Resveratrol (RES) (trans-3, 5,-4′-trihydroxystilebene) is a multi-biofunctional compound found in a variety of plants such as grapes and mulberries. Studies of nanoencapsulated resveratrol have indicated that this compound can inhibit the growth of cancer cells and free radicals. The aim of this study was to isolate resveratrol from Vitis vinifera, develop and evaluate resveratrol nanostructured lipid carriers (NLCs) and/or resveratrol encapsulated chitosan-coated nanostructured lipid carriers (CSNLCs) using low-viscous chitosan for anticancer therapy. In addition, our study was carried out to examine the prophylactic potential of RES, NLC, and CSNLC on paraquat-induced injury in rat hepatocytes. In this study we isolated resveratrol and encapsulated NLCs in phosphate-buffered saline solution using a phase inversion method. In addition, CSNLCs were prepared by ionic gelation method of NLCs using chitosan. NLCs and CSNLCs were then characterized for their particle size, zeta potential, morphology, and entrapment efficiency. Furthermore, NLCs and CSNLCs were evaluated for their cytotoxic effect on Hep-G2, human HCT-116 (colorectal cancer cell line), lymphoblastic leukemia (1301), and human MCF-7 (Michigan Cancer Foundation-7) cells as well as their effect on caspase-3 and death receptor (DR-4). In addition, incubation of hepatocytes with paraquat resulted in increased formation of TBARS (thiobarbituric acid reactive substances) with a parallel increase in lactate dehydrogenase (LDH) leakage at 1 h after incubation. Time-dependent depletion of cellular glutathione (GSH) was observed starting 2 h after incubation with paraquat. The mean particle size of NLC and CSNLC were 67.0 and 98.41 nm, zeta potential were (−) 24.8 and (+) 31.6 mV, entrapment efficiency were 74.15% and 85.46%, respectively, with the observed shapes of nanoparticle being spherical. The treatment of Hep-G2, human HCT-116, lymphoblastic leukemia (1301), and human MCF-7 cells with NLC led to high inhibition in the cell proliferation as concluded by the low IC₅₀ values 27.7, 17.43, 35.39, and 47.66 μg/mL, respectively, whereas CSNLC had high cytotoxic effect on Hep-G2, human HCT-116, lymphoblastic leukemia (1301), and human MCF-7 cells with low IC₅₀ values 13.29, 10.56, 16.79 and 22.60 μg/mL, respectively. Both NLC and CSNLC possess apoptotic properties through activation of the caspase-3 and death receptor (DR-4). In addition, incubation of hepatocytes with RES, NLC, and CSNLC markedly protected against paraquat-induced formation of TBARS, increase in LDH leakage, and prevented GSH depletion. The most effective doses for ethyl acetate, ethanolic, and aqueous extracts were 7.5, 10, and 12.5 μg, respectively. The results presented here may suggest that nanoencapsulated resveratrol isolated from the stems of V. vinifera to obtain NLC and CSNLC possess anticancer and apoptotic effects on cell proliferation, and therefore, can be used as new approach of pharmaceutical drugs. In addition, the results clearly suggest that the RES, NLC, and CSNLC exerted protective effect against cytotoxicity induced by paraquat. On the contrary, the effect decreased in order of CSNLC, NLC, and RES.

中文翻译：

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白藜芦醇：分离及其纳米结构，抑制细胞增殖，在某些人类细胞系癌中诱导细胞凋亡，并具有抗百草枯诱导的肝毒性的保护作用。

白藜芦醇（RES）（反式-3、5，-4'-三羟基芪）是一种多生物功能化合物，存在于多种植物中，例如葡萄和桑berries。纳米胶囊中白藜芦醇的研究表明，该化合物可以抑制癌细胞和自由基的生长。这项研究的目的是从葡萄中分离白藜芦醇，使用低粘度壳聚糖开发和评估白藜芦醇纳米结构脂质载体（NLC）和/或白藜芦醇封装的壳聚糖包被的纳米结构脂质载体（CSNLC），用于抗癌治疗。此外，我们的研究旨在检查RES，NLC和CSNLC对百草枯引起的大鼠肝细胞损伤的预防潜力。在这项研究中，我们使用相转化法分离了白藜芦醇并在磷酸盐缓冲盐溶液中包裹了NLC。另外，使用壳聚糖通过NLC的离子凝胶化方法制备了CSNLC。然后对NLC和CSNLC的粒径，ζ电势，形态和包封效率进行表征。此外，还评估了NLC和CSNLC对Hep-G2，人HCT-116（结肠直肠癌细胞系），淋巴细胞白血病（1301），以及人类MCF-7（密歇根州癌症基金会-7）细胞，以及它们对caspase-3和死亡受体（DR-4）的影响。此外，肝细胞与百草枯的孵育导致TBARS（硫代巴比妥酸反应性物质）的形成增加，并且孵育后1小时乳酸脱氢酶（LDH）的泄漏量平行增加。与百草枯一起孵育2小时后，观察到了细胞谷胱甘肽（GSH）的时间依赖性消耗。NLC和CSNLC的平均粒径分别为67.0和98.41 nm，ζ电位分别为（-）24.8和（+）31.6 mV，包封效率分别为74.15％和85.46％，观察到的纳米颗粒形状为球形。Hep-G2，人HCT-116，淋巴母细胞白血病的治疗（1301），_50个值27.7，17.43，35.39，和47.66  μ克/毫升，分别，而CSNLC不得不对Hep-G2高的细胞毒效果，人HCT-116，成淋巴细胞性白血病（1301），和人MCF-7细胞具有低IC ₅₀值13.29，10.56，16.79和22.60  μ克/毫升，分别。NLC和CSNLC都通过激活caspase-3和死亡受体（DR-4）而具有凋亡特性。此外，将肝细胞与RES，NLC和CSNLC一起孵育可显着防止百草枯诱导的TBARS形成，增加LDH泄漏并防止GSH耗竭。乙酸乙酯，乙醇和水提取物的最有效剂量为7.5、10和 12.5μg，分别。此处提出的结果可能表明，从酿酒葡萄茎中分离得到的纳米胶囊白藜芦醇获得了NLC和CSNLC对细胞增殖具有抗癌和凋亡作用，因此，可以用作药物的新方法。此外，结果清楚地表明，RES，NLC和CSNLC对百草枯引起的细胞毒性具有保护作用。相反，效果按CSNLC，NLC和RES的顺序降低。