Dept. of Chemistry and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.
Dept. of Surgery, Hospital "A. Cardarelli", Campobasso, Italy.
Fitoterapia. 2018 Jun;127:173-178. doi: 10.1016/j.fitote.2018.02.016. Epub 2018 Feb 13.
Re-expression of fetal hemoglobin (HbF) was proposed as a possible therapeutic strategy for β-haemoglobinopathies. Although several inducers of HbF were tested in clinical trials, only hydroxyurea (HU) received FDA approval. Despite it produced adequate HbF levels only in half of HU-treated SCD patients, and was ineffective at all in β-thalassemia patients, beneficial effects of this approach suggested to continue in this direction identifying further molecules capable of inducing HbF. We tested the potential of essential oil isolated from Ocimum basilicum L. leaves (ObEO) in inducing hemoglobin biosynthesis. Initially, dose-dependent effect and kinetics of hemoglobin accumulation in K562 cells after treatment with ObEO were evaluated. ObEO induced dose-dependent hemoglobin accumulation superior to hydroxyurea and rapamycin and a strongest γ-globin mRNA expression. Terpenes composition of ObEO was studied by GC-MS. Three main constituents, linalool, eugenol and eucalyptol, represented about 75% of total. A blend of these three terpenes fully replicated the ObEO's biological effect, thus indicating that one of them or all together could be the active ingredients. When terpenes were tested individually, eugenol was the only one inducing stable hemoglobin accumulation, while eucalyptol and linalool produced only a small transient response. However, eugenol potential was strongly enhanced in the presence of eucalyptol and linalool, suggesting a synergistic effect on hemoglobin accumulation. By these results, the discovery of a new inducer and the interesting activity of a blend of major terpenes from ObOE on Hb accumulation could have positive fallouts on β-thalassemia and sickle cells anemia.
重新表达胎儿血红蛋白 (HbF) 被提出作为治疗β-地中海贫血症的一种可能的治疗策略。尽管已经在临床试验中测试了几种 HbF 诱导剂，但只有羟基脲 (HU) 获得了 FDA 的批准。尽管 HU 仅在一半接受治疗的 SCD 患者中产生足够的 HbF 水平，并且在所有β-地中海贫血症患者中均无效，但这种方法的有益效果表明应继续寻找能够诱导 HbF 的其他分子。我们测试了从罗勒 (Ocimum basilicum L.) 叶中分离出的精油 (ObEO) 诱导血红蛋白生物合成的潜力。最初，评估了 ObEO 处理后 K562 细胞中血红蛋白积累的剂量依赖性效应和动力学。ObEO 诱导的血红蛋白积累呈剂量依赖性，优于羟基脲和雷帕霉素，γ-珠蛋白 mRNA 表达最强。通过 GC-MS 研究了 ObEO 的萜烯组成。三种主要成分，芳樟醇、丁香酚和桉叶油醇，约占总成分的 75%。这三种萜烯的混合物完全复制了 ObEO 的生物学效应，表明其中一种或全部可能是有效成分。当单独测试萜烯时，只有丁香酚能够诱导稳定的血红蛋白积累，而桉叶油醇和芳樟醇仅产生短暂的反应。然而，在存在桉叶油醇和芳樟醇的情况下，丁香酚的潜力得到了极大的增强，表明它们对血红蛋白积累有协同作用。根据这些结果，发现了一种新的诱导剂，以及 ObOE 中主要萜烯混合物对血红蛋白积累的有趣活性，可能对β-地中海贫血症和镰状细胞贫血产生积极影响。
