Morin hydrate promotes inner ear neural stem cell survival and differentiation and protects cochlea against neuronal hearing loss

Abstract

We aimed to investigate the effect of morin hydrate on neural stem cells (NSCs) isolated from mouse inner ear and its potential in protecting neuronal hearing loss. 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) and bromodeoxyuridine incorporation assays were employed to assess the effect of morin hydrate on the viability and proliferation of in vitro NSC culture. The NSCs were then differentiated into neurons, in which neurosphere formation and differentiation were evaluated, followed by neurite outgrowth and neural excitability measurements in the subsequent in vitro neuronal network. Mechanotransduction of cochlea ex vivo culture and auditory brainstem responses threshold and distortion product optoacoustic emissions amplitude in mouse ototoxicity model were also measured following gentamicin treatment to investigate the protective role of morin hydrate against neuronal hearing loss. Morin hydrate improved viability and proliferation, neurosphere formation and neuronal differentiation of inner ear NSCs, and promoted in vitro neuronal network functions. In both ex vivo and in vivo ototoxicity models, morin hydrate prevented gentamicin‐induced neuronal hearing loss. Morin hydrate exhibited potent properties in promoting growth and differentiation of inner ear NSCs into functional neurons and protecting from gentamicin ototoxicity. Our study supports its clinical potential in treating neuronal hearing loss.

Therapeutic potential of the mitochondria-targeted antioxidant MitoQ in mitochondrial-ROS induced sensorineural hearing loss caused by Idh2 deficiency

“…In that respect, organotypic culture of cochlear explants have strong advantages to explore the underlying mechanisms for a particular pathogenesis or development, because the cultured cochlear explants have been proven to maintain intact conformation of the hair cells and neuronal innervation with following normal processes of development during it is cultured [46] , [47] . Importantly, most of hearing loss studies that performed both ex vivo and in vivo experiments have shown strong consistency in the results between these two systems [48] , [49] , [50] , [51] , which suggest that ex vivo studies also could provide significant and reliable massages.…”

Mulberry Leaf-Derived Morin Activates β-Catenin by Binding to Frizzled7 to Promote Intestinal Stem Cell Expansion upon Heat-Stable Enterotoxin b Injury

“…Morin (2′,3,4′,5,7-pentahydroxyflavone) is rich in mulberry leaves, which are widely planted in the South China region . A large amount of evidence suggests that morin has various pharmacological effects, such as anti-cancer, anti-inflammation, and inhibition of apoptosis. − Although morin has been reported to repair chronic experimental colitis, mechanisms that regulate the regenerative response of the intestinal epithelium upon injury remain largely unknown.…”

Morin improves functional recovery after spinal cord injury in rats by enhancing axon regeneration via the Nrf2/HO‐1 pathway

“…Morin, a natural bioflavonoid originally isolated from members of the Moraceae family, has been reported to possess antiinflammatory, antioxidant, anticancer and neuroprotective properties (Caselli, Cirri, Santi, & Paoli, 2016; Sharma, Kumar, Chellappan, & Nagarajan, 2018; Sinha, Sadhukhan, Saha, Pal, & Sil, 2015; Zhao et al, 2017). Morin protects neural stem cells in the mouse inner ear in an in vitro ototoxicity model (He, Jia, Zhang, & Ren, 2017). In vivo, morin alleviates hippocampal neuron damage in REM sleep‐deprived mice (Olonode, Aderibigbe, Adeoluwa, Eduviere, & Ben‐Azu, 2019).…”