Perennial herb Hymenocallis littoralis(Amaryllidaceae) boasts anti-tumor, anti-virus, and anti-inflammatory activities. As the representative constituents, alkaloids have attracted much attention, whereas the non-alkaloid constituents have been rarely reported. Therefore, this study investigated the non-alkaloid constituents of H. littoralis and their contribution to the various pharmacological activities of the herb. Thirteen non-alkaloid compounds were isolated from the 95% ethanol extract of dried whole plant of H. littoralis after a series of chromatographic separation steps and spectral analysis, and they were identified as 5,7-dihydroxy-6,8-dimethoxy-2-hydroxymethyl-4H-chromoen-4-one(1), undulatoside A(2),(2S)-7,4'-dihydroxyflavane(3), naringenin(4), 4',7-hydroxy-8-methylflavanone(5), 8-methylnaringenin(6), 8-demethylfarrerol(7), 6-methyl-aromadendrin(8), 4',5,7-trihydroxy-8-methylflavanone(9), syzalterin(10), 6-methylapigenin(11), isoliquiritigenin(12), and undatuside C(13) based on the spectroscopic data analysis. Among them, compound 1 was a new chromone derivative, and compounds 2 and 4-13 were isolated form this plant for the first time.
Alkaloids ; Amaryllidaceae ; Chromones ; Liliaceae

In order to investigate the effects of phenylalanine, tyrosine and tyramine on the growth of Lycoris radiata suspension cells and the accumulation of alkaloids, the growth quantity of the cells as well as the content of alkaloids in cells were determined, which were treated with above three kinds of precursors alone and phenylalanine combined with tyrosine respectively. The results indicate that the addition of phenylalanine alone and addition of phenylalanine on the basis of tyrosine at high concentration (200 micromol/L) had no significant effect on the growth of Lycoris radiata suspension cells and the content of alkaloids in cells; whereas tyrosine and tyramine promoted the growth of the cells and alkaloids accumulation. Treated with tyrosine at high concentration (200 micromol/L), the content of alkaloids of the cells was 2.56-fold higher than that of the control group, the amounts of lycoramine (3.77 mg/g) and galanthamine (4.46 mg/g) were 6.61-fold and 6.97-fold higher than that of the control group, respectively. When treated with tyramine (200 micromol/L), the amount of alkaloids in Lycoris radiata suspension cells was 2.63-fold higher than that of the control group, and the amounts of lycoramine (4.45 mg/g) and galanthamine (5.14 mg/g) were 9.08-fold and 9.18-fold higher than that of the control group, respectively. The above results demonstrate that adding tyrosine and tyramine in the media significantly promoted the growth of the Lycoris radiata suspension cells and alkaloids accumulation in the cells.
Amaryllidaceae Alkaloids ; chemistry ; Cells, Cultured ; Culture Media ; chemistry ; Galantamine ; chemistry ; Lycoris ; chemistry ; growth & development ; Phenylalanine ; chemistry ; Plant Cells ; chemistry ; Plant Extracts

A rapid, sensitive, and selective liquid chromatography-tandem mass spectrometry was developed for the simultaneous determination of lycorine and galanthamine, two major constituents in Lycoris radiata extract, in rat plasma. Liquid-liquid extraction with ethyl ether was carried out using diphenhydramine as the internal standard. The two bioactive alkaloids were separated on a Zorbax SB-C18 reserved-phase column (150 mm × 4.6 mm, i.d., 5 μm) by gradient elution using a mobile phase consisting of methanol with 0.1% formic acid (A) and water with 0.1% formic acid (B) at a flow rate of 0.6 mL/min. All analytes showed good linearity over a wide concentration range (r (2)>0.99) and the lower limit of quantification was 3.00 ng/mL for each analyte. The average extraction recovery of the analytes from rat plasma was more than 82.15%, and the intra-day and inter-day accuracy and precision of the assay were less than 12.6%. The validated method was successfully applied to monitoring the concentrations and pharmacokinetic studies of two Amaryllidaceous alkaloids in rat plasma after an oral administration of Lycoris radiata extract.
Amaryllidaceae Alkaloids ; pharmacokinetics ; Animals ; Chromatography, Liquid ; Galantamine ; pharmacokinetics ; Lycoris ; chemistry ; Male ; Parasympathomimetics ; pharmacokinetics ; Phenanthridines ; pharmacokinetics ; Plant Extracts ; chemistry ; pharmacokinetics ; pharmacology ; Rats ; Rats, Wistar ; Tandem Mass Spectrometry ; methods

OBJECTIVETo investigate the antitumor effect of lycorine on renal cell carcinoma ACHN cells and explore the possible mechanism.

METHODSWe used flow cytometry to examine the effect of lycorine on ACHN cell cycle and apoptosis. The cell proliferation, migration and invasion were assessed with MTS assay, wound healing assay, and Transwell assay, respectively. Colony forming assay was performed, and the mRNA and protein levels of Bax, Bcl-2, survivin, caspase-3, cyclin D1 and CDK4 were measured with qRT-PCR and Western blotting.

RESULTSLycorine obviously inhibited the proliferation of ACHN cells with an IC(50) of 24.34 µmol/L. Lycorine also induced apoptosis of ACHN cells, caused cell cycle arrest at G(0)/G(1) phase, and suppressed the colony forming ability of the cells in a dose-dependent manner. The migration and invasion of ACHN cells were significantly inhibited by 5 µmol/L lycorine. Lycorine up-regulated the mRNA levels of CDK4, Bax, caspase-3 while down-regulated the levels of survivin, Bcl-2 and Cyclin D1; the protein levels of CDK4 and Bax were increased and cyclin D1, Bcl-2 and surviving expressions were decreased, but caspase-3 expression showed no significant changes following the treatment.

CONCLUSIONLycorine has obvious antitumor effect against ACHN cells, suggesting its value as a new therapeutic agent for renal cell carcinoma.

Amaryllidaceae Alkaloids ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; Carcinoma, Renal Cell ; pathology ; Caspase 3 ; metabolism ; Cell Cycle Checkpoints ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase 4 ; metabolism ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Phenanthridines ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; bcl-2-Associated X Protein ; metabolism

This paper reviewed the phytochemical and pharmacological research progress in Leontopodium medicinal plants, including the resource distribution, the chemical constitutes, the pharmacological activities and clinical application. The review has provided some information for the study and development of Leontopodium medicinal plants in future.
Amaryllidaceae Alkaloids ; isolation & purification ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; therapeutic use ; Asteraceae ; chemistry ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; therapeutic use ; Flavanones ; isolation & purification ; Humans ; Isoquinolines ; isolation & purification ; Nephritis ; drug therapy ; Oils, Volatile ; isolation & purification ; Phytotherapy ; Plants, Medicinal ; chemistry

To explore the effect of lycorine in inducing apoptosis of pulmonary carcinoma cell A549 and its mechanism. In the study, pulmonary carcinoma cell A549 were taken as the experimental subject and processed with different concentrations of lycorine (0, 0.5, 1.0, 2.0, 4.0 and 8.0 μmol x L(-1)). The MTT method was used to observe the cell proliferation. The apoptosis rate of A549 cells was determined by Annexin FITC/PI double staining. The microplate reader was used to detect the activities of Bcl-2, Bax and p53. The changes in mitochondrial membrane potential were measured by the flow cytometry. The expressions of apoptosis-related factors Bcl-2, Bax, p53 and Survivin were determined by Real-time PCR. The results showed that lycorine significantly inhibited the proliferation of A549 cells (P < 0.05), induced the apoptosis on A549 cells (P < 0.05), increased the activities of Bax and p53, reduced Bcl-2 activity and mitochondrial membrane potential, and notably changed the gene expressions of Bcl-2, Bax, p53 and Survivin (P < 0.05). In conclusion, lycorine can induce the apoptosis of A549 cells and be applied to treat pulmonary carcinoma. Its mechanism may be related to the activation of relevant factors in Bcl-2 signaling pathway.
Amaryllidaceae Alkaloids ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Carcinoma ; drug therapy ; genetics ; metabolism ; physiopathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology ; Phenanthridines ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Signal Transduction ; drug effects ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; bcl-2-Associated X Protein ; genetics ; metabolism

Among the Acetylcholinesterase inhibitors as used for Alzheimer's disease treatment, Galantamine has been recently developed and widely used owing to proven its clinical efficacy and safety. However, it has reported that prolonged QT interval, which can lead to ventricular arrythimias such as Torsade de points, has developed in Galantamine-treated patients. A 74-year-old female Alzheimer's patient been treated with galantamine for 8 months visited the hospital complaining about frequent dizziness. ECG monitor was performed promptly, it was informed that the prolonged QTc interval was increased 450 ms to 486 ms. So, we made her stop taking the galantamine, and after that QTc interval has normalized to 406 ms. In this article, we reported the first case on prolonged QT interval associated with galantamine in Korea.
Aged ; Alzheimer Disease ; Cholinesterase Inhibitors ; Dizziness ; Electrocardiography ; Female ; Galantamine ; Humans ; Korea ; Organothiophosphorus Compounds

OBJECTIVES: The purpose of this study was to compare the efficacy of galantamine treatment, especially attention ability between patients with pure Alzheimer's disease (AD) and Mixed dementia (MD) during a 24-week trial. METHODS: A total of 40 patients were recruited for this 24-week study. The effect of galantamine on attention was measured using Seoul Computerized NeuroCognitive Function Test (SCNT) and frontal functions test of Seoul Neuropsychological Screening Battery (SNSB). Patients'activities of daily living using the Seoul-Activities of Daily Living (S-ADL) and the Seoul-Instrumental Activities of Daily Living (S-IADL) ; behavioral symptoms using the Korean version Neuropsychiatric Inventory (K-NPI) were measured at baseline and 24-week. RESULTS: 17 pure AD patients and 23 MD patients were analyzed in this study. Attention as measured by SCNT was not significantly different from baseline after 24 weeks of treatment in both groups. There was no significant difference between two groups in mean change from baseline in the SCNT, S-ADL, S-IADL and K-NPI scores at 24-week. CONCLUSION: Galantamine showed a therapeutic effect on cognition, activities of daily living, neuropsychiatric symptoms in pure AD and MD. Furthermore, Galantamine may specifically help to maintain attention and it may have positive effects on other cognitive and functional abilities.
Activities of Daily Living ; Alzheimer Disease ; Attention ; Behavioral Symptoms ; Cognition ; Dementia ; Galantamine ; Humans ; Mass Screening

Cholineacetyltrasnferase (ChAT) is a key enzyme that facilitates synthesis of acetylcholine affecting the memory, learning, awakening and sleep process of the cerebrum. The object of this study was to test the hypothesis that the ChAT-gene 2384G>A (rs3810950) polymorphism is associated with Alzheimer's disease (AD) susceptibility, and galantamine response. To elucidate a genetic predisposition of AD, we studied ChAT-gene 2384G>A (rs3810950) polymorphism in 52 AD patients in 93 normal controls. We also examined the association of this polymorphism and galantamine therapeutic response in 52 AD patients who received a 24-week galantamine treatment. There were no significant differences in the genotype or allele frequency of the ChAT polymorphism between the AD and control groups. However, we found that the allele-carrier distributions, allele frequency for the ChAT polymorphism differed significantly between responders and non-responders. The frequency of A-allele carriers (GA+AA) was higher in responders than in non-responders (chi-square=4.282, df=1, p=0.039), as was the A-allele frequency (chi-square=5.216, df=1, p=0.022). These results suggest that the ChAT-gene 2384G>A (rs3810950) polymorphism is associated with galantamine therapeutic response.
Acetylcholine ; Alzheimer Disease ; Cerebrum ; Galantamine ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Learning ; Memory

BACKGROUND AND PURPOSE: The positive effects of galantamine on cognition and activities of daily living (ADL) in Alzheimer's disease (AD) are thought to be mediated via improvements in attention. The purpose of this study was to determine the effect of galantamine on attention in AD patients using a computerized attention test and to elucidate the relationship between improvements in attention and change in cognition and ADL. METHODS: In this multicenter, open-label, prospective study, patients with mild to moderate AD received galantamine and then submitted to computerized attention tests, the Alzheimer's Disease Assessment Scale-cognitive subscale, and instrumental ADL (IADL) at baseline, 4 weeks, and 12 weeks. The differences in reaction time on computerized tests were explored relative to the changes in cognition and IADL. RESULTS: After 12 weeks of taking the trial medication there was a significant reduction from baseline levels in the choice reaction time (baseline, 5,216+/-3,650 sec; 12 weeks, 4,139+/-2,920 sec; p<0.01) and the simple reaction time (baseline, 1,089+/-782 sec; 12 weeks, 908+/-606 sec; p<0.01). Correlation analyses of changes in choice or simple reaction times relative to cognition and ADL measures yielded no significant associations. The improvement in attention observed at 4 weeks of galantamine treatment was not associated with any significant changes in outcome measures at the end of trial. CONCLUSIONS: This study found no significant association between the improvement in attention after treatment with galantamine and changes in cognition and ADL in patients with mild to moderate AD, despite the significant improvement in attention over the course of the treatment.
Activities of Daily Living* ; Alzheimer Disease* ; Cognition* ; Galantamine* ; Humans ; Outcome Assessment (Health Care) ; Prospective Studies ; Reaction Time