Curbing environmental pollution of water hyacinth by using it in drug discovery
Water hyacinth (Eichhornia crassipes) is an aquatic plant that is also considered the world's worst weed. It grows rapidly by spreading dense mats over water bodies that hinder aquatic life from flourishing, halt fishing activities, and fester mosquito habitats. Its biomass poses a danger to the aquatic ecosystem making it an urgent environmental concern. Even though water hyacinth is considered a nuisance to the environment, its biomass possesses useful properties that are harnessed in phytoremediation and biofuel production. It is also reported to be abundant in phytochemicals with medicinal properties. There are various potential biomedical applications of water hyacinth described in literature, however, the description of its anticancer mechanisms is limited and information on its potential for male contraceptive application is lacking. This study set out to find alternative uses for water hyacinth by exploring gaps in drug discovery and the objective was to; (1) Evaluate the extraction yield of Nigerian water hyacinth extracts (derived from chloroform, ethyl acetate, and petroleum ether), determine their antioxidant capacity and bioactive compound profile; (2) Determine the cytotoxic effects of the crude extracts on MCF7 breast cancer cell line’s confluency/proliferation, viability, morphology, ROS levels, and membrane integrity; (3) To evaluate functional changes in cancer cells' antioxidant stress response (ARE) promoter and tumour suppressor (p53 transcription activity) mechanisms, during extract treatment; and (4) Evaluate the effect of extracts and bioactive compounds on male fertility parameters and the effect of the most potent extract on spermatogonia stem cell viability. We describe, for the first time the bioactive compound profile of water hyacinth samples from Adamawa state Nigeria and its antioxidant capacity using GC-MS and ABTS free radical inhibition assay. Using live imaging (IncuCyte) we demonstrated that all the water hyacinth extracts analysed at 1mg/ml inhibited confluency/proliferation of MCF7 breast cancer cells by elevating ROS, diminishing membrane integrity and viability depletion. Also, observable morphological changes unique to each extract were motility by chloroform extract (E2), cell shrinkage by ethyl acetate extract (E4), and cell size expansion by petroleum ether extract (E5). Through luciferase reporter ARE-promoter activity, we report for the first time that water hyacinth extracts are potent inducers of Nrf2 (Nuclear factor erythroid 2-related factor 2) dependent ARE-promoter activity. Furthermore, we assessed the impact of extracts on donor human sperm function parameters using CASA and we found that E2 especially, induced ROS and diminished total and progressive sperm motility to below WHO recommendation similar to asthenozoospermia infertility disease pathology. E2 also decreased the viability of spermatogonia stem cells which could impact spermatogenesis. The findings in this thesis provide novel information on Nigerian water hyacinths' biological activities as an anticancer and potential male contraceptive, offering novel leads for drug discovery. Since the World Health Organization (WHO) have estimated that up to 80% of the world’s population relies on traditional herbs for primary health care, the findings in this study can also prove useful to communities that use water hyacinth as medicine. It informs on the caution of contraindication with drugs or diseases that are not compatible with Nrf2-ARE induction.
Water hyacinth (Eichhornia crassipes), Bioactive compounds, Nigerian water hyacinth, Phytochemicals, Antioxidant capacity, GC-MS analysis, ABTS assay, MCF7 breast cancer cells, ROS induction, ARE-promoter activity, Nrf2 activation, p53 transcription activity, Spermatogonia stem cells, Male fertility, Sperm motility, Asthenozoospermia, Drug discovery, Anticancer mechanisms, Male contraceptive potential, Phytoremediation, Biofuel production, Traditional medicine, Environmental concern, Live imaging (IncuCyte), Cell viability, Membrane integrity, Cancer cell morphology, Contraceptive research, Medicinal plant applications
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