Amaryllidaceae plants are the commercial source of galanthamine, an alkaloid approved for the clinical treatment of Alzheimer’s disease. The chemistry and bioactivity of Chilean representatives of Rhodophiala genus from the family of Amaryllidaceae have not been widely studied so far. Ten collections of five different Chilean Rhodophiala were analyzed in vitro for activity against enzymes such as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) as well as for their alkaloid composition by GC-MS. To obtain an insight into the potential AChE and BuChE inhibitory activity of the alkaloids identified in the most active samples, docking experiments were carried out. Although galanthamine was found neither in aerial parts nor in bulbs of R. splendens, these plant materials were the most active inhibitors of AChE (IC50: 5.78 and 3.62 μg/mL, respectively) and BuChE (IC50: 16.26 and 14.37 μg/mL, respectively). Some 37 known alkaloids and 40 still unidentified compounds were detected in the samples, suggesting high potential in the Chilean Amaryllidaceae plants as sources of both novel bioactive agents and new alkaloids.
The expression of HIGD2A is dependent on oxygen levels, glucose concentration, and cell cycle progression. This gene encodes for protein HIG2A, found in mitochondria and the nucleus, promoting cell survival in hypoxic conditions. The genomic location of HIGD2A is in chromosome 5q35.2, where several chromosomal abnormalities are related to numerous cancers. The analysis of high definition expression profiles of HIGD2A suggests a role for HIG2A in cancer biology. Accordingly, the research objective was to perform a molecular biosystem analysis of HIGD2A aiming to discover HIG2A implications in cancer biology. For this purpose, public databases such as SWISS-MODEL protein structure homology-modelling server, Catalogue of Somatic Mutations in Cancer (COSMIC), Gene Expression Omnibus (GEO), MethHC: a database of DNA methylation and gene expression in human cancer, and microRNA-target interactions database (miRTarBase) were accessed. We also evaluated, by using Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR), the expression of Higd2a gene in healthy bone marrow-liver-spleen tissues of mice after quercetin (50 mg/kg) treatment. Thus, among the structural features of HIG2A protein that may participate in HIG2A translocation to the nucleus are an importin α-dependent nuclear localization signal (NLS), a motif of DNA binding residues and a probable SUMOylating residue. HIGD2A gene is not implicated in cancer via mutation. In addition, DNA methylation and mRNA expression of HIGD2A gene present significant alterations in several cancers; HIGD2A gene showed significant higher expression in Diffuse Large B-cell Lymphoma (DLBCL). Hypoxic tissues characterize the “bone marrow-liver-spleen” DLBCL type. The relative quantification, by using qRT-PCR, showed that Higd2a expression is higher in bone marrow than in the liver or spleen. In addition, it was observed that quercetin modulated the expression of Higd2a gene in mice. As an assembly factor of mitochondrial respirasomes, HIG2A might be unexpectedly involved in the change of cellular energetics happening in cancer. As a result, it is worth continuing to explore the role of HIGD2A in cancer biology.
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