• Biomolecules & Therapeutics
• /
• 제17권4호
• /
• pp.455-460
• /
• 2009

Foods of plant origin, especially fruits and vegetables, have attracted attention because of their potential benefits to human health. In this report, Rubi Fructus (RF), the dried unripe fruit of Rubus coreanus Miq (Rosaceae) and ellagic acid (EA) purified from RF were used to test their potential hepatoprotective effect against acetaminophen (AAP)-induced hepatotoxicity in rats. RF extract (RFext) and EA reduced the elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in serum and the content of lipid peroxide in liver by AAP administration, while the increment of the cellular glutathione (GSH) content and the induction of glutathione S-transferase (GST) and glutathione peroxidase (GSH-PX) which were decreased by AAP administration. RFext and EA from RFext did not affect the two major form of cytochrome P450s, cytochrome P450 2E1 (CYP2E1) and cytochrome P450 1A2 (CYP1A2), but downregulated the cytochrome P450 3A4 (CYP3A4) related to the conversion of AAP to N-acetyl-P-benzoquinone imine (NAPQI). These results suggest that RFext and EA from RF exhibit a hepatoprotective effect not only by increasing antioxidant activities but also by down-regulating CYP3A4 in the AAP-intoxicated rat.

• Journal of Microbiology and Biotechnology
• /
• 제18권6호
• /
• pp.1101-1108
• /
• 2008

Geldanamycin and its analogs are important anticancer agents that inhibit the newly targeted heat-shock protein (Hsp) 90, which is a chaperone protein in eukaryotic cells. To resolve which geldanamycin biosynthetic genes are responsible for particular post-polyketide synthase (PKS) processing steps and in which order the reactions occur, we individually inactivated candidate genes in Streptomyces hygroscopicus subsp. duamyceticus JCM4427 and isolated and elucidated the structures of intermediates from each mutant. The results indicated that gel7 governs at least one of the benzoquinone ring oxidation steps. The gel16 was found to be involved in double-bond formation between C-4 and C-5 of 4,5-dihydrogeldanamycin, which confirmed our previous findings that this double bond is reduced during the post-PKS modification of the polyketide assembly. In addition, pro-geldanamycin, which does not possess a double bond at C-4/5, was purified from the gel7 and gel8 double-gene-inactivated mutant.

• 한국식품영양과학회지
• /
• 제28권5호
• /
• pp.1113-1123
• /
• 1999

The purpose of this study was to see the effect of anti inflammatory and analgesic action of the glucosamine hydrochloride(GA HCl) or taurine. Male Sprague Dawley rats(100~250g) and ICR mice(20 ~30g) were used. Experimental groups were divided into seven groups, one control group given as saline and six groups given as oral administration of GA HCl or taurine; GA HCl 250mg/kg, b.w group, taurine 250mg/kg, b.w group, GA HCl 250mg/kg, b.w＋taurine 250mg/kg, b.w group, GA HCl 500mg/kg, b.w group, taurine 500mg/kg, b.w group, GA HCl 500mg/kg, b.w＋taurine 500mg/kg, b.w group. Carrageenan induced edema test were shown to be significantly inhibited in the GA HCl 250mg/kg group and taurine 250mg/kg group compared to the control group, but the GA HCl 500mg/kg＋taurine 500mg/kg group were significantly inhibited than the control group. Capillary permeability test were shown to be sig nificantly inhibited in the taurine 500mg/kg group, but the GA HCl 500mg/kg＋taurine 500mg/kg group were significantly inhibited than the control group. Leucocyte emigration test were shown to be significantly inhibited in the GA HCl 250mg/kg＋ taurine 250mg/kg group and GA HCl 500mg/kg＋taurine 500mg/kg group compared to the control group. Acetic acid, Phenyl p benzoquinone writhing syndrome were shown to be significantly inhibited in the GA HCl 500mg/kg＋taurine 500mg/kg group compared to the control group. Inhibitory action against COX 1 and COX 2 were not significantly inhibited in the experimental group. These results suggest that the combined administration of the GA HCl and taurine have potential action in anti inflammatory and analgesic action.

• Clinical and Experimental Pediatrics
• /
• 제49권3호
• /
• pp.329-331
• /
• 2006

알캅톤뇨증은 상염색체 열성으로 유전하는 드문 질환으로 homogentisic acid oxidase 결핍에 의해 homogentisic acid가 체내 축적되고 소변으로 다량 배설되는 대사 이상 질환이다. 주로 도미니카 공화국과 슬로바키아에서 보고되고 있으나 한국에는 아직 보고된 바 없다. 증상으로는 소아 때에는 주로 배뇨 후 시간이 지나면 소변 색이 검어지는 특징이 보이고, 나이가 들면서 연골과 결체 조직의 착색, 관절염, 갈색증, 심장 질환, 신장 질환 등이 발생할 수 있다. 특별히 효과가 입증된 치료제는 없는 것으로 보고되고 있고, 진단은 뇨유기산분석을 통해 할 수 있다. 저자들은 내원 당시 13개월이었던 여자 환아에서 기저귀에 묻은 소변이 시간이 지나면서 연분홍 갈색빛을 보여 시행한 뇨유기산분석에서 homogentisic acid (normal range <2 mmol/molCr)가 1,158.3 mmol/molCr로 현저한 증가 소견을 보여 보고하는 바이다. 재검사에서도 역시 910.7 mmol/molCr 로 증가된 소견을 보였으며 환아 신체 어디에서도 연갈색이나 검은색의 착색된 부위를 찾을 수 없었다. 환아는 현재 ascorbic acid 투여하며 추적관찰 중이다.

• Journal of Photoscience
• /
• 제7권1호
• /
• pp.1-4
• /
• 2000

The photosensory ciliates Blepharisma japonicum and Stentor coeruleus use the hypericin-derived pigments blepharismin and stentorin, respectively, as photoreceptor chromophores. Fluorescence quenching studies have shown that the first excited singlet state of hypericin and the purified chromophores blepharismin and stentorin can be deactivated by electron transfer to an acceptor molecule with a suitable reducing potential [1,2]. This paper reports the result of a series of photobehavioral experiments performed with the aim to ascertain if the same electron accepters which quench the photoreceptor pigment fluorescence in vitro may also compete with the native acceptor molecule in its natural physiological environment. Individual cell trajectories were examined before and after light stimulation, in the presence and in the absence of potential "in vivo" electron accepters, with a microvideo-recording apparatus. Our data, on Blepharisma cells, showed that as the negative reduction potential of the electron acceptor increases, a pronounced decrease in cell photoresponsiveness was detected. A dramatic effect on cell photoresponsiveness was noticed in the presence of 1,4-benzoquinone that has the lowest negative reduction potential. Such an effect on the percentage of photoreacting cells was moderate in the case of 1,4-naphthoquinone, with a relatively higher negative reduction potential. In the presence of benzophenone, which has the highest negative reduction potential, no significant effect on photoreacting cells was noticed. Our results can support the hypothesis that in the pigment granules such a light-induced charge transfer from excited blepharismin to a suitable electron acceptor triggers sensory transduction processes in B. japonicum.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
• /
• pp.178-178
• /
• 1998

We reported that the hexane fraction of Torilis Fructus have an anti-inflammatory and analgesic effect. Therefore, in order to isolate the active compound, the hexan fraction of Torilis Fructus was chromatographed on silica gel column. The subfraction of hexane fraction was crystallized as colorless stout needles. The chemical structure of this compound was verified to be torilin through m.p., UV, IR, GC-MS, and NMR spectral data. In pharmacological tests, torilin exhibited strong anticarrageenan activity at the dose of 90 and 270 mg/kg, p.o. in rats, and it had inhibitory effect on the vascular permeability at the dose of 30 and 90 mg/kg, p.o. in mice. Torilin showed potent inhibition of leucocyte emigration in CMC-pouch at the dose of 3 and 9 mg/rat, s.c. Torilin have the analgesic effect at the dose of 30, 90 and 270 mg/kg, p.o. in both of the acetic acid- and phenyl-p-benzoquinone-induced writhing syndrome. It also increased the pain threshold at the dose of 30, 90 and 270 mg/kg, p.o. in the tail pressure method and the Randall-Selitto method. Torilin did not show a hypothermic action at the dose of 30 and 90 mg/kg, p.o. in mice. The acute toxicity of torilin was very weak: the LD$\_$50/ value was more than 5000 mg/kg, p.o. and 2000 mg/kg, Lp. in mice. From the above mentioned results, it was suggested that torilin had potent anti-inflammatory and analgesic activities in animals.

• Archives of Pharmacal Research
• /
• 제26권12호
• /
• pp.1047-1054
• /
• 2003

Molecular chaperones have a crucial role in the folding of nascent polypeptides in endoplasmic reticulum. Some of them are known to be sensitive to the modification by electrophilic metabolites of organic pro-toxicants. In order to identify chaperone proteins sensitive to alkyators, ER extract was subjected to alkylation by 4-acetamido-4 -maleimidyl-stilbene-2,2 -disulfonate (AMS), and subsequent SDS-PAGE analyses. Protein spots, with molecular mass of 160, 100, 57 and 36 kDa, were found to be sensitive to AMS alkylation, and one abundant chaperon protein was identified to be protein disulfide isomerase (PDI) in comparison with the purified PDI. To see the reactivity of PDI with cysteine alkylators, the reduced form ($PDI_{red}$) of PDI was incubated with various alkylators containing Michael acceptor structure for 30 min at $38^{\circ}C$ at pH 6.3, and the remaining activity was determined by the insulin reduction assay. Iodoacetamide or N-ethylmaleimide at 0.1 mM remarkably inactivated $PDI_{red}$ with N-ethylmaleimide being more potent than iodoacetamide. A partial inactivation of $PDI_{oxid}$ was expressed by iodoacetamide, but not N-ethylmaleimide (NEM) at pH 6.3. Of Michael acceptor compounds tested, 1,4-benzoquinone ($IC_{50}, 15 \mu$ M) was the most potent, followed by 4-hydroxy-2-nonenal and 1,4-naphthoquinone. In contrast, 1,2-naphthoquinone, devoid of a remarkable inactivation action, was effective to cause the oxidative conversion of $PDI_{red}$ to $PDI_{oxid}$. Thus, the action of Michael acceptor compounds differed greatly depending on their structure. Based on these, it is proposed that POI, one of chaperone proteins in ER, could be susceptible to endogenous or xenobiotic Michael acceptor compounds in vivo system.

• 대한의생명과학회지
• /
• 제15권1호
• /
• pp.97-99
• /
• 2009

Geldanamycin is a benzoquinone ansamycin antibiotic that binds to cytosol HSP90 (Heat Shock Protein 90) and changes its biological function. HSP90 is involved in the intracellular important roles for the regulation of the cell cycle, cell growth, cell survival, apoptosis, angiogenesis and oncogenesis. To identify genes expressed during geldanamycin treatment against neurons of rats (PC12 cells), DNA microarray method was used. We have isolated 2 gene groups (up-or down-regulated genes) which are geldanamycin differentially expressed in neurons. Granzyme B is the gene most significantly increased among 204 up-regulated genes (more than 2 fold over-expression) and Chemokine (C-C motif) ligand 20 is the gene most dramatically decreased among 491 down-regulated genes (more than 2 fold down-expression). The gene increased expression of Cxc110, Cyp11a1, Gadd45a, Gja1, Gpx2, Ifua4, Inpp5e, Sox4, and Stip1 are involved stress-response gene, and Cryab, Dnaja1, Hspa1a, Hspa8, Hspca, Hspcb, Hspd1, Hspd1, and Hsph1 are strongly associated with protein folding. Cell cycle associated genes (Bc13, Brca2, Ccnf, Cdk2, Ddit3, Dusp6, E2f1, Illa, and Junb) and inflammatory response associated genes (Cc12, Cc120, Cxc12, Il23a, Nos2, Nppb, Tgfb1, Tlr2, and Tnt) are down-regulated more than 2 times by geldanamycin treatment. We found that geldanamycin is related to expression of many genes associated with stress response, protein folding, cell cycle, and inflammation by DNA microarray analysis. Further experimental molecular studies will be needed to figure out the exact biological function of various genes described above and the physiological change of neuronal cells by geldanamycin. The resulting data will give the one of the good clues for understanding of geldanamycin under molecular level in the neurons.

• Molecules and Cells
• /
• 제39권6호
• /
• pp.477-483
• /
• 2016

Heat shock factors (Hsfs) are central regulators of abiotic stress responses, especially heat stress responses, in plants. In the current study, we characterized the activity of the Hsf gene HsfA3 in Arabidopsis under oxidative stress conditions. HsfA3 transcription in seedlings was induced by reactive oxygen species (ROS), exogenous hydrogen peroxide ($H_2O_2$), and an endogenous $H_2O_2$ propagator, 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB). HsfA3-overexpressing transgenic plants exhibited increased oxidative stress tolerance compared to untransformed wild-type plants (WT), as revealed by changes in fresh weight, chlorophyll fluorescence, and ion leakage under light conditions. The expression of several genes encoding galactinol synthase (GolS), a key enzyme in the biosynthesis of raffinose family oligosaccharides (RFOs), which function as antioxidants in plant cells, was induced in HsfA3 overexpressors. In addition, galactinol levels were higher in HsfA3 overexpressors than in WT under unstressed conditions. In transient transactivation assays using Arabidopsis leaf protoplasts, HsfA3 activated the transcription of a reporter gene driven by the GolS1 or GolS2 promoter. Electrophoretic mobility shift assays showed that GolS1 and GolS2 are directly regulated by HsfA3. Taken together, these findings provide evidence that GolS1 and GolS2 are directly regulated by HsfA3 and that GolS enzymes play an important role in improving oxidative stress tolerance by increasing galactinol biosynthesis in Arabidopsis.

• Bulletin of the Korean Chemical Society
• /
• 제15권2호
• /
• pp.132-138
• /
• 1994

Bis(diethylamino)aluminum hydride was utilized in a systematic study of the approximate rates and stoichiometry of the reaction of excess reagent with 55 selected organic compounds containing representative functional groups under standardized conditions (THF, $0^{\circ}C$, reagent to compound=4 : 1) in order to define the characteristics of the reagent for selective reductions. The reducing action of BEAH was also compared with that of the parent aluminum hydride. The reducing action of the reagent is quite similar to that of aluminum hydride, but the reducing power is much weaker. Aldehydes and ketones were readily reduced in 1-3 h to the corresponding alcohols. However, unexpectedly, a ready involvement of the double bond in cinnamaldehyde was realized to afford hydrocinnamyl alcohol. The introduction of diethylamino group to the parent aluminum hydride appears not to be appreciably influential in stereoselectivity on the reduction of cyclic ketones. Both p-benzoquinone and anthraquinone utilized 2 equiv of hydride readily without evolution of hydrogen, proceeded cleanly to the 1,4-reduction products. Carboxylic acids and acid chlorides underwent reduction to alcohols slowly, whereas cyclic anhydrides utilized only 2 equiv of hydride slowly to the corresponding hydroxylacids. Especially, benzoic acid with a limiting amount of hydride was reduced to benzaldehyde in a yield of 80%. Esters and lactones were also readily reduced to alcohols. Epoxides examined all reacted slowly to give the ring-opened products. Primary and tertiary amides utilized 1 equiv of hydride fast and further hydride utilization was quite slow. The examination for possibility of achieving a partial reduction to aldehydes was also performed. Among them, benzamide and N,N-dimethylbenzamide gave ca, 90% yields of benzaldehyde. Both the nitriles examined were also slowly reduced to the amines. Unexpectedly, both aliphatic and aromatic nitro compounds proved to be relatively reactive to the reagent. On the other hand, azo- and azoxybenzenes were quite inert to BEAH. Cyclohexanone oxime liberated 1 equiv of hydrogen and utilized 1 equiv of hydride for reduction, corresponding to N-hydroxycyclohexylamine. Pyridine ring compounds were also slowly attacked. Disulfides were readily reduced with hydrogen evolution to the thiols, and dimethyl sulfoxide and diphenyl sulfone were also rapidly reduced to the sulfides.