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Objective:To explore the hepatoprotective effect and its mechanism of the geraniin on mice with acute liver injury induced by D-galactosamine (D-GalN). Method:A total of 60 Kunming mice were randomly divided into normal group, model group, Silymarin group (positive group 180 mg·kg-1), and low, medium and high-dose geraniin groups (50, 100, 200 mg·kg-1). All the mice were given with saline or corresponding dose of drugs (10 mL·kg-1) by gavage once a day for 10 d. After 2 h of the last administration, except the normal group, the mice of other groups were injected intraperitoneally with D-GalN (500 mg·kg-1) to induce the acute liver injury. After 16 h, the eye balls of mice were removed to take blood, and all mice were put to death to collect samples of liver. Activity or content of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) in liver were determined by biochemical method. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), γ-interferon (IFN-γ) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA), and expressions of Toll-like receptor-4(TLR-4) and nuclear factor(NF)-κB proteins were detected by Western blot. Liver histopathological changes were observed by hematoxylin-eosin (HE) staining. Result:Compared with the normal group, the serum levels of ALT, AST, ALP, TBIL and liver MDA in the model group were significantly increased (PPPPPPα, IL-1β, IL-6, IFN-γ and the expressions of TLR-4 and NF-κB proteins in serum (PPConclusion:Geraniin has an obvious protective effective on acute liver injuries induced by D-GalN in mice. Its mechanism may be correlated with oxidative stress, inflammation and TLR-4/NF-κB signaling pathway.
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OBJECTIVE@#A preliminary study showed that geraniin extracted from Nephelium lappaceum L. at 50 mg/kg caused reduction in blood glucose and insulin resistance. The present study serves to further investigate the effects of geraniin at increasing doses between 3.125 and 100 mg/kg in high-fat diet-treated rats.@*METHODS@#Geraniin (95% purity) was extracted and purified from rambutan rind. Two groups of male Sprague-Dawley rats were fed with 60% high-fat diet and standard rat chow, respectively, for 12 weeks. High-fat diet-treated rats were then administered geraniin at different doses. Body weight, blood pressure and blood glucose readings were measured. At the end of treatment, blood was collected for analysis of glycated haemoglobin A1c (HbA1c), insulin, advanced glycation end-product (AGE) levels, renin, aldosterone and electrolytes.@*RESULTS@#Within the first week of treatment, even the lowest dose of geraniin caused a significant reduction in blood pressure, which was comparable to control diet-treated rats. There were no changes in serum electrolytes, renin or aldosterone. Similarly, there was a significant reduction in serum insulin, insulin resistance and AGE levels at the lowest dose. However, there was no significant decrease in fasting blood glucose or HbA1c. The effects of decreasing insulin, insulin resistance and AGEs were observed only at the lower doses, unlike the results observed for blood pressure reduction.@*CONCLUSION@#Geraniin at lower doses improved blood pressure and other metabolic parameters. Secondary metabolites of geraniin, associated with antihypertensive activity, are relatively different to those involved in inhibiting AGE formation and increasing insulin sensitivity. The secondary metabolites of geraniin may be individually responsible for the bioactivities demonstrated.
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Objective To investigate the the effects of geraniin on modulating the mRNA expression of corebinding factor α 1 (Cbfα 1). Methods The m RNA expressions of Cbfα 1 were detected by real time fluorescence quantitative PCR. Results As compared with the sham group, the expressions of Cbfα 1 mRNA were markedly suppressed in the model group, 12 and 24 w after OPF (P ＜ 0.05). Compared with the model group, geraniin significantly increased mRNA expressions of Cbfα 1. Conclusion Geraniin can upregulate Cbfα 1 gene expression and improve the treatment for OPF.
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In this study, the effects of geraniin on osteoprotegerin/receptor activator of nuclear factor-κB ligand(OPG/RANKL) in regulating the proliferation of osteoblasts and suppression of osteoclast-like cells (OLC) in OLC-osteoblast co-cultured system in vitro were investigated. Osteoblasts were cultured and identified with alkaline phosphatase (ALP), gomori stain, and mineralized nodule stain. OLCs were isolated from long bones of Sprague-Dawley (SD) rats and identified with tartrate-resistant acid phosphatase(TRAP) stain. Methyl thiazolyl tetrazolium assay was used to examine the proliferation of osteoblasts, and immunocytochemistry and in situ hybridization to analyze the expression OPG/RANKL in osteoblasts co-cultured with osteoclasts under the action of geraniin, respectively. Geraniin could regulate the proliferation of osteoblasts MC3T3-E1, decrease the number of OLC in OLC-osteoblast co-cultured system, and inhibit the bone resorption areas and resorption pits of OLC in vitro experiments. Geraniin could promote the mRNA and protein expression levels of OPG and suppress those of RANKL in osteoblasts. These results indicate that geraniin has a promoting effect on the proliferation of osteoblasts and an inhibitory effect on the osteoclastic bone-resorption through regulating OPG/RANKL signaling pathway in OLC-OB co-cultured system.
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Animals , Male , Female , Rats , RANK Ligand/classification , Osteoprotegerin/adverse effects , Osteoblasts , Phyllanthus/classification , Plant Components, AerialABSTRACT
Objective To investigate the effect of geraniin on expression of Wnt3a protein and mRNA in bone marrow stromal cell (BMSC) from osteoporotic rats. Methods The model of osteoporosis (OP) was duplicated by ovariectomy in rats. BMSCs were isolated and cultured. BMSCs from shamed rats were routinly cultured and taken as normal control, and BMSCs from OP rats were divided into model group, 1μmol/L simvastatin positive group, and geraniin group (0.01, 0.1, 1, 10, 100 μmol/L), respectively. The methods of realtime-PCR and western blot were used to assay the protein and mRNA expression of wnt3a, respectively.Results As compared with normal control group, the protein and mRNA expression of wnt3a in model group were significantly suppressed;Compared with model group, 1 μmol/L simvastatin, and 0.1, 1, 10 and 100 μmol/L geraniin significantly increased the expression of wnt3a protein and mRNA. Conclusion It is suggested that geraniin activates wnt/β-catenin pathway though increasing the expression of signaling protein wnt 3a in BMSCs from OP rats. It would be beneficial to osteogenic differentiation of BMSCs and osteogenesis.
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Spondias mombin L. (Anacardiaceae) é uma árvore de porte elevado, frutífera, frequente no Oeste da Índia, México, Peru, Brasil e conhecida popularmente como cajazeira. Todas as suas partes têm sido utilizadas pela medicina tradicional. A planta faz parte da REPLAME (Relação de Plantas Medicinais) do estado do Ceará e do projeto Farmácias Vivas com a indicação para o tratamento da herpes. O objetivo do presente estudo foi desenvolver um fitoproduto padronizado a partir das folhas de S. mombin, e avaliar seu potencial antiinflamatórioe antiviral (Herpes simplex 1). Para isso, inicialmente, foram estabelecidos o método de preparação (secagem em estufa com circulação/ renovação de ar) a 60 ± 5 ºC por 4horas e as especificações para o controle de qualidade da droga vegetal (DV). O método extrativo para obtenção do extrato padronizado de S. mombin foi a maceração dinâmica por2,5 h, a 30 °C e relação DV: solvente (etanol 30 % em água) de 0,3, caracterizado pelo teor defenóis totais (FT: 17,52 mg/mL), resíduo seco (RS: 7,12 %, p/v) e perfil cromatográfico por CLAE-DAD (Ácido clorogênico - AC: 0,83 mg/mL e Geraniina - GR: 7,37 mg/mL). Naavaliação do potencial anti-inflamatório, extrato de S. mombin (ESM) (1, 10, 50, 100 μg/mL)inibiu parcialmente a liberação de MPO (Mieloperoxidase) induzida por PMA (Folbol-12-miristato-13-acetato), sendo observado melhor efeito na maior concentração (% inibição:50,4), enquanto que o padrão GR (1, 10, 25, 50 e 100 μg/mL) promoveu um efeito dual, ampliando a desgranulação de neutrófilo induzida por PMA nas menores concentrações (1 25 μg/mL) e inibindo esta (40,3 e 83,5 %) nas maiores concentrações (50 e 100 μg/mL). Apenas a concentração de 200 μg/mL do ESM mostrou citotoxicidade em neutrófilos humanos no teste do MTT...
Spondias mombin L. (Anacardiaceae) is a large-sized tree, fruitful, frequent in western India,Mexico, Peru, Brazil and popularly known as cajazeira. All the parts have been used bytraditional medicine. The plant is part of REPLAME (List of Medicinal Plants) of the state ofCeará and Farmacias Vivas projects, indicated for the herpes treatment. The aim of this studywas to develop a standardized product from the leaves of S. mombin and evaluate its antiviral(Herpes Simplex 1) and anti-inflammatory potential. Therefore, was initially established onemethod of preparation (drying oven with air circulation / renovation) under 60 ± 5 ° C heating4 hours, and the specifications for quality control of plant drug (PD). The extractive methodfor obtaining a standardized extract of S. mombin was the dynamic maceration for 2.5 h at 30° C and a relation PD:solvent (30% ethanol in water) of 0.3, characterized as total phenolscontent (TF: 17.52 mg/mL), dry residue (7.12%, w/v) and chromatographic profile by HPLCPAD(Chlorogenic acid - CA: 0.83 mg/mL and Geraniin - GR: 7.3 mg/mL). The evaluation ofanti-inflammatory potential showed that extract of S. mombin (ESM) (1, 10, 50 and 100µg/mL) partially inhibited MPO (Myeloperoxidase) release induced by PMA (Phorbol-12-Myristate-13-Acetate), with best effect seen at the biggest concentration (% inhibition: 50,4),while the standard GR (1, 10, 25, 50 and 100 µg/mL) promoted a dual effect, expanding thedegranulation of neutrophils induced by PMA at low concentrations (1 - 25 µg/mL) andinhibiting (40.3 and 83.5%) at biggest concentrations (50 and 100 µg/mL). Only theconcentration 200 µg/mL of ESM showed citotoxicity on human neutrophils in MTT test...
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Humans , Chlorogenic Acid , Anti-Inflammatory AgentsABSTRACT
Objective To investigate the effects of geraniin on platelet aggregation and platelet-neutrophil interactions.Methods Platelet aggregation,in vitro and ex vivo,was determined by use of Born's method,and the binding of thrombin-stimulated platelets to neutrophils was observed based on the rosette assay.Intracellular calcium concentration of platelets was measured by using Fura-2-AM.Results Geraniin in vitro significantly inhibited arachidonic acid (AA)-,adenosine diphosphate (ADP)-,or platelet activating factor (PAF)-induced platelet aggregation,in a concentration-dependent manner.The medium inhibitory concentrations (IC50) were 2.4,0.4 and 1.1 μmol/L,respectively.Intragastric geraniin at 5 mg/kg markedly suppressed platelet aggregation induced by AA,ADP,or PAF.Geraniin decreased the total rise of [Ca2+]i,Ca2+ release,and Ca2+ influx,in a concentration-dependant manner.The IC50 values were 71.9,84.9,and 62.9 μmol/L,respectively.Geraniin decreased the binding of thrombin-stimulated platelets to neutrophils,and significantly inhibited washed platelet aggregation stimulated by fMLP-activated neutrophils.The IC50 values were 3.2 and 10.2 μmol/L,respectively.Conclusion It is suggested that geraniin inhibited platelet aggregation in vitro and ex vivo,decreased the calcium mobilization of platelets,and suppressed the interactions between platelets and neutrophils.