RESUMO
Hyperatins A-D (1-4), four previously undescribed polycyclic polyprenylated acylphloroglucinols, were isolated from Hypericum perforatum L. (St. John's wort). Compound 1 possessed a unique octahydroindeno[1,7a-b]oxirene ring system with a rare 2,7-dioxabicyclo[2.2.1]heptane fragment. Compounds 2-4 had an uncommon decahydrospiro[furan-3,7'-indeno[7,1-bc]furan] ring system. Their structures were established by spectroscopic analyses and X-ray crystallography. Plausible biosynthetic pathways of 1-4 were also proposed. Compounds 1 and 2 exerted promising hypoglycemic activity by inhibiting glycogen synthase kinase 3 expression in liver cells.
Assuntos
Antineoplásicos , Hypericum , Hypericum/química , Cristalografia por Raios X , Fígado , Furanos , Floroglucinol/farmacologia , Floroglucinol/química , Estrutura MolecularRESUMO
Hepatic ischemia/reperfusion injury (IRI) is a major factor contributing to the failure of hepatic resection and liver transplantation. As part of our ongoing investigation into bioactive compounds derived from fungi, we isolated eight indole alkaloids (1-8) from the endophytic fungus Aspergillus amoenus TJ507. Among these alkaloids, one previously undescribed compound, amoenamide D (1), was identified. The planar structure of 1 was elucidated by extensive spectroscopic analysis, including HRESIMS and NMR spectra. The absolute configuration of 1 was elucidated by using electronic circular dichroism calculations. Notably, in the CoCl2-induced hepatocyte damage model, notoamide Q (3) exhibited significant anti-hypoxia injury activity. Furthermore, in a murine hepatic ischemia/reperfusion injury model, treatment with 3 prevents IRI-induced liver damage and hepatocellular apoptosis. Consequently, 3 might serve as a potential lead compound to prevent hepatic ischemia/reperfusion injury.
Assuntos
Hepatopatias , Traumatismo por Reperfusão , Camundongos , Animais , Fígado , Fungos , Alcaloides Indólicos/química , Traumatismo por Reperfusão/tratamento farmacológico , IsquemiaRESUMO
(±)-Walskiiglucinol A (1a/1b), a pair of rearranged acylphloroglucinol derivatives with a new carbon skeleton, was obtained from Hypericum przewalskii. Compounds 1a/1b were the first examples of naturally occurring acylphloroglucinol derivatives possessing a unique 1-oxaspiro[4.4]nonane core bearing a new 5/5 ring system. Their planar and relative structures were identified by extensive spectroscopic analysis and NMR chemical shift calculations with DP4+ probability analysis, and their absolute configurations were determined by electronic circular dichroism (ECD) calculations. A plausible biogenetic pathway of 1a/1b was proposed in which the breakage of the C-2/C-3 linkage via a retro-Claisen reaction and the cyclization between C-3 and C-1 were proposed as key steps. The isolates were evaluated for cytotoxic activities against a panel of cancer cell lines and anti-inflammatory activities against lipopolysaccharide (LPS)-induced NO production, and compounds 1a/1b showed moderate cytotoxic activities with IC50 values ranging from 9.72 to 36.75 µM.
Assuntos
Antineoplásicos Fitogênicos , Hypericum , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Hypericum/química , Estrutura Molecular , Floroglucinol/química , EstereoisomerismoRESUMO
Norprzewalsone A (1), a rearranged polyprenylated polycyclic acylphloroglucinol (PPAP) with a new carbon skeleton, along with a new congener, norprzewalsone B (2), were isolated from Hypericum przewalskii. Compound 1 possessed a new 5/6/5/6/6 pentacyclic ring system based on a spiro[cyclopentane-1,3'-tricyclo[7.4.0.01,6]tridecane] core, which might be derived from the common [3.3.1]-type bicyclic polyprenylated acylphloroglucinol (BPAP) via the key retro-Claisen, intramolecular cyclization, and Diels-Alder cyclization reactions. Their structures and absolute configurations were confirmed by spectroscopic data, calculated 1D NMR data with DP4+ probability analyses, and electronic circular dichroism calculations and comparison. More significantly, compound 1 exhibited a moderate inhibitory effect on NO production in lipopolysaccharide-stimulated RAW264.7 cells.
Assuntos
Hypericum , Compostos de Espiro/química , Alcanos , Ciclopentanos , Hypericum/química , Estrutura Molecular , Floroglucinol/química , Floroglucinol/farmacologiaRESUMO
Kiiacylphnols A-H, eight previously undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs), along with two known congeners (hyperforcinol F and oxepahyperforin), were obtained from Hypericum przewalskii Maxim. The structures of these metabolites were confirmed by spectroscopic analyses, quantum-chemical 1H and 13C NMR calculations with DP4+ analyses, electronic circular dichroism (ECD) comparisons and calculations. Kiiacylphnols A and B were the first [3.3.1]-type PPAPs with an unusual octahydrooxireno[2,3-i]chromene scaffold bearing a rare 6/6/6/3 ring system. More significantly, kiiacylphnol A and oxepahyperforin displayed cytotoxicity against acute myeloid leukemia and diffuse large B-cell lymphoma cell lines by inducing cell apoptosis.
Assuntos
Hypericum , Apoptose , Dicroísmo Circular , Hypericum/química , Estrutura Molecular , Floroglucinol/química , Floroglucinol/farmacologiaRESUMO
Prunella vulgaris is a widely used edible Chinese medicinal plant. In the present study, two new abietane-type diterpenoids, abietoquinones A (1) and B (2), were isolated from this plant by an immunosuppressive bioassay-guided isolation procedure. Their structures were elucidated unambiguously by NMR spectroscopic analysis, single-crystal X-ray crystallography, and electronic circular dichroism calculations. Compounds 1 and 2 bear a cyclohex-2-ene-1,4-dione moiety, which is uncommon among abietane diterpenes. Also, abietoquinone A (1) suppressed murine splenocyte proliferation and decreased the production of proinflammatory cytokines induced by concanavalin A (Con A) in vitro. In Con A-challenged mice, preinjection with 1 significantly ameliorated liver injury. Additionally, abietoquinone A (1) exhibited inhibitory activities against the proliferation of murine splenocytes and human T cells induced by anti-CD3/anti-CD28 monoclonal antibodies (mAbs).
Assuntos
Abietanos/farmacologia , Hepatite Autoimune/tratamento farmacológico , Substâncias Protetoras/farmacologia , Prunella/química , Abietanos/isolamento & purificação , Animais , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Concanavalina A , Citocinas , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Plantas Medicinais/química , Substâncias Protetoras/isolamento & purificação , Baço/citologia , Linfócitos T/efeitos dos fármacosRESUMO
Eleven new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperwilsones A-K (1-11), along with five known PPAPs (12-16), were isolated from Hypericum wilsonii. Their structures were established via spectroscopic methods, the careful analysis of calculated and experimental electronic circular dichroism (ECD) spectra, single-crystal X-ray diffraction, the modified Mosher's method, and [Rh2(OCOCF3)4]-induced ECD. Hyperwilsone A (1) and hyperwilsone B (2) possessed the unique acetal functionality. Hyperwilsone C (3) was a rare example of [3.3.1]-type PPAP possessing a 3-isopropylfuran moiety. In bioassay, compounds 9 and 10 showed potent anti-inflammatory activity against LPS-induced NO production by inhibiting the nuclear translocation of NF-κB p65 and thus reducing the production of proinflammatory cytokines. Compounds 5, 8, 11, and 14 exhibited moderate inhibitory activity against SUDHL-4 and HL60 cancer cells with IC50 values in the range of 5.74-19.82 µM.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Descoberta de Drogas , Hypericum/química , Floroglucinol/farmacologia , Compostos Policíclicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Floroglucinol/química , Floroglucinol/isolamento & purificação , Compostos Policíclicos/química , Compostos Policíclicos/isolamento & purificação , Células RAW 264.7 , Relação Estrutura-AtividadeRESUMO
Hyperformitins A-I (1-9), nine undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) with double-bond migration, along with four new isomers hyperformitins J-M (10-13), were isolated from Hypericum perforatum. Their structures and absolute configurations were determined by spectroscopic analyses including HRESIMS, IR, UV, NMR, and ECD, as well as optical rotation (OR) calculations. The absolute configurations of previously reported analogues, garsubellins D and C as well as garcinielliptones L and M, were assigned for the first time by NMR spectra and specific rotations analyses assisting with OR calculations. Selected compounds were tested for their immunosuppressive activities against lipopolysaccharide (LPS)-induced B lymphocyte proliferation. Compounds 1, 3, 4, 5, 7, and 11 showed inhibition activities against the proliferation of B lymphocyte with IC50 values ranging from 4.1 to 9.7 µM. Furthermore, the neuroprotective activities of the isolates against corticosterone (CORT)-induced injury in PC12 cells were also tested, and compounds 1, 12, and 13 exhibited neuroprotective effects with cell viabilities of 68.0%, 71.3%, and 68.4%, respectively under the concentration of 10 µM.
Assuntos
Antineoplásicos/farmacologia , Hypericum/química , Imunossupressores/farmacologia , Fármacos Neuroprotetores/farmacologia , Floroglucinol/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linfócitos B/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Imunossupressores/química , Imunossupressores/isolamento & purificação , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Células PC12 , Floroglucinol/química , Floroglucinol/isolamento & purificação , Ratos , Relação Estrutura-AtividadeRESUMO
Hypaluton A (1), an unprecedented nor-polycyclic polyprenylated acylphloroglucinol (PPAP) bearing a new 8/6 bicyclic architecture, along with a new congener, hypaluton B (2), was obtained from Hypericum patulum. Their structures were confirmed by spectroscopic analyses, quantum-chemical 13C NMR calculations, electronic circular dichroism comparisons, and calculations. Hypaluton A is the first PPAP possessing an unparalleled 3,4-nor-bicyclic polyprenylated acylphloroglucinol (BPAP) scaffold, which might be derived from the common [5.3.1]-type-BPAP by losing seven carbons (C-3/4 of the acylphloroglucinol core and the isoprenyl at C-3) via the breakage at C-4-C-5 and C-2-C-3 bonds in the acylphloroglucinol core, together with the benzoyl migration through the hemiketalization/retro-Claisen cascade. More significantly, compound 1 is also the first discovered [6.3.0]-PPAP, which displayed pronounced inhibitory activity against lipopolysaccharide-induced B lymphocyte proliferation.
Assuntos
Hypericum , Dicroísmo Circular , Espectroscopia de Ressonância Magnética , Estrutura Molecular , FloroglucinolRESUMO
Five new 2-nor-bicyclic polyprenylated acylphloroglucinols (BPAPs), norhyperpalums A-E (1-5), three new 2,3-nor-BPAPs, norhyperpalums F-H (8-10), one new 2,3,4-nor-BPAP (13), and four known analogs (6, 7, 11 and 12) were obtained from Hypericum patulum. Their structures were confirmed by spectroscopic data, electronic circular dichroism (ECD) calculations and comparisons, quantum-chemical 13C NMR calculations with DP4 + probability analysis, the modified Mosher's method, Rh2(OCOCF3)4-induced ECD, and X-ray crystallographic data. Norhyperpalums A-E (1-5) are rare 2-nor-BPAPs bearing a 6/5/5 system based on a hexacyclic-fused 1,6-dioxaspiro[4.4]nonane core, and norhyperpalums F and G (8 and 9) exhibit an unusual 6-oxabicyclo[3.2.1]octane architecture. More significantly, compound 2 displayed pronounced cytotoxicities against hepatoma cell lines by the induction of S-phase cell cycle arrest and promotion of cell apoptosis.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Descoberta de Drogas , Hypericum/química , Floroglucinol/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Floroglucinol/química , Floroglucinol/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Three previously undescribed compounds, including a meroterpenoid, guignardone T (1), and two ophiobolin-type sesterterpenoids, maydispenoids A and B (2 and 3), along with four known compounds (4-7), were isolated from the phytopathogenic fungus Bipolaris maydis collected from Anoectochilus roxburghii (Wall.) Lindl leaves. The structures of all undescribed compounds were elucidated by spectroscopic analysis, electronic circular dichroism (ECD) calculations and single-crystal X-ray diffraction. Structurally, maydispenoids A was characterized by a fascinating decahydro-3-oxacycloocta[cd]pentalene fragment. It is notable that the compounds 2 and 3 exhibited potential inhibitory activity in anti-CD3/anti-CD28 monoclonal antibodies (mAbs) stimulated murine splenocytes proliferation, with IC50 values of 5.28 and 9.38 µM, respectively, and also suppress the murine splenocytes proliferation activated by lipopolysaccharide (LPS), with IC50 values of 7.25 and 16.82 µM, respectively. This is the first report of ophiobolin-type sesterterpenoids as immunosuppressor, and may provide new chemical templates for the development of new immunosuppressive drugs for autoimmune disease treatment.
Assuntos
Bipolaris/química , Imunossupressores/farmacologia , Sesterterpenos/farmacologia , Animais , Bipolaris/metabolismo , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Imunossupressores/química , Imunossupressores/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Orchidaceae/química , Orchidaceae/metabolismo , Folhas de Planta/química , Folhas de Planta/metabolismo , Sesterterpenos/química , Sesterterpenos/metabolismo , Baço/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
Six new compounds, including two new isochromane lactones, versicoisochromanes A and B (1 and 2), two new benzolactones, versicobenzos A and B (3 and 4), one furancarboxylic derivate, asperfuran A (6) and one ergosterol-type steroid, asperergoster A (7), along with five known steroids (8-12), were isolated from the Anoectochilus roxburghii endophytic fungus Aspergillus versicolor. The structures of these new compounds were determined by extensive spectroscopic techniques and electronic circular dichroism (ECD) calculations. It is notable that the new compound 7 exhibited obvious IL-1ß, NO and TNF-α inhibitory activity in LPS-stimulated RAW264.7 macrophages, with IC50 values of 35.5, 33.9 and 31.3 µM, respectively. Furthermore, compounds 7 and 8 displayed potential inhibitory effects on murine splenocytes proliferation stimulated by anti-CD3/anti-CD28 monoclonal antibodies (mAbs), meanwhile suppress the lipopolysaccharide (LPS) irritated murine splenocytes proliferation.
Assuntos
Anti-Inflamatórios/farmacologia , Aspergillus/química , Orchidaceae/microbiologia , Esteroides/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Dicroísmo Circular , Endófitos/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Células RAW 264.7 , Metabolismo Secundário , Baço/citologia , Esteroides/isolamento & purificaçãoRESUMO
Lactobacillus paracasei subsp. paracasei L1 was previously isolated from sweet potato sour liquid. This bacterial species specifically binds onto starch granular surfaces, triggering the enzymatic hydrolysis of raw starch. We investigated the functional and safety properties of strain L1 in vitro to establish its probiotic potential, and analyzed its effect on growth performance and intestinal microflora of chicken in feeding experiments. The optimal growth conditions of strain L1 included low pH and high concentrations of bile salts and NaCl. Its 1-, 2-, and 24-h autoaggregation values were 15.8 ± 1.2%, 20.4 ± 2.3%, and 47.2 ± 0.8%, respectively, with the surface hydrophobicity value at 560 nm of 38.1 ± 2.7%. Further, its adhesion rate to Caco-2 cells was 22.37 ± 1.44%. Strain L1 was resistant to erythromycin and azithromycin, but sensitive to other antibiotics tested. For the feeding experiments, 240 chickens with similar weights were randomly divided into a control (C) group and strain L1 (L) group and fed for 8 weeks. Strain L1 promoted the weight gain of chickens in L group. A significant increase in the population size of the two phyla and 23 genera in the small intestine was observed in the presence of strain L1 (P < 0.05), with 0 phyla and 4 genera showing significant increase in the cecum (P < 0.05). In the small intestine, the abundance of six functional genes at Kyoto Encyclopedia of Genes and Genomes (KEGG) level 2 and 49 genes at KEGG level 3 was significantly increased in group L (P < 0.05), with lesser changes noted in the cecum. An increase in the metabolic pathway functions, including enzyme families and the digestive system, was observed in the intestinal microbiota in the L group compared to the C group. However, the other metabolic pathway functions, including metabolism of fatty acid biosynthesis, as well as metabolism of glycerolipids and propanoate, increased in the cecal microbiota of the L group relative to the C group. These changes are most likely related to the changes in the gut microbiota composition. Collectively, strain L1 supplementation may promote growth performance and improve the intestinal microflora in chicken although further studies are needed to confirm this.
RESUMO
Chemical investigation of the extracts of the aerial parts of Hypericum przewalskii Maxim. resulted in the isolation and identification of six new epoxychromene-containing polycyclic polyprenylated acylphloroglucinols (PPAPs), named przewalcyrones A-F (1-6), and one known analogue (7). All of the structures were determined based on extensive spectroscopic analyses, X-ray crystallographic analysis, modified Mosher's method, [Rh2(OCOCF3)4]-induced ECD, and electronic circular dichroism (ECD) comparison. Structurally, przewalcyrones A-F represent the first examples of PPAPs containing an unexpected 8,8-dimethyl-3,9-epoxychromene moiety. All these compounds were evaluated for the immunosuppressive activity in anti-CD3/anti-CD28 monoclonal antibody (mAb)-stimulated human T cells. Among them, przewalcyrones C and D exhibited potential in vitro immunosuppressive activity, with IC50 values of (5.01 ± 0.52) µM and (5.26 ± 0.56) µM, respectively, highlighting those compounds as a promising starting point for the development of new immunosuppressive agents.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Hypericum/química , Imunossupressores/farmacologia , Floroglucinol/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Voluntários Saudáveis , Humanos , Imunossupressores/química , Imunossupressores/isolamento & purificação , Leucócitos Mononucleares/efeitos dos fármacos , Conformação Molecular , Floroglucinol/análogos & derivados , Floroglucinol/química , Estereoisomerismo , Relação Estrutura-Atividade , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
Hyperforatins L-U, ten undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) bearing a terminal double bond, together with a known compound hypericumoxide J, were isolated from the aerial parts of Hypericum perforatum L. Their structures were elucidated by spectroscopic methods, including HRESIMS, IR, UV, and NMR (1H, 13C, DEPT, HSQC, HMBC, 1H-1H COSY, and NOESY experiments). Their absolute configurations were determined by comprehensive analyses of their experimental ECD spectra in conjunction with a modified Mosher's method. Evaluation of their neuroprotective activities highlighted hyperforatin L, which displayed mild activity at a concentration of 10⯵M.
Assuntos
Inibidores da Colinesterase/farmacologia , Hypericum/química , Fármacos Neuroprotetores/farmacologia , Floroglucinol/farmacologia , Acetilcolinesterase/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Corticosterona , Relação Dose-Resposta a Droga , Conformação Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Células PC12 , Floroglucinol/análogos & derivados , Floroglucinol/química , Ratos , Relação Estrutura-AtividadeRESUMO
To investigate the hematological abnormality and clinical characteristics in systemic lupus erythematosus (SLE), the hematological data of 58 SLE and the curative effects of corticosteroid and immunosuppressive agents on SLE were retrospectively analysed by using SPSS/PC software. The results showed that the incidence of hematological abnormalities in 58 cases was as follows: 50 cases of hemogram abnormality (86.2%), 41 of anemia (70.7%), 34 of thrombocytopenia (58.7%), 37 of leukopenia (63.8%). Peripheral cytopenia of every cell lineage was common in SLE. The cell abnormalities of two or three lineages were seen in 41 cases (70.7%). The initial symptoms with hematological abnormality were found in 12 cases (20.7%), 7 out of 12 cases were erroneously diagnosed as hematology diseases (12.1%). In 30 out of 58 patients, the results of bone marrow examination showed that 23 had hyperplasia (76.7%) and 7 were hypoplasia. In 25 out of 38 cases, splenomegaly (65.8%) was found by B ultrasonography. In 25 patients with SLE receiving Coombs test, 3 were positive (12.0%). PAIg increased in 16 out of 22 cases of thrombocytopenia (72.7%). 26 cases of SLE with two or three lineage cytopenia in peripheral blood were treated by corticosteroid and immunosuppressive agent. The hemogram improved in all patients including 6 cases of bone marrow hypoplasia. It is concluded that the hematological abnormalities are frequent in SLE patients, which are short of specialty. The cytopenia of two or more lineage in peripheral blood is most common when bone marrow shows hyperplastic. The therapy with corticosteroid and immunosuppressive agents is efficacious.