Hepato-, neuroprotective effects and QSAR studies on flavoalkaloids and flavonoids from Astragalus monspessulanus
2019
Kondeva-Burdina, Magdalena | Doytchinova, Irini | Krasteva, Ilina | Ionkova, Iliana | Manov, Vasil
This study investigated the possible hepato- and neuroprotective effects of flavoalkaloids and flavonoids isolated from Astragalus monspessulanus ssp. monspessulanus and ssp. illyricus. Rat hepatocytes obtained by in situ two-stepp collagenase perfusion, and rat brain synaptosomes obtained by multiple centrifugation and Percoll gradient were used. Administered alone, on hepatocytes, all of the compounds increased statistically significantly the lactate dehydrogenase (LDH) activity and malondialdehyde (MDA) production and decreased the reduced glutathione (GSH) level, compared to the control (non-treated hepatocytes). Some of the compounds (1–7) had lower toxicity on the exam parameters than silybin. The main structural features accounting for the lower hepatotoxicity (evaluated by quantitative structure–activity relationship (QSAR) studies) are the increased number of hexoses and the number of aromatic OH groups. On the two in vitro toxicity models, all the 13 compounds had statistically significant hepato- and neuroprotective activities. They preserved the hepatocyte and synaptosome viability, as well as the GSH level and decreased the LDH leakage and MDA production. On isolated rat hepatocytes, in tert-butyl hydroperoxide- and on isolated rat synaptosomes, in 6-OH-dopamine-induced oxidative stress, flavoalkaloids and flavonoids isolated from A. monspessulanus ssp. monspessulanus and ssp. illyricus, were effective hepato- and neuroprotectors, as well as antioxidants. The observed higher hepato- and neuroprotective effects of 1, 2, 4, 7 and eight may be assigned to the different substituents present in either the aglycone or the sugar moieties.
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