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Ficus umbellata Vahl. (Moraceae) Stem Bark Extracts Exert Antitumor Activities In Vitro and In Vivo.

ABSTRACT: A Ficus umbellata is used to treat cancer. The present work was therefore designed to assess antitumor potentials of F. umbellata extracts in nine different cell lines. Cell cycle, apoptosis, cell migration/invasion, levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), caspases activities as well as Bcl-2 and Bcl-xL protein content were assessed in MDA-MB-231 cells. The 7,12-dimethylbenz(a)anthracene (DMBA)-induced carcinogenesis in rats were also used to investigate antitumor potential of F. umbellata extracts. The F. umbellata methanol extract exhibited a CC₅₀ of 180 μg/mL in MDA-MB-231 cells after 24 h. It induced apoptosis in MCF-7 and MDA-MB-231 cells, while it did not alter their cell cycle phases. Further, it induced a decrease in MMP, an increase in ROS levels and caspases activities as well as a downregulation in Bcl-2 and Bcl-xL protein contents in MDA-MB-231 cells. In vivo, F. umbellata aqueous (200 mg/kg) and methanol (50 mg/kg) extracts significantly (p < 0.001) reduced ovarian tumor incidence (10%), total tumor burden (58% and 46%, respectively), average tumor weight (57.8% and 45.6%, respectively) as compared to DMBA control group. These results suggest antitumor potential of F. umbellata constituents possibly due to apoptosis induction mediated through ROS-dependent mitochondrial pathway.

SUBMITTER: Silihe KK

PROVIDER: S-EPMC5485928 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:In recent years, chronic degenerative diseases such as certain types of cancers, are becoming an evident issue. DNA damage has been for long recognized as a causal factor for cancer development because mutations or chromosomal aberrations affect oncogenes and tumor suppressor genes leading cells to malignant transformation and to the subsequent cancerous growth. Medicinal plants are often used for the prevention or treatment of various diseases with great scientific interest. Among the medicinal plants distributed in the Mediterranean region, Fraxinus angustifolia Vahl. has been used in traditional medicine for its remarkable curative properties. However, in spite of this popularity, little works have been performed on the activity so that further studies should be performed to investigate in depth the antimutagenic, antigenotoxic and antiproliferative activities of the plant. Thus, the present study was aimed to the evaluation of the potential antimutagenic, antigenotoxic and antiproliferative properties of leaves and stem bark extracts of this well-known tree. Antimutagenic activity was evaluated by Salmonella mutagenicity assay in Salmonella typhimurium TA98 and TA100 strains. The antigenotoxic potential was assessed by umu test in the strain of S. typhimurium TA1535/pSK1002. Antiproliferative activity was studied on human hepatoblastoma (HepG-2) and on breast adenocarcinoma (MCF-7) cell lines by MTT assay. Furthermore, the antiproliferative activity observed on cancer cells was compared with that on the human normal-like fibroblasts (TelCOFS02MA) and the selectivity index was calculated to understand if extracts were able to exert selective toxicity towards cancer cells. Moreover, phenolic compounds are plant substances with a large spectrum of biochemical activities with antioxidant, antimutagenic and anticarcinogenic effects. Based on the strong evidence of biological activities of phenolic compounds, the study was focused on the determination of total phenolics and flavonoids contents, and the phytochemical composition of the extracts assessed by LC/MS. The ethanol extracts of both leaves and stem barks showed significant from moderate to strong antimutagenic and antigenotoxic effects. In addition, selective cytotoxicity towards cancer cells was shown by ethanolic leaves extract and aqueous/chloroform leaves and stem bark extracts. The latter showed high levels of total phenolic contents among all the other extracts. Identified phenylethanoids (calceolariosides, verbascoside) and secoiridoids (oleuropein and ligstroside) could be responsible for the demonstrated broad spectrum of healthy properties.

Project description:Cognitive impairment (CI) is among the leading causes of disability in humans. It is estimated that over 35.6 million people are suffering from Alzheimer's disease- (AD-) associated cognitive deficits globally with these statistics projected to rise over 115.4 million by the year 2050. There is no specific etiology for this cognitive impairment; however, various contributing factors including advancing age (>60 years old), oxidative stress, cerebral injuries, infections, neurologic disorders, and cancer have been implicated. Despite various attempts to manage CI, no curative medicines are yet available. The current drugs used to manage symptoms of AD-associated CI including Donepezil and Rivastigmine among others are only palliative rather than therapeutic. Furthermore, these agents have been associated with undesirable side effects. This calls for alternative and complementary approaches aimed at either preventing or reverting AD-related CI in a curative way without causing adverse events. It is estimated that over 80% of the world's population utilize herbal medicines for basic healthcare as it is considered safe, affordable, and easily accessible as opposed to conventional healthcare. Various parts of P. thonningii are used in traditional medicine to manage various conditions including CI. However, empirical and scientific data to validate these uses is lacking. In this study, the Morris water maze (MWM) experiment was adopted to evaluate the cognitive-enhancing effects of the studied plant extracts. The malondialdehyde (MDA) profiles in the brains of experimental mice were determined using the thiobarbituric acid reactive substances (TBARS) test. Moreover, qualitative phytochemical profiling of the studied plant extracts was performed using standard procedures. The results showed remarkable cognitive-enhancing activities which were reflected in significantly shorter transfer latencies, navigation distances, longer time spent in platform quadrant, and lower MDA levels compared with those recorded for the negative control mice (p < 0.05). Phytochemical screening of the studied plant extracts revealed the presence of antioxidant phytocompounds, which may have played key roles in the extracts' potency. Based on the findings herein, P. thonningii extracts, especially the aqueous ones have a promising potential for the management of AD-associated CI. Further studies aimed at isolating and characterizing specific active compounds for CI from P. thonningii are recommended. Additionally, specific mode(s) of action of active principles should be elucidated. Moreover, toxicity studies should be done on the studied plant extracts to ascertain their safety.

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Ficus umbellata Vahl. (Moraceae) Stem Bark Extracts Exert Antitumor Activities In Vitro and In Vivo.

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