• Journal of Applied Biological Chemistry
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• v.64 no.4
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• pp.375-382
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• 2021

Biorenovation is a microbial enzyme-based structural modification of component compounds in natural products and synthetic compounds including plant extracts with the potential benefits of improved biological activities compared with its reaction substrates. In this study, we investigated the anti-inflammatory activity of Distylium racemosum leaf extract and D. racemosum leaf biorenovation extract (DLB). As a result, DLB inhibited nitric oxide, prostaglandin E2, and inflammatory cytokines including tumor necrosis factor-α, interleukin-6, interleukin-1β at non-toxic concentrations. In addition, DLB significantly inhibited inducible nitric oxide synthase and cyclooxygenase-2 on LPS-treated RAW 264.7 macrophages. Based on these results, we suggest that the DLB could be used as a potent anti-inflammatory agents. It also suggests that the application of biological evolution has potential usefulness to increase the practical value of natural products.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.199-207
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• 1998

Ginseng saponin (G5) purified from Panax ginseng, increase renal blood flow in rats. Nitric oxide (NO) is thought to be a substance endogenously released by G5 in preconstricted lungs and cultured endothelial cells. The present study aims to determine whether G5 could stimulate endogenous 1'elease of NO in rat kidney and urine levels of the stable NO metabolites, nitrite (NO,) and nitrate (NO,) and urinary COMP levels were measured 8 hr after a single intraperitoneal injection of GS (200 mg/kg) Into rats. The effects of the WO synthesis inhibitor, Nu-nitro-L-arginine methyl ester, .1nd the NO precursor, L-arginine, on the G5-induced changes were also determined. The activity of NO synthase, as determined by conversion of ('"C)-L-arginine to ('"C)-L-citrulline, in whole kidney, glomeruli and cortical tubules were also investigated. A single injection of GS resulted in endogenous production of NO as reflected by increase in serum and urine levels of N021N03 and urinary cGMP levels, which were inhibited by the addition o ( N-nitro-L-arginine methyl ester and restored fly L-arginine. GS also stimulated the activity of NO synthase in whole kidney as well as glomeruli and cortical tubules, and Nu-nitro-L-arginine methyl tilter significantly prevented this increase. In conclusion, GS stimulates endogenous NO production and thus, may play a protective role 1 11 the kidney by modulating renal blood flow.

• Journal of Microbiology and Biotechnology
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• v.15 no.4
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• pp.895-898
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• 2005

In the course of searching for potent chitin synthase 1 inhibitors from natural resources, Streptomyces sp. A6705 was found to exhibit potent inhibitory activity against the chitin synthase 1 from C. albicans (CaCHS1p). As a result, the inhibitor was isolated and identified using a series of chromatographies. Through chemical analyses with UV spectrophotometry, MS spectrometry, and various NMR techniques, the inhibitor was identified as N,N-bis(2-phenylethyl)urea. The compound exhibited strong inhibitory activity against the chitin synthase 1 from C. albicans with an $IC_{50}$ of 14 ${\mu}g$/ml, representing a similar inhibitory activity to that of the well-known chitin synthase inhibitor, polyoxin D ($IC_{50}$ 15 ${\mu}g$/ml). However, the compound showed no inhibitory activity against the chitin synthase 2 of Saccharomyces cerevisiae up to 280 ${\mu}g$/ml, which is structurally and functionally analogous to CaCHS 1 p. In addition, the compound exhibited weak antifungal activities against Cryptococcus neoformans and Rhizoctonis solani.

• Journal of Periodontal and Implant Science
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• v.35 no.4
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• pp.1081-1095
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• 2005

본 연구는 치주질환 주요 병인균주 중의 하나인 Porphyromonas gingivalis의 세균내독소가 마우스 대식 세포주인 RAW264.7 세포에서의 nitric oxide의 생성과 iNOS의 발현에 미치는 영향을 분석하고 그 기전을 규명하기 위해 수행되었다. Butanol추출법과 phenol-water법에 의해 P. gingivalis 381로부터 세균내독소를 추출하였으며, NO의 생성은 배양 상층액 내의 nitrite 농도를 측정하여 결정하였다. 또한, iNOS의 western blot 분석과 reverse transcription (RT)-PCR 산물의 분석을 수행하였다. P. gingivalis의 세균내독소는 부가적인 자극이 없는 상태에서도 iNOS의 발현과 NO 생성을 유발하였으며, NF- ${\kappa}B$, microtubule polymerization, protein tyrosine kinase, 그리고 protein kinase C 등이 P. gingivalis 세균내독소에 의한 NO 생성에 간여하는 것으로 여겨진다. 또한, P. gingivalis 세균내독소에 의한 NO 생성에는 L-arginine이 요구되었다. P. gingivalis 세균내독소에 의한 NO 생성은 염증성 치주질환의 발병과 진행에 있어 중요한 역할을 하는 것으로 여겨진다.

• Archives of Pharmacal Research
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• v.21 no.4
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• pp.481-484
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• 1998

In activated macrophages the inducible form of nitric oxide synthase (i-NOS) generates high amounts of toxic mediator, nitric oxide (NO) which contributes to the circulatory failure associated with septic shock. A sesquiterpene lactone compound (yomogin) isolated from medicinal plant Artemisia princeps Pampan inhibited the production of NO in LPS-activated RAW 264.7 cells by suppressing i-NOS enzyme expression. Thus, yomogin may be a useful candidate for the development of new drugs to treat endotoxemia and inflammation accompanied by the overproduction of NO.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.313.1-313.1
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• 2002

Nitric oxide (NO) production through the inducible nitric-oxide synthase (iNOS) pathway has been implicated in inflammatory diseases and cellular injury. Inhibition of various genes related to inflammation, including iNOS is one of the major roles of well-known anti-inflammatory drugs. In the present study, the effects of ceramide analogs on iNOS expression and NO production were evaluated to investigate how ceramide and its structurally related analogs modulate NO-mecliated cellular signals and inflammation. (omitted)

• Korean Journal of Pharmacognosy
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• v.38 no.2 s.149
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• pp.170-175
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• 2007

Activated microglia by neuronal injury or inflammatory stimulation overproduce nitric oxide (NO) by inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) such as superoxide anion, resulting in neurodegenerative diseases. The toxic peroxynitrite (ONOO$^-$), the reaction product of NO and superoxide anion further contributes to oxidative neurotoxicity. We tried to evaluate the effects of two kinds of varieties of Perilla frutescens var japnica Hara on the NO production in lipopolysaccharide (LPS)-activated microglia. The perilla cultivars of Namcheondeulkkae (NC) and Boradeulkkae (BR) were developed by pure line from the local variety and by a cross between 'deulkkae' and 'chajogi', respectively. Spirit, hexane, chloroform and butanol fractions of the leaves of NC and BR inhibited the production of NO in LPS-activated microglia. The fractions of BR showed stronger activity than NC and the spirit extracts was the most potent in both cultivars. The solvent fractions of BR suppressed the expression of protein and mRNA of iNOS in LPS-activated microglial cells. Moreover, the extracts of NC and BR showed the activity of peroxynitrite scavenging in cell free bioassay system. These results imply that Namcheondeulkkae and Boradeulkkae might have neuroprotective activity through the inhibition of NO production by activated microglial cells and peroxynitrite scavenging activity.

• YAKHAK HOEJI
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• v.49 no.4
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• pp.347-354
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• 2005

Lipopolysaccharide (LPS) induces synthesis of several inflammatory cytokines and nitric oxide (NO). NO in brain is involved not only in the regulation of important metabolic pathways via intracellular cyclic GMP-dependent path­ways, but also in neurotoxic damage by reacting with superoxide ion leading to form peroxynitrite radical. Oxidative stress has suggested to be related to the inhibition of NO synthase/cyclic GMP pathway. OQ21 is a new fluorinated quinone compound that is recently known to have inhibitory effects on both NO synthase (NOS) and guanylyl cyclase (GC). In this study, we examined effects of OQ21, other known NOS or GC inhibitors, or an antioxidant, melatonin, on the oxidative stress produced by LPS in rat brain. Oxidative stress was observed by using the 2',7'-dichlorofluorescin diacetate to measure intra-cellular reactive oxygen species (ROS) production and by measuring the formation of thiobarbituric acid reactive substances to measure lipid peroxidation. LPS induced significant increase in both ROS produdction and lipid peroxidation in all brain regions tested (striatum, hippocampus and cortex), which were dissected 6hr after intraperitoneal administration of LPS to rats. Direct striatal injection of two NOS inhibitors, N-nitro-L-arginine methyl ester and diphenyleneiodonium, or a GC inhibitor, IH-[1,2,4]oxadiazolo[4,3-a]quinoxaline-l-one, produced no significant ROS increase. However, OQ21 enhanced ROS formation in striatal tissues from LPS-treated rats. Melatonin decreased LPS-induced ROS formation and decreased ROS formation increased by OQ21 in striatum of LPS-treated rats.

• Asian-Australasian Journal of Animal Sciences
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• v.18 no.5
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• pp.626-631
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• 2005

Nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) is involved in cell apoptosis, which contributes to luteal regression and luteolysis in some species. In large domestic animals, no direct evidence for the relationship between NO and cell apoptosis in the process of corpus luteum regression is reported. The present study was conducted to investigate the localization of iNOS on porcine corpora lutea (CL) during the oestrus cycle and its relation to cell DNA fragmentation and CL regression. According to morphology, four luteal phases throughout the estrous cycle were defined as CL1, CL2, CL3 and CL4. By isoform-specific antibody against iNOS, the immunochemial staining was determined. Luteal cell DNA fragmentation was determined by flow cytometry. The results showed that no positive staining for iNOS was in CL1 and that iNOS was produced but limited to the periphery of CL2, while in the CL3, the spreading immunochemical staining was found inside the CL. No iNOS positive staining was detected in CL4. Meanwhile, DNA fragmentation increased dramatically when CL developed from CL2 to CL3 (p<0.05). In CL4, higher proportion of luteal cells still had fragmented DNA than that of luteal cells from CL1 or CL2 (p<0.05). These results indicate that iNOS expression is closely related to luteal cell apoptosis and then to luteal regression.

• Archives of Pharmacal Research
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• v.29 no.2
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• pp.145-151
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• 2006

We investigated the effects of Ginsenoside $R_e$ on human sperm motility in fertile and asthenozoospermic infertile individuals in vitro and the mechanism by which the Ginsenosides play their roles. The semen samples were obtained from 10 fertile volunteers and 10 asthenozoospermic infertile patients. Spermatozoa were separated by Percoll and incubated with 0, 1, 10 or $100\;{\mu}M$ of Ginsenoside $R_e$. Total sperm motility and progressive motility were measured by computer-aided sperm analyzer (CASA). Nitric oxide synthase (NOS) activity was determined by the $^{3}H$-arginine to $^{3}H$-citrulline conversion assay, and the NOS protein was examined by the Western blot analysis. The production of sperm nitric oxide (NO) was detected using the Griess reaction. The results showed that Ginsenoside $R_e$ significantly enhanced both fertile and infertile sperm motility, NOS activity and NO production in a concentration-dependent manner. Sodium nitroprusside (SNP, 100 nM), a NO donor, mimicked the effects of Ginsenoside $R_e$. And pretreatment with a NOS inhibitor $N^{w}$-Nitro-L-arginine methyl ester (L-NAME, $100\;{\mu}M$) or a NO scavenger N-Acetyl-L-cysteine (LNAC, 1 mM) completely blocked the effects of Ginsenoside $R_e$. Data suggested that Ginsenoside $R_e$ is beneficial to sperm motility, and that induction of NOS to increase NO production may be involved in this benefit.