• Title/Summary/Keyword: inhibitory mechanism

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Anti-obese effects of mulberry (Morus alba L.) root bark through the inhibition of digestive enzymes and 3T3-L1 adipocyte differentiation (소화효소 저해 및 지방세포 분화 억제활성에 의한 상백피의 항비만 효능)

  • Wu, Yong-Xiang;Kim, You-Jeong;Li, Sha;Yun, Myung-Chul;Yoon, Jin-Mi;Kim, Jin-Young;Cho, Sung-Il;Son, Kun-Ho;Kim, Taewan
    • Food Science and Preservation
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    • v.22 no.1
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    • pp.27-35
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    • 2015
  • Anti-obese effects of mulberry (Morus alba L.) root bark was investigated in vitro by measuring its inhibitory effect against 3T3-L1 preadipocyte differentiation and digestive enzymes such as ${\alpha}$-amylase, ${\alpha}$-glucosidase and pancreatic lipase. Ethanol extract of mulberry root bark (MRE) showed the potent inhibitory activities on ${\alpha}$-amylase, ${\alpha}$-glucosidase and pancreatic lipase with $IC_{50}$ values of $7.86{\pm}0.36$, $0.12{\pm}0.03$ and $7.93{\pm}0.11mg/mL$, respectively. Furthermore, MRE significantly suppressed cellular lipid accumulation in 3T3-L1 cells in a dose-dependent manner. To elucidate the mechanism of MRE, we performed qRT-PCR and Western blotting for the expression of genes related with adipogenesis and lipogenesis. Treatment of MRE markedly suppressed the protein expression of $PPAR{\gamma}$, $C/EBP{\alpha}$ and SREBP-1c, as well as FAS and ACC, which are the key transcription factors and metabolic enzymes in adipogenesis and lipogenesis. In addition, qRT-PCR analysis indicated that the anti-adipogenesis effect of MRE might be due to its inhibition at transcription levels. These results demonstrate that MRE can effectively suppress adipocyte differentiation and inhibit key enzymes related to obesity. Our findings suggest that mulberry root bark may have a potential benefit in preventing obesity.

Inhibition of Adipocyte Differentiation through G1 Arrest by Extract of Sophora tonkinensis Gapnep in 3T3-L1 Preadipocytes (산두근 추출물의 세포주기 정지를 통한 3T3-L1 지방전구세포의 분화 억제)

  • Jeong, Hyun-Young;Hyun, Sook-Kyung;Choi, Yung-Hyun;Kim, Byung-Woo;Kwon, Hyun-Ju
    • Journal of Life Science
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    • v.21 no.9
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    • pp.1346-1353
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    • 2011
  • Sophora tonkinensis Gapnep has been used as a traditional herbal medicine in oriental regions since ancient times. In this study, the effect and mechanism of the MeOH extract of Sophora tonkinensis Gapnep (STME) on adipocite differentiation and adipogenesis in 3T3-L1 preadipocites were investigated. Treatment with STME in the concentration range of 0-200 ${\mu}g$/ml significantly inhibited the differentiation of 3T3-L1 preadipocites in a dose-dependent manner, as determined by a decrease in intracellular lipid droplets and lipid contents measured by Oil Red O staining. In association with the inhibitory effect of lipid accumulation, the expressions of the proteins concerned with adipogenesis in 3T3-L1 preadipocites were also investigated. Treatment with STME reduced the expressions of peroxisome proliferator-activated receptor ${\gamma}$ (PPAR${\gamma}$), cytidine-cytidine-adenosine-adenosine-thymine (CCAAT)/enhancer-binding proteins ${\alpha}$ and ${\beta}$ (C/EBP${\alpha}$ and C/EBP${\beta}$) and sterol regulatory element binding protein (SREBP), which are adipocyte specific markers. In flow cytometry analysis, the inhibitory effect of differentiation was caused by G1 arrest and following mitotic clonal expansion cease. Therefore, we also investigated the alteration of G1 phase arrest-related proteins. As a result, the expression of p21 protein was significantly increased, while the expressions of Cdk2, E2F-1 and phospho-Rb were reduced in a dose-dependent manner in STME treated 3T3-L1 cells. According to these results, STME might inhibit differentiation through G1 arrest in 3T3-L1 preadipocytes adipogenesis, and further studies, which are in progress, have to be completed to identify the active compounds.

Two new triterpenoid saponins derived from the leaves of Panax ginseng and their antiinflammatory activity

  • Li, Fu;Cao, Yufeng;Luo, Yanyan;Liu, Tingwu;Yan, Guilong;Chen, Liang;Ji, Lilian;Wang, Lun;Chen, Bin;Yaseen, Aftab;Khan, Ashfaq A.;Zhang, Guolin;Jiang, Yunyao;Liu, Jianxun;Wang, Gongcheng;Wang, Ming-Kui;Hu, Weicheng
    • Journal of Ginseng Research
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    • v.43 no.4
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    • pp.600-605
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    • 2019
  • Background: The leaves and roots of Panax ginseng are rich in ginsenosides. However, the chemical compositions of the leaves and roots of P. ginseng differ, resulting in different medicinal functions. In recent years, the aerial parts of members of the Panax genus have received great attention from natural product chemists as producers of bioactive ginsenosides. The aim of this study was the isolation and structural elucidation of novel, minor ginsenosides in the leaves of P. ginseng and evaluation of their antiinflammatory activity in vitro. Methods: Various chromatographic techniques were applied to obtain pure individual compounds, and their structures were determined by nuclear magnetic resonance and high-resolution mass spectrometry, as well as chemical methods. The antiinflammatory effect of the new compounds was evaluated on lipopolysaccharide-stimulated RAW 264.7 cells. Results and conclusions: Two novel, minor triterpenoid saponins, ginsenoside $LS_1$ (1) and 5,6-didehydroginsenoside $Rg_3$ (2), were isolated from the leaves of P. ginseng. The isolated compounds 1 and 2 were assayed for their inhibitory effect on nitric oxide production in LPS-stimulated RAW 264.7 cells, and Compound 2 showed a significant inhibitory effect with $IC_{50}$ of $37.38{\mu}M$ compared with that of NG-monomethyl-L-arginine ($IC_{50}=90.76{\mu}M$). Moreover, Compound 2 significantly decreased secretion of cytokines such as prostaglandin $E_2$ and tumor necrosis factor-${\alpha}$. In addition, Compound 2 significantly suppressed protein expression of inducible nitric oxide synthase and cyclooxygenase-2. These results suggested that Compound 2 could be used as a valuable candidate for medicinal use or functional food, and the mechanism is warranted for further exploration.

Inhibitory Effects of Locusta migratoria Ethanol Extracts on RANKL-induced Osteoclast Differentiation (RANKL 유도된 파골세포 분화에 대한 풀무치 에탄올 추출물의 분화 억제 효과)

  • Baek, Minhee;Seo, Minchul;Lee, Joon Ha;Lee, Hwa Jeong;Kim, In-Woo;Kim, Sun Young;Kim, Mi-Ae;Kim, Sunghyun;Hwang, Jae-Sam
    • Journal of Life Science
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    • v.29 no.10
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    • pp.1104-1110
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    • 2019
  • Recently, there has been an increase in the elderly population of the world. Consequently, bone metabolic diseases such as osteoporosis are emerging as a social problem. Osteoclasts play a role in bone resorption, and osteoporosis is induced when bone resorption occurs excessively. Because currently used bone resorption inhibitors may cause side effects when used for a long period of time, it is necessary to develop a new material that effectively inhibits osteoclast differentiation. This study aimed to confirm the inhibitory effect of ethanol extract of Locusta migratoria on RANKL-induced osteoclast differentiation and its mechanism. The toxicity and proliferation effects of LME on RAW264.7 osteoclasts were measured by an MTS assay. There was no cytotoxicity or proliferation when the osteoclasts were treated with up to $2,000{\mu}g/ml$ of LME. In order to confirm the effect of LME on the differentiation of osteoclasts, osteoclasts were treated with RANKL alone or with LME for 3 days. As a result of a TRAP (tartrate-resistant acid phosphatase) assay, the increasing osteoclast differentiation by RANKL decreased in a concentration-dependent manner with the treatment of LME. In addition, LME suppressed the expression of differentiation-related marker genes (TRAP, RANK, NFATc1, and CK) and proteins (NFATc1 and c-Src) that had been increased by RANKL. Also, LME influenced the $NF-{\kappa}B$, ERK and JNK signaling pathways, resulting in the inhibition of osteoclast differentiation. These results suggest that LME may be used as a novel functional material for the prevention and treatment of osteoporosis by playing a role in inhibiting bone absorption.

Leaves of Cudrania tricuspidata on the Shoot Positional Sequence Show Different Inhibition of Adipogenesis Activity in 3T3-L1 Cells (꾸지뽕 신초 엽위별 잎 추출물의 항비만 효과)

  • Park, Ju Ha;Guo, Lu;Kang, He Mi;Son, Beung Gu;Kang, Jum Soon;Lee, Yong Jae;Park, Young Hoon;Je, Byoung Il;Choi, Young Whan
    • Journal of Life Science
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    • v.31 no.2
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    • pp.209-218
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    • 2021
  • This study aimed to evaluate the anti-obesity effects of Cudrania tricuspidata leaf extract in the order of leaf development on the shoot (L0, L1, L2, L3, L4, and L5). The leaves at the apex of a Cudrania tricuspidata shoot were classified as L0; the next leaves of the apex were classified as L1, L2, L3, and L4 from highest to lowest; and the lowest leaf was classified as L5. A series of 70% ethyl alcohol leaf extracts were screened for the inhibitory effects of adipogenesis in 3T3-L1 preadipocytes. We found that the apical leaf extract of Cudrania tricuspidata (CTL0) was the most effective. Next, a study was conducted on the inhibitory action mechanism of CTL0. Treatment with CTL0 significantly suppressed the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner, as confirmed by the decrease in lipid droplet content observed with Oil Red O staining. Treatment with 12.5 ㎍/ml, 25 ㎍/ml, and 50 ㎍/ml of CTL0 significantly reduced the lipid droplet content. Glucose and cellular triglyceride concentrations were reduced in the 3T3-L1 cells on the CTL0-treated medium compared to the differentiation medium (DM control, DMEM + insulin + dexamethasone + rosiglitazone). Compared with DM, CTL0 significantly inhibited the expression of key pro-adipogenic transcription factors, including peroxisome proliferator-activated receptor γ (PPARγ), LPL, A-FABP, and Glut4. These findings show that CTL0 extract has potent anti-obesity effects.

Skin Whitening Effects of Angelica koreana and Cnidium monnieri Extracts (강활과 벌사상자 추출물의 피부 미백효과)

  • Cho, Wan Goo;Kim, Cheong Tack
    • Journal of Digital Convergence
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    • v.12 no.4
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    • pp.419-425
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    • 2014
  • The objective of this study is to estimate the inhibition of skin melanin formation by extract of Angelica koreana and Cnidium monnieri and the possibility of functional cosmetic materials through anti-irritation and stability test. The extract used in this experiment is White-$AK^{TM}$ and the INCI name is Osthole. The main component of White-$AK^{TM}$ was identified as coumarin and EC50 value was 2.7ppm by mouse melanoma B 16 cell test. White-$AK^{TM}$ showed inhibitory effects 100 times lower concentration than arbutin. The main mechanism for skin whitening effect thought to be inhibition of tyrosinase-related gene expression. The basic essence formulation of White-$AK^{TM}$ 5% solution applied to the skin showed the effect of relieving skin irritation. White-$AK^{TM}$ in an opaque container, under UV conditions for 4 weeks, and showed close to 100% recovery and 97% recovery under $50^{\circ}C$ for 4 weeks. Therefore, it is thought that White-$AK^{TM}$ which helps skin whitening, relieving skin irritation and stable in UV condition is able to be used as the functional component in the cosmetic formulation.

Inhibitory Effect of Jeungaektang Water Extract on Nitric Oxide and Cytokine Production in Lipopolysaccharide - activated RAW 264.7 Cells (증액탕(增液湯) 물추출물이 LPS로 유도된 RAW 264.7 cell에서의 Nitric Oxide 및 Cytokine에 미치는 영향)

  • Ahn, Sun-June;Lee, Jong-Rok;Kim, Sang-Chan;Jee, Seon-Young
    • Herbal Formula Science
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    • v.15 no.1
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    • pp.163-173
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    • 2007
  • Jeungaektang (JAT) is the herbal formula, has the effect of moistening the dryness by activating lung Qi and by nourishing Yin, has being used for dryness syndromes. Generally the herbal formulae for moistening dryness are used for exogenous or endogenous dryness syndromes. JAT has been clinically used for the treatment of endogenous dryness syndromes. It is composed of Scrophulariae Radix. Rehmanniae Radix and Liriopis Tuber. Recent studies showed that JAT has a protective effect against $CCl_{4}-induced$ hepatotoxicity and anti-inflammatory effects against ear swelling of mouse induced by Crotonis Fructus. However, the effect of JAT on the immunological activity was rarely studied. Therefore, this study evaluated the effects of JAT the regulatory mechanism of nitric oxide (NO) and cytokines in the lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. After the treatment of JAT water extract, cell viability was measured by MTT assay, NO production was monitored by measuring the nitrite content in culture medium. Cyclooxygenase-2 (COX -2) and inducible nitric oxide synthase (iNOS) were determined by immunoblot analysis, and levels of cytokine were analyzed by sandwich immunoassays. Results provided evidence that JAT inhibited the production of nitrite and nitrate ($0.1{\sim}1.0$ mg/ml), iNOS ($0.1{\sim}1.0$ mg/ml), $interleukin-1{\beta}$ ( $0.1{\sim}1.0$ mg/ml) and tumor necrosis $factor-{\alpha}$ ($0.1{\sim}1.0$ mg/ml) in RAW 264.7 cells activated with LPS. Furthermore, JAT inhibited the expression of COX-2 expression and production of prostagladin E2 ($0.1{\sim}1.0$ mg/ml). These findings suggest that JAT can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections.

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Inhibitory Effect of Phellinus Igniarius water extract on TNF-$\alpha$, IL-1$\beta$, IL-6 and Nitric Oxide Production in lipopolysaccharide - activated Raw 264.7 cells (상황 물추출물이 LPS로 유도된 Raw 264.7 cell에서의 TNF-$\alpha$, IL-1$\beta$, IL-6 및 Nitric Oxide production에 미치는 영향)

  • Kim Sang Chan;Jung Youn Suk;Lee Jae Ryung;Kim Young Woo;Byun Boo Hyeong;Kwon Teag Kyu;Suh Seong Il;Byun Sung Hui;Kwon Young Kyu
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.3
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    • pp.880-886
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    • 2004
  • Phellinus igniarius has been clinically used for the treatment of hemorrhoidal fistula, dysmenorrhea and the prevention of cancer in traditional oriental medicine. Recent studies showed that Phellinus igniarius produced anti-cancer, anti-metastasis and immuno-modulatory effects, There is lack of studies regarding the effects of Phellinus igniarius on the immunological activities. The present study was conducted to evaluate the effect of Phellinus igniarius on the regulatory mechanism of cytokines and nitric oxide (NO) for the immunological activities in Raw 264,7 cells. After the treatment of Phellinus igniarius water extract, cell viability was measured by MTT assay, NO production was monitored by measuring the nitrite content in culture medium. COX-2 and iNOS were determined by Immunoblot analysis, and levels of cytokine were analyzed by sandwich immunoassays. Results provided evidence that Phellinus igniarius inhibited the production of nitrite and nitrate (NO), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and the activation of phospholylation of inhibitor κBα (p-IκBα) in Raw 264.7 cells activated with lipopolysaccharide (LPS). These findings suggest that Phellinus igniarius can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections.

The Effect of Garlic (Allium Sativum L.f. Pekinense Makino) Juice on the Motility of the Isolated Duodenum (척출가토장관운동(剔出家兎腸管運動)에 미치는 마늘(Allium Sativum L.f. Pekinense Makino)의 영향(影響))

  • Ha, Jae-Kyo;Shin, Hong-Kee;Kim, Kee-Soon
    • The Korean Journal of Physiology
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    • v.15 no.1
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    • pp.61-66
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    • 1981
  • In 1944 Cavallito and Bailey first extracted an essential oil, a powerful antibacterial principle, from the garlic and named it allicin. Later Stoll and Seeback elucidated that allicin was produced from alliin by the enzymatic action of arinase. Damaru observed the depressor responses following intraperitoneal administration of garlic juice in cats. And Thiersch presented evidence that garlic had a protective action against experimental arterosclerosis in cholesterol-fed animals. On the other hand it was also reported that anemias were caused by long-term ingestion of garlic as a result of reduction in hemoglobin and RBC. From the experiment in which the effect of garlic on the blood sugar level was studied, Lee insisted garlic elevated blood sugar level. However, August and Jain claimed that hypoglycemia was induced by garlic administration. Recently Bordia and Bansal suggested that essential oils extracted from onion and garlic have a strong preventive effect on hyperlipemia and prolonged coagulation time resulted from fat-feeding. Furthermore Bordia et al indicated that garlic exerted a strong fibrinolytic activity. In early 1920 s Sugihara reported that essential oil of garlic not only decreased arterial blood pressure but also had a paralytic effect on the isolated heart and intestinal strip of animals. The present study was proposed to investigate the effect of garlic juice and the mechanism of its action on the motility of the isolated rabbit duodenum. The motility of the isolated duodenum was recorded on polygraph by means of force transducer connected with Magnus apparatus. And the isolated duodenum was separtely pretreated with $acetylcholine(5{\times}10^{-7}\;gm/ml)$, $pilocarpine(2.5{\times}10^{-6}\;gm/ml)$, $histamine(5{\times}10^{-6}\;gm/ml)$ and barium $chloride(2.5{\times}10^{-5}\;gm/ml)$ in order to find out interations of these drugs with ASJ. The results obtained were as follows; At concentrations of 0.25%, 0.5% and 1.0% ASJ markedly inhibited contractions of isolated duodenum while tonus as well as contractility of the isolated intestine were decreased also with 0.5% and 1.0% ASJ. Since ASJ markedly abolished augmented motility of isolated intestine by histamine and partly reduced that by $BaCl_2$, it is strongly suggested that inhibitory action of ASJ on the intestinal motility is caused mainly by its antihistamine effect and partly by its direct action on the intestinal smooth muscle.

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Isolation of a Quinone-rich Fraction from Ardisia crispa Roots and its Attenuating Effects on Murine Skin Tumorigenesis

  • Yeong, Looi Ting;Hamid, Roslida Abdul;Yazan, Latifah Saiful;Khaza'ai, Huzwah
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2301-2305
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    • 2013
  • Ardisia crispa (Family: Myrsinaceae) is an evergreen, fruiting shrub that has been traditionally used as folklore medicine. Despite a scarcity of research publications, we have succeeded in showing suppressive effects on murine skin papillomagenesis. In extension, the present research was aimed at determining the effect of a quinone-rich fraction (QRF) isolated from the same root hexane extract on both initiation and promotion stages of carcinogenesis, at the selected dose of 30 mg/kg. Mice (groups I-IV) were initiated with a single dose of 7,12-dimethylbenz(${\alpha}$)anthracene (DMBA, $100{\mu}g/100{\mu}l$) followed by repeated promotion of croton oil (1%) twice weekly for 20 weeks. In addition, group I (anti-initiation) received QRF 7 days before and after DMBA; group II (anti-promotion) received QRF 30 minutes before each croton oil application; group III (anti-initiation/promotion) was treated with QRF as a combination of group I and II. A further two groups served as vehicle control (group V) and treated control (group VI). As carcinogen control, group IV showed the highest tumor volume ($8.79{\pm}5.44$) and tumor burden ($3.60{\pm}1.17$). Comparatively, group III revealed only 20% of tumor incidence, tumor burden ($3.00{\pm}1.00$) and tumor volume ($2.40{\pm}1.12$), which were significantly different from group IV. Group II also showed significant reduction of tumor volume (3.11), tumor burden (3.00) and tumor incidence (11.11%), along with prominent increase of latency period of tumor formation (week 12). Group I, nonetheless, demonstrated marked increment of tumor incidence by 40% with prompted latency period of tumor formation (week 7). No tumor formation was observed in groups V and VI. This study provided clear evidence of inhibitory effects of QRF during promotion period which was in agreement with our previous findings. The mechanism(s) underlying such effects have yet to be elucidated.