Biosíntesis y mejoramiento de la producción de alcaloides en la familia Amaryllidaceae / Review biosynthesis and enhancement of alkaloid production in the Amaryllidaceae family

INTRODUCCIÓN: la presente revisión bibliográfica referencia diversos estudios que describen la biosíntesis de alcaloides en la familia Amaryllidacea. Se toman en cuenta los procesos enzimáticos que rigen la biosíntesis de los metabolitos secundarios y los métodos de estimulación y mejoramiento de la producción de alcaloides. OBJETIVO: determinar, mediante una amplia revisión bibliográfica, los posibles métodos de mejora de la producción de alcaloides. METODOLOGÍA: se realizó una revisión bibliográfica de los documentos más relevantes sobre la biosíntesis de alcaloides de Amaryllidaceae. RESULTADOS: en esta revisión, es posible establecer una metodología de mejoramiento de la producción de alcaloides tipo crinina/haemantamina en plantas de la familia Amaryllidaceae nativas de Bolivia y evaluar la posibilidad de aplicarla con éxito para la obtención de mejores rendimientos.(AU)

INTRODUCTION: the referenced studies in this bibliographic review show the alkaloid biosynthesis in the Amaryllidaceae family. Some of the processes involved in the improvement and stimulation of alkaloid production are also taken into account and the enzymatic processes that rule secondary metabolites synthesis are described. OBJECTIVE: to determine, through a bibliographic review, possible methods of improving alkaloid production. METHODS: a wide bibliographic review of the most relevant articles about the Amaryllidaceae family alkaloid production was applied. RESULTS: it was possible to demonstrate that there is the possibility to stablish and develop a successful method to improve the production of crinine/haemanthamine type alkaloids in the Bolivian native family Amaryllidacea and to evaluate the possibility of applying it successfully to obtain better yields.(AU)

Chemical evaluation and anticholinesterase activity of Hippeastrum puniceum (Lam. ) Kuntz bulbs (Amaryllidaceae)

Hippeastrum puniceum is a species that belongs to the Amaryllidaceae family. A particular characteristic of this family is the consistent and very specific presence of isoquinoline alkaloids, which have demonstrated a wide range of biological activities such as antioxidant, antiviral, antifungal, antiparasitic, and acetylcholinesterase inhibitory activity, among others. In the present work, fifteen alkaloids were identified from the bulbs of Hippeastrum puniceum (Lam.) Kuntz using a GC-MS approach. The alkaloids 9-O-demethyllycoramine, 9-demethyl-2α-hydroxyhomolycorine, lycorine and tazettine were isolated through chromatographic techniques. The typical Amaryllidaceae alkaloids lycorine and tazettine, along with the crude and ethyl acetate extract from bulbs of the species were evaluated for their inhibitory potential on α-amylase, α-glucosidase, tyrosinase and acetylcholinesterase activity. Although no significant inhibition activity was observed against α-amylase, α-glucosidase and tyrosinase from the tested samples, the crude and ethyl acetate extracts showed remarkable acetylcholinesterase inhibitory activity. The biological activity results that correlated to the alkaloid chemical profile by GC-MS are discussed herein. Therefore, this study contributed to the knowledge of the chemical and biological properties of Hippeastrum puniceum (Lam.) and can subsidize future studies of this species

Antitumor activity of lycorine in renal cell carcinoma ACHN cell line and its mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the antitumor effect of lycorine on renal cell carcinoma ACHN cells and explore the possible mechanism.</p><p><b>METHODS</b>We 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.</p><p><b>RESULTS</b>Lycorine 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.</p><p><b>CONCLUSION</b>Lycorine has obvious antitumor effect against ACHN cells, suggesting its value as a new therapeutic agent for renal cell carcinoma.</p>

Study on effect of lycorine in inducing apoptosis of pulmonary carcinoma cell A549 / 中国中药杂志

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.

An LC-MS/MS method for the simultaneous determination of lycorine and galanthamine in rat plasma and its application to pharmacokinetic study of Lycoris radiata extract in rats / 华中科技大学学报（医学）（英德文版）

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.

Effect of precursor on growth and accumulation of alkaloids of Lycoris radiata suspension cells / 生物工程学报

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.

Avaliação in vitro das atividades antiinflamatória, antioxidante e antimicrobiana do alcalóide montanina / In vitro evaluation of the antioxidant, anti-inflammatory and antimicrobial activities of the montanine alkaloid

Diversas propriedades biológicas, dentre as quais atividade antiparasitária, antitumoral, antiviral e anticolinesterásica são associadas aos extratos e produtos isolados, incluindo alcalóides de espécies de Amarilidáceas. Neste trabalho verificou-se para o alcalóide montanina, isolado dos bulbos de Rhodophiala bifida (Herb.) Traub (Amaryllidaceae), atividade antioxidante e ação inibitória sobre o crescimento de culturas de Saccharomyces cerevisae (ATCC 2601), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 6538), Staphylococcus epidermides (ATCC 12228) e Escherichia coli (ATCC 25922). A atividade antiinflamatória avaliada através da determinação da capacidade antiquimiotáxica da amostra apresentou resultados não significativos na dose empregada.

Several biological properties, such as antiparasite, antitumor, antiviral and anticholinesterasic activities, are associated with extracts and isolated products, including alkaloids from Amaryllidaceae species. In this study, the antioxidant activity and inhibitory action on the growth of cell cultures of Saccharomyces cerevisae (ATCC 2601), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 6538), Staphylococcus epidermides (ATCC 12228) and Escherichia coli (ATCC 25922) were observed to the montanine alkaloid, isolated from the bulbs of Rhodophiala bifida (Herb.) Traub (Amaryllidaceae). The anti-inflammatory activity, which was evaluated through the sample antichemotaxis ability determination, was not significant in the used dose.

Phytochemical and pharmacological research progress in Leontopodium medicinal plants / 中国中药杂志

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.