Reno-Hepatoprotective and Antidiabetic Properties of Methanol Leaf Extract of Laportea Aestuans in Wistar Rats.

Toxicities due to exposure to arsenic-contaminated water and the occurrence of diabetes mellitus are major health concerns. Treatment of these concerns using therapeutic measures have recorded limited success. Traditionally, Laportea aestuans (LA) has been used in managing various diseases. Hence, we investigated the reno-hepatoprotective/antidiabetic potentials of methanol leaf extract of LA (MeLELA) in male Wistar rats. Thirty rats (100-150 g) were equally distributed into 6 groups: Group I (vehicle-treated); group II received 2.5 mg/kg sodium arsenite (SA) thrice a week for 2 weeks; group III received streptozotocin (STZ, 50 mg/kg once); group IV received 200 mg/kg LA daily for 14 days; group V received SA and LA; group VI received STZ and LA. Sodium arsenite and STZ induced reno-hepatotoxicity and diabetes, respectively. Phytochemical screening, biomarkers/enzyme activities, blood glucose levels, micronucleus assay, kidney, liver and pancreas histologies were determined according to standard procedures. Alkaloids, carotenoids and flavonoids were present in abundance. Both SA-and STZ-treated groups recorded significant (p < 0.05) reductions in serum protein concentrations, while co-treatment with LA significantly restored the levels. The SA-induced significant increase in creatinine/urea levels were significantly reduced by LA. Co-treatment of each of SA-and STZ-treated groups, respectively, with LA significantly decreased the elevated serum alanine and aspartate aminotransferases' activities. Increased blood glucose level in diabetic group was remarkably lowered by LA. Also, the SA-induced frequency of micronucleated polychromatic erythrocytes was significantly ameliorated by LA. Conclusively, LA is protective against SA-induced toxicity and STZ-induced diabetes in Wistar rats.

Mitigation of aflatoxin B1- and sodium arsenite-induced cytotoxicities in HUC-PC urinary bladder cells by curcumin and Khaya senegalensis.

Background Concomitant exposure to environmental/occupational toxicants such as aflatoxin B1 (AFB1) and arsenic in some regions of the world has been well reported. Therefore, this calls for the assessment of the efficacy of agents such as phytochemicals, which are already known for their ethno-medicinal uses in prophylaxis/remediation. We investigated the possible cytotoxic bio-interactions between AFB1 and sodium arsenite (SA) in urinary bladder cells. We also assessed the cytoprotective effects of curcumin and the ethanol stem bark extract of Khaya senegalensis (K2S). Methods The cells were exposed to graded levels of AFB1, SA, curcumin, and K2S for 24, 48, and 72 h. Subsequently, using optimum toxic concentrations of AFB1 and SA, respectively, the influence of non-toxic levels of curcumin and/or K2S was tested on exposure of the cells to AFB1 and/or SA. Hoechst 33342/propidium iodide staining technique was used to determine the end-points due to cytotoxicity with changes in adenosine triphosphate (ATP) levels determined using Promega's CellTiter-Glo luminescent assay. Results Co-treatment of the cells with AFB1 and SA resulted in synergy in cytotoxic effects. Cytotoxicity was reduced by 3.5- and 2.9-fold by pre-treatment of the cells with curcumin and K2S before treatment with AFB1, while post-treatment resulted in 1.1- and 2.6-fold reduction, respectively. Pre-exposure of the cells with curcumin and K2S before treatment with SA ameliorated cytotoxicity by 3.8- and 3.0-fold, but post-treatment caused a 1.2- and 1.3-fold reduction, respectively. Conclusions Pre-treatment of the cells with either curcumin or K2S exhibited cytoprotective effects by ameliorating AFB1- and SA-induced cytotoxicity with inferred tendencies to prevent carcinogenesis.

A comparative assessment of antiproliferative properties of resveratrol and ethanol leaf extract of Anogeissus leiocarpus (DC) Guill and Perr against HepG2 hepatocarcinoma cells.

BACKGROUND: Epidemiological and experimental evidences have shown cancer as a leading cause of death worldwide. Although the folklore use of plants as a reliable source of health-restoring principles is well-documented, the search for more of such plants that are active against diseases, such as cancer, continues. We report here a laboratory-based evidence of the relevance of an ethanol leaf extract of Anogeissus leiocarpus (A2L) in comparison with resveratrol, a natural polyphenol, in cancer therapy. METHODS: The quantitative assessment of flavonoid and phenolic contents involved quercetin and gallic acid as standards, respectively were determined using spectrophotometry. Cytotoxicity was determined fluorometrically using propidium-iodide-staining method. Antioxidant status, adenosine triphosphate (ATP) levels, caspase activities and mitochondrial integrity were assessed using fluorometry/luminometry. RESULTS: The antioxidant assay demonstrated that A2L possesses a strong antioxidant capacity as compared with the reference compounds, ascorbic acid and butylated hydroxytoluene. This is further buttressed by the significantly high level of phenolics obtained in the quantitative assessment of the extract. A 72-h post-treatment examination indicated that both A2L and resveratrol modulate the proliferation of HepG2 liver carcinoma cells in a time- and concentration-dependent manner. Determination of the total nuclei area, propidium-iodide negative and positive nuclei areas all further buttress the modulation of cell proliferation by A2L and resveratrol with the indication that the observed cell death is due to apoptosis and necrosis at lower and higher concentrations of treatments respectively. At lower concentrations (0.39-3.13 µg/mL), resveratrol possesses higher tendencies to activate caspases 3 and 7. Bioenergetically, both resveratrol and A2L do not adversely affect the cells at lower concentrations (0.39-6.25 µg/mL for resveratrol and 12.5-100.0 µg/mL for A2L) except at higher concentrations (12.5-25.0 µg/mL for resveratrol and 200-800 µg/mL for A2L) which are more pronounced in A2L-treated cells. Furthermore, the antioxidant status of HepG2 cells is not perturbed by resveratrol as compared with A2L. Assessment of 24-h post-treatment mitochondrial function shows that resveratrol is not mitotoxic as compared with A2L which exhibits mitotoxicity at its highest concentration. CONCLUSIONS: Taken together, findings from this study showed that A2L possesses strong antiproliferative activity and its prospect in the management of hepatocellular carcinoma deserves further investigation.

Atomic force microscopy correlates antimetastatic potentials of HepG2 cell line with its redox/energy status: effects of curcumin and Khaya senegalensis.

OBJECTIVE: The fatality of cancer is mostly dependent on the possibility of occurrence of metastasis. Thus, if the development of metastasis can be prevented through novel therapeutic strategies targeted against this process, then the success of cancer treatment will drastically increase. In this study, therefore, we evaluated the antimetastatic potentials of an extract of Khaya senegalensis and curcumin on the metastatic liver cell line HepG2, and also assessed the anticancer property of the extract. METHODS: Cells were cultured and treated with graded concentrations of test substances for 24, 48, or 72 h with provisions made for negative controls. Treated cells were assessed as follows: nanotechnologically - atomic force microscopy (AFM) was used to determine cell stiffness; biochemically - cell cytotoxicity, glutathione level and adenosine triphosphate status, caspase activation and mitochondrial toxicity were considered; and microbiologically - a carrot disk assay was used to assess the anticancer property of the extract of K. senegalensis. RESULTS: Curcumin and K. senegalensis increased the cell stiffness by 2.6- and 4.0-fold respectively, indicating their antimetastatic effects. Corresponding changes in redox (glutathione level) and energy (adenosine triphosphate) status of the cells were also demonstrated. Further mechanistic studies indicated that curcumin was not mitotoxic in HepG2 cells unlike the K. senegalensis extract. In addition, the extract potently inhibited the Agrobacterium tumefaciens-induced genetic transformation based on carrot disk assay. CONCLUSION: Cell elasticity measurement data, using AFM, strongly suggested, for the first time, that both curcumin and the extract of K. senegalensis exhibited antimetastatic properties on HepG2 cells.