University of Illinois at Chicago
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Pharmacognostic Studies of Natural Deep Eutectic Solvents

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posted on 2018-11-28, 00:00 authored by Yang Liu
Recently, natural deep eutectic solvents (NADES) were found as natural media in living plants. This provided a clue that some “basic” metabolites, such as sugars, organic acids, and amino acids, may form NADES and, thus, act as important roles that serve unrecognized, important functions in traditional medicine (TRM) and botanical dietary supplements (BDSs). To evaluate this hypothesis, the present work initially reviews NADES properties and applications in literatures. The present thorough chronological and statistical analysis of existing reports adds to the recognition of the distinctiveness of (NA)DES, involves a discussion of NADES-related observations in NP research, and reports applications of these eutectic mixtures. In addition, this study investigates the interface of NADES liquid and lipophilic metabolites in botanical extracts, and their cooperative effects. Therefore, this study seeks (Aim 1) to develop methods for NADES analysis: (i) A reproducible ultrasound-vacuum NADES preparation method is developed; (ii) 1H-1H nuclear Overhauser effect (nOe) NMR spectroscopy is used to determine intermolecular interactions in NADES matrix, and to demonstrate the existence of NADES; (iii) A countercurrent separation is trialed to “fully” isolate lipophilic NPs from NADES matrix. In this way, it can provide a tool to investigate the potential roles of the NADES-forming metabolome in botanical extracts, which is the essential forms in botanical dietary supplements and traditional medicine. Meanwhile, countercurrent separation is also used to isolate some NADES components in botanical materials, e.g., citric acid and malic acid in Schisandra chinensis. (iv) Quantitative NMR and some reviewed data are used to discover new NADES species in a NP lab. The present work then (Aim 2)studies the roles of NADES in solubilizing natural products. Except “hole theory”, a “binding theory” is proposed to explain NADES extraordinary solubilizing ability for some lipophilic NPs. The nOe NMR experiment provides some specific evidence to support this hypothesis. To observe the NADES behavior in a hydrophilic environment, a hydrophilic hydrogel model is developed. The results show that either artificial NADES solution or botanical extract (e.g., crude extract of S. chinensis) can load lipophilic NPs in hydrogel. Interacting with hydrogel polymers, the NADES may act as a “shuttle” in this delivery mechanism, where NADES help to load some lipophilic NPs in polymer network, and then move out of the polymers driven by diffusion. At the end, this study (Aim 3) studies the NADES stability using sucrose-based NADES and the NADES influence on metabolic stability. As NADES involved, ligustilide stability in Angelica sinensis-related materials and isoflavone glucosides in Trifolium pratense-based hydrolysis model are investigated. The results suggest that herbal extracts or their mixture exhibit NADES properties, stabilizing NPs in study models. Towards the understanding of the importance of NADES in biological systems, this study also discusses both NADES species and their phenomenon observed in NP research. This aims at rationalizing the applications and assisting future users of NADES by raising some critical NADES applications.



Pauli, Guido F.


Pauli, Guido F.


Medicinal Chemistry & Pharmacognosy

Degree Grantor

University of Illinois at Chicago

Degree Level

  • Doctoral

Committee Member

Chen, Shao-Nong McAlpine, James B. Soejarto, Djaja D. Orjala, Jimmy Friesen, J. Brent Seigler, David S.

Submitted date

August 2018

Issue date