Yoon Young Cho, Jeong Hill Park, Jung Hee Lee, Sungkwon Chung
{"title":"Ginsenosides Decrease β-Amyloid Production via Potentiating Capacitative Calcium Entry.","authors":"Yoon Young Cho, Jeong Hill Park, Jung Hee Lee, Sungkwon Chung","doi":"10.4062/biomolther.2023.172","DOIUrl":"https://doi.org/10.4062/biomolther.2023.172","url":null,"abstract":"Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by extracellular amyloid plaques composed of amyloid β-peptide (Aβ). Studies have indicated that Ca<sup>2+</sup> dysregulation is involved in AD pathology. It is reported that decreased capacitative Ca<sup>2+</sup> entry (CCE), a refilling mechanism of intracellular Ca<sup>2+</sup>, resulting in increased Aβ production. In contrast, constitutive activation of CCE could decrease Aβ production. Panax ginseng Meyer is known to enhance memory and cognitive functions in healthy human subjects. We have previously reported that some ginsenosides decrease Aβ levels in cultured primary neurons and AD mouse model brains. However, mechanisms involved in the Aβ-lowering effect of ginsenosides remain unclear. In this study, we investigated the relationship between CCE and Aβ production by examining the effects of various ginsenosides on CCE levels. Aβ-lowering ginsenosides such as Rk1, Rg5, and Rg3 potentiated CCE. In contrast, ginsenosides without Aβ-lowering effects (Re and Rb2) failed to potentiate CCE. The potentiating effect of ginsenosides on CCE was inhibited by the presence of 2-aminoethoxydipherryl borate (2APB), an inhibitor of CCE. 2APB alone increased Aβ42 production. Furthermore, the presence of 2APB prevented the effects of ginsenosides on Aβ42 production. Our results indicate that ginsenosides decrease Aβ production via potentiating CCE levels, confirming a close relationship between CCE levels and Aβ production. Since CCE levels are closely related to Aβ production, modulating CCE could be a novel target for AD therapeutics.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140570215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heui-Jin Park, Kyuri Kim, Eun-Young Lee, Prima F Hillman, Sang-Jip Nam, Kyung-Min Lim
{"title":"Methylanthranilate, a Food Fragrance Attenuates Skin Pigmentation through Downregulation of Melanogenic Enzymes by cAMP Suppression.","authors":"Heui-Jin Park, Kyuri Kim, Eun-Young Lee, Prima F Hillman, Sang-Jip Nam, Kyung-Min Lim","doi":"10.4062/biomolther.2023.103","DOIUrl":"10.4062/biomolther.2023.103","url":null,"abstract":"<p><p>Methyl anthranilate (MA) is a botanical fragrance used in food flavoring with unexplored potential in anti-pigment cosmetics. MA dose-dependently reduced melanin content without affecting cell viability, inhibited dendrite elongation and melanosome transfer in the co-culture system of human melanoma cells (MNT-1) and human keratinocyte cell line (HaCaT), and downregulated melanogenic genes, including tyrosinase, tyrosinase-related protein 1 and 2 (TRP-1, TRP-2). Additionally, MA decreased cyclic adenosine monophosphate (cAMP) production and exhibited a significant anti-pigmentary effect in Melanoderm™. These results suggest that MA is a promising anti-pigmentary agent for replacing or complementing existing anti-pigmentary cosmetics.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"231-239"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inhaled Volatile Molecules-Responsive TRP Channels as Non-Olfactory Receptors.","authors":"Hyungsup Kim, Minwoo Kim, Yongwoo Jang","doi":"10.4062/biomolther.2023.118","DOIUrl":"10.4062/biomolther.2023.118","url":null,"abstract":"<p><p>Generally, odorant molecules are detected by olfactory receptors, which are specialized chemoreceptors expressed in olfactory neurons. Besides odorant molecules, certain volatile molecules can be inhaled through the respiratory tract, often leading to pathophysiological changes in the body. These inhaled molecules mediate cellular signaling through the activation of the Ca<sup>2+</sup>-permeable transient receptor potential (TRP) channels in peripheral tissues. This review provides a comprehensive overview of TRP channels that are involved in the detection and response to volatile molecules, including hazardous substances, anesthetics, plant-derived compounds, and pheromones. The review aims to shed light on the biological mechanisms underlying the sensing of inhaled volatile molecules. Therefore, this review will contribute to a better understanding of the roles of TRP channels in the response to inhaled molecules, providing insights into their implications for human health and disease.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"192-204"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9951654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hydroxychavicol Inhibits In Vitro Osteoclastogenesis via the Suppression of NF-κB Signaling Pathway.","authors":"Sirada Srihirun, Satarat Mathithiphark, Chareerut Phruksaniyom, Pitchanun Kongphanich, Wisutthaporn Inthanop, Thanaporn Sriwantana, Salunya Tancharoen, Nathawut Sibmooh, Pornpun Vivithanaporn","doi":"10.4062/biomolther.2023.067","DOIUrl":"10.4062/biomolther.2023.067","url":null,"abstract":"<p><p>Hydroxychavicol, a primary active phenolic compound of betel leaves, previously inhibited bone loss <i>in vivo</i> by stimulating osteogenesis. However, the effect of hydroxychavicol on bone remodeling induced by osteoclasts is unknown. In this study, the anti-osteoclastogenic effects of hydroxychavicol and its mechanism were investigated in receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclasts. Hydroxychavicol reduced the number of tartrate resistance acid phosphatase (TRAP)-positive multinucleated, F-actin ring formation and bone-resorbing activity of osteoclasts differentiated from RAW264.7 cells in a concentration-dependent manner. Furthermore, hydroxychavicol decreased the expression of osteoclast-specific genes, including cathepsin K, MMP-9, and dendritic cell-specific transmembrane protein (DC-STAMP). For mechanistic studies, hydroxychavicol suppressed RANKL-induced expression of major transcription factors, including the nuclear factor of activated T-cells 1 (NFATc1), c-Fos, and c-Jun. At the early stage of osteoclast differentiation, hydroxychavicol blocked the phosphorylation of NF-κB subunits (p65 and Iκβα). This blockade led to the decrease of nuclear translocation of p65 induced by RANKL. In addition, the anti-osteoclastogenic effect of hydroxychavicol was confirmed by the inhibition of TRAP-positive multinucleated differentiation from human peripheral mononuclear cells (PBMCs). In conclusion, hydroxychavicol inhibits osteoclastogenesis by abrogating RANKL-induced NFATc1 expression by suppressing the NF-κB signaling pathway <i>in vitro</i>.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"205-213"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ji-Yong Jung, Joong Hyun Shim, Su Hae Cho, Il-Hong Bae, Seung Ha Yang, Jinsick Kim, Hye Won Lim, Dong Wook Shin
{"title":"The Anti-Diabetic Pinitol Improves Damaged Fibroblasts.","authors":"Ji-Yong Jung, Joong Hyun Shim, Su Hae Cho, Il-Hong Bae, Seung Ha Yang, Jinsick Kim, Hye Won Lim, Dong Wook Shin","doi":"10.4062/biomolther.2023.220","DOIUrl":"10.4062/biomolther.2023.220","url":null,"abstract":"<p><p>Pinitol (3-O-Methyl-D-chiro-inositol) has been reported to possess insulin-like effects and is known as one of the anti-diabetic agents to improve muscle, liver, and endothelial cells. However, the beneficial effects of pinitol on the skin are not well known. Here, we investigated whether pinitol had effects on human dermal fibroblasts (HDFs), and human dermal equivalents (HDEs) irradiated with ultraviolet A (UVA), which causes various damages including photodamage in the skin. We observed that pinitol enhanced wound healing in UVA-damaged HDFs. We also found that pinitol significantly antagonized the UVA-induced up-regulation of matrix metalloproteinase 1 (MMP1), and the UVA-induced down-regulation of collagen type I and tissue inhibitor of metalloproteinases 1 (TIMP1) in HDEs. Electron microscopy analysis also revealed that pinitol remarkably increased the number of collagen fibrils with regular banding patterns in the dermis of UVA-irradiated human skin equivalents. Pinitol significantly reversed the UVA-induced phosphorylation levels of ERK and JNK but not p38, suggesting that this regulation may be the mechanism underlying the pinitol-mediated effects on UVA-irradiated HDEs. We also observed that pinitol specifically increased Smad3 phosphorylation, which is representative of the TGF-β signaling pathway for collagen synthesis. These data suggest that pinitol exerts several beneficial effects on UVA-induced damaged skin and can be used as a therapeutic agent to improve skin-related diseases.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"224-230"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139085741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hae Ran Lee, Seong-Min Hong, Kyohee Cho, Seon Hyeok Kim, Eunji Ko, Eunyoo Lee, Hyun Jin Kim, Se Yeong Jeon, Seon Gil Do, Sun Yeou Kim
{"title":"Potential Role of Dietary Salmon Nasal Cartilage Proteoglycan on UVB-Induced Photoaged Skin.","authors":"Hae Ran Lee, Seong-Min Hong, Kyohee Cho, Seon Hyeok Kim, Eunji Ko, Eunyoo Lee, Hyun Jin Kim, Se Yeong Jeon, Seon Gil Do, Sun Yeou Kim","doi":"10.4062/biomolther.2024.010","DOIUrl":"10.4062/biomolther.2024.010","url":null,"abstract":"<p><p>New supplements with preventive effects against skin photodamage are receiving increasing attention. This study evaluated the anti-photoaging effects of salmon nasal cartilage proteoglycan (SPG), acting as a functional material for skin health. We administered SPG to <i>in vitro</i> and <i>in vivo</i> models exposed to ultraviolet B (UVB) radiation and assessed its moisturizing and anti-wrinkle effects on dorsal mouse skin and keratinocytes and dermal fibroblasts cell lines. These results showed that SPG restored the levels of filaggrin, involucrin, and AQP3 in the epidermis of UVB-irradiated dorsal skin and keratinocytes, thereby enhancing the keratinization process and water flow. Additionally, SPG treatment increased the levels of hyaluronan and skin ceramide, the major components of intercellular lipids in the epidermis. Furthermore, SPG treatment significantly increased the levels of collagen and procollagen type 1 by down-regulating matrix metalloproteinase 1, which play a crucial role in skin fibroblasts, in both <i>in vitro</i> and <i>in vivo</i> models. In addition, SPG strongly inhibited mitogen-activated protein kinase (MAPKs) signaling, the including extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK), and p38. These findings suggest that dietary SPG may be an attractive functional food for preventing UVB-induced photoaging. And this SPG product may provide its best benefit when treating several signs of skin photoaging.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"249-260"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dimethyl α-Ketoglutarate Promotes the Synthesis of Collagen and Inhibits Metalloproteinases in HaCaT Cells.","authors":"Bo-Yeong Yu, Da-Hae Eom, Hyun Woo Kim, Yong-Joo Jeong, Young-Sam Keum","doi":"10.4062/biomolther.2023.131","DOIUrl":"10.4062/biomolther.2023.131","url":null,"abstract":"<p><p>We observed that treatment with dimethyl α-ketoglutarate (DMK) increased the amount of intracellular α-ketoglutarate significantly more than that of α-ketoglutarate in HaCaT cells. DMK also increased the level of intracellular 4-hydroxyproline and promoted the production of collagen in HaCaT cells. In addition, DMK decreased the production of collagenase and elastase and down-regulated the expression of selected matrix metalloproteinases (MMPs), such as MMP-1, MMP-9, MMP-10, and MMP-12, via transcriptional inhibition. The inhibition of MMPs by DMK was mediated by the suppression of the IL-1 signaling cascade, leading to the attenuation of ERK1/2 phosphorylation and AP-1 transactivation. Our study results illustrate that DMK, an alkylated derivative of α-ketoglutarate, increased the level of 4-hydroxyproline, promoted the production of collagen, and inhibited the expression of selected MMPs by affecting the IL-1 cascade and AP-1 transactivation in HaCaT cells. The results suggest that DMK might be useful as an anti-wrinkle ingredient.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"240-248"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ji-Hye Song, Hyo-Jin Kim, Jangho Lee, Seung-Pyo Hong, Min-Yu Chung, Yu-Geun Lee, Jae Ho Park, Hyo-Kyoung Choi, Jin-Taek Hwang
{"title":"Robinetin Alleviates Metabolic Failure in Liver through Suppression of p300-CD38 Axis.","authors":"Ji-Hye Song, Hyo-Jin Kim, Jangho Lee, Seung-Pyo Hong, Min-Yu Chung, Yu-Geun Lee, Jae Ho Park, Hyo-Kyoung Choi, Jin-Taek Hwang","doi":"10.4062/biomolther.2023.061","DOIUrl":"10.4062/biomolther.2023.061","url":null,"abstract":"<p><p>Metabolic abnormalities in the liver are closely associated with diverse metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and obesity. The aim of this study was to evaluate the ameliorating effect of robinetin (RBN) on the significant pathogenic features of metabolic failure in the liver and to identify the underlying molecular mechanism. RBN significantly decreased triglyceride (TG) accumulation by downregulating lipogenesis-related transcription factors in AML-12 murine hepatocyte cell line. In addition, mice fed with Western diet (WD) containing 0.025% or 0.05% RBN showed reduced liver mass and lipid droplet size, as well as improved plasma insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values. CD38 was identified as a target of RBN using the BioAssay database, and its expression was increased in OPA-treated AML-12 cells and liver tissues of WD-fed mice. Furthermore, RBN elicited these effects through its anti-histone acetyltransferase (HAT) activity. Computational simulation revealed that RBN can dock into the HAT domain pocket of p300, a histone acetyltransferase, which leads to the abrogation of its catalytic activity. Additionally, knock-down of <i>p300</i> using siRNA reduced CD38 expression. The chromatin immunoprecipitation (ChIP) assay showed that p300 occupancy on the promoter region of CD38 was significantly decreased, and H3K9 acetylation levels were diminished in lipid-accumulated AML-12 cells treated with RBN. RBN improves the pathogenic features of metabolic failure by suppressing the p300-CD38 axis through its anti-HAT activity, which suggests that RBN can be used as a new phytoceutical candidate for preventing or improving this condition.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"214-223"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ram Hari Pokhrel, Suman Acharya, Sunil Mishra, Ye Gu, Umar Manzoor, Jeon-Kyung Kim, Youngjun Park, Jae-Hoon Chang
{"title":"AMPK Alchemy: Therapeutic Potentials in Allergy, Aging, and Cancer.","authors":"Ram Hari Pokhrel, Suman Acharya, Sunil Mishra, Ye Gu, Umar Manzoor, Jeon-Kyung Kim, Youngjun Park, Jae-Hoon Chang","doi":"10.4062/biomolther.2023.222","DOIUrl":"10.4062/biomolther.2023.222","url":null,"abstract":"<p><p>All cells are equipped with intricate signaling networks to meet the energy demands and respond to the nutrient availability in the body. AMP-activated protein kinase (AMPK) is among the most potent regulators of cellular energy balance. Under ATP -deprived conditions, AMPK phosphorylates substrates and affects various biological processes, such as lipid/glucose metabolism and protein synthesis. These actions further affect the cell growth, death, and functions, altering the cellular outcomes in energy-restricted environments. AMPK plays vital roles in maintaining good health. AMPK dysfunction is observed in various chronic diseases, making it a promising target for preventing and alleviating such diseases. Herein, we highlight the different AMPK functions, especially in allergy, aging, and cancer, to facilitate the development of new therapeutic approaches in the future.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"171-182"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10902700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}