Fagonia cretica

Abstract: Background - Plants have proved to be an important source of anti-cancer drugs. Here we have investigated the cytotoxic action of an aqueous extract of Fagonia cretica, used widely as a herbal tea-based treatment for breast cancer. Methodology/Principal Findings - Using flow cytometric analysis of cells labeled with cyclin A, annexin V and propidium iodide, we describe a time and dose-dependent arrest of the cell cycle in G0/G1 phase of the cell cycle and apoptosis following extract treatment in MCF-7 (WT-p53) and MDA-MB-231 (mutant-p53) human breast cancer cell lines with a markedly reduced effect on primary human mammary epithelial cells. Analysis of p53 protein expression and of its downstream transcription targets, p21 and BAX, revealed a p53 associated growth arrest within 5 hours of extract treatment and apoptosis within 24 hours. DNA double strand breaks measured as ?-H2AX were detected early in both MCF-7 and MDA-MB-231 cells. However, loss of cell viability was only partly due to a p53-driven response; as MDA-MB-231 and p53-knockdown MCF-7 cells both underwent cell cycle arrest and death following extract treatment. p53-independent growth arrest and cytotoxicity following DNA damage has been previously ascribed to FOXO3a expression. Here, in MCF-7 and MDA-MB-231 cells, FOXO3a expression was increased significantly within 3 hours of extract treatment and FOXO3 siRNA reduced the extract-induced loss of cell viability in both cell lines. Conclusions/Significance - Our results demonstrate for the first time that an aqueous extract of Fagonia cretica can induce cell cycle arrest and apoptosis via p53-dependent and independent mechanisms, with activation of the DNA damage response. We also show that FOXO3a is required for activity in the absence of p53. Our findings indicate that Fagonia cretica aqueous extract contains potential anti-cancer agents acting either singly or in combination against breast cancer cell proliferation via DNA damage-induced FOXO3a and p53 expression.

Abstract: According to traditional knowledge, Fagonia cretica has medicinal potential, especially against cancer and tumors. In the present study, this information was analyzed at laboratory level by performing cytotoxic, antitumor (potato disc) and DNA damage assay. Significant cytotoxic activity was found against brine shrimps at LD50 118.89 ppm, while antitumor assay showed that the extract inhibited tumor induction on potato discs. Significant antitumor activity was found against all the tumor-inducing Agrobacterium strains tested (At6, At10 and At77), with maximum tumor inhibition (77.04%) against At10. However, the extract did not show any lethal activity against Agrobacterium tumefaciens strains, and furthermore, no DNA damaging activity was observed. The overall results indicate a strong anti-cancerous potential of this plant.

Abstract: Ethnopharmacological relevance The two plants investigated here (Fagonia cretica L. and Hedera nepalensis K. Koch) have been previously reported as natural folk medicines for the treatment of diabetes but until now no scientific investigation of potential anti-diabetic effects has been reported. Materials and methods In vitro inhibitory effect of the two tested plants and their five isolated compounds on the dipeptidyl peptidase 4 (DPP-4) was studied for the assessment of anti-diabetic activity. Results A crude extract of Fagonia cretica possessed good inhibitory activity (IC50 value: 38.1 μg/ml) which was also present in its n-hexane (FCN), ethyl acetate (FCE) or aqueous (FCA) fractions. A crude extract of Hedera nepalensis (HNC) possessed even higher inhibitory activity (IC50 value: 17.2 μg/ml) and this activity was largely retained when further fractionated in either ethyl acetate (HNE; IC50: 34.4 μg/ml) or n-hexane (HNN; 34.2 μg/ml). Bioactivity guided isolation led to the identification of four known compounds (isolated for the first time) from Fagonia cretica: quinovic acid (1), quinovic acid-3β-O-β- d -glycopyranoside (2), quinovic acid-3β-O-β- d -glucopyranosyl-(28→1)-β- d -glucopyranosyl ester (3), and stigmasterol (4) all of which inhibited DPP-4 activity (IC50: 30.7, 57.9, 23.5 and >100 µM, respectively). The fifth DPP-4 inhibitor, the triterpenoid lupeol (5) was identified in Hedera nepalensis (IC50: 31.6 μM). Conclusion The experimental study revealed that Fagonia cretica and Hedera nepalensis contain compounds with significant DPP-4 inhibitory activity which should be further investigated for their anti-diabetic potential.

Abstract: Plants have been extensively used as a remedy for the treatment of snake bites. The aim of this study was to determine the antivenom potentials of methanolic extract from the aerial parts (leaves and twigs) of Fagonia cretica L. on a haemorrhage induced by venom from Naja naja karachiensis. The haemorrhagic response of venom was dose dependent from 0.1 to 4.0 µg per 1.5 µL phosphate buffer saline (PBS) on vitelline veins of fertilised hens’ eggs in their shells. The extract effectively eliminated and neutralised, in a dose-dependent manner, the haemorrhagic activity of snake venom. The minimum effective neutralising dose of F. cretica extract was found to be 15 µg per 1.5 µL PBS. The extract possesses potentials as haemorrhagic inhibitor against snake venom compared to the standard antiserum and various plants reported in the literature. This study also provides a scientific base for the use of F. cretica in traditional medicine for the treatment of snake bite.

Abstract: Effects of powdered Fagonia cretica plant and its two major triterpenoid saponins (saponin-I and saponin-II), isolated from its ethanolic extract, on red blood cells (RBC) count, haemoglobin concentration (HC), mean corpuscular haemoglobin (MCH) and on total leucocyte (WBC) count of normal male rabbits were investigated. Saponins treated three dose groups of animals indicated significant decrease in RBC count during the experimental period of 16 days. This effect was more pronounced in animals treated with saponin-II than saponin-I. The 0.50 and 1.0g crude drug treated animals and 10 and 20mg of both the saponins treated animals, indicated a decreasing tendency of HC up to the 4th day, which increased afterwards up to the 16th day. The third dose of these materials (1.50g of crude drug and 30mg of both saponins) exhibited a highly significant decreasing pattern, up the 16 days. The decreasing effect of haemoglobin concentration was more distinct in the saponin-II treated animals than saponin-I and the crude drug. The MCH followed a reverse pattern than RBC and HC. A continued decreasing trend was found in total WBC during the 16 days treatment. An amount of 1.50g of the crude drug and 30mg of both the saponins had highly significant decreasing effects on the amount of total leukocyte count of rabbit's blood.