KR20220032936A - Composition for preventing or treating hearing loss comprising Gingerone as an active ingredient - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating hearing loss comprising Zingerone as an active ingredient, wherein Zingerone protects inner ear hair cells or spiral ganglion cells, and can reduce oxidative stress, thereby effectively preventing or treating hearing loss. The present invention is the pharmaceutical composition for preventing or treating hearing loss comprising Zingerone or a pharmaceutically acceptable salt thereof as an active ingredient.

Description

Composition for preventing or treating hearing loss comprising Gingerone as an active ingredient

It relates to a composition for preventing or treating hearing loss comprising Gingeron as an active ingredient.

Among various sensory organ diseases, inner ear disease has the highest incidence. Until now, research and development for diseases related to the ear has mostly been on diseases caused by inflammation such as bacterial otitis externa, malignant otitis, fungal otitis externa, otomycosis, otitis media, or otitis media. was mainly done However, in modern society, it has been reported that more than 40% of people over 50 and over 70% of people over 70 have hearing loss. In particular, oxidative stress is known to be a common major cause of degenerative hearing loss and ototoxic hearing loss.

As such, in modern society, due to an increase in noise exposure and an aging population, problems related to hearing loss due to cell or nerve damage rather than the above inflammation-based ear-related diseases are on the rise. Moreover, most of the general public can distinguish the difference between ear-related diseases caused by inflammation such as bacterial otitis externa, malignant otitis, fungal otitis externa, otomycosis, otitis media, or otitis media, and diseases of hearing loss due to cell or nerve damage. Hearing loss is one of the most common diseases with a high incidence in modern society. Hearing loss due to damage to cells or nerves can be caused by ototoxic drugs, neurotoxic chemicals, viruses, genetics, etc., in addition to causes such as noise or aging, and there are cases where the cause is unknown.

One of the new causes of hearing loss is hearing loss due to side effects of cancer treatment. In modern society, cancer has established itself as a disease that accounts for the number one mortality rate, and accordingly, the number of the population taking anticancer drugs has increased exponentially. However, the use of anticancer drugs could damage hearing. These side effects usually appear 1 to 2 weeks after administration of the anticancer drug, but in some cases, it has been reported that they appear after 6 months. As the number of cancer patients increases and the use of anticancer drugs increases, the number of patients with hearing loss is also rapidly increasing.

For the treatment of gastric hearing loss, a number of specialists and pharmaceutical industry-related practitioners still aim to treat gastric diseases as therapeutic agents based on existing antibiotics or anti-inflammatory drugs, but this cannot be used as a suitable therapeutic agent for hearing loss. The use of the above existing treatment is because, firstly, there is no known treatment for hearing loss, and secondly, many specialists and pharmaceutical industry-related workers do not clearly recognize the treatment for hearing loss. Due to these problems, the problem that the treatment of hearing loss cannot be properly performed is continuously occurring.

In particular, the treatment of sensorineural hearing loss was studied focusing on steroid therapy, but the effect was limited to the acute phase.

Accordingly, preclinical studies on various drugs have been reported as studies to find substances effective for prevention and treatment of hearing loss, but it has been confirmed that there is a limit to proceeding with clinical trials. In addition, there is no drug approved for the prevention and treatment of hearing loss to date. Moreover, there are hardly any developed drugs for hearing loss treatment using natural products or natural materials that can be used without toxicity or risk to the human body. That is, unlike ear-related diseases caused by inflammation, a suitable therapeutic agent for hearing loss has not been developed at all.

Under this background, there is an urgent need to research and develop a composition for preventing or treating hearing loss using a material that can be easily used as a material for food or pharmaceuticals.

One aspect is to provide a pharmaceutical composition for preventing or treating hearing loss comprising Zingerone or a pharmaceutically acceptable salt thereof as an active ingredient.

Another aspect is to provide a health functional food composition for preventing or improving hearing loss, which includes Zingerone or a pharmaceutically acceptable salt thereof as an active ingredient.

One aspect provides a pharmaceutical composition for preventing or treating hearing loss comprising Zingerone or a pharmaceutically acceptable salt thereof as an active ingredient.

In the present invention, the term "Zingerone" may be named 4-(4-hydroxy-3-methoxyphenyl)-butan-2-one or vanillylacetone. In addition, Gingeron may be one comprising the following formula (1).

[Formula 1]

The gingivism may be to reduce damage to the inner ear or cochlea in an individual. Gingeron can prevent or treat hearing loss in an individual by regulating an inflammatory response or oxidative stress. The Gingeron may be synthesized or obtained using a known purchasing agent.

As used herein, the term “hearing loss” refers to any state in which hearing is impaired or lost.

The hearing loss includes conductive hearing loss or sensorineural hearing loss.

The conductive hearing loss is a hearing loss caused by an ear disease, and is caused by a problem in organs such as the eardrum and ossicles, which are organs that transmit sound. Sensorineural hearing loss is a hearing loss caused by problems with the cochlea, the organ that senses sound, the auditory nerve, which transmits sound with electrical energy, and the brain, which plays a comprehensive role in sound discrimination and understanding. The cause of sensorineural hearing loss may be hearing loss caused by noise, drugs, aging, trauma, and the like, for example, ototoxic hearing loss.

The ototoxic hearing loss may be due to damage caused by drug use. The damage may be damage to the subject's inner ear, specifically, the cochlea.

In one embodiment, the ototoxic hearing loss may be caused by antibiotics. For example, the ototoxic hearing loss is gentamicin, streptomycin, kanamycin, neomycin, amikacin, tobramycin, netylmycin ( netilmicin), dibekacin, sisomycin, ribodomycin, cisplatin, carboplatin, and oxaliplatin of any one or more drugs selected from the group consisting of This may be due to administration.

In one embodiment, the ototoxic hearing loss may be caused by an anticancer agent. The anticancer agent may be an anticancer chemotherapeutic agent, an immunotherapeutic agent, or a targeted anticancer agent.

For example, the ototoxic hearing loss is cisplatin, asparaginase, azacitidine, belotecan, bleomycin, busulfan, capecitabine, carboplatin, carmustine, chlorambucil, cladribine, cyclophospha Mead, cytarabine, dacarbazine, dactinomycin, daunorubicin, decitabine, docetaxel, doxorubicin, enocitabine, epirubicin, etoposide, fludarabine, fluorouracin, gemcitabine, hydroxyuria, Idarubicin, ifosfamide, irinotecan, ixabepilone, lomustine, melphaline, mercaptopurine, methotrexate, mitomycin, mitoxantrone, nimustine, oxariplatin, paclitaxel, pemetrexed, temozolimide, Any one selected from the group consisting of thiotepa, topotecan, TSONE, vinplastin, vincristine, vinorelbine, gleevec, velcade, iresa, avastin, yerboy, impingi, thycentric, babencio, opdivo and keytruda This may be due to the administration of more than one drug.

In addition, the hearing loss may include a state in which hearing is reduced or lost, for example, noise-induced hearing loss, age-related hearing loss, sudden hearing loss, auditory neuropathy due to diabetes, traumatic hearing loss, viral hearing loss, and the like.

The pharmaceutical composition has an anti-inflammatory effect by regulating the expression of P450, 1A1, CYP1B1, iNOS, NFkB, TNFα, or IL6 mRNA or protein, and oxidative stress by regulating the expression of Ahr, HO1, SOD2 or Caspase3 mRNA or protein It may be effective in preventing or treating hearing loss by controlling the inner ear of the individual and inducing the regeneration of damage.

As used herein, the term “treatment” refers to alleviation, progression inhibition, or prevention of a disease, disorder or condition, or one or more symptoms thereof.

In the present invention, the term "active ingredient" or "pharmaceutically effective amount" refers to any of the compositions used in the practice of the invention provided herein sufficient for alleviation, progression inhibition or prevention of a disease, disorder or condition, or one or more symptoms thereof. can mean the amount of

As used herein, the terms “administering,” “introducing” and “implanting” are used interchangeably and into a subject by a method or route that results in at least partial localization of the composition according to one embodiment to a desired site. It may mean a batch of a composition according to an embodiment. A composition according to one embodiment may be administered by any suitable route that delivers at least a portion of a cell or cellular component to a desired location in a surviving individual. The survival period of the cells after administration to a subject may be as short as several hours, for example, 24 hours to several days, or as long as several years.

The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier, and each of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., oral dosage forms, external preparations, suppositories, and It may be formulated in the form of a sterile injectable solution.

The pharmaceutically acceptable carriers include those commonly used in the art, such as lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate yt, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. . In addition, the pharmaceutical composition of the present invention includes a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, and other pharmaceutically acceptable additives.

When the pharmaceutical composition is formulated as a solid preparation for oral use, it includes tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one or more excipients, for example, starch, calcium carbonate, water It may include cross (sucrose) or lactose, gelatin, and the like, and includes, but is not limited to, lubricants such as magnesium stearate and talc.

When the pharmaceutical composition is formulated as a liquid formulation for oral use, it includes suspensions, solutions, emulsions, syrups, and the like, and includes, but is not limited to, water and diluents such as liquid paraffin, wetting agents, sweeteners, fragrances, and preservatives.

When the pharmaceutical composition is formulated for parenteral use, it includes sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories, and non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, olive oil. vegetable oils such as, but not limited to, injectable esters such as ethyl oleate. As a suppository base, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, etc. may be used, but are not limited thereto.

The dosage of Gingerone contained in the pharmaceutical composition varies depending on the patient's condition and weight, age, degree of disease, drug form, administration route and period, but may be appropriately selected by those skilled in the art. For example, the composition may be administered at a dose of 0.0001 to 300 mg/kg per day, preferably 0.001 to 100 mg/kg, and the administration may be administered once or in several divided doses per day.

In one embodiment, the administration is 0.001 to 100 mg/kg/day, 0.1 to 90 mg/kg/day, 1 to 80 mg/kg/day, 5 to 75 mg/kg/day, 10 to 70 mg/kg/day or 20 to 60mg/kg/day may be administered for 1 to 10 days, 2 to 9 days, 3 to 8 days, or 4 to 8 days.

The pharmaceutical composition of the present invention is administered to mammals such as rats, mice, livestock, and humans by various routes, for example, oral, intraperitoneal, spinal, intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebrovascular injection. can be

Another aspect provides a food composition for preventing or improving hearing loss, comprising as an active ingredient Zingerone or a pharmaceutically acceptable salt thereof.

The Gingeron, the active ingredient, the hearing loss or the active ingredient is as described above.

The food composition may be used as a health functional food.

The term "health functional food" means a food manufactured and processed using raw materials or ingredients useful for the human body in accordance with the Health Functional Food Act, and "functionality" refers to the structure and function of the human body. It refers to ingestion for the purpose of obtaining useful effects for health purposes such as nutrient control or physiological action.

The food composition may contain ordinary food additives, and the suitability as the "food additive" is determined according to the general rules and general test methods of food additives approved by the Ministry of Food and Drug Safety, etc., unless otherwise specified. It is judged according to the relevant standards and standards.

The items listed in the "Food Additives Code" include, for example, chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid; Mixed preparations such as sodium L-glutamate preparation, noodle-added alkali agent, preservative agent, and tar color agent can be mentioned.

The preferred content of Gingeron or a pharmaceutically acceptable salt thereof in the food composition is not limited thereto, but may be, for example, 0.001 to 30% by weight of the finally prepared food. Preferably, it may be 0.01 to 20% by weight of the finally prepared food.

In order to use the Gingeron or its salt in the form of a food additive, it may be prepared and used in the form of a powder or a concentrate.

Another aspect provides a method for preventing or treating hearing loss in a subject, comprising administering to the subject Zingerone or a pharmaceutically acceptable salt thereof.

Administration may be administered by methods known in the art. Administration can be administered directly to a subject by any means, for example, intravenous, intramuscular, oral, transdermal, mucosal, intranasal, intratracheal or subcutaneous administration. can The administration may be systemically or locally. The administration may be administered locally to the site of the wound. In one embodiment, the administration may be oral administration, intraperitoneal administration, or direct spinal administration.

The composition may be administered in combination with drugs such as steroids, anti-inflammatory agents, antihistamines, antibiotics, and antifungals in order to effectively prevent or treat hearing loss in an individual. The combined administration may be administered sequentially, simultaneously, or separately to the subject.

The subject may be a mammal, such as a human, cow, horse, pig, dog, sheep, goat, or cat. The subject may be a subject in need of prevention or treatment of hearing loss.

The subject may have a hearing impairment or may be a subject suspected of hearing impairment. In one embodiment, the subject may be an individual with cochlear damage, and may be an individual with a history of receiving anticancer drugs or antibiotics. With respect to the anticancer agent or antibiotic, it is as described above.

In one embodiment, the administration is 0.001 to 100 mg/kg/day, 0.1 to 90 mg/kg/day, 1 to 80 mg/kg/day, 5 to 75 mg/kg/day, 10 to 70 mg/kg/day or 20 to 60mg/kg/day may be administered for 1 to 10 days, 2 to 9 days, 3 to 8 days, or 4 to 8 days.

According to the pharmaceutical composition for preventing or treating hearing loss according to one aspect, it has an effect of protecting inner ear hair cells or spiral ganglion cells, and can reduce oxidative stress, thereby effectively treating hearing loss.

1 is a diagram schematically showing a method of administering a pharmaceutical composition according to an embodiment to an animal model.
2 is a graph showing the threshold of auditory brainstem response (ABR) according to the administration of the pharmaceutical composition according to an embodiment.
Figure 3 is a graph showing the waveform of the auditory brainstem response (ABR) according to the administration of the pharmaceutical composition according to an embodiment.
4 is a view showing cross-sections of ganglion cells and hair cells according to magnification according to administration of the pharmaceutical composition according to an embodiment.
5 is a graph showing the mRNA expression of P450, 1A1, CYP1B1, iNOS, NFkB, TNFα, and IL6 according to the administration of the pharmaceutical composition according to an embodiment.
6 is a graph showing the protein expression of Ahr, HO1, SOD2 and Caspase3 according to the administration of the pharmaceutical composition according to an embodiment.
7 is a view showing the Western blot results of Ahr, HO1, SOD2 and Caspase3 according to the administration of the pharmaceutical composition according to an embodiment.

Hereinafter, it will be described in more detail through examples. However, these examples are for illustrative purposes of one or more embodiments, and the scope of the present invention is not limited to these examples.

Example 1. Administration of Gingeron in Animal Models

To test the effect of Gingeron on the treatment of hearing loss, 8-week-old female mice (n = 24) were used in the experiment. All mice were approved by the Animal Care and Use Committee (IACUC170162), College of Medicine, Cha Medical University, and all experiments were performed according to the guidelines of the committee. The experimental group and control group were classified into 8 negative controls, 8 cisplatin (CXP) administered groups, and 8 cisplatin and gingerone administered groups.

1 is a diagram schematically showing a method of administering a pharmaceutical composition according to an embodiment to an animal model.

The cisplatin administration group was intraperitoneally administered with cisplatin at a dose of 5 mg/kg per day from day 1 to day 5. In the cisplatin and gingerone administration group, after cisplatin administration from day 1 to day 7, gingerone was administered intraperitoneally at 50 mg/kg per day. The negative control group was administered by intraperitoneal injection of the same amount of physiological saline from day 1 to day 7.

Example 2. Conduct and results of auditory brainstem response in animal model

To confirm the effect of Gingeron on the treatment of hearing loss, auditory brainstem response (ABR) was performed at 4, 8, 16 or 32 kHz.

Thresholds (ABRT) of auditory brainstem response (ABR) were measured on days 0 and 10. The mice were anesthetized by injecting a mixture of zoletyl (40 mg/kg) and xylazine (10 mg/kg) intraperitoneally. Next, electrodes were inserted behind the ears of the mice. Tone bursts (duration, 1562 μs, envelope, Blackman, stimulation rate, 21.1/s) were delivered to electrodes inserted into mice through EC1 electrostatic speakers. By sweeping 1,024 times, auditory evoked responses were averaged. The auditory threshold was defined as the lowest sound intensity eliciting a III wave.

As a result, as shown in FIGS. 2 and 3 , it was observed that there was a hearing protection effect in the group administered with Gingeron.

2 is a graph showing the threshold of auditory brainstem response (ABR) according to the administration of the pharmaceutical composition according to an embodiment. Figure 3 is a graph showing the waveform of the auditory brainstem response (ABR) according to the administration of the pharmaceutical composition according to an embodiment.

According to FIGS. 2 and 3 , it was confirmed that the threshold decibel of the group administered with the pharmaceutical composition according to one embodiment at all kHz was lower than that of the group administered with cisplatin. These results suggest that the hearing impaired by cisplatin was restored by the administration of Gingeron.

Example 3. Animal model cochlear analysis results

3.1 Cross-section identification of ganglion cells and hair cells

In order to confirm the regenerative effect of cochlear tissue due to the administration of Gingeron, histological analysis of the cochlea was performed through H & E staining.

The cochlea of the animal model of Example 1 was obtained on the 10th day. The cochlea was immersed and fixed in 4% paraformaldehyde solution for histological examination.

Specifically, for H&E staining, paraffin blocks were generated using the cochlea. A 10 micron thick cochlear section was prepared from a paraffin block using a rotating microtome. After mounting the section on a glass slide, the section was removed from paraffin, incubated in hematoxylin for 5 minutes, and then stained with eosin for 45 seconds.

Next, histological examination of the cochlea was performed using the EVOS ^™ XL core imaging system (Invitrogen from Thermo Fisher Scientific, # AMEX1000). In the cochlea, the outer hair cells were excised after descaling. The outer hair cells of the dissected cochlea were stained with DAPI and observed using a confocal microscope. As a result, as shown in FIG. 4 , cross-sections of ganglion cells and hair cells according to magnification were confirmed.

4 is a view showing cross-sections of ganglion cells and hair cells according to magnification according to the administration of the pharmaceutical composition according to an embodiment.

According to FIG. 4 , as a result of staining, the density of spiral ganglion cells was higher in the group administered with cisplatin and ginger than the group administered with cisplatin. In addition, the cisplatin-administered group contained vacuoles with condensed chromatin, and it was confirmed that they had a disordered arrangement. These results indicate that ganglion cells and hair cells were damaged in the cisplatin-administered group. However, in the case of the cisplatin and Gingerone administration group, it was confirmed that cell damage was reduced. The survival rate of hair cells was 82.25% in the cisplatin-administered group and 90.3% in the cisplatin and gingerone-administered group. These results suggest that the hearing impaired by cisplatin was restored by the administration of Gingeron.

3.2 P450, 1A1, CYP1B1, iNOS, NFkB, TNF α , and confirmation of mRNA expression of IL6

In order to confirm the regenerative effect of cochlear tissue due to the administration of Gingeron, RT-PCR was performed.

The cochlea of the animal model of Example 1 was obtained on the 10th day. After obtaining the cochlea, the labyrinth tissue was collected. The cochlea of mice was analyzed by quantitative reverse transcription polymerase chain reaction (RT-PCR).

To perform quantitative RT-PCR, total RNA was first extracted from the cochlea using TRI Reagent® (Sigma-Aldrich, St. Louis, MO, USA). The reverse transcription reaction was performed using TOPscriptTM RT DryMIX (dT18 plus; Enzynomics Co. Ltd., Daejeon, Korea). Next, the CFX96 TouchTM Real-Time PCR Detection System (Bio-Rad, Hercules, CA, USA), TOPreal ?? Quantitative RT-PCR was performed using qPCR 2x PreMIX (SYBR Green; Enzynomics, Daejeon, Korea) and oligonucleotides.

Table 1 below shows the sequences of the primers used.

gene Primer sequence (forward) Primer sequence (reverse) annealing temperature
(°C) Length
(bp) RefSeq Number CYP1A1 5'-CATCCCCCACAGCACCATAA -3' 5'-TTCGCTTGCCCAAACCAAAG -3' 60 212 NM_012540.2 CYP1B1 5'-TGCTACTCGTTTCGGTCCTG -3' 5'-CAAGGCGAGCGAAGTACAAG -3' 60 162 NM_012940.2 iNOS 5'-AGGCCACCTCGGATATCTCT -3' 5'-TCTCTGGGTCCTCTGGTCAA -3' 60 85 NM_012611.3 NF-κB 5'-TGTCTGCACCTGTTCCAAAAGA-3' 5'-TGCCAGGTCTGTGAACACTC-3' 60 143 NM_199267.2 IL-6 5'-AGAGACTTCCAGCCAGTTGC-3' 5'-TGAAGTCTCCTCTCCGGACT-3' 60 88 NM_012589.2 TNFα 5'-CGTCAGCCGATTTGCCATTT -3' 5'-TCCCTCAGGGGTGTCCTTAG -3' 60 88 NM_012675.3

The mRNA expression level was derived based on the expression level of the reference gene glyceraldehyde 3-phosphate dehydrogenase (GAPDH).

5 is a graph showing the mRNA expression of P450, 1A1, CYP1B1, iNOS, NFkB, TNFα, and IL6 according to the administration of the pharmaceutical composition according to an embodiment.

According to FIG. 5 , the protein expression levels of AhR, HO1, SOD2, and caspase3 were higher in the cisplatin-administered group than in the negative control group. In addition, the expression of P450, 1A1, CYP1B1, iNOS, NFkB, TNFα, and IL6 in the cisplatin and gingerone-administered group was lower than in the cisplatin group, and was similar to that of the negative control group. These results suggest that cisplatin can induce hearing loss and that Gingeron can restore hearing loss caused by cisplatin.

3.3 Confirmation of expression of Ahr, HO1, SOD2 and Caspase3

In order to confirm the regenerative effect of cochlear tissue due to the administration of Gingeron, Western blot was performed.

The cochlea of the animal model of Example 1 was obtained on the 10th day. After obtaining the cochlea, the labyrinth tissue was collected. The cochlea of mice was analyzed by Western blot.

Specifically, the cochlea was lysed using a radioimmunoprecipitation assay buffer (Cell Signaling Technology, Danvers, Massachusetts, USA), and the protein concentration of the lysate was calculated using the Bio-Rad protein assay kit. Next, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (8%) was performed to separate the protein, and the separated protein was transferred to a polyvinylidene difluoride membrane (Merck Millipore, Burlington, MA, USA). After immersing the isolated protein in blocking buffer for 1 hour, the primary antibody and the membrane were incubated together. The primary antibody is an aryl hydrocarbon receptor (AhR; mouse monoclonal, Santa Cruz Biotechnology, # SC-133088), heme oxygenase 1 (HO1; ADI-SPA-895, rabbit polyclonal, Enzo Stressgen), superoxide Dismutase 2 (superoxide dismutase 2: SOD2) (ab13533, rabbit IgG, Abcam), and caspase 3 (rabbit polyclonal, Cell Signaling Technology, # 9662S) was used. Next, secondary antibodies, anti-rabbit IgG HRP-conjugated antibody (Cell Signaling Technology, #7074S) and goat anti-mouse IgG H&L (HRP) antibody (Abcam, # ab97023) were applied. After application, samples were detected with a chemiluminescence kit (Bio-Rad). The protein expression level was expressed using ImageJ gel analysis software (National Institutes of Health, Bethesda, MD, USA), and the expression of the protein to be analyzed was compared with the expression level of beta actin.

As a result, as shown in FIGS. 6 and 7 , it was confirmed that the protein expression of Ahr, HO1, SOD2 and Caspase3 was changed according to the administration of Gingeron.

6 is a graph showing the protein expression of Ahr, HO1, SOD2 and Caspase3 according to the administration of the pharmaceutical composition according to an embodiment. 7 is a view showing the Western blot results of Ahr, HO1, SOD2 and Caspase3 according to the administration of the pharmaceutical composition according to an embodiment.

6 and 7, the protein expression levels of Ahr, HO1, SOD2 and Caspase3 were higher in the cisplatin-administered group than in the negative control group. In addition, the expression of Ahr, HO1, SOD2 and Caspase3 in the cisplatin and gingerone administration group was lower than that in the cisplatin administration group. These results suggest that cisplatin can induce hearing loss and that Gingeron can restore hearing loss caused by cisplatin.

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Claims (8)

A pharmaceutical composition for preventing or treating hearing loss comprising Zingerone or a pharmaceutically acceptable salt thereof as an active ingredient. The pharmaceutical composition of claim 1 , wherein the ginger reduces damage to the inner ear. The pharmaceutical composition of claim 1, wherein the hearing loss is conductive hearing loss or sensorineural hearing loss. The pharmaceutical composition according to claim 1, wherein the hearing loss is any one selected from the group consisting of noise-induced hearing loss, senile hearing loss, sudden hearing loss, diabetes-induced hearing loss, ototoxic hearing loss, traumatic hearing loss, and viral hearing loss. The pharmaceutical composition of claim 4, wherein the ototoxic hearing loss is due to damage caused by drug use. The pharmaceutical composition of claim 5, wherein the damage is damage to the cochlea. The pharmaceutical composition of claim 5, wherein the drug is an anticancer agent. A food composition for preventing or improving hearing loss comprising Zingerone or a pharmaceutically acceptable salt thereof as an active ingredient.

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