Maiuolo Jessica, Musolino Vincenzo, Guarnieri Lorenza, Macrì Roberta, Coppoletta Anna Rita, Cardamone Antonio, Serra Maria, Gliozzi Micaela, Bava Irene, Lupia Carmine, Tucci Luigi, Bombardelli Ezio, Mollace Vincenzo
Laboratory of Pharmaceutical Biology, IRC-FSH Center, Department of Health Sciences, University "Magna Græcia" of Catanzaro, 88100 Catanzaro, Italy.
IRC-FSH Center, Department of Health Sciences, University "Magna Græcia" of Catanzaro, 88100 Catanzaro, Italy.
Plants (Basel). 2022 Jul 22;11(15):1905. doi: 10.3390/plants11151905.
L. () belongs to the Apiaceae family and is a herbaceous plant with various pharmaceutical properties, due to the different contents of bioactive compounds extracted mainly from its roots, as well as its leaves and rhizome. To date, this plant extract has demonstrated estrogenic, anti-inflammatory, antiproliferative, cytotoxic, antimicrobial and anti-neoplastic properties. Its estrogenic activity is justified by the presence of ferutinin, an ester of a sesquiterpenic alcohol that acts as an agonist for estrogen receptors, with a chemical formula equal to CHO. The component present in responsible for the toxicity of the plant is ferulenol, a prenylated coumarin with the chemical formula CHO. This compound is capable of inducing mortality via its strong anti-coagulant properties, leading to a lethal hemorrhagic syndrome, ferulosis, in animals that feed on a chemotype of containing a high amount of ferulenol. The removal of the component ferulenol makes extracts of non-toxic. In fact, the remaining prenylated coumarins are not present in concentrations sufficient to induce toxicity. The intake of high concentrations of the extract of this plant leads a double dose-dependent effect that is typical of sesquiterpenes such as ferutinin. Here, we assessed the cytotoxicity and the estrogenic properties of the phytocomplex obtained through extraction using a mixture of acetone and water. Among the active constituents of , the identification of ferutinin and ferulenol was performed using HPLC. The effects of the extract were evaluated, following the removal of ferulenol, on three cell lines: human breast cancer MCF-7, human cervical cancer HeLa and human osteoblastic sarcoma Saos-2. The choice of these cell lines was justified by the need to mimic certain processes which may occur in vivo and which are estrogen-dependent. The obtained results demonstrated that extract, in addition to possessing an estrogenic-like property, showed a dose-dependent effect. Low concentrations (0.1-0.8 μM) demonstrated a hyperproliferative effect, whereas higher concentrations (1.6-50 μM) were toxic. Therefore, this extract could be an excellent candidate to make up for a reduction or lack of estrogen.
L.（）属于伞形科，是一种具有多种药用特性的草本植物，这归因于主要从其根、叶和根茎中提取的生物活性化合物含量不同。迄今为止，这种植物提取物已表现出雌激素样、抗炎、抗增殖、细胞毒性、抗菌和抗肿瘤特性。其雌激素活性归因于阿魏宁的存在，阿魏宁是一种倍半萜醇酯，可作为雌激素受体的激动剂，化学式为C₁₅H₂₂O₃。该植物中导致毒性的成分是阿魏烯醇，一种异戊烯基香豆素，化学式为C₁₈H₂₂O₃。这种化合物能够通过其强大的抗凝血特性诱导死亡，导致以含有大量阿魏烯醇的化学型为食的动物出现致命的出血综合征，即阿魏中毒。去除阿魏烯醇成分后，该植物提取物无毒。事实上，剩余的异戊烯基香豆素浓度不足以诱导毒性。摄入高浓度的这种植物提取物会产生倍半萜类化合物（如阿魏宁）典型的双剂量依赖性效应。在此，我们评估了通过丙酮和水的混合物提取得到的该植物复合物的细胞毒性和雌激素特性。在该植物的活性成分中，使用高效液相色谱法鉴定了阿魏宁和阿魏烯醇。在去除阿魏烯醇后，评估了提取物对三种细胞系的影响：人乳腺癌MCF - 7、人宫颈癌HeLa和人骨肉瘤Saos - 2。选择这些细胞系是因为需要模拟体内可能发生的某些雌激素依赖性过程。获得的结果表明，该植物提取物除了具有雌激素样特性外，还表现出剂量依赖性效应。低浓度（0.1 - 0.8 μM）表现出增殖增强效应，而高浓度（1.6 - 50 μM）具有毒性。因此，这种提取物可能是弥补雌激素减少或缺乏的极佳候选物。
