The influence of silver fir (Abies alba) branch extract on human brain arteries contractility

Cerebrovaskularne bolezni predstavljajo velik javnozdravstveni problem in vključujejo bolezenska stanja, ki prizadenejo možganske žile in pretok krvi skozi možgane. Največjo smrtnost povzročata možganska kap in demence, med katerimi sta najpogostejši Alzheimerjeva bolezen in vaskularna demenca. Na tržišču je že prisotnih veliko zdravilnih učinkovin, ki upočasnijo možgansko degeneracijo, vendar je zaenkrat še ne ustavijo, ker možganski sistem zaradi svoje posebnosti v zgradbi, funkciji in selektivni prepustnosti predstavlja velik izziv pri načrtovanju novih zdravilnih učinkovin. Namen magistrske naloge je bil raziskati učinek dveh izvlečkov (pod zaščitenim imenom Belinal®) iz vej bele jelke (Abies alba) na delovanje izoliranih človeških možganskih arterij. Delovanje izvlečkov smo primerjali z učinki standardnega izvlečka ginka EGb 761®. Za primerjavo smo se odločili, ker bi naj poleg antioksidacijskega učinka, ginko pozitivno deloval tudi na kognitivne funkcije in relaksiral arterije in s tem povečal pretok krvi skozi možgane ter tako pripomogel k izboljšanju spomina. Predvidevali smo, da bosta tudi izvlečka iz vej bele jelke relaksirala možganske arterije. Za mehanizem delovanja smo predvidevali, da je povezan z delovanjem v žilnem endoteliju in sicer z aktivacijo sistema eNOS in zaviranjem nastajanja kisikovih radikalov. S pomočjo naprave za delo z izoliranimi žilami in DMT napravo smo merili izometrično silo krčenja žilnih obročkov in preučevali njihov odziv po štirih protokolih. Poskušali smo ugotoviti, ali izvlečka relaksirata žilne obročke (protokol 1), mehanizem delovanja (protokol 2), vpliv izvlečkov na vnetje (protokol 3) in učinek obeh izvlečkov na žilne obročke po inkubaciji (protokol 4). Ugotovili smo, da oba izvlečka iz vej bele jelke relaksirata žilne obročke v nasprotju z ginkom, ki jih krči. Mehanizem po katerem izvlečka relaksirata žilne obročke ni značilno povezan z aktivacijo sistema eNOS. Izvleček iz vej bele jelke z višjo vsebnostjo lignanov bolj relaksira žilne obročke kot tisti z nižjo vsebnostjo. Izvlečka iz vej bele jelke sta pokazala učinkovitost pri relaksaciji človeških možganskih arterij in bi lahko v prihodnosti imela pomembno vlogo pri zdravljenju in preprečevanju cerebrovaskularnih bolezni.Cerebrovascular diseases present a major public health problem and include conditions that affect cerebral vessels and blood flow through the brain. The highest mortality is caused by stroke and dementias, among which Alzheimer’s disease and vascular dementia are the most common. There are already many active pharmaceutical ingredients on the market that slow down brain degeneration, but at the moment they can\u27t prevent it, because the brain system, due to its special features in its structure, function and selective permeability, presents a major challenge in the design of new active pharmaceutical ingredients. The purpose of the master’s thesis was to determine the effects of two extracts (Belinal®) from the branches of the silver fir (Abies alba) on the functioning of isolated human brain arteries. The effects of the extracts were compared with the standard ginkgo EGb 761® extract. We decided to compare both extracts with ginkgo, because it is declared to relax brain arteries. We assumed both extracts from branches of silver fir would also relax the brain arteries. For the mechanism of action, we assumed that it was related to the action in the vascular endothelium by activating the eNOS system and inhibiting the formation of oxygen radicals. We measured the isometric force of the contraction of vascular rings with the help of a device of working with isolated vessels and a DMT device. We examined their response according to the four protocols. We tried to determine whether the extracts caused contraction or relaxation of the vascular rings (protocol 1), the mechanism of action (protocol 2), the effects of extracts on inflammation (protocol 3) and the effects of both extracts on vascular rings after incubation (protocol 4). We found that both extracts caused relaxation of the vascular rings in the contrast to ginkgo, which contracted the rings. The mechanism by which the extracts relaxes the vascular rings is not significantly related to the activation of the eNOS system. Extract from branches of silver fir with higher content of lignans relaxes vascular rings more than extract with lower content. Extracts from branches of silver fir showed effectiveness in the relaxation of human brain arteries and could have an important role in treatment and prevention of cerebrovascular diseases in the future