| According to the survey,the number of drug-induced hearing loss patients has increased year by year,accounting for about 20% of people with hearing loss,which has become the main cause of congenital deafness in newborns and acquired deafness in adults.In addition,drug-induced hearing loss patients are often accompanied by tinnitus,dizziness,ataxia and other symptoms,which greatly affect the patients’ physical and mental health and quality of life.The common drugs that cause drug-induced hearing loss are mainly aminoglycoside antibiotics and platinum-based chemotherapeutics,which can lead irreversible damage to cochlear hair cells and deafness.There are currently no drugs for the prevention and treatment of drug-induced hearing loss,so finding drugs that protect and promote hair cell regeneration is a major challenge to researchers.Traditional Chinese medicine is a valuable resource in China,which has the characteristics of low toxicity and a large number of bioactive molecules.In addition,the variety of marine microbial metabolites makes it one of the research hotspots in recent years.Both traditional Chinese medicines and microorganisms are rich in active substances,which can be used for anti-tumor,anti-inflammatory,anti-viral,hearing impairment and other diseases.It is an important resource for finding active ingredients for the protection or treatment of drug-induced deafness.Therefore,in this study,in vitro and in vivo experiments were performed with HEI-OC1(House Ear Institute-Organ of Corti 1)cells and zebrafish models induced by gentamicin or cisplatin.Through the screening of extracts from 11 kinds of traditional Chinese medicine and 13 compounds from traditional Chinese medicine and marine microorganisms,the active ingredients of preventing and treating drug-induced deafness were rapidly searched.The main research contents are as follows:After literature research,it is found that 11 kinds of traditional Chinese medicine are widely used in the treatment of ear diseases.Subsequently,they were extracted with 75% ethanol to obtain crude extracts,which were studied in vitro using the HEI-OC1 cell damaged model induced by gentamicin or cisplatin.The results have shown that traditional Chinese medicines with preventive effect on gentamicin induced damage include PH,CGE,GA,PMR,Cyperi Rhizoma and PQR.The preventive effect on cisplatin-induced damage was Cyperi Rhizoma.The extracts from 11 kinds of traditional Chinese medicine was studied in the body using preventive model of damage to zebrafish hair cells caused by gentamicin or cisplatin.The results have shown that traditional Chinese medicines with preventive effect on gentamicin induced damage include Cyperi Rhizoma,CSF and ALR.The preventive effect on cisplatin-induced damage were AOR,PMR and PH.Cyperi Rhizoma showed preventive activity in both cell experiments and zebrafish experiments,and its active ingredients were further studied.According to literature research,it is speculated that the active ingredients in Cyperi Rhizoma are mainly flavonoids.The total flavonoids were extracted and the activity was verified by gentamicin-induced zebrafish hair cells damage model.Comparing the activities of Cyperi Rhizoma from three places,the results showed that the activity of Shandong origin was lower than that of Anhui and Guangdong,and there was no difference between Anhui and Guangdong origin.The Cyperi Rhizoma of Anhui origin was separated by the method of activity tracking guidance separation,and three known flavonoids were obtained by analyzing the active segment by LC-MS/MS.Then,ten compounds were isolated and purified from each fraction,which were: Stigmasterol(LJ-1),Obtusifolin(LJ-2),and 5-methoxy-2-methylnaphthalene-1,4-dione(LJ-3),Emodin(LJ-4),Aurantio-obtusin(LJ-5),Syringic acid(LJ-6),Succinic acid(LJ-7),Luteolin(LJ-8),Cyperenoic acid(LJ-9),and Caprolactam(LJ-10).Compound LJ-3 was first discovered from natural products.The prevention and treatment models on zebrafish hair cell damage caused by gentamicin or cisplatin were used to screen 8 compounds from traditional Chinese medicine and 5 compounds from marine microorganisms.The results showed that the preventive models,flavonoids LJ-8 had a preventive effect on the zebrafish hair cell damage caused by gentamicin.Sterols LJ-1 and 11,terpenoids LJ-16 and organic acids LJ-7 had a preventive effect on the damage of cisplatin-induced zebrafish hair cells.The results showed that the therapeutic models,sterols LJ-13 had a therapeutic effect on the zebrafish hair cell damage caused by gentamicin,Sterols LJ-11 and 12 had therapeutic effect on the damage of cisplatininduced zebrafish hair cells.Scientists point out that the damage of human cochlear hair cells is non-renewable,making a lot of research limited to controlling the cause and relieving symptoms.Recent studies have found that although hair cells cannot be regenerated directly,the supporting cells located around the hair cells can and differentiate into hair cells,which shows that the regeneration of hair cells is feasible.A few of currently available drugs(SENS-401,AM-125,Ebselen)for the treatment of hearing loss have entered clinical trials,but the mechanism has not been fully clarified.In summary,through the screening of 11 extracts from traditional Chinese medicine and 13 compounds for the prevention and treatment drug-induced hearing loss,nine extracts and seven compounds all showed preventive or therapeutic activity.This study has shown that two sterols have the ability to promote the proliferation of zebrafish hair cells,which provides new ideas for lead compounds research in the prevention and treatment of drug-induced hearing loss. |
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