RESUMEN
This work reports the antiproliferative activity of seco-oxacassanes 1-3, isolated from Acacia schaffneri, against human colon (HT-29), lung (A-549), and melanoma (UACC-62) cancer cell lines, as well as against their non-malignant counterparts CCD-841 CoN, MRC-5, and VH-10, respectively, using the sulforhodamine B test. While compounds 1 and 3 were inactive, 2 presented strong activity with IC50 values between 0.12 and 0.92 µg mL(-1). The cytotoxicity mechanisms of 2 were investigated by cell cycle analysis and through DNA repair pathways, indicating that the compound is capable of arresting the cell cycle in the G0/G1 phase. This effect might be generated through damage to DNA by alkylation. In addition, compound 2 was able to decrease HT-29 migration.
Asunto(s)
Acacia/química , Proliferación Celular/efectos de los fármacos , Diterpenos/farmacología , Inhibidores de Crecimiento/farmacología , Melanoma/fisiopatología , Extractos Vegetales/farmacología , Ciclo Celular/efectos de los fármacos , Diterpenos/química , Inhibidores de Crecimiento/química , Células HT29 , Humanos , Melanoma/tratamiento farmacológico , Extractos Vegetales/química , Relación Estructura-ActividadRESUMEN
AIM: To evaluate the effect of an extract of Geranium schiedeanum (Gs) as a hepatoprotective agent against ethanol (EtOH)-induced toxicity in rats. METHODS: Male Wistar rats weighing 200-230 g were subjected to a 70% partial hepatectomy (PH); they were then divided into three groups (groups 1-3). During the experiment, animals in group 1 drank only water. The other two groups (2-3) drank an aqueous solution of EtOH (40%, v/v). Additionally, rats in group 3 received a Gs extract daily at a dose of 300 mg/kg body weight intragastically. Subsequently, to identify markers of liver damage in serum, alanine aminotransferase, aspartate aminotransferase, albumin and bilirubin were measured by colorimetric methods. Glucose, triglyceride and cholesterol concentrations were also determined. In addition, oxidative damage was estimated by measuring lipid peroxidation [using thiobarbituric-acid reactive substances (TBARS)] in both plasma and the liver and by measuring the total concentration of antioxidants in serum and the total antioxidant capacity in the liver. In addition, a liver mass gain assessment, total DNA analysis and a morpho-histological analysis of the liver from animals in all three groups were performed and compared. Finally, the number of deaths observed in the three groups was analyzed. RESULTS: Administration of the Geranium shiedeanum extract significantly reduced the unfavorable effect of ethanol on liver regeneration (restitution liver mass: PH-EtOH group 60.68% vs PH-Gs-EtOH group 69.22%). This finding was congruent with the reduced levels of hepatic enzymes and the sustained or increased levels of albumin and decreased bilirubin in serum. The extract also modified the metabolic processes that regulate glucose and lipid levels, as observed from the serum measurements. Lower antioxidant levels and the liver damage induced by EtOH administration appeared to be mitigated by the extract, as observed from the TBARs (PH-EtOH group 200.14 mmol/mg vs PH-Gs-EtOH group 54.20 mmol/mg; P < 0.05), total status of antioxidants (PH-EtOH group 1.43 mmol/L vs PH-Gs-EtOH group 1.99 mmol/L; P < 0.05), total antioxidant capacity values, liver mass gain and total DNA determination (PH-EtOH group 4.80 mg/g vs PH-Gs-EtOH 9.10 mg/g; P < 0.05). Overall, these processes could be related to decreased mortality in these treated animals. CONCLUSION: The administered extract showed a hepatoprotective effect, limiting the EtOH-induced hepatotoxic effects. This effect can be related to modulating oxido-reduction processes.
Asunto(s)
Antioxidantes/farmacología , Etanol , Geranium , Hepatopatías Alcohólicas/tratamiento farmacológico , Regeneración Hepática/efectos de los fármacos , Hígado/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Antioxidantes/metabolismo , Biomarcadores/sangre , Citoprotección , Replicación del ADN/efectos de los fármacos , Modelos Animales de Enfermedad , Geranium/química , Hepatectomía , Hígado/metabolismo , Hígado/patología , Hígado/fisiopatología , Hepatopatías Alcohólicas/sangre , Hepatopatías Alcohólicas/patología , Hepatopatías Alcohólicas/fisiopatología , Masculino , Estrés Oxidativo/efectos de los fármacos , Fitoterapia , Plantas Medicinales , Ratas Wistar , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
BACKGROUND: Geranium bellum Rose, locally known as "Pata de león", is a perennial plant distributed in the mountains of Hidalgo, Mexico. It is widely used in Mexican traditional medicine to treat fever, pain, and gastrointestinal disorders. To date, there are not published studies regarding the in vivo antinociceptive and anti-inflammatory potential of the acetone-aqueous extract from the aerial parts of G. bellum. METHODS: Antinociceptive effects of the acetone-aqueous G. bellum (AGB) extract and the isolated compounds were assessed using experimental pain models, including thermal nociception like hot plate test, and chemical nociception induced by intraperitoneal acetic acid or subplantar formalin injection in vivo. The anti-inflammatory properties of the extract were studied using systemic administration in carrageenan-induced paw edema. RESULTS: Intra-gastric administration of AGB (75, 150, and 300 mg/kg) showed a dose-dependent antinociceptive effect in intraperitoneal acetic acid (writhing), thermal nociception in CD1 mice, and subplantar formalin models, as well as anti-inflammatory effect in carrageenan- induced paw edema in Wistar rats. Geraniin and quercetin showed the highest antinociceptive activity in writhing test, whereas ellagic acid was the most active compound in the hot plate model. CONCLUSION: These studies provide evidences that G. bellum shows antinociceptive and anti- inflammatory effects, and gives support to its use in treating pain in Mexican traditional medicine.
Asunto(s)
Analgésicos/uso terapéutico , Antiinflamatorios/uso terapéutico , Geranium/química , Inflamación/tratamiento farmacológico , Dolor/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/uso terapéutico , Ácido Acético , Analgésicos/aislamiento & purificación , Analgésicos/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Carragenina , Edema/tratamiento farmacológico , Ácido Elágico/aislamiento & purificación , Ácido Elágico/farmacología , Ácido Elágico/uso terapéutico , Femenino , Formaldehído , Glucósidos/aislamiento & purificación , Glucósidos/farmacología , Glucósidos/uso terapéutico , Calor , Taninos Hidrolizables/aislamiento & purificación , Taninos Hidrolizables/farmacología , Taninos Hidrolizables/uso terapéutico , Inflamación/inducido químicamente , Masculino , México , Ratones , Dolor/inducido químicamente , Dimensión del Dolor , Extractos Vegetales/química , Extractos Vegetales/farmacología , Quercetina/aislamiento & purificación , Quercetina/farmacología , Quercetina/uso terapéutico , Ratas WistarRESUMEN
The use of medicinal plants in treating illnesses has been reported since ancestral times. In the case of hepatic diseases, several species such as Silybum marianum, Phyllanthus niruri, and Panus giganteus (Berk.) have been shown to ameliorate hepatic lesions. Silymarin is a natural compound derived from the species Silybum marianum, which is commonly known as Milk thistle. This plant contains at least seven flavoligands and the flavonoid taxifolin. The hepatoprotective and antioxidant activity of silymarin is caused by its ability to inhibit the free radicals that are produced from the metabolism of toxic substances such as ethanol, acetaminophen, and carbon tetrachloride. The generation of free radicals is known to damage cellular membranes and cause lipoperoxidation. Silymarin enhances hepatic glutathione and may contribute to the antioxidant defense of the liver. It has also been shown that silymarin increases protein synthesis in hepatocytes by stimulating RNA polymerase I activity. A previous study on humans reported that silymarin treatment caused a slight increase in the survival of patients with cirrhotic alcoholism compared with untreated controls.
RESUMEN
The aerial parts of Geranium potentillaefoium afforded geraniin (1), corilagin (2), gallic acid (4), methyl gallate (6), methyl brevifolincarboxylate (7), quercetin, quercetin 3-O-beta-D-glucopyranoside, quercetin 3-O-beta-D-[6"-O-galloyl)glucopyranoside, kaempferol, beta-sitosterol 3-O-beta-D-glucopyranoside and beta-sitosterol, while the aerial parts of G. bellum gave the same compounds in addition to kaempferol 3-O-beta-D-glucopyranoside, isolated instead of kaempferol. The substances were identified by 1D and 2D NMR spectroscopy in comparison with published data. The water decoction preparations from air-dried plant materials (2.5 g) contain ca. 4.6 % of the ellagitannin 1, envisaging that when such decoction is ingested (250 mL), a therapeutic dose of ca. 36 mg of the antitumor ellagic acid (3) may be incorporated into the organism.