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1.
Sci Rep ; 13(1): 14999, 2023 09 11.
Article in English | MEDLINE | ID: mdl-37696922

ABSTRACT

This study differentiates myocardial infarction (MI) and strangulation death (STR) from the perspective of amino acid metabolism. In this study, MI mice model via subcutaneous injection of isoproterenol and STR mice model by neck strangulation were constructed, and were randomly divided into control (CON), STR, mild MI (MMI), and severe MI (SMI) groups. The metabolomics profiles were obtained by liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics. Principal component analysis, partial least squares-discriminant analysis, volcano plots, and heatmap were used for discrepancy metabolomics analysis. Pathway enrichment analysis was performed and the expression of proteins related to metabolomics was detected using immunohistochemical and western blot methods. Differential metabolites and metabolite pathways were screened. In addition, we found the expression of PPM1K was significantly reduced in the MI group, but the expression of p-mTOR and p-S6K1 were significantly increased (all P < 0.05), especially in the SMI group (P < 0.01). The expression of Cyt-C was significantly increased in each group compared with the CON group, especially in the STR group (all P < 0.01), and the expression of AMPKα1 was significantly increased in the STR group (all P < 0.01). Our study for the first time revealed significant differences in amino acid metabolism between STR and MI.


Subject(s)
Metabolomics , Myocardial Infarction , Animals , Mice , Amino Acid Motifs , Blotting, Western , Myocardial Infarction/diagnosis , Amino Acids
2.
Nat Prod Res ; 37(24): 4099-4111, 2023.
Article in English | MEDLINE | ID: mdl-36710469

ABSTRACT

The targeted identification of α-glucosidase inhibitors from the crude ethyl acetate of Lycopodiella cernua (L.) Pic. Serm (L.cernua) was guided by high-resolution inhibition profiling. The α-glucosidase inhibition profiling and HPLC-QTOF-MS showed tannins and serratenes were the corresponding antidiabetic constituents. Two new serratenes named 3ß, 21ß-dihydroxyserra-14-en-24-oic acid-3ß-(4'-methoxy-5'-hydroxybenzoate) (4), 3ß, 21α-dihydroxyserra-14-en-24-oic acid-3ß-(4'-methoxy-5'-hydroxybenzoate) (7), together with two known compounds (5 and 6) were isolated. Their structures were elucidated by HR-ESI-MS and NMR. Compounds 5-7 inhibited the α-glucosidase activity in a non-competitive manner with Ki values ranging from 1.29 to 12.9 µM. The molecular docking result unveiled that 4-7 bound to the residues at the channel site, which enabled to block the substrate access. In addition, the molecular dynamics (MD) simulation of the most active compound 7 and α-glucosidase indicated the 4'-methoxy-5'-hydroxybenzoate group formed the stable hydrogen bonds and pi-pi T-shaped interactions with Arg312, Gln350 and Phe300 residues, while the rings D and E were stabilized by hydrophobic interaction.


Subject(s)
Hypoglycemic Agents , alpha-Glucosidases , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , alpha-Glucosidases/metabolism , Molecular Docking Simulation , Selective Estrogen Receptor Modulators , Plant Extracts/pharmacology , Plant Extracts/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Hydroxybenzoates
3.
Tissue Cell ; 80: 101984, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36434828

ABSTRACT

Determining myocardial infarction (MI) and mechanical asphyxia (MA) was one of the most challenging tasks in forensic practice. The present study aimed to investigate the potential of fatty acid (FAs) metabolism, and lipid alterations in determining MI and MA. MA and MI mouse models were constructed, and metabolic profiles were obtained by LC-MS-based untargeted metabolomics. The metabolic alterations were explored using the PCA, OPLS-DA, the Wilcoxon test, and fold change analysis. The contents of lipid droplets (LDs) were detected by the transmission scanning electron microscope and Oil red O staining. The immunohistochemical assay was performed to detect CD36 and dysferlin. The ceramide was assessed by LC-MS. PCA showed considerable differences in the metabolite profiles, and the well-fitting OPLS-DA model was developed to screen differential metabolites. Thereinto, 9 metabolites in the MA were reduced, while metabolites were up- and down-regulated in MI. The increased CD36 suggested that MI and MA could enhance the intake of FAs and disturb energy metabolism. The increased LDs, decreased dysferlin, and increased ceramide (C18:0, C22:0, and C24:0) were observed in MI groups, confirming the lipid deposition. The present study indicated significant differences in myocardial FAs metabolism and lipid alterations between MI and MA, suggesting that FAs metabolism and related proteins, certain ceramide may harbor the potential as biomarkers for discrimination of MI and MA.


Subject(s)
Asphyxia , Ceramides , Fatty Acids , Myocardial Infarction , Animals , Mice , Asphyxia/complications , Biomarkers/metabolism , Ceramides/metabolism , Dysferlin , Fatty Acids/metabolism , Myocardial Infarction/diagnosis , Pilot Projects
4.
Phytochemistry ; 195: 113056, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34953266

ABSTRACT

Phytochemical investigation of Lycopodium cernuum L. afforded seven undescribed serratene triterpenoids named 3ß, 21ß-dihydroxyserra-14-en-24-oic acid-3ß-(5'-hydroxybenzoate) (1), 3ß, 21ß, 24-trihydroxyserrat-14-en-3ß-(5'-hydroxyl benzoate) (2), 3ß, 14α, 15α, 21ß-tetrahydroxyserratane-24-methyl ester (3), 3ß, 14α, 21ß-trihydroxyserratane-15α-(4'-methoxy-5'-hydroxybenzoate)-24-methyl ester (4), 3ß, 14α, 21ß-trihydroxyserratane-15α-(4'-methoxy-5'-hydroxybenzoate) (5), 3ß-hydroxy-21ß-acetate-16-oxoserrat-14-en-24-oic acid (6), 3ß, 21ß-dihydroxy-16α, 29-epoxyserrat-14-en-24-methyl ester (7), together with eleven known compounds (8-18), whose chemical structures were elucidated through spectroscopic analysis of HRESIMS, 1D NMR, 2D NMR and comparison between the literature. All compounds were evaluated for their α-glucosidase inhibitory activity for the first time. The results showed that compounds 1, 2, 4, 5, 6, 10, 13, 15, and 16 were among the most potent α-glucosidase inhibitors, with IC50 values ranging from 23.22 ± 0.64 to 50.65 ± 0.82 µM. Structure-activity relationship (SAR) studies indicated that the combined properties of the 5-hydroxybenzoate moiety at C-3, ß-OH at C-21, COOH- at C-24, and Δ14,15 groups enabled an increase in the α-glucosidase inhibitory effect. In addition, molecular docking studies showed that the potential inhibitors mainly interact with key amino acid residues in the active site of α-glucosidase through hydrogen bonds and hydrophobic forces.


Subject(s)
Lycopodium , Triterpenes , Glycoside Hydrolase Inhibitors/pharmacology , Imidazoles , Molecular Docking Simulation , Molecular Structure , Structure-Activity Relationship , Sulfonamides , Thiophenes , Triterpenes/pharmacology
5.
Fitoterapia ; 84: 54-7, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23103953

ABSTRACT

An alkaloid with novel skeleton, sinoscrewtine (1), has been isolated from the roots of Sinomenium acutum. Its structure was established by spectral analysis and X-ray crystallographic study, and its possible biosynthetic pathway was delivered. In vitro experiments, 1 showed weak injurious effects against H(2)O(2)/Aß(25-35) induced oxidative injury in PC-12 cells and DPPH radical scavenging activity with IC(50) of 32.6µM.


Subject(s)
Alkaloids/chemistry , Alkaloids/pharmacology , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacology , Plant Roots/chemistry , Sinomenium/chemistry , Animals , Models, Molecular , Molecular Structure , PC12 Cells , Rats
6.
Fitoterapia ; 82(6): 793-7, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21596111

ABSTRACT

Four new fluorenone alkaloids, caulophylline A-D (1-4), and one new dihydroazafluoranthene alkaloid, caulophylline E (5) were isolated from the roots of Caulophyllum robustum Maxim. Their structures were elucidated by spectroscopic analysis. Among the isolated alkaloids, Caulophylline E showed good scavenging effects against DPPH radical with IC(50) of 39 µM.


Subject(s)
Alkaloids/isolation & purification , Caulophyllum/chemistry , Fluorenes/chemistry , Fluorenes/isolation & purification , Alkaloids/chemistry , Alkaloids/pharmacology , Biphenyl Compounds/antagonists & inhibitors , Dibenzazepines/chemistry , Dibenzazepines/isolation & purification , Dibenzazepines/pharmacology , Fluorenes/pharmacology , Inhibitory Concentration 50 , Medicine, Chinese Traditional , Molecular Structure , Picrates/antagonists & inhibitors , Plant Roots/chemistry
7.
J Asian Nat Prod Res ; 13(6): 523-8, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21623515

ABSTRACT

Two new morphinane alkaloids, 1-hydroxy-10-oxo-sinomenine (1) and 4,5-epoxy-14-hydroxy sinomenine N-oxide (2), have been isolated from the stems of Sinomenium acutum. Their structures were established by various spectral analyses, especially 2D NMR experiments. The structure of 2 was confirmed by single crystal X-ray diffraction. The absolute configurations of 1 and 2 were deduced by comparison of CD spectra with the known alkaloid sinomenine (3). Compound 1 was tested for DPPH inhibition and gave IC(50) of 27.9 µM. Compound 2 was tested for neuroprotective effect and showed significant activity against ß-amyloid(25-35)-induced oxidative injury (*P < 0.05) at 10 µM in PC-12 cells.


Subject(s)
Alkaloids/isolation & purification , Cyclic N-Oxides/isolation & purification , Drugs, Chinese Herbal/isolation & purification , Morphinans/isolation & purification , Neuroprotective Agents/isolation & purification , Alkaloids/chemistry , Alkaloids/pharmacology , Animals , Biphenyl Compounds/pharmacokinetics , Cyclic N-Oxides/chemistry , Cyclic N-Oxides/pharmacology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Molecular Structure , Morphinans/chemistry , Morphinans/pharmacology , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacology , Nuclear Magnetic Resonance, Biomolecular , PC12 Cells , Picrates/pharmacokinetics , Plant Stems/chemistry , Rats , Sinomenium/chemistry , X-Ray Diffraction
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