ABSTRACT
A new alkaloid featured with a dibenz[c,e]azepin-5-one scaffold, namely emililactam A (3), together with a known pyrrolidine alkaloid (emilisonchine, 1) and a known flavonoid alkaloid [8-(2â³-pyrrolidinone-5â³-yl)-quercetin, 2] were isolated from the aerial parts of Emilia sonchifolia. Compounds 1 and 2 were isolated as racemic forms which were further separated, for the first time, to their corresponding enantiomers [(+)-1/(-)-1 and (+)-2/(-)-2], respectively, by using chiral-phase HPLC. The structure of new compound 3 was elucidated by extensive spectroscopic analysis. In addition, the absolute configurations of optically pure (+)-1/(-)-1 and (+)-2/(-)-2 were determined by the time-dependent density functional theory electronic circular dichroism (TDDFT-ECD) calculations. In an in vitro bioassay, compounds (+)-1, (-)-1, (±)-1, and 3 exhibited moderate neuroprotective effects against corticosterone-induced injuries of PC12 cells.
Subject(s)
Alkaloids , Asteraceae , Neuroprotective Agents , Alkaloids/chemistry , Asteraceae/chemistry , Circular Dichroism , Corticosterone , Molecular Structure , Neuroprotective Agents/pharmacology , Plant Components, Aerial/chemistry , Pyrrolidines , Pyrrolidinones/analysis , QuercetinABSTRACT
The gut epithelium is a mechanical barrier that protects the host from the luminal microenvironment and interacts with the gut microflora, which influences the development and progression of ulcerative colitis (UC). Licochalcone A (LA) exerts anti-inflammatory effects against UC; however, whether it also regulates both the gut barrier and microbiota during colitis is unknown. The current study was conducted to reveal the regulatory effects of LA on the intestinal epithelium and gut microflora in C57BL/6 mice subjected to dextran sodium sulfate (DSS). Sulfasalazine (SASP) was used as the positive control. Results of clinical symptoms evaluation, hematoxylin, and eosin (H&E) staining, and enzyme-linked immunosorbent (ELISA) assays showed that LA significantly inhibited DSS-induced weight loss, disease activity index (DAI) increase, histological damage, and gut inflammation. Additionally, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and immunohistochemical (IHC) analysis showed that LA maintained the integrity of the intestinal barrier by suppressing cell apoptosis and preserving the expression of tight junction (TJ) proteins. Notably, the optimal dose of LA for gut barrier preservation was low, while that for anti-inflammatory effects was high, indicating that LA might preserve gut barrier integrity via direct effects on the epithelial cells (ECs) and TJ proteins. Furthermore, 16S rRNA analysis suggested that the regulatory effect of LA on the gut microbiota differed distinctly according to dose. Correlation analysis indicated that a low dose of LA significantly modulated the intestinal barrier-associated bacteria as compared with a moderate or high dose of LA. Western blot (WB) analysis indicated that LA exhibited anti-UC activity partly by blocking the mitogen-activated protein kinase (MAPK) pathway. Our results further elucidate the pharmacological activity of LA against UC and will provide valuable information for future studies regarding on the regulatory effects of LA on enteric diseases.
Subject(s)
Chalcones/pharmacology , Colitis/drug therapy , Gastrointestinal Microbiome/drug effects , Animals , Chalcones/metabolism , Colitis/physiopathology , Colitis, Ulcerative/chemically induced , Colon/metabolism , Dextran Sulfate/pharmacology , Disease Models, Animal , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Male , Mice , Mice, Inbred C57BL , Sulfasalazine/pharmacology , Tight Junction Proteins/metabolismABSTRACT
This study was to analyze the pyrrolizidine alkaloids (PAs) in Eupatorium fortunei herbs and its derived finished products with a view to evaluating their effects on the proliferation and oligodendrogenesis of neural progenitor cells (NPCs). Using a LC-MS/MS method with 32 PAs reference standards, 8 PAs including intermedine, intermedine N-oxide, lycopsamine, lycopsamine N-oxide, retronecine, seneciphylline and senkirkine and 7-acetylintermedine N-oxide were identified with intermedine N-oxide and lycopsamine N-oxide being most abundant. The total PA amounts were found to vary from 0.18 to 61.81 µg/g in 30 batches of herbs and from 0.86 to 36.96 µg/g in 4 commercial finished products, respectively. Risk assessments indicated that the short-term intake seemed unlikely lead to acute toxic effects but the chronic use warranted cautions. Using NPCs derived from mouse induced pluripotent stem cells as an in vitro testing model, intermedine, intermedine N-oxide and lycopsamine N-oxide appeared to decrease cell viability at 30 µM whereas intermedine N-oxide inhibited oligodendrogenesis of NPCs at 10 µM. The present results suggested that the PAs in the majority of E. fortunei herbs and the derived products not only resulted in their exposure far exceeding the acceptable intake limit (i. e. 1.0 µg PA per day for adults) in herbal medicinal products recommended by the European Medicines Agency but also induced neurotoxicity to NPCs in vitro.
Subject(s)
Eupatorium/chemistry , Oligodendroglia/drug effects , Pyrrolizidine Alkaloids/analysis , Pyrrolizidine Alkaloids/toxicity , Animals , Chromatography, Liquid/methods , In Vitro Techniques , Mice , Neural Stem Cells/cytology , Oligodendroglia/cytology , Reproducibility of Results , Tandem Mass Spectrometry/methodsABSTRACT
Pyrrolizidine alkaloids(PAs) are a group of naturally occurring alkaloids with a pyrrolizidine skeleton which can be found in about 3% of the world's flowering plants. It is notorious that PAs are cause the hepatoxic and genotoxic-carcinogenic effects by taking PA-containing herbs, food and dietary supplements. In order to control the poisoning caused by PAs, European Medicines Agency has set a limit of intake of PAs from herbal medicinal products at 0.007 μg of 1,2-unsaturated PAs/kg body weight. Nonetheless, a systematic overview of the amount of PAs in the herb has not been provided. Therefore, this paper is to systematically review the current status of PAs content analysis of herbal medicines and foods reported in the literature, and to provide theoretical and experimental support for the safety risk assessment and control of PAs in Chinese herbal medicines.
Subject(s)
Food , Herbal Medicine , Phytotherapy , Plants, Medicinal , Pyrrolizidine Alkaloids/toxicityABSTRACT
Glycyrrhetinic acid (GA) is one of the main components of the traditional Chinese medicine of licorice, which can coordinate and promote the effects of other medicines in the traditional prescription. We found that GA could promote the proliferation, decrease the apoptotic rate, and attenuate DFMO-elicited growth arrest and delay in restitution after wounding in IEC-6 cells via HuR. GA failed to promote proliferation and to suppress apoptosis after silencing HuR by siRNA in IEC-6 cells. Furthermore, with the model of small intestinal organoids developed from intestinal crypt stem cells, we found that GA could increase HuR and its downstream ki67 levels to promote intestinal organoid development. In the in vivo assay, GA was shown to maintain the integrity of the intestinal epithelium under the circumstance of 48 h-fasting in rats via raising HuR and its downstream genes such as EGF, EGFR, and MEK. These results suggested that via HuR modulation, GA could promote intestinal epithelium homeostasis, and therefore contribute to the absorption of constituents from other medicines co-existing in the traditional prescription with licorice in the small intestine. Our results provide a new perspective for understanding the effect of licorice on enhancing the therapeutic effect of traditional prescriptions according to the traditional Chinese medicine theory.
ABSTRACT
Pyrrolizidine alkaloids (PAs) are natural toxins found in some genera of the family Asteraceae. However, it has not been reported whether PAs are present in the widely used Asteraceae plant Artemisia capillaris Thunb. (A. capillaris). The purpose of this study was to establish a sensitive and rapid UPLC-MS/MS method together with chemometrics analysis for simultaneous determination and risk assessment of PAs in A. capillaris. The developed UPLC-MS/MS method was validated and was confirmed to display desirable high selectivity, precision and accuracy. Risk assessment was conducted according to the European Medicines Agency (EMA) guideline. Chemometrics analysis was performed with hierarchical clustering analysis and principal component analysis to characterize the differences between PAs of A. capillaris. Finally, PAs were found in 29 out of 30 samples and at least two were detected in each sample, besides, more than half of the samples exceeded the EMA baseline. Nevertheless, the chemometrics results suggested that the PAs contents of A. capillaris from different sources varied significantly. The method was successfully applied to the detection and risk evaluation of PAs-containing A. capillaris for the first time. This study should provide a meaningful reference for the rational and safe use of A. capillaris.
Subject(s)
Artemisia/chemistry , Chromatography, Liquid/methods , Pyrrolizidine Alkaloids/analysis , Tandem Mass Spectrometry/methodsABSTRACT
A new drimane-type sesquiterpene with an isocitric acid moiety, cryptoporic acid S (1), together with six known compounds, cryptoporic acid D (2), ß-sitosterol (3), ß-daucosterol (4), stigmast-4-en-3-one (5), ergosterol (6), and (22E,24R)-ergosta-7,22-diene-3ß,5α,6ß-triol (7), was isolated from the fruiting bodies of Cryptoporus volvatus. The structures of these compounds were established on the basis of UV, IR, MS, 1D and 2D NMR analysis. In the meanwhile, compounds 1 and 2 were evaluated for antioxidant activity using the methods of 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity (DPPH-RSA) and ferric reducing antioxidant power (FRAP) assay, and they exhibited moderate antioxidant activities.
Subject(s)
Antioxidants/isolation & purification , Coriolaceae/chemistry , Isocitrates/isolation & purification , Sesquiterpenes/isolation & purification , Antioxidants/chemistry , Antioxidants/pharmacology , Biphenyl Compounds/pharmacology , China , Ergosterol/chemistry , Ethers , Fruiting Bodies, Fungal/chemistry , Isocitrates/chemistry , Isocitrates/pharmacology , Molecular Structure , Picrates/pharmacology , Polycyclic Sesquiterpenes , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Sitosterols/chemistry , Stigmasterol/analogs & derivatives , Stigmasterol/chemistry , Stigmasterol/isolation & purificationABSTRACT
A sesquiterpene coumarin, sinkiangenorin E, consisting of a novel bicyclo[4.3.1]decane-type sesquiterpene system, was isolated from the seeds of Ferula sinkiangensis. The structure of sinkiangenorin E including the relative stereochemistry and the absolute configuration was elucidated on the basis of spectroscopic data. The new compound showed cytotoxic activity against AGS cells (IC50, 12.7 µM) and inhibiting effect against influenza A H1N1 (IC50, 4.0 µM), which provided important clues for the study on the bioactivities of this type of sesquiterpene coumarins.
Subject(s)
Coumarins/isolation & purification , Drugs, Chinese Herbal/isolation & purification , Ferula/chemistry , Sesquiterpenes/isolation & purification , Coumarins/chemistry , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Electron Spin Resonance Spectroscopy , Humans , Influenza A Virus, H1N1 Subtype/drug effects , Molecular Structure , Plant Roots/chemistry , Seeds/chemistry , Sesquiterpenes/chemistryABSTRACT
OBJECTIVE: To determine the effect and mechanism of combination treatment of the total glycosides from Cimicifuga dahurica (TGCD) and cisplatin (CDDP) in vitro in human colon cancer cells (HCT-8) and in vivo in mouse hepatoma cells (H22)-bearing mice. METHODS: H22 tumor-bearing imprinting control region (ICR) mice were treated with TGCD, CDDP, and TGCD + CDDP for 10 days. Tumor volume and tumor weight were evaluated. TGCD and CDDP in different concentrations were added separately and in combination to cultures of different cancer cell lines, including the HCT-8. Effects of TGCD and CDDP on cell proliferation were detected by 3-(4,5-dimethyl-2-thiazole)-2-5-biphenly-tetrazole bromide (MTT) method and effects on cell apoptosis were tested by flfl ow cytometry and western blotting at 24 h after treatment. RESULTS: Combination index values (CI<0.8) suggested the synergistic effects of the TGCD + CDDP. This combination resulted in the highest increase in the percentage of apoptotic HCT-8 cells, caused cell cycle arrest in G2/M phase and increased expression of cleaved caspase-3, -8, and -9, Bax, phospho-c-Jun N-terminal kinase (p-JNK), and phospho-p38 mitogen-activated protein kinase (p-p38 MAPK), as well as decreased expression of Bcl-2, JNK, p38 MAPK, Poly (ADP-ribose) polymerase 1 (PARP1), caspase-3, and caspase-8 compared with single-agent treated and control groups. TGCD + CDDP treatment reduced tumor weight by 86.1%±7.2% compared with 64.5%±6.8% by CDDP or 46.9%±6.9% by the TGCD alone in vivo. CONCLUSIONS: TGCD enhanced the anticancer activity of CDDP in an additive-to-synergistic manner by activating multiple signaling pathways (including apoptosis). These fifi ndings suggest the potential benefifi t of combined treatment of the TGCD and CDDP against cancer of the colon and liver.
ABSTRACT
In order to find the cardiotonic constituents of lateral roots of Aconitum carmichaelii Debx., the investigation was carried out. Silica gel column chromatography, Sephadex LH-20, medium-pressure MCI and reverse phase ODS column chromatography were used to separate the 90% EtOH extract of the lateral roots of Aconitum carmichaelii Debx. The structures of the isolated compounds have been identified by chemical properties and spectroscopic analyses. Ten compounds were isolated and their structures were elucidated as benzoic acid-5-hydroxy-2-benzoyl-amino methyl ester (1), honokiol (2), pinoresinol (3), salicylic acid (4), p-hydroxy-cinnamic acid (5), songorine (6), karakoline (7), mesaconitine (8), hypaconitine (9) and 14-benzoylhypaconitine (10), separetely. Compound 1 is a new compound and its structure has been established by NMR, HR-ESI-MS, UV, IR and X-Ray. Compound 2-5 are isolated from the lateral roots of Aconitum carmichaelii Debx. for the first time.
Subject(s)
Aconitum/chemistry , Cardiotonic Agents/chemistry , Plant Roots/chemistry , Cardiotonic Agents/isolation & purificationABSTRACT
BACKGROUND/AIMS: Cajaninstilbene acid (3-hydroxy-4-prenyl-5-methoxystilben-2 -carboxylic acid, CSA), a natural stilbene isolated from the leaves of Cajanus cajan, has attracted considerable attention for its wide range of pharmacological activities. This study investigated whether CSA protects against corticosterone (CORT)-induced injury in PC12 cells and examined the potential mechanisms underlying this protective effect. METHODS: Cell viability and cytotoxicity were detected using a 3-(4,5-desethyithiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and a lactate dehydrogenase (LDH) assay kit, respectively. PC12 cell apoptosis was measured using Hoechst 33342 staining and a DNA fragmentation assay kit, and intracellular Ca(2+) concentrations were assessed by fluorescent labelling. Next, the mitochondrial permeability transition pores (mPTPs) and mitochondrial membrane potentials (∆Ψm) were detected using a colorimetric mPTP detection kit and a 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) kit, respectively. Finally, cytochrome c, caspase-3 and inhibitor of caspase-activated deoxyribonuclease (ICAD) expression levels were monitored by western blot analysis. RESULTS: Treatment with 100 µmol/l CORT induced cytotoxicity in PC12 cells. However, CSA dose-dependently increased cell viability and decreased LDH release as well as CORT-induced apoptosis. Mechanistically, compared with the CORT-treated group, CSA strongly attenuated intracellular Ca(2+) overload and restored mitochondrial functions, including mPTPs and ∆Ψm. Furthermore, the down-regulation of cytochrome c and ICAD protein expression and the blockage of caspase-3 activity were observed upon CSA treatment. CONCLUSIONS: In summary, our data are the first to show that the in vitro antidepressant-like effect of CSA may be attributed to the cytoprotection of neurons and that such neuroprotective mechanisms are correlated with intracellular Ca(2+) homeostasis and mitochondrial apoptotic pathways.
Subject(s)
Apoptosis/drug effects , Corticosterone/antagonists & inhibitors , Mitochondria/drug effects , Salicylates/pharmacology , Stilbenes/pharmacology , Animals , Corticosterone/pharmacology , DNA Fragmentation/drug effects , PC12 Cells , RatsABSTRACT
Conducted research on new allelochemicals phellamurine extracted from deciduous of Phellodendron amurense, which worked in allelopathy effect to seed germination and growth process of P. amurense and P. chinense in order to interpret the causes of rare seedlings of wild populations of P. amurense. Extracted and separated phellamurine from P. amurense deciduous, and treated the seeds of P. amurense and P. chinense in after-ripening stage and germination stage with different concentrations of phellamurine solution, then detection of the seed germination rate, germination index, seedling height, root length and seed vigor index to evaluate the allelopathic effect of phellamurine. The results show that: phellamurine solution at 0.30 g x L(-1) produce significant inhibition to seed after-ripening of P. amurense, and also the solution at 0.15 g x L(-1) produce significant inhibition to seeds germination of P. amurense; the solution at 0.15 g x L(-1) produce significant inhibition to seeds after-ripening and seeds germination of P. chinense, inhibition intensity increased with the concentration and enhanced. For both species, the presence of phellamurine can lower the seed germination rate, extend the germination time, reduce the ability of seedlings to adapt to the environment, thus the phellamurine may be one of the causes of rare seedlings in the wild population of P. amurense.
Subject(s)
Phellodendron/chemistry , Pheromones/pharmacology , Plant Extracts/pharmacology , Allelopathy , Ecosystem , Environment , Germination/drug effects , Phellodendron/drug effects , Phellodendron/growth & development , Seeds/chemistry , Seeds/drug effects , Seeds/growth & development , TemperatureABSTRACT
Luteolin, a flavonoid that exhibits antioxidative properties, exerts myocardial protection effects. However, the underlying molecular mechanisms are not yet fully understood. To investigate the effects of luteolin on myocardial injury protection and its possible mechanisms, a myocardial injury model was established with intragastric administration of 4 mg/kg isoproterenol (ISO) to male Sprague-Dawley rats (200-220 g) daily for 2 days. We found that pretreatment of luteolin (160, 80 and 40 mg/kg, i.g., respectively) daily for 15 days can prevent ISO-induced myocardial damage, including decrease of serum cardiac enzymes, improvement electrocardiography and heart vacuolation. Luteolin also improved the free radical scavenging and antioxidant potential, suggesting one possible mechanism of luteolin-induced cardio-protection is mediated by blocking the oxidative stress. To clarify the mechanisms, we performed the in vitro study by hydrogen peroxide (H(2)O(2))-induced cytotoxicty model in H9c2 cells. We found that luteolin pretreatment prevented apoptosis, increased the expression of heme oxygenase-1 (HO-1), and enhanced the binding of Nrf2 to the antioxidant response element, providing an adaptive survival response against H(2)O(2)-derived oxidative cytotoxicity. The addition of Znpp, a selective HO-1 competitive inhibitor, reduced the cytoprotective ability of luteolin, indicating the vital role of HO-1 on these effects. Luteolin also activated Akt and ERK, whereas the addition of LY294002 and U0126, the pharmacologic inhibitors of PI3K and ERK, attenuated luteolin-induced HO-1 expression and cytoprotective effect. Taken together, the above findings suggest that luteolin protects against myocardial injury and enhances cellular antioxidant defense capacity through the activation of Akt and ERK signal pathways that leads to Nrf2 activation, and subsequently HO-1 induction.
Subject(s)
Heart/drug effects , Heme Oxygenase-1/biosynthesis , Luteolin/pharmacology , Myocardium/metabolism , Oxidative Stress/drug effects , Animals , Antioxidant Response Elements/physiology , Aspartate Aminotransferases/blood , Cell Line , Cell Survival/drug effects , Creatine Kinase/blood , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Extracellular Signal-Regulated MAP Kinases/metabolism , L-Lactate Dehydrogenase/blood , Male , Myocardium/enzymology , NF-E2-Related Factor 2/metabolism , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Proto-Oncogene Proteins c-akt/metabolism , Random Allocation , Rats , Rats, Sprague-DawleyABSTRACT
This study is to investigate the protective effect of longistyline A against corticosterone-induced neurotoxicity in PC12 cells. While PC12 cells were exposed to 100 micromol x L(-1) corticosterone for 48 h, cell survival rate was reduced and lactate dehydrogenase (LDH) release increased. In parallel, corticosterone caused significant elevations of DNA fragmentation, [Ca2+]i and caspase-3 activity. However, when the PC12 cells were incubated with longistyline A (4.0, 8.0 and 16.0 micromol x L(-1)) in the presence of 100 micromol x L(-1) corticosterone for 48 h, the effects were evidently alleviated, but dose-dependent manner was not obvious. In summary, longistyline A could generate a neuroprotective effect against corticosterone-induced neurotoxicity in PC12 cells possibly by decreasing [Ca2+]i and caspase-3 activity.
Subject(s)
Calcium/metabolism , Caspase 3/metabolism , Cell Survival/drug effects , Neuroprotective Agents/pharmacology , Phenols/pharmacology , Animals , Cajanus/chemistry , Corticosterone/toxicity , DNA Fragmentation/drug effects , L-Lactate Dehydrogenase/metabolism , Molecular Structure , Neuroprotective Agents/isolation & purification , PC12 Cells , Phenols/isolation & purification , Plant Leaves/chemistry , Plants, Medicinal/chemistry , RatsABSTRACT
OBJECTIVE: To study the chemical constituents contained in ethanol extracts from aerial parts of Emilia sonchifolia. METHOD: The compounds were separated and purified with various chromatographic techniques, and their structures were identified on the basis of physicochemical properties and spectral data. RESULT: Fifteen compounds were separated from ethyl acetate fraction of 90% ethanolic extract and identified as rhamnetin (1), isorhamnetin (2), quercetin (3), luteolin (4), tricin-7-O-beta-D-glucopyranoside (5), 8-(2"-pyrrolidinone-5"-yl) -quercetin (6), 5, -2', 6'-trihydroxy-7, 8-dimethoxyflavone-2'-O-beta-D-glucopyranoside (7), succinic acid (8), fumaric acid (9), p-hydroxybenzoic acid (10), 4-hydroxy isophthalic acid (11), 3, 4-dihydroxycinnamic acid (12), esculetin (13), isowedelolactone (14) and uracil (15), respectively. CONCLUSION: All compounds except compound 3 were separated from this genus for the first time.
Subject(s)
Asteraceae/chemistry , Plant Extracts/analysisABSTRACT
Cajanus cajan (L.) is a traditional Chinese herb medicine which contains a lot of potential active components. In the present study, we identified the effects of the stilbenes containing extract-fraction from C. cajan L. (sECC) on Abeta(25-35)-induced cognitive deficits, oxidative stress and cholinergic dysfunction in mice. Mice were treated with sECC (100 and 200mg/kg/d) for 1-week, and then received a single intracerebroventricular (i.c.v.) injection of Abeta(25-35) (5mug/mice). Behavioral changes and neuron apoptosis in mice were evaluated using Morris water maze and TUNEL tests. Furthermore, superoxide dismutase (SOD), choline acetyl transferase (ChAT) and acetylcholine esterase (AchE) activity in hippocampus and cortex were analyzed by spectrophotometric method. The data showed that consumption of sECC (200mg/kg) significantly ameliorated the cognitive deficits and neuron apoptosis caused by i.c.v. injection of Abeta(25-35). At the same time, the decreased SOD and ChAT activity in hippocampus and cortex were markedly increased by sECC (200mg/kg). sECC has no effect on AchE activity in hippocampus and cortex. These findings suggest that sECC may be a potential candidate for the development of therapeutic agents to manage cognitive impairment associated with Alzheimer's disease (AD) through increasing the activity of ChAT and anti-oxidative mechanism.
Subject(s)
Amyloid beta-Peptides , Antioxidants/pharmacology , Cajanus , Cognition Disorders/prevention & control , Peptide Fragments , Plant Extracts/pharmacology , Stilbenes/pharmacology , Acetylcholinesterase/metabolism , Animals , Apoptosis , Brain/drug effects , Brain/metabolism , Brain/pathology , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Choline O-Acetyltransferase/metabolism , Cognition Disorders/metabolism , Cognition Disorders/pathology , Diethylstilbestrol/analogs & derivatives , Diethylstilbestrol/pharmacology , Female , Hippocampus/drug effects , Hippocampus/metabolism , In Situ Nick-End Labeling , Maze Learning , Mice , Mice, Inbred BALB C , Neurons/drug effects , Neurons/pathology , Oxidative Stress/drug effects , Superoxide Dismutase/metabolismABSTRACT
Two new cyclolanostane diglycosides, cimifoetiside A (1) and cimifoetiside B (2), were isolated from an 80% ethanolic extract of the aerial part of Cimicifuga foetida L. (Ranuculaceae). Using spectral data and chemical analysis, the structures of 1 and 2 were identified as (23R, 24S) cimicigenol 3-O-beta-D-glucopyranosyl-(1''-->3')-beta-D-xylopyranoside and (23R, 24S) cimicigenol 3-O-beta-D-glucopyranosyl-(1''-->2')-beta-D-xylopyranoside, respectively. The in vitro immunosuppressive effects of the two new compounds 1 and 2, as well as four other known cyclolanostane saponins 3-6 on T cells were evaluated. All the agents tested effectively inhibited the proliferation of murine splenocytes induced by Concanavalin A (ConA), with IC(50) values ranging from 12.7 nM to 33.3 nM.
Subject(s)
Cimicifuga/chemistry , Glycosides/pharmacology , Immunosuppressive Agents/pharmacology , Triterpenes/pharmacology , Animals , Cell Proliferation/drug effects , Cells, Cultured , Concanavalin A/pharmacology , Female , Glycosides/chemistry , Glycosides/isolation & purification , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/isolation & purification , Inhibitory Concentration 50 , Mice , Mice, Inbred BALB C , Molecular Structure , Plant Components, Aerial/chemistry , Spleen/cytology , Spleen/immunology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Triterpenes/chemistry , Triterpenes/isolation & purificationABSTRACT
Cajanus cajan L. is a natural plant, which contains a lot of potential active components. In the present study, we identified the effects of the stilbene extract from Cajanus cajan L. (sECC) on hepatic cholesterol metabolism in diet-induced (for 4 weeks) hyperlipidemic Kunming mice. All experimental mice were divided into 5 groups: control group, high lipid model group, sECC-treated with 200 or 100 mg kg(-1), and simvastatin (Sim, 12 mg kg(-1)) treated group. The mice were fed with fat and cholesterol-enriched chow except control mice that were fed with standard diet. The effects of sECC were investigated by monitoring serum and liver lipid profile (i. e. cholesterol homeostasis) in mice. To further explore the mechanism of sECC, hepatic cholesterol 7alpha-hydroxylase (CYP7A1) and low density lipoprotein (LDL) receptor expressions in cholesterol homeostasis were analyzed by reverse transcription PCR. After 4 weeks pretreatment, the mice in the high lipid model group showed markedly higher serum and hepatic lipid contents than control group (P< 0.01). Compared with high lipid model group, the increased serum and hepatic lipid contents were markedly attenuated by sECC (200 mg kg(-1)), the serum and hepatic total cholesterol were reduced by 31.5% and 22.7% (P<0.05), respectively. The triglyceride contents of serum and liver were also lowered by 23.0% and 14.4%, respectively. At the same times, serum LDL cholesterol decreased by 53.0% (P<0.01). The mRNA expressions of hepatic CYP7A1 and LDL-receptor were significantly enhanced in the mice administered with sECC (200 mg kg(-1)), whereas those expressions were suppressed by the fat and cholesterol-enriched diet. These data indicate that sECC reduces the atherogenic properties of dietary cholesterol in mice. It is indicated that expression enhancement of hepatic LDL-receptor and cholesterol 7alpha-hydroxylase may be responsible for the hypercholesterolemic effect.
Subject(s)
Anticholesteremic Agents/pharmacology , Cholesterol 7-alpha-Hydroxylase/biosynthesis , Hypercholesterolemia/metabolism , Receptors, LDL/biosynthesis , Stilbenes/pharmacology , Animals , Anticholesteremic Agents/isolation & purification , Body Weight/drug effects , Cajanus/chemistry , Cholesterol/blood , Cholesterol/metabolism , Cholesterol 7-alpha-Hydroxylase/genetics , Cholesterol, LDL/blood , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/pharmacology , Gene Expression Regulation , Hypercholesterolemia/blood , Hypercholesterolemia/genetics , Hypercholesterolemia/pathology , Liver/metabolism , Liver/pathology , Male , Mice , Organ Size/drug effects , Plant Leaves/chemistry , Plants, Medicinal/chemistry , RNA, Messenger/metabolism , Receptors, LDL/genetics , Stilbenes/isolation & purification , Triglycerides/blood , Triglycerides/metabolismABSTRACT
Cajanus cajan (L) is a natural plant which contains a lot of potential active components. In the present study, we identified the effects of the stilbenes containing extract-fraction from Cajanus cajan L (sECC) on diet-induced (for 4 weeks) hypercholesterolemia in Kunming mice. All experimental mice were divided into 5 groups: control group, model group, sECC-treated with 200 or 100 mg/kg/day, and simvastatin group. The effects of sECC were investigated by monitoring serum and liver lipid profile (cholesterol homeostasis and triglyceride) as well as serum superoxide dismutase activity in those mice. To further explore the mechanism of sECC, hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase), cholesterol 7α-hydroxylase (CYP7A1), and low density lipoprotein receptor (LDL receptor) expressions in cholesterol homeostasis were analyzed by reverse transcription PCR. After 4 weeks pretreatment, compared with model group, the increased serum and hepatic total cholesterol were markedly attenuated by sECC (200 mg/kg) by 31.4% and 22.7% (p<0.01), respectively, the triglyceride levels of serum and liver were also lowered by 22.98% and 14.39%, respectively. At the same time, serum LDL cholesterol decreased by 52.8% (p<0.01) accompanied with the activities of serum superoxide dismutase increased by 20.98%. Atherogenic index and body weight were also reduced markedly. The mRNA expressions of HMG-CoA reductase, CYP7A1, and LDL-receptor were significantly enhanced in the mice administered with sECC (200 mg/kg/day), whereas those expressions were suppressed by the hypercholesterolemic diet. These data indicate that sECC reduces the atherogenic properties of dietary cholesterol in mice. Its hypocholesterolemic effect may involve enhancement of the hepatic LDL-receptor and cholesterol 7alpha-hydroxylase expression levels and bile acid synthesis.
Subject(s)
Cajanus/chemistry , Hypercholesterolemia/drug therapy , Plant Extracts/pharmacology , Stilbenes/pharmacology , Animals , Anticholesteremic Agents/pharmacology , Body Weight/drug effects , Cholesterol/metabolism , Cholesterol 7-alpha-Hydroxylase/genetics , Cholesterol 7-alpha-Hydroxylase/metabolism , Cholesterol, LDL/metabolism , Hydroxymethylglutaryl CoA Reductases/genetics , Hydroxymethylglutaryl CoA Reductases/metabolism , Hypercholesterolemia/chemically induced , Hypercholesterolemia/metabolism , Lipids/blood , Liver/drug effects , Liver/metabolism , Male , Mice , Receptors, LDL/genetics , Receptors, LDL/metabolism , Superoxide Dismutase/bloodABSTRACT
The progress in the studies on chemical constituents and pharmacological activity of the genus Pfaffia is summarized in recent 20 years. These plants contain various chemical constituents and have broad bioactivities such as sthenic, anti-tumor, analgesic and anti-inflammatory and should be further investigated.