Background: Cardiovascular complications during drug therapy is worrisome and has been known to increase morbidity and mortality. The aim of this study was to investigate the effect of metformin on BP, HR, and ECG, after subacute administration of doxorubicin in rats.Methods: Laboratory acclimatised animals were divided into 4 experimental groups consisting of group I as the control, given 0.5ml normal saline. Group II, received 3mg/kg doxorubicin on alternate days, while group III was given 300mg/kg metformin. The last group of animals were treated with 300mg/kg metformin, 30 min later, the animals were injected doxorubicin ip. The treatment lasted for 15 days thereafter, ECG, HR and BP were measured with anaesthesia.Results: Result showed that doxorubicin induced ECG changes in terms of increased PR and QT intervals significantly. Whereas, QRS and RR intervals were at same time significantly decreased. Metformin was observed to significantly attenuate these changes. In addition, metformin restored decreases in HR that was caused by doxorubicin in a significant fashion. However, metformin alone produced a decrease in HR compared with control. The observed reduced SBP and DBP produced by doxorubicin were also alleviated by the administration of metformin. There were increases in BP parameters measured in normotensive rats with metformin alone.Conclusions: In conclusion, metformin was found to attenuate doxorubicin-induced alteration in ECG pattern and restored the mechanical and physiological functions of the rat heart. Our data further suggests monitoring of CVS changes such as ECG particularly with drugs known to cause myocardial injury.
The main objective of current study was to investigate the in vitro and in vivo antidiabetic activity of Terfezia claveryi methanol extract. In vitro antidiabetic assays such as inhibition of α-amylase enzyme and non-enzymatic glycosylation of hemoglobin were carried out. The results of α- amylase inhibition assay revealed that the inhibitory activity (IC50) of Terfezia claveryi methanol extract (38.7µg/ml) is stronger when compared with positive control (Acarbose IC50 value of 45.3 µg/ml). The inhibition of glycosylation of hemoglobin of Terfezia claveryi methanol extract showed almost the same IC50 (33.1µg/ml) when compared the positive control, alpha-tocopherol (35.4µg/ml). In vivo antidiabetic study revealed that Terfezia claveryi methanol extract possessed good activity at a dose of 200 mg/kg through reducing the fasting plasma glucose level (122.1±3.0 mg/dl) when compared with positive control (Glibenclamide of 79.4±1.4 mg/dl) (p < 0.001). The results from this study indicated that Terfezia claveryi methanol extract exhibited considerable in vitro and in vivo antidiabetic activities. These possible activities could be useful to consider Terfezia claveryi as therapeutic antidiabetic candidate.
Purpose: To investigate the phytochemical contents of Launaea capitata (L. capitate) and its potential cytotoxic activity. Also, to examine its molecular modeling by docking of the isolated compounds.Methods: L. capitata was methanol-extracted and successively fractionated followed by determination of the total phenolic and flavonoid contents. Major constituents were isolated and purified. 3-(4, 5- Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cytotoxicity assays were conducted for all fractions. In silico studies were conducted using four anticancer target kinases, namely, protein kinase B (PKB/AKT), phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), and rapidly accelerated fibrosarcoma kinases (RAFK).Results: The results showed that total phenolic constituents ranged from 0.150 ± 0.004 to 60.229 ± 0.822 mg Gallic Acid Equivalent/g of dry extract, while the total flavonoid content varied from 0.004 ± 0.002 to 18.129 ± 1.599 mg quercetin equivalent/g of dry extract. Furthermore, the ethyl acetate fraction contained the highest amount of phenolic and flavonoid contents, which seemed to constitute the most effective anti-proliferative fraction. The plant’s major constituent was apigenin-7-O-glycoside and was isolated from the ethyl acetate fraction. The MTT cytotoxicity assay revealed the anti-proliferative activity of ethyl acetate and butanol fractions, and apigenin-7-O-glycoside with half-maximal concentration (IC50) comparable to that of doxorubicin. In silico studies revealed that apigenin-7-Oglycoside showed a better binding score and ligand efficiency when compared with standard ligands/inhibitors for AKT/PKB and PI3K, suggesting potential multiple targets for its anti-cancer activities.Conclusion: L. capitata contains considerable amounts of phenolic and flavonoid components. Its major constituent, apigenin-7-O-glycoside is a potential lead compound for developing new anticancer compounds. Keywords: Launaea capitata, Total phenolics, Total flavonoids, Docking, Cytotoxicity
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