• Preventive Nutrition and Food Science
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• 제18권2호
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• pp.124-132
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• 2013

In this study, novel peptides (NIPP-1, NIPP-2) derived from Navicula incerta (microalgae) protein hydrolysate were explored for their inhibitory effects on collagen release in hepatic fibrosis with the investigation of its underlying mechanism of action. TGF-${\beta}1$ activated fibrosis in LX-2 cells was examined in the presence or absence of purified peptides NIPP-1 and NIPP-2. Besides the mechanisms of liver cell injury, protective effects of NIPP-1 and NIPP-2 were studied to show the protective mechanism against TGF-${\beta}1$ stimulated fibrogenesis. Our results showed that the core protein of NIPP-1 peptide prevented fibril formation of type I collagen, elevated the MMP level and inhibited TIMP production in a dose-dependent manner. The treatment of NIPP-1 and NIPP-2 on TGF-${\beta}1$ induced LX-2 cells alleviated hepatic fibrosis. Moreover, ${\alpha}$-SMA, TIMPs, collagen and PDGF in the NIPP-1 treated groups were significantly decreased. Therefore, it could be suggested that NIPP-1 has potential to be used in anti-fibrosis treatment.

• Archives of Pharmacal Research
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• 제29권1호
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• pp.67-72
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• 2006

The abnormal proliferation of aortic vascular smooth muscle cells (VSMCs) plays a central role in the pathogenesis of atherosclerosis and restenosis after angioplasty and possibly also in the development of hypertension. The present study was designed to examine the inhibitory effects and the mechanism of luteolin 7-glucoside (L7G) on the platelet-derived growth factor (PDGF)-BB-induced proliferation of VSMCs. L7G significantly inhibited the PDGF-BB-induced proliferation and the DNA synthesis of the VSMCs in a concentration-dependent manner. Pre-incubation of the VSMCs with L7G significantly inhibited the PDGF-BB-induced extracellular signal-regulated kinase 1/2 (ERK1/2), Akt and the phospholipase C $(PLC)-{\gamma}1$ activation. However, L7G had almost no affect on the phosphorylation of $PDGF-{\beta}$ receptor tyrosine kinase, which was induced by PDGF-BB. These results suggest that L7G inhibits the PDGF-BB-induced proliferation of VSMCs via the blocking of $(PLC)-{\gamma}1$, Akt, and ERK1/2 phosphorylation.

• 대한기관식도과학회지
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• 제4권1호
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• pp.64-72
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• 1998

This study aimed at observing the effect of diazepam on the contractility of trachealis muscle isolated from canine trachea, possible involvement of central or peripheral type benzodiazepine receptor, and the calcium related mechanism of action of diazepam. Trachealis muscle strips of 15 mm long were suspended in an isolated organ bath containing 1 ml of physiologic salt solution maintained at $37^{\circ}C$, and aerated with 95% $O_2$ /5% $CO_2$. Isometric myography was performed. Diazepam reduced the basal tone concentration dependently, and this inhibitory action was not affected by neither flumazenil, a central benzodiazepine receptor antagonist, nor PK11195, a peripheral benzodiazepine receptor antagonist. Pretreatment with diazepam showed the inhibitory effect on the concentration-response curves to agonists such as bethanechol, 5-hydroxytryptamine and histamine. Diazepam also caused concentration-related inhibition of contraction with potassium chloride 30 mM. The effect of diazepam on the basal tone and potassium chloride-induced contraction with calcium channel blockers were compared. Similar results were obtained in canine trachealis with verapamil, nifedipine and diltiazem. These results suggest that diazepam relax an airway muscle not via specific receptors but by a similar action as calcium channel blockers in canine trachealis muscle.

• 대한의생명과학회지
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• 제27권4호
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• pp.248-254
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• 2021

Ulcerative colitis (UC), chronic inflammatory bowel disease, is characterized by severe inflammation in the colon. Tea is one of the most popular beverages consumed worldwide. Pu-erh tea, a unique Chinese tea produced by microbial activities, possesses a broad range of health-promoting effects, including anti-aging, anti-Alzheimer's disease, antioxidation and anti-obesity. However, the inhibitory effect of Pu-erh tea on intestinal inflammation and the underlying mechanism remain unclear. The present study was designed to evaluate the regulatory effect of Pu-erh tea extract (PTE) on dextran sulfate sodium (DSS)-induced colitis clinical signs by analyzing the weight loss and colon length in mice. The inhibitory effects of PTE on inflammatory mediators, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, and the activation of nuclear factor-κB (NF-κB) were also determined in DSS-treated colitis tissue. We observed that PTE treatment significantly inhibited the DSS-induced clinical symptoms of weight loss, decrease,in colon length, and colon tissue damage in mice. Moreover, PTE attenuated the DSS-induced levels of IL-6 and TNF-α in colon tissue. We also demonstrated the anti-inflammatory mechanism of PTE by suppressing the activation of NF-κB in DSS-treated colon tissues. Collectively, the findings provide experimental evidence that PTE may be effective in preventing and treatment of intestinal inflammatory disorders, including UC.

• 한국축산식품학회지
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• 제32권5호
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• pp.678-684
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• 2012

본 연구는 tyrosinase 활성 저해효과가 있는 젖산균인 L plantarum M23 균주를 이용하여 멜라닌 형성을 억제하기 위한 최적 발효유 제조조건을 설정하는데 그 목적이 있다. 3수준 4인자 중심합성 계획법을 통해 실험설계하여 반응표면분석법을 사용하였다. 독립변수로는 yeast extract 농도(%, $X_1$), 포도첨가량(%, $X_2$), 배양온도($^{\circ}C$, $X_3$), 배양시간(h, $X_4$)을 설정하였고, 종속변수로는 pH(pH, $Y_1$), 종합적 기호도(score, $Y_2$)와 tyrosinase inhibitory activity(%, $Y_3$)를 설정하였으며, tyrosinase inhibitory activity가 가장 높고 pH는 4.4를 동시에 만족하는 최적화를 실시한 결과 yeast extract 농도는 0.13%, 포도 첨가량은 2.95%, 배양 온도는 $37.1^{\circ}C$, 배양 시간은 14.8 h일 때 예상되는 pH는 4.42, 기호도는 7.06, tyrosinase inhibitory activity은 86.65%이었으며, 실제 실험 결과 pH는 4.35, 기호도는 6.86, tyrosinase inhibitory activity은 84.05%로서 큰 차이를 나타내지 않았다. 이러한 결과를 토대로 melanin 생합성과정의 key enzyme인 tyrosinase을 활성억제하는 L. plantarum M23을 이용한 발효유는 피부의 미백 작용과 노화 억제 작용에 기여할 것으로 사료되었다.

• 동의생리병리학회지
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• 제28권3호
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• pp.288-295
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• 2014

Bojungchiseub-tang (BJCST) has been used in symptoms and signs of edema, dampness-phlegm, kidney failure, and so on. BJCST is also expected to have strong anti-obesity activities. However, little is known about the mechanisms of its inhibitory effects on adipocyte differentiation and adipogenesis. In the present study, we examined the effects and mechanism of BJCST on transcription factors and adipogenic genes of 3T3-L1 preadipocytes to understand its inhibitory effects on adipocyte differentiation and adipogenesis. Our results showed that BJCST significantly inhibited differentiation and adipogenesis of 3T3-L1 preadipocytes in a dose-dependent manner. To elucidate the mechanism of the effects of BJCST on lowering lipid content in 3T3-L1 adipocytes, we examined whether BJCST modulate the expressions of transcription factors to induce adipogenesis and adipogenic genes related to regulate accumulation of lipids. As a result, the expression of steroid regulatory element-binding protein (SREBP)1, cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer binding proteins ${\alpha}$ ($C/EBP{\alpha}$), $C/EBP{\beta}$, $C/EBP{\delta}$, and peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) genes, which induce the adipose differentiation, liver X receptor $(LXR){\alpha}$ and fatty acid synthase (FAS) genes, which induce lipogenesis and adipose-specific aP2, Adipsin, lipoprotein lipase (LPL), CD36, TGF-${\beta}$, leptin and adiponectin genes, which compose fat formation were decreased. BJCST also reduced the expression of acyl CoA oxidase (ACO) and uncoupling protein (UCP) genes related to lipid oxidation. In conclusion, BJCST could regulate transcript factor related to induction of adipose differentiation and inhibited the accumulation of lipids and expression of adipogenic genes.

• 대한약리학회지
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• 제19권1호
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• pp.85-92
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• 1983

Intestine is innervated by an interconnected plexus of both sympathetic and parasympathetic nerve fibers. Sympathetic influence causes inhibition of intestinal motility mediated by both ${\alpha}-\;and\;{\beta}-adrenergic$ receptors. The mechanism of intestinal relaxation by ${\beta}-receptors$ has been extensively studied, but the function of ${\alpha}-receptors$ in intestinal motility is still unclear. Although it is suggested that catecholamine reduces acetylcholine release and this may play an important role in ${\alpha}-receptor$ mediated intestinal relaxation, there is no definite evidences about the mechanism and site of action of ${\alpha}-receptor$ mediated relaxation. In this experiment, therefore, the effect and site of action of ${\alpha}-receptor$ agonists were investigated in the guinea pig ileum using electrical field stimulation. The results are summarized as follows : 1) Electrical field stimulation elicited tonic contraction in isolated guinea pig ileum ana this contraction was completely inhibited by the pretreatment of tetrodotoxin or atropine. 2) Norepinephrine, epinephrine and dopamine inhibited the contraction induced by electrical field stimulation but methoxamine and phenylephrine had little effects. 3) Inhibitory effects of norepinephrine and dopamine was partially blocked by yohimbine and phentolamine pretreatment. But haloperidol and propranolol pretreatment cause no effects on the electrical field stimulation induced contraction. Inhibitory effect of dopamine was completely blocked by both haloperidol and yohimbine pretreatment. 4) Inhibitory effects of norepinephrine and dopamine were little affected by the pretreatment with hexamethonium. It is suggested that electrical field stimulation causes tonic contraction of guinea pig ileum by releasing acetylcholine from postganglionic fiber, and this release is blocked by presynaptic ${\alpha}-receptor$ activation.

• 대한한방부인과학회지
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• 제19권3호
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• pp.135-149
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• 2006

Purpose : This study was aimed to investigate the inhibitory effect of Millettia Reticulatas on the proliferation of human uterine leiomyoma cells and the expression of gene related the mechanism of cell apoptosis. Methods : We counted the number of death cells treated with indicated concentration of Millettia Reticulatas and investigated cell death rate by MTS assay. Furthermore, flow cytometry analyis and DNA fragmentation assay were used to dissect between necrosis and apoptosis. and then we observed the differential gene expression by western blot analysis. Results : 1) The inhibitory effect on the growth of uterine leiomyoma cell treated with Millettia Reticulatas was increased in a concentration proportional. 2) The result of flow cytometry analysis. subG1 phase arrest related3 cell apoptosis was investigated 23.49% in uterine leiomyoma cell treated Millettia Reticulatas and showed the fession of proportional concentration. 3) The gene expression of p27, p53, p21, p16 related cell cycle was increased according to increasing concentration but cyclin E was none exchanged. 4) The character of apoptosis, DNA fragmentation was significantly observed the fession of proportional concentration. 5) The expression of pro-caspase3 and PARP were decreased dependent on treatment concentration. Conclusion : This study showed that Millettia Reticulatas have the inhibitory effect on the proliferation of human uterine leiomyoma cell and the effect was related with apoptosis. The apoptotic mechanism was observed that the gene expression of p27, p53, p21, p16 related cell cycle was increased according to increasing treatment concentration, induced G1 phase arrest and finally cell death was occurred. The decreased expression of pro-caspase 3 and PARP were noted that apoptosis was related with caspase pathway.

• 한국약용작물학회지
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• 제24권1호
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• pp.7-13
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• 2016

Background : Ginger has been extensively used in foods and traditional medicines in Asian countries. Despite its frequent consumption in daily life, the mechanism of potential interactions between ginger components-drug has not been examined. To elucidate the mechanism of governing the effects of 6-shogaol, a primary constituent of dried ginger, on human cytochrome P450 (CYP) isoenzymes an incubation studies were carried out using pooled human liver microsome (HLM). Methods and Results : CYP isoenzyme specific substrate was incubated with multiple concentrations of inhibitor, HLM and cofactors. 6-shogaol showed a potent inhibitory effect on CYP2C9, CYP1A2 and CYP2C19 with half maximal inhibitory concentration ($IC_{50}$) values of 29.20, 20.68 and $18.78{\mu}M$ respectively. To estimate the value of the inhibition constant ($K_i$) and the mode of inhibition, an incubation study with varying concentrations of each CYP isoenzyme-specific probe was performed. 6-shogaol inhibited CYP2C9 and CYP2C19 noncompetitively ($K_i=29.02$ and $19.26{\mu}M$ respectively), in contrast, the inhibition of CYP1A2 was best explained by competitive inhibition ($K_i=6.33{\mu}M$). Conclusions : These findings suggest that 6-shogaol may possess inhibitory effects on metabolic activities mediated by CYP1A2, CYP2C9 and CYP2C19 in humans.

• 한방안이비인후피부과학회지
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• 제28권1호
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• pp.41-52
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• 2015

Objective : This study investigated the inhibitory mechanism of the hypopigmentating effects on ethanol extract of Rosae rugosae Flos (ERR) that has not yet been examined. Methods : We analyzed the anti-melanogenic effects of ethanol extracts from Rosae rugosae Flos by tyrosinase activity, melanin contents. We also examined protein expression levels of tyrosinase, TRP-1, TRP-2, MITF and ERK by western blot analysis in melanoma cells. Results : In this investigation, ERR effectively reduced ${\alpha}$-MSH-stimulated melanin synthesis by suppressing expression of tyrosinase and tyrosinase-related protein-1 (TRP-1). On the other hand, the expression of tyrosinase-related protein-2 (TRP-2) were not affected by treatment with ERR. ERR inhibited the expression of microphthalmia-associated transcription factor (MITF) as a key transcription factor for tyrosinase expression regulating melanogenesis. The upstream signaling pathway including cAMP response element-binding protein (CREB) and MAPKs were also inhibited by ERR. Pretreatment with PD98059, ERK inhibitor, attenuated the inhibitory effect of ERR on ${\alpha}$-MSH-induced tyrosinase activity. Conclusions : Our study suggested that the anti-melanogenic activity of ERR is correlated with the suppression of tyrosinase gene through CREB/MITF/ERK pathway.