• Toxicological Research
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• v.24 no.2
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• pp.129-135
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• 2008

The results of recent studies indicate that high levels of free fatty acids(FFAs) and adipokines may be the main causes of non-alcoholic liver disease; however, the molecular mechanism that links FFAs to lipotoxicity remains unclear. In the present study, we treated HepG2 cells with FFA(either palmitate or oleate) to investigate the mechanisms involved in lipotoxicity in the liver cells. We also treated cells with palmitate in the presence of a chemical chaperone, 4-phenylbutyric acid(PBA), to confirm the involvement of ER stress in lipotoxicity. Palmitate significantly induced cytotoxicity in dose- and time-dependent manners. Apoptosis was also significantly induced by palmitate as measured by caspase-3 activity and DAPI staining. Palmitate led to increased expressions of the spliced form of X-box-protein(Xbp)-1 mRNA and C/EBP homologous transcription factor(CHOP) protein, suggesting activation of the unfolded-protein response. PBA co-incubation significantly attenuated apoptosis induced by palmitate. The above data demonstrate that high levels of palmitate induce apoptosis via the mediation of ER stress in the liver cells and that chemical chaperones act to modulate ER stress and accompanying apoptosis.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.22 no.1
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• pp.40-59
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• 1996

Retinyl Palmitate, the skin normalzer, is useful to promote greater skin elasticity, to diminish lipid peroxidation and skin roughness following UV exposure, and promote a youthfull general skin appearance. We knew that the reduction of retinyl palmitate in W/O, W/S, O/W, MLV cream was caused by variable compound factors. Among the retinoids, we chose retinyl palmitate and studied the stability behavior of retinyl palmitate is liposomed. Furthermore, HPLC, CHROMA METERS, LASER SIGHT SCATTERING SYSTEM and FREEZE FRACTURE SCANNING ELECTROM MICROSCOPY was used to analyzing the stability and efficacy of UV and heat.

• Journal of Pharmaceutical Investigation
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• v.30 no.4
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• pp.259-266
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• 2000

Vitamin A palmitate, an oily drug which has low chemical stability and is poorly absorbed in the intestine, was formulated into a novel powdered dosage form. This is designated as a redispersible dry emulsion by freeze-drying technique. Before preparing a dry emulsion, vitamin A palmitate oil in solid in water (O/S/W) emulsion with soybean oil and coconut oil using Aerosil 200 as an emulsion stabilizer and polyoxyethylene-polyoxypropylene-blockcopolymer (Pluronic F68) as a surfactant was prepared. The resultants of the stability tests indicated that vitamin A palmitate O/S/W emulsion was improved on increasing the oil content of the formulation. The resultant dry emulsion particles have a good stabilities and free flow properties and readily released the oily droplets to form stable emulsions on rehydration. The drug releasing property from the resultant dry emulsion particles was dependent on factors such as amount of oily carrier(soybean oil) and surfactant(Pluronic F68) formulated. Above 80% of vitamin A palmitate content was released from the dry emulsion for 1 hour. It was deduced that vitamin A palmitate dry emulsion was definitely suitable for oral administration, since small droplets of vitamine A palmitate from the dry emulsion may alter the drug absorption profile resulting in bioavailability enhancement.

• The Journal of Korean Medicine
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• v.32 no.1
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• pp.109-120
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• 2011

Objectives: The aim of this investigation was to evaluate the efficacy of KHchunggan-tang aqueous extract on the experimental nonalcoholic fatty liver disease(NAFLD) induced by palmitate. Materials and Methods: To generate a cellular model of NAFLD, we used HepG2 cells, a human hepatoma cell line, treated with 0.5 mM palmitate. By this cellular model, effects of KHchunggan-tang aqueous extract were evaluated. Intracellular lipid accumulation, free radical formation, and apoptosis were detected by Nile red staining, 2',7'-dichloroflourescin diacetate(H2DCF-DA), and 4',6-diamidino-2-phenylindole(DAPI)/propidium iodide(PI) staining, respectively. Some proteins related with NAFLD were determined by western blot. Results: Typical pathological features of NAFLD occurred in the cellular model. Palmitate increased the levels of intracellular lipid vacuoles, decreased cell viability, and increased apoptosis. Palmitate increased free radical formation and lipid peroxidation, too. However, KHchunggan-tang aqueous extract reduced palmitate-induced pathologic features, i.e. steatosis, free radical formation, and apoptosis. In addition, KHchunggan-tang aqueous extract suppressed palmitate-activated c-Jun N-terminal kinase(JNK) signaling, and SP600125, a JNK inhibitor, significantly reversed the palmitate-induced pathologic changes as KHchunggan-tang aqueous extract. It means that the signaling pathway other than JNK can be involved in the KHchunggan-tang mediated cellular protection of palmitate-treated Hep G2 cells. Conclusions: These results suggest that KHchunggan-tang aqueous extract has hepatoprotective effects on NAFLD with combined properties in cellular steatosis, ROS production, and cytoprotection, and thus may have valuable clinical applications for treatment of this chronic liver disease.

• Journal of the Korean Chemical Society
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• v.37 no.3
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• pp.302-308
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• 1993

Monolayers of calcium palmitate were deposited on a piezoelectric quartz crystal plate by the Langmuir-Blodgett(LB) technique, and it was found from frequency changes of the quartz crystal deposited LB films. The usual carbonyl absorbance at 1704 cm$^{-1}C$ was replaced by the split band in the 1540~1590 cm$^{-1}C$. The two absorptions at 1580 cm$^{-1}C$ and 1540 cm$^{-1}C$ were assigned to the antisymmetric stretching vibration of the calcium carboxylate group and the hydrated species due to the lowering carbonyl stretching frequency by hydrogen bonding$^1$ respectively. Besides, it was demonstrated by X-ray diffraction analysis. The swelling behaviour of LB films in water phase at 23$^{\circ}C$ was observed from the frequency change of the LB films deposited quartz crystal with time. Calcium palmitate LB films has been found to swell substantially in water without flaking, whereas hexadecanol LB films hardly swelled in water. Amount of swelling of calcium palmitate LB films was equivalent to 47 wt.${\%}$ of the dry LB films, which means that ca. 7 water molecules were incorporated per calcium palmitate amphiphile. Chemical structure of calcium palmitate LB film was estimated as [CH$_3$(CH$_2$)$_{14}$COO]$_2$Ca${\cdot}$XH$_2$O, and the hydration number was 1.

• Korean Journal of Veterinary Research
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• v.44 no.2
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• pp.185-193
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• 2004

The effects of membrane lipid peroxidation and retinyl palmitate on rat liver microsomal functions were investigated in vitro. Rat liver homogenates exposed to oxygen tension for 0, 3, 6, 9 or12 hours and lipid peroxidation levels were evaluated by the measurements of fluorescence intensity, malondialdehyde (MDA) and retinyl palmitate. The fluorescence intensity of homogenates and microsomes were elevated and retinyl palmitate concentrations were decreased. But the concentration of MDA was not affected to exposure time. Therefore, fluorescence intensity and retinyl palmitate concentration were used to analyze the correlation between lipid peroxidation and microsomal functions. To investigate the liver microsomal functions, the microsome was isolated from rat liver homogenates exposed to oxygen. The concentration of cytochrome P450 and the activity of NADPH-cytochrome P450 reductase in liver microsomes were gradually decreased with increasing the exposure time. The correlation between fluorescence intensity of microsomes showed a very high inverse correlation of -0.97 and -0.93, respectively. The decrease of cytochrome P450 concentration was due to the regeneration of cytochrome P450 to cytochrome P420. Also, the activities of cytochrome P450-dependent aminopyrine demethylase and benzpyrene hydroxylase of liver microsomes were gradually decreased with increasing the exposure time. The correlation with fluorescence intensity of microsome showed a high inverse correlation of -0.97 and -0.91, respectively. The retinyl palmitate concentrations of rat liver homogenates were decreased with increasing the exposure time. The decrease of retinyl palmitate concentration was followed by a low concentration of cytochrome P450 and activity of NADPH-cytochrome P450 reductase. The correlation indicated high direct correlation of 0.92 and 0.93, respectively. The decrease of retinyl palmitate concentration was also accompanied by the reduction of aminopyrine demethylase and benzpyrene hydroxylase activities. The correlation was analyzed a high direct correlation of 0.90 and 0.85, respectively. In conclusion, these studies have shown that the membrane lipid peroxidation of rat liver microsome proportionally decreased microsomal enzyme activities in vitro experiments.

• Journal of the Korean Applied Science and Technology
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• v.25 no.1
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• pp.48-51
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• 2008

Dipalmitoyl phosphatidyl choline and p-nitrophenyl palmitate were directly sonicated in acidic water for 6 minutes to give clear stock solutions. The catalytic hydrolysis of p-nitrophenyl palmitate was studied at $30-50^{\circ}C$ in the presence of unilamellar vesicle and mixture of unilamellar and multilamellar aggregates. The difference of reaction rate between unilamellar and multilamellar was observed. The rate of unilamellar reaction compared to the rate of mixture reaction showed more catalytic effect. The phase transition temperature of vesicle was measured at $37-44^{\circ}C$.

• The Korean Journal of Zoology
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• v.36 no.1
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• pp.84-96
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• 1993

한국산 도롱뇽(Hynobius leechii) 유생의 다리 발생 과정을 관찰하고 잠재적 돌연변이 유발물질인 제-methyl-N'-nitro-N-nitrosoguanidine(MNNG)과 잠재적 기형 유발물질인 retinol palmitate가 다리 발생에 미치는 영향을 알아보았다. 정상적인 개체에서 됫다리의 발생 단계는 외부와 내부의 형태적 특징을 기준으로 하여 7단계로 나누어 볼 수 있었으며 전연골세포의 밀집에 따른 골격형성은 다리 발생아의 근위부에서 시작하여 원위부로 진행됨을 확인할 수 있었다. 도롱뇽 유생을 MNNG(10 rpm)나 retinol palmitate(37.5 lpm)로 처리한 경우, 공통적으로 다리 원위부의 골격 형성이 억제되었으며, 특히 이러한 골격 형성 억제 현상은 처리시기가 이를수록 보다 심하게 나타났다. 이러한 결과는 발생을 저해하는 물질에 대한 미분화 상태의 세포들의 반응성이 발생과정 중 특정 단계에 국한됨을 시사하는 것으로 해석된다.

• BMB Reports
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• v.42 no.6
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• pp.367-372
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• 2009

In this study, we showed that WAX9D, a nonspecific lipid-transfer protein found in broccoli, binds palmitate (C16) and stearate (C18) with dissociation constants of 0.56 ${\mu}M$ and 0.52 ${\mu}M$, respectively. WAX9D was fused to thioredoxin protein by genetic manipulation to enhance its solubility. The data revealed strong interaction of Trx-WAX9D with palmitate and stearate. The dissociation constants of Trx-WAX9D for palmitate and stearate were 1.1 ${\mu}M$ and 6.4 ${\mu}M$, respectively. The calculated number of binding sites for palmitate and stearate was 2.5 to 2.7, indicating that Trx-WAX9D can bind three molecules of fatty acids. Additionally, Trx-WAX9D was shown to inhibit the apoptotic effect of palmitate in endothelial cells. Our data using Trx-WAX9D provide insight into the broad spectrum of its biological applications with specific palmitate binding.

• Journal of Life Science
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• v.29 no.9
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• pp.964-971
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• 2019

Hepatic lipid accumulation and insulin resistance increases in patients with non-alcoholic fatty liver disease. Piperine is a major compound found in black pepper (Piper nigrum) and long pepper (P. longum). Piperine has been used in fine chemical for its anti-cancer, anti-obesity, anti-diabetic, anti-inflammatory and anti-oxidant properties. However, the signaling-based mechanism of piperine and its role as an inhibitor of lipogenesis and insulin resistance in human hepatocyte cells remains ill-defined. In the present study, we explored the effects of piperine on lipid accumulation and insulin resistance, and explored the potential underlying molecular mechanisms in palmitate-treated HepG2 cells. Piperine treatment resulted in a significant reduction of triglyceride content. Furthermore, piperine treatment decreased palmitate-treated intracellular lipid deposition by inhibiting the lipogenic target genes, sterol-regulatory-element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS); whereas the expression of carnitine palmitoyl transferase (CPT-1) and phosphorylation of acetyl coenzyme A carboxylase (ACC) gene involved in fatty acid oxidation was increased. Moreover, piperine also inhibited the phosphorylation of insulin receptor substrate (IRS)-1 (Ser307). Piperine treatment modulated palmitate-treated lipid accumulation and insulin resistance in HepG2 cells with concomitant reduction of lipogenic target genes, such as SREBP-1 and FAS, and induction of CPT-1-ACC and phosphorylation of IRS-1 (Tyr632)-Akt pathways. Therefore, piperine represents a promising treatment for the prevention of lipid accumulation and insulin resistance.