Concentrations Of Aloe-emodin Research Articles

Investigation of Effect of Phytoconstituents Aloe Emodin and Quercetin on Bioavailability of Albendazole

Abstract: Background/Aim: Albendazole is a drug with benzimidazole nucleus and is poorly absorbed from the gastrointestinal tract due to its low aqueous solubility. The objective of present work was to study the effect of two phytoconstituents aloe emodin and quercetin on the bioavailability of albendazole. Materials and Methods: Estimation was done through UV spectroscopy and HPLC analysis using different concentration of both the phytoconstituents. In-vivo study was conducted to investigate the pharmacokinetics and pharmacodynamic parameters. Results: Results revealed no change in Tmax of albendazole and significant changes were observed in Cmax values. The Cmax was maximum i.e. 0.138 μg/ml when 20mg/kg of quercetin was added as compared to aloe-emodin. The increase in bioavailability of Albendazole was due to the presence of flavonoids in quercetin. The retention time of albendazole as estimated through HPLC chromatogram was found to be 3.2 minutes with acetonitrile and phosphate buffer as the mobile phase. However; albendazole was not detectable in 24 hr plasma sample and values of AUC were found to be zero in all the concentration of aloe emodin and quercetin. Conclusion: Thus, the phytoconstituents rich in flavonoids could be used to increase the bioavailability of poor soluble drugs. Key words: Albendazole, Aloe emodin, Quercetin, Bioavailability, Pharmacokinetics.

Anti-tumor effect of aloe-emodin on cervical cancer cells was associated with human papillomavirus E6/E7 and glucose metabolism.

Background：Aloe-emodin, an anthraquinone present in aloe latex, has been shown to have anti-proliferative properties in cervical cancer disease, all cases of which are almost caused by human papillomavirus (HPV), with the products of E6/E7. It is suggested that aloe-emodin may play an important role in HPV-induced cervical cancer cells.Methods：Hela and SiHa cells were treated with various concentrations of aloe-emodin. MTT assay and flow cytometry were used to identify the cell growth and apoptosis. The expressions of HPV E6, E7 and GLUT1 (glucose transporter-1) were detected by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot (WB). The glucose uptake, lactate production and ATP production in HeLa and SiHa cells were also investigated.Result：The results indicate that aloe-emodin promoted the apoptosis of HeLa and SiHa cells and decreased the expressions of HPV-related protein E6 and E7. Furthermore, aloe-emodin inhibited glucose metabolism by reducing GLUT1 expression. Overexpression of GLUT1 significantly weakened the apoptosis induced by aloe-emodin in HeLa cells.Conclusion：In this study, we found that aloe-emodin induce apoptosis of cervical cancer cells, which was associated with HPV E6 and E7 and glucose metabolism.

Photodynamic Therapy Mediated by Aloe-Emodin Inhibited Angiogenesis and Cell Metastasis Through Activating MAPK Signaling Pathway on HUVECs.

Photodynamic therapy is a clinically used, minimally invasive therapeutic procedure that involves the application of photosensitizers which can locate in target cells and so be irradiated at a corresponding wavelength. Laser light irradiation activation of photosensitizers generates free reactive oxygen species, which induces selective cytotoxic activity in target cells. Within recent years, aloe-emodin as a photosensitizer has been successfully applied in photodynamic therapy applications. Angiogenesis plays an important role in tumor growth and metastasis; thus, the development of a novel target treatment for angiogenesis is essential in order to improve treatment therapeutics for cancer treatment. An essential step in angiogenesis involves the formation of tube-like structures during matrix degradation, rearrangement, and apoptosis of endothelial cells. In the present study, we investigated the mechanisms of photocytotoxicity induced by aloe-emodin in human umbilical vein endothelial cells. Analysis of cell proliferation results noted a significant decrease in cultured cells which received various concentrations of aloe-emodin and photodynamic therapy–induced light doses. Additionally, mitochondrial mechanisms of apoptotic cell death were observed in aloe-emodin photodynamic therapy–treated cells, as tube formation assays noted angiogenesis suppression after treatment. The capacity of migration and invasion of human umbilical vein endothelial cells was measured using the transwell assay and demonstrated that aloe-emodin photodynamic therapy significantly inhibited the migration and invasion of human umbilical vein endothelial cells. The expression of p38, extracellular signal-regulated kinase, the c-Jun N-terminal kinases, and vascular endothelial growth factor suggested that the cellular metastasis was related to mitogen-activated protein kinase signal pathway. Furthermore, disorganization of F action cytoskeleton components was observed after aloe-emodin photodynamic therapy. Overall, the findings from this study suggest that aloe-emodin photodynamic therapy inhibited angiogenesis and cellular metastasis in human umbilical vein endothelial cells by activating the mitogen-activated protein kinase apoptotic signaling cell death pathway.

ALOE EMODIN ENHANCES TAMOXIFEN CYTOTOXICITY EFFECT ON ERa-POSITIVE BREAST CANCER CELLS, MCF-7, THROUGH DOWNREGULATION OF MEK1 AND MEK2

The positive response to tamoxifen in ERa-positive breast cancer patients is usually of a short duration as manyof the patients eventually develop resistance. Our preliminary results show that aloe emodin extracted fromthe leaves of the Aloe barbadensis Miller demonstrated a cytotoxicity that is selective to ERa-positive breastcancer cells (MCF-7), but not to ERa-negative breast cancer cells (MDA-MB-231) and to the control cells (MCF-10A). The objective of this study was to test the hypothesis that aloe emodin may enhance the response ofMCF-7 cells to treatment with tamoxifen. MCF-7 cells were treated with aloe emodin alone, tamoxifen aloneor a combination of emodin and tamoxifen, at their respective IC50 concentrations and at different time pointsof 24 hours, 48 hours and 72 hours. The respective IC50s were the concentrations of aloe emodin and tamoxifenrequired to achieve 50% inhibition of the cells in the study. Cell viability and apoptosis were determined usingtrypan blue exclusion and DNA fragmentation assays, respectively. The involvement of RAS/MEKs/ERKs genesof MAPK signalling pathways with aloe emodin was determined using QuantiGene 2.0 Plex assay. Data wasevaluated using the one-way ANOVA test. Our findings showed that aloe emodin enhanced the cytotoxicity oftamoxifen on MCF-7 cells through apoptosis by downregulation of MEK1/2 genes. Our research may provide arational basis for further in vivo studies to verify the efficacy of a combination of aloe emodin and tamoxifenon the viability of ERa-positive-breast cancer cells.

Analysis of the pharmacokinetics and metabolism of aloe-emodin following intravenous and oral administrations in rats.

Aloe-emodin, a natural polyphenolic anthraquinone, has shown various beneficial bioactivities in vitro. The aim of this study was to investigate the pharmacokinetics and metabolism of aloe-emodin. Aloe-emodin was intravenously and orally administered to rats. The concentrations of aloe-emodin and rhein, a metabolite of aloe-emodin, were determined by HPLC method prior to and after hydrolysis with β-glucuronidase and sulfatase/β-glucuronidase. The results showed that the systemic exposures of aloe-emodin and its metabolites were ranked as aloe-emodin glucuronides (G)>rhein sulfates (S)>aloe-emodin > rhein and rhein G when aloe-emodin was given intravenously. In contrast, when aloe-emodin was administered orally, the parent form of aloe-emodin was not absorbed per se, and the systemic exposures of its metabolites were ranked as aloe-emodin G>rhein G>rhein. In conclusion, the metabolites of aloe-emodin are more important than the parent form for the bioactivities in vivo. Copyright © 2016 John Wiley & Sons, Ltd.

Intestinal absorption of aloe-emodin using single-passintestinal perfusion method in rat

The intestinal absorption of aloe-emodin was investigated using the single pass intestinal perfusion (SPIP) technique in S/D rats. SPIP was performed in each isolated segment of the intestine (i.e., duodenum, jejunum, ileum and colon) and the different concentrations inhibitor group of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP2) with the concentrations of aloe-emodin (0.238 mg x L(-1)) at a flow rate of 0.28 mL x min(-1). The effective absorption rate constant (Ka) and apparent absorption coefficient (Papp) of aloe-emodin for each segment were determined before and after treated with different concentrations of inhibitors of P-gp and MRP2 respectively. Aloe-emodin exhibits a high intestinal permeability except the the ileum, indicative that the compounds are well absorbed. Decreases of Ka and Papp values in the duodenum, jejunum, colon and ileum, furthermore, the duodenum has significant increased compared with the ileum, there are have no significant difference in other isolated region of the intestine. Compared with the group which have no inhibitor of P-gp, the Ka and Papp were significantly increased in inhibitor of P-gp groups. Compared with the group of no inhibitor of MRP2, the Ka and Papp were significantly increased in inhibitor of MRP2 groups with the highest and the middle concentration. The results suggested that the inhibitors of P-gp and MRP2 all can promote the intestinal absorption of aloe-emodin.

Aloe-emodin induced in vitro G2/M arrest of cell cycle in human promyelocytic leukemia HL-60 cells

In this study, we have evaluated the chemopreventive role of aloe-emodin in human promyelocytic leukemia HL-60 cells in vitro by studying the regulation of proliferation, cell cycle and apoptosis. Aloe-emodin inhibited cell proliferation and induced G2/M arrest and apoptosis in HL-60 cells. Investigation of the levels of cyclins B1, E and A by immunoblot analysis showed that cyclin E level was unaffected, whereas cyclin B1 and A levels increased with aloe-emodin in HL-60 cells. Investigation of the levels of cyclin-dependent kinases, Cdk1 and 2, showed increased levels of Cdk1 but the levels of Cdk2 were not effected with aloe-emodin in HL-60 cells. The levels of p27 were increased after HL-60 cells were cotreated with various concentrations of aloe-emodin. The increase of the levels of p27 may be the major factor for aloe-emodin to cause G2/M arrest in these examined cells. Flow cytometric assays and DNA fragmentation gel electrophoresis also confirmed aloe-emodin induced apoptosis in HL-60 cells. The levels of caspase-3 were increased after HL-60 cells were cotreated with 10 μM aloe-emodin for 12, 24, 48, and 72 hours. Taken together, aloe-emodin therefore appears to exert its anticarcinogenesis properties by inhibiting proliferation and inducing cell cycle arrest and apoptosis underwent activation of caspase-3 in human leukemia HL-60 cells.