• BMB Reports
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• 제47권1호
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• pp.45-50
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• 2014

Aspirin has been demonstrated to be effective in inhibiting COX-2 and $PGE_2$ in Alveolar macrophages (AMs). However, the mechanisms have not been fully understood. In the present study, we found that pretreatment with aspirin inhibited LPS-induced COX-2 and$PGE_2$ upregulation, $I{\kappa}B{\alpha}$ degradation, NF-${\kappa}B$ activation and the increase of PKC activity, but elevated LPS-induced the decrease of PTP activity. The PKC inhibitor calphostin C dramatically reduced the COX-2 mRNA and $PGE_2$ levels, but the PTP inhibitor peroxovanadium (POV) significantly increased the COX-2 mRNA and$PGE_2$ levels. Furthermore, the PTP inhibitor mitigated the inhibitory effect of aspirin on COX-2 and$PGE_2$ upregulation and NF-${\kappa}B$ activation, whereas the PKC inhibitor enhanced the inhibitory effects of aspirin on the production of COX-2 and$PGE_2$. Our data indicate a novel mechanism by which aspirin acts as a potent anti-inflammatory agent in alveolus macrophages and ALI.

• Bulletin of the Korean Chemical Society
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• 제32권3호
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• pp.1000-1006
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• 2011

The discovery of carbohydrate-based bioactive compounds has recently received considerable interest in the drug development. This paper stresses on the application of 1-methoxy-O-glucoside as the central scaffold, whereas salicylic pharmacophores were introduced with diverse spatial orientations probing into the structural preference of an enzymatic target, i.e. protein tyrosine phosphatase 1B (PTP1B). By employing regioselective protection and deprotection strategy, 2,6-, 3,4-, 4,6- and 2,3-di-O-propynyl 1-methoxy-O-glucosides were previously synthesized and then coupled with azido salicylate via click chemistry in forming the desired bidentate salicylic glucosides with high yields. The inhibitory assay of the obtained triazolyl derivatives leads to the identification of the 2,3-disubstituted salicylic 1-methoxy-O-glucoside as the structurally privileged PTP1B inhibitor among this bidentate compound series with micromole-ranged $IC_{50}$ value and reasonable selectivity over other homologous PTPs tested. In addition, docking simulation was conducted to propose a plausible binding mode of this authorized inhibitor with PTP1B. This research might furnish new insight toward the construction of structurally different bioactive compounds based on the monosaccharide scaffold.

• Natural Product Sciences
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• 제26권4호
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• pp.326-333
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• 2020

The aerial parts of Eclipta prostrata is used as a traditional medicine and vegetable. In traditional folk medicine, it is used for treatment of hemorrhages, hepatic, disease, renal injuries, hair loss, tooth mobility, and viper bites. In this study, ten compounds (1 - 10) were isolated from the aerial parts of E. prostrata. A reliable high performance liquid chromatography equipped with photometric diode array detector (HPLC-PDA) method was developed to simultaneously quantitate 10 marker compounds [chlorogenic acid (1), paratensein 7-O-��-ᴅ-glucoside (2), quercetin 7-O-��-ᴅ-glucoside (3), luteolin 7-O-��-ᴅ-glucoside (4), apigenin 7-O-��-ᴅ-glucoside (5), apigenin 4'-O-��-ᴅ-glucoside (6), apigenin (7), luteolin (8), wedelolactone (9), and paratensein (10)]. In addition, compounds 5 and 6 showed considerable inhibitory effects against protein-tyrosine phosphatase 1B (PTP1B) enzyme. Moreover, compounds 6 - 8, and 10 exhibited potent α-glucosidase inhibitory effects with IC50 values of 24.5 ± 1.9, 33.0 ± 0.5, 45.5 ± 0.1, and 23.8 ± 1.0 µM, respectively. All compounds (1 - 10) showed considerable acetylcholinesterase (AChE) inhibitory effects with IC50 ranging from 30.1 to 75.2 µM.

• Bulletin of the Korean Chemical Society
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• 제24권10호
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• pp.1455-1464
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• 2003

Several series of compounds (benzoic acids, pyrazolecarboxylic acids, phenoxyacetic acids, and quinolinoxyacetic acids) were prepared and evaluated for their inhibitory activity against PTP-1B. Several compounds showed submicromolar inhibitory activity.

• Journal of Applied Biological Chemistry
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• 제50권2호
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• pp.52-57
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• 2007

Quantitative structure-activity relationships (QSARs) on the inhibition activities by oleanolic acid analogues (1-19) as a potent inhibitor against protein tyrosine phosphatase-1B were studied quantitatively using 2D-QSAR and HQSAR methodologies. The inhibition activity was dependent on the variations of $R_{4-}$substituent, and as shown in 2D-QSAR model ($r^2=0.928$), it has a tendency to increase as the negative Randic Indice (RI) goes up. The size of the molecular fragments used in HQSAR varied from five to eight. The fragment distinctions had the best statistic value, whose predictability is $q^2=0.785$ and correlation coefficient is $r^2=0.970$, on condition of connections. From the atomic contribution maps, the factor that contributes to the inhibition activities is the $C_{15}{\sim}C_{17}$ bond in the D ring. From the analysis result of these two the models, the structural distinctions and descriptors that contribute to the inhibition activities were obtained.

• 생약학회지
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• 제45권3호
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• pp.194-199
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• 2014

The roots of Paeonia lactiflora (PL) has been traditionally used as analgesic, spasmolytic and tonic in Korea, China, and Japan. As part of a search for herbal medicine to treat diabetes and obesity, we confirmed hypoglycemic effect of PL through high fat diet-induced obese and diabetic mice experiments in vivo. Treatment of ethanolic extract from PL led to a significant decrease in glucose level, which is comparable to that of an antidiabetic drug metformin. In addition, PL selectively stimulates the transcriptional activities of both peroxisome proliferator-activated receptor $(PPAR){\alpha}$ and ${\gamma}$, and inhibits enzymatic activity of protein tyrosine phosphatase 1B (PTP1B), which are predicted to be therapeutic target in treatment of type2 diabetes and obesity. Especially, the n-hexane fraction (Hx) from PL ethanol extract showed more potent activities on $PPAR{\alpha}$ and than others and exihibited moderate inhibitory activity against PTP1B.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.243.2-244
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• 2002

Protein-tyrosine phosphatases (PTPs) constitute a family of receptor-like and cytoplasmic enzymes. which catalyze the dephosphorylation of phosphotyrosine residues in a variety of receptors and signaling molecules. Thirty subtypes of PTPs have been identified in human genomes. Among PTPs, PTP1 B has been suggested as a negative regulator of insulin signaling. Overexpression of this enzyme has been known as a cause of obesity and type II diabetes, so it is a target for drug discovery. (omitted)

• The Korean Journal of Physiology and Pharmacology
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• 제3권3호
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• pp.293-303
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• 1999

The influences of specific protein phosphatase and protein kinase inhibitors on the ATP-sensitive $K^+\;(K_{ATP})$ channel-opening effect of pinacidil were investigated in single rat ventricular myocytes using patch clamp technique. In cell-attached patches, pinacidil $(100\;{\mu}M)$ induced the opening of the $K_{ATP}$ channel, which was blocked by the pretreatment with H-7 $(100\;{\mu}M)$ whereas enhanced by the pretreatment with genistein $(30\;{\mu}M)$ or tyrphostin A23 $(10\;{\mu}M)$. In inside-out patches, pinacidil $(10\;{\mu}M)$ activated the $K_{ATP}$ channels in the presence of ATP (0.3 mM) or AMP-PNP (0.3 mM) and in a partial rundown state. The effect of pinacidil $(10\;{\mu}M)$ was not affected by the pretreatment with protein tyrosine phosphatase 1B $(PTP1B,\;10\;{\mu}g\;ml^{-1}),$ but blocked by the pretreatment of protein phosphatase 2A $(PP2A,\;1\;U\;ml^{-1})$. In addition, pinacidil $(10\;{\mu}M)$ could not induce the opening of the reactivated $K_{ATP}$ channels in the presence of H-7 $(100\;{\mu}M)$ but enhanced it in the presence of ATP (1 mM) and genistein $(30\;{\mu}M).$ These results indicate that the $K_{ATP}$ channel-opening effect of pinacidil is not mediated via phosphorylation of $K_{ATP}$ channel protein or associated protein, although it still requires the phosphorylation of serine/threonine residues as a prerequisite condition.

• 대한의생명과학회지
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• 제18권1호
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• pp.1-9
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• 2012

Differentially expressed genes by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were identified in order to evaluate them as dioxin-sensitive markers and crucial signaling molecules to understand dioxin-induced toxic mechanisms in human bronchial cells. Gene expression profiling was analyzed by cDNA microarray and ten genes were selected for further study. They were cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1), S100 calcium binding protein A8 (calgranulin A), S100 calcium binding protein A9 (calgranulin B), aldehyde dehydrogenase 1 family, member A3 (ALDH6) and peroxiredoxin 5 (PRDX5) in up-regulated group. Among them, CYP1B1 was used as a hallmark for dioxin and sharply increased by TCDD exposure. Down-regulated genes were IK cytokine, interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), nuclease sensitive element binding protein 1 (NSEP1), protein tyrosine phosphatase type VI A, member 1 (PTP4A1), ras oncogene family 32 (RAB32). Although up-regulated 4 genes in microarray were coincided with northern hybridization, down-regulated 5 genes showed U-shaped expression pattern which is sharply decreased at lower doses and gradually increased at higher doses. These results introduce some of TCDD-responsive genes can be sensitive markers against TCDD exposure and used as signaling cues to understand toxicity initiated by TCDD inhalation in pulmonary tissues.

• 생명과학회지
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• 제31권2호
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• pp.183-191
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• 2021

본 연구에서는 다양한 생리활성을 나타내는 compound를 함유하고 있는 것으로 알려진 Euglena gracilis를 hot water로 추출하고(HWE), 그 잔존물을 methanol로 추출(HWME)한 후, murine macrophage RAW 264.7 cell에 처리하여 면역활성을 측정하였다. Murine macrophage RAW 264.7 cell에서 HWE 처리로 IL-1β와 TNF-α가 농도의존적으로 증가되었고, lipopolysaccharide에 의해 유도되는 IL-6와 TNF-α 생성이 HWME 처리에 의해 유의적으로 억제되는 것을 확인하였다. 또한 α-glucosidase, protein tyrosine phosphatase (PTP1B), tyrosinase, xanthine oxidase (XO), angiotensin converting enzyme (ACE) 등에 대한 저해활성을 조사하였다. 그 결과, E. gracilis HWE 추출물에서는 α-glucosidase, tyrosinase, ACE에서 약한 억제 활성을 보였으나, HWME 추출물에서는 PTP1B와 XO에서 유의적인 억제활성을 나타냈다. 따라서 본 연구를 통하여 E. gracilis 추출물의 면역조절 활성 뿐 만 아니라 당뇨와 심혈관 질환에 대한 유의적인 억제활성을 통해 다양한 건강기능성 식품의 소재로 활용될 수 있을 것으로 사료된다.