• Biomolecules & Therapeutics
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• 제29권5호
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• pp.519-526
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• 2021

In a search for effective PPAR-γ agonists, 110 clinical drugs were screened via molecular docking, and 9 drugs, including parecoxib, were selected for subsequent biological evaluation. Molecular docking of parecoxib to the ligand-binding domain of PPAR-γ showed high binding affinity and relevant binding conformation compared with the PPAR-γ ligand/antidiabetic drug rosiglitazone. Per the docking result, parecoxib showed the best PPAR-γ transactivation in Ac2F rat liver cells. Further docking simulation and a luciferase assay suggested parecoxib would be a selective (and partial) PPAR-γ agonist. PPAR-γ activation by parecoxib induced adipocyte differentiation in 3T3-L1 murine preadipocytes. Parecoxib promoted adipogenesis in a dose-dependent manner and enhanced the expression of adipogenesis transcription factors PPAR-γ, C/EBPα, and C/EBPβ. These data indicated that parecoxib might be utilized as a partial PPAR-γ agonist for drug repositioning study.

• 한국식품영양과학회지
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• 제45권5호
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• pp.651-663
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• 2016

옥수수수염, 율무, 표고버섯 그리고 사과껍질 70% 주정 추출물들(CS, JT, LE, AP)은 항산화 활성이 있었고, 그것 중에 CS가 총폴리페놀 함량, 플라보노이드 함량, DPPH 라디칼 소거작용, ABTS 라디칼 소거작용 그리고 환원력과 같은 항산화 효과가 가장 높았다. 지방분화는 CS, JT, LE, AP 그리고 옥수수수염, 율무, 표고버섯 그리고 사과껍질을 함유한 개발 빵 추출물(DB)을 각각 처리한 3T3-L1 지방세포에서 연구하였다. DB1과 DB2는 지방 전구세포 분화 억제 및 항산화 효과가 있었다. 3T3-L1 지방세포에서 중성지방 축적은 실험한 시료들(CS, JT, LE, AP) 중에서 CS가 분화된 3T3-L1 지방세포에서 TG 축적을 가장 억제하였고 3T3-L1에서 지방분화와 관련된 인자들을 조절하였다. CS는 3T3-L1 세포에서 지방구 형성과 지방세포 분화를 농도 의존적으로 억제하였다. 지방분화 동안 다양한 농도(10, 50, $100{\mu}g/mL$)에서 CS와 함께 처리한 3T3-L1 세포에서 $C/EBP{\beta}$, $PPAR{\gamma}$ 그리고 aP2 mRNA와 단백질 수준에 대한 CS의 영향력을 실험하였고, 3T3-L1 지방세포에 CS 처리는 $PPAR{\gamma}$와 aP2 mRNA 발현을 감소시켰다. CS는 역시 지방분화 중에 $C/EBP{\beta}$, $PPAR{\gamma}$와 aP2 단백질의 증가를 현저하게 저해하였다. 개발된 빵들은 CS에 의해 지방 전구세포(3T3-L1 preadipocytes) 분화 억제 효과가 있고, CS는 3T3-L1 지방세포에서 $C/EBP{\beta}$, $PPAR{\gamma}$와 aP2 신호전달경로를 저해함으로써 지방 전구세포 분화 억제 효과를 나타내었다. JT, LE와 AP는 지방 전구세포 분화 억제 효과는 없었지만 강한 항산화 효과가 있었다. 이들 결과는 개발된 빵이 비만예방 및 억제뿐만 아니라 산화적 스트레스에 의해 유발되는 질병에 도움을 줄 수 있는 건강빵이라는 것을 제안하였다.

• 한국자원식물학회지
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• 제25권6호
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• pp.670-681
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• 2012

Herb extracts commercially used in Korea were screened for PPAR-${\gamma}$ agonist test and ${\alpha}$-glucosidase inhibition assay. Total 16 herb plants had a PPAR-${\gamma}$ agonist activity. Specially, Alisma orientale Juz (108.41%), Ephedra sinica (98.22%), Sasa japonica Makino var. purpurascens Nakai (140.68%), Astragalus membranaceus Bunge (106.79%) and Cnidium officinale Makino (113.00%) showed high PPAR-${\gamma}$ agonist activity rate compared with rosiglitazone's (167.46%). And Cornus officinalis S. et Z. (90.3%), Cinnamomum cassia Blume (89.2%), Psoralea corylifolia L. (89.8%), Paeonia japonica (Makino) Miyabe (92.4%) and Paeonia suffruticosa Andr (93.2%), showed high ${\alpha}$-glucosidase inhibition rates. These results support previous reports of the efficacy of Oriental medicinal plants used for diabetes mellitus.

• Journal of Microbiology and Biotechnology
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• 제28권10호
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• pp.1645-1653
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• 2018

The genus Acer contains several species with various bioactivities including antioxidant, antitumor and anti-inflammatory properties. However, Acer okamotoanum Nakai, one species within this genus has not been fully studied yet. Therefore, in this study, we investigated the anti-adipogenic activities of leaf extract from A. okamotoanum Nakai (LEAO) on 3T3-L1 preadipocytes. Adipogenesis is one of the cell differentiation processes, which converts preadipocytes into mature adipocytes. Nowadays, inhibition of adipogenesis is considered as an effective strategy in the field of anti-obesity research. In this study, we observed that LEAO decreased the accumulation of lipid droplets during adipogenesis and down-regulated the expression of key adipogenic transcription factors such as peroxisome proliferator-activated receptor ${\gamma}$ (PPAR ${\gamma}$) and CCAAT/enhancer binding protein ${\alpha}$ (C/EBP ${\alpha}$). In addition, LEAO inactivated PI3K/Akt signaling and its downstream factors that promote adipogenesis by inducing the expression of PPAR ${\gamma}$. LEAO also activated ${\beta}$-catenin signaling, which prevents the adipogenic program by suppressing the expression of PPAR ${\gamma}$. Therefore, we found that treatment with LEAO is effective for attenuating adipogenesis in 3T3-L1 cells. Consequently, these findings suggest that LEAO has the potential to be used as a therapeutic agent for preventing obesity.

• Korean Journal of Acupuncture
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• 제32권3호
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• pp.116-123
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• 2015

Objectives : The present study was designed to investigate effects and molecular mechanisms of Atractylodes macrocephala Koidzumi extracts(AMK) on the improvement of adipocyte dysfunction induced by TNF-${\alpha}$ in 3T3-L1 adipocytes. We examined whether AMK could directly influence the inflammation and insulin resistance in 3T3-L1 adipocytes. Methods : Potential roles of AMK in the lipolysis, production of inflammatory adipokines and ROS, expression and phosphorylation of ERK, JNK, and $I{\kappa}B{\alpha}$ protein, and expression of $PPAR{\gamma}$ and C/EBP${\alpha}$ were investigated in this study. Results : Our data demonstrated that TNF-${\alpha}$ significantly increased lipolysis, levels of MCP-1, IL-6, and ROS and phosphorylation of ERK, JNK, and $I{\kappa}B{\alpha}$ protein, while TNF-${\alpha}$ reduced the expression of $PPAR{\gamma}$ and C/EBP${\alpha}$ in adipocytes, suggesting that TNF-${\alpha}$ induced a condition with the occurrence of inflammation and insulin resistance. Those alterations induced by TNF-${\alpha}$ were prevented by the treatment of AMK. AMK down-regulated the phosphorylation of ERK, JNK, and $I{\kappa}B{\alpha}$ protein and up-regulated the expression of $PPAR{\gamma}$ and C/EBP${\alpha}$ on TNF-${\alpha}$-induced inflammation and insulin resistance. Conclusions : Thus, our results indicate that AMK can be used to prevent from the TNF-${\alpha}$-induced adipocyte dysfunction through MAPK, $NF{\kappa}B$ and $PPAR{\gamma}$ pathways.

• Food Science and Biotechnology
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• 제18권4호
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• pp.928-931
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• 2009

Effects of perilla leaf extracts (PLE) on adipocytes differentiation of 3T3-L1 cells were examined. Ethanol extract of PLE treatment significantly decreased lipid accumulation, a marker of adipogenesis, in a dose-dependent manner. Moreover, gene expression levels of peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$), the key adipogenic transcription factor, were markedly decreased by PLE. PLE also suppressed adipocyte fatty acid binding protein (aP2) and glycerol-3-phosphate dehydrogenase (GPDH), which are adipogenic marker proteins. These results suggest that PLE treatment suppressed differentiation of 3T3-L1 adipocytes, in part by down-regulating expression of adipogenic transcription factor and other specific target genes.

• Nutrition Research and Practice
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• 제8권2호
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• pp.158-164
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• 2014

BACKGROUD/OBEJECTIVES: This study aims to find out the effects of peanut sprout extracts on weight controls and protein expressions of transcription factors related to adipocyte differentiation and adipocytokine in rats under high-fat diets. MATERIALS/METHODS: Four week-old Sparague-Dawley (SD) were assigned to 4 groups; normal-fat (NF) diets (7% fat diet), high-fat (HF) diets (20% fat diet), high fat diets with low peanut sprout extract (HF + PSEL) diet (20% fat and 0.025% peanut sprout extract), and high fat diets with high peanut sprout extract (HF + PSEH) diet (20% fat and 0.05% peanut sprout extract). Body weight changes, lipid profiles in adipose tissue, and the mRNA protein expressions, such as peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$), CCAAT element binding protein ${\alpha}$ (C/EBP ${\alpha}$), leptin, and adiponectin, were determined. RESULTS: After 9 weeks of feeding, the HF + PSEH group had significantly less weight gains than the HF group (P < 0.05). However, the total dietary intakes or food efficiency ratios among groups were not significantly different. The weight of epididymal fat in HF + PSEH group, $3.61{\pm}0.5g$, or HF + PSEL group, $3.80{\pm}0.7g$, was significantly lower than the HF group, $4.39{\pm}0.4g$, (P < 0.05). Total lipids and total cholesterol in adipose tissue were significantly decreased in HF + PSEH group compared to those in the HF group, respectively (P < 0.05). PSEH supplementation caused AST and ALT levels to decrease when it compared to HF group, but it was not statistically significant. The protein expression of $PPAR{\gamma}$ in HF + PSEH group was significantly lower than the HF group (P < 0.05). Comparing with the HF group, the protein expression of adiponectin in HF + PSEH group was significantly increased (P < 0.05). The protein expressions of C/EBP ${\alpha}$ and leptin in HF + PSEH group were lower than the HF group, but it was not statistical significant. CONCLUSIONS: In conclusion, peanut sprout extract has anti-obesity effect by lowering the expressions of $PPAR{\gamma}$ which regulates the expression of adiponectin.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제23권4호
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• pp.346-355
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• 2020

Purpose: Peroxisome proliferator-activated receptor gamma (PPAR-γ) has a key role in hepatic fibrogenesis by virtue of its effect on the hepatic stellate cells (HSCs). Although many studies have shown that PPAR-γ agonists inhibit liver fibrosis, the mechanism remains largely unclear, especially regarding the cross-talk between PPAR-γ and other potent fibrogenic factors. Methods: This experimental study involved 25 male Wistar rats. Twenty rats were subjected to bile duct ligation (BDL) to induce liver fibrosis, further divided into an untreated group (BDL; n=10) and a group treated with the PPAR-γ agonist thiazolidinedione (TZD), at 14 days post-operation (BDL+TZD; n=10). The remaining 5 rats had a sham operation (sham; n=5). The effect of PPAR-γ agonist on liver fibrosis was evaluated by histopathology, protein immunohistochemistry, and mRNA expression quantitative polymerase chain reaction. Results: Histology and immunostaining showed markedly reduced collagen deposition, bile duct proliferation, and HSCs in the BDL+TZD group compared to those in the BDL group (p<0.001). Similarly, significantly lower mRNA expression of collagen α-1(I), matrix metalloproteinase-2, platelet-derived growth factor (PDGF)-B chain, and connective tissue growth factor (CTGF) were evident in the BDL+TZD group compared to those in the BDL group (p=0.0002, p<0.035, p<0.0001, and p=0.0123 respectively). Moreover, expression of the transforming growth factor beta1 (TGF-β1) was also downregulated in the BDL+TZD group (p=0.0087). Conclusion: The PPAR-γ agonist inhibits HSC activation in vivo and attenuates liver fibrosis through several fibrogenic pathways. Potent fibrogenic factors such as PDGF, CTGF, and TGF-β1 were downregulated by the PPAR-γ agonist. Targeting PPAR-γ activity may be a potential strategy to control liver fibrosis.

• Asian-Australasian Journal of Animal Sciences
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• 제23권11호
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• pp.1519-1526
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• 2010

Serum lipid (SL) is a commercially available cholesterol-rich, proteinaceous compound extracted from bovine serum. Here we investigated the adipogenic transdifferentiation potential of SL on bovine myogenic satellite cells. Exposure of satellite cells to SL could generate lipid droplets on day 2, and further exposure to SL increased cytoplasmic lipid accumulation giving adipocyte morphology. The expression analysis of PPAR gamma and GPDH adipocyte markers along with Oil-red-O staining results confirmed the transdifferentiation potential of SL. When cells were treated at different concentrations (5, 10, 20, $40{\mu}l$/ml) of SL, the results indicated that even levels as low as $5{\mu}l$ SL /ml could induce transdifferentiation, and maximum induction was obtained at $20{\mu}l$ SL/ml. After treatment with SL at different concentrations the expression levels of PPAR gamma varied significantly (p<0.05), whereas the expression of other adipogenic transcription factors showed no difference, indicating that SL acts through PPAR gamma. The combined effect of SL and troglitazone proved to be the best combination for induction of transdifferentiation compared to the individual effect of SL or troglitazone. Thus, overall results clearly show that SL induces transdifferentiation of bovine myogenic satellite cells to adipocytes.

• 동의생리병리학회지
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• 제24권1호
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• pp.118-123
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• 2010

Piper nigrum Linne has been used spice as well as herbal medicine in worldwide and has function of anti-oxidant, anti-inflammation, anti-cancer, bioavailability of drugs and etc. In this study, anti-adipogenic activity of Piper nigrum Linne extract and its constituent piperine were investigated in 3T3-L1 differentiation. Adipogenic effects and lipid accumulation in 3T3-L1 was measured by RT-PCR and Oil Red O staining assays respectively in stimulation of Piper nigrum Linne extract and piperine. Piper nigrum Linne and piperine reduced lipid accumulation in 3T3-L1 differentiation and expression of genes associated with adipogenesis such as PPAR${\gamma}$, adipsin, SERBP-1c and LPL. All of taken, anti-adipogenic mechanism of Piper nigrum Linne and piperine were related with regulation of SREBP-1c and PPAR${\gamma}$ expression.