Document Details
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Document Type |
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Thesis |
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Document Title |
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GENOMIC APPROACHES TO DELINEATE THE MECHANISM OF ACTION OF PHYTOCHEMICALS FROM SOME SAUDI MEDICINAL PLANTS دراسات جينومية لوصف ميكانيكية عمل المواد الكيميائية النباتية لبعض النباتات الطبية في المملكة العربية السعودية |
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Subject |
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Faculty of Sciences |
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Document Language |
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Arabic |
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Abstract |
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For centuries, medicinal and aromatic plants have been exploited for treating and curing various human diseases, due to their extensive biological and pharmacological activities. The fact that more than 60% of the modern drugs were derived from plants is a testimony to their immense potential. Natural products are proved to be effective and rich source of bioactive compounds for the discovery of novel drugs with lesser side effects compared to chemically synthesized ones. However, there is utmost need to isolate the active phytochemicals and delineate their mechanism of action to develop new potent and safe drugs for therapeutic use in humans.
Genomics approaches such as whole genome sequencing and transcriptome analysis of gene expression profiling are gaining a significant momentum currently. These techniques can be applied for deciphering the mechanism underlying biological activity of various phytochemicals. This work exploits the latest advances in genomic technology to characterize the mode of action of these novel herbal compounds thus opening up new avenues for new therapeutics.
The medicinal plant diversity in Saudi Arabia presents an enormous untapped genetic, biochemical and ecologically large pool that can be leveraged to discover new drugs against a wide variety of diseases. A number of these plants grow under drought, distress and extreme weather conditions, which makes their genomes remarkably unique. Various plants including Ricinus communis (R.communis), Allium ampeloprasum and Rhazya stricta (R.stricta) were shown to have antibacterial, anti-cancer, antifungal and anti-inflammatory properties. In the current thesis, two Saudi Arabian medicinal plants R. communis and R. stricta were evaluated for their antimicrobial and anticancer mechanisms, respectively.
Ricinus communis dried leaves were extracted with absolute ethanol, and the antibacterial activity was evaluated using agar well assay and liquid broth assay and subsequently observed their morphological changes by Transmission Electron Microscopy (TEM) techniques. Two bacterial strains: Escherichia coli (E.coli) and Klebsiella oxytoca (K.oxytoca) were exposed to sub-lethal doses of plant extract for four weeks to generate resistant strains. Finally, genomic DNA was extracted from wild and mutant bacteria treated with and without Ricinus ethanol extract (REE), and whole genome sequencing was performed for eventual identification of affected genes. Whole genome sequencing of resistant bacteria species revealed the affected genes, involved in antimicrobial resistance development, which includes DNA replication, transcription, two-component signal transduction (TCS) and transporter genes.
Rhazya stricta leaves were extracted with ethanol and were subjected to purification for various alkaloids. The alkaloids fraction were tested for their anticancer activity. One of the novel alkaloid, termed Isopicrinine exhibited potent anticancer activity against breast cancer cell line, MCF-7. RNA-Seq experiment was performed to delineate the mechanism of its anticancer activity. Exposure of MCF-7 cells with Isopicrinine affected the genes involved in apoptosis, cell cycle, transcription, mitosis and cell proliferation. One of the crucial pro-apoptotic gene PUMA (p53 upregulated modulator of apoptosis) was upregulated. Survivin – anti-apoptotic gene- was downregulated.
The current studies demonstrate the potential of genomics-based approaches in understanding the mechanism of action of phytochemicals derived from various traditional medicinal plants, which would further lead to the development of novel drugs with more efficacy and better safety profile. |
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Supervisor |
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Prof Jamal Sabir Mohammed Sabir |
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Thesis Type |
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Doctorate Thesis |
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Publishing Year |
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1439 AH
2018 AD |
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Co-Supervisor |
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Prof Kulvinder Singh Saini |
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Added Date |
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Monday, March 19, 2018 |
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Researchers
| محمد عبدل وسيم | Waseem, Mohammed Abdul | Researcher | Doctorate | |
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