RESUMO
There is an intense search for natural compounds that can inhibit the oligomerization and fibrillation of α-synuclein (α-Syn), whose aggregation is key to the development of Parkinson's disease (PD). Rosa damascena is a medicinal herb widely used in Middle Eastern food, ceremonies, and perfumes. The herb is known to contain many different polyphenols. Here we investigated the existence of α-Syn fibrillation inhibitors in R. damascena extract. Different HPLC fractions of the extract were assessed in α-Syn fibrillation and toxicity assays. The most active fractions led to the formation of more α-Syn oligomers but with less toxicity to SH-SY5Y cells, according to MTT and LDH assays. LC-MS analysis identified gallic acid, kaempferol 3-glucoside, kaempferol-3-O-ß-rutinoside, and quercetin which were subsequently shown to be strong α-Syn fibrillation inhibitors. Our results highlight the benefits of R. damascena extract to combat PD at the population level.
Assuntos
Rosa , alfa-Sinucleína , Flavonoides/farmacologia , Glicosídeos/farmacologia , Humanos , Fenóis/toxicidadeRESUMO
Willow (Salix spp.) is well known as a source of medicinal compounds, the most famous being salicin, the progenitor of aspirin. Here we describe the isolation, structure determination, and anti-cancer activity of a cyclodimeric salicinoid (miyabeacin) from S. miyabeana and S. dasyclados. We also show that the capability to produce such dimers is a heritable trait and how variation in structures of natural miyabeacin analogues is derived via cross-over Diels-Alder reactions from pools of ortho-quinol precursors. These transient ortho-quinols have a role in the, as yet uncharacterised, biosynthetic pathways around salicortin, the major salicinoid of many willow genotypes.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias/tratamento farmacológico , Salix/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/uso terapêutico , Álcoois Benzílicos/química , Vias Biossintéticas/genética , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Glucosídeos/biossíntese , Glucosídeos/química , Humanos , Concentração Inibidora 50 , Casca de Planta/química , Casca de Planta/metabolismo , Salix/genética , Salix/metabolismoRESUMO
Willow (Salix sp.) is a historically well-known herbal medicine that provided the lead compound (salicin) for the discovery of aspirin, one of the most successful plant derived drugs in human medicine. During a metabolomics screen of 86 Salix species contained in the UK National Willow Collection, we have discovered, isolated and fully characterised a new natural salicinoid - salicin-7-sulfate. This molecule may have important human pharmacological actions that need to be considered in determining the efficacy and safety of willow herbal medicines.