Characterization of Ginkgo biloba Leaf Flavonoids as Neuroexocytosis Regulators.

Choongjin Ban,Sora Cho,Hakhee Kang,Yong Sub Shin,Davin Jang,Dae-Ok Kim,Chinhan Kim,Yong Joon Kim,Joon-Bum Park,Hye Rin Kim,Hyunggun Kim,Hyungjin Bae,Dae-Hyuk Kweon

doi:10.3390/molecules25081829

Abstract

Ginkgo biloba leaf (GBL) is known as a potential source of bioactive flavonoids, such as quercetin, arresting the neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-zippering. Here, the GBL flavonoids were isolated in two different manners and then examined for their bioactivity, physicochemical stability, and biocompatibility. The majority of flavonoids in the non-hydrolyzed and acidolyzed isolates, termed non-hydrolyzed isolate (NI) and acidolyzed isolate (AI) hereafter, were rich in flavonol glycosides and aglycones, respectively. Glycosidic/aglyconic quercetin and kaempferol were abundant in both NI and AI, whereas a little of apigenin, luteolin, and isorhamnetin were found in AI. NI was more thermostable in all pH ranges than quercetin, kaempferol, and AI. NI and AI both inhibited neurotransmitter release from differentiated neuronal PC-12 cells. NI and AI showed 1/2–1/3 lower EC50/CC50 values than quercetin and kaempferol. The NI and AI exhibited no toxicity assessed by the tests on chorioallantoic membranes of hen’s eggs, removing toxicological concerns of irritation potential. Moreover, GBL isolates, particularly AI, showed antioxidant and anti-inflammatory activities in the use below the CC50 levels. Taken together, these results suggest that GBL isolates that are rich in antioxidant flavonoids are effective anti-neuroexocytotic agents with high stability and low toxicity.

Highlights

Flavonoids are known to have various health benefits, such as antioxidant, antimutagenic, antibacterial, antiangiogenic, anti-inflammatory, antiallergic, and anticancer activities [1,2,3]
The release of neurotransmitters from the neuronal cells can be regulated by the flavonoids, as sensitive factor attachment protein receptor (SNARE) complex formation is essential for the complete fusion between the synaptic vesicular membrane and plasma membrane
The presence of flavonoid glycosides in non-hydrolyzed isolate (NI) and acidolyzed isolate (AI) derived from Ginkgo biloba leaf (GBL), NI, imparted pH and thermal stabilities in aqueous conditions

Summary

Introduction

Flavonoids are known to have various health benefits, such as antioxidant, antimutagenic, antibacterial, antiangiogenic, anti-inflammatory, antiallergic, and anticancer activities [1,2,3]. The release of neurotransmitters from the neuronal cells can be regulated by the flavonoids, as SNARE complex formation is essential for the complete fusion between the synaptic vesicular membrane and plasma membrane. In vitro studies suggest that various stages of membrane fusion, including docking, hemifusion, and pore formation, are affected by the flavonoids because of direct interaction with both SNARE complex intermediate and membranes [4,7,8]. Flavonols, such as myricetin and Q, can mimic the activity of botulinum neurotoxins (BoNTs) by inhibiting SNARE complex formation since BoNTs block acetylcholine release by proteolyzing SNARE proteins [9]

Methods

Results

Conclusion