Correlation between immune-related Tryptophan-Kynurenine pathway and severity of severe pneumonia and inflammation-related polyunsaturated fatty acids.

BACKGROUND: Immune dysfunction and oxidative stress caused by severe pneumonia can lead to multiple organ dysfunction and even death, causing a significant impact on health and the economy. Currently, great progress has been made in the diagnosis and treatment of this disease, but the mortality rate remains high (approximately 50%). Therefore, there is still potential for further exploration of the immune response mechanisms against severe pneumonia. OBJECTIVE: This study analyzed the difference in serum metabolic profiles between patients with severe pneumonia and health individuals through metabolomics, aiming to uncover the correlation between the Tryptophan-Kynurenine pathway and the severity of severe pneumonia, as well as N-3/N-6 polyunsaturated fatty acids (PUFAs). METHODS: In this study, 44 patients with severe pneumonia and 37 health controls were selected. According to the changes in the disease symptoms within the 7 days of admission, the patients were divided into aggravation (n = 22) and remission (n = 22) groups. Targeted metabolomics techniques were performed to quantify serum metabolites and analyze changes between groups. RESULTS: Metabolomics analysis showed that serum kynurenine and kynurenine/tryptophan (K/T) were significantly increased and tryptophan was significantly decreased in patients with severe pneumonia; HETE and HEPE in lipids increased significantly, while eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), α-linolenic acid (linolenic acid, α-LNA), arachidonic acid (ARA), Dihomo-γ-linolenic acid (DGLA), and 13(s)-hydroperoxylinoleic acid (HPODE) decreased significantly. Additionally, the longitudinal comparison revealed that Linolenic acid, DPA, and Tryptophan increased significantly in the remission group, while and kynurenine and K/T decreased significantly. In the aggravation group, Kynurenine and K/T increased significantly, while ARA, 8(S)-hydroxyeicosatetraenoic acid (HETE), 11(S)-HETE, and Tryptophan decreased significantly. The correlation analysis matrix demonstrated that Tryptophan was positively correlated with DGLA, 12(S)-hydroxyeicosapentaenoic acid (HEPE), ARA, EPA, α-LNA, DHA, and DPA. Kynurenine was positively correlated with 8(S)-HETE and negatively correlated with DHA. Additionally, K/T was negatively correlated with DGLA, ARA, EPA, α-LNA, DHA, and DPA. CONCLUSION: This study revealed that during severe pneumonia, the Tryptophan-Kynurenine pathway was activated and was positively correlated with the disease progression. On the other hand, the activation of the Tryptophan-Kynurenine pathway was negatively correlated with N-3/N-6 PUFAs.

Network Pharmacology Strategy to Investigate the Pharmacological Mechanism of HuangQiXiXin Decoction on Cough Variant Asthma and Evidence-Based Medicine Approach Validation.

OBJECTIVE: To investigate the pharmacological mechanism of HuangQiXiXin decoction (HQXXD) on cough variant asthma (CVA) and validate the clinical curative effect. METHODS: The active compounds and target genes of HQXXD were searched using TCMSP. CVA-related target genes were obtained using the GeneCards database. The active target genes of HQXXD were compared with the CVA-related target genes to identify candidate target genes of HQXXD acting on CVA. A medicine-compound-target network was constructed using Cytoscape 3.6.0 software, and a protein-protein interaction (PPI) network was constructed using the STRING database. Gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using RGUI3.6.1 and Cytoscape 3.6.0. We searched the main database for randomized controlled trials of HQXXD for CVA. We assessed the quality of the included studies using the Cochrane Reviewers' Handbook. A meta-analysis of the clinical curative effect of HQXXD for CVA was conducted using the Cochrane Collaboration's RevMan 5.3 software. RESULTS: We screened out 48 active compounds and 217 active target genes of HQXXD from TCMSP. The 217 active target genes of HQXXD were compared with the 1481 CVA-related target genes, and 132 candidate target genes for HQXXD acting on CVA were identified. The medicine-compound-target network and PPI network were constructed, and the key compounds and key targets were selected. GO function enrichment and KEGG pathway enrichment analysis were performed. Meta-analysis showed that the total effective rate of the clinical curative effect was significantly higher in the experimental group than the control group. CONCLUSION: The pharmacological mechanism of HQXXD acting on CVA has been further determined, and the clinical curative effect of HQXXD on CVA is remarkable.

Chemical constituents from branch of Fraxinus sieboldiana.

Using a combination of various chromatographic techniques including column chromatography over silica gel, Sephadex LH-20, macroporous adsorbent resin, and reversed-phase HPLC, 115 compounds including diterpenes, sesquiterpenes, treterpenes, coumarins, lignans, fatty acid derivatives, and simple aromatic derivatives were isolated from an ethanol extract of branch of Fraxinus sieboldiana (Oleaceaue), and their structures of the compounds were elucidated by spectroscopic methods including 1 D, 2D NMR and MS techniques. Among them, 41 compounds were new. In previous reports, we have been described the isolation, structure elucidation, and bioactivities of the 41 new compounds and 22 known orii including 8 coumarins, 4 phenolic and 12 phenylethanoidal glycosides. As a consequence, we herein reported the isolation and structure elucidation of the remaining 50 known compounds including 8- hydroxy-12-oxoabieta-9(11),13-dien-20-oic 8, 20-lactone(1), 6beta-hydroxyfcrruginol(2),(+)-pisiferic acid(3), (+)-pisiferal(4),(+)-7-dehydroabiet6none(5), 1-oxomiltirone(6), subdigitatone(7), linarionoside B(8), (9S)-linarionoside B(9), (3R,9R)-3-hydroxy-7,8-dihydro-beta-ionol 9-O-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside(10), ursolic acid(11), betulinic acid(12), euscaphic acid(13), (+)-syringaresinol(14), (+)-fraxiresinol(15), (+)-1-hydroxysyringaresinol(16), pinoresinol(17), medioresinol(18), 8-acetoxypinoresinol(19), epipinoresinol(20), (-)-olivil(21), (+)-cyclo-olivil(22), 3,3'-dimethoxy-4,4',9-trihydroxy-7,9'-epoxylignan-7'-one(23),(+)-1-hydroxypinoresinol 4'-O-beta-D-glucopyranoside (24), (+)-1-hydroxypinoresinol 4"-O-beta-D-glucopyranoside(25),(+)-syringaresinol O-beta-D-glucopyranoside (26), liriodendrin (27), ehletianol D(28), icariside E5(29) (-)-(7R, 8R)-threo-1-C-syringylglycerol(30),(-)-(7R, 8S)-erythro-guaiacylglycerol (31),(-)-(7R, 8R)-threo-guaiacylglycerol(32), 3-(4-beta-D-glucopyranosyloxy-3-methoxy)-phenyl-2E-propenol(33),2,3-dihydroxy-l-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(34), 2,3-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)-1-propanone (35), 3-hydroxy-l-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(36), omega-hydroxypropioguaiacone(37), sinapyladehyde(38), trans-p-hydroxycinnamaldehyde(39), syringic acid(40), vanilic acid(41), vanillin(42), 4-hydroxy-benzaldehyde (43), (24R)-24-ethyl-5alpha-cholestane-3beta,5,6beta-triol(44), beta-sitosterol(45), daucosterol(46), 2,6-dimethoxy-I,4-benzoquinone(47), 2,6-dimethoxy-pyran-4-one(48), 1-(beta-D-ribofuranosyl)uracil(49), and mannitol(50). Compouds 1-7,12,18,28-37,44 and 48 were obtained from the genus Fraxinus for the first time.

Quantitative LC-MS/MS analysis of seven ginsenosides and three aconitum alkaloids in Shen-Fu decoction.

BACKGROUND: Shen-Fu decoction is a traditional Chinese medicine prescription with a 3:2 ratio of Radix Ginseng and Fuzi (Radix Aconiti lateralis praeparata). Ginsenosides and alkaloids are considered to be the main active components of Shen-Fu decoction. However, no analytical methods have been used to quantitatively analyse both components in Shen-Fu decoction simultaneously. RESULTS: We successfully developed a rapid resolution liquid chromatography coupled with tandem mass spectrometry (RRLC-MS/MS) method for the simultaneous analysis of seven ginsenosides and three aconitum alkaloids in Shen-Fu decoction, the decoction of Radix ginseng and Fuzi (Radix Aconiti lateralis praeparata). Chromatogrpahic separation by RPLC was achieved using a reversed-phase column and a water/acetonitrile mobile phase, containing 0.05% formic acid and using a gradient system. The method was optimized to allow for simultaneous analysis of all analytes in 11minutes without the need for baseline resolution of the components. Furthermore, the separation demonstrated good linearity (r > 0.9882), repeatability (RSD < 7.01%), intra- and inter-day precisions (RSD < 5.06%) and high yields of recovery (91.13-111.97%) for ten major constituents, namely ginsenoside-Re, Rg1, Rb1, Rc, Rb2, Rd, Rf, aconitine, hypacoitine and mesaconitine. CONCLUSIONS: The developed method could be used as a rapid and reliable approach for assessment of the quantity of the major constituents in Shen-Fu decoction.

Dammarane glycosides from the root of Machilus yaoshansis.

Nine new dammarane triterpene glycosides (1-3 and 8-13) and 12 known analogues have been isolated from an ethanol extract of the roots of Machilus yaoshansis. Compounds 1-7 have an uncommon 20,23-dihydroxydammar-24-en-21-oic acid-21,23-lactone moiety that was previously reported in compounds isolated from Gynostemma pentaphyllum. The configurations of the lactone moieties in 1-3 were determined by comparison of the experimental ECD spectra of 1-3 and the hydrolysates, 1a and 1b, with the corresponding calculated ECD spectra. On the basis of NMR and ECD data analysis of 1-7, the previously reported C-20 and C-23 configurations of 4-7 and related derivatives from Gynostemma pentaphyllum were revised. In addition, the application of NMR data and Cotton effects to the determination of the relative and absolute configurations of the γ-lactone moiety in 3ß,20,23-trihydroxydammar-24-en-21-oic acid-21,23-lactone derivatives is discussed.

[Chemical constituents from roots of Machilus yaoshansis].

To study chemical constituents contained in ethanol extracts from roots of Machilus yaoshansis. Fifteen compounds were separated from the roots of M. yaoshansis by using various chromatographic techniques. Their structures were identified on the basis of their physicochemical properties and spectral data as twelve lignans(+)-guaiacin (1), kadsuralignan C (2), (+)-isolariciresinol (3), 5'-methoxy-(+)-isolariciresinol (4), (7'S, 8R, 8'R)-lyoniresinol (5), meso-secoisolariciresinol (6), isolariciresinol-9'-O-beta-D-xylopyranoside (7), 5'-methoxy-isolariciresinol-9'-O-beta-D-xylopyranoside (8), lyoniresinol-9'-O-beta-D-xylopyranoside (9), (2R, 3R) -2, 3-dihydro-2-(4-hydroxy-3-methoxyphenyl)-7-methoxy-3-methyl-5-(E)-propenylbenzofuran (10), 3, 5'-dimethoxy-4', 7-epoxy-8, 3'-neolignan-4, 9, 9'-triol (11), nectandrin B (12), and three flavanes(+)-catechin (13), (-)-epicatechin (14), and bis-8, 8'-catechinylmethane (15). All of the compounds 1-15 were separated from M. yaoshansis for the first time.

Butanolide derivatives from the bark of Machilus yaoshansis.

Six new butanolide derivatives with long aliphatic side chains (1-6), together with 23 known lipophilic constituents, were isolated from the bark of Machilus yaoshansis. Their structures were elucidated by spectroscopic and chemical methods. All the isolates were evaluated for cytotoxic and anti-inflammatory activities.

Methoxylated fatty acids from the bark of Fraxinus sieboldiana.

Nine new fatty acid derivatives, including seven methoxylated (1, 2, and 4-8) and two hydroxylated (3 and 9) fatty acids, have been isolated from the ethanol extract of the stem bark of Fraxinus sieboldiana. Their structures were determined by spectroscopic methods including IR, MS, 1D, and 2D NMR experiments. The 3- or 9-methoxylated fatty acids are reported for the first time in nature.

Cucurbitane glucosides from the root of Machilus yaoshansis.

Seven new cucurbitane triterpene glucosides (1-5, 8, and 9) and five known analogues (6, 7, 10, cucurbitacin I 2-O-ß-d-glucopyranoside, and khekadaengoside K) have been isolated from an ethanol extract of roots of Machilus yaoshansis. Compounds 1 and 2 have an unusual 16,23:22,25-diepoxy unit, 4 is an uncommon cucurbitane 25-carbamate with the carbamoyl amino group attached at C-24 to form an oxazolidinone ring in the side chain, and 8 is the first example of a trinorcucurbitane derivative. The configurations in several pairs of C-24 epimeric cucurbitacins with 24,25-dihydroxy-22-one side chains were assigned, and the validity of J(23a,24) and J(23b,24) values to differentiate the configuration at C-24 in these cucurbitane derivatives is discussed. Compounds 2-4 showed in vitro activity against protein tyrosine phosphatase 1B with IC50 values of 8.63, 2.81, and 4.26 µM, respectively. Cucurbitacin E 2-O-ß-d-glucopyranoside (10) showed selective cytotoxicity against BGC-823 and A549 cancer cells with IC50 values of 4.98 and 3.20 µM, respectively.

[Phenolic and phenylethanoidal glycosides from branch of Fraxinus sieboldiana].

OBJECTIVE: To investigate chemical constituents from an ethanolic extract of the branch of Fraxinus sieboldiana (Oleaceaue) METHOD: The constituents were isolated and purified by a combination of various chromatographic techniques including silica gel, macroporous adsorbent resin, Sephadex LH-20, and preparative HPLC. Structures of the isolates were elucidated by spectroscopic methods including 1D and 2D NMR and MS techniques. RESULT: Four phenolic and twelve phenylethanoidal glycosides were obtained and their structures were identified as 2,6-dimethoxy-p-hydroquinone-4-O-beta-D-glucopyranoside (1), 2,6-dimethoxy-p-hydroquinone-1-O-beta-D-glucopyranoside (2), 4-hydroxy-3-methoxyphenyl beta-D-glucopyranoside (3), 4-hydroxy-3-methoxyphenyl beta-D-xylopyranosyl (1-->6)-O-beta-D-glucopyranoside (4), osmanthuside H (5), 2-(4-hydroxyphenyl) ethyl beta-D-glucopyranoside (6), 2-(3, 4-dihydroxyphenyl) ethyl beta-D-glucopyranoside (7), 2-hydroxy-4-(2-hydroxyethyl)-phenyl beta-D-glucopyranoside (8), 4-(2-hydroxyethyl)-2-methoxyphenyl beta-D-glucopyranoside (9), calceolarioside B (10), calceolarioside A (11), ferruginoside A (12), isolugrandoside (13), acteoside (14), chiritotoside C (15), and plantasisoside (16). CONCLUSION: Compounds 1-4,9,12, 13 and 16 were obtained from the genus Fraxinus for the first time.

[Coumarins from branch of Fraxinus sieboldiana and their antioxidative activity].

OBJECTIVE: To investigate the chemical constituents from the branch of Fraxinus sieboldiana, and evaluate their antioxidative activity. METHOD: The chemical constituents were isolated and purified by chromatographic techniques over silica gel, macroporous adsorbent resin, Sephadex LH-20, and preparative HPLC. Structures of the compounds were identified by spectroscopic methods. The antioxidant activity was evaluated by Fe(+2)-cystine induced rat liver microsomal lipid peroxidation. RESULT: Eight coumarins were obtained and their structures were elucidated as esculin (1) , esculetin (2), fraxin (3), fraxetin (4), 6, 7-di-O-beta-D-glucopyranosylesculetin (5), scopoletin (6), cleomiscosin D (7) and cleomiscosin B (8). At a concentration of 10(-6) mol x L(-1), compound 4 showed antioxidative activity inhibiting Fe(+2)-cystine induced rat liver microsomal lipid peroxidation with inhibitory rate of 60%. CONCLUSION: Compounds 5, 7 and 8 were obtained from the genus Fraxinus for the first time. Compound 4 showed remarkable antioxidative activity, which was higher than that of VE (35%).

Glycosidic constituents of the tubers of Gymnadenia conopsea.

Ten minor new glycosidic constituents (1- 10), together with 10 known compounds, have been isolated from a neuroprotective fraction of an ethanolic extract of the tubers of Gymnadenia conopsea. The structures of 1-10 were determined using spectroscopic and chemical methods. The compounds isolated were evaluated for activity in in vitro assays for acetylcholine esterase and monoamine oxidase inhibitory activities.

Pyridinium alkaloid-coupled secoiridoids from the flower buds of Lonicera japonica.

Three pyridinium inner salt alkaloids, lonijaposides A-C (1-3), based on an unprecedented skeleton of an N-substituted nicotinic acid nucleus coupled through C-5 with C-7 of a secoiridoid, together with seven known iridoids, have been isolated from the flower buds of Lonicera japonica. Their structures were elucidated by spectroscopic and chemical analyses. Lonijaposide C (3) showed activity against the release of glucuronidase in rat polymorphonuclear leukocytes induced by the platelet-activating factor.

Glycosides from the root of Iodes cirrhosa.

Seven new neolignan glycosides ( 1- 7), two arylglycerol glycosides ( 8, 9), and 18 known glycosides have been isolated from an ethanolic extract of the root of Iodes cirrhosa. Their structures including absolute configurations were determined by spectroscopic and chemical methods. Based on analysis of the NMR data of threo and erythro 8-4'-oxyneolignans and arylglycerols in different solvents, the validity of J 7,8 and Deltadelta C8-C7 values to distinguish threo and erythro derivatives was discussed. In the in vitro assays, compound 4 and liriodendrin ( 17) both showed activity against glutamate-induced PC12 cell damage at 10 (-5) M.

Glycosides from the bark of Adina polycephala.

Four new dimeric phenolic glycosides (1- 4), a new iridoid diglycoside (5), and 15 known glycosides have been isolated from an ethanolic extract of the bark of Adina polycephala. Their structures were determined by spectroscopic and chemical methods. Compounds 1, 3, and 5 showed in vitro inhibitory activity against the release of beta-glucuronidase in rat polymorphonuclear leukocytes induced by platelet-activating factor.

Glycosides from the stem bark of Fraxinus sieboldiana.

A norditerpene glucopyranoside with a novel carbon skeleton (1), eight new aromatic glycosides (2-9), and 25 known glycosides have been isolated from a H2O-soluble portion of an ethanolic extract of the stem bark of Fraxinus sieboldiana. Their structures were determined by spectroscopic and chemical methods. Based on analysis of the NMR data of threo- and erythro-arylglycerols in different solvents, an application of Delta delta C8-C7 values to distinguish threo-arylglycerol and erythro-arylglycerol isomers was proposed. In the in vitro assays, compound 5 displayed TNF-alpha secretion inhibitory activity with an IC50 value of 1.6 microM, compound 6 showed antioxidative activity inhibiting Fe+2-cystine-induced rat liver microsomal lipid peroxidation with an IC50 value of 0.9 microM, and plantasioside (10) showed selective activity against the human colon cancer cell line (HCT-8) with an IC50 value of 3.4 microM.