Electronic Theses and Dissertations

Date of Award

2019

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

Department

Pharmaceutics and Drug Delivery

First Advisor

Ikhlas Khan

Second Advisor

David Colby

Third Advisor

Samir Ross

Relational Format

dissertation/thesis

Abstract

The first chapter discusses the significance of natural products, safety challenges, and quality issues concisely. Specifically, the impact of herb-drug interaction on consumers and the quest for chemical markers for chemical fingerprinting development are provided. Rooibos tea (Aspalathus linearis) is a popular South African herbal tea enjoyed worldwide. Limited reports indicate the potential of rooibos tea to alter the activity of CYP450 isozymes. In chapter two, the phytochemical investigation of A. linearis resulted in the isolation and characterization of 14 phenolic compounds. Safety assessment of the phytochemicals through interaction with CYP, PXR, and P gp was conducted. The results indicate that a high intake of nutraceuticals containing rooibos extracts may pose a risk of herb-drug interactions when consumed with clinical drugs that are substrates of CYP enzymes. In chapter three, a comprehensive quantitative analysis of phenolic compounds from rooibos tea and dietary supplements using UHPLC-PDA-MS was developed to determine14 chemical constituents. The compounds were detected in the range from 1.50-9.85 %in twenty-one dietary supplements with higher content observed for the unfermented products. The characterization and confirmation of components were achieved by LC-ESI-MS. Selective ion monitoring with the positive and negative ion modes was involved for this purpose. Moringa oleifera Lam. is known as a miracle tree that cultivated in subtropical and tropical provinces. In chapter four, phytochemical investigation of M. oleifera resulted in the isolation and characterization of one new compound, namely omoringone, alongside fifteen known secondary metabolites. Structure elucidation was achieved by interpretation of the spectroscopic data and confirmation by HR-ESI-MS. A plausible biosynthetic pathway for omoringone was provided. Because of the low isolation yields and limited supply, omoringone and niazirin were successively synthesized. All the isolates were evaluated for their potential cytotoxicity and drug interaction potential. In chapter five, profiling and quantification of key phytochemicals from M. oleifera and herbal supplements by UHPLC-PDA-MS were implemented for the determination of nine phytochemicals with an efficient separation performed within 7 min. The optimized method was robust, economical and suitable for chemical fingerprint analysis of M. oleifera herbal supplements.

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