Faculty of Pharmacy, University of Medicine and Pharmacy "Carol Davila", Traian Vuia 6, 020956 Bucharest, Romania.
Center for Mountain Economics, "Costin C. Kiriţescu" National Institute of Economic Research (INCE-CEMONT), Romanian Academy, 725700 Vatra-Dornei, Romania.
Molecules. 2024 Apr 29;29(9):2053. doi: 10.3390/molecules29092053.
(L.) has remarkable ethnopharmacological properties and is widely used in traditional medicine. The present study investigated stem bark (Berberidis cortex) by extraction with 50% ethanol. The main secondary metabolites were quantified, resulting in a polyphenols content of 17.6780 ± 3.9320 mg Eq tannic acid/100 g extract, phenolic acids amount of 3.3886 ± 0.3481 mg Eq chlorogenic acid/100 g extract and 78.95 µg/g berberine. The dried hydro-ethanolic extract (BVE) was thoroughly analyzed using Ultra-High-Performance Liquid Chromatography coupled with High-Resolution Mass Spectrometry (UHPLC-HRMS/MS) and HPLC, and 40 bioactive phenolic constituents were identified. Then, the antioxidant potential of BVE was evaluated using three methods. Our results could explain the protective effects of Berberidis cortex ECFRAP = 0.1398 mg/mL, ICABTS = 0.0442 mg/mL, ICDPPH = 0.2610 mg/mL compared to ascorbic acid (IC = 0.0165 mg/mL). Next, the acute toxicity and teratogenicity of BVE and berberine-berberine sulfate hydrate (BS)-investigated on sp. revealed significant BS toxicity after 24 h, while BVE revealed considerable toxicity after 48 h and induced embryonic developmental delays. Finally, the anticancer effects of BVE and BS were evaluated in different tumor cell lines after 24 and 48 h of treatments. The MTS assay evidenced dose- and time-dependent antiproliferative activity, which was higher for BS than BVE. The strongest diminution of tumor cell viability was recorded in the breast (MDA-MB-231), colon (LoVo) cancer, and OSCC (PE/CA-PJ49) cell lines after 48 h of exposure (IC < 100 µg/mL). However, no cytotoxicity was reported in the normal epithelial cells (HUVEC) and hepatocellular carcinoma (HT-29) cell lines. Extensive data analysis supports our results, showing a significant correlation between the BVE concentration, phenolic compounds content, antioxidant activity, exposure time, and the viability rate of various normal cells and cancer cell lines.
（黄连）具有显著的民族药理学特性，广泛应用于传统医学。本研究通过 50%乙醇提取黄连茎皮。定量分析主要次生代谢产物，得到鞣质含量为 17.6780±3.9320mg 没食子酸当量/100g 提取物，绿原酸含量为 3.3886±0.3481mg 咖啡酸当量/100g 提取物和 78.95μg/g 小檗碱。干燥的水-乙醇提取物（BVE）使用超高效液相色谱与高分辨率质谱联用（UHPLC-HRMS/MS）和高效液相色谱法进行了全面分析，鉴定出 40 种生物活性酚类成分。然后，使用三种方法评估了 BVE 的抗氧化潜力。与抗坏血酸（IC = 0.0165mg/mL）相比，我们的结果可以解释黄连 ECFRAP = 0.1398mg/mL、ICABTS = 0.0442mg/mL、ICDPPH = 0.2610mg/mL 的保护作用。接下来，研究了 BVE 和小檗碱-硫酸小檗碱盐（BS）对 sp. 的急性毒性和致畸性，结果发现 BS 在 24 小时后毒性显著，而 BVE 在 48 小时后毒性较大，并诱导胚胎发育延迟。最后，在 24 和 48 小时的处理后，评估了 BVE 和 BS 在不同肿瘤细胞系中的抗癌作用。MTS 试验证明了剂量和时间依赖性的增殖抑制活性，BS 的活性高于 BVE。在暴露 48 小时后，乳腺癌（MDA-MB-231）、结肠癌（LoVo）和口腔鳞状细胞癌（PE/CA-PJ49）细胞系中肿瘤细胞活力的最强降低记录（IC <100μg/mL）。然而，在正常上皮细胞（HUVEC）和肝癌（HT-29）细胞系中没有报道细胞毒性。广泛的数据分析支持我们的结果，表明 BVE 浓度、酚类化合物含量、抗氧化活性、暴露时间与各种正常细胞和癌细胞系的存活率之间存在显著相关性。
