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1.
J Antibiot (Tokyo) ; 77(5): 265-271, 2024 May.
Article in English | MEDLINE | ID: mdl-38531967

ABSTRACT

During our screening for anti-mycobacterial agents against Mycobacterium avium complex (MAC), two new polycyclic tetramate macrolactams (PTMs), named hydroxycapsimycin (1) and brokamycin (2), were isolated along with the known PTM, ikarugamycin (3), from the culture broth of marine-derived Streptomyces sp. KKMA-0239. The relative structures of 1 and 2 were elucidated by spectroscopic data analyses, including 1D and 2D NMR. Furthermore, the absolute configuration of 1 was confirmed by a single-crystal X-ray diffraction analysis. Compounds 2 and 3 exhibited moderate antimycobacterial activities against MAC, including clinically isolated drug-resistant M. avium.


Subject(s)
Anti-Bacterial Agents , Lactams , Microbial Sensitivity Tests , Streptomyces , Streptomyces/metabolism , Streptomyces/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Mycobacterium avium Complex/drug effects , Magnetic Resonance Spectroscopy , Lactams, Macrocyclic/pharmacology , Lactams, Macrocyclic/chemistry , Lactams, Macrocyclic/isolation & purification , Crystallography, X-Ray , Antitubercular Agents/pharmacology , Antitubercular Agents/chemistry , Antitubercular Agents/isolation & purification , Polycyclic Compounds/pharmacology , Polycyclic Compounds/isolation & purification , Polycyclic Compounds/chemistry , Molecular Structure
2.
Bioorg Chem ; 115: 105246, 2021 10.
Article in English | MEDLINE | ID: mdl-34371372

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Drug Discovery , Hypericum/chemistry , Phloroglucinol/pharmacology , Polycyclic Compounds/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Proliferation/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Humans , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Mice , Molecular Structure , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/biosynthesis , Phloroglucinol/chemistry , Phloroglucinol/isolation & purification , Polycyclic Compounds/chemistry , Polycyclic Compounds/isolation & purification , RAW 264.7 Cells , Structure-Activity Relationship
3.
Pharm Biol ; 59(1): 860-867, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34214019

ABSTRACT

CONTEXT: Schizandrin A (Sch A) is a major phytochemical from Schisandra chinensis (Turcz.) Baill. (Schisandraceae), which exerts a neuroprotective effect in Alzheimer's disease (AD). OBJECTIVE: To investigate the mechanism of Sch A in AD. MATERIALS AND METHODS: AD group: APP/PS1 transgenic mice served as AD models; AD + SCH group: APP/PS1 received 2 mg/kg Sch A by intragastric administration; WT: C57BL/6 mice were used as control. For in vitro assay, mouse microglial BV2 cells were treated with 0.5 µg/mL lipopolysaccharide or combined with 10 µmol/L Sch A for 24 h. The cognitive function and apoptosis in the mice was estimated. Microglial polarisation in the mice and cells was analysed. RESULTS: Sch A treatment effectively improved spatial learning and memory ability and suppressed apoptosis in the brain tissues of APP/PS1 mice. APP/PS1 mice exhibited an increase in the levels of Aß1-42 (2367.9 ± 431.1 pg/mg) and Aß1-40 (1753.3 ± 253.4 pg/mg), which was abolished by Sch A treatment. Moreover, Sch A treatment repressed the proportions of iNOS+/Iba-1+ cells and IL-6 expression, while enhanced the proportions of Arg-1+/Iba-1+ cells and IL-10 expression in APP/PS1 mice. In vitro, Sch A treatment reduced the proportions of CD16/32+ cells, iNOS expression and IL-6 levels (25.7 ± 5.3 pg/mL) repressed M1 polarisation, and enhanced the proportions of CD206 cells, Arg-1 expression and IL-10 levels (75.9 ± 12.8 pg/mL) in BV2 cells. CONCLUSIONS: This research confirms the neuroprotective effect of Sch A in AD, suggesting that Sch A may become a potential anti-AD agent.


Subject(s)
Alzheimer Disease/drug therapy , Cognition/drug effects , Cyclooctanes/pharmacology , Lignans/pharmacology , Neuroprotective Agents/pharmacology , Polycyclic Compounds/pharmacology , Alzheimer Disease/physiopathology , Animals , Apoptosis/drug effects , Brain/drug effects , Brain/physiopathology , Cell Line , Cyclooctanes/isolation & purification , Disease Models, Animal , Lignans/isolation & purification , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Microglia/drug effects , Microglia/metabolism , Neuroprotective Agents/isolation & purification , Polycyclic Compounds/isolation & purification , Schisandra/chemistry
4.
Food Chem ; 360: 130063, 2021 Oct 30.
Article in English | MEDLINE | ID: mdl-34029927

ABSTRACT

Here, we detail the biomineralization-assisted separation and concentration of crude food extract and an evaluation of its effectiveness. Schisandra chinensis fruit extract was used as a model plant extract. Hybrid grape-like mineral was assembled by calcium carbonate mineralization. The hybrid particles of S. chinensis mineral were fully characterized using field emission scanning electron microscopy, X-ray diffraction, thermogravimetric analysis, and particle size analysis. Data including the Brunauer-Emmett-Teller surface area, single point total pore volume, and adsorption/desorption analysis of pore size were also investigated. Organic molecules, including lipids such as palmitic acid, stearic acid, and linolenic acid in the Schisandra chinensis fruit, affect the formation of complex structures involving the CaCO3 mineralization pathway by inhibiting crystallization. However, the cosmetic active primary components were entrapped in a similar proportion in the preserved extract, and were efficiently separated without additional filtering and concentration steps for purification. In addition, the hybrid mineral was enriched (10.5 times) in Gomisin N, a representative component of S. chinensis fruit, relative to its concentration in the initial extract samples. The hybrid mineral inhibited both intracellular and extracellular melanin production and increased the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity. The data provide the first evidence of the potential use of fruit extract for obtaining hybrid minerals and the effectiveness of the biomineralization-based separation and concentration strategy.


Subject(s)
Plant Extracts/chemistry , Schisandra/chemistry , Animals , Antioxidants/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Cyclooctanes/chemistry , Cyclooctanes/isolation & purification , Cyclooctanes/pharmacology , Fruit/chemistry , Fruit/metabolism , Lignans/chemistry , Lignans/isolation & purification , Lignans/pharmacology , Mice , Plant Extracts/pharmacology , Polycyclic Compounds/chemistry , Polycyclic Compounds/isolation & purification , Polycyclic Compounds/pharmacology , Schisandra/metabolism
6.
J Nat Prod ; 84(3): 814-823, 2021 03 26.
Article in English | MEDLINE | ID: mdl-33523676

ABSTRACT

Natural product congeners serve a useful role in the understanding of natural product biosynthesis and structure-activity relationships. A minor congener with superior activity, selectivity, and modifiable functional groups could serve as a more effective lead structure and replace even the original lead molecule that was used for medicinal chemistry modifications. Currently, no effective method exists to discover targeted congeners rapidly, specifically, and selectively from producing sources. Herein, a new method based on liquid-chromatography tandem-mass spectrometry combination is evaluated for targeted discovery of congeners of platensimycin and platencin from the extracts of Streptomyces platensis. By utilizing a precursor-ion searching protocol, tandem mass spectrometry not only confirmed the presence of known congeners but also provided unambiguous detection of many previously unknown congeners of platensimycin and platencin. This high-throughput and quantitative method can be rapidly and broadly applied for dereplication and congener discovery from a variety of producing sources, even when the targeted compounds are obscured by the presence of unrelated natural products.


Subject(s)
Adamantane/chemistry , Aminobenzoates/chemistry , Aminophenols/chemistry , Anilides/chemistry , High-Throughput Screening Assays/methods , Polycyclic Compounds/chemistry , Streptomyces/chemistry , Adamantane/isolation & purification , Aminobenzoates/isolation & purification , Aminophenols/isolation & purification , Anilides/isolation & purification , Biological Products/chemistry , Biological Products/isolation & purification , Chromatography, Liquid , Molecular Structure , Polycyclic Compounds/isolation & purification , Structure-Activity Relationship , Tandem Mass Spectrometry
7.
Naunyn Schmiedebergs Arch Pharmacol ; 394(6): 1091-1102, 2021 06.
Article in English | MEDLINE | ID: mdl-33416934

ABSTRACT

The hepatoprotective activity of heliomycin obtained from the culture broth of actinomycete AB5 against diethylnitrosamine (DEN)-induced hepatic cancer in Wistar rats was estimated. Heliomycin exhibited a significant decrease in the levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) compared to the positive control. For instance, the heliomycin group after 20 weeks showed a significant decline in ALT, AST, and ALP values (70.75 ± 5.12, 140.25 ± 11.75, and 163.25 ± 18.66, respectively) compared to the positive control group (170.00 ± 9.55, 252.75 ± 12.33, and 278.00 ± 21.32, respectively). Additionally, the isolated compound showed a highly significant decrease in serum alpha-fetoprotein (AFP) levels. After 8, 16, and 20 weeks, the mean values of AFP in the heliomycin group revealed a highly significant decrease (33.62 ± 2.46, 30.00 ± 4.05, and 28.50 ± 2.64, respectively) compared to the positive control group (49.45 ± 3.03, 81.90 ± 6.70, and 90.75 ± 5.12, respectively). The histopathological investigation of liver sections supported the results of biochemical analysis. It was demonstrated that heliomycin showed histological improvement of hepatocytes and marked increase of nuclear pyknotic with clear cytoplasm, which is a sign of improving the apoptotic pathway of malignant cells. It also displayed marked fibrosis at most of the malignant cells and the development of some regenerative nodules. Heliomycin showed moderate immunoreactivity with alpha-fetoprotein (AFP), and proliferation cell nuclear antigen (PCNA) compared to the positive control group. To the best of our knowledge, this is the first study to report the anticancer activity of heliomycin against hepatocellular carcinoma in vivo.


Subject(s)
Actinobacteria/metabolism , Carcinoma, Hepatocellular/prevention & control , Liver Neoplasms, Experimental/prevention & control , Polycyclic Compounds/pharmacology , Alanine Transaminase/blood , Animals , Anticarcinogenic Agents/isolation & purification , Anticarcinogenic Agents/pharmacology , Aspartate Aminotransferases/blood , Diethylnitrosamine , Male , Polycyclic Compounds/isolation & purification , Rats , Rats, Wistar , Time Factors , alpha-Fetoproteins/metabolism
8.
J Ethnopharmacol ; 264: 113381, 2021 Jan 10.
Article in English | MEDLINE | ID: mdl-32946961

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Recently, a new drug combination GRS comprising ginsenoside Rb1 (G-Rb1), ruscogenin (R-Rus) and schisandrin (S-SA) was screened based on ShengMai preparations, which exhibited a prominent cardioprotective effects against myocardial ischemia/reperfusion (MI/R) injury. AIM OF THE STUDY: To investigate their systemic and individual mechanism of each compound in combination GRS. MATERIALS AND METHODS: The mice model of MI/R and hypoxia/reoxygenation (H/R)-induced cardiomyocytes injury were performed to explore the respective characteristics of each compound in GRS against myocardial injury. RESULTS: Each component in the combination GRS attenuated MI/R injury as evidenced by decreased myocardial infarct size, ameliorated histological features, and improved biochemical indicators. Meanwhile, ingredient G, R and S in combination also individually performed a significant decrease of apoptotic index in MI/R mice and H/R-induced cardiomyocytes injury. Mechanistically, component G in GRS could markedly increase the ATP content in cardiomyocytes through activation of AMPKα phosphorylation. Interestingly, the anti-apoptotic actions of G were profoundly attenuated by knockdown of AMPKα, while no alteration was observed on composition R and S. Moreover, component R in GRS significantly reduced the IL-6 and TNF-α mRNA expression, as well as the content of IL-6 via the modulation of NF-κB signaling pathway. Further, component S exhibited the most powerful anti-oxidative capacity in GRS and remarkably decreased the production of MDA and ROS, and potential mechanisms might at least in part through activating the Akt-14-3-3 signaling pathway and inhibiting the phosphorylation of Bad and ERK1/2. CONCLUSIONS: Our results indicated that the respective mechanism of each compound in combination GRS against MI/R injury might closely associated with energy metabolism modulation, suppression of inflammation and oxidative stress.


Subject(s)
Cyclooctanes/administration & dosage , Drugs, Chinese Herbal/administration & dosage , Ginsenosides/administration & dosage , Lignans/administration & dosage , Myocardial Reperfusion Injury/drug therapy , Polycyclic Compounds/administration & dosage , Spirostans/administration & dosage , Animals , Cell Line , Cell Survival/drug effects , Cell Survival/physiology , Cyclooctanes/isolation & purification , Drug Combinations , Drugs, Chinese Herbal/isolation & purification , Ginsenosides/isolation & purification , Inflammation Mediators/antagonists & inhibitors , Inflammation Mediators/metabolism , Lignans/isolation & purification , Male , Mice , Mice, Inbred ICR , Myocardial Reperfusion Injury/metabolism , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Polycyclic Compounds/isolation & purification , Rats , Spirostans/isolation & purification , Treatment Outcome
9.
Pharmazie ; 75(11): 559-564, 2020 11 01.
Article in English | MEDLINE | ID: mdl-33239129

ABSTRACT

The co-administration of voriconazole (VCZ) and Wuzhi tablet (WZ) is frequently prescribed for solid organ transplantation patients in China. However, the pharmacokinetic interactions between VCZ and WZ as well as its bioactive constituents, such as schisandrin A and schisandrol B, remain unknown. Therefore, the effects of WZ and the two lignans on the metabolism of VCZ and the potential role of cytochromeP450 (CYP450), especially cytochrome P450 2C19 (CYP2C19), were investigated. The results showed that WZ extensively inhibited the activities of CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. Noteworthy, 2.5 mg/mL WZ almost completely inhibited the activity of 2C19, and the inhibition ratio reached 78.6±3% and 63.5±4.6% for schisandrin A and schisandrol B at concentrations 100 µM, respectively. In addition, rats were treated with a single or consecutive 14 day oral dose of WZ (250 mg/kg), schisandrol B (10 mg/kg) and schisandrin A (10 mg/ kg). In rats treated with WZ, the AUC0-∞ value for intravenous VCZ dosing was increased by 80.2% (single dose, p < 0.05) and 66.4% (dosage for 14 day, p < 0.05) and the Cmax was increased by 10.5% (p < 0.05) and (20.6%, p < 0.05), respectively, much greater than that when VCZ (28 mg/kg) was given alone. Unexpectedly, the AUC and Cmax values after schisandrol B and schisandrin A treatment were significantly increased. However, the mRNA expression of liver CYP2C19 and the protein expression of liver CYP2C19 were surprisingly increased after treatment with WZ, schisandrol B and schisandrin A in rats. Therefore, attention should be paid to when WZ and VCZ are administered concomitantly, as dosage adjustment might become necessary. Further clinical study is warranted to validate the interaction between WZ and VCZ.


Subject(s)
Cytochrome P-450 CYP2C19/genetics , Drugs, Chinese Herbal/pharmacology , Herb-Drug Interactions , Voriconazole/pharmacokinetics , Animals , Antifungal Agents/administration & dosage , Antifungal Agents/pharmacokinetics , Area Under Curve , Cyclooctanes/isolation & purification , Cyclooctanes/pharmacology , Cytochrome P-450 Enzyme System/metabolism , Dioxoles/isolation & purification , Dioxoles/pharmacology , Drugs, Chinese Herbal/administration & dosage , Humans , Lignans/isolation & purification , Lignans/pharmacology , Liver/metabolism , Male , Polycyclic Compounds/isolation & purification , Polycyclic Compounds/pharmacology , Rats , Rats, Sprague-Dawley , Tablets , Voriconazole/administration & dosage
10.
Biomolecules ; 10(9)2020 09 02.
Article in English | MEDLINE | ID: mdl-32887413

ABSTRACT

Modulation of major histocompatibility complex (MHC) expression using drugs has been proposed to control immunity. Phytochemical investigations on Garcinia species have allowed the isolation of bioactive compounds such as polycyclic polyprenylated acylphloroglucinols (PPAPs). PPAPs such as guttiferone J (1), display anti-inflammatory and immunoregulatory activities while garcinol (4) is a histone acetyltransferases (HAT) p300 inhibitor. This study reports on the isolation, identification and biological characterization of two other PPAPs, i.e., xanthochymol (2) and guttiferone F (3) from Garcinia bancana, sharing structural analogy with guttiferone J (1) and garcinol (4). We show that PPAPs 1-4 efficiently downregulated the expression of several MHC molecules (HLA-class I, -class II, MICA/B and HLA-E) at the surface of human primary endothelial cells upon inflammation. Mechanistically, PPAPs 1-4 reduce MHC proteins by decreasing the expression and phosphorylation of the transcription factor STAT1 involved in MHC upregulation mediated by IFN-γ. Loss of STAT1 activity results from inhibition of HAT CBP/p300 activity reflected by a hypoacetylation state. The binding interactions to p300 were confirmed through molecular docking. Loss of STAT1 impairs the expression of CIITA and GATA2 but also TAP1 and Tapasin required for peptide loading and transport of MHC. Overall, we identified new PPAPs issued from Garcinia bancana with potential immunoregulatory properties.


Subject(s)
Garcinia/chemistry , Phloroglucinol/analogs & derivatives , Phloroglucinol/pharmacology , Polycyclic Compounds/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 2/metabolism , Acylation , Benzophenones/chemistry , Benzophenones/isolation & purification , Benzophenones/pharmacology , Down-Regulation/drug effects , Endothelial Cells/drug effects , GATA2 Transcription Factor/metabolism , Humans , Interferon-gamma/metabolism , Major Histocompatibility Complex/drug effects , Major Histocompatibility Complex/genetics , Membrane Transport Proteins/metabolism , Molecular Docking Simulation , Nuclear Proteins/metabolism , Phloroglucinol/chemistry , Phloroglucinol/isolation & purification , Polycyclic Compounds/chemistry , Polycyclic Compounds/isolation & purification , Prenylation , Primary Cell Culture , STAT1 Transcription Factor/metabolism , Terpenes/chemistry , Terpenes/pharmacology , Trans-Activators/metabolism , p300-CBP Transcription Factors/antagonists & inhibitors , p300-CBP Transcription Factors/chemistry
11.
Org Lett ; 22(17): 7041-7046, 2020 09 04.
Article in English | MEDLINE | ID: mdl-32841036

ABSTRACT

Terreuspyridine (1), the first 3,5-demethylorsellinic acid (DMOA) derived meroterpenoid alkaloid, was isolated from the fungus Aspergillus terreus, which represents a new type of meroterpenoid possessing an unexpected tetracyclic 6/6/6/6 architecture. The structure of 1 with absolute configuration was determined by X-ray diffraction analysis. Biogenetically, it was proposed to be derived from the fusion of a DMOA-meroterpenoid and a glutamate. Terreuspyridine (1) exhibited moderate inhibitory activity against the BChE with an IC50 value of 16.4 µM.


Subject(s)
Alkaloids/chemistry , Polycyclic Compounds/chemistry , Pyridines/chemistry , Aspergillus , Crystallography, X-Ray , Molecular Structure , Polycyclic Compounds/isolation & purification , Pyridines/isolation & purification , Terpenes/chemistry , Terpenes/isolation & purification
12.
Bioorg Chem ; 101: 103954, 2020 08.
Article in English | MEDLINE | ID: mdl-32506015

ABSTRACT

With a combined strategy of bioinformatics analysis, gene manipulation coupled with variation of growth conditions, the targeted activation of polycyclic tetramate macrolactams (PTMs) in the deepsea-derived Streptomyces somaliensis SCSIO ZH66 was conducted, which afforded a new (1) PTM, named somamycin A, along with three enol-type tetramic acid tautomers (2-4, somamycins B-D) of 10-epi-hydroxymaltophilin, 10-epi-maltophilin and 10-epi-HSAF, respectively. The structures of compounds 1-4 were elucidated by extensive spectroscopic analyses together with ECD calculations. Compound 1 exhibited notable growth inhibition against plant pathogenic fungi Fusariumoxysporum MHKW and Alternariabrassicae BCHB with the MIC values of 1.6 and 3.1 µg/mL, respectively, which were more potent than those of the positive control nystatin; and compounds 3 and 4 displayed moderate antifungal activities. Moreover, compounds 1-4 exhibited moderate cytotoxicity against the human cancer cell lines of HCT116 and K562.


Subject(s)
Lactams/isolation & purification , Polycyclic Compounds/isolation & purification , Seawater/microbiology , Streptomyces/chemistry , Spectrum Analysis/methods
13.
Biomed Pharmacother ; 127: 110051, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32428832

ABSTRACT

Xiaosheng prescription (XSP) has been used for dry eye disease (DED) for more than 10 years in Eye Hospital of China Academy of Chinese Medicine Sciences. However, the effective ingredients involved have remained unclear, which was investigated in this study by the correlation of ingredient and therapeutic activity. Human corneal epithelial cells (HCEC) cultured with 110 mM NaCl solution in vitro and C57BL/6 mice injected subcutaneously with scopolamine hydrobromide were used to establish dry eye models, and the therapeutic effect of XSP extract 1 was better than that of XSP extract 2 significantly. Then, UPLC-Q-TOF/MS and data analysis program Progenesis QI and Makerlynx XS were used to analyze the potential effective ingredients of XSP, and 4 compounds were speculated and identified, in which Schisandrin and 1 µM of Schisantherin A could obviously increase the cell survival rate of injured cells on the cell model. It can be indicated that Schisandrin and Schisantherin A are probably the potential effective ingredients in XSP for DED.


Subject(s)
Cyclooctanes/pharmacology , Dioxoles/pharmacology , Lignans/pharmacology , Plant Extracts/pharmacology , Polycyclic Compounds/pharmacology , Animals , Cyclooctanes/isolation & purification , Dioxoles/isolation & purification , Drugs, Chinese Herbal/chemistry , Epithelium, Corneal/physiopathology , Female , Humans , Lignans/isolation & purification , Mice , Plant Extracts/chemistry , Polycyclic Compounds/isolation & purification
14.
Bioorg Chem ; 100: 103887, 2020 07.
Article in English | MEDLINE | ID: mdl-32371250

ABSTRACT

Fusicoccane-derived diterpenoids bearing a unique bridgehead double-bond-containing tricyclo[9.2.1.03,7]tetradecane (5-9-5 ring system) core skeleton represent a rarely reported class of rearranged terpenoids, which traced back to fusicoccanes with a classical dicyclopenta[a,d]cyclooctane (5-8-5 ring system) core skeleton via a crucial Wagner-Meerwein rearrangement reaction. In this research, alterbrassicenes B-D (1-3), three new rearranged fusicoccane diterpenoids bearing a rare bridgehead double-bond-containing tricyclo[9.2.1.03,7]tetradecane core skeleton, together with two known congeners, brassicicenes O and K (4 and 5), were isolated from the modified cultures of fungus Alternaria brassicicola. Their structures were elucidated by comprehensive analyses of the NMR and HRESIMS data, and the absolute configurations of 1 and 4 were further confirmed via a combination of 13C NMR and ECD calculations and single-crystal X-ray diffraction analysis (Cu Kα). Interestingly, alterbrassicene B (1) represented the second case of bridgehead C-10-C-11 double-bond-containing natural products with a bicyclo[6.2.1]undecane core skeleton, and also featured an undescribed oxygen bridge between C-6 and C-14 to construct an unprecedentedly caged tetracyclic system. Alterbrassicenes B-D showed moderate cytotoxic activity against certain human tumor cell lines with IC50 values in the range of 15.87-36.85 µM.


Subject(s)
Alkanes/chemistry , Alternaria/chemistry , Antineoplastic Agents/chemistry , Diterpenes/chemistry , Alkanes/isolation & purification , Alkanes/pharmacology , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Crystallography, X-Ray , Diterpenes/isolation & purification , Diterpenes/pharmacology , Humans , Models, Molecular , Neoplasms/drug therapy , Polycyclic Compounds/chemistry , Polycyclic Compounds/isolation & purification , Polycyclic Compounds/pharmacology
15.
Nutrients ; 12(5)2020 Apr 28.
Article in English | MEDLINE | ID: mdl-32354126

ABSTRACT

Muscle wasting is caused by various factors, such as aging, cancer, diabetes, and chronic kidney disease, and significantly decreases the quality of life. However, therapeutic interventions for muscle atrophy have not yet been well-developed. In this study, we investigated the effects of schisandrin A (SNA), a component extracted from the fruits of Schisandra chinensis, on dexamethasone (DEX)-induced muscle atrophy in mice and studied the underlying mechanisms. DEX+SNA-treated mice had significantly increased grip strength, muscle weight, and muscle fiber size compared with DEX+vehicle-treated mice. In addition, SNA treatment significantly reduced the expression of muscle degradation factors such as myostatin, MAFbx (atrogin1), and muscle RING-finger protein-1 (MuRF1) and enhanced the expression of myosin heavy chain (MyHC) compared to the vehicle. In vitro studies using differentiated C2C12 myotubes also showed that SNA treatment decreased the expression of muscle degradation factors induced by dexamethasone and increased protein synthesis and expression of MyHCs by regulation of Akt/FoxO and Akt/70S6K pathways, respectively. These results suggest that SNA reduces protein degradation and increases protein synthesis in the muscle, contributing to the amelioration of dexamethasone-induced muscle atrophy and may be a potential candidate for the prevention and treatment of muscle atrophy.


Subject(s)
Cyclooctanes/pharmacology , Cyclooctanes/therapeutic use , Dexamethasone/adverse effects , Gene Expression/drug effects , Lignans/pharmacology , Lignans/therapeutic use , Muscle, Skeletal/metabolism , Muscular Atrophy/genetics , Muscular Atrophy/prevention & control , Phytotherapy , Polycyclic Compounds/pharmacology , Polycyclic Compounds/therapeutic use , Schisandra/chemistry , Animals , Cells, Cultured , Cyclooctanes/administration & dosage , Cyclooctanes/isolation & purification , Lignans/administration & dosage , Lignans/isolation & purification , Male , Mice, Inbred C57BL , Muscle Proteins/genetics , Muscle Proteins/metabolism , Muscle Strength/drug effects , Muscle, Skeletal/drug effects , Muscular Atrophy/chemically induced , Muscular Atrophy/physiopathology , Myosin Heavy Chains/genetics , Myosin Heavy Chains/metabolism , Myostatin/genetics , Myostatin/metabolism , Organ Size/drug effects , Polycyclic Compounds/administration & dosage , Polycyclic Compounds/isolation & purification , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , SKP Cullin F-Box Protein Ligases/genetics , SKP Cullin F-Box Protein Ligases/metabolism , Tripartite Motif Proteins/genetics , Tripartite Motif Proteins/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism
16.
Fitoterapia ; 142: 104535, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32145311

ABSTRACT

Three new homoadamantane-type polyprenylated acylphloroglucinols, hyperacmosins E-G (1-3), with seven known compounds were isolated from the air-dried aerial parts of Hypericum asmosepalum. Their structures were determined by NMR, HRESIMS and experimental electronic circular dichroism (ECD) spectra. The hepatoprotective activity of these compounds were evaluated. Compounds 4 and 8 exhibited hepatoprotective activity against paracetamol-induced HepG2 cell damage.


Subject(s)
Hypericum/chemistry , Phloroglucinol/analogs & derivatives , Polycyclic Compounds/isolation & purification , Adamantane/analogs & derivatives , Adamantane/isolation & purification , Hep G2 Cells , Humans , Polycyclic Compounds/chemistry , Protective Agents/isolation & purification
17.
Nat Prod Res ; 34(18): 2595-2601, 2020 Sep.
Article in English | MEDLINE | ID: mdl-30623674

ABSTRACT

One new sesquiterpene (α-iso-cubebenol acetate, 8), together with 9 known compounds (1-7, 9, 10) were isolated from the stems of Schisandra chinensis (Turcz.) Baill. by repeated silica gel column chromatography. Based on the results of MS, NMR spectra and comparing with literature data, the six dibenzocyclooctadiene lignans were identified as schizandrin A to C (1-3), schizandrin (4), schisantherin A (5) and gomisin J (6), the two sesquiterpenes were identified as α-iso-cubebenol (7) and α-iso-cubebenol acetate (8), while the two triterpenic acids were identified as ganwuweizic acid (9) and kadsuric acid (10). The antifeedant activity of the 10 compounds against Tribolium castaneum adults was tested. Gomisin J (6) exhibited activity at 1500 ppm concentration with 40.3% antifeeding index percentages. As for the dibenzocyclooctene lignans (compounds 1-3, 6), the number of methylenedioxies and the position of hydroxyl groups were the main factors to affect their antifeedant activities.


Subject(s)
Cyclooctanes/chemistry , Feeding Behavior/drug effects , Lignans/chemistry , Plant Stems/chemistry , Schisandra/chemistry , Tribolium , Animals , Cyclooctanes/analysis , Cyclooctanes/isolation & purification , Dioxoles/isolation & purification , Lignans/analysis , Lignans/isolation & purification , Polycyclic Compounds/isolation & purification , Sesquiterpenes/analysis , Sesquiterpenes/isolation & purification , Structure-Activity Relationship , Tribolium/drug effects , Triterpenes/analysis , Triterpenes/isolation & purification
18.
Biol Pharm Bull ; 43(1): 145-152, 2020 Jan 01.
Article in English | MEDLINE | ID: mdl-31666439

ABSTRACT

Schisandra chinensis is widely used and effective in protecting liver. There are many mechanisms of drug-induced hepatocyte injury, among which endoplasmic reticulum (ER) stress-induced cell injury plays an important role. However, little is known about whether schisandra chinensis can inhibit rifampicin (RFP)-induced hepatocyte injury by affecting ER stress. In our study, firstly, L02 cells were treated with different concentrations of RFP for different time intervals, and the apoptosis, survival rate and endoplasmic reticulum stress gene and protein expressions of glucose-regulated protein 78 (GRP 78), PKR-like ER kinase (PERK), activating transcription factor (ATF)4, C/EBP-homologus protein (CHOP), ATF6, arginine-rich, mutated in early stage tumors (ARMET), p-inositol-requiring enzyme 1 (IRE1) and X-box binding protein 1 (XBP-1) were measured. We found that RFP increased apoptosis of L02 cells, decreased cell survival, and increased the gene and protein expression levels of GRP78, PERK, ATF4, CHOP, ATF6, ARMET, p-IRE1 and XBP-1, suggesting that RFP could induce hepatocyte injury, and the degree of injury was positively correlated with the dose and time of RFP. Next, we treated RFP-damaged hepatocytes with schizandrin B. We found that schizandrin B increased cell survival rate in dose-dependent and time-dependent manner, decreased cell apoptosis rate, and reduced protein and gene expression levels of GRP78, PERK, ATF4, CHOP, ATF6, ARMET and XBP-1. These results indicate that schizandrin B alleviates RFP-induced injury in L02 cells by inhibiting ER stress.


Subject(s)
Apoptosis/drug effects , Chemical and Drug Induced Liver Injury, Chronic/prevention & control , Endoplasmic Reticulum Stress/drug effects , Hepatocytes/drug effects , Lignans/pharmacology , Polycyclic Compounds/pharmacology , Protective Agents/pharmacology , Animals , Cell Line , Cell Survival/drug effects , Chemical and Drug Induced Liver Injury, Chronic/metabolism , Cyclooctanes/isolation & purification , Cyclooctanes/pharmacology , Dose-Response Relationship, Drug , Endoplasmic Reticulum Chaperone BiP , Endoplasmic Reticulum Stress/genetics , Hepatocytes/metabolism , Humans , Lignans/isolation & purification , Polycyclic Compounds/isolation & purification , Protective Agents/isolation & purification , Schisandra/chemistry
19.
Molecules ; 24(17)2019 Aug 29.
Article in English | MEDLINE | ID: mdl-31470638

ABSTRACT

Despite significant advances in the understanding, prevention, and treatment of cancer, the disease continues to affect millions of people worldwide. Chemoradiation therapy is a rational approach that has already proven beneficial for several malignancies. However, the existence of toxicity to normal tissue is a serious limitation of this treatment modality. The aim of the present study is to investigate the ability of polar steroids from starfish Patiria (=Asterina) pectinifera to enhance the efficacy of radiation therapy in colorectal carcinoma cells. The cytotoxic activity of polar steroids and X-ray radiation against DLD-1, HCT 116, and HT-29 cells was determined by an MTS assay. The effect of compounds, X-ray, and their combination on colony formation was studied using the soft agar method. The molecular mechanism of the radiosensitizing activity of asterosaponin P1 was elucidated by western blotting and the DNA comet assay. Polar steroids inhibited colony formation in the tested cells, and to a greater extent in HT-29 cells. Asterosaponin P1 enhanced the efficacy of radiation and, as a result, reduced the number and size of the colonies of colorectal cancer cells. The radiosensitizing activity of asterosaponin P1 was realized by apoptosis induction through the regulation of anti- and pro-apoptotic protein expression followed by caspase activation and DNA degradation.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/genetics , Asterina/chemistry , Gene Expression Regulation, Neoplastic , Polycyclic Compounds/pharmacology , Radiation-Sensitizing Agents/pharmacology , Saponins/pharmacology , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Apoptosis/drug effects , Apoptosis/radiation effects , Caspase 3/genetics , Caspase 3/metabolism , Caspase 9/genetics , Caspase 9/metabolism , Cell Line, Tumor , Combined Modality Therapy , HCT116 Cells , HT29 Cells , Humans , Polycyclic Compounds/chemistry , Polycyclic Compounds/isolation & purification , Radiation-Sensitizing Agents/chemistry , Radiation-Sensitizing Agents/isolation & purification , Saponins/chemistry , Saponins/isolation & purification , Tumor Stem Cell Assay , X-Rays , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolism , bcl-X Protein/genetics , bcl-X Protein/metabolism
20.
Chem Pharm Bull (Tokyo) ; 67(7): 713-716, 2019 Jul 01.
Article in English | MEDLINE | ID: mdl-31006725

ABSTRACT

A reverse phase (RP)-HPLC method for separation and determination of Schisandrin A and Schisandrin B was presented, using a C18 Bondclone column, with methanol-water (v/v = 68 : 32) as mobile phase at a flow-rate of 1.00 mL·min-1, and UV detection at 220 nm. The tested parameters included mobile phase composition and UV detection wavelength. Good linearities were observed within concentration ranges of Schisandrin A 0.008-4.8 mg·L-1 (r = 0.9996), and Schisandrin B 0.005-3.1 mg·L-1 (r = 0.9994), respectively. The limit of detection (LOD) (S/N = 3) were 0.005 mg·L-1 Schisandrin A and 0.002 mg·L-1 Schisandrin B, respectively. The method was applied to determine the 2 compounds in a traditional Chinese medicine preparation for treatment of hepatic diseases, Huganpian tablet. To eliminate matrix effect, Oasis hydrophilic lipophilic balance (HLB) solid-phase extraction (SPE) was used to purify the ultra-sonicately extracted solution of the drug sample. Combined with the HLB SPE purification procedure, the HPLC method gave satisfactory results for quantitation of Schisandrin A and Schisandrin B in 3 types of Huganpian tablet samples, with spiking recoveries ca. 98% (relative standard deviation (R.S.D.) ≤ 3.5%) (n = 5).


Subject(s)
Chromatography, High Pressure Liquid , Cyclooctanes/analysis , Lignans/analysis , Polycyclic Compounds/analysis , Tablets/chemistry , Chromatography, Reverse-Phase , Cyclooctanes/isolation & purification , Lignans/isolation & purification , Limit of Detection , Medicine, Chinese Traditional , Polycyclic Compounds/isolation & purification , Solid Phase Extraction
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