Study On The Biological Activity Of Hederagenin Against Amyloid Protein Damage

Alzheimer’s disease(AD)is a slowly progressing neurodegenerative disease,with clinical symptoms typically manifested as memory impairment and comprehensive dementia such as personality and behavioral changes,which is a major disease that seriously endangers the health of the elderly,and has become a serious public health problem facing China and even the world.With the continuous deepening of the research on the neurobiological mechanism of AD,various possible pathogenesis has been proposed,among which Aβ theory is still the mainstream theory at present.The senile plaques formed by extracellular Aβ deposition in the cerebral cortex and hippocampus are the most prominent anatomical features of AD,which are mainly composed of different lengths of Aβ form.Aβ is a polypeptide composed of 39 to 42 amino acids,in which hydrophobic and easily aggregating Aβ1-42 deposition is a characteristic pathological change of AD.Aβ theory holds Aβ1-42 can exert neurotoxicity through various ways,and can combine with nerve growth factor receptor to induce neuron apoptosis.Combined with NMDA receptor,it can cause oxidative stress damage to neurons,reduce synapses and interfere with synaptic function.It combines with curl protein receptor to form neurofibrillary winding,etc.At present,the five drugs approved by the FDA mainly treat AD by regulating neurotransmitters,but can only alleviate symptoms and cannot cure the disease.Furthermore,traditional Chinese medicine and natural products have gradually been recognized by researchers as new research objects.Hederagenin(HG),as a rich aglycone,exists in a variety of traditional drugs.HG shows a variety of biological activities,including anti-tumor,anti-inflammatory,antidepressant,antineurodegenerative and can penetrate the blood brain barrier.But whether it has anti-Aβ1-42 activity has not been reported,so according to Aβ1-42 the way to exert neurotoxicity and the characteristics of HG are speculated that HG has anti-Aβ1-42 biological activity.In this article,using neuroblastoma cells(SH-SY5Y)to establish Aβ1-42 model,to evaluate the effect of HG on Aβ1-42 injury in vitro,using a temperature inducible expression Aβ1-42 to evaluate the transgenic Caenorhabditis elegans(C.elegans)CL4176 strain HG versus Aβ1-42 injury protection in vivo.The results show that the concentration is 20 μM of Aβ1-42 incubation in 37℃ incubator for 24 h can induce cell damage,which is consistent with the results of literature Aβ1-42 injury cell model.MTT method screening determination 2.5 μM HG vs.Aβ1-42 injured cell model has protective effect,which can increase the cell survival rate to 73.17%(p<0.01).Compared with the model group,the apoptosis rate of injured cells decreased by 6.14%(p<0.05),the content of ROS decreased by 25.30%(p<0.01);thioflavin T(ThT)results show that HG may not act directly on Aβ142;Western Blot was used to analyze the effect of HG on Aβ1-42,the protective mechanism of injury model shows that HG can reduce oxidative stress and cell apoptosis,and exert Aβ1-42 at the level of SH-SY5Y cells through PI3K/AKT signal pathway Damage protection.In order to further explore the anti-Aβ1-42 injury effect of HG in vivo model,select CL4176 strain got 100 μM and 300 μM through paralysis rate test HG of which can reduce the paralysis rate of CL4176 nematode by 30.87%and 20.58%,and prolong the life of N2 and CL4176 nematode.Therefore,these two concentrations were selected for subsequent experiments.The results showed that compared with the control group,100 μM and 300 μM.The content of ROS in group was 78.81%(p<0.01)and 83.17%(p<0.01),respectively the deposition of Aβ1-42 was 77.79%(p<0.05)and 84.67%(p<0.05)respectively.The above results show that HG can delay the paralysis of CL4176 nematode by regulating oxidative stress,prolong the life span,and play a role in Aβ damage protection.It will lay an experimental foundation for the future research on more animal models and clinical application of HG.The study holds the active ingredient HG from the natural product,in the Aβ1-42 induced cell injury model,the oxidative damage and apoptosis were reduced,and the injured cells were protected by PI3K/AKT signal pathway;improve antioxidant capacity in CL4176 nematode and inhibit Aβ142 deposition can inhibit its toxicity and delay the aging and paralysis of nematodes and upregulate the levels of transcription factors skn-1,sir-2.1,hsf-1,and daf-16.This study explored the effect of HG on Aβ1-42.The signal pathway that plays a role in the protective effect of injured cells was first found in SH-SY5Y cells and C.elegans evaluated HG’s anti-Aβ1-42 toxic effect,which proves that it may play a certain role in the prevention and treatment of AD.