPLC) and high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. Ten common peaks were detected by HPLC fingerprint similarity evaluation system. Meanwhile, 100 compounds belonging to 4 structural characteristics, including 23 bufadienolides, 36 organic acids, 34 saponins and 7 other types, were systematically identified as the basic components in STP. This study could be used for clarifying the multiple bioactive substances and developing a comprehensive quality evaluation method of STP.

Enhanced immunomodulation and periodontal regeneration efficacy of subgingivally delivered progranulin-loaded hydrogel as an adjunct to non-surgical treatment for Class II furcation involvement in dogs.

AIM: To evaluate the effect of subgingival delivery of progranulin (PGRN)/gelatin methacryloyl (GelMA) complex as an adjunct to scaling and root planing (SRP) on an experimental periodontitis dog model with Class II furcation involvement (FI). MATERIALS AND METHODS: A Class II FI model was established, and the defects were divided into four treatment groups: (a) no treatment (control); (b) SRP; (c) SRP + GelMA; (d) SRP + PGRN/GelMA. Eight weeks after treatment, periodontal parameters were recorded, gingival crevicular fluid and gingival tissue were collected for ELISA and RT-qPCR, respectively, and mandibular tissue blocks were collected for micro computed tomography (micro-CT) scanning and hematoxylin and eosin (H&E) staining. RESULTS: The SRP + PGRN/GelMA group showed significant improvement in all periodontal parameters compared with those in the other groups. The expression of markers related to M1 macrophage and Th17 cell significantly decreased, and the expression of markers related to M2 macrophage and Treg cell significantly increased in the SRP + PGRN/GelMA group compared with those in the other groups. The volume, quality and area of new bone and the length of new cementum in the root furcation defects of the PGRN/GelMA group were significantly increased compared to those in the other groups. CONCLUSIONS: Subgingival delivery of the PGRN/GelMA complex could be a promising non-surgical adjunctive therapy for anti-inflammation, immunomodulation and periodontal regeneration.

Construction of a methodology framework to characterize dynamic full-sector land-use carbon emissions embodied in trade.

The globally massive land-use changes associated with unprecedented urbanization rate are leading to prodigious quantities of carbon emissions. Nonetheless, the dynamics of land-use carbon emissions, particularly driven by supply-chain activities across all relevant industrial sectors, remain largely unexplored, especially in non-agricultural sectors. Here, we constructed a novel methodological framework to quantify full-sector land-use carbon emissions in Shenzhen, China, an international megacity grappling with acute land resource scarcity. Then, we integrated this framework with multiregional input-output analysis to uncover the multi-scale embodied land-use emissions propelled by Shenzhen's supply-chain activities. Our results indicate a marked increase in Shenzhen's embodied carbon emissions, approximately two orders of magnitude greater than its physical emissions, tripling during 2005-2018. Remarkably, non-agriculture sectors contributed 81.3-90.5 % of physical and 46.6-58.4 % of embodied land-use emissions. The land-use changes occurred outside Shenzhen accounted for 6.5-13.3 % of Shenzhen's total embodied land-use emissions. The sectoral analysis revealed a transition from traditional manufacturing (e.g., metallurgy, chemical products, textiles, wood products) in 2010-2015 to high-tech sectors (e.g., electronic equipment and other manufacture) in 2015-2018. This shift was primarily attributed to concurrent industry transfer actions, leading to aggressive changes in land-use emission intensity discrepancies within and outside Shenzhen. This study provides a scientific basis for designing effective strategies to mitigate land-use carbon emissions associated with supply-chain activities.

Optimizing the development of contaminated land in China: Exploring machine-learning to identify risk markers.

Often available for use, previously developed land, which includes residential and commercial/industrial areas, presents a significant challenge due to the risk to human health. China's 2018 release of health risk assessment standards for land reuse aimed to bridge this gap in soil quality standards. Despite this, the absence of representative indicators strains risk managers economically and operationally. We improved China's land redevelopment approach by leveraging a dataset of 297,275 soil samples from 352 contaminated sites, employing machine learning. Our method incorporating soil quality standards from seven countries to discern patterns for establishing a cost-effective evaluative framework. Our research findings demonstrated that detection costs could be curtailed by 60% while maintaining consistency with international soil standards (prediction accuracy = 90-98%). Our findings deepen insights into soil pollution, proposing a more efficient risk assessment system for land redevelopment, addressing the current dearth of expertise in evaluating land development in China.

Plastic waste discharge to the global ocean constrained by seawater observations.

Marine plastic pollution poses a potential threat to the ecosystem, but the sources and their magnitudes remain largely unclear. Existing bottom-up emission inventories vary among studies for two to three orders of magnitudes (OMs). Here, we adopt a top-down approach that uses observed dataset of sea surface plastic concentrations and an ensemble of ocean transport models to reduce the uncertainty of global plastic discharge. The optimal estimation of plastic emissions in this study varies about 1.5 OMs: 0.70 (0.13-3.8 as a 95% confidence interval) million metric tons yr-1 at the present day. We find that the variability of surface plastic abundance caused by different emission inventories is higher than that caused by model parameters. We suggest that more accurate emission inventories, more data for the abundance in the seawater and other compartments, and more accurate model parameters are required to further reduce the uncertainty of our estimate.

[Spatiotemporal Distribution and Driving Factors of Polycyclic Aromatic Hydrocarbons (PAHs) in Inland Sediments of China].

This study reviewed the spatial and temporal distributions of polycyclic aromatic hydrocarbons (PAHs) during 2000-2010 in inland sediments of China and quantified the underlying socioeconomic determinants based on the structural equation model and gravity model. We found that PAHs concentrations in the sediments of eight different regions followed the order of Northern coast>Northeast>Eastern coast>Southern coast>Middle Yellow River>Middle Yangtze River>Southwest>Northwest. The Southern coast, Middle Yangtze River, and Southern coast regions showed large contributions to the high-molecular weight PAHs, whereas the Northeast, Northwest, and Middle Yellow River regions showed high contributions to the low-molecular weight PAHs. PAHs concentrations continuously increased from the year 2000 followed by a gradual decline after 2006, with significant differences in the year when PAHs levels reached their peak. PAHs concentrations of sediment in developed regions declined in recent years following a continuous increase in the 2000s; however, they still increased rapidly in developing regions owing to fast economic development. In addition, the increment rate of PAHs concentrations in sediment at the remote or less-developed regions was slower than that at the developed regions. Urbanization and industrialization had an important effect on PAHs in the sediments, and the largest influencing factor was the economic development.

A Study on the Association between Korotkoff Sound Signaling and Chronic Heart Failure (CHF) Based on Computer-Assisted Diagnoses.

Background: Korotkoff sound (KS) is an important indicator of hypertension when monitoring blood pressure. However, its utility in noninvasive diagnosis of Chronic heart failure (CHF) has rarely been studied. Purpose: In this study, we proposed a method for signal denoising, segmentation, and feature extraction for KS, and a Bayesian optimization-based support vector machine algorithm for KS classification. Methods: The acquired KS signal was resampled and denoised to extract 19 energy features, 12 statistical features, 2 entropy features, and 13 Mel Frequency Cepstrum Coefficient (MFCCs) features. A controlled trial based on the VALSAVA maneuver was carried out to investigate the relationship between cardiac function and KS. To classify these feature sets, the K-Nearest Neighbors (KNN), decision tree (DT), Naive Bayes (NB), ensemble (EM) classifiers, and the proposed BO-SVM were employed and evaluated using the accuracy (Acc), sensitivity (Se), specificity (Sp), Precision (Ps), and F1 score (F1). Results: The ALSAVA maneuver indicated that the KS signal could play an important role in the diagnosis of CHF. Through comparative experiments, it was shown that the best performance of the classifier was obtained by BO-SVM, with Acc (85.0%), Se (85.3%), and Sp (84.6%). Conclusions: In this study, a method for noise reduction, segmentation, and classification of KS was established. In the measured data set, our method performed well in terms of classification accuracy, sensitivity, and specificity. In light of this, we believed that the methods described in this paper can be applied to the early, noninvasive detection of heart disease as well as a supplementary monitoring technique for the prognosis of patients with CHF.

Exploring Potential Ways to Reduce the Carbon Emission Gap in an Urban Metabolic System: A Network Perspective.

To meet the global need for carbon neutrality, we must first understand the role of urban carbon metabolism. In this study, we developed a land-energy-carbon framework to model the spatial and temporal variation of carbon flows in Beijing from 1990 to 2018. Based on the changes in carbon sequestration and energy consumption, we used ecological network analysis to identify the critical paths for achieving carbon neutrality during land-use changes, thereby revealing possible decarbonization pathways to achieve carbon neutrality. By using GIS software, changes in the center of gravity for carbon flows were visualized in each period, and future urban construction scenarios were explored based on land-use policy. We found that the direct carbon emission peaked in 2010, mostly due to a growing area of transportation and industrial land. Total integrated flows through the network decreased at an average annual rate of 3.8%, and the change from cultivated land to the socioeconomic sectors and the paths between each socioeconomic component accounted for 29.5 and 31.7% of the integrated flows during the study period. The socioeconomic sectors as key nodes in the network should focus both on their scale expansion and on using cleaner energy to reduce carbon emissions. The center of gravity gradually moved southward, indicating that the new emission centers should seek a greener mixture of land use. Reducing carbon emission will strongly relied on transforming Beijing's energy consumption structure and increasing green areas to improve carbon sinks. Our results provide insights into carbon flow paths that must be modified by implementing land-use policies to reduce carbon emission and produce a more sustainable urban metabolism.

Morphochemical investigation on the enrichment and transformation of hazardous elements in ash from waste incineration plants.

The transformation of heavy metals in ash from waste incineration plants is significant for ash management. The migration behavior of trace elements in ash after combustion, semidry deacidification, fabric filtration, and chelating agent stabilization was investigated from one waste incineration plant. The hazardous elements Zn, Pb, and As were enriched in raw fly ash (ash produced at a combustion temperature of 850-1100 °C) due to their relatively high volatility. Mercury, Cd, and Pb were captured in fly ash2 and processed by activated carbon and fabric filters. The removal rate of As (71%) was the highest among all studied elements due to a large amount of quinquevalent As removed. However, the average removal rate of elements in fly ash was only 13%. In the finally obtained fly ash3 (after chelating agent stabilization), a larger particle size (~100 µm) was found than that of raw ash. Furthermore, fly ash3 contains HgSO4 and trivalent As, which are toxic and likely to be precipitated when the fly ash3 is next utilized or deposited in a landfill, causing environmental risks.

Pharmacokinetics and brain distribution studies of 6-hydroxykynurenic acid and its structural modified compounds.

OBJECTIVES: 6-Hydroxykynurenic acid (6-HKA) is an organic acid component in extracts of Ginkgo biloba leaves and acts as a major contributor to neurorestorative effects, while its oral bioavailability was low. Therefore, using prodrug method to improve the bioavailability and brain content of 6-HKA is significant. METHODS: Three structural modified compounds of 6-HKA were synthesized, and ultra performance liquid chromatography-tandem mass spectrometry methods for quantification of these structural modified compounds in rat plasma and rat brain homogenate were established and comprehensively validated. The methods were effectively applied to investigate the effects of structural modification on apparent permeability coefficients in cells, the pharmacokinetics and the brain distribution in rats. KEY FINDINGS: The results illustrated that esterification can greatly improve the apparent permeability coefficient and bioavailability of 6-HKA. Comparing with direct oral administration of 6-HKA, the bioavailability of isopropyl ester was greatly improved (from 3.96 ± 1.45% to 41.8 ± 15.3%), and the contents of 6-HKA in rat brains (49.7 ± 9.2 ng/g brain) were significantly higher after oral administration. CONCLUSIONS: The bioavailability and the brain content of 6-HKA can be improved by the prodrug method. Among three structural modified compounds, isopropyl-esterified 6-HKA was the most promising treatment.

[Emission Characteristics and Toxicity Effects of Halogenated Polycyclic Aromatic Hydrocarbons from Coal-Fired and Waste Incineration Power Plants].

Coal-fired power plants (CFPPs) and waste incineration power plants (WIPPs) represent a large portion of polycyclic aromatic hydrocarbons (PAHs) sources in the environment, among which halogenated PAHs (HPAHs) are more toxic to the human body compared with their corresponding parent PAHs. In the current work, we investigated the occurrence, formation mechanism, and toxicity effects of HPAHs in the coal and waste combustion products from three CFPPs and one WIPP. The results indicate that the contents of chlorinated PAHs (Cl-PAHs) in the fly ash from the CFPPs and WIPP were 1.06-1.67 ng·g-1 and 2.76 ng·g-1, respectively, and the contents of brominated PAHs (Br-PAHs) in the fly ash from the CFPPs and WIPP were 26.4-44.2 ng·g-1 and 6.31 ng·g-1, respectively. The HPAH contents in the fly ash from the WIPP were significantly higher than those from the CFPPs primarily due to the abundant plastics in the domestic waste, represented by polyvinyl chloride, resulting in the formation of Cl-PAHs during combustion. The HPAH contents in the fly ash from the pulverized coal-fired (PC) boiler were significantly higher than those from the circulating fluidized bed (CFB) boiler mostly due to the higher combustion temperature operated in the PC boiler. The HPAHs in the fly ash from coal combustion were predominantly 7-BrBaA and 9-ClPhe, and those from domestic combustion were predominantly 9-BrPhe and 2-ClAnt. In addition, the contents of 7-BrBaA and 9,10-Br2 Ant in the coal combustion fly ash were significantly higher than those in domestic waste combustion fly ash, whereas 2-BrFle exhibited a contrasting profile. The content of Br-PAHs in the fly ash treated by semi-dry deacidification was twice that in dust removal fly ash but significantly increased in the chelating agent stabilization fly ash. The Pearson correlation analysis indicated the the formation mechanism of Cl-PAHs and Br-PAHs were the same but a secondary formation of HPAHs during the chelating agent stabilization of the fly ash was deduced. The TEQ values of the HPAHs in the fly ash (8.87×10-3-15.0×10-3 ng·g-1) from the WIPP were similar to those in the fly ash from the CFPPs (10.0×10-3 ng·g-1), which were significantly reduced in the fly ash treated by semi-dry deacidification due to the removal of 7-BrBaA. Moreover, the TEQ values of the HPAHs in the fly ash increased 5.4 times after the chelating agent stabilization. The ecological risk should be considered for the CFPP fly ash due to their massive amount of discharge and high TEQ values.

The characterisation of the in vitro metabolism and transport of 6-hydroxykynurenic acid, an important constituent of Ginkgo biloba extracts.

6-Hydroxykynurenic acid (6-HKA) is a nitrogen-containing phenolic acid compound in Ginkgo biloba leaves. The pharmacological activities of 6-HKA have been reported and shown that 6-HKA has the potential to become a therapeutic drug and may play an important role in the treatment of nervous system diseases. However, there are few studies on the drug metabolism and transport of 6-HKA. The aim of this study is to investigate the in vitro metabolism of 6-HKA and its interaction with multiple important drug transporters.The in vitro metabolism experiments in the present study demonstrate that 6-HKA might not undergo phase-I or phase-II metabolism in hepatic microsomes/S9 of rats. In addition, some drug transporters, including OAT1/3, OCT2, MDR1, OATP1B1, MATE1/2K and OCTN2, were investigated. The cellular uptake assays indicate that 6-HKA exhibits inhibition to the transport of classical substrates mediated by OAT3, OCT2, MATE2K and OCTN2 but has no significant effect on the transport of substrates mediated by MDR1, OAT1, OATP1B1 or MATE1. Further investigation of cellular accumulation assays shows that 6-HKA might be the substrate of OAT3, but not OCT2 or OCTN2. The bidirectional transport study suggests that 6-HKA is not a substrate of MDR1.The information about the in vitro metabolism of 6-HKA and the interaction between 6-HKA and some transporters will help us to better understand the pharmacokinetic properties of 6-HKA and provide reference for its pharmacodynamics, DDIs and drug-food interactions studies.

Construction of a regional inventory to characterize polycyclic aromatic hydrocarbon emissions from coal-fired power plants in Anhui, China from 2010 to 2030.

The infrastructures of coal-fired power plants in China have changed significantly since 2010, but the magnitude and characteristics of polycyclic aromatic hydrocarbon (PAH) emissions remain to be updated. In the present study, a unit-based PAH emission inventory for coal-fired power plants between 2010 and 2017 was constructed for Anhui Province, China. Atmospheric PAH emissions from pulverized coal (PC) and circulating fluidized bed (CFB) units in 2017 were 8600 kg and 7800 kg, respectively. The emission rates and intensities for CFB units (7.2 kg ton-1 and 2.1 kg MW-1) were significantly higher than those for PC units (1.1 kg ton-1 and 0.19 kg MW-1), primarily because CFB boilers were operated at lower combustion temperatures and poor combustion conditions compared to PC boilers. The distribution patterns of PAH emissions across different age groups largely reflected the time periods for constructing coal-fired units in Anhui and for the transition of small units to large ones. The accomplishment of ultralow emission technologies and phase-out of outdated coal-fired units were responsible for the decreasing trend of PAH emissions between 2012 and 2017. The warmer summer in 2013 and 2017 and colder winter in 2011 compared to other years probably caused increased use of air conditioners, resulting in increased electricity consumption and PAH emissions. Future PAH emissions would decrease by 45-57% during 2017-2030, benefitting from power plant fleet optimization, i.e., phasing out outdated coal-fired units and replacing them with large ones. With the best available optimized power plant fleets and end-of-pipe control measures accomplished in Anhui's CFPPs, PAH emissions in 2030 would potentially be reduced by 56-65%.

Sediment Records of Polybrominated Diphenyl Ethers (PBDEs) from the Anhui Province Section of Yangtze River, China.

This study investigated the temporal changes of PBDEs in the sediment cores from the Anhui Province section of Yangtze River (YR), China. The dramatic increase of ∑Br3-Br9-BDEs and BDE-209 concentrations in cores in the period of ca. 1990-2008 was consistent with the booming of regional and national production and consumption of household appliances and electronics. Following declines in BDE-209 and ∑Br3-Br9-BDEs concentrations can be associated with the deceasing use of legacy commercial PBDE mixtures in recent years. Compared with the different regions around the world, sediments in the YR were moderately polluted by PBDEs. The levels and the detection rates of BDE-209 were highest among the detected PBDEs single congener. The composition analysis indicated that Deca-BDE, Octa-BDE, and Penta-BDE were the dominant forms in the YR. The increasing trends of both BDE-209 and ∑Br3-Br9-BDEs in the YR during 1990s and 2000s largely reflected the time periods for transferring PBDE sources from the developed countries to China. TOC and finer particles were strongly correlated with distributions of PBDEs in sediments.

Denitrification devices in urban boilers change mercury isotope fractionation signatures of coal combustion products.

The installation rate of denitrification devices is accelerating in Chinese urban boilers. Previous studies on pulverized coal-fired boilers without denitrification devices showed that combustion products containing mainly oxidized mercury (Hg) preferably enriched lighter Hg isotopes than feed coals. However, the magnitude of this enrichment becomes less pronounced if denitrification devices are installed. The underlying Hg isotope fractionation mechanisms are still unclear. In this study, three types of urban boilers (two pulverized coal-fired boilers, one circulating fluidized bed boiler and one municipal waste incinerator boiler) all installed with denitrification devices were measured for Hg isotope compositions of their feed fuels and corresponding combustion products. We observed little mass independent fractionation but very significant mass dependent fractionation (MDF) between feed fuels and combustion products. The fly ash and desulfurization products both enriched heavier Hg isotopes than feed coals in three coal-fired boilers, and the enrichment of heavy Hg isotopes increased with sequential removal of combustion products in all boilers. Different from previously suggested kinetic MDF for gaseous Hg0(g)→HgII(g) and gaseous HgII(g)→particulate HgII(p) in coal combustion flue gases, we propose an equilibrium MDF for Hg0(g)↔HgII(g) followed by a kinetic MDF for HgII(g)→HgII(p). This equilibrium MDF most likely occurs during Hg0(g) oxidation in denitrification devices, which enriches heavy Hg isotopes in oxidized products (HgII(g) and HgII(p)) that are then sequestrated in fly ash and desulfurization products. The paradigm shift of MDF in boilers with denitrification devices was further verified by parallel Hg isotope measurement in urban atmosphere particulates. Our study clearly demonstrates that modern coal-fired boilers with denitrification devices have a quite different MDF compared to traditional boilers without denitrification devices. This has important implications for estimating isotope signatures of urban boiler Hg emissions, and for isotope tracing of anthropogenic Hg emissions.

A Mass Spectrometry Based Metabolite Profiling Workflow for Selecting Abundant Specific Markers and Their Structurally Related Multi-Component Signatures in Traditional Chinese Medicine Multi-Herb Formulae.

In Traditional Chinese Medicine (TCM), herbal preparations often consist of a mixture of herbs. Their quality control is challenging because every single herb contains hundreds of components (secondary metabolites). A typical 10 herb TCM formula was selected to develop an innovative strategy for its comprehensive chemical characterization and to study the specific contribution of each herb to the formula in an exploratory manner. Metabolite profiling of the TCM formula and the extract of each single herb were acquired with liquid chromatography coupled to high-resolution mass spectrometry for qualitative analyses, and to evaporative light scattering detection (ELSD) for semi-quantitative evaluation. The acquired data were organized as a feature-based molecular network (FBMN) which provided a comprehensive view of all types of secondary metabolites and their occurrence in the formula and all single herbs. These features were annotated by combining MS/MS-based in silico spectral match, manual evaluation of the structural consistency in the FBMN clusters, and taxonomy information. ELSD detection was used as a filter to select the most abundant features. At least one marker per herb was highlighted based on its specificity and abundance. A single large-scale fractionation from the enriched formula enabled the isolation and formal identification of most of them. The obtained markers allowed an improved annotation of associated features by manually propagating this information through the FBMN. These data were incorporated in the high-resolution metabolite profiling of the formula, which highlighted specific series of related components to each individual herb markers. These series of components, named multi-component signatures, may serve to improve the traceability of each herb in the formula. Altogether, the strategy provided highly informative compositional data of the TCM formula and detailed visualizations of the contribution of each herb by FBMN, filtered feature maps, and reconstituted chromatogram traces of all components linked to each specific marker. This comprehensive MS-based analytical workflow allowed a generic and unbiased selection of specific and abundant markers and the identification of multiple related sub-markers. This exploratory approach could serve as a starting point to develop more simple and targeted quality control methods with adapted marker specificity selection criteria to given TCM formula.

Sediment records of polybrominated diphenyl ethers (PBDEs) in Yangtze River Delta of Yangtze River in China.

The spatial and temporal distributions of polybrominated diphenyl ethers (PBDEs) were investigated in five sediment cores from the Yangtze River Delta of Yangtze River in China. The surficial concentrations of nine tri- through hepta-BDE congeners (Σ9BDEs) and BDE209 were highest at urban sites S3 and S2, followed by rural site S1 and estuary sites S5 and S4, respectively, based on dry sediment weight. Both BDE209 and ∑9BDE concentrations exponentially increased between 1990 and 2008. Commercial deca-BDE, penta-BDE, and octa-BDE products were likely PBDE sources in the study area. The relative abundances of BDE209 were higher in sediment cores from estuary than those from urban and rural locations, ascribing to the atmospheric transport from the adjacent densely populated northern and eastern coastal regions. This conclusion was further confirmed by the higher ratios of BDE47/BDE99 and BDE100/BDE99 in cores from the estuary than those from other locations.

[Similarities and differences between Ginkgo biloba and Panax notoginseng in treatment of ischemic cerebrovascular disease].

Ginkgo biloba and Panax notoginseng are both herb medicines for cerebrovascular disease, and play an active role in treating ischemic cerebrovascular disease(ICVD). Their mechanisms of action include antioxidant stress, nerve protection, vascular protection. According to the comparative study of literatures, G. biloba has a certain protective effect from the early stage of free radical formation throughout the whole process of causing cell inflammation and apoptosis in antioxidant stress; while P. notoginseng has mainly anti-inflammatory, anti-apoptosis effects. In the nerve protection and repair of nerve damage caused by glutamate, both could promote neurogenesis, repair damaged axons and protect nerve cells. In addition, G. biloba could also relieve neurotoxicity caused by glutamate damage, while P. notoginseng have a unique effect in repairing blood-brain barrier(BBB) and blood vessel regeneration. In clinic, they are used as auxiliary drugs in combination with thrombolytic therapy, and play curative effects in alleviating inflammation, eliminating edema, improving the cure rate and the prognosis. For cerebral diseases caused by chronic cerebral hypoperfusion, G. biloba could reduce inflammation and improve cognition. In addition, G. biloba could protect neurocyte by adjusting the secretion of dopamine in vivo, and has a certain effect on antidepressant diseases, which however needs further studies.

Ginkgo biloba and Its Constituent 6-hydroxykynurenic-acid as well as Its Proanthocyanidins Exert Neurorestorative Effects against Cerebral Ischemia.

Neuroprotective effects against cerebral ischemia/reperfusion (I/R) injury by Ginkgo biloba leaves are commonly attributed to the antioxidant activity of its proanthocyanidins. Furthermore, preliminary experiments identified 6-hydroxykynurenic acid (6-HKA) as a major contributor to this effect of extract of G. biloba leaves (EGb) prepared according to the Chinese Pharmacopoeia (ChP). In order to elucidate the specific contribution of both proanthocyanidins and 6-HKA to the overall neurorestorative effects of this extract according to ChP, EGb ChP was separated into pure 6-HKA and a newly developed Ginkgo proanthocyanidin extract (GPE), enriched in proanthocyanidins but not containing 6-HKA. Male Sprague-Dawley rats were divided into the groups: sham: 8; model (placebo): 25; GPE 80 mg/kg: 13; GPE 40 mg/kg: 13; GPE 20 mg/kg: 16; grape seed extract (negative control) 40 mg/kg: 18; nimodipine (positive control) 2 mg/kg: 8. All non-sham animals were subjected to cerebral I/R injury by occluding the middle cerebral artery with a nylon suture that was removed after 2 h of ischemia to establish reperfusion. For comparison, a parallel series of experiments were performed with 6-HKA. In these in vivo experiments, neurological dysfunctions were reduced by both GPE and 6-HKA, and both average infarct size and concentrations of malondialdehyde (MDA) and super oxide dismutase (SOD) were significantly ameliorated as compared to the model group. This data, therefore, demonstrates that the neuroprotective effects of EGb cannot be explained by a purely chemical antioxidative effect alone as has been previously proposed, especially with regards to the proanthocyanidins. A pharmacological neurorestorative effect of EGb on neurons and brain tissue itself seems to be a much more straightforward explanation for the presented observations. This effect is most likely explained by the synergistic action of both its numerous phenolic constituents (GPE) and 6-hydroxykynurenic acid (6-HKA), which could be identified as one major contributor to the observed activity.