• Archives of Pharmacal Research
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• v.8 no.3
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• pp.119-132
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• 1985

The apparent effectiveness of 1-naphthyl-N-methyl carbamate (carbaryl) against a wide variety of insects motivated the study of its mammalian toxicity. In this toxicological study of carbaryl, mature male rats inhaled carbaryl at a mean concentration of 112mg, 168mg and 224 mg/$m^{3}$ for one hour. After inhalation, pentobarbital sleeping time, Nadph-cytochrome c reductase activity, cytochrome p-450 and protein content in liver microsomes, various tissue residues, cholinesterase inhibition in plasma and histopathological findings at autopsy were observed. The pentobarbital sleeping time was prolonged in rats inhaled with carbaryl for one day while the sleeping time was shortened in the 3 days inhaled group. The changes of cytochrome p-450 content and NADPH-cytochrome c reductase activity exhibited biphasic response showing the decrease in the one day inhaled group and the increase in the 3 days inhaled group. The marked depression of plasma ChE activity was observed in rats inhaled with carbaryl at 112 mg/$m^{3}$, however no more progressive effect was observed at the higher concentration of the compound. The main observations in histopathological finding were ciliary detachment, epithelial swelling and subepithelial inflammatory cellular infiltration in trachea due to the irritation.

• Biomolecules & Therapeutics
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• v.25 no.4
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• pp.417-426
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• 2017

4-O-methylhonokiol, a neolignan compound from Magnolia Officinalis, has been reported to have various biological activities including hair growth promoting effect. However, although transforming growth factor-${\beta}$ (TGF-${\beta}$) signal pathway has an essential role in the regression induction of hair growth, the effect of 4-O-methylhonokiol on the TGF-${\beta}$ signal pathway has not yet been elucidated. We thus examined the effect of 4-O-methylhonokiol on TGF-${\beta}$-induced canonical and noncanonical pathways in HaCaT human keratinocytes. When HaCaT cells were pretreated with 4-O-methylhonokiol, TGF-${\beta}1$-induced G1/G0 phase arrest and TGF-${\beta}1$-induced p21 expression were decreased. Moreover, 4-O-methylhonokiol inhibited nuclear translocation of Smad2/3, Smad4 and Sp1 in TGF-${\beta}1$-induced canonical pathway. We observed that ERK phosphorylation by TGF-${\beta}1$ was significantly attenuated by treatment with 4-O-methylhonokiol. 4-O-methylhonokiol inhibited TGF-${\beta}1$-induced reactive oxygen species (ROS) production and reduced the increase of NADPH oxidase 4 (NOX4) mRNA level in TGF-${\beta}1$-induced noncanonical pathway. These results indicate that 4-O-methylhonokiol could inhibit TGF-${\beta}1$-induced cell cycle arrest through inhibition of canonical and noncanonical pathways in human keratinocyte HaCaT cell and that 4-O-methylhonokiol might have protective action on TGF-${\beta}1$-induced cell cycle arrest.

• Applied Biological Chemistry
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• v.37 no.3
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• pp.203-209
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• 1994

When $^{14}C-{\alpha}-endosulfan$ was incubated with carp liver, kidney and gut preparations, it was metabolized to water soluble and organosoluble metabolites. In an in vitro test, endosulfan was converted to endosulfan ${\alpha}-hydroxyether$ (EHE), endosulfan alcohol (EA) and endosulfan ether (EE). The addition of NADPH resulted in rapid conversion of endosulfan to the metabolites in 105,000 g soluble fraction and microsomes. However, the rate of metabolism of endosulfan in liver, kidney and gut supplemented with NADPH as a cofactor was higher in the 105,000 g soluble fraction than that in the microsomes of carp under incubation conditions. The enzymes probably involved in the metabolism of endosulfan include the glutathione S-transferase (GST) and the mixed function oxidases (MFO), based on the evidence that addition of either GSH or NADPH increased the degradation of endosulfan.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.3-5
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• 2003

여성호르몬으로 잘 알려진 estrogen은 난소의 granulosa 세포와 정소의 Sertoli 세포에서 주로 생성되는 것으로 알려져 있으며 최근엔 사람의 지방, 근육, 뇌, 뼈세포 등에서의 합성 가능성과 각 조직에서 생성되는 estrogen 의 생리학적인 기능에 관해 많은 관심이 모여져 왔다. 다른 steroid처럼 지방친화적인 (lipophilic) estrogen은 세포막과 핵막을 쉽게 통과하여 목표세포 (target cell)의 핵에 존재하는 estrogen receptor (ER)에 결합하여 특정 유전자를 발현에 관여하는 것으로 알려져 있다. Cytochrome P450 Aromatase (간략히, aromatase)는 steroid hormone을 합성하는 마지막 단계에서 androgens을 estrogens으로 전환시키는데 관여하는 효소이다. Aromatase의 substrate (기질)로 사용되는 androgen에는 androstenedione과 testosterone 등이 있으며, 최종 산물로써 estrone(E1)이나 17$\beta$-estradiol(E2) 등의 estrogen이 생성된다. Aromatase는 steroidogenic tissues의 세포내 골지체에 존재하는 것으로 알려져 있으며, NADPH-cytochrome P450 reductase와 함께 복합체로써 존재한다. NADPH-cytochrome P450 reductase는 다른 steroid hormone에 관여하는 효소들과도 복합체를 형성하여 다른 steroid hormone을 합성할 수 있으므로, 어떤 조직에서 여성호르몬이 만들어질 수 있느냐 하는 것은 그 조직에서 aromatase 단백질이 만들어지느냐에 따라서 결정된다.

• Journal of Life Science
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• v.24 no.1
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• pp.98-103
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• 2014

NAD(P)H quinone oxidoreductase 1 (NQO1) is a flavoprotein that catalyzes the two electron reduction of diverse substrates, including quinones. It uses NADH or NADPH as a cofactor for enzymatic machinery. In the metabolism of quinones, NQO1 has two conflicting functions because of the different stability of converted hydroquinones. The stable form of hydroquinone is excreted from cells by conjugation with glutathione or glucuronic acid. The unstable form of hydroquinone induces cell death by induction of oxidative stress and DNA damage. Certain quinones known as bio-reductive agents have a cytotoxic function following reduction by NQO1. Bio-reductive agents, such as ${\beta}$-lapachone or mitomycin C, induce the depletion of NAD(P)H and the generation of oxidative stress in an NQO1-dependent manner. NQO1 is highly expressed in several cancer tissues. Therefore, NQO1 is a good therapeutic target for cancer treatment with bio-reductive agents.

• Journal of Acupuncture Research
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• v.26 no.6
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• pp.51-65
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• 2009

Objectives : This study was built to investigate the effect of Trachelospermi Caulis herbal-acupuncture on the Collagen-induced arthritis(CIA) in rats. Methods : Arthritis was induced by intradermal injection of Bovine type II collagen solution into base of tail. Experimental group were divided into 5 groups ; Normal(N) group, Control(C) group, Trachelospermi Caulis high(TH) group, Trachelospermi Caulis low(TL) group, Saline(S) group(n=7 for each group). Normal group was had no management. Control group was injected with Bovine type II collagen solution and taken no treatment. Trachelospermi Caulis high group was injected with Bovine type II collagen solution and taken high-intensity(10mg/kg) herbal-acupuncture treatment on $ST_{36}$. Trachelospermi Caulis low group was injected with Bovine type II collagen solution and taken low-intensity(5mg/kg) herbal-acupuncture treatment on $ST_{36}$. Saline group was injected with Bovine type II collagen solution and taken saline injection on $ST_{36}$. Body weight, paw edema volume and ankle joint thickness were measured during experimental day. On the last experimental day, we analyzed WBC count, TNF-$\alpha$ & IL-$1{\beta}$ concentration, c-fos immunohistochemistry and NADPH-d histochemistry for evaluating the effect of Trachelospermi Caulis herbal-acupuncture. Results : The results were as follows ; 1. In the change of paw edema volume, TH group only has significant difference compared with C group. 2. In the change of ankle joint thickness, TH group only has significant difference compared with C group. 3. In WBC count of serum, TH, TL groups have significant decrease compared with C group. 4. In TNF-$\alpha$ concentration of effusion, TH, TL groups have significant decrease compared with C group. and TH group has significant decrease compared with TL group. 5. In IL-$1{\beta}$ concentration of effusion, TH, TL groups have significant decrease compared with C group. and TH group has significant decrease compared with TL group. 6. In c-fos positive neurons of S1S2(cortex) region, TH, TL, S groups have significant decrease compared with C group. 7. In NADPH-d positive neurons of CPu(caudate putamen) region, TH, TL groups have significant decrease compared with C group. 8. In NADPH-d positive neurons of Tfp(transverse fibers of pons) region, TH, TL, S groups have significant decrease compared with C group. and TH group has significant decrease compared with S group. Conclusions : According to above results, we hope that Trachelospermi Caulis herbal-acupuncture may have the effect that decreases progression and development of CIA. And it can be suggested that Trachelospermi Caulis herbal-acupuncture may reduce the expression of c-fos and NOS.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.91-102
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• 1992

In $Ca^{++}$ containing media, arachidonic acid markedly stimulated superoxide and $H_2O_2$ generation and activated NADPH oxidase. In $Ca^{++}$ free media, stimulatory action of arachidonic acid on NADPH oxidase was not detected. Arachidonic acid-stimulated respiratory burst was inhibited by EGTA, TMB-8, verapamil, diltiazem, nifedipine, dibucaine, lidocaine, CCCP, 2,4-dinitrophenol, sodium arsenate, chlorpromazine, theophylline, $HgCl_2$, PCMB and PCMBSA but not affected by tetrodotoxin, tetraethylammonium chloride and procaine. EGTA almost completely inhibited release of ${\beta}-glucuronidase$ by arachidonic acid and verapamil, CCCP and theophylline slightly inhibited it, whereas dibucaine did not show any significant effect. Arachidonic acid induced $Ca^{++}$ release from intact neutrophils and it was decreased by TMB-8. Arachidonic acid-induced elevation of intracellular free $Ca^{++}$ level was inhibited by EGTA and CCCP and slightly inhibited by TMB-8. Amount of intracellular free $Ca^{++}$ increased by either arachidonic acid plus verapamil or arachidonic acid plus dibucaine was greater than that by arachidonic acid alone. These results suggest that various changes of biochemical events may be implicated in the functional expression in neutrophils activated by arachidonic acid. Arachidonic acid appears to elevate cytosolic free $Ca^{++}$ level by stimulating $Ca^{++}$ release from intracellular $Ca^{++}$ storage sites. During activation of neutrophils, $Ca^{++}$ influx and efflux may be accomplished, simultaneously.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.214.2-215
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• 2003

Reactive oxygen species play an important role in aging. carcinogenesis, and certain neurological disorders of human beings in addition to the host-defensive mechanism of inflammatory response. Murine macrophages Raw264.7 released superoxide anions via NADPH oxidase complex and nitric oxide (NO) via iNOS synthase when the cells were stimulated with unopsonized zymosan binding to complement receptor. (omitted)

• Toxicological Research
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• v.30 no.3
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• pp.149-157
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• 2014

Smoking is one of the most serious but preventable causes of cardiovascular disease (CVD). Key aspects of pathological process associated with smoking include endothelial dysfunction, a prothrombotic state, inflammation, altered lipid metabolism, and hypoxia. Multiple molecular events are involved in smoking-induced CVD. However, the dysregulations of reactive oxygen species (ROS) generation and metabolism mainly contribute to the development of diverse CVDs, and NADPH oxidase (NOX) has been established as a source of ROS responsible for the pathogenesis of CVD. NOX activation and resultant ROS production by cigarette smoke (CS) treatment have been widely observed in isolated blood vessels and cultured vascular cells, including endothelial and smooth muscle cells. NOX-mediated oxidative stress has also been demonstrated in animal studies. Of the various NOX isoforms, NOX2 has been reported to mediate ROS generation by CS, but other isoforms were not tested thoroughly. Of the many CS constituents, nicotine, methyl vinyl ketone, and ${\alpha}$,${\beta}$-unsaturated aldehydes, such as, acrolein and crotonaldehyde, appear to be primarily responsible for NOX-mediated cytotoxicity, but additional validation will be needed. Human epidemiological studies have reported relationships between polymorphisms in the CYBA gene encoding p22phox, a catalytic subunit of NOX and susceptibility to smoking-related CVDs. In particular, G allele carriers of A640G and $-930^{A/G}$ polymorphisms were found to be vulnerable to smoking-induced cardiovascular toxicity, but results for C242T studies are conflicting. On the whole, evidence implicates the etiological role of NOX in smoking-induced CVD, but the clinical relevance of NOX activation by smoking and its contribution to CVD require further validation in human studies. A detailed understanding of the role of NOX would be helpful to assess the risk of smoking to human health, to define high-risk subgroups, and to develop strategies to prevent or treat smoking-induced CVD.

• Journal of Microbiology
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• v.35 no.4
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• pp.360-364
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• 1997

A ${\beta}$-ketothiolase was purified 180-fold from the cell extracts of Alcaligenes sp. SH-69 by a series of chromatography on DEAE-Dephadex A-50, Sephacryl S-200, and hydrozyapatitie columns, The optimum pH values of the partially purified enzyme were 7.5 for condensation reaction and 8.3 for thiolysis reaction were estimated to be 0.12mM and $18.7\;{\mu}M$, respectively. The $K_m$ valued for acetoacetyl-CoA and free CoASH in the thiolusis in the condensation reaction was 0.70mM. The condensation reaction of the ${\beta}$-ketothiolase was inhibited even by low concentrations of free CoASH($K_i=30.4{\mu}M$). Pretreatment of the enzyme with NADH and NADPH markedly inhibited the thiolysis reaction of the enzyme. The potent inhibition of the enzyme by sulfhydryl reagents suggests the involvement of cystein residue in the active site.