Evaluación genotóxica de las moléculas con efectos tripanocida y leishmanicida cantin-6-ona y 5-metoxicantin-6-ona en células de médula ósea de ratones / Genotoxic evaluation of the molecules with trypanocidal and leishmanicidal effects, canthin-6-one and 5-methoxycanthin-6-one in mouse bone marrow cells

La tripanosomiasis americana y la leishmaniasis son problemas de salud pública relevantes en Iberoamérica. Las drogas utilizadas actualmente para el tratamiento de estas enfermedades poseen efectos colaterales tóxicos severos. Varios grupos de investigación están abocados a la búsqueda de productos naturales y sintéticos para encontrar nuevos agentes terapéuticos efectivos que no presenten reacciones colaterales adversas. En la evaluación de compuestos de la especie vegetal Zanthoxylum chiloperone (Rutaceae), se demostró que compuestos aislados del extracto presentaban actividad leishmanicida, tripanocida y antifúngica in vivo. Teniendo como antecedentes estos resultados, en el presente estudio se evaluaron los efectos genotóxico y citotóxico del cantín-6-ona y del 5-metoxicantin-6-ona, moléculas aisladas de la planta, en células de médula ósea de animales tratados. El estudio de los efectos genotóxicos se hizo a través del ensayo de modificaciones en la frecuencia de micronúcleos y el efecto citotóxico por modificaciones en la relación entre eritrocitos policromáticos y eritrocitos normocromáticos. Se realizaron 2 ensayos independientes y en cada ensayo los animales fueron divididos en tres grupos de tratamiento: GRUPO I: control negativo que recibió 200 uL de agua y 2.1% de DMSO, vía oral, GRUPO II: compuesto a ser evaluado (canthin-6-ona o 5-methoxicantin-6-ona) con 2.1% de DMSO, y GRUPO III: control positivo que recibió ciclofosfamida 50mg/kg/peso del animal, vía intraperitoneal. El análisis estadístico mostró que ambos compuestos no presentaron efectos genotóxicos ni citotóxicos. Estos resultados permiten proponer a estas moléculas como candidatas a ser sometidas a estudios más detallados como potenciales fármacos contra estas dos enfermedades

American trypanosomiasis and leishmaniasis are relevant public health problems in Latin America. The drugs currently used to treat these diseases have severe toxic side effects. Several research groups are dedicated to the search of natural and synthetic products to find new effective therapeutic agents that do not present adverse collateral reactions. In the evaluation of compounds of the plant species Zanthoxylum chiloperone (Rutaceae), it was shown that isolated compounds of the extract had leishmanicidal, trypanocidal and antifungal in vivo activities. Based on these results, the genotoxic and cytotoxic effects of canthin-6-one and 5-methoxycanthin-6-one, molecules isolated from the plant, on bone marrow cells of treated mice were evaluated in the present study. The study of genotoxic effects was made through the test of modifications in the frequency of micronuclei and the cytotoxic effects by modifications in the relationship between polychromatic erythrocytes and normochromic erythrocytes. Two independent assays were performed and in each assay the animals were divided into three treatment groups: GROUP I: negative control that received 200 µL of water and 2.1% of DMSO, orally, GROUP II: compound to be evaluated (canthin-6 -one or 5-methoxycanthin-6-one) with 2.1% DMSO, and GROUP III: positive control that received cyclophosphamide 50mg /kg animal weight, intraperitoneal. Statistical analysis showed that both compounds had neither genotoxic nor cytotoxic effects. These results allow these molecules to be proposed as candidates to be subjected to more detailed studies as potential drugs against these two diseases

A new β-carboline alkaloid from stems of Picrasma quassioidies / 中草药

Objective To study the alkaloids from the stems of Picrasma quassioidies. Methods The isolation and purification were carried out by column chromatography on CG161M, silica gel, ODS, and Sephadex LH-20. The structures were elucidated on the basis of physicochemical properties and spectroscopic analysis. Results A total of 16 alkaloids were isolated and identified from 85% ethanol aqueous extract of the stems of P. quassioidies. It included 12 β-carboline alkaloids including 1-(1-hydroxy)-ethyl-6-hydroxy-β-carboline (1), 6-hydroxy-β-carboline-1-carboxylic acid (2), β-carboline-1-carboxylic acid (3), β-carboline-1-propanoic acid (4), 3-hydroxy-β-carboline (5), 1-acetyl-β-carboline (6), 1-ethoxycarbonyl-β-carboline (7), 1-(9H-β-carbolin-1-yl)-ethanol (8), picrasidine X (9), 1-hydroxymethyl-β-carboline (10), 9H-pyrido [3,4-b] indole (11), 6-hydroxy-2-methyl-9H-β-carbolin-2-ium (12); and four cantin-6-one alkaloids, including 4,5-dimethoxycanthin-6-one (13), 3-methylcanthin-5,6-dione (14), 5-hydroxy-4-methoxylcanthin-6-one (15), and picrasidine O (16). Conclusion Compound 1 is a new β-carboline alkaloid named picrasidine Z, and compound 12 is a new natural product.

Chemical constituents of total alkaloids from Picrasma quassioides and its effects on collagen induced arthritis in rats / 中国药科大学学报

@#This study aimed to investigate the effects of total alkaloids from Picrasma quassioides(TAPQ)on collagen-induced arthritis(CIA)in rats. TAPQ were prepared by acid extraction and alkali precipitation. The qualitative analysis of TAPQ by HPLC-Q-TOF-MS/MS was carried out. Fourteen alkaloids were obtained and three of them were quantitatively analyzed by HPLC. The anti-inflammatory activity of TAPQ was investigated on RAW264. 7 induced by LPS. Dexamethasone was used as a positive control. The model of bovine type II collagen-induced rheumatoid arthritis in SD rats was established. Daily tail intravenous injection of 0. 907 or 1. 814 mg/kg of TAPQ was administered for 18 days continuously, using dexamethasone as a positive control. The changes of mean arthritis scores in the paw of the rats and the volume of the paw were measured every day. Compared with the model group, the TAPQ significantly reduced the degree of paw swelling(P< 0. 001). After the rats were sacrificed, the levels of TNF-α and IL-6 in the serum were measured. The TAPQ could significantly reduce the level of TNF-α(P< 0. 01)and IL-6(P< 0. 001). The pathological changes of the joints were observed by HE staining, the anti-inflammatory activity of TAPQ was good, and the degree of joint damage in rats was obviously reduced.

Chemical constituents from roots of Ailanthus altissima / 中草药

Objective: To study the chemical constituents from the roots of Ailanthus altissima. Methods: Compounds were isolated and purified by silica gel column chromatography and HPLC, and their structures were identified by spectral analysis. Results: Fourteen compounds were isolated and identified as 20-hydroxydammar-24-en-3-one (1), β-sitosterol (2), ocotillone (3), 5,6,7,8-tetramethoxycoumarin (4), niloticin (5), isofouquierone peroxide (6), 20S,24S-dihydroxydammar-25-en-3-one (7), piscidinol A (8), eichlerianic acid (9), dihydroniloticin (10), dammar-24-ene-12β,20β-diol-3-one (11), canthin-6-one (12), 12β-hydroxy ocotillone (13), and 20S,25-epoxy-24R-hydroxy-3-dammaranne (14). Conclusion: Compounds 3, 4, 6, 9, 10, and 13 are isolated from this plant for the first time.

Alkaloids from twigs and leaves of Picrasma quassioides / 中草药

Objective To study alkaloids from the twigs and leaves of Picrasma quassioides. MethodsCompounds were isolated and purified by column chromatography over Sephadex LH-20 and silica gel column. Their chemical structures were elucidated on the basis of physicochemical properties and spectral data. Results Sixteen alkaloids were isolated, purified, and identified as: 5-methoxycanthin-6-one (Ⅰ), 11-hydroxycanthin-6-one (Ⅱ), canthin-6-one (Ⅲ), 4, 5-dimethoxycanthin-6-one (Ⅳ), 4-methoxy-5-hydroxycanthin-6-one (Ⅴ), 3-methylcanthin-2, 6-dione (Ⅵ), 1-formyl-4-methoxy-?-carboline (Ⅶ), 1-methoxy-?-carboline (Ⅷ), 1-ethyl-4, 8-dimethoxy-?-carboline (Ⅸ), 1-methoxycarbonyl-4-hydroxyl-?-carboline (Ⅹ), 1-methyl-4-methoxy-?-carboline (Ⅺ), 1-ethoxycarbonyl-?-carboline (ⅩⅡ), 1-formyl-?-carboline (ⅩⅢ), 1-methoxycarbonyl-?-carboline (ⅩⅣ), 1-ethyl-4-methoxy-?-carboline (ⅩⅤ), and 1, 2, 3, 4-tetrahydro-1, 3, 4-trioxo-?-carboline (ⅩⅥ). Conclusion Compound Ⅺ is separated from the natural plant for the first time and compounds Ⅱ, Ⅷ, and ⅩⅤ are separated from plants of Picrasma Bl. for the first time.