Fraxinus mandshurica (Oleaceae, Fraxinus) seeds serve as food and condiments in traditional American and European diets. This study provides the first systematic evaluation of the therapeutic effects of F. mandshurica seed extract on T2DM. This study evaluated the effects of F. mandshurica seed extract on glucose-lipid metabolism, hepatorenal function, and gut microbiota in an HFD/STZ-induced T2DM mouse model. Through UPLC-Q-TOF-MS chemical characterization and phytochemical analysis, combined with network pharmacology and molecular docking techniques, potential active components and their corresponding targets were predicted. Critically, the predicted activity of 18 iridoid monomers was confirmed by evaluating their ability to enhance glucose consumption in L02 cells. F. mandshurica seed extract significantly reduced body weight, TC, TG, and blood glucose levels, improved insulin sensitivity and glucose tolerance, and alleviated hepatorenal injury. Additionally, it regulated the gut microbiota by reducing the Firmicutes/Bacteroidetes ratio. Network pharmacology analysis identified AGE-RAGE and TNF signaling as core anti-diabetic pathways. Key active components, including bisandrographolide A, ligstroside, reptoside, oleuropein, fraxoside, koaburside, and mudanpioside D, were identified and selected for molecular docking. The results indicate that these active components form stable ligand-receptor complexes with target proteins (HRAS, MAPK1, HSP90AA1, MMP9 and AKT1) via hydrogen bonds, hydrophobic interactions, π-π stacking and salt bridges. Finally, 18 iridoid glucosides from the F. mandshurica seed were shown to promote glucose consumption, with efficacy ranging from 7.27% to 71.52%. This study reveals that F. mandshurica seeds and their characteristic iridoid components possess promising prospects as candidates for developing natural anti-diabetic therapeutics.

We herein report a palladium-catalyzed cascade reaction that enables the de novo synthesis of spirooxindoles from simple ortho-iodoaniline derivatives, in which tertiary O-benzoyl hydroxylamines serve as bifunctional single-nitrogen sources through sequential C-H diamination and C-N activation. The reaction features a broad substrate scope and accommodates both diamination and triamination pathways. Preliminary asymmetric studies afford the desired product in up to 92% ee, providing a concise route to structurally diverse spirooxindoles.

Ulcerative colitis (UC) urgently needs effective and safe therapeutic options. Natural procyanidins show promise, but the relationship between their degree of polymerization and anti-colitis efficacy remains unclear. The mature stem of Aganosma cymosa is a rich source of procyanidins, offering an ideal model to address this question. To compare the protective effects of a tetramer-enriched procyanidin oligomer (ACrGD) and its monomeric subunit (-)-epicatechin (ODG) from A. cymosa in a DSS-induced mouse colitis model, and to elucidate their distinct molecular mechanisms using multi-omics approaches, C57BL/6J mice with DSS-induced colitis were treated with ACrGD or ODG. Disease activity index (DAI), histopathology, inflammatory cytokines and oxidative stress markers were evaluated. Gut microbiota and short-chain fatty acids (SCFAs) were analyzed by 16S rRNA sequencing and targeted metabolomics. Colonic transcriptome and proteome were integrated, and splenic transcriptome was analyzed to construct a multi-omics regulatory network. Both ACrGD and ODG ameliorated DSS-induced colitis, but ACrGD more effectively elevated SCFA levels, particularly butyrate. Integrated colonic multi-omics revealed that ACrGD predominantly reversed genes/proteins involved in ferroptosis, extracellular matrix remodeling, and barrier function, whereas ODG mainly affected the NF-kappa B pathway. Splenic transcriptomics further demonstrated that ACrGD suppressed aberrant proliferation and ferroptosis in the spleen via the "gut-spleen axis". The tetramer-enriched procyanidin oligomer alleviates colitis by rewiring the gut microbiota-SCFAs-ferroptosis axis, exerting both local and systemic effects. This study establishes a relationship between procyanidin polymerization degree and bioactivity, and provides a scientific basis for developing oligomeric procyanidins as functional foods or therapeutics for UC.

In-depth chemical characterization provides key fingerprints for honey authentication. An integrated approach combining UHPLC-Q-TOF/MS-based molecular networking (MN) with HSQC NMR-based small molecule accurate recognition technology (SMART) was applied to characterize the chemical profile of Apis cerana honey from the Qinling Mountains. Twenty-eight metabolites were identified, with alkaloids and lipids being the most abundant. Targeted isolation of predominant fractions yielded four alkaloids (lumichrome, chestnutamide, deoxyvascinone, and 2-quinolone), one ionone derivative (plasiaticine I), and one ester (cetyl triacontanoate), all first reported in A. cerana honey as potential markers. 1H NMR-based metabolomics coupled with OPLS-DA showed 13 unifloral honeys clustered by botanical origin. With this model, characteristic NMR signals of A. cerana honey (δH 2.28 [t], 3.45 [s], 4.05 [t] ppm) were identified, among which the two triplets match the oxygenated methylene of the isolated compounds. These findings clarify the chemical basis of A. cerana honey and provide an integrated approach for authentication.

The rapid and targeted identification of bioactive constituents from complex natural product matrices remains a significant challenge in natural product research. This study employs an integrated biochemometrics workflow combining 1H Nuclear Magnetic Resonance (1H NMR) and mass spectrometry (MS) to efficiently pinpoint antioxidant components from Aganosma cymosa. Systematic separation of the crude extract yielded 37 microfractions (MFs), which were subjected to both antioxidant activity evaluation and UHPLC-MS/MS profiling. An active molecular network was constructed by calculating Spearman rank correlation coefficients between MS feature abundances and the corresponding antioxidant activity data, enabling visualization of activity-correlated features within the GNPS platform. To address the limitation of MS-based annotation in distinguishing structural isomers, feature-based GNPS analysis was integrated with 1H NMR heterospectral covariance analysis (HetCA). The HetCA pseudo-spectra provided orthogonal validation and precise spectroscopic targets for subsequent isolation. Through this combined strategy, the main antioxidant constituents were successfully predicted, isolated, and structurally verified by NMR data. In conclusion, this study demonstrates that the synergistic integration of Spearman rank correlation-based active molecular networking, a multi-level prioritization strategy, and 1H NMR HetCA orthogonal validation provides a powerful paradigm for the precise identification of bioactive components in complex plant matrices.

Sensitive and comprehensive measurement of systemic metabolites of Trp, Phe and Glu in biological samples is effective for understanding the pathogenesis of pain, anxiety, depression, PTSD and other neurological diseases. This study developed a LC-MS/MS method for simultaneous monitoring the 10 neurotransmitters in mouse hippocampus, and applied it to investigate their changes in five neuroinflammatory mouse models. The quantitative analysis of 10 neurotransmitters, including Gamma-aminobutyric acid (γ-GABA), l-Glutamate (Glu), l-Glutamine (Gln), l-Tryptophan (Trp), Serotonin (5-HT), 5-Hydroxyindoleacetic acid (5-HIAA), l-Phenylalanine (Phe), l-Tyrosine (L-Tyr), Dopamine (DA), Levodopa (L-DOPA) was achieved within a chromatographic separation time of 4.5 min by the application of ThermoFisher Scientific™ Vanquish™ HPLC coupled to ThermoFisher ScientificTM TSQ QuantisTM mass spectrometer. Optimized chromatographic separation as well as high sensitivity allow the simultaneous analysis and precise quantification of ten neurotransmitters in mouse hippocampus. The limits of detection in sample ranged from 0.3pg (Phe) to 0.1 μg (γ-GABA). Recoveries were between 88.0 to 113.8 %, the mean intra - day and inter - day coefficient of variation of 5.56 % and 4.72 %, respectively. The matrix effect was from 85.1 to 114.9 %. A series of significant changes in five neuroinflammatory mouse models can be detected. γ-GABA, Glu, Gln, DA, Phe, l-Tyr, 5-HIAA were decreased in depression model. Gln and Glu were decreased in PTSD model. 5-HIAA was elevated in anxiety. 5-HIAA and l-Trp were decreased in CFA and SNI model, respectively. In conclusion, a LC-MS/MS method for simultaneous measurement of 10 neurotransmitters in mouse hippocampus was developed and successfully applied to investigation of the changes in five neuroinflammatory mouse models. The method would be expected to provide applicability to the study of the mechanisms of neurological diseases associated with these neurotransmitters.

Dearomatization of planar aromatics offers unparalleled opportunities for the construction of three-dimensional stereochemical frameworks. However, the inherent instability of dearomatized intermediates, particularly bearing labile C(sp3)-heteroatom bonds, has hindered progress due to competing rearomatization pathways. By capitalizing on arene dearomatization and transforming the rearomatization predicament into a new opportunity, we herein present a stability-driven catalytic asymmetric dearomatization/rearomatization (CADA/RA) cooperative strategy to resolve racemic P-stereogenic compounds. Through the systematic engineering of phenolic substrates, bench-stable P-site dearomatized products with dual C(sp3)-P and C(sp3)-Cl bonds were isolated. Chiral Lewis acid catalysis enabled kinetic resolution (KR) and parallel kinetic resolution (PKR), achieving full enantiomeric separation with exceptional stereocontrol across diverse substrates. Mechanistic analysis revealed competing substrate- and catalyst-controlled pathways for stereochemical precision. Postsynthetic chemoselective Cl- or P-liberation furnished enantioenriched P-chiral compounds. This method transforms the challenges of dearomatization and rearomatization into opportunities for stereochemical complexity generation, offering a robust platform to synthesize P-chiral building blocks and ligand precursors.

We herein report a unified strategy integrating catalytic asymmetric chlorinative dearomatization and stereoselective dechlorinative rearomatization for resolving axially chiral 1-aryl-2-naphthols. By using a Sc(III)/Py-BOX catalytic system, naphthol-based biaryls underwent kinetic resolution through asymmetric chlorinative dearomatization. This process converted the intrinsic C(sp2)-C(sp2) axial chirality of one enantiomer into a conformationally favored C(sp2)-C(sp3) axis by generating a chlorine-containing C(sp3)-stereogenic center. The reaction showed high functional group tolerance and excellent enantioselectivities across a wide range of substrates. Subsequently, a stereospecific rearomatization protocol using triethylamine under blue-light irradiation was developed. This dechlorination method exploited an electron donor-acceptor (EDA) complex mechanism, efficiently converting the stored C(sp2)-C(sp3) axial chirality back to the original C(sp2)-C(sp2) axis, thus enabling full resolution of the biaryl atropisomers. The resolved 1-aryl-2-naphthols can be readily transformed into various catalytically and synthetically valuable molecules, such as axially chiral monophosphine, bisphosphine, aldehyde, and carboxylic acid.

The bark of Fraxinus mandshurica is a traditional folk herb used to clear heat and dry dampness. To investigate the differences in coumarins content in the bark of F. mandshurica, 24 batches of samples from four origins were collected and analyzed. Eight coumarins were obtained by traditional natural product extraction, isolation and identification techniques and quantified by high performance liquid chromatography-photodiode array (HPLC-DAD). The quantitative results showed that the overall content of compound 30 (Fraxinol) was higher at 100.23 mg/g, while the overall content of compound 23 (Cichoriin) was lower, which may be related to environmental factors in different regions. The method validation showed that the linear range of the eight standards was between 10 and 2500 mu g/mL with correlation coefficient (R-2) values >0.9991; the relative standard deviation (RSD, %) values of intra-day precision were between 0.35 and 1.38, while the RSD values of inter-day precision were between 0. 29-1.78; the RSD (%) values for the reproducibility experiments ranged from 0.29 to 1.87, while the RSD (%) values for the stability experiments ranged from 0.22 to 2.33; the spiked recovery of the samples ranged from 98.65 to 101.34%, and the RSD (%) values ranged from 0.22 to 1.96. The method validation results showed that the instrument used for the analysis had good precision, the reproducibility and stability of the samples were good, and the accuracy of the experimental method was high. In addition, a total of 54 chemical components were identified from F. mandshurica bark by ultra performance liquid chromatography-electrospray quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS). Based on this, fingerprinting, heatmap and multivariate analysis, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), were established for 24 batches of samples, and four marker compounds that could be used to distinguish different origins of F. mandshurica were screened. To further investigate the bioactivities of the eight coumarins, in vitro enzyme activity inhibition studies were performed, and the results showed that they all exhibited different degrees of inhibition of acetylcholinesterase, tyrosinase and alpha-glucosidase, thus having potential applications in the treatment of Alzheimer's disease, blemish whitening and anti-diabetes, and becoming a new source of natural enzyme activity inhibitors. This study established an identification and evaluation method applicable to plants of different origins, which provides a strong reference for quality control, origin evaluation and clinical application of traditional medicinal plants.

BackgroundActinidia arguta leaves (AAL) are traditionally consumed as a vegetable and as tea in folk China and Korea. Previous studies have reported the anti-diabetic effect of AAL, but its bioactive components and mechanism of action are still unclear.Aim of the studyThis study aims to identify the hypoglycemic active components of AAL by combining serum pharmacochemistry and network pharmacology and to elucidate its possible mechanism of action.MethodsFirstly, the effective components in mice serum samples were characterized by UPLC-Q/TOF-MSE. Furthermore, based on these active ingredients, network pharmacology analysis was performed to establish an “H-C-T-P-D” interaction network and reveal possible biological mechanisms. Finally, the affinity between serum AAL components and the main proteins in the important pathways above was investigated through molecular docking analysis.ResultsSerum pharmacochemistry analysis showed that 69 compounds in the serum samples were identified, including 23 prototypes and 46 metabolites. The metabolic reactions mainly included deglycosylation, dehydration, hydrogenation, methylation, acetylation, glucuronidation, and sulfation. Network pharmacology analysis showed that the key components quercetin, pinoresinol diglucoside, and 5-O-trans-p-coumaroyl quinic acid butyl ester mainly acted on the core targets PTGS2, HRAS, RELA, PRKCA, and BCL2 targets and through the PI3K-Akt signaling pathway, endocrine resistance, and MAPK signaling pathway to exert a hypoglycemic effect. Likewise, molecular docking results showed that the three potential active ingredients had good binding effects on the five key targets.ConclusionThis study provides a basis for elucidating the pharmacodynamic substance basis of AA against T2DM and further exploring the mechanism of action.

Fraxinus mandshurica (Oleaceae) is used as a traditional medicinal plant for the treatment of red eyes, menstrual disorders, excessive leucorrhea, chronic bronchitis and psoriasis. To perform chemical characterization of the secondary metabolites of F. mandshurica roots, bark, stems and leaves, 32 samples were collected from eight provinces in this study. A total of 64 chemical components were detected from four different parts of F. mandshurica by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Meanwhile, a total of nine secoiridoids were obtained by natural product chemical extraction, isolation and identification methods. Quantitative analysis by high-performance liquid chromatography-diode array detection-mass spectrometry showed the highest total content of secoiridoids in the bark, which is also consistent with the traditional medicinal parts. The results of methodological validation showed that the correlation coefficient (R2) values were all >0.9993, indicating a good linear range of the standard curve, while the relative standard deviations of precision, reproducibility and stability were <3%, and the spiked recoveries ranged from 98.22 to 102.27%, indicating that the experimental method was reliable and stable. In addition, fingerprinting and a heatmap were established to demonstrate the content trends of F. mandshurica more visually from different origins. Multivariate analysis, including principal component analysis and partial least squares discriminant analysis, was performed to determine the chemical characteristics of different parts of F. mandshurica, and six characteristic secoiridoids that could be used to distinguish different origins were screened. Finally, the inhibition of tyrosinase, α-glucosidase, acetylcholinesterase and pancreatic lipase activities by the nine characteristic compounds and extracts from different parts were investigated, and the results showed that they all exhibited different degrees of enzyme activity inhibition and thus have potential applications in whitening and blemish removal, hypoglycemia, anti-Alzheimer's disease and anti-obesity as a new source of natural enzyme activity inhibitors. This study establishes an identification and evaluation method applicable to phytochemistry of different origins, which is a guideline for quality control, origin evaluation and clinical application of traditional medicinal plants. This is also an unprecedented study on the identification of the chemical composition of different parts of F. mandshurica, characteristic compounds and the inhibition of enzyme activity of extracts from different parts.

The monofloral honey from Schefflera octophylla (Lour.) Harms (MH-Sco) are of high economic value due to their rarity and potential medicinal benefits. However, the limited investigations on the relationship of phytogenic components between the plant S. octophylla (P-Sco) and MH-Sco have an impact on MH-Sco authentication. Herein, the tentative phytogenic markers of MH-Sco were screened by comparing the metabolites of MH-Sco obtained by ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS)-based untargeted metabolomics with the identified phytogenic chemicals from P-Sco. Combined with the mass and NMR spectral information, 3α-hydroxylup-20(29)-ene-23,28-dioic acid (HLEDA) was finally identified as the phytogenic marker of MH-Sco. A targeted ultrahigh-performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS)-based method was established and validated based on the purified monomer standard to measure HLEDA levels in honey samples. HLEDA determined in MH-Sco was with the content from 0.303 to 0.440 mg/kg, while HLEDA was absent in honey samples from other botanical origins, indicating the reliability of HLEDA as a chemical marker in MH-Sco authentication. This study provides the theoretical basis and industry guidance for honey quality control for commercial consumption.

BACKGROUND:Multiple brain disorders are treated by Scutellaria Radix (SR), including cerebral ischemia-reperfusion (CI/R). However, more studies are needed to clarify the molecular mechanism of SR for CI/R. METHODS:The active substances and potential targets of SR and CI/R-related genes were obtained through public databases. Overlapping targets of SR and CI/R were analyzed using proteinprotein interaction (PPI) networks. GO and KEGG enrichment analyses were performed to predict the pathways of SR against CI/R, and the key components and targets were screened for molecular docking. The results of network pharmacology analysis were verified using in vitro experiments. RESULTS:15 components and 64 overlapping targets related to SR and CI/R were obtained. The top targets were AKT1, IL-6, CAS3, TNF, and TP53. These targets have been studied by GO and KEGG to be connected to a number of signaling pathways, including MAPK, PI3K-Akt pathway, and apoptosis. Molecular docking and cell experiments helped to further substantiate the network pharmacology results. CONCLUSION:The active compound of SR was able to significantly decrease the apoptosis of HT- 22 cells induced by OGD/R. This finding suggests that SR is a potentially effective treatment for CI/R by modulating the MAPK and PI3K-Akt pathways.

A. arguta leaves, as an important by-product during the ripening of A. arguta fruits, are usually discarded. It contains numerous flavonoid components. In the present research, a simple and reproducible HPLC-DAD method was established and verified for simultaneous identification and quantification analysis of 25 flavonoid components in A. arguta leaves. The findings indicated that the highest concentration of flavonoid compounds in A. arguta leaves was quercetin ( 2 ), with a content of 8.97 +/- 0.09 mg/g. The content of flavonoids in samples from different cultivation bases was different, indicating that the varied flavonoid contents are possibly determined by geographical variance. This method can be used for the quality control of Actinidia arguta . The 25 flavonoids showed good alpha-glucosidase inhibitory activity with IC 50 values ranging from 0.35 to 4.15 mM, and the activity difference varied with the different structures. 2"- O -galloylhyperin ( 18 ) showed the best antihyperglycemic action (IC 50 = 0.35 +/- 0.01 mM), followed by quercetin ( 2 , IC 50 = 0.38 +/- 0.01 mM), quercetin 4 ' - O -galactoside ( 19 , IC 50 = 0.41 +/- 0.01 mM), kaempferol ( 3 , IC 50 = 0.42 +/- 0.01 mM), and kaempferol-3-rutinoside ( 6 , IC 50 = 0.53 +/- 0.01 mM). Molecular docking analysis demonstrated that the interaction modes of these five stronger inhibitors with alpha-glucosidase were mainly hydrogen bonding and hydrophobic interaction. The results showed that compounds with different structural skeletons interacted with different amino acid residues and exerted different degrees of alpha-glucosidase inhibition. Therefore, A. arguta leaves and their flavonoids may be beneficial against diabetes, and higher levels of flavonoids are considered to have greater potential for medicinal use.

Fraxinus mandshurica is widely distributed around the world, which has significant economic value and pharmacological effects. However, its roots are often overlooked during processing and use. In this study, the preliminary identification of chemical components in F. mandshurica roots was carried out using ultra-performance liquid chromatography coupled with electrospray quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS), and a total of 37 characteristic components were identified, including 13 secoiridoids, 7 lignans, 6 coumarins, 4 flavonoids, 4 phenylethanols, 1 terpenoid and 2 other compounds. Meanwhile, to evaluate the 6 lignans content of F. mandshurica roots, the identification, quantitation analysis and methodological validation were performed by high-performance liquid chromatography with diode array detection mass spectrometry (HPLC-DAD-MS), which showed that the concentration range of standard compounds was 0.5-1000 μg/mL. The standard curve correlation coefficients (R2) were all greater than 0.9991, indicating that the linearity of the fitted curves was good. The highest lignan content in F. mandshurica roots was olivil (461.11 μg/g) and the lowest in buddlenol E (11.14 μg/g), and the total lignan content was 764.63 μg/g. The relative standard deviations (RSD, %) of both intra-day and inter-day precision were less than 1.95%. The RSD (%) of the reproducibility and stability experiments was less than 2.91%. The spiked recoveries of the samples were in the range of 98.29-102.62%, and the RSD (%) was in the range of 0.43-1.73, indicating that the method has high accuracy. In addition, a total of 20 volatile components in F. mandshurica roots were identified and quantified by gas chromatography-mass spectrometer (GC-MS) in this study, which laid a solid foundation for the comprehensive development and utilization of F. mandshurica resources.

A novel [4 + 1] and [5 + 1] dearomative spiroannulation has been developed by the use of commercial naphthols and phenols with dielectrophiles. Various spirocycles, including spiro[4.5] and spiro[5.5] have been constructed successfully by employing four-atom or five-atom dielectrophilic synthons. This transformation was realized through a sequence of site-selective C-alkylation/dearomative spiroannulation. Moreover, the potential application of this method was exemplified by several further transformation.

Actinidia arguta, an edible berry plant with high nutritional values, has been widely used in Asian countries as a food and traditional medicinal herb. The well-recognized health-promoting properties of A. arguta were associated with its bioactive components in its different botanical parts. To rapidly screen and identify chemical components and simultaneously determine the potential metabolites from different parts of A. arguta, UPLC-Q-TOF-MSE coupled with UNIFI platform and multivariate statistical analysis approach was established in this study. As a result, a total of 107 components were identified from the four different parts of A. arguta, in which 31 characteristic chemical markers were discovered among them, including 12, 8, 6, and 5 compounds from the fruits, leaves, roots, and stems, respectively. These results suggested that the combination of UPLC-Q-TOF-MSE and metabolomic analysis is a powerful method to rapidly screen characteristic markers for the quality control of A. arguta.

Fraxinus mandshurica is widely used in folk medicine and has significant pharmacological effects. In order to make full use of its resources, the roots were studied. Firstly, 12 lignans were obtained by natural product extraction, isolation and identification methods, and identification and quantification analysis were performed using high-performance liquid chromatography with photodiode array (HPLC-DAD). The results of the quantification analysis showed that the highest lignin content in the roots of Fraxinus mandshurica was compound 9 with 102.30 mg/g, while the overall lignin content in Shanxi was low. The results of methodological validation showed that the RSD values of intra-day precision ranged from 0.35-1.38%, while the RSD values of inter-day precision were within 1.97%; the RSD values of reproducibility experiments ranged from 0.35-1.96%, while the RSD values of stability experiments were less than 2.97%; the spiked recoveries of samples were within 102.84%, and the RSD values were within 102.84% and the RSD values were between 0.39% and 1.77%, which fully confirmed the high precision and good reproducibility of the analytical method. In addition, fingerprinting and heatmap were established for 12 lignin from 16 batches of samples from 8 origins. Multivariate analysis, including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), was performed to investigate the differences in lignans in the roots of Fraxinus mandshurica from different origins, and seven lignans that could be used to distinguish between the roots of Fraxinus mandshurica from different origins were screened. Finally, 12 lignans were evaluated for enzyme activity inhibition using α-glucosidase, tyrosinase and acetylcholinesterase, and the results showed that all 12 lignans exhibited enzyme activity inhibition to different degrees, and have potential applications in antidiabetic, whitening and anti-Alzheimer's disease, becoming a new source of natural product enzyme activity inhibitors. This study establishes a method applicable to the identification and evaluation of plants of different origins, and provides a certain theoretical basis for the comprehensive exploitation of Fraxinus mandshurica.

A palladium-catalyzed C-H arylation/arene dearomatization of α-aryl-β-naphthol with o-dihalobenzenes was realized in a redox-neutral manner. This bimolecular domino reaction was initiated by an in situ-formed Pd(II) species generated from the dihalobenzene, followed by phenolic-group-directed C-H activation, biaryl cross-coupling, and naphthol dearomatization, thus rendering the rapid assembly of a class of spiro[4,5]fluorenes in high yields with good chemoselectivity. Remarkably, malononitrile-derived spirofluorene 6 was found to exhibit mechanoresponsive luminescence, which can be applied to optical memory devices.

Fraxinus mandshurica is widely used in folk medicine to treat various diseases and has significant pharmacological effects. To make full use of this resource, its roots were studied. Twelve lignans were first obtained by natural product extraction, selective separation and identification, and were identified and quantified by high perfor-mance liquid chromatography-photodiode array (HPLC-DAD). The results of quantitative analysis showed that the highest lignin content in F. mandshurica roots was compound 9 with 102.02 mg/g, while the overall lignin content in Shanxi was low. The results of methodological validation showed that the RSD values of intra-day precision ranged from 0.35% to 1.38%, while the RSD values of inter-day precision were within 1.97%; the RSD values of reproducibility experiments ranged from 0.35% to 1.96%, while the RSD values of stability experi-ments were less than 2.97%; the spiked recovey of samples were within 102.84%, and the RSD values ranged from 0.39% to 1.77%, which fully confirmed the high precision and good reproducibility of the analytical method. In addition, fingerprinting and heatmap were established for 40 batches of samples from 8 origins. Next, multi-variate analysis, including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), was performed to investigate the differences in lignin content in the roots of F. mandshurica from different origins, and four lignins that could be used to distinguish F. mandshurica from different origins were screened. Finally, 12 lignans were evaluated for enzyme activity inhibition with alpha-glucosidase, tyrosinase and acetylcholinesterase, and the results showed that all 12 lignans exhibited enzyme activity inhibition to dif-ferent degrees, which have potential applications in anti-diabetic, whitening and light spot and anti-Alzheimer's disease, and become a new source of natural enzyme activity inhibitors. This study established an identification and evaluation method applicable to plants of different origins, which provides a certain theoretical basis for the comprehensive exploitation of F. mandshurica.