A new pyrazine from Hypecoum erectum L / 药学学报

Four pyrazines were isolated from the n-butanol fraction of Hypecoum erectum L. by using various chromatographic methods, including MCI gel, ODS, silica gel and semi-preparative HPLC. The structures of the isolated compounds were identified as hyperectpyrazin A (1), 1′S-(6-methylpyrazin-2-yl)-ethane-1′,2′-diol (2), 2-hydroxymethyl-6-methylpyrazin (3) and pyrazine-2-carboxylic acid (4) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, MS, etc.). The absolute configuration of compound 2 was determined by using the Mo2(OAc)4 induced CD analysis for the first time. Compound 1 was a new compound, compounds 2-4 were isolated from H. erectum for the first time. Compounds 1-4 were evaluated for their inhibition against acetylcholinesterase and nitric oxide generation induced by lipopolysaccharide-RAW264.7 macrophage cells. At a concentration of 50 μmol·L-1, compounds 2 and 4 displayed inhibitory effects on acetylcholinesterase with the inhibition rates of 44.40% and 43.99%, respectively.

A new flavonoid glycoside from Epimedium sagittatum / 药学学报

Fourteen flavonoids were isolated and purified from Epimedium sagittatum by various chromatography techniques such as macroporous adsorbent resin, silica gel, ODS, Sephadex LH-20, HW-40C and semi-preparative HPLC. Their structures were identified by analysis of physicochemical properties and spectral data, and determined as 3′-hydroxy-baohuoside-Ⅱ (1), huazhongilexone-7-O-β-D-glucopyranoside (2), kaempferol-3-O-α-L-rhamnoside (3), baohuoside-Ⅱ (4), icariside-Ⅱ (5), kaempferol 3,7-di-O-α-L-rhamnopyranoside (6), (+)-aromadendrin (7), kaempferol 3-O-(2-O-β-D-apiofuranosyl)-α-L-rhamnopyranoside (8), sagittatoside A (9), 2″-O-rhamnosyl icariside-II (10), apigenin-7-O-β-D-glucoside (11), quercetin 3-O-β-D-apiofuranoyl-(1→2)-α-L-rhamnopyranoside (12), kaempferol (13), icariin (14). Among them, compound 1 is a new compound, while compounds 2, 6-8, 11, and 12 were isolated from E.sagittatum for the first time.

Alkaloids from fruit of Lycium chinense var. potaninii / 中国中药杂志

Ten alkaloids(1-10) were isolated from the ethyl acetate extract of the fruit of Lycium chinense var. potaninii by silica gel, ODS, and preparative high performance liquid chromatography(HPLC), and identified by NMR and MS as methyl(2S)-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(1), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(2), 3-hydroxy-4-ethyl ketone pyridine(3), indolyl-3-carbaldehyde(4),(R)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde(5),(R)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-car-baldehyde(6), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(4-hydroxyphenyl)propanoate(7), dimethyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanedioate(8), 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoate(9), 4-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid(10). All the compounds were isolated from the plant for the first time. Among them, compounds 1-3 were new compounds. Compounds 1-9 were evaluated for hypoglycemic activity in vitro with the palmitic acid-induced insulin resistance in HepG2 cells. At 10 μmol·L~(-1), compounds 4, 6, 7, and 9 can promote the glucose consumption of HepG2 cells with insulin resistance.

Isolation and identification of two new compounds from Semen Persicae / 药学学报

Five compounds were isolated from the ethyl acetate fraction of Semen Persicae by using various chromatographic methods, including ODS, Sephadex LH-20, HPLC and semipreparative HPLC. Their structures were identified by 1D-NMR, 2D-NMR, HR-ESI-MS, UV, IR, circular dichroism (CD) and ECD calculation techniques: (2R,3R)-5,7,4′-trihydroxy-3′-methoxy-3-formylflavan-3-ol-5-O-β-D-glucopyranoside (1), (7R,8S)-dihydrodehydrodiconiferyl 6″-benzoyl alcohol-9-O-β-D-glucopyranoside (2), (7R,8S)-dihydrodehydrodiconiferyl alcohol-9-β-O-D-glucopyranosid (3), 2-methoxy-4-(2-propenyl)-phenyl-O-β-D-glucopyranoside (4), 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-propane-1,3-diol (5). Compound 1 and 2 are new compounds, and compounds 3-5 were obtained from Prunus davidiana (Carr.) Franch. for the first time.

Two new terpene glycosides from the Alpiniae Oxyphyllae Fructus / 药学学报

Two undescribed terpene glycosides and two compounds were isolated from the n-butanol fraction of Alpiniae Oxyphyllae Fructus by using various chromatographic methods, including MCI Gel, Sephadex LH-20, ODS, silica gel and semi-preparative HPLC. The structures of the isolated compounds were identified by spectroscopy methods (1D, 2D NMR, UV, IR, MS, etc.), and the absolute configuration of the compound 1 was determined by ECD calculation and acid hydrolysis. Compounds 1 and 2 are new compound, and compounds 3 and 4 were isolated from Alpiniae Oxyphyllae Fructus for the first time.

Chemical constituents from fruits of Cornus officinalis and their anti-Alzheimer's disease activity / 药学学报

Fifteen compounds were isolated from fruits of Cornus officinalis by various chromatographic techniques such as Toyopearl HW-40C, Sephadex LH-20, silica gel, and the semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as neolignan A (1), caffeic acid (2), trans-p-hydroxy cinnamic acid (3), esculetin (4), scopoletin (5), benzyl-7-O-β-D-glucopyranoside (6), tachioside (7), 6-O-(4-hydroxybenzoyl) arbutin (8), 2-(3′,4′-dihydroxyphenyl)-1,3-benzodioxole-5-carboxaldehyde (9), (-)-pinoresinol-4-O-β-D-glucopyranoside (10), (7S,8R)-dihydrodehydrodiconiferyl alcohol-9-O-β-D-glucopyranoside (11), (7S,8R)-dihydrodehydrodiconiferyl alcohol-9′-O-β-D-glucopyranoside (12), (+)-lyoniresinol (13), (+)-isolariciresinol-9-O-β-D-glucopyranoside (14), and isolariciresinol-9′-O-β-D-glucopyranoside (15). Compound 1 was a new compound and named as neolignan A, and compounds 6-9 and 14 were isolated from Cornus officinalis for the first time. Compounds 2, 3 and 15 efficiently alleviated the PC12 cells injury induced by Aβ25-35, suggesting their potential anti-Alzheimer's disease activity.

A new diterpenoid acid from the rosin of Pinus kesiya var. langbianensis (A.Chev.) Gaussen ex Bui / 药学学报

One undescribed diterpenoid acid and six compounds were isolated from the 95% ethanol fraction of Pinus kesiya var. langbianensis (A.Chev.) Gaussen ex Bui resin by using various chromatographic methods, including MCI Gel, Sephadex LH-20, ODS, silica gel and semi-preparative HPLC. The planar structures were identified by spectroscopy methods (1D, 2D NMR, UV, IR, MS, etc.), and the absolute configuration of the new compound was determined by ECD calculation. Compound 1 is a new compound, and compounds 2, 5-7 were isolated from Pinus kesiya var. langbianensis (A.Chev.) Gaussen ex Bui for the first time.

Effects of Tingli Dazao Xiefei Decoction on the immune inflammation and intestinal flora in asthmatic rats / 药学学报

The study aims to explore the intervention mechanism of Tingli Dazao Xiefei Decoction on asthma from the perspective of immune inflammation and intestinal flora, providing a theoretical basis for guiding clinical medication. The ovalbumin (OVA) asthmatic rat model was established by intraperitoneal injection of OVA sensitization solution and aerosol challenge, and divided into control (CON), model (M), dexamethasone group (DEX, 0.075 mg·kg-1) and Tingli Dazao Xiefei Decoction (TLDZ, 3.5 g·kg-1). Firstly, the effects of Tingli Dazao Xiefei Decoction on asthma symptoms of rats, lung and trachea pathological changes of asthmatic rats were observed by inducing cough and asthma experiment, phenol red excretion, hematoxylin-eosin staining (H&E), Masson and periodic acid Schiff (PAS) staining; the levels of transforming growth factor β1 (TGF-β1), interleukin (IL) 6 and IL-10 in rat serum and the levels of interferon γ (IFN-γ), immunoglobulin E (IgE), IL-4, IL-17A and tumor necrosis factor α (TNF-α) in bronchoalveolar lavage fluid (BALF) were detected by ELISA; the mRNA levels of IL-5, IL-13 and IL-33 in the lung were determined by qRT-PCR; the levels of macrophages and neutrophils in the spleen and the levels of natural killer cell (NK), helper T cell (Thc), dendritic cell (DC), regulatory T cell (Treg) and T helper cell 17 (Th17) in the peripheral blood were measured by flow cytometry combined with immunohistochemistry; the intestinal flora of asthmatic rats were analyzed by 16S rDNA high-throughput sequencing. Pathology and inflammatory results showed that Tingli Dazao Xiefei Decoction could effectively alleviate the asthma symptoms in rats, improve the pathological changes of lung tissue, reduce the production of goblet cells and collagen fibers, and reduce the inflammatory response in asthmatic rats; the results of immune cells showed that Tingli Dazao Xiefei Decoction could effectively increase the levels of NK, Thc, DC and Treg cells and reduce the levels of macrophages, neutrophils and Th17 cells in asthmatic rats; the results of intestinal flora showed that Tingli Dazao Xiefei Decoction could increase the levels of Lactobacillus, Ruminococcus, Christensenellaceae, Bifidobacterium and Eubacterium]_xylanophilum-group, and decrease the levels of Firmicutes, Desulfovibrio, Mucispirillum and Romboutsia in asthmatic rats. Therefore, it is speculated that Tingli Dazao Xiefei Decoction can improve the symptom of asthmatic rats by regulating the immune inflammation and intestinal flora in the asthmatic rats. All animal experiments in this article were approved by the Ethics Committee of Henan University of Chinese Medicine.

Active components of Descurainia sophia improve lung permeability in rats with allergic asthma by regulating airway inflammation and epithelial damage / 中国中药杂志

The present study investigated the effect of active components of Descurainia sophia on allergic asthma and explored the underlying mechanism. SD male rats were randomly divided into a normal group(NC), a model group(M), a D. sophia decoction group(DS), a D. sophia fatty oil group(FO), a D. sophia flavonoid glycoside group(FG), a D. sophia oligosaccharide group(Oli), and a positive drug dexamethasone group(Y). The allergic asthma model was induced in rats by intraperitoneal injection of ovalbumin(OVA) and aluminum hydroxide gel adjuvant(sensitization) and atomization of OVA solution(excitation). After modeling, asthma-related indicators, tracheal phenol red excretion, inflammatory cell levels in the peripheral blood, lung permeability index(LPI), and oxygenation index(OI) of rats were detected. The pathological changes of lung tissues were observed by HE staining. Enzyme-linked immunosorbent assay(ELISA) was used to detect the content of inflammatory factors immunoglobulin E(IgE), interleukin-4(IL-4), and interferon-γ(IFN-γ) in the bronchoalveolar lavage fluid(BALF) and the content of endothelin-1(ET-1) and angiotensin-converting enzyme(ACE) in lung tissue homogenate. The serum content of nitric oxide(NO) was detected by colorimetry. Western blot was employed to determine the protein expression of Toll-like receptor 4(TLR4), nuclear factor κB-p65(NF-κB-p65), phosphorylated NF-κB-p65(p-NF-κB-p65), myosin light chain kinase(MLCK), vascular endothelial cadherin(VE cadherin), connexin 43, and claudin 5, and the mechanism of active components of D. sophia on allergic asthma was explored. As revealed by the results, the M group showed extensive infiltration of inflammatory cells around the bronchus of the lung tissues of the allergic asthma rats, thickened bronchial wall, severely deformed alveolar structure, increased number of wheezes, the content of IgE, IL-4, ET-1, and ACE, inflammatory cells, and LPI, and reduced latency of asthma, tracheal phenol red excretion, IFN-γ, NO content, and OI. After the intervention of the active components of D. sophia, the DS, FO, FG, Oli, and Y groups showed improved asthma-related indicators, tracheal phenol red excretion, and lung tissue lesions in allergic asthma rats, and the effects in the FO and Oli groups were superior. The content of inflammatory factors in BALF was recovered in the DS, FO, and Y groups and the FG and Oli groups. The number of inflammatory cells in rats was reduced in the DS and FO groups, and the FG, Oli, and Y groups to varying degrees, and the effect in the FO group was superior. DS, FO, Oli, and Y reduced ET-1, ACE, and LPI and increased NO and OI. FG recovered NO, ET-1, ACE, LPI, and OI to improve lung epithelial damage and permeability. Further investigation of inflammation-related TLR4/NF-κB pathways, MLCK, and related skeleton protein levels showed that TLR4, NF-κB-p65, p-NF-κB-p65, and MLCK levels were increased, and VE cadherin, connexin 43, and claudin 5 were reduced in the M group. DS, FO, FG, Oli, and Y could reduce the protein expression related to the TLR4 pathway to varying degrees, and regulate the protein expression of MLCK, VE cadherin, connexin 43, and claudin 5. It is inferred that the active components of D. sophia improve lung permeability in rats with allergic asthma presumedly by regulating the TLR4/NF-κB signaling pathway to improve airway inflammation, mediating MLCK and connexin, and regulating epithelial damage.

A new nucleoside from the Oenothera biennis L / 药学学报

Seven nucleoside compounds were isolated from the Oenothera biennis L. by various chromatographic techniques such as Diaion HP-20, silica gel, Sephadex LH-20, MCI and semi-preparative HPLC. Their structures were identified by analysis of physicochemical properties and spectral data, and determined as 9-(3′-carbonyl methyl)hydroxypurine (1), 1-(3′-carbonyl methyl)purine-6,8-dione (2), N-methyl-2-pyridone-5-carboxamide (3), uracil (4), uridine (5), thymidine (6) and 2′-Ο-methoxy luridine (7). Compound 1 is a new nucleoside and compounds 2-7 were newly isolated from the Oenothera biennis L. Compounds 1-2 can significantly increase the viability of BEAS-2B cells induced by TGF-β1, showing potent anti-pulmonary fibrosis activity.

A new diarylheptane dimer from Zingiber officinale peel / 药学学报

Three diarylheptanoids were isolated from the n-butanol fraction of Zingiber officinale peel by MCI Gel CHP-20, Sephadex LH-20, ODS and semipreparative high performance liquid chromatography. Their structures were identified by MS and NMR spectroscopy techniques: (2S,2'S,3R,3'R,4R,4'R,6R,6'R)-6,6'-bis((S)-1-hydroxy-2-(4-hydroxyphenyl)ethyl)-2,2'-bis(4-hydroxy-3-methoxyphenyl)octahydro-2H,2'H-[3,3'-bipyran]-4,4'-diol (1), (E)-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)hept-4-en-3-one (2), and alpinin B (3). Compound 1 is a new compound, and compounds 2-3 were obtained from Zingiber officinale peel for the first time.

A new polyacetylene from the stems and leaves of Chrysanthemum morifolium Ramat / 药学学报

Eight polyacetylenes were isolated from the extract of the stems and leaves of Chrysanthemum morifolium by various chromatographic methods. Their structures were determined as 2E,4E,12Z-tetradecatriene-1-pyrrolidine-1-oxo-8,10-diynoic (1), tetradeca-2E,4E,12E-trien-8,10-diynoic acid pyrrolidide (2), tetradeca-2E,4E-dien-8,10-diynoic acid pyrrolidide (3), tetradeca-2E,4E,10Z-trien-8-ynoic acid pyrrolidide (4), 2E,4E,12E-tetradecatriene-8,10-diynoic acid isobutylamide (5), 2E,4E-undecyldiene-8,10-diynoic acid isobutylamide (6), 2E,4E,10E-N-isobutyl-2,4,10-tetradecatrien-8-ynoic acid amide (7), and undeca-2E,4E-diene-8,10-diynoic acid phenylethylamide (8) by spectroscopic methods, including UV, IR, ESI-MS, HR-ESI-MS, 1D and 2D NMR spectra. Among them, compound 1 is a new polyacetylene, and compounds 2-8 were isolated from this plant for the first time. Compounds 5-8 inhibited the proliferation of A549 cell significantly at certain concentration, showing potent antitumor activity.

A new monoterpene ester from Zingiberis Rhizoma Recens / 中国中药杂志

Five monoterpenoid compounds(1-5) were isolated and purified from the acetone fraction of the aqueous extract of Zingiberis Rhizoma Recens by MCI, Sephadex LH-20, silica gel, semi-preparative HPLC, and TLC. Their structures were identified with multiple spectroscopical methods including 1 D-NMR, 2 D-NMR, and MS. The five compounds were identified as(2E,6Z)-8-hydroxy-2,6-dimethylocta-2,6-dien-1-yl-(E)-3-(4-hydroxy-3-methoxyphenyl) acrylate(1),(2E,6E)-8-hydroxy-3,7-dimethylocta-2,6-die-noic acid(2),(E)-1,8-dihydroxy-3,7-dimethyl-2-octenoic acid(3), linalyl-β-D-glucopyranoside(4), and β-D-glucopyranoside-(2E)-3,7-dimethyl-2,6-octadien-1-yl(5), respectively.Compound 1 was a new monoterpene ester, and compounds 4-5 were isolated from this plant for the first time.

A new lignan from Gleditsiae spina / 药学学报

The chemical constituents from ethyl acetate extract of Gleditsiae spina were isolated and purified by various chromatographic methods such as MCI gel CHP-20, ODS, Sephadex LH-20, silica gel and semi-preparative HPLC. Seven lignans were isolated and identified by spectroscopic data analyses as (7R,8S,7'E,7''S,8''R)-buddlenol P (1), (+)-syringaresinol (2), (+)-isolariciresinol (3), (7S,8R)-cedrusin (4), (7S,8R)-4,9,9'-trihydroxy-3,3'-dimethoxy-7,8-dihydrobenzofuran-1'-propylneolignan (5), 3',4-O-dimethylcedrusin (6), balanophonin (7). Among them, compound 1 is a new lignan, compounds 2-7 are isolated from the Gleditsia L. for the first time. MTT method was used to investigate the effect of compounds 2-7 on LPS-induced injury of NRK-52e cells. As a result, compounds 2, 3 and 7 exhibit protective effects against LPS-induced damage to NRK-52e cells.

Five new gingerol compounds from Zingiberis Rhizoma / 药学学报

We separated and purified five chemical constituents of dried ginger by Diaion HP-20, Sephadex LH-20, silica gel and semi-preparative high performance liquid chromatography. Five gingerols were identified by physicochemical properties and MS and NMR spectroscopy techniques: 4-(2-butyl-6-methyl-4H-pyran-4-yl)-2-methoxyphenol (1), 4-(2-hexyl-6-methyl-4H-pyran-4-yl)-2-methoxyphenol (2), 1-(4-hydroxy-3-methoxyphenyl)tridecane-3,5-diol (3), [10]-gingerdiol (4) and 1-[1-(4-hydroxy-3-methoxy phenyl)-3-oxodecan-5-yl]pyrrolidin-2-one (5a, 5b). Compounds 1-3, 5a, 5b are new compounds.

A new alkaloid from Rehmanniae Radix Preparata / 药学学报

The chemical constituents of Rehmanniae Radix Preparatawere prepared according to the traditional method of "jiu zheng jiu shai" and investigated using multiple chromatographic methods. Six alkaloids were isolated and their structures were elucidated from spectral data and physicochemical properties, as follows: rehmanniae alkaloid A (4-{[(5-O-á-D-galactopyranosyloxy)methyl]-1H-pyrrole-2-carbaldehyde-1-yl}butyric acidmethyl ester) (1), baimantuoluoamide B (2), capparisine C (3), harman-3-carboxylic acid (4), (2S)-1-[2-(furan-2-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carboxylate (5), and 1-[2-(furan-2-yl)-2-oxoethyl]pyrrolidin-2-one (6). Among them, compound 1 is a new alkaloid. Compounds 2-6 were newly isolated from Rehmannia glutinosa Libosch.The effect of compounds 1-6 on NRK-52e cell injury induced by LPS was investigated. The results show that compounds 1-3 exhibit protective effects against LPS-induced damage to NRK-52e cells.

Two new monoterpenoids of Zingiber officinale peel / 药学学报

The chemical constituents of Zingiber officinale peel were isolated and purified by various chromatographic separation techniques such as Diaion HP-20, MCI Gel CHP-20, Sephadex LH-20, ODS, silica gel and semi-preparative HPLC. Seven terpenoids were identified by physicochemical properties and spectral data: (4R,6S)-1-(hydroxymethyl)-5,5-dimethylbicyclo[3.1.1]hept-2-en-4-ol (1), 4-(hydroxymethyl)-1-isopropylcyclohex-2-ene-3,4-diol (2), 3,5,6-trihydroxy-7-megastigmen-9-one (3), 3-(3-hydroxybutyl)-2,4,4-trimethyl-2,5-cyclohexadien-1-one (4), angelicoidenol (5), grasshopper ketone (6), and dihydrophaseic acid (7), in which compounds 1, 2 are new compounds, named: (4R,6S)-1-(hydroxymethyl)-5,5-dimethylbicyclo[3.1.1]hept-2-en-4-ol and 4-(hydroxymethyl)-1-isopropylcyclohex-2-ene-3,4-diol, and compounds 3-7 were obtained from this plant for the first time.

Cloning and Expression Analysis of PaAACT Gene from Phytolacca americana / 中国实验方剂学杂志

Objective: To clone the key enzyme gene involved in the biosynthesis of esculentoside A(EsA),acetoacetyl-CoA transferase(AACT) gene was cloned from Phytolacca americana for bioinformatics analysis and prokaryotic expression. Method: Total RNA was extracted from the root of P. americana, and then cDNA was synthesized through the reverse transcription. Based on analysis of the transcriptome data of P. americana, the specific primers of PaAACT gene were designed,and the cDNA sequence of PaAACT gene was amplified by polymerase chain reaction(PCR) method. Prokaryotic induction,expression and purification of the target protein were induced through the construction of the prokaryotic expression vector pET-32a-PaAACT. Result: The open reading frame (ORF) of PaAACT gene was 1 254 bp,and encoded 417 amino acid residues. Bioinformatic analysis showed that the molecular formula of PaAACT protein was C1 914H3 120N538O576S17,inferring that its molecular weight was 43.43 kDa,the theoretical isoelectric point was 8.90,and the instability index of PaAACT protein was 32.27,which was a stable protein. According to bioinformatics analysis,PaAACT protein was a member of the thiolase family and contained one conserved site and one active site of the thiolase family at the C-terminal. PaAACT protein may be located in the cytoplasm,without a signal peptide or transmembrane domain. The phylogenetic analysis indicated that PaAACT protein showed the highest homology with AACT protein from polygonaceae plants (such as Beta vulgaris). The recombinant PaAACT protein was successfully expressed in Escherichia coli BL21(DE3) strain through IPTG induction, and the purified target protein was obtained by Ni2+ affinity chromatography. Conclusion: In this study,the PaAACT gene was cloned from P. americana,which lays a foundation for further determination of enzyme activity assay of PaAACT and preparation of antibody,and provides the theoretical basis for studying its role in the biosynthesis pathway of EsA.

Effect of Nature and Flavor Subdivision of Ephedrae Herba on Rats Model of Harmful Fluid Retention in Upper Jiao / 中国实验方剂学杂志

Objective: To study the effective substance foundation of Ephedrae Herba and explore its mechanism, in order to further enrich the theory of drug resistance of Ephedrae Herba.Method: In this experiment, a compound model was used to establish rat model of Harmful Fluid Retention in upper Jiao. The Rats were randomly divided into model group, captopril group (4.38 mg·kg-1), Ephedrae Herba decoction group(468 mg·kg-1), polysaccharide group (265.36 mg·kg-1), volatile oil group (2.34 mg·kg-1), alkaloid group(40.71 mg·kg-1) and phenolic acid group (210.60 mg·kg-1), and normal group (10 mL·kg-1). The normal group and the model group were given the same volume of normal saline for four weeks. The 24 h urine volume of rats was collected by metabolic cage method. The changes of heart and lung tissue morphology were observed under light microscope. The heart index, lung index, left ventricular ejection fraction(LVEF), left ventricular short axis shortening rate(LVFS) and pulmonary permeability index, number(LPI), lung dry-wet ratio(W/D), creatine kinase isoenzyme(CK-MB), angiotensin Ⅱ(Ang Ⅱ), aldosterone(ALD), cardiac aquaporin 1(AQP1), lung AQP1, aquaporin-3(AQP3) and kidney AQP1, aquaporin-2(AQP2), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) change were detected.Result: Compared with the normal group, heart and lungs of the model group were significantly damaged. The amount of 24 h urine, LVEF, LVFS of model rats were significantly reduced(Pα were significantly increased(PPα were significantly increased (PPα were significantly reduced (PPConclusion: Alkaloid components "Wen" and "Xin" are the effective substance basis of its action. The mechanism may be related to the inhibition of renin angiotensin aldosterone system (RAAS) and the anti-inflammatory effect.

Caffeoyl quinic acids in Chrysanthemum morifolium improve LPS-induced HUVEC vascular endothelial cell injury by regulating ERK/MAPK signaling pathway / 药学学报

To explore the effect of total extract of Chrysanthemum morifolium on lipopolysaccharide (LPS)-induced acute lung injury in mice, we studied the effects of three caffeoyl quinic acids isolated from Chrysanthemum morifolium on vascular endothelial cell injury and their mechanisms of action. All animal experiments were carried out strictly in accordance with the National Animal Welfare Ethics and Protection Regulations. A mouse model of acute lung injury was established by intranasal instillation of LPS. After 6 days of oral administration of chrysanthemum extract, the lung wet weight/dry weight ratio, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were measured in mouse bronchoalveolar lavage fluid. Human umbilical vein endothelial cells (HUVEC) were serum starved for 12 h and treated with 2.5 μg·mL-1 LPS for 24 h to establish the in vitro model of vascular endothelial cell injury. After 24 h of treatment of caffeoyl quinic acids from Chrysanthemum morifolium, the levels of TNF-α, IL-6, IL-1β, vascular cell adhesion molecule-1 (VCAM-1) and endothelin-1 (ET-1) were measured by ELISA in the cell culture supernatant, the malondialdehyde (MDA) level was detected by TBA method, the superoxide dismutase (SOD) level was determined by hydroxylamine method, and the nitric oxide (NO) level was assayed by a one-step method. The levels of p-MEK1/2, MEK1/2, p-ERK1/2, ERK1/2, p-JNK, JNK, p-P38 and P38 of mitogen-activated protein kinase (MAPK) signaling pathway were detected by Western blot. The total extract of Chrysanthemum morifolium can significantly reduce the wet weight/dry weight ratio of lung in mice and the levels of TNF-α, IL-6 and IL-1β in alveolar lavage fluid. The caffeoyl quinic acids from Chrysanthemum morifolium significantly increased the levels of SOD and NO, decreased the levels of TNF-α, IL-6, IL-1β, VCAM-1, ET-1 and MDA, and significantly reduced the levels of p-MEK1/2, p-ERK1/2. In conclusion, total extracts of Chrysanthemum morifolium exhibit certain protective effect on mice with acute lung injury, and three caffeoyl quinic acids from Chrysanthemum morifolium may improve LPS-induced vascular endothelial cell injury by inhibiting inflammatory cytokines and oxidative stress, and regulating inter-cellular adhesion molecule and vasomotor factors through ERK/MAPK signaling pathway.