PUBLICATION
Trigonelline promotes auditory function through nerve growth factor signaling on diabetic animal models
- Authors
- Castañeda, R., Rodriguez, I., Nam, Y.H., Hong, B.N., Kang, T.H.
- ID
- ZDB-PUB-171122-5
- Date
- 2017
- Source
- Phytomedicine : international journal of phytotherapy and phytopharmacology 36: 128-136 (Journal)
- Registered Authors
- Keywords
- Auditory brainstem response (ABR), Hair cells, Molecular docking, Transient evoked otoacoustic emission (TEOAE), Zebrafish, db/db mice
- MeSH Terms
-
- Alkaloids/chemistry
- Alkaloids/pharmacology*
- Animals
- Auditory Threshold/drug effects*
- Carbazoles/pharmacology
- Catalytic Domain
- Computer Simulation
- Diabetes Mellitus, Experimental/complications*
- Diabetes Mellitus, Experimental/physiopathology
- Evoked Potentials, Auditory, Brain Stem/drug effects
- Female
- Ganglia, Spinal/drug effects
- Ganglia, Spinal/metabolism
- Hair Cells, Auditory/drug effects*
- Indole Alkaloids/pharmacology
- Male
- Mice
- Mice, Inbred C57BL
- Molecular Docking Simulation
- Nerve Growth Factor/chemistry
- Nerve Growth Factor/metabolism*
- Otoacoustic Emissions, Spontaneous/drug effects
- Rats, Sprague-Dawley
- Zebrafish
- PubMed
- 29157806 Full text @ Phytomedicine
Citation
Castañeda, R., Rodriguez, I., Nam, Y.H., Hong, B.N., Kang, T.H. (2017) Trigonelline promotes auditory function through nerve growth factor signaling on diabetic animal models. Phytomedicine : international journal of phytotherapy and phytopharmacology. 36:128-136.
Abstract
Background Protection of cochlear function and reconstruction of neuronal networks in damaged auditory sensory structures is crucial for therapeutic treatment of diabetic hearing loss. Nerve growth factor (NGF) has been used as a novel therapeutic target to protect against the neurodegenerative effects of Diabetes Mellitus (DM).
Purpose We aimed to evaluate the potential effect of trigonelline (TRG) on reducing auditory damage produced by DM using NGF as a potential marker.
Method Docking simulations were carried out using Autodock Vina software and visualized using Discovery Studio. Morphological analysis of hair cells and neuromasts was performed on alloxan-induced diabetic zebrafish by fluorescence and scanning electron microscopy. Blockage of NGF receptor phosphorylation with K-252a was used to evaluate TRG and NGF action. Further assessment of NGF by ELISA on a primary culture of spiral ganglion cells was performed as a marker of neuronal function on the hearing system. Finally, auditory function was assessed in LepR(db/db) mice using auditory brainstem response (ABR) and transient evoked otoacoustic emission (TEOAE) during 8 weeks.
Results Docking simulations showed that TRG binds to the active site of NGF through molecular interactions with Lysine88 (Lys88) and Tyrosine52 (Tyr52). TRG treatment significantly reduced hair cell loss and neuromast damage in diabetic zebrafish (P < .05). Further evaluation revealed a significant increase in the number of neuromasts after NGF administration (P < .001). TRG and NGF action was suppressed during blockage of NGF receptor phosphorylation. Moreover, spiral ganglion cells revealed significant elevation on NGF values after TRG treatment (P < .05). In vivo evaluation of LepR(db/db) mice revealed a significant reduction in the auditory damage produced under diabetic progression, characterized by reduced ABR hearing threshold shifts and increased signal-to-noise ratio in TEOAE (P < .05).
Conclusions This study suggests that the enhanced hearing function produced by TRG may be mediated by NGF, providing a potential therapeutic strategy for diabetic hearing loss.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping