Simultaneous extraction of several targets by using non-toxic dual template molecularly imprinted polymers in vivo and in vitro

doi:10.1016/j.talanta.2020.121283

Talanta

Volume 219, 1 November 2020, 121283

https://doi.org/10.1016/j.talanta.2020.121283 Get rights and content

Highlights

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Dual Template Molecularly Imprinted Polymers (DMIPs) was synthesized with DES as functional monomers.
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DMIP was used to enrich quercetin and schisandrin b from the mixed crude extracts.
•
Enrich several target molecules simultaneously from complex biological systems.

Abstract

In this report, a non-toxic Dual Template Molecularly Imprinted Polymers (DMIPs) was synthesized with quercetin and schisandrin b as template molecules, using deep-eutectic solvents as functional monomers for the first time. The DMIPs were used to efficiently and simultaneously enrich quercetin and schisandrin b from the mixed crude extracts of penthorum and schisandra. The results indicated that the DMIPs exhibited rapid adsorption kinetics (80 min for adsorption equilibrium) and high selectivity. The largest adsorbing capacities to quercetin and schisandrin b were 23.58 mg/g and 41.64 mg/g, respectively. After presaturation with quercetin and schisandrin b, the nontoxic saturated DMIPs were fed to the mice. Blood samples of the mice were taken and both quercetin and schisandrin b were successfully detected. The pharmacokinetics of quercetin and schisandrin b were similar to reports in the literature where mice were directly fed with botanicals. Our study provides a reliable protocol such that DMIPs can be used to separate and enrich several target molecules simultaneously from complex biological systems. Our findings suggested that the DMIPs have potential application as a drug delivery system of compound herbal formulas.

Graphical abstract

Introduction

Liver, the largest detoxification organ, is sometimes referred to as the integrated chemical plant of the human body. However, liver is relatively fragile, it is very important to protect the sensitive hero [1]. As botanicals and food plants, penthorum chinense and schisandra can be used as a nourishing tea diet to protect the liver effectively [[2], [3], [4]]. Studies have shown that the flavonoids of penthorum and the lignans of the schisandra are the main active components of liver protection [5,6]. In this paper, the representative component of flavonoids in penthorum and lignans in schisandra were selected as the templates to synthesis the double templates molecularly imprinted polymers (DMIPs). The DMIPs were used to extract quercetin and schisandrin b from the crude extract of penthorum chinense and schisandra.

At present, molecularly imprinting techniques (MIT) are widely concerned for its high selectivity. In addition, molecularly imprinted polymers (MIPs) are synthesized in the presence of template molecules, functional monomers and cross-linkers [[7], [8], [9]]. Common functional monomers such as methacrylic acid, 4-vinylpyridine, etc. are mostly toxic and harmful reagents, and the synthesized MIPs are limited in application due to their toxic components [[10], [11], [12]]. It is highly desirable to develop some non-toxic and harmless monomers to prepare safe MIPs.

Deep eutectic solvents (DES) is a kind of ionic liquid, which is a two-component or three-component molecular complex that composed of certain stoichiometric ratio of hydrogen bond receptors (such as quaternary ammonium salt) and hydrogen bond donors (such as amides, carboxylic acids and polyols) [13,14]. DES has advantages of low or non-toxicity, good solubility and good thermal stability [15,16]. Therefore, DES is widely used in the fields of synthesis, biochemistry, separation analysis and so on. Combining DES and MIT can enhance the ability of affinity and selectivity of MIPs towards templates molecular, and decrease or eliminate the toxicity of MIPs [[17], [18], [19], [20]]. Such as, ShiRu Liang used DES as solvent and phenylephrine as template to prepare molecularly imprinted resin for identifying chlorpromazine and bambuterol from urine [21]. The experimental results showed that this method had highly selective for template molecules.

In this paper, quercetin and schisandrin b as double template, DES as functional monomer, ethylene glycol dimethyl acrylate (EGDMA) as cross-linker agent, DMIPs were synthesized by bulk polymerization method in acetonitrile. And the DMIPs was successfully applied to enrich the quercetin and schisandrin b from the crude extracts of penthorum and schisandra simultaneously. Then, the saturated DMIPs with quercetin and schisandrin b were directly administered to the mice. The mice after feeding were safe and sound, the quercetin and schisandrin b were successfully detected in the blood of the mice. The results indicated the DMIPs were non-toxic and can successfully release quercetin and schisandrin b in vivo.

Section snippets

Materials

Icariin, luteolin, quercetin, schisandrin b, schisandrin and doxyschizandrin were obtained from Pu Yi Biological Technology Co., Ltd (Nanjing, China). Caffeic acid, choline chloride, formic acid, methanol, anhydrous ethanol and acetonitrile were obtained from Chengdu Kelong Chemical Corporation (Chengdu, China). EGDMA was purchased from Aldrich (Shanghai, China) and used as received. Methacrylic acid (MAA), azodiisobutyronitrile (AIBN) and trichloromethane were supplied by Chuandong Chemical

Preparation of DMIPs

In order to determine the optimal conditions, nine kinds of DMIPs were synthesized and compared in this study. As shown in Table 1, the reaction solvent and the stoichiometric or volumetric ratio of monomer to cross-linker had a great influence on the adsorption capacity of DMIPs. Quercetin could be dissolved in methanol, acetonitrile, and ethanol, and the adsorption capacity of DMIP1 (5.60 mg/g), DMIP2 (7.16 mg/g) and DMIP4 (4.96 mg/g) to quercetin were more than that of DMIP3 (2.57 mg/g).

Conclusion

In this study, nontoxic DMIPs were synthesized by bulk polymerization employing DES as the function monomer and using quercetin and schisandrin b as dual templates. The morphology and physical properties of DMIPs were characterized by SEM, TGA and FT-IR. Analysis revealed that DMIPs possessed high selectivity and fast binding kinetic behavior for quercetin and schisandrin b. DMIPs were successfully applied to simultaneously enrich quercetin and schisandrin b from the crude extract mixture of

CRediT authorship contribution statement

Jia-Wei Zhang: Investigation, Data curation, Formal analysis, Writing - original draft. Jia-Yuan He: Investigation, Data curation, Formal analysis, Writing - review & editing, Visualization. Chong-Zhi Wang: Formal analysis, Methodology. Feng-Qing Yang: Writing - review & editing. Lian-Di Zhou: Supervision, Visualization. Qi-Hui Zhang: Conceptualization, Validation, Resources, Project administration, Funding acquisition. Zhi-Ning Xia: Project administration. Chun-Su Yuan: Writing - review &

Declaration of competing interest

The authors declare no competing financial interest.

Acknowledgements

This work was supported by National Natural Science Foundation of China (Grant No.81973451); Fundamental Research Funds for the Central Universities (Grant No. 2019CDYGYB027, 2019CDXYHG0013 and 2017CDJXFLX0014); Fundamental and Frontier Research Fund of Chongqing (Grant No. cstc2018jcyjAX0661); Science and Technology Research Program of Chongqing Municipal Education Commission (Grant No. KJZD-K201800103); Graduate research and innovation foundation of Chongqing, China (Grant No. CYS18033);

References (25)

T. Minami et al.
Novel hybrid three-dimensional artificial liver using human induced pluripotent stem cells and a rat decellularized liver scaffold
Regenerative Therapy
(2019)
Z. Li et al.
A review of polysaccharides from Schisandra chinensis and Schisandra sphenanthera: properties, functions and applications
Carbohydr. Polym.
(2018)
J.N. Chun et al.
The protective effects of Schisandra chinensis fruit extract and its lignans against cardiovascular disease: a review of the molecular mechanisms
Fitoterapia
(2014)
Y.W. Cao et al.
Protective effects of Penthorum chinense Pursh against chronic ethanol-induced liver injury in mice
J. Ethnopharmacol.
(2015)
Y. Gao et al.
Characterization of lignans in Schisandra chinensis oil with a single analysis process by UPLC-Q/TOF-MS
Chem. Phys. Lipids
(2019)
H. Zhang et al.
Bio-inspired construction of cellulose-based molecular imprinting membrane with selective recognition surface for paclitaxel separation
Appl. Surf. Sci.
(2019)
M. Cantarella et al.
Molecularly imprinted polymer for selective adsorption of diclofenac from contaminated water
Chem. Eng. J.
(2019)
O.S. Ahmad et al.
Molecularly imprinted polymers in electrochemical and optical sensors
Trends Biotechnol.
(2019)
J. Zhou et al.
Surface molecularly imprinted thermo-sensitive polymers based on light-weight hollow magnetic microspheres for specific recognition of BSA
Appl. Surf. Sci.
(2019)
S. Shi et al.
Effective synthesis of magnetic porous molecularly imprinted polymers for efficient and selective extraction of cinnamic acid from apple juices
Food Chem.
(2017)

F.W. Scheller et al.

Molecularly imprinted polymer-based electrochemical sensors for biopolymers

Current Opinion in Electrochemistry

(2019)

J. Chen et al.

Green and efficient extraction of resveratrol from peanut roots using deep eutectic solvents

J. Chem. Neuroanat.

(2018)

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Molecular imprinting technique is becoming an appealing and prominent strategy to synthesize materials for target recognition and rapid separation. In recent years, it has been applied in separation of active compounds from various plants and has achieved satisfying results. This review aims to make a brief introduction of molecular imprinting polymers and their efficient application in the separation of various active components from plants, including flavonoids, organic acids, alkaloids, phenylpropanoids, anthraquinones, phenolics, terpenes, steroids, and diketones, which will provide some clues to help stimulating research into this fascinating and useful area.
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¹: Zhang and He contributed equally to this work.

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Simultaneous extraction of several targets by using non-toxic dual template molecularly imprinted polymers in vivo and in vitro

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Materials

Preparation of DMIPs

Conclusion

CRediT authorship contribution statement

Declaration of competing interest

Acknowledgements

Regenerative Therapy

Carbohydr. Polym.

Fitoterapia

J. Ethnopharmacol.

Chem. Phys. Lipids

Appl. Surf. Sci.

Chem. Eng. J.

Trends Biotechnol.

Appl. Surf. Sci.

Food Chem.

Current Opinion in Electrochemistry

J. Chem. Neuroanat.