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Title Phytochemical, anticancer and antidiabetic studies on Libyan plants : Arum cyrenaicum, Pituranthos tortuosus, Teucrium zanonii, Hypochaeris radicata and Solanum sodomaeum / Ebtisam Salem Saleh Saad
Name Saad, Ebtisam Salem Saleh .
Abstract This thesis examined the in vitro anticancer and/ or antidiabetic activities of five Libyan medicinal plants which are traditionally used. They included: Arum cyrenaicum, Pituranthos tortuosus, Teucrium zanonii, Hypochaeris radicata and Solanum sodomaeum. Plants were investigated phytochemically and a range of compounds, including daucosterol ester of trans p-coumaric acid, were elucidated; one of which appears to be novel. In addition, phenolic compounds, phenolic acids, flavonoids, flavonoids glycosides, pheophytins, phenylethanoid glycoside, steroidal glycoalkaloid and fatty acid were isolated from these plants.
Abstract The work focused on the evaluation of the plant extracts and some of the isolated compounds for cytotoxicity based on metabolic activity to evaluate the potential anticancer activity against human melanoma A375, HeLa cervical, prostate LNCaP and PC-3M, pancreas PANC-1and liver HepG2 and non cancerous cells PNT2 and HEKa cells as the normal controls. Crude extracts and isolated compounds that showed weak or no inhibitory activity on the cell lines were then further investigated for hypoglycaemic activity by evaluating inhibition of carbohydrate-hydrolising enzymes protein tyrosine phosphatase 1B (PTP1B), alpha-glycosidase and alpha-amylase.
Abstract Among the A. cyrenaicum extracts, the root hexane extract showed weak activity at 250 μg/ml on cancer cells and HeLa, HepG2, HEKa and PNT2 cells with an IC50 of 181.3, 128.3, 136.6, and 140.7 μg/ml, respectively, while A. cyrenaicum fruit showed toxicity on normal cells. The hexane extract of P. tortuosus showed no selective toxicity toward cancers cells, as it killed normal and cancer cells (A375, PANC-1 and PNT2) at the lowest concentration with IC50 values of 76.97, 86.57 and 80.30 μg/ml, respectively and this extract was toxic to LNCaP, PC-3M and HepG2 at 250 μg/ml. However, PTH-6-7 from hexane extract, showed selective activity on A375, PC-3M and PANC-1 cells with an IC50 of 70.11, 72.20 and 75.88 μg/ml, respectively. The ethyl acetate extract of P. tortuosus showed weak activity at 250 μg/ml against A375, PANC-1 and PNT2 cells, but the methanol extract of P. tortuosus showed no toxicity on cancer cells.
Abstract The ethyl acetate extract of T. zanonii showed selective activity against A375 and LNCaP cancer cells, while the methanol extract showed selective activity against PANC-1 cells with an IC50 of 62.02 μg/ml and this effect was linked in part to the extracts’ contents of phenylethanoid glycoside types. However, the hexane extract of T. zanonii showed weak activity on PANC-1 cells with an IC50 of 132.9 μg/ml; this could be due to the presence of salvigenin.
Abstract The hexane extract of H. radicata showed no selective activity against cancer cells, but the ethyl acetate extract of H. radicata showed selective activity against hepatoma cells with an IC50 of 63.43 μg/ml and this effect was linked in part to the extracts’ flavonoids. The methanol extract of H. radicata did not exhibit activity on cancer cells.
Abstract S.sodomaeum methanol crude extract (SSM) and chlorogenic acid (SSM-56) were the most active against cancer cells. SSM showed toxicity against LNCaP, PC-3M, A375, HeLa, PANC-1 and HepG2 cells at different concentrations with different IC50 values 18.95 μg/ml, 18.37 μg/ml, 93.58 μg/ml, 29.20 μg/ml, 8.72 μg/ml and 18.98 μg/ml, respectively. Compound SSM-56 was toxic to LNCaP, PC-3M and HepG2 with IC50 values of 371.90 μM, 266.97 μM and 337.83 μM, respectively. However, both SSM and SSM-56 were most toxic to PANC-1 cells with IC50 values of 15.6 μg/ml and 20.19 μg/ml, respectively. On PNT2, the SSM extract showed toxic effects at concentrations above 125 μg/ml while SSM-56 did not show toxicity on normal cells. Therefore SSM extract and SSM-56 showed selective activity on PANC-1 cells. On further analysis, both SSM and SSM-56 had an inhibitory effect on adhesion, migration and invasion of PANC-1 cells. The effect of SSM and SSM-56 inhibited adhesion of PANC-1 cells to fibronectin and collagen IV. Therefore, SSM and SSM-56 have the potential to treat pancreatic cancer by inhibition of cell migration and invasion as a result of reduced or inhibited attachment to ECM proteins (collagen IV and fibronectin).
Abstract In terms of antidiabetic assessment, protein tyrosine phosphatase inhibition was observed for the hexane extract of T. zanonii (Ki 1.18±0.006 μg/ml), hexane and ethyl acetate extracts of H. radicata (Ki 1.207 ± 0.008 and 1.301± 0.006 μg/ml) and the hexane root and aerial part extracts of A. cyrenaicum (Ki 1.902± 1.51 μg/ml and 1.65± 1.37 μg/ml). The extract of H. radicata displayed alpha-glucosidase inhibition (Ki value of 2.160±1.007 μg/ml) and no activity for alpha-amylase. Results obtained indicated that all four plant extracts tested had the potential to lower blood glucose levels to some extent and therefore in part corroborates the ethnomedicinal use of these four species in the treatment of diabetes.
Abstract In conclusion, traditional Libyan plants can provide an excellent source of natural raw material to isolate anticancer or antidiabetic’s agents, in addition, to phytochemicals, preliminary data showed the possibility from these plants having an anti-cancer or anti-diabetic role to play.
Publication date 2019.
Name Ferro, Valerie degree supervisor.
Name Gray, Alexander I., degree supervisor.
Name University of Strathclyde. Strathclyde Institute of Pharmacy and Biomedical Sciences.
Thesis note Thesis Ph. D. University of Strathclyde 2019 T15478
System Number 000006116

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