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The inhibitory Effects of Coenzyme Q10 on Melanogenesis of cultured Human Melanocytes and in vivo Guinea Pig Model (Coenzyme Q10의 멜라닌 생성억제효과)

  • 황재성;박원만;안수미;강병영;이병곤;심영철
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.26 no.1
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    • pp.149-162
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    • 2000
  • Coenzyme Q10 is found in all tissues including skin and it is the well-known coenzyme for mitochondrial enzymes. The electron and proton transfer functions of the quinone ring are of fundamental importance for the oxidative phosphorylation pathway to generate energy in the cells. Coenzyme Q10 has been studied as a potent antioxidant molecule in the skin. It is involved in the skin's response to UVR irradiation. The concentration of this antioxidant in UVR exposed skin is higher than in non-exposed skin. However, recent studies have also shown that coenzyme Q10 is one of the first antioxidants to be depleted when skin is UVR-irradiated. This indicates that coenzyme Q10 is primarily involved in defense mechanisms of the skin. Therefore, we questioned whether coenzyme Q10 shows reulatory effect of melanogenesis. Here we report that coenzyme Q10 inhibits melanin neosynthesis of normal human melanocytes grown in culture, and lightens UVB-induced hyperpigmentation of the guinea pig skin in vivo. We treated human melanocytes with 0.05mM to 0.5mM of coenzyme Q10 for a total of two days. This inhibited melanin neosynthesis of cultured human melanocytes dose-dependently. The inhibitory effect of coenzyme Q10 was as effective as kojic acid or vitamin C on cultured human melanocytes. CoQ10 didn't have direct inhibitory effect on tyrosinase activity in in vitro tyrosine hydroxylase activity To further clarify the effect of coenzyme Q10 on the melanogenesis, we established UVB-induced hyperpigmentation on the shaved backs of brownish guinea pigs. The UVB intensity was 500mJ/$\textrm{cm}^2$ and the total energy dose was 1,500 mJ/$\textrm{cm}^2$. The animals were exposed to UVB radiation one times a week for three consecutive weeks. Coenzyme Q10, kojic acid, Arbutin, vitamin C(1% in vehicle) or vehicle alone as a control were then topically applied daily to the hyperpigmented areas twelve times per week far four successive weeks. The lightening effect was evaluated by visual scoring, chromameter and immunohistochemistry. Coenzyme Q10 had lightening effect on the UVB-induced hyperpigmentation without any other side effects, whereas another compounds showed weak lightening efficacies. Therefore, these results suggest that coenzyme Q10 may be useful for solving physiological hyperpigmenting problems for cosmetic purposes.

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Effects and Molecular Mechanisms of Eupatorium chinensis var. simplicifolium Extract on Abnormal Proliferation of Vascular Smooth Muscle Cells (등골나물추출물의 혈관 평활근 세포의 비정상 증식에 대한 억제 효과 및 분자기작)

  • Kim, Min-Jeong;Kim, Jihee;Lee, Jin-Ho;Kim, Minah;Woo, Keunjung;Kim, Han Sung;Kim, Tack-Joong
    • Journal of Life Science
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    • v.31 no.9
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    • pp.787-795
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    • 2021
  • Eupatorium chinensis var. simplicifolium (EUC) has anti-inflammatory and antioxidant effects. Young sprouts of EUC have been used as food for a long time, and the whole EUC plant has been used as an herbal remedy in oriental medicine. Arteriosclerosis, or chronic inflammation in arterial vessels, is a cardiovascular disease and is involved in various disorders. Cardiovascular diseases such as restenosis and neuropathic hyperplasia are mainly caused by abnormal growth and movement due to multiple growth factors in vascular smooth muscle cells (VSMCs). Platelet-derived growth factor (PDGF) is a mitogen released from damaged vessel walls and is involved in the proliferation and migration of VSMCs. To determine the effects of EUC on the abnormal proliferation and migration of VSMCs, the present study investigated intracellular signaling pathways in PDGF-BB-induced VSMCs treated with and without EUC. Pretreating PDGF-BB-induced VSMCs with EUC tended to effectively decrease cell proliferation and migration. Subsequently, the intracellular growth-related signaling pathways of AKT, phospholipase C gamma (PLC-γ), and mitogen-activated protein kinase (MAPK) were investigated using western blotting to confirm inhibited phosphorylation. Furthermore, flow cytometry data showed that EUC blocked the cell cycle of VSMCs. These results suggest that EUC can inhibit the proliferation and migration of VSMCs by controlling the cell cycle and growth factor receptors. Furthermore, this indicates that EUC can be used as a preventative against cardiovascular disease resulting from abnormal proliferation and migration of VSMCs.

Attenuation of Lipopolysaccharide-induced Inflammatory and Oxidative Response by 5-Aminolevulinic Acid Phosphate in RAW 264.7 Macrophages (RAW 264.7 대식세포에서 lipopolysaccharide 자극에 의한 염증성 및 산화적 스트레스에 미치는 5-aminolevulinic acid phosphate의 영향)

  • Ji, Seon Yeong;Kim, Min Yeong;Hwangbo, Hyun;Lee, Hyesook;Hong, Su Hyun;Cha, Hee-Jae;Kim, Heui-Soo;Kim, Suhkmann;Choi, Yung Hyun
    • Journal of Life Science
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    • v.31 no.9
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    • pp.818-826
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    • 2021
  • 5-Aminolevulinic acid phosphate (5-ALA-p) is a substance obtained by eluting 5-ALA (a natural delta amino acid) with aqueous ammonia, adding phosphoric acid to the eluate, and then adding acetone to confer properties suitable for use in photodynamic therapy applications. However, its pharmacological efficacy, including potential mechanisms of antioxidant and anti-inflammatory reactions, remains unclear. This study aimed to investigate the effects of 5-ALA-p on oxidative and inflammatory stresses in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Our data showed that 5-ALA-p significantly inhibited excessive phagocytic activity via LPS and attenuated oxidative stress in LPS-treated RAW 264.7 cells. Furthermore, 5-ALA-p improved mitochondrial biogenesis reduced by LPS, suggesting that 5-ALA-p restores mitochondrial damage caused by LPS. Additionally, 5-ALA-p significantly suppressed the release of nitric oxide (NO) and pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6, which are associated with the inhibition of inducible NO synthase and respective cytokine expression. Furthermore, 5-ALA-p reduced the nuclear translocation of nuclear factor-kappa B (NF-κB) and inhibited phosphorylation of mitogen-activated protein kinases (MAPKs), indicating that the anti-inflammatory effect of 5-ALA-p is mediated through the suppression of NF-κB and MAPK signaling pathways. Based on these results, 5-ALA-p may serve as a potential candidate to reduce inflammation and oxidative stress.

A Formulated Korean Red Ginseng Extract Inhibited Nitric Oxide Production through Akt- and Mitogen Activated Protein Kinase-dependent Heme Oxygenase-1 Upregulation in Lipoteichoic Acid-stimulated Microglial Cells (홍삼추출액은 lipoteichoic acid로 자극된 소교세포에서 Akt 및 MAPK 의존적으로 heme oxygenase-1 발현을 유도함으로써 NO 생성을 억제함)

  • Shin, Ji Eun;Lee, Kyungmin;Kim, Ji-Hee;Madhi, Iskander;Kim, YoungHee
    • Journal of Life Science
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    • v.29 no.4
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    • pp.402-409
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    • 2019
  • Korean red ginseng made from steaming and drying fresh ginseng has long been used as a traditional herbal medicine due to its effects on the immune, endocrine, and central nerve systems and its anti-inflammatory activity. In this study, we investigated the molecular mechanism responsible for the anti-inflammatory effects of a formulated Korean red ginseng extract (RGE) in response to lipoteichoic acid (LTA), a cell wall component of gram-positive bacteria. RGE inhibited LTA-induced nitric oxide (NO) secretion and inducible nitric oxide synthase (iNOS) expression in BV-2 microglial cells, without affecting cell viability. RGE also inhibited nuclear translocation of nuclear factor kappa B ($NF-{\kappa}B$) p65 and degradation of $I{\kappa}B-{\alpha}$. In addition, RGE increased the expression of heme oxygenase-1 (HO-1) in a dose-dependent manner, and the inhibitory effect of RGE on iNOS expression was abrogated by small interfering RNA-mediated knockdown of HO-1. Moreover, RGE induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. Furthermore, the phosphoinositide-3-kinase (PI-3K) inhibitor and mitogen-activated protein kinase (MAPK) inhibitors suppressed RGE-mediated expression of HO-1, and RGE enhanced the phosphorylation of Akt, extracellular signal-regulated kinases (ERKs), p38, and c-JUN N-terminal kinases (JNKs). These results suggested that RGE suppressed the production of NO, a proinflammatory mediator, by inducing HO-1 expression via PI-3K/Akt- and MAPK-dependent signaling in LTA-stimulated microglia. The findings indicate that RGE could be used for the treatment of neuroinflammation induced by grampositive bacteria and that it may have therapeutic potential for various neuroinflammation-associated disorders.

Anti-inflammatory Activities of Ethanol Extracts of Dried Lettuce (Lactuca sativa L.) (건조 상추 에탄올 추출물의 항염증 활성)

  • Lee, Eun-Joo;Seo, Yu-Mi;Kim, Yong-Hyun;Chung, Chungwook;Sung, Hwa-Jung;Sohn, Ho-Yong;Park, Jong-Yi;Kim, Jong-Sik
    • Journal of Life Science
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    • v.29 no.3
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    • pp.325-331
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    • 2019
  • Lettuce (Lactuca sativa L.) is one of the most popular green leafy vegetables, and it contains various beneficial components including polyphenolic compounds and has been known to possess various biological functions such as anti-microbial, anti-oxidative, and anti-inflammatory activities. In the present study, we prepared ethanol extract of dried lettuce (DLE) and investigated its anti-inflammatory activity. To evaluate the anti-inflammatory activity of DLE, nitric oxide (NO) production was measured in LPS-activated mouse macrophage RAW 264.7 cells. DLE significantly suppressed NO production in these cells without affecting cell viabilities while resveratrol was used as a positive control. DLE dramatically decreased the expression of pro-inflammatory genes such as iNOS and COX-2 at the mRNA and protein levels and reduced the expression of several cytokines including $IL-1{\alpha}$, $IL-1{\beta}$, IL-1F6, $TNF-{\alpha}$, CSF2 and CXCL10. In addition, DLE suppressed phosphorylation of MAPKs and the nuclear translocation of $NF-{\kappa}B$ p65 indicating DLE shows its anti-inflammatory activity via regulating MAPKs pathway and $NF-{\kappa}B$ pathways. And also, DLE reduced the production of reactive oxygen species in a dose-dependent manner. DLE increased HO-1 protein expression, and also increased the nuclear translocation of Nrf2. Overall, our results suggest that lettuce down-regulate various pro-inflammatory genes and have its anti-inflammatory activity via regulating MAPKs, $NF-{\kappa}B$, and Nrf2/HO-1 pathways.

Anti-oxidative and Anti-cancer Activities of Ethanol Extract of Litsea populifolia (인체 폐암 세포주 A549에서 Litsea populifolia 추출물의 항산화 및 항암활성 분석)

  • Jin, Soojung;Oh, You Na;Jeong, Hyun Young;Yun, Hee Jung;Park, Jung-ha;Kwon, Hyun Ju;Kim, Byung Woo
    • Journal of Life Science
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    • v.29 no.6
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    • pp.679-687
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    • 2019
  • Litsea populifolia, a plant species of the Lauraceae family, is widely distributed in the tropical and subtropical areas of Asia. The phylogenetic relationships and botanical characteristics of L. populifolia have been reported; however, its anti-oxidative and anti-cancer activities remain unclear. In this study, we evaluated the anti-oxidative and anti-cancer effects of ethanol extracts of L. populifolia (EELP) together with the molecular mechanism of its anti-cancer activity in human lung adenocarcinoma A549 cells. EELP showed significant anti-oxidative effects with a 50% inhibitory concentration at $11.71{\mu}g/ml$, which was measured by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. EELP exhibited cytotoxic activity and induced cell cycle arrest at the G1 phase in A549 cells in a dose-dependent manner, whereas EELP did not have the cytotoxic effect on the normal human lung cell line IMR90. Treatment with EELP also resulted in a decreased expression of G1/S transition-related molecules-including cyclin-dependent kinase (CDK) 2, CDK6, cyclin D1, and cyclin E-both for the transcription and translation levels. EELP-induced G1 arrest was associated with the phosphorylation of checkpoint kinase 2 (CHK2), p53, cell division cycle 25 homolog A (CDC25A), and the reduction of CDC25A expression in A549 cells. Collectively, these results suggest that EELP may exert an anti-cancer effect by cell cycle arrest at the G1 phase through both p53-dependent and p53-independent (ATM/CHK2/CDC25A/CDK2) pathways in A549 cells.

Immunomodulating activity of Sargassum horneri extracts in RAW264.7 macrophages (RAW264.7 대식세포에서 괭생이 모자반 추출물의 면역활성 증진 효과)

  • Kim, Dong-Sub;Sung, Nak-Yun;Park, Sang-Yun;Kim, Geon;Eom, Ji;Yoo, Jin-Gon;Seo, In-Ra;Han, In-Jun;Cho, Young-Baik;Kim, Kyung-Ah
    • Journal of Nutrition and Health
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    • v.51 no.6
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    • pp.507-514
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    • 2018
  • Purpose: Sargassum horneri (S. horneri) is a species of brown macroalgae that is common along the coast of Japan and Korea. The present study investigated the immuno-modulatory effects of different types of S. horneri extracts in RAW264.7 macrophages. Methods: S. horneri was extracted by three different methods, hot water extraction, 50% ethanol extraction, and supercritical fluid extraction. Cell viability was then measured by MTT assay, while the production levels of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6), and nitric oxide (NO) were measured by enzyme-linked immunosorbent assay and Griess assay, respectively. The expression and activation levels of inducible NO synthase (iNOS), mitogen-activated protein kinase (MAPK) and nuclear factor ${\kappa}B$ ($NF-{\kappa}B$) were examined by western blot analysis. Results: The three different S. horneri extracts were nontoxic against RAW 264.7 cells up to $50{\mu}g/mL$, among which treatment with hot water extract (HWE) of S. horneri significantly enhanced the production of TNF-${\alpha}$, IL-6, and NO in a dose-dependent manner. Hot water extract of S. horneri also increased the expression level of iNOS, suggesting that up-regulation of iNOS expression by HWE of S. horneri was responsible for the induction of NO production. In addition, treatment of RAW 264.7 macrophages with HWE of S. horneri increased the phosphorylation levels of ERK, p38 and JNK. Furthermore, the activation and subsequent nuclear translocation of $NF-{\kappa}B$ was enhanced upon treatment with HWE of S. horneri, indicating that HWE of S. horneri activates macrophages to secrete TNF-${\alpha}$, IL-6 and NO and induces iNOS expression via activation of the $NF-{\kappa}B$ and MAPKs signaling pathways. Conclusion: Taken together, these findings suggest that HWE of S. horneri possesses potential as a functional food with immunomodulatory activity.

The Functional Effects on Anti-oxidant and Anti-inflammation of Veronica persica Poir. Extracts (큰개불알풀 추출물의 항산화 및 항염증 기능성 평가)

  • Park, Jin-Cheon;Nam, Hyeon-Hwa;Nan, Li;Choo, Byung-Kil
    • Korean Journal of Organic Agriculture
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    • v.26 no.4
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    • pp.661-676
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    • 2018
  • Veronica persica (V. persica) is a perennial plant that is broadly distributed in Europe, Asia and so on. V. persica is used for pain about the lower abdomen and low back. The aim of this study was to investigate the anti-oxidant and anti-inflammatory effects of V. persica ethanol extract in LPS-induced RAW 264.7 cells. To evaluate the anti-oxidant activity, the DPPH and ABTS radical scavenging, total polyphenol and flavonoid contents, and reducing power activity were carried out. The DPPH and ABTS radical scavenging activity were evaluated as 72.0% and 73.0% at the concentrations of 200 and $500{\mu}g/mL$, respectively. Total polyphenol and flavonoid contents of V. persica extracts were measured as 65.22 mg/g and 43.82 mg/g at the concentration of 1 mg/mL. The reducing power activity measurement showed 53.0% activity at 1 mg/mL. The anti-inflammatory effects of the V. persica extract were evaluated in LPS induced RAW 264.7 cells. In the evaluation of cell viability by proliferation & cytotoxicity assay kit, the cytotoxicity of the extract was not confirmed at $0{\sim}800{\mu}g/mL$ concentration. And the V. persica significantly inhibited NO production in a concentration dependent manner. The inhibition effects of NO in cell medium of V. persica was over 80% at $800{\mu}g/mL$. The V. persica also suppressed the expression of iNOS, COX-2, and phosphorylation of $NF-{\kappa}B$ and $IkB-{\alpha}$ proteins. These results indicate that the V. persica has anti-oxidant and anti-inflammatory effects by modulating $NF-{\kappa}B$ signaling pathways and can be used as natural functional materials.

Tenebrio molitor (Mealworm) Extract Improves Insulin Sensitivity and Alleviates Hyperglycemia in C57BL/Ksj-db/db Mice (C57BL/Ksj-db/db 제 2형 당뇨모델을 이용한 갈색거저리 유충(밀웜) 추출물의 인슐린 감수성 및 혈당개선효과)

  • Kim, Seon Young;Park, Jae Eun;Han, Ji Sook
    • Journal of Life Science
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    • v.29 no.5
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    • pp.570-579
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    • 2019
  • Diabetes is one of the serious chronic metabolic diseases caused by Westernized eating habits, and the goal of diabetes treatment is to keep blood glucose at a normal level and prevent diabetic complications. This study was designed to investigate the anti-diabetic effects of a mealworm (Tenebrio molitor larva) extract (MWE) on hyperglycemia in an animal model with type 2 diabetes. Diabetic C57BL/Ksj-db/db mice were divided into three groups: diabetic control, rosiglitazone, and MWE. The mice supplemented with MWE showed significantly lower blood levels of glucose and glycosylated hemoglobin when compared with the diabetic control mice. The homeostatic index of insulin resistance was significantly lower in mice supplemented with MWE than in diabetic control mice. MWE supplementation significantly stimulated the phosphorylation of insulin receptor substrate-1 and Akt, and activation of phosphatidylinositol 3-kinase in insulin signaling pathway of skeletal muscles. Eventually, MWE increased the expression of the plasma membrane glucose transporter 4 (GLUT4) via PI3K/Akt activation. These findings demonstrate that the increase in plasma membrane GLUT4 expression by MWE promoted the uptake of blood glucose into cells and relieved hyperglycemia in skeletal muscles of diabetic C57BL/Ksj-db/db mice. Therefore, mealworms are expected to prove useful for the prevention and treatment of diabetes, and further studies are needed to improve type 2 diabetes in the future.

Effect of Scytosiphon lomentaria Ethanol Extracts on Myostatin Activity and Zebrafish Obesity Induced by High Feeding (고리매(Scytosiphon lomentaria) 에탄올 추출물이 마이오스타틴 활성과 고 급식으로 유도된 비만 제브라피쉬에 미치는 영향)

  • Jung, Jun Gyo;Kim, Jae Hong;Kim, Jeong Hwan;Kim, Yong Soo;Jin, Deuk-Hee;Jin, Hyung-Joo
    • Journal of Life Science
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    • v.31 no.8
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    • pp.699-709
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    • 2021
  • Muscle mass improvement through lifestyle modification has been shown to reduce the risk of metabolic syndrome. This study examined the capacity of ethanol extracts of Scytosiphon lomentaria (SLE) to suppress the bioactivity of myostatin, a potent negative regulator of skeletal muscle mass, as well as the effect of SLE treatment on metabolic homeostasis in obese zebrafish induced by high feeding. A total of 10 ㎍/ml SLE completely blocked myostatin (1 nM/ml) signaling in the pGL3-(CAGA)12 luciferase assay and suppressed myostatin-induced Smad2 phosphorylation in the Western blot analysis. In the zebrafish larvae analysis, the whole body glucose concentration of the high feeding control (HFC) group was significantly higher than that of the normal feeding control (NFC) group. However, the glucose levels of the high feeding group treated with 12.5 ug SLE and of the high feeding group treated with 18.75 ug SLE were similar to those of the NFC group. The mRNA expression level of the GLUT2 gene of the HFC group was significantly lower than that of the NFC group. SLE treatment restored the expression of the GLUT2 gene to a level that was close to that of the NFC group, indicating that SLE is capable of regulating glucose levels in zebrafish larvae. The current results highlight the potential of SLE as a natural MSTN inhibitor and supplement that can be used to facilitate the treatment of metabolic syndrome.