Khojah, Alaa; (2022) In Vitro Antidiabetic Activity and Phytochemical Characterization of Saudi Arabian Medicinal Plants. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Background: Diabetes mellitus type 2 is a life-threatening disease with a global increase in reported cases. Hyperglycaemia manifests the condition, and the current treatments focus on managing blood glucose levels. Inhibiting carbohydrate digestive enzymes, α-glucosidase and α-amylase is considered a therapeutic target for modulating postprandial hyperglycaemia. Past studies have shown that many medicinal plants are used traditionally to treat Diabetes mellitus, and several isolated phytochemicals can reduce blood glucose levels by possessing their activity on different molecular targets. In vitro models can be utilized for the screening of plant material and to identify the mechanism of action of bioactive chemicals. Aim: This research aims to find a lead compound or extract as an adjuvant treatment for diabetes mellitus type 2 by screening extracts and metabolites derived from plant species native to Saudi Arabia, targeting α-glucosidase and α-amylase. This project also aims to understand the biological and chemical properties of medicinal plants used traditionally for the treatment of Diabetes mellitus. Methods: Specific inclusion and exclusion criteria have been set for the selection of plant species. Samples derived from selected medicinal plants were collected from Saudi Arabia during different seasons. A total of 24 authenticated samples were extracted with six solvents of different polarities. Obtained extracts were tested for their inhibitory potential against α-glucosidase and α-amylase. Plant extracts exhibiting potent inhibitory activities were subjected to chemical characterization through a dereplicating technique utilizing LC-ESI-MS/MS and online databases. Bio-guided fractionation was conducted on active extracts employing different separating techniques along with LC-ESI-MS/MS to identify compounds related to the activity. Aggregation assays using 0.01% Triton X- 3 100 were performed on obtained extracts and fractions as well as detected compounds to assess their specificity of action in vitro experiments. Results: Seven medicinal plant species were selected, including, Anisotes trisulcus, Barbeya oleoides, Capparis cartilaginea, Caralluma retorospiciens, Maerua crassifolia, Maerua oblongifolia, and Nepeta deflersiana. The conducted review of available literature illustrates the current knowledge of their traditional uses and pharmacological and chemical properties. In vitro screening revealed the potent inhibitory activities of methanol extracts of A. trisulcus and B. oleoides aerial parts on α-glucosidase. The latter showed moderate inhibitory activity against α-amylase. A total of twenty-four and twenty-two compounds were tentatively identified in the methanolic extract of B. oleoides and A. trisulcus, respectively. The inhibitory activity of B.oleoides fractions was attenuated with the addition of non-ionic detergent. The detergent did not affect the inhibitory activity of A. trisulcus methanolic extract and several fractions. Conclusion: The study findings suggest that the enzyme inhibitory activity of B. oleoides is mainly due to aggregation-based inhibition linked to polyphenols (tannins and flavonol glycosides). Further study is required to isolate and identify detected metabolites in A. trisulcus fraction and characterize their potential as α-glucosidase inhibitors.

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