Centro de Estudos Farmacêuticos e Cosméticos (CEFAC), Faculdade de Farmácia, Odontologia e Enfermagem, Departamento de Farmácia, Universidade Federal do Ceará, Fortaleza, CE, Brazil; Embrapa Agroindústria Tropical, Fortaleza, CE, Brazil.
Centro de Estudos Farmacêuticos e Cosméticos (CEFAC), Faculdade de Farmácia, Odontologia e Enfermagem, Departamento de Farmácia, Universidade Federal do Ceará, Fortaleza, CE, Brazil.
J Pharm Biomed Anal. 2021 May 30;199:114061. doi: 10.1016/j.jpba.2021.114061. Epub 2021 Apr 3.
Hippeastrum elegans is an Amaryllidaceae species producing alkaloids with pharmaceutical potential including lycorine and galanthamine. Herein, we developed a non-targeted metabolomic study associated to chemometrics and biological evaluations to identify the H. elegans constituents that were able to reduce the human neutrophils proinflammatory mechanisms. The alkaloid fractions were extracted from bulbs cultivated for 15 months (m) and harvested in six harvest periods (5, 7, 9, 11, 13, and 15 m). The GC-MS analysis allowed the detection of 41 alkaloids being 31 identified. All alkaloid components varied over the cultivation and most of them were lycorine-type skeletons. Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) distinguished three groups according to the chemical profile (group I: 5, 7, and 9 m; group II: 11 m and group III: 13 and 15 m). Therefore, the biological assays were only performed with one of the representative samples of each group: 7 m, 11 m and 15 m. None of them was toxic to human neutrophils by LDH activity and MTT test. The 7 m and 15 m-alkaloid fractions showed anti-inflammatory effects by reducing human neutrophil degranulation. However, the former one was more effective in inhibiting the cell activation based on the reduction of myeloperoxidase (MPO) release and reactive oxygen species (ROS) production. Afterwards, Partial Least Squares analysis (PLS) indicated lycorine and 11,12-dehydro-2-methoxy-assoanine as the compounds responsible for the anti-inflammatory activity of the bioactive fraction. Thus, the 7 m-alkaloid fraction of H. elegans seems to be a promising anti-inflammatory drug that deserves additional research.
朱顶红是石蒜科植物，可产生具有潜在药用价值的生物碱，包括石蒜碱和加兰他敏。在此，我们开展了一项非靶向代谢组学研究，结合化学计量学和生物学评价，以鉴定能够减轻人中性粒细胞促炎机制的朱顶红成分。生物碱部分从种植 15 个月（m）的鳞茎中提取，并在六个收获期（5、7、9、11、13 和 15 m）收获。GC-MS 分析可检测到 41 种生物碱，其中 31 种已鉴定。所有生物碱成分在种植过程中均有变化，其中大多数为石蒜碱型骨架。主成分分析（PCA）和层次聚类分析（HCA）根据化学特征将三个组区分开来（组 I：5、7 和 9 m；组 II：11 m 和组 III：13 和 15 m）。因此，仅对每组的一个代表性样本进行了生物测定：7 m、11 m 和 15 m。它们都没有通过 LDH 活性和 MTT 试验对人中性粒细胞产生毒性。7 m 和 15 m-生物碱部分通过减少人中性粒细胞脱粒显示出抗炎作用。然而，前者在基于髓过氧化物酶（MPO）释放和活性氧（ROS）产生的细胞激活抑制方面更为有效。随后，偏最小二乘法分析（PLS）表明石蒜碱和 11,12-脱氢-2-甲氧基-阿索氨酸是具有抗炎活性的生物活性部分的化合物。因此，朱顶红的 7 m-生物碱部分似乎是一种有前途的抗炎药物，值得进一步研究。
