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Youn Hee Nam,Seo Yule Jeong,Yun Hee Kim,Isabel Rodriguez,Wanlapa Nuankaew,Ujjal K. Bhawal,Bin Na Hong,Tong Ho Kang 고려인삼학회 2021 Journal of Ginseng Research Vol.45 No.1
Background: The circadian rhythm is the internal clock that controls sleep-wake cycles, metabolism, cognition, and several processes in the body, and its disruption has been associated with aging. The differentiated embryo chondrocyte (Dec) gene is related to circadian rhythm. To our knowledge, there are no reports of the relationship between dec gene expression and KRG effect. Therefore, we treated Dec gene knockout (KO) aging mice with KRG to study anti-aging related effects and possible mechanisms. Methods: We evaluated KRG and expression of Dec genes in an ototoxicity model. Dec genes expression in livers of aging mice was further analyzed. Then, we assessed the effects of DEC KO on hearing function in mice by ABR. Finally, we performed DNA microarray to identify KRG-related gene expression changes in mouse liver and assessed the results using KEGG analysis. Results: KRG decreased the expression of Dec genes in ototoxicity model, which may contribute to its anti-aging efficacy. Moreover, KRG suppressed Dec genes expression in liver of wild type indicating inhibition of senescence. ABR test indicated that KRG improved auditory function in aging mouse, demonstrating KRG efficacy on aging related diseases. Conclusion: Finally, in KEGG analysis of 238 genes that were activated and 158 that were inhibited by KRG in DEC KO mice, activated genes were involved in proliferation signaling, mineral absorption, and PPAR signaling whereas the inhibited genes were involved in arachidonic acid metabolism and peroxisomes. Our data indicate that inhibition of senescence-related Dec genes may explain the anti-aging efficacy of KRG.
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Electrophysiological changes in auditory evoked potentials in rats with salicylate-induced tinnitus
Castañ,eda, Rodrigo,Natarajan, Sathishkumar,Jeong, Seo Yule,Hong, Bin Na,Kang, Tong Ho Elsevier/North Holland 2019 Brain research Vol.1715 No.-
<P><B>Abstract</B></P> <P>Early-response auditory evoked potentials (AEPs) in humans are significantly altered in tinnitus. These changes are closely related to that seen in animals, leading to new approaches to study tinnitus based on objective parameters. The purpose of this study was to characterize the AEPs in animals with tinnitus, by assessing early to late latency responses. For behavioral evaluation, rats were trained using positive reinforcement to press a lever in the presence of an auditory stimulus and to not press during silence. The auditory brainstem response (ABR), middle latency response (MLR) and auditory late latency response (LLR) were correlated to the false-positive responses (pressing the lever during silence), after oral administrations of Sodium Salicylate (SS, 350 mg/kg). In the present study, SS significantly increased the hearing thresholds and reduced ABR peak I amplitudes across the frequency range (4–32 kHz). In contrast, increased amplitudes were observed for several peaks in ABR, MLR, and LLR. Moreover, reduced ABR latencies in response to 8, 16 and 24 kHz tone bursts were observed after SS administration. Similarly, the central evaluation also revealed significantly reduced latencies in MLR and LLR during SS administration. In contrast, increased latencies were observed for ABR latencies in response to 32 kHz tone bursts, and at the P1-N1 component of LLR. Correlational analysis revealed that latencies and amplitudes of peaks II and IV (8 and 16 kHz) of ABR, and N2 latency and P2-N2 amplitude of LLR were associated with behavioral tinnitus. We suggest that AEPs can be used in the rat to evaluate the reduced sensory input and the increased central gain in SS-induced tinnitus, as well as reduced latencies (8–16 kHz) to distinguish between hearing loss and tinnitus.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Objective parameters of the AEPs were identified in rats treated with SS. </LI> <LI> Reduced sensory input was shown by hearing thresholds and ABR peak I amplitudes. </LI> <LI> Reduced latencies were found in the ABR (8-24kHz), MLR and LLR in SS-induced tinnitus. </LI> <LI> Central gain was reflected by increased amplitudes in ABR, MLR, and LLR. </LI> <LI> Behavioral tinnitus was correlated to peak IV of ABR, and P2 and N2 of LLR. </LI> </UL> </P>
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Castañ,eda, Rodrigo,Natarajan, Sathishkumar,Jeong, Seo Yule,Hong, Bin Na,Kang, Tong Ho Elsevier 2019 Journal of Ethnopharmacology Vol.231 No.-
<P><B>Abstract</B></P> <P><B>Ethnopharmacological relevance</B></P> <P>In Traditional Oriental Medicine (TOM), the development of hearing pathologies is related to an inadequate nourishment of the ears by the kidney and other organs involved in regulation of bodily fluids and nutrients. Several herbal species have historically been prescribed for promoting the production of bodily fluids or as antiaging agents to treat deficiencies in hearing.</P> <P><B>Aim of review</B></P> <P>The prevalence of hearing loss has been increasing in the last decade and is projected to grow considerably in the coming years. Recently, several herbal-derived products prescribed in TOM have demonstrated a therapeutic potential for acquired sensorineural hearing loss and tinnitus. Therefore, the aims of this review are to provide a comprehensive overview of the current known efficacy of the herbs used in TOM for preventing different forms of acquired sensorineural hearing loss and tinnitus, and associate the traditional principle with the demonstrated pharmacological mechanisms to establish a solid foundation for directing future research.</P> <P><B>Methods</B></P> <P>The present review collected the literature related to herbs used in TOM or related compounds on hearing from Chinese, Korean, and Japanese herbal classics; library catalogs; and scientific databases (PubMed, Scopus, Google Scholar; and Science Direct).</P> <P><B>Results</B></P> <P>This review shows that approximately 25 herbal species and 40 active compounds prescribed in TOM for hearing loss and tinnitus have shown <I>in vitro</I> or <I>in vivo</I> beneficial effects for acquired sensorineural hearing loss produced by noise, aging, ototoxic drugs or diabetes. The inner ear is highly vulnerable to ischemia and oxidative damage, where several TOM agents have revealed a direct effect on the auditory system by normalizing the blood supply to the cochlea and increasing the antioxidant defense in sensory hair cells. These strategies have shown a positive impact on maintaining the inner ear potential, sustaining the production of endolymph, reducing the accumulation of toxic and inflammatory substances, preventing sensory cell death and preserving sensory transmission. There are still several herbal species with demonstrated therapeutic efficacy whose mechanisms have not been deeply studied and others that have been traditionally used in hearing loss but have not been tested experimentally. In clinical studies, <I>Ginkgo biloba</I>, <I>Panax ginseng</I>, and <I>Astragalus propinquus</I> have demonstrated to improve hearing thresholds in patients with sensorineural hearing loss and alleviated the symptoms of tinnitus. However, some of these clinical studies have been limited by small sample sizes, lack of an adequate control group or contradictory results.</P> <P><B>Conclusions</B></P> <P>Current therapeutic strategies have proven that the goal of the traditional oriental medicine principle of increasing bodily fluids is a relevant approach for reducing the development of hearing loss by improving microcirculation in the blood-labyrinth barrier and increasing cochlear blood flow. The potential benefits of TOM agents expand to a multi-target approach on different auditory structures of the inner ear related to increased cochlear blood flow, antioxidant, anti-inflammatory, anti-apoptotic and neuroprotective activities. However, more research is required, given the evidence is very limited in terms of the mechanism of action at the preclinical <I>in vivo</I> level and the scarce number of clinical studies published.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
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Kyun Mi-lang,박탐이나,Jung Hyewon,Kim Inhye,Kwon Ji-In,Jeong Seo Yule,Choi Myeongjin,Park Daeui,Lee Yu Bin,Moon Kyoung-Sik 한국조직공학과 재생의학회 2023 조직공학과 재생의학 Vol.20 No.7
BACKGROUND: The emergence of various infectious diseases and the toxic effects of hyperinflammation by biotherapeutics have highlighted the need for in vitro preclinical models mimicking the human immune system. In vitro models studying the relationship between hyperinflammation and acute renal injury mainly rely on 2D culture systems, which have shown limitations in recapitulating kidney function. Herein, we developed an in vitro kidney toxicity model by co-culturing 3D engineered kidney proximal tubules cells (RPTEC/TERT1) with human peripheral blood mononuclear cells (PBMC). METHODS: RPTEC/TERT1 were sandwich cultured to form 3D renal tubules for 16 days. The tubules were then cocultured with PBMC using transwell (0.4 lm pores) for 24 h. Hyperinflammation of PBMC was induced during co-culture using polyinosinic-polycytidylic acid (polyI:C) and lipopolysaccharide (LPS) to investigate the effects of the induced hyperinflammation on the renal tubules. RESULTS: Encapsulated RPTEC/TERT1 cells in Matrigel exhibited elevated renal function markers compared to 2D culture. The coexistence of PBMC and polyI:C induced a strong inflammatory response in the kidney cells. This hyperinflammation significantly reduced primary cilia formation and upregulated kidney injury markers along the 3D tubules. Similarly, treating co-cultured PBMC with LPS to induce hyperinflammation resulted in comparable inflammatory responses and potential kidney injury. CONCLUSION: The model demonstrated similar changes in kidney injury markers following polyI:C and LPS treatment, indicating its suitability for detecting immune-associated kidney damage resulting from infections and biopharmaceutical applications.
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Nam, Youn Hee,Le, Hoa Thi,Rodriguez, Isabel,Kim, Eun Young,Kim, Keonwoo,Jeong, Seo Yule,Woo, Sang Ho,Lee, Yeong Ro,Castaneda, Rodrigo,Hong, Jineui,Ji, Min Gun,Kim, Ung-Jin,Hong, Bin Na,Kim, Tae Woo,Ka The Korean Society of Ginseng 2017 Journal of Ginseng Research Vol.41 No.1
Background: 20(S)-Protopanaxadiol 20-O-D-glucopyranoside, also called compound K (CK), exerts antidiabetic effects that are mediated by insulin secretion through adenosine triphosphate (ATP)-sensitive potassium ($K_{ATP}$) channels in pancreatic ${\beta}$-cells. However, the antidiabetic effects of CK may be limited because of its low bioavailability. Methods: In this study, we aimed to enhance the antidiabetic activity and lower the toxicity of CK by including it with ${\beta}$-cyclodextrin (CD) (CD-CK), and to determine whether the CD-CK compound enhanced pancreatic islet recovery, compared to CK alone, in an alloxan-induced diabetic zebrafish model. Furthermore, we confirmed the toxicity of CD-CK relative to CK alone by morphological changes, mitochondrial damage, and TdT-UTP nick end labeling (TUNEL) assays, and determined the ratio between the toxic and therapeutic dose for both compounds to verify the relative safety of CK and CD-CK. Results: The CD-CK conjugate ($EC_{50}=2.158{\mu}M$) enhanced the recovery of pancreatic islets, compared to CK alone ($EC_{50}=7.221{\mu}M$), as assessed in alloxan-induced diabetic zebrafish larvae. In addition, CD-CK ($LC_{50} =20.68{\mu}M$) was less toxic than CK alone ($LC_{50}=14.24{\mu}M$). The therapeutic index of CK and CD-CK was 1.98 and 9.58, respectively. Conclusion: The CD-CK inclusion complex enhanced the recovery of damaged pancreatic islets in diabetic zebrafish. The CD-CK inclusion complex has potential as an effective antidiabetic efficacy with lower toxicity.
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Nam, Youn Hee,Moon, Hyo Won,Lee, Yeong Ro,Kim, Eun Young,Rodriguez, Isabel,Jeong, Seo Yule,Castaneda, Rodrigo,Park, Ji-Ho,Choung, Se-Young,Hong, Bin Na,Kang, Tong Ho The Korean Society of Ginseng 2019 Journal of Ginseng Research Vol.43 No.2
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.
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