FHB resistance conferred by Fhb1 is under inhibitory regulation of two genetic loci in wheat (Triticum aestivum L.).

KEY MESSAGE: Two loci inhibiting Fhb1 resistance to Fusarium head blight were identified through genome-wide association mapping and validated in biparental populations. Fhb1 confers Fusarium head blight (FHB) resistance by limiting fungal spread within spikes in wheat (type II resistance). However, not all lines with Fhb1 display the expected resistance. To identify genetic factors regulating Fhb1 effect, a genome-wide association study for type II resistance was first performed with 72 Fhb1-carrying lines using the Illumina 90 K iSelect SNP chip. Of 84 significant marker-trait associations detected, more than half were repeatedly detected in at least two environments, with the SNPs distributed in one region on chromosome 5B and one on chromosome 6A. This result was validated in a collection of 111 lines with Fhb1 and 301 lines without Fhb1. We found that these two loci caused significant resistance variations solely among lines with Fhb1 by compromising the resistance. In1, the inhibitory gene on chromosome 5B, was in close linkage with Xwgrb3860 in a recombinant inbred line population derived from Nanda2419 × Wangshuibai and a double haploid (DH) population derived from R-43 (Fhb1 near isogenic line) × Biansui7 (with Fhb1 and In1); and In2, the inhibitory gene on chromosome 6A, was mapped to the Xwgrb4113-Xwgrb4034 interval using a DH population derived from R-43 × PH8901 (with Fhb1 and In2). In1 and In2 are present in all wheat-growing areas worldwide. Their frequencies in China's modern cultivars are high but have significantly decreased in comparison with landraces. These findings are of great significance for FHB resistance breeding using Fhb1.

CMNPD: a comprehensive marine natural products database towards facilitating drug discovery from the ocean.

Marine organisms are expected to be an important source of inspiration for drug discovery after terrestrial plants and microorganisms. Despite the remarkable progress in the field of marine natural products (MNPs) chemistry, there are only a few open access databases dedicated to MNPs research. To meet the growing demand for mining and sharing for MNPs-related data resources, we developed CMNPD, a comprehensive marine natural products database based on manually curated data. CMNPD currently contains more than 31 000 chemical entities with various physicochemical and pharmacokinetic properties, standardized biological activity data, systematic taxonomy and geographical distribution of source organisms, and detailed literature citations. It is an integrated platform for structure dereplication (assessment of novelty) of (marine) natural products, discovery of lead compounds, data mining of structure-activity relationships and investigation of chemical ecology. Access is available through a user-friendly web interface at https://www.cmnpd.org. We are committed to providing a free data sharing platform for not only professional MNPs researchers but also the broader scientific community to facilitate drug discovery from the ocean.

Identification of Potential Factors for the Promotion of Fucoxanthin Synthesis by Methyl Jasmonic Acid Treatment of Phaeodactylum tricornutum.

Fucoxanthin, a vital secondary metabolite produced by marine diatoms, has great economic value and research potential. However, its popularization and application have been greatly restricted due to its low content, difficult extraction, and high production cost. Methyl jasmonic acid (MeJA) exerts similar inductive hormones in the growth and development as well as metabolic processes of plants. In Phaeodactylum tricornutum (P. tricornutum), MeJA treatment can increase fucoxanthin content. In this study, the effects of different concentrations of MeJA on the cell growth and the fucoxanthin content of P. tricornutum were explored. Meanwhile, this study used high-throughput sequencing technology for transcriptome sequencing of P. tricornutum and subsequently performed differential gene expression analysis, gene ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and weighted gene co-expression network analysis (WGCNA) for screening the hub genes for the promotion of fucoxanthin synthesis with MeJA-treated P. tricornutum. On this basis, the functions of the hub genes for the promotion of fucoxanthin synthesis with MeJA-treated P. tricornutum were further analyzed. The results revealed that the carotenoid synthesis-related genes PHATRDRAFT_54800 and PHATRDRAFT_20677 were the hub genes for the promotion of fucoxanthin synthesis with MeJA-treated P. tricornutum. PHATRDRAFT_54800 may be a carotenoid isomerase, while PHATRDRAFT_20677 may be involved in the MeJA-stimulated synthesis of fucoxanthin by exerting the role of SDR family NAD(P)-dependent oxidoreductases.

Exploring the key genes of fucoxanthin biosynthesis in Phaeodactylum tricornutum under phosphorus deficiency, red light and yellow light using WGCNA.

Weighted gene co-expression network analysis (WGCNA) is a method for analysing gene expression patterns across multiple samples, clustering genes with similar expression patterns and identifying key genes associated with specific traits or phenotypes. In this study, we investigated the effects of fucoxanthin accumulation in Phaeodactylum tricornutum in response to abiotic stresses of phosphorus deficiency, red light, and yellow light using transcriptome sequencing and weighted gene co-expression network analysis. The results showed that compared to the control, the fucoxanthin content of P. tricornutum was significantly increased after phosphorus deficiency and red light treatment (P<0.05), but significantly decreased after yellow light treatment (P<0.05). A weighted gene co-expression network was constructed using 10,392 genes obtained from transcriptome sequencing, and ß=18 (R2>0.8) was chosen as a soft threshold in order to ensure a scale-free network. A total of 10 co-expression modules were identified by correlation analysis of fucoxanthin content, with the purple module positively correlated with fucoxanthin content (r=0.9, P=1E-200), and 9 key genes were identified, including five genes in the fucoxanthin biosynthesis pathway (DXR, PSY, PDS1, ZEP2, VDL2) and 4 transcription factors (bHLH5, HOX2, CCHH13, HSF1b). Further qRT-PCR confirmed that key genes were more highly expressed in the phosphorus deficiency treatment and linear regression analysis showed that the relative gene expressions were all highly correlated with the transcriptome data. The results of this study provide a basis for further investigation of the complex regulatory mechanisms of fucoxanthin in P. tricornutum.

Genome-wide identification of mitogen-activated protein kinase (MAPK) gene family in yellow catfish (Pelteobagrus fulviadraco) and their expression profiling under the challenge of Aeromonas hydrophila.

As serine/threonine protein kinases, mitogen-activated protein kinases (MAPK) take part in cellular metabolism. This work found 14 MAPK genes in the yellow catfish (Pelteobagrus fulviadraco) genome and evaluated their taxonomy, conserved domains and evolutionary linkages for a better understanding of the MAPK gene family's evolutionary relationship and antibacterial immune response. The findings revealed that several MAPK genes are activated in response to immunological and inflammatory responses. Collinearity research revealed that in yellow catfish and zebrafish, there are six pairs of highly similar MAPK genes, indicating that these genes have been more conserved throughout evolution. The MAPK gene quantification findings revealed that JNK1a, JNK1b, p38delta and p38alpha b expression levels were considerably upregulated, indicating that they act in fish innate immunity. The findings implied that MAPK genes may involve in defence against detrimental microbe in yellow catfish, which will help researchers better understand how MAPK genes work in the innate immune system.

Genome-wide identification of the traf gene family in yellow catfish (Pelteobagrus fulvidraco) and analysis of their expression in response to bacterial challenge.

Tumour necrosis factor (TNF) receptor-associated factor (TRAF) is a receptor protein that has important functions in the immune system. Nonetheless, there have been few reports of traf genes in teleost fishes. The present study aimed to identify the traf genes from the genomic information of yellow catfish (Pelteobagrus fulvidraco). Eight traf genes were identified and named, which are distributed on different chromosomes but have similar conserved protein domains. Phylogenetic and syntenic analyses demonstrated conservation of traf genes during evolution. In addition, yellow catfish has the relatively rare traf1 and traf5 genes. Gene structure and motif analysis revealed the homology and distribution diversity of the traf genes. Quantitative real-time reverse transcription PCR was used to study the expression patterns of traf genes in healthy fish tissues and after infection by Aeromonas hydrophila. The results demonstrated significant changes in traf gene expression, indicating a potential role in innate immunity.

Chemical Space, Scaffolds, and Halogenated Compounds of CMNPD: A Comprehensive Chemoinformatic Analysis.

The comprehensive marine natural products database (CMNPD) is a new free access and comprehensive database developed originally by Lyu's team of our research group, including more than 30 000 marine natural products (MNPs) reported from the 1960s. In this article, we aimed to present CMNPD's value in drug discovery and to present several characteristics of MNPs based on our new comprehensive data. We used chemoinformatic analysis methods to report the molecular properties, chemical space, and several scaffold assessments of CMNPD compared with several databases. Then, we reported the characteristics of MNPs from the aspect of halogens, comparing MNPs with terrestrial natural products (TNPs) and drugs. We found that CMNPD had a low proportion (2.91%) of scaffolds utilized by drugs, and high similarities between CMNPD and NPAtlas (a microbial natural products database), which are worth further investigation. The proportion of bromides in MNPs is outstandingly higher (11.0%) in contrast to other halogens. Furthermore, the results showed great differences in halogenated structures between MNPs and drugs, especially brominated substructures. Finally, we found that many marine species (2.52%) reported only halogenated compounds. It can be concluded from these results that CMNPD is a promising source for drug discovery and has many scientific issues relative to MNPs that need to be further investigated.

Exploring the potential of photosynthetic induction factor for the commercial production of fucoxanthin in Phaeodactylum tricornutum.

Currently, the market price of fucoxanthin-based drugs remains high primarily because, on one hand, the main natural source of fucoxanthin, Phaeodactylum tricornutum (P. tricornutum), is extremely low in endogenous fucoxanthin, while, on the other hand, fucoxanthin mass production has proved to be very challenging. In this study, we demonstrated the feasibility of increasing fucoxanthin bioaccumulation in P. tricornutum by promoting photosynthetic activity of this diatom. Specifically, this study investigated the effects of different concentrations of the photosynthetic induction factor (PIF) on fucoxanthin content and biosynthesis, on chlorophyll fluorescence characteristics, and on the expression of photosynthesis-related genes in P. tricornutum. The results showed that the optimal PIF concentration was 1 µg L-1, while optimal time was 48 h, with the effect decreasing at 72 h. Fucoxanthin content increased by 44.2% compared to that of the control group in 48 h. Correlation analysis showed a significant positive correlation between fucoxanthin content and the actual photosynthetic yield of PS II (r = 0.949, P < 0.01). The total amount of energy actually used in photosystem II (PS II) by photosynthesis may be used as the main components affecting the biosynthesis of fucoxanthin in P. tricornutum. In addition, we found that using PIF to promote photosynthesis in P. tricornutum effectively increased the growth rate and bioaccumulation of fucoxanthin to an economically advantageous level, thereby providing a novel strategy for the commercial production of fucoxanthin.

Characterization of Aroma Compounds in Cooked Sorghum Using Comprehensive Two-Dimensional Gas Chromatography-Time-of-Flight Mass Spectrometry and Gas Chromatography-Olfactometry-Mass Spectrometry.

Sorghum is the major raw material for the production of Chinese Baijiu (Chinese liquor) and has a great effect on the flavor of Baijiu. Volatiles in cooked glutinous and non-glutinous sorghum samples were extracted using solid-phase microextraction (SPME) and analyzed via comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC×GC-TOFMS) and gas chromatography-olfactometry/mass spectrometry (GC-O/MS). A total of 145 volatile compounds and 52 potent odorant compounds were identified from both sorghum types according to the retention index, MS, aroma, and standards. Based on their aroma features, the compounds were grouped into eight general categories, and the intensities of each aroma group were summed. Moreover, most of the compounds detected in the cooked sorghums were also detected in commercial Chinese Baijiu, indicating that the aroma compounds produced during the sorghum cooking process have a direct and significant influence on the final flavor quality of Baijiu.

UHPLC-MS-Based Serum and Urine Metabolomics Reveals the Anti-Diabetic Mechanism of Ginsenoside Re in Type 2 Diabetic Rats.

Panax ginseng was employed in the treatment of "Xiao-Ke" symptom, which nowadays known as diabetes mellitus, in traditional Chinese medicine for more than a thousand years. Ginsenoside Re was the major pharmacologic ingredient found abundantly in ginseng. However, the anti-diabetic of Ginsenoside Re and its underlying mechanism in metabolic level are still unclear. Serum and urine metabolomic method was carried out to investigate the anti-diabetic pharmacological effects and the potential mechanism of Ginsenoside Re on high-fat diet combined streptozotocin-induced type 2 diabetes mellitus (T2DM) rats based on ultra-high-performance liquid chromatography coupled with quadrupole exactive orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap/MS). Serum and urine samples were collected from the control group (CON), T2DM group, metformin (MET) treatment group, and ginsenoside Re treatment group after intervention. The biochemical parameters of serum were firstly analyzed. The endogenous metabolites in serum and urine were detected by UHPLC-MS. The potential metabolites were screened by multivariate statistical analysis and identified by accurate mass measurement, MS/MS, and metabolite databases. The anti-diabetic-related metabolites were analyzed by KEGG metabolic pathway, and its potential mechanism was discussed. The treatment of ginsenoside Re significantly reduced the blood glucose and serum lipid level improved the oxidative stress caused by T2DM. Biochemical parameters (urea nitrogen, uric acid) showed that ginsenoside Re could improve renal function in T2DM rats. Respective 2 and 6 differential metabolites were found and identified in serum and urine of ginsenoside Re compared with T2DM group and enriched in KEGG pathway. Metabolic pathways analysis indicated that the differential metabolites related to T2DM were mainly involved in arachidonic acid metabolism, Vitamin B6, steroid hormone biosynthesis, and bile secretion metabolic pathways. This study verified the anti-diabetic and anti-oxidation effects of ginsenoside Re, elaborated that ginsenoside Re has a good regulation of the metabolic disorder in T2DM rats, which could promote insulin secretion, stimulated cannabinoid type 1 receptor (CB1), and CaMKK ß to activate AMPK signaling pathway, inhibited insulin resistance, and improved blood glucose uptake and diabetic nephropathy, so as to play the role of anti-diabetic.

Expression analysis of different ß-carotenoid hydroxylase gene families in stress response in Dunaliella viridis.

ß-carotenoid hydroxylase (CHYB) is an important rate-limiting enzyme in the biosynthesis of plant carotenoid. In this study, chyb1 and chyb2, two gene families in Dunaliella viridis were obtained by RNA-seq. The fragment of promoters of CHYB family genes, 1 080 bp for chyb1 (GenBank No. KY012338) and 1 155 bp for chyb2 (GenBank No. KY012339) were cloned by the Genome Walking Technology, respectively. Cis-acting elements of two promoters were analyzed by Plantcare soft. The results show that the chyb1 gene promoter contains more cis-acting elements in responses to abiotic stresses, such as methyl jasmonate, arachidonic acid, acetylsalicylic acid, and so on. On the other hand, the chyb2 promoter contains more cis-acting elements in response to light stress. qRT-PCR results show that the mRNA expression levels of CHYBs are modulated by their promoters, and different CHYB gene families response to distinct stresses.

[Transcriptome analysis of Dunaliella viridis].

In order to understand the gene information, function, haloduric pathway (glycerolipid metabolism) and related key genes for Dunaliella viridis, we used Illumina HiSeqTM 2000 high-throughput sequencing technology to sequence its transcriptome. Trinity soft was used to assemble the data to form transcripts. Based on the Clusters of Orthologous Groups (COG), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG ) databases, we carried out functional annotation and classification, pathway annotation, and the opening reading fragment (ORF) sequence prediction of transcripts. The key genes in the glycerolipid metabolism were analyzed. The results suggested that 81,593 transcripts were found, and 77,117 ORF sequences were predicted, accounting for 94.50% of all transcripts. COG classification results showed that 16,569 transcripts were assigned to 24 categories. GO classification annotated 76,436 transcripts. The number of transcripts for biologcial processes was 30,678, accounting for 40.14% of all transcripts. KEGG pathway analysis showed that 26,428 transcripts were annotated to 317 pathways, and 131 pathways were related to metabolism, accounting for 41.32% of all annotated pathways. Only one transcript was annotated as coding the key enzyme dihydroxyacetone kinase involved in the glycerolipid pathway. This enzyme could be related to glycerol biosynthesis under salt stress. This study further improved the gene information and laid the foundation of metabolic pathway research for Dunaliella viridis.

Construction of a Novel Semiautomated Electrochemical Sensor Array Platform and Its Application in Multiplexed Monitoring of Antibiotic Therapy.

At present, traditional analytical methods suffer from issues such as complex operation, expensive equipment, and a lengthy testing time. Electrochemical sensors have shown great advantages and application potential as an alternative solution. In this study, we proposed a novel semiautomated electrochemical sensor array (SAESA) platform. The sensor array was fabricated using screen-printed technology with a tubular design where all electrodes were printed on the inner wall. The integration of the tubular sensor array with a pipet allows for a semiautomated process including sampling and rinsing, which simplifies operation and reduces overall time. Each working electrode in the tubular sensor array underwent distinct decoration to get specific sensing responses toward the target analytes in a mixture environment (e.g., blood samples). To demonstrate the applicability of the developed sensing platform for simultaneous multianalyte detection, we chose antibiotic treatment for inflammatory infection as a model scenario and continuously measured three biomarkers, namely, tigecycline (TGC), procalcitonin (PCT), and alanine aminotransferase (ALT). The detection limits were 0.3 µM, 0.3 ng/L, and 2.76 U/L, respectively. The developed semiautomated electrochemical sensor array exhibits characteristics such as rapid and simple operation, portability, good selectivity, and excellent stability.

Fermented Ginsenosides Alleviate Acute Liver Injury Induced by CCl4 in Mice by Regulating the AKT/mTOR Signaling Pathway.

This study investigated the alleviating effect of fermented ginsenosides obtained through yeast strain fermentation transformation on acute liver injury (ALI) induced by CCl4. Strains were screened for their ability to produce ß-glucosidase, the transformation ability of the strain was verified by high-performance liquid chromatography, and the Saccharomyces cerevisiae strain F6 was obtained by 26S rRNA sequencing. After fermentation by F6 strain, it was found that the content of ginsenosides Re, Rb1, and Rb2 was significantly decreased (P < 0.05), and rare ginsenosides were detected, with the content of Rh4 and Rg5 reaching 2.65 mg·g-1 and 2.56 mg·g-1. We also explored the preventive effect of fermented ginsenoside extract (FGE) on ALI. Mice were evenly divided into 9 groups as follows: control group, ALI model group, positive drug bifendate group, and treatment group, which included 3 ginsenoside extract (GE) groups and 3 FGE groups (dosage of 150, 300, and 450 mg·kg-1 b.w.). The results showed that compared with the ALI model group, FGE significantly increased the levels of glutathione peroxidase, hydroperoxidase, and superoxide dismutase and also decreased the malondialdehyde level. The levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin markers were significantly reduced, and the levels of inflammatory cytokines TNF-α, IL-6, and IL-1ß were significantly decreased. Bioinformatics analysis combined with Western blot validation explored the molecular mechanism of the effect of FGE. It was found that FGE could downregulate the expression of the p-AKT/AKT and the p-mTOR/mTOR ratios. These results suggested that FGE played an alleviative role in ALI by promoting autophagy to inhibit the AKT/mTOR signaling pathway.

Four-Dimensional Label-Free Quantitative Proteomics of Ginsenoside Rg2 Ameliorated Scopolamine-Induced Memory Impairment in Mice through the Lysosomal Pathway.

Alzheimer's disease (AD) is a neurodegenerative disease. Ginsenoside Rg2 has shown potential in treating AD, but the underlying protein regulatory mechanisms associated with ginsenoside Rg2 treatment for AD remain unclear. This study utilized scopolamine to induce memory impairment in mice, and proteomics methods were employed to investigate the potential molecular mechanism of ginsenoside Rg2 in treating AD model mice. The Morris water maze, hematoxylin and eosin staining, and Nissl staining results indicated that ginsenoside Rg2 enhanced cognitive ability and decreased neuronal damage in AD mice. Proteomics, western blot, and immunofluorescence results showed that ginsenoside Rg2 primarily improved AD mice by downregulating the expression of LGMN, LAMP1, and PSAP proteins through the regulation of the lysosomal pathway. Transmission electron microscopy and network pharmacology prediction results showed a potential connection between the mechanism of ginsenoside Rg2 treatment for AD mice and lysosomes. The comprehensive results indicated that ginsenoside Rg2 may improve AD by downregulating LGMN, LAMP1, and PSAP through the regulation of the lysosomal pathway.

Comparative evaluation of fermented ginseng on alleviating antibiotic-associated diarrhea in mice.

Antibiotic associated diarrhea (AAD) was a common side effect of antibiotics, and fermented ginseng exhibited potential in treating AAD. In this study, the effects of fermented red, white, and black ginseng on AAD were investigated, with a focus on intestinal flora and inflammation. Clindamycin was used to induce AAD in mice, which caused severe diarrhea and weight loss. However, treatment with fermented ginseng effectively alleviated diarrhea, and reduced inflammation in colonic serosal tissue, thereby mitigating antibiotic-induced intestinal tissue damage. 16S rRNA sequencing revealed that clindamycin disrupted the Bacteroides/Firmicutes ratio (P < 0.001), which was reversed by fermented ginseng treatment. Furthermore, inflammatory cytokines like IL-1ß, IL-6, and TNF-α significantly decreased (P < 0.05) after clindamycin treatment but returned to normal levels following fermented ginseng treatment. In conclusion, fermented red, white, or black ginseng (at a dosage of 0.5 g/kg) exhibited efficacy against AAD in mice, reinstating gut flora balance and easing inflammation.

[Pollution Characteristics and Source Apportionment of VOCs in Urban Areas of Shijiazhuang in Spring].

Samples of ambient volatile organic compounds （VOCs） were collected using SUMMA canisters at three Country Control Sites in Shijiazhuang during the spring of 2019, 2021, and 2022, which were detected using gas chromatography/mass spectrometry （GC/MS）. To investigate the characteristics and temporal variations of VOCs mass concentration levels, the online monitoring data of ozone （O3） and PM2.5 at the same site were also collected. Subsequently, the ozone formation potential （OFP） and secondary organic aerosol formation potential （SOAFP） were utilized to assess the chemical activity of VOCs. Additionally, the potential source areas of VOCs in spring in Shijiazhuang were further identified using the potential source contribution factor （PSCF） method and concentration weight trajectory analysis （CWT）. Hence, the major VOCs sources were evaluated with the VOCs initial mixing ratio. The results demonstrated that the averaged concentration of VOCs during the polluted period and clean period of spring in Shijiazhuang were 191.17 µg·m-3 and 122.18 µg·m-3, respectively. Meanwhile, the OFP was 361.23 µg·m-3 during the polluted period and 266.96 µg·m-3 during the clean period, whereas the SOAFP was 1.98 µg·m-3 and 1.61 µg·m-3, respectively. Therefore, effective control of benzene, toluene, ethylbenzene, and xylene （BTEX） is crucial for reducing PM2.5 and O3 pollution. Based on the results obtained from weight PSCF and CWT, the potential source areas of VOCs were further identified to be primarily located in the eastern Yuhua District, the high-tech district, and the northern Luancheng District of Shijiazhuang. These areas were influenced not only by local emissions but also by transport from neighboring regions, in which consistency between the CWT and PSCF results further supported these findings. Furthermore, the results obtained from the benzene/toluene/ethylbenzene （B/T/E） and xylene/benzene （X/B） ratios indicated that the main sources of VOCs in Shijiazhuang in spring were vehicle exhaust sources and burning sources, leading to a more serious air mass aging phenomenon. Hence, controlling vehicle emissions and implementing regional cooperative measures are the effective strategies for optimizing the air quality of Shijiazhuang.

Discovery of drug lead compounds for Anti-Alzheimer's disease on the basis of synaptic plasticity.

Alzheimer's disease (AD) is a progressive neurodegenerative disease commonly seen in the middle-aged and the elder. Its clinical presentations are mainly memory impairment and cognitive impairment. Its cardinal pathological features are the deposition of extracellular Amyloid-ß (Aß), intracellular neurofibrillary tangles and synaptic dysfunction. The etiology of AD is complex and the pathogenesis remains unclear. Having AD would lead to awful living experience of it's patients, which may be a burden to the patient even to the public health care system. However, there are no certain cure for AD. Thus it's significant for both medical value and social meaning to find the way to cure or prevent AD and to research on the pathogenesis of AD. In this work, the molecular docking technology, pharmacokinetic analysis and pharmacological experiments were employed to analyse the natural active compounds and the mechanisms against AD based on the synaptic plasticity. A total of seven target proteins related to the synaptic plasticity and 44 natural active compounds with potential to enhance the synaptic plasticity were obtained through a literature review and network pharmacological analysis. Computer-Aided Drug Design (CADD) method was used to dock the anti-AD key target proteins with the 44 compounds. The compounds with good binding effect were screened. Three anti-AD active compounds based on the synaptic plasticity were obtained, including Curcumin, Withaferin A and Withanolide A. In addition, pharmacological experiments were carried out on Withaferin A and Withanolide A based on its good docking results. The experimental results showed that Withaferin A has good anti-AD potential and great potential to enhance synaptic plasticity. The anti-AD effect can be achieved through a multi-target synergistic mechanism.

Evaluation and Screening of Hypoglycemic Activity of Total Ginsenosides GBE-5 Fraction From Panax Ginseng Berry Based on UHPLC-MS Metabolomics.

Objective: Ginseng berry (GB) was the mature fruit of medicinal and edible herb, Panax ginseng C.A. Meyer, with significant hypoglycemic effect. Ginsenoside was the main hypoglycemic active component of GB. Evaluating and screening the effective components of GB was of great significance to further develop its hypoglycemic effect. Methods: The polar fractions of ginseng berry extract (GBE) were separated by a solvent extraction, and identified by ultra-high performance liquid chromatography-high-resolution mass spectrometry (UHPLC-MS). The insulin resistance model of HepG2 cells was established, and the hypoglycemic active fraction in GBE polar fractions were screened in vitro. Rat model of type 2 diabetes mellitus (T2DM) was established to verify the hypoglycemic effect of the GBE active fraction. The metabolomic study based on UHPLC-MS was used to analyze the differential metabolites in the serum of T2DM rats after 30 days of intervention with hypoglycemic active GBE fraction. The kyoto encyclopedia of genes and genomes (KEGG) metabolic pathway enrichment analysis was used to study the main metabolic pathways involved in the regulation of hypoglycemic active parts of GBE. Results: It was found that GBE-5 fraction had better hypoglycemic activity than other GBE polar fractions in vitro cell hypoglycemic activity screening experiment. After 30 days of treatment, the fasting blood glucose value of T2DM rats decreased significantly by 34.75%, indicating that it had significant hypoglycemic effect. Eighteen differential metabolites enriched in KEGG metabolic pathway were screened and identified in the rat serum from T2DM vs. GBE-5 group, and the metabolic pathways mainly involved in regulation include arachidonic acid (AA) metabolism, linoleic acid (LA) metabolism, unsaturated fatty acid biosynthesis, and ferroptosis. Conclusions: The hypoglycemic effect of GBE-5 fraction was better than that of total ginsenoside of GB. The AA metabolism, LA metabolism, unsaturated fatty acid biosynthesis, and ferroptosis were the potential metabolic pathways for GBE-5 fraction to exert hypoglycemic regulation.

Serum metabolomic analysis of the anti-diabetic effect of Ginseng berry in type II diabetic rats based on ultra high-performance liquid chromatography-high resolution mass spectrometry.

Serum metabolomic method was used to investigated the anti-diabetic effects and mechanism of Ginseng berry (GB) on high-fat diet combined streptozotocin induced type II diabetes mellitus (T2DM) rats based on ultra high performance liquid chromatography coupled with quadrupole Exactive orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap/MS). Serum samples from control group, T2DM group, metformin treatment group, and GB ginsenoside treatment group rats were collected after intervention. The biochemical parameters of serum were firstly analyzed. Then metabolomic studies based on UHPLC-Q-Exactive Orbitrap/MS and multivariate statistical analysis were performed for the pattern recognition and characteristic metabolites identification. The differential metabolites were analyzed by KEGG metabolic pathway to study the potential mechanism. The treatment of GB ginsenoside significantly reduced the blood glucose level, increased the content of serum SOD, and reduced the content of malondialdehyde. Respectively 16, 9, and 24 differential metabolites were found and identified in T2DM compared to control group, metformin compared to T2DM group and GB compared to T2DM group. Metabolic pathways analysis indicated that GB ginsenoside regulated bile acid metabolism, arachidonic acid metabolism, glucuronization to play a role in the treatment of T2DM. This study verified the anti-diabetic and anti-oxidation effects of ginseng berry, elaborated that GB regulated the secretion of bile acids, activated GLP-1 pathway, increased the secretion of insulin, promoted the hydrolysis of fat and triglyceride, inhibited the activity of 5α - reductase, reduced weight and insulin resistance, so as to improved and treated T2DM, and laid the foundation for the further development and utilization.