Bin Na Hong

Coffee improves auditory neuropathy in diabetic mice

Coffee is a widely consumed beverage and has recently received considerable attention for its possible beneficial effects. Auditory neuropathy is a hearing disorder characterized by an abnormal auditory brainstem response. This study examined the auditory neuropathy induced by diabetes and investigated the action of coffee, trigonelline, and caffeine to determine whether they improved diabetic auditory neuropathy in mice. Auditory brainstem responses, auditory middle latency responses, and otoacoustic emissions were evaluated to assess auditory neuropathy. Coffee or trigonelline ameliorated the hearing threshold shift and delayed latency of the auditory evoked potential in diabetic neuropathy. These findings demonstrate that diabetes can produce a mouse model of auditory neuropathy and that coffee consumption potentially facilitates recovery from diabetes-induced auditory neuropathy. Furthermore, the active constituent in coffee may be trigonelline.

Synergistic Potentials of Coffee on Injured Pancreatic Islets and Insulin Action via KATP Channel Blocking in Zebrafish.

Pancreatic islets (PIs) are damaged under diabetic conditions, resulting in decreased PI size. This study examined the regenerative effects of coffee and its components (caffeine, CFI; trigonelline, TRG; chlorogenic acid, CGA) on zebrafish larval PIs and β-cells damaged by administration of alloxan (AX). In addition, the influence of coffee and its active components on KATP channels was investigated using diazoxide (DZ) as a KATP channel activator. PI size and fluorescence intensity were significantly increased in the coffee-treated group relative to the no-treatment group (P < 0.0001). In addition, coffee exerted significant regenerative effects on pancreatic β-cells (p = 0.006). Treatment with TRG and CGA rescued PI damage, and the combination of TRG/CGA had a synergistic effect. In conclusion, the results indicate that coffee has beneficial effects on AX-damaged PIs and may also be useful as a blocker of pancreatic β-cell K(+) channels.

Effect of baicalein from Scutellaria baicalensis on prevention of noise-induced hearing loss.

Noise-induced hearing loss (NIHL) has been thought to primarily involve damage to the sensory hair cells of the cochlea via mechanical and metabolic mechanisms. This study examined the effects of baicalin, baicalein, and Scutellaria baicalensis (SB) extract against NIHL in a mouse model. Mice received oral treatment with SB, baicalin, baicalein beginning 30 min prior to noise exposure and continuing once daily throughout the study. Hearing threshold shift was assessed by auditory brain stem responses for 35 days following noise exposure. Central auditory function was evaluated by auditory middle latency responses. Cochlear function was determined based on transient evoked otoacoustic emissions. SB significantly reduced threshold shift, central auditory function damage, and cochlear function deficits, suggesting that SB may protect auditory function in NIHL and that the active constituent may be a flavonoid, baicalein.

Post-exposure treatment with ginsenoside compound K ameliorates auditory functional injury associated with noise-induced hearing loss in mice

Noise-induced hearing loss (NIHL) is thought to primarily involve damage to the sensory hair cells of the cochlea via mechanical and metabolic mechanisms. Unfortunately, initial studies assessing the effectiveness of post-exposure treatment after hearing loss have yielded largely disappointing results. This study explored the effects of oral treatment with Korean red ginseng (RG) and with two bioavailable ginsenoside metabolites, ginsenoside Rh1 and ginsenoside compound K (GCK), in response to NIHL in a murine model. Pharmacological treatments began 24h after noise exposure and were continued once daily for 7 days. Central auditory function was evaluated using auditory middle latency responses, and cochlear function was determined based on transient evoked otoacoustic emissions. Additionally, cochlear hair cell morphology was investigated after noise exposure. Both Korean red ginseng and compound K reduced threshold shifts, central auditory function damage, and cochlear functional and morphological deficits. In contrast, treatment with ginsenoside Rh1 did not result in recovery of NIHL in mice. These results suggest that consumption of Korean red ginseng may facilitate recovery from noise-induced hearing loss. Furthermore, one of the active constituents in ginseng is likely ginsenoside compound K.

Amelioration of Auditory Response by DA9801 in Diabetic Mouse

Diabetes mellitus (DM) is a metabolic disease that involves disorders such as diabetic retinopathy, diabetic neuropathy, and diabetic hearing loss. Recently, neurotrophin has become a treatment target that has shown to be an attractive alternative in recovering auditory function altered by DM. The aim of this study was to evaluate the effect of DA9801, a mixture of Dioscorea nipponica and Dioscorea japonica extracts, in the auditory function damage produced in a STZ-induced diabetic model and to provide evidence of the mechanisms involved in enhancing these protective effects. We found a potential application of DA9801 on hearing impairment in the STZ-induced diabetic model, demonstrated by reducing the deterioration produced by DM in ABR threshold in response to clicks and normalizing wave I–IV latencies and Pa latencies in AMLR. We also show evidence that these effects might be elicited by inducing NGF related through Nr3c1 and Akt. Therefore, this result suggests that the neuroprotective effects of DA9801 on the auditory damage produced by DM may be affected by NGF increase resulting from Nr3c1 via Akt transformation.

Distinction between auditory electrophysiological responses in type 1 and type 2 diabetic animal models.

Neurological research has focused recently on determining the molecular mechanisms of common causes of damage to the peripheral and central nervous systems. One of the metabolic systemic diseases that can result in sensorineural hearing loss is diabetic mellitus (DM). In this study, we aimed to compare the auditory electrophysiological responses present in animal models of type 1 and type 2 DM using auditory brainstem response (ABR), auditory middle latency response (AMLR), and transient evoked otoacoustic emission (TEOAE) in animal model. We found that ABR threshold shifts and latency delays were similar in both types of DM. On the other hand, we found that type 2 diabetic mice exhibited more severe dysfunction to the central auditory pathway, as measured AMLRs and the cochlear hair cells, as measured TEOAEs. These results together suggest that hyperglycemia associated with type 1 or type 2 DM causes auditory nerve dysfunction, while hyperinsulinemia associated with type 2 DM causes dysfunction to both the central auditory pathways and cochlear hair cells.

Skin depigmenting action of silkworm (Bombyx mori L.) droppings in zebrafish

The excrement of silkworms (Bombyx mori L.), referred to here as silkworm droppings (SDs), is used as a traditional drug in eastern medicine to treat skin diseases such as urticaria and atopy. However, the depigmentation effects of SDs have not previously been evaluated. We focused on the depigmentation effect of a methanol extract of SDs and isolated components of the extract using a zebrafish model system. (+)-Dehydrovomifoliol (M-1), (6R,7E,9R)-9-hydroxy-4,7-megastigmadien-3-one (M-2), (3S,5R,8R)-3,5-dihydroxymegastigma-6,7-dien-9-one (M-3), roseoside (M-4), and citroside A (M-5) were isolated from only SDs extract (SDE), and chemical structures were identified through spectroscopic methods. Toxicity of SDE was evaluated by assessing its effect on the viability of human fibroblast cells and the hatching rate of zebrafish embryos. In addition, the depigmentation ability of SDE and isolated constituents was evaluated using a zebrafish model. Binary threshold, histograms, and the size of the black spots on the dorsal region of zebrafish larvae were analyzed using image analysis tools. Finally, SDE is a non-toxic material and has a dose-dependent depigmentation effect in zebrafish larvae. Moreover, various doses of compounds isolated from SDE, namely, M-1 to M-5, had a depigmentation effect. In particular, M-5 inhibited melanin synthesis in melanocytes stimulated by α-melanocyte stimulating hormone (α-MSH). Together, our results suggest that SDs can be used for depigmentation purposes in health and/or cosmetic applications.

Chlorogenic acid rescues sensorineural auditory function in a diabetic animal model

Recently, many studies have reported that sensorineural hearing impairment related to neurological disorders may be caused by diabetes mellitus. However, to date, only a small number of studies have investigated the treatment of sensorineural hearing impairment. In the present study, the effects of chlorogenic acid on diabetic auditory pathway impairment were evaluated by neuro-electrical physiological measurements and morphological investigations. We have shown that CA efficiently prevents the progression of auditory pathway dysfunction caused by DM using auditory brainstem responses and auditory middle latency responses in mice. Additionally, using transient-evoked otoacoustic emissions measurement and scanning electron microscope observation of hair cells in DM mice, we found that CA may aid in the recovery from outer hair cell and otic hair cell damage. In conclusion, CA has beneficial effects for the management of diabetic sensorineural auditory dysfunction.

Panax ginseng (Korea Red Ginseng) repairs diabetic sensorineural damage through promotion of the nerve growth factor pathway in diabetic zebrafish

Background Diabetic sensorineural damage is a complication of the sensory neural system, resulting from long-term hyperglycemia. Red ginseng (RG) has shown efficacy for treatment of various diseases, including diabetes mellitus; however, there is little research about its benefit for treating sensorineural damage. Therefore, we aim to evaluate RG efficacy in alloxan-induced diabetic neuromast (AIDN) zebrafish. Methods In this study, we developed and validated an AIDN zebrafish model. To assess RG effectiveness, we observed morphological changes in live neuromast zebrafish. Also, zebrafish has been observed to have an ultrastructure of hair-cell cilia under scanning electron microscopy. Thus, we recorded these physiological traits to assess hair cell function. Finally, we confirmed that RG promoted neuromast recovery via nerve growth factor signaling pathway markers. Results First, we established an AIDN zebrafish model. Using this model, we showed via live neuromast imaging that RG fostered recovery of sensorineural damage. Damaged hair cell cilia were recovered in AIDN zebrafish. Furthermore, RG rescued damaged hair cell function through cell membrane ion balance. Conclusion Our data suggest that RG potentially facilitates recovery in AIDN zebrafish, and its mechanism seems to be promotion of the nerve growth factor pathway through increased expression of topomyosin receptor kinase A, transient receptor potential channel vanilloid subfamily type 1, and mitogen-activated protein kinase phosphorylation.

Curculigo orchioides Protects Cisplatin-Induced Cell Damage

Cisplatin is commonly used as a chemotherapeutic agent against many human cancers. However, it generates reactive oxygen species (ROS) and has serious dose-limiting side effects, including ototoxicity. The roots of Curculigo orchioides (C. orchioides) have been used to treat auditory diseases such as tinnitus and hearing loss in Chinese traditional medicine. In the present study, we investigated the protective effects of an ethanol extract obtained from C. orchioides rhizome (COR) on cisplatin-induced cell damage in auditory cells (HEI-OC1). COR (2.5-25 μg/ml) inhibited cisplatin-induced HEI-OC1 cell damage in a dose-dependent manner. To investigate the protective mechanism of COR on cisplatin cytotoxicity in HEI-OC1 cells, we measured the effects of COR on ROS generation and lipid peroxidation in cisplatin-treated cells as well as its scavenging activities against superoxide radicals, hydroxyl radicals, hydrogen peroxide, and DPPH radicals. COR (1-25 μg/ml) had scavenging activities against superoxide radicals, hydroxyl radicals, hydrogen peroxide, and DPPH radicals, as well as reduced lipid peroxidation. In in vivo experiments, COR was shown to reduce cochlear and peripheral auditory function impairments through cisplatin-induced auditory damage in mice. These results indicate that COR protects from cisplatin-induced auditory damage by inhibiting lipid peroxidation and scavenging activities against free radicals.