• The Korean Journal of Physiology and Pharmacology
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• v.24 no.3
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• pp.213-221
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• 2020

Salvianolic acid B (SAB) is an active phytocomponent of a popular Chinese herb called Radix Salvia militiorrhiza with numerous biological properties. The anti-psoriasis activity of SAB was examined by evaluating various psoriasis inflammatory and keratin markers against imiquimod (IMQ)-induced psoriasis on BALB/c mice. Totally 50 healthy BALB/c mice were evenly divided into 5 groups including control, drug control (SAB; 40 mg/kg), IMQ-induced psoriasis (5%), IMQ exposure and treated with SAB (40 mg/kg), or standard methotrexate (MTX; 1 mg/kg). Mice supplemented with either SAB or MTX significantly lowered the values of psoriasis area severity index (PASI), erythema, scaling, skin thickness, inflammatory markers (interleukin [IL]-22/23/17A/1β/6) and lipid peroxidation product (malondialdehyde). Also, IMQ exposed BALB/c mice treated with SAB or MTX display lesser histopathological changes with enhanced antioxidant activities (catalase, superoxide dismutase). Moreover, the protein expression of keratin markers (K16 and K17) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling proteins (pAkt/Akt and pPI3K/PI3K) were significantly downregulated after administration with SAB and MTX as compared with IMQ induced mice. Taking together, SAB and MTX significantly ameliorate psoriatic changes by inhibiting psoriatic inflammatory and keratin markers through abolishing PI3K/Akt signaling pathway. However, further studies (clinical trials) are needed to confirm the anti-psoriatic property of SAB before recommending to psoriasis patients.

• The Korean Journal of Food & Health Convergence
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• v.5 no.2
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• pp.27-34
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• 2019

RNases plays a pivotal role in biological system and different RNases are known for their various functions like angiogenesis, immunological response, antiviral, antitumour activity and apoptosis. In which anti tumour activity of RNase is proved to improve genome stability in normal cells up to some extent. RNases like RNase L shows antiviral and antitumour activities against virus infected cells and cancer cells through 2'-5' oligo adenylate pathway and induces RNaseL dependent apoptosis where as RNase A modulates various proliferative pathways like MAP kinase, JNK, TGF-${\beta}$ and activates apoptosis in cancer cells and promotes immunological response through processing of Ags. IRE1 RNase acts as both tumour suppressor gene and oncogene in normal and cancer cells and involved in both antitumour and tumorigenic activities. RNase III upregulates miRNA in cancer cells there by acting via posttranscriptional level and proven to be effective against colorectal adeno carcinoma. In addition to this IRE1 RNase is a double edged sword through RIDD pathway in ER (18). To some of the cancers expressing c-myc IRE1 acts as tumour suppressor where as in cancers where myc is downregulated IRE1 acts as tumour provoking through RIDD pathway (18). Thus RNases play vital role in regulating the genome stability.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.2
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• pp.95-100
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• 2004

Ischemic preconditioning (IPC) has been accepted as a heart protection phenomenon against ischemia and reperfusion (I/R) injury. The activation of ATP-sensitive potassium $(K_{ATP})$ channels and the release of myocardial nitric oxide (NO) induced by IPC were demonstrated as the triggers or mediators of IPC. A common action mechanism of NO is a direct or indirect increase in tissue cGMP content. Furthermore, cGMP has also been shown to contribute cardiac protective effect to reduce heart I/R-induced infarction. The present investigation tested the hypothesis that $K_{ATP}$ channels attenuate DNA strand breaks and oxidative damage in an in vitro model of I/R utilizing rat ventricular myocytes. We estimated DNA strand breaks and oxidative damage by mean of single cell gel electrophoresis with endonuclease III cutting sites (comet assay). In the I/R model, the level of DNA damage increased massively. Preconditioning with a single 5-min anoxia, diazoxide $(100\;{\mu}M)$, SNAP $(300\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP) $(100\;{\mu}M)$ followed by 15 min reoxygenation reduced DNA damage level against subsequent 30 min anoxia and 60 min reoxygenation. These protective effects were blocked by the concomitant presence of glibenclamide $(50\;{\mu}M)$, 5-hydroxydecanoate (5-HD) $(100\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer (Rp-8-pCPT-cGMP) $(100\;{\mu}M)$. These results suggest that NO-cGMP-protein kinase G (PKG) pathway contributes to cardioprotective effect of $K_{ATP}$ channels in rat ventricular myocytes.

• Molecular & Cellular Toxicology
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• v.4 no.3
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• pp.177-182
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• 2008

Caveolin proteins are mediators of cell death or the survival of injured cells, and they are inhibitors of various signaling pathways. The expression of caveolin-, which is involved in the protein kinase A (PKA) signaling pathway, was examined in the differentiated mouse vestibular cell line UB/UE-1 after gentamicin ototoxicity. Caveolae in the vestibular hair cell of healthy guinea pigs were observed through an electron microscope. UB/UE-1 cells were cultured at 95% $CO_2$ with 5% $O_2$ at $33^{\circ}C$ for 48 hours and at 95% $CO_2$ with 5% $O_2$ at $39^{\circ}C$ for 24 hours for differentiation. Cells were treated with 1 mM gentamicin, 0.02 mM H89 (PKA inhibitor), and then incubated for 24 hours. Caveolin-1 expression was examined by western blotting and PKA activity by a $PepTag^{(R)}$ assay. Caveolae were observed in the vestibular hair cells of healthy guinea pigs by electron microscopy. Caveolin-1 was expressed spontaneously in differentiated UB/UE-1 cells and increased after gentamicin treatment. PKA was also over-activated by gentamicin treatment. Both gentamicin-induced caveolin-1 expression and PKA over-activation were inhibited by H89. These results indicate that gentamicin-induced caveolin-1 expression is mediated by the PKA signaling pathway. We conclude that caveolae/ caveolin activity, induced via a PKA signaling pathway, may be one of the mechanisms of gentamicin-induced ototoxicity.

• Childhood Kidney Diseases
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• v.10 no.1
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• pp.45-51
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• 2006

Hypocomplementemia is found in all types of membranoproliferative glomerulonephritis (MPGN) but not in all patients. Hypocomplementemia can be ascribed to at least two circulating complement reactive modalities. The activation of the classical pathway produced by circulating immune complexes and the presence in the blood of anticomplement autoantibodies, called 'nephritic factor'(NF). The activation of the classical pathway by circulating immune complexes is probably the major mechanism responsible for hypocomplementemia in idiopathic MPGN type I. Nephritic factors have been shown to be responsible for the hypocomplementemia in both MPGN type II and III. NFa is probably the major mechanism responsible for the hypocomplementemia of idiopathic MPGN type II. NFt appears to be solely responsible for the hypocomplementemia in MPGN type III. Judging from the complement profile, NFt also may be present in some patients with MPGN type I. Although infection by meningococcus has been associated with deficiency of any of the plasmatic proteins of complement, it more commonly involves deficiency of the terminal components of the complement pathway(C5-C9). We experienced a patient who had MPGN and meningococcal meningitis. We examined the complement level and significantly lower levels of C3, C5 were found persistently. C7 was low at first and it returned to normal range after 2 months. C9 was normal at first, and was low after 2 months. This is the first reported case in which MPGN with meningococcal meningitis occurred.

• Archives of Pharmacal Research
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• v.20 no.5
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• pp.420-424
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• 1997

By human intestinal bacteria, saikosaponin c was transformed to four metabolites, prosaikogenin E1 (E1) prosaikogenin E2 (E2), prosaikogenin E3 (E3) and saikogenin E. Metabolic time course of saikosaponin c was as follows; in early time, saikosaponin c was converted to E1 and E2, and then these were transformed to saikogenin E via E3. Also, this metabolic pathway was similar to the metabolism of saikosaponin c by rat intestinal bacteria. Bacteroides JY-6 and Bacteroides YK-4, the bacteria isolated from human intestinal bacteria, could transform saikosaponin c to E via E1 (or E2) and E3. However, these bacteria were not able to directly transform El and E2 to saikogenin E. Naringin was mainly transformed to naringenin by human intestinal bacteria. The minor metabolic pathway transformed naringin to naringenin via prunin. By JY-6 or YK-4, naringin was metabolized to naringenin only via prunin.

• Applied Biological Chemistry
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• v.51 no.4
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• pp.258-262
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• 2008

To establish the biosynthetic pathway of decursin in Angelica gigas Nakai, feeding experiment with stable isotope-labeled precursors were conducted. Umbelliferone and decursin were labeled with deuterium at C-3. The umbelliferone, the decursin, and other commercially available putative precursors, L-phenylalanine-ring-$d_5$ and trans-cinnamic acid-$d_7$, were fed to the hairy root culture of A. gigas. Each deuterated compound was incorporated into decursinol, decursinol angelate, and decursin as determined by mass spectrometric analysis. These findings confirmed the coumarin biosynthesis pathway sequence is composed of phenylalanine, cinnamic acid, umbelliferone, decursinol, and decursin.

• Macromolecular Research
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• v.16 no.1
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• pp.1-5
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• 2008

The enzymatic hydrolysis of chitin has been studied for almost a century, and early work established that at least two enzymes are required, a chitinase that mainly yields the disaccharide N,N'-diacetylchitobiose, or $(GlcNAc)_2$, and a "chitobiase", or ${\beta}$-N-acetylglucosaminidase, which gives the final product G1cNAc. This pathway has not been completely identified but has remained the central concept for the chitin catabolism through the $20^{th}$ century1 including in marine bacteria. However, the chitin catabolic cascade is quite complex, as described in this review. This report describes three biologically functional genes involved in the chitin catabolic cascade of Vibrios in an attempt to better understand the metabolic pathway of chitin.

• Korean Journal of Ecology and Environment
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• v.34 no.1 s.93
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• pp.54-61
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• 2001

Changes in methanogenic pathway at low temperature were studied by incubation experiments of sediment slurries from the littoral zone of Reservoir Paldang. Methane production rates in sediment slurries increased exponentially between $5＾{\circ}C$and $45＾{\circ}C$, reached a maximum rate of $7.4\;nmol\;{\cdot}\;g^{-1}\;{\cdot}\;h^{-1}$ at $45＾{\circ}C$, and then declined to low rate. The shift of incubation temperature from high temperature ($30＾{\circ}C$) to lowtemperature ($15＾{\circ}C$) resulted in a decrease of methane production rate and of hydrogen accumulation rate, and the transient accumulation of acetate concentration. Chlorofarm inhibited perfectly methanogenesis and resulted in the accumulation of hydrogen and acetate as immediate precursors for metltane formation at both incubation temperatures of $15＾{\circ}C$ and $30＾{\circ}C$. In terms of equivalent methane which was calculated from the two intermediary metabolites accumulated in absence of methanogenesis, methane production from acetate was accounted for 14% of total methanogenesis at $30＾{\circ}C$ and 75% at $15＾{\circ}C$, respectively. When the high acetate concentrations above 19 mM were added to sediment slurries, methane production was inhibited at the low temperature ($15＾{\circ}C$) . Our results demonstrate that contribution of acetate on methanogenesis increases at low temperature, but this pathway is inhibited by high concentration of acetate. Therefore acetate-utilizing methanogensis appears to be a key reaction at low temperature, and seems to be one of bottlenecks of the low temperature anaerobic degradation of organic matter in littoral sediments of the reservoir.

• BMB Reports
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• v.47 no.11
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• pp.609-618
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• 2014

DNA methylation at cytosines (5mC) is a major epigenetic modification involved in the regulation of multiple biological processes in mammals. How methylation is reversed was until recently poorly understood. The family of dioxygenases commonly known as Ten-eleven translocation (Tet) proteins are responsible for the oxidation of 5mC into three new forms, 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Current models link Tet-mediated 5mC oxidation with active DNA demethylation. The higher oxidation products (5fC and 5caC) are recognized and excised by the DNA glycosylase TDG via the base excision repair pathway. Like DNA methyltransferases, Tet enzymes are important for embryonic development. We will examine the mechanism and biological significance of Tet-mediated 5mC oxidation in the context of pronuclear DNA demethylation in mouse early embryos. In contrast to its role in active demethylation in the germ cells and early embryo, a number of lines of evidence suggest that the intragenic 5hmC present in brain may act as a stable mark instead. This short review explores mechanistic aspects of TET oxidation activity, the impact Tet enzymes have on epigenome organization and their contribution to the regulation of early embryonic and neuronal development.