Screening And Excavation Of Anti-amyloid Aggregation Components In Natural Materia Medica

Protein amyloid diseases belong to protein misfolding diseases.common amyloid diseases include Alzheimer's disease,Type II diabetes,Spongiform encephalopathy,Parkinson's disease,and the like.Amyloid fibers are deposited due to misfolding of proteins in the formation of the native conformation.The presence of amyloid aggregates induces these diseases.Therefore,these diseases can be collectively referred to as protein conformational diseases.There are still no specific drugs for the treatment of amyloid-related diseases.One treatment option is to interfere,intervene or inhibit the various stages of protein fibrillation.In order to inhibit,delay the formation of fibers,to achieve the purpose of the prevention,control and,eventually,the treatment of such diseases.Previouse studies have AFown that monoflavonoids such as myricetin and morin can inhibit the fiber formation of Hen Egg Whilte lysozyme(HEWL).This experiment is to study whether the related components of monoflavonoids,such as pantosyl flavone,have similar inhibitory effects.In this experiment,fluorescence detection combined with computer simulations demonstrated that the inhibitory fibrillation ability of pantocerein was slightly weaker.On the other hand,Amyloid fibrils often deposit in the heart and brain blood vessels,kidneys,nerves and other parts,leading to the decline of the function of related organs.Based on the advantages of traditional Chinese medicine,drugs with similar functions can be screened from drugs with anti-cardiovascular and anti-cerebrovascular diseases.In this experiment,Panax notoginseng,Cornus officinalis,salvia miltiorrhiza,Carthamus,Scindapsus aureus,thamnolia vermicularis,and Moringa seed were selected as raw materials following extraction of the natural ingredients by different methods.The study found that the extract of Panax notoginseng,Scindapsus aureus and thamnolia vermicularis had AFown the inhibitory effect on HEWL fiber formation.With the thamnolia vermicularis water extract the best effect.Comparing different extraction methods,the effect ofthamnolia vermicularis water extract is better.thamnolia vermicularis water extract has an IC50 value of 0.018 mg/mL.By using liquid chromatography-mass spectrometry(LC-MS),the molecular weight of the active ingredients in thamnolia vermicularis water extract can be roughly determined.However,the identification of specific chemical componds and the determination of the structure still needs further study.Yeast experiments AFowed that when the concentration of thamnolia vermicularis was 5 mg/mL with water as the solvent,no significant antibacterial activity was observed when the OD value of the liquid yeast culture was 4.The results of protein expression AFowed that thamnolia vermicularis aqueous extract inhibited the extracellular formation of aggregates of the chicken cystatin mutant I66 Q in a concentration-dependent manner.When the concentration reaches1.5mg/mL,it will have a certain inhibitory effect on the secretion of the protein.However,the specific mechanism remains to be explored.To sum up,this study is based on the common structure of the compounds found in previous studies,and carries out a preliminary screening of the main structure and derivatives of the derivatives.It is found that the main structure of the compound is very important to its ability to inhibit the fiber formation.On the other hand,in the attempt to continue to excavate small molecules of natural products,we have identified several traditional Chinese and Tibetan herbs with anti-amyloid fibril formation potential,nevertheless,identification of the effective ingredients still need further experimental data support.