Co-Crystals of Resveratrol and Polydatin with L-Proline: Crystal Structures, Dissolution Properties, and In Vitro Cytotoxicities.

Yijie Lou,Jianwei Wang,Yunxi Ji,Hanxiao Bao,Kaxi Yu,Zhaojun Wang,Xiajun Wu,Yusheng Cui,Xiurong Hu,Guping Tang

doi:10.3390/molecules26185722

Yijie Lou, Jianwei Wang + Show 8 more

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https://doi.org/10.3390/molecules26185722

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Abstract

Resveratrol (RSV) and polydatin (PD) have been widely used to treat several chronic diseases, such as atherosclerosis, pulmonary fibrosis, and diabetes, among several others. However, their low solubility hinders their further applications. In this work, we show that the solubility of PD can be boosted via its co-crystallization with L-proline (L-Pro). Two different phases of co-crystals, namely the RSV-L-Pro (RSV:L-Pro = 1:2) and PD-L-Pro (PD:L-Pro = 1: 3), have been prepared and characterized. As compared to the pristine RSV and PD, the solubility and dissolution rates of PD-L-Pro in water (pH 7.0) exhibited a 15.8% increase, whereas those of RSV-L-Pro exhibited a 13.8% decrease. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine RSV, PD, RSV-L-Pro, and PD-L-Pro against lung cancer cell line A549 and human embryonic kidney cell line HEK-293 indicated that both compounds showed obvious cytotoxicity against A549, but significantly reduced cytotoxicity against HEK-293, with PD/PD-L-Pro further exhibiting better biological safety than that of RSV/RSV-L-Pro. This work demonstrated that the readily available and biocompatible L-Pro can be a promising adjuvant to optimize the physical and chemical properties of RSV and PD to improve their pharmacokinetics.

Highlights

Polydatin (PD) is a natural precursor and the glucose derivative of trans-3,5,4’trihydroxystilbene [1]
Various studies have confirmed that RSV and PD are widely used to treat several chronic diseases, such as atherosclerosis, pulmonary fibrosis, diabetes, cerebral ischemia, steatohepatitis, and various carcinomas (Figure 1) [3,5,6,7,8,9,10,11]
The RSV-L-Pro and PD-L-Pro both were prepared as single crystals from a molar equivalent of RSV and PD with L-Pro in EtOH at 60 ◦C

Summary

Introduction

Polydatin (PD) is a natural precursor and the glucose derivative of trans-3,5,4’trihydroxystilbene (resveratrol; denoted as RSV) [1]. As the main active ingredients of traditional Chinese medicine (TCM), they show good therapeutic properties, such as anti-inflammatory, anti-oxidant, and anti-apoptotic effects [1]. RSV exhibits the advantages of anti-aging, weight loss, and skin protection, while PD performs better in anti-virus and anti-fibrosis activities, and in the promotion of lipid metabolism [2,3,4,5]. Both RSV and PD are used as anti-oxidants, and complement each other in clinical treatment. Various studies have confirmed that RSV and PD are widely used to treat several chronic diseases, such as atherosclerosis, pulmonary fibrosis, diabetes, cerebral ischemia, steatohepatitis, and various carcinomas (Figure 1) [3,5,6,7,8,9,10,11]

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