• Title/Summary/Keyword: downregulation

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Does the Gut Microbiota Regulate a Cognitive Function? (장내미생물과 인지기능은 서로 연관되어 있는가?)

  • Choi, Jeonghyun;Jin, Yunho;Kim, Joo-Heon;Hong, Yonggeun
    • Journal of Life Science
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    • v.29 no.6
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    • pp.747-753
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    • 2019
  • Cognitive decline is characterized by reduced long-/short-term memory and attention span, and increased depression and anxiety. Such decline is associated with various degenerative brain disorders, especially Alzheimer's disease (AD) and Parkinson's disease (PD). The increases in elderly populations suffering from cognitive decline create social problems and impose economic burdens, and also pose safety threats; all of these problems have been extensively researched over the past several decades. Possible causes of cognitive decline include metabolic and hormone imbalance, infection, medication abuse, and neuronal changes associated with aging. However, no treatment for cognitive decline is available. In neurodegenerative diseases, changes in the gut microbiota and gut metabolites can alter molecular expression and neurobehavioral symptoms. Changes in the gut microbiota affect memory loss in AD via the downregulation of NMDA receptor expression and increased glutamate levels. Furthermore, the use of probiotics resulted in neurological improvement in an AD model. PD and gut microbiota dysbiosis are linked directly. This interrelationship affected the development of constipation, a secondary symptom in PD. In a PD model, the administration of probiotics prevented neuron death by increasing butyrate levels. Dysfunction of the blood-brain barrier (BBB) has been identified in AD and PD. Increased BBB permeability is also associated with gut microbiota dysbiosis, which led to the destruction of microtubules via systemic inflammation. Notably, metabolites of the gut microbiota may trigger either the development or attenuation of neurodegenerative disease. Here, we discuss the correlation between cognitive decline and the gut microbiota.

Antiadipogenic Activity of Solvent-partitioned Fractions from Limonium tetragonum in 3T3-L1 Preadipocytes (갯질경이 용매분획물의 3T3-L1전지방세포에서의 지방생성억제 효과)

  • Kwon, Myeong Sook;Kim, Jung-Ae;Oh, Jung Hwan;Karadeniz, Fatih;Lee, Jung Im;Seo, Youngwan;Kong, Chang-Suk
    • Journal of Life Science
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    • v.29 no.1
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    • pp.60-68
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    • 2019
  • Limonium tetragonum, an edible halophyte that grows on salt marshes in Korea, is thought to possess various health benefits (e.g., antioxidant, antitumor, and hepatoprotective). In the present study, different solvent partitioned subfractions, water ($H_2O$), buthanol (n-BuOH), 85% aqueous methanol (85% aq. MeOH), and hexane (n-hexane), from crude extract of L. tetragonum were tested for their ability to prevent adipogenesis in differentiating 3T3-L1 preadipocytes. The treatment of differentiating 3T3-L1 preadipocytes with L. tetragonum subfractions (LTFs) resulted in suppressed adipogenesis and reduced expression of adipogenesis-related transcription factors such as peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$), CCAATT/enhancer-binding protein alpha ($C/EBP{\alpha}$), and sterol regulatory element-binding protein 1c (SREBP-1c) at both mRNA and protein levels. In addition, the LTF treatment notably decreased the levels of phosphorylated p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) of the mitogen-activated protein kinase (MAPK) pathway in association with $PPAR{\gamma}$-linked adipogenesis. Among all the tested LTFs, $H_2O$ and n-hexane were the most effective in lowering lipid accumulation and regulating the adipocyte differentiation via $PPAR{\gamma}$ pathway. Taken together, the results indicated that the $H_2O$ and n-hexane LTFs contain bioactive compounds that may exhibit significant antiadipogenesis activity by downregulation of the $PPAR{\gamma}$ pathway and inactivation of the MAPK signal pathway in 3T3-L1 preadipocytes.

Anti-stress and Sleep-enhancing Effects of Ptecticus tenebrifer Water Extract Through the Regulation of Corticosterone and Melatonin Levels (코르티코스테론 및 멜라토닌 수치 조절을 통한 동애등에 물 추출물의 항스트레스 및 수면 개선 효과)

  • Oh, Dool-Ri;Ko, Haeju;Hong, Seong Hyun;Kim, Yujin;Oh, Kyo-Nyeo;Kim, Yonguk;Bae, Donghyuck
    • Journal of Life Science
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    • v.32 no.8
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    • pp.601-610
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    • 2022
  • P. tenebrifer (PT) belongs to the Diptera order and Stratiomyidae family. Recently, insect industry have been focused as food, animal feed and environmental advantages. γ-aminobutyric acid (GABA) and melatonin have been associated with regulating sleep and depression. GABA is the primary inhibitory neurotransmitter and is synthesized via biotransformation of monosodium glutamate (MSG) to GABA by lactic acid bacteria. In this study, we first used a GABA-enhanced PT extract, wherein GABA was enhanced by feeding MSG to PT. The underlying mechanisms preventing stress and insomnia were investigated in a corticosterone (CORT)-induced endoplasmic reticulum (ER) stress and chronic restraint stress (CRS)-exposed mouse model, as well as in pentobarbital (45 mg/kg)-induced sleep behaviors in mice. In the present study, the GABA peak was detected in high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) analysis and showed in Ptecticus tenebrifer water extract (PTW) but not in non-PTW extract. The results showed that PTW and Ptecticus tenebrifer with 70% ethanol extract (PTE) exerted neuroprotective effects by protecting against CORT-induced downregulation of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP-response element binding protein (CREB) expression. In addition, PTW (300 mg/kg) significantly reduced CORT levels in CRS-exposed mice. Furthermore, PTW (100 and 300 mg/kg) significantly reduced sleep latency and increased total sleep duration in pentobarbital (45 mg/kg)-induced sleeping behaviors, which was related to serum melatonin levels. In conclusion, our results suggest that PTW exerts anti-stress and sleep-enhancing effects by regulating serum CORT and melatonin levels.

Germinated Rhynchosia nulubilis Hydrolysate Ameliorates Dexamethasone-induced Muscle Atrophy by Downregulating MAFbx Expression in C2C12 Cells and C57BL/6 Mice (발아 서목태 가수분해물의 근위축 억제 효과)

  • Won Keong Lee;Eun Ji Kim;Sang Gon Kim;Young Min Goo;Young Sook Kil;Seung Mi Sin;Min Ju Ahn;Min Cheol Kang;Young-Sool Hah
    • Journal of Life Science
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    • v.33 no.3
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    • pp.277-286
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    • 2023
  • Sarcopenia is the age-related loss of muscle mass and function. It is a natural part of aging and can lead to decreased mobility and increased frailty. The ubiquitin-proteasome pathway, which is involved in muscle protein degradation, is closely linked to sarcopenia. Germinated Rhynchosia nulubilis hydrolysate (GRH) has been reported to have anti-inflammatory and antioxidant properties, but there have been no reports on its inhibitory effect on muscle reduction. However, no study has yet explored the relationship between GRH and muscle loss inhibition. In this study, we evaluated the effects of GRH on muscle atrophy inhibitory activity in dexamethasone (Dexa)-induced muscle atrophy C2C12 myotubes and mouse models. Moreover, we identified a molecular pathway underlying the effects of GRH on skeletal muscle. May Grunwald-Giemsa staining showed that the length and area of myotubes increased in the groups treated with GRH. In addition, the GRH-treated group significantly reduced the expression of muscle ring finger protein 1 and muscular atrophy F-box (MAFbx) in the Dexa-induced muscular atrophy C2C12 model. GRH also improved muscle strength in C57BL/6 mice with Dexa-induced muscle atrophy, resulting in prolonged running exhaustive time and increased grip strength. We found that muscle strengthening by GRH was correlated with a decreased expression of the MAFbx gene in mouse muscle tissue. In conclusion, GRH can attenuate Dexa-induced muscle atrophy by inhibiting the ubiquitin-proteasome pathway via downregulation of the MAFbx gene expression.

Tyrosinase Inhibition-mediated Anti-melanogenic Effects by Catechin Derivatives Extracted from Ulmus parvifolia (참느릅나무에서 추출된 catechin 유도체 화합물의 멜라닌 생성 억제 효과)

  • Taehyeok Hwang;Hyo Jung Lee;Dong-Min Kang;Kyoung Mi Moon;Jae Cheal Yoo;Mi-Jeong Ahn;Dong Kyu Moon;Dong Kyun Woo
    • Journal of Life Science
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    • v.33 no.2
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    • pp.169-175
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    • 2023
  • As a protective defensive mechanism against ultraviolet (UV) light exposure in skin tissue, melanocytes produce the pigment melanin. Tyrosinase plays a key role in melanin production in melanocytes. However, the overproduction of melanin can lead to lesions, such as freckles and dark spots. Thus, it is clinically important to find a modulating molecule to control melanogenesis by regulating tyrosinase expression and/or activity. It is known that catechin, a plant flavonoid, can reduce melano- genesis through the downregulation of tyrosinase expression. Here, we tested whether catechin derivatives isolated from the stem bark of Ulmus parvifolia have an effect on melanin production by regulating tyrosinase in mouse melanoma cells and in vitro mushroom tyrosinase. The catechin derivatives used in this study included C5A, C7A, C7G, and C7X. Treatments using these catechin derivatives reduced melanin production in mouse melanoma B16F10 cells in which melanogenesis was stimulated by α-MSH. Notably, the anti-melanogenic effects of catechin derivatives were similar to those of kojic acid, a well-known anti-melanogenic molecule. Both C5A and C7A directly inhibited the activity of tyrosinase isolated from mushrooms in vitro. Furthermore, our in silico computational simulation showed that these two compounds were expected to bind to the active site of tyrosinase, which is similar to kojic acid. In addition, all four catechin derivatives reduced tyrosinase protein expression. In summary, our results showed that catechin derivatives can reduce melanogenesis by regulating tyrosinase activity or expression. Thus, this study suggests that catechin derivatives isolated from U. parvifolia can be novel modulators of melanin production.