Efecto quimioprotector del extracto alcaloideo de Melocactus bellavistensis (cactus globoso) sobre el cáncer de colon inducido con 1,2-dimetilhidrazina en ratas / Chemoprotective effect of the alkaloid extract of Melocactus bellavistensis against colon cancer induced in rats using 1,2-dimethylhydrazine

RESUMEN Objetivos Determinar la toxicidad y el efecto quimioprotector del extracto alcaloideo de Melocactus bellavistensis (cactus globoso) sobre el cáncer de colon inducido en ratas con 1,2 dimetilhidrazina (DMH). Materiales y métodos Se obtuvo el extracto alcaloideo de la parte carnosa de Melocactus bellavistensis, posteriormente, se realizó un ensayo de toxicidad aguda en 30 ratones de cepas Balb C57. Para evaluar su efecto quimioprotector se indujo el cáncer de colon en 45 ratas Holtzmann con DMH, según el siguiente diseño experimental: un grupo control con: polisorbato de sodio (PS) a 2 mL/kg y cuatro grupos con DMH 20 mg/kg más 0, 1, 5 y 10 mg/kg de extracto alcaloideo de Melocactus bellavistensis respectivamente. Resultados Con una muestra de 5 g de extracto alcaloideo se determinó una DL50 mayor a 1000 mg/mL en el ensayo de toxicidad aguda del extracto alcaloideo de Melocactus bellavistensis. Los resultados del efecto quimioprotector en los indicadores de estudio histopatológico revelaron que a las dosis de 5 y 10 mg/kg demostraron actividad antitumoral significativa en el cáncer de colon inducido por dimetilhidrazina en ratas con 100% de inhibición de neoplasia. Conclusiones En condiciones experimentales, el extracto de alcaloides de Melocactus bellavistensis demostró tener efecto quimioprotector en cáncer de colon inducido por dimetilhidrazina en ratas.

ABSTRACT Objectives To determine the toxicity and chemoprotective effect of the alkaloid extract of Melocactus bellavistensis against colon cancer induced in rats using 1,2-dimethylhydrazine (DMH). Materials and methods The alkaloid extract was obtained from the fleshy part of M. bellavistensis, and an acute toxicity test was then carried out on 30 mice of the Balb C57 strain. To assess its chemoprotective effect, colon cancer was induced in 45 Holtzman rats using DMH according to the following experimental design: one control group received 2 mL/kg sodium polysorbate, and four groups received 20 mg/kg DMH plus 0, 1, 5, or 10 mg/kg M. bellavistensis alkaloid extract. Results With a sample of 5 g of alkaloid extract, an LD50 greater than 1000 mg/mL was determined in the acute toxicity test. Histological indicators revealed that the 5 and 10 mg/kg doses had significant anti-tumor activity with 100% neoplasia inhibition against DMH- induced colon cancer in rats. Conclusions Under experimental conditions, the alkaloid extract of M. bellavistensis has a chemoprotective effect against DMH-induced colon cancer in rats.

Cytotoxic effects of alkaloids on cervical carcinoma cell lines: a review / Efeitos citotóxicos de alcaloides sobre linhagens de células do câncer cervical: uma revisão

Cervical cancer is the fourth type of women neoplasia, with thousands of new cases annually. It is closely related to human papillomavirus (HPV) infection, which has more than 13 oncogenic types, among them HPV 16 and 18 are implicated in 70% of cervical carcinoma cases. Alkaloids are nitrogenated and naturally occurring compounds, showing several uses in medical treatment, including cytotoxic and antineoplastic activities. In this work we aim to evaluate the cytotoxic and chemotherapeutic potential of alkaloids against cervical cancer. In order to accomplish this purpose, we have made a survey of potentially effective alkaloids with cytotoxic activities over HPV-16+ and HPV-18+ cells (HeLa cells). Through a literature review between the years of 1980 and 2015, we described the major alkaloid sources, distribution in nature and also discussed the mechanisms of action for their cytotoxicity. We found that alkaloids showed efficacy as cytotoxic agents, inhibiting cell growth of the HPV-transformed cells in vitro and in vivo by means of activation of intrinsic and extrinsic pathways of apoptosis, which included the clivage of caspases and PARP-1 (Poli-Adenosyl- Ribose Protease 1), increase in p53 expression, release of cytochrome C and increase of cell death receptors expression like Fas, mainly observed in HeLa (HPV- 18+) cell lines. Moreover, these secondary metabolites helped in modulating the MDR (Multi-Drug Resistance) against the cell lines studied, which lead us to suggest their possible use as chemotherapeutic agents on the lesions caused by these viruses

O câncer cervical é a quarta neoplasia incidente em mulheres, com o surgimento de milhares de novos casos anualmente. Está altamente relacionado à infecção pelo papilomavírus humano (HPV), que apresenta mais de 13 tipos oncogênicos, dentre os quais os tipos 16 e 18 são encontrados em 70% dos casos de câncer do colo do útero (câncer cervical). Alcaloides são substâncias naturais nitrogenadas que apresentam diversos usos na terapia, incluindo atividades antineoplásica e citotóxica. Neste sentido, objetivamos neste trabalho avaliar o potencial citotóxico e quimioterápico de alcaloides sobre o câncer cervical. Para tanto, relacionamos os alcaloides com potencial citotóxico sobre HPV- 16+ e HPV-18+ (células HeLa), bem como mostramos suas principais fontes de obtenção, distribuição na natureza e discutimos os mecanismos de ação pelos quais realizam seu efeito citotóxico, através de uma revisão bibliográfica realizada entre o período de 1980 e 2015. Os alcaloides mostraram-se eficazes como drogas citotóxicas, inibindo o crescimento de células alteradas pelo HPV tanto in vitro quanto in vivo, com ativação de mecanismos intrínsecos e extrínsecos de apoptose, tais como ativação das caspases, clivagem de PARP-1 (Poli-ADP-Ribose Protease 1), aumento da expressão de p53, liberação de citocromo C e aumento da expressão de receptores de morte como o Fas, principalmente em células das linhagens HeLa (HPV-18+). Adicionalmente, esses metabólitos secundários auxiliaram na modulação da resistência a múltiplas drogas pelas linhagens de células estudadas, o que nos leva a sugerir o seu possível uso na quimioterapia das lesões provocadas por estes vírus.

Oxymatrine ameliorates renal ischemia-reperfusion injury from oxidative stress through Nrf2/HO-1 pathway

PURPOSE: To investigate if oxymatrine pretreatment could ameliorate renal I/R injury induced in rats and explore the possible role of oxymatrine in Nrf2/HO-1 pathway. METHODS: Unilaterally nephrectomized rats were insulted by I/R in their left kidney. Twenty four rats were randomly divided into three groups: sham group, I/R + saline-treated group, I/R + OMT-treated group. Oxymatrine or vehicle solution was administered intraperitoneally injected 60 min before renal ischemia, respectively. Renal function, histology, makers of oxidative stress, cell apoptosis and Nrf2/HO-1 expressions were assessed. RESULTS: Oxymatrine pretreatment exhibited an improved renal functional recovery, alleviated histological injury and oxidative stress, inhibiting tubular apoptosis, and accompanied by upregulated the expression of Nrf2/HO-1 proteins. CONCLUSION: Oxymatrine may attenuate renal ischemia/reperfusion injury, and this renoprotective effect may be through activating the Nrf2/HO-1 pathway. .

Evaluation of hepatoprotective activity of vasicinone in mice.

Justicia adhatoda (vasaka) leaves have long been used in Indian Ayurvedic system of medicine as antitussive. Its crude extract has been previously reported to have hepatoprotective activity. Vasicinone was isolated from leaves of J. adhatoda, column purified and characterized using, TLC UV, FT-IR and 1H NMR. The isolated vasicinone was evaluated for hepatoprotective activity using (CCl4)-induced acute hepatotoxicity model in mice. CCl4 treatments lead to significant increase in SGOT, SGPT, ALP levels. Pre-treatment with vasicinone and silymarin (25 mg/kg/day for 7 days) significantly decreased these enzyme levels. Histopathology of the livers from vasicinone and silymarin pre-treated animals showed normal hepatic cords and absence of necrotic changes suggesting pronounced recovery from CCl4 induced liver damage. Both vasicinone and silymarin significantly decrease the CCl4 mediated increase in pentobarbital indiced sleeping time in experimental animals, thus indicating recovery of liver function. Based on the above results it can be concluded that vasicinone may act as hepatoprotective in mice and warrants further investigation on human volunteers.

In vivo growth-inhibition of Sarcoma 180 by piplartine and piperine, two alkaloid amides from Piper

Piplartine {5,6-dihydro-1-[1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-2(1H)pyridinone} and piperine {1-5-(1,3)-benzodioxol-5-yl)-1-oxo-2,4-pentadienyl]piperidine} are alkaloid amides isolated from Piper. Both have been reported to show cytotoxic activity towards several tumor cell lines. In the present study, the in vivo antitumor activity of these compounds was evaluated in 60 female Swiss mice (N = 10 per group) transplanted with Sarcoma 180. Histopathological and morphological analyses of the tumor and the organs, including liver, spleen, and kidney, were performed in order to evaluate the toxicological aspects of the treatment with these amides. Administration of piplartine or piperine (50 or 100 mg kg-1 day-1 intraperitoneally for 7 days starting 1 day after inoculation) inhibited solid tumor development in mice transplanted with Sarcoma 180 cells. The inhibition rates were 28.7 and 52.3 percent for piplartine and 55.1 and 56.8 percent for piperine, after 7 days of treatment, at the lower and higher doses, respectively. The antitumor activity of piplartine was related to inhibition of the tumor proliferation rate, as observed by reduction of Ki67 staining, a nuclear antigen associated with G1, S, G2, and M cell cycle phases, in tumors from treated animals. However, piperine did not inhibit cell proliferation as observed in Ki67 immunohistochemical analysis. Histopathological analysis of liver and kidney showed that both organs were reversibly affected by piplartine and piperine treatment, but in a different way. Piperine was more toxic to the liver, leading to ballooning degeneration of hepatocytes, accompanied by microvesicular steatosis in some areas, than piplartine which, in turn, was more toxic to the kidney, leading to discrete hydropic changes of the proximal tubular and glomerular epithelium and tubular hemorrhage in treated animals.

Merging ethnoppharmacology with chemotaxonomy: An approach to unveil bioactive natural products. The case of Psychotria alkaloids as potential analgesics

Psychotria colorata (Will ex R&S) Muell.Arg. flowers are used by "caboclos" in the Amazon as the basis for a homemade analgesic. The study of P. colorata revealed the presence of several pyrrolidinoindoline alkaloids, some with opioid-like analgesic activity in vivo. Neurochemical studies of active alkaloids proved their capability of inhibiting [3H] naloxone binding, confirming the opioid nature of the analgesic activity. These data launched a broader screening of Psychotria species, including P. carthagenensis, P. brachyceras, P. leiocarpa, P. myriantha, P. suterella and P. brachypoda. The analysis of the analgesic activity of several Psychotria species, as well as of specific isolated compounds, allowed a tentative structure/activity relationship and opened a promising research avenue in the search for new analgesic drugs.

Botanical, chemical and pharmacological investigation on Cissampelos species from Paraíba (Brazil)

In our continuing search for biologically active compounds of local medicinal flora, we have investigated the genus Cissampelos (Meninspermaceae) whose species are used in ethnomedicine mainly for treatment of the diseases of the respiratory system. From the three species found in Paraiba: C. sympodialis, C. glaberrima and C. ovalifolia, only the first one was analyzed more extensively due to its greater availability and the high yield of warifteine, a bisbenzyltetrahydroisoquinoline alkaloid isolated from it. The water soluble fractions of the ethanolic extracts of the root, leaf and warifteine obtained from either of the fractions caused nonspecific smooth muscle relaxation in tissues such as the guinea pig trachea. The leaf fraction also showed bronchodilatory activity in whole animal experiments and inhibited human neutrophil degranulation induced by the peptide formyl-methionine-leucine-proline. The mechanism of action of the fraction involves on increase in intracellular cyclic adenosine monophosphate levels possibly as a result of the inhibition of nucleotide phosphodiesterase enzymes. The antiasthmatic use of the plant Cissampelos sympodialis may have scientific justification.

Estudio clínico de la efectividad de extractos alcaloideos obtenidos de los frutos del solanun americanum Miller sobre el herpes simplex herpes zoster y herpes genitalis / Clinic study of the affectiveness of alkaloids extracted of obtains of the fruts of the solanun americanum Miller on the herpes genitalis herpes zoster and herpes simplex

Una mezcla de Solanum alcaloides extraídos de Solanum americanum Miller, consiste principalmente de Solamargina y Solasodina, fue preparada sobre una base de crema hidrofólica y aplicado tópicamente a 46 pacientes de edades comprendidas entre 13 meses y 79 años, 34 de ellos con Herpes simplex, 9 con Herpes zoster y 3 con Herpes genitalis. Los pacientes con Herpes simplex, en un tratamiento de una duración máxima de 3 días obtuvieron una mejoría 24 horas después de la aplicación de la crema, con una sustancial disminución de prurito, el eritema y de las vesícula, mientras que los pacientes con Herpes zoster, en un tratamiento con una duración máxima de 10 días, presentaron una mejoría a las 24 horas, con aparición de costras a los 5 día y cicatrización a los 10 días. En el caso de los pacientes con Herpes genitalis se observó la desaparición de las lesiones en un tratamiento de un máximo de 5 días 91 por ciento de los pacientes con Herpes simplex tratados, no presentaron síntomas de recurrencia de la enfermedad después de 9 meses de iniciado el tratamiento. Ninguno de los 46 pacientes presentó efectos adversos

Propiedades farmacológicas in vitro de algunos extractos de Mimosa tenuiflora (tepescohuite) / In vitro pharmacological properties of some extracts of Mimosa tenuiflora (tepescohuite)

Se investigaron las propiedades de varios extractos de corteza de tepescohuite, Mimosa tenuiflora (Willd.) Poir. utilizando modelos biológicos in vitro, se observó que el extracto de acetato de etilo, cuyo contenido en taninos fue elevado, presentó actividad antimicrobiana; el extracto butanólico, rico en alcaloides, modificó de manera importante la excitabilidad de la musculatura lisa. Los extractos butanólico y metanólico produjeron hemólisis, posiblemente atribuible a su contenido en saponinas. Se discute la variedad de compuestos con propiedades biodinámicas que contiene este producto natural