• Journal of Chest Surgery
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• v.32 no.2
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• pp.138-143
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• 1999

Background: The endothelium-dependent vasorelaxation has been largely accounted for by the release of nitric oxide (NO). Three distinct isoforms of NO synthases (NOS) have been characterized, i.e., brain(bNOS), inducible (iNOS), and endothelial constitutive (ecNOS). Although hypertension hasbeen associated with a vascular endothelial dysfunction, changes in the vascular expression of NOS isoforms have not been established. The present study was aimed at exploring the vascular expression of NOS isozymes in hypertension. Material and Method: Two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertension were induced in rats. The expression of different NOS isozymes in the thoracic aorta was determined by Western blot analysis. The vascular tissue contents of nitrites were measured by colorimetric assay. Result: Arterial blood pressure was significantly higher in experimental groups of 2K1C and DOCA-salt rats compared with their corresponding control rats. The vascular expression of bNOS as well as that of ecNOS was decreased in both models of hypertension. iNOS was not changed in DOCA-salt hypertension, but was also decreased in 2K1C hypertension. The vascular contents of nitrites were significantly decreased in DOCA-salt as well as in 2K1C hypertension. Conclusion: These results suggest that 2K1C and DOCA-salt hypertension are associated with decreases in the vascular expression of NOS isozymes and nitrite contents.

• Natural Product Sciences
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• v.5 no.3
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• pp.113-120
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• 1999

Nitric oxide (NO) is a free radical synthesized from L-arginine by nitric oxide synthase (NOS). It is believed that NO is an important mediator in numerous physiological and inflammatory responses. Particularly, a large amount of NO released from the inducible nitric oxide synthase (iNOS) is mostly associated with inflammatory processes. Overproduction of NO in these processes including sepsis and autoimmune diseases can have deleterious consequences and pathophysiologic relevance. Therefore, for the discovery of new inhibitory agents against iNOS activity, we have evaluated about 100 kinds of natural products after partition into three layers (n-hexane, ethyl acetate and aqueous) from 100% methanol extracts to study inhibitory effects on iNOS activity induced by lipopolysaccharide (LPS) in RAW264.7 cells culture system. As a positive control, curcumin, which is known as an anti-tumor promoter, anti-inflammatory agent as an iNOS inhibitor, was used and showed the dose-dependent inhibitory effect $(IC_{50},\;2.5\;{\mu}g/ml)$. Among tested fractions, the n-hexane fraction of Cimicifuga heracleifolia $(IC_{50}:\;9.65\;{\mu}g/ml)$, Forsythiae fructus $(IC_{50}:\;6.36\;{\mu}g/ml)$, Saposhnikovia divaricata $(IC_{50}:\;5.92\;{\mu}g/ml)$, and the ethyl acetate fraction of Chrysanthemum sibiricum $(IC_{50}:\;2.56\;{\mu}g/ml)$, Gastrodia elata $(IC_{50}:\;3.46\;{\mu}g/ml)$, and the aqueous fraction of Dianthus chinensis $(IC_{50}:\;6.73\;{\mu}g/ml)$, Euonymus alatus $(IC_{50}:\;6.78\;{\mu}g/ml)$, Mechania urticifoloria $(IC_{50}:\;8.01\;{\mu}g/ml)$ showed strong inhibitory activity against LPS-stimulated iNOS. Especially, the ethyl acetate fraction of Chrysanthemum sibiricum $(IC_{50}:\;2.56\;{\mu}g/ml)$, which exhibited the strongest inhibition against iNOS, was fractionated with silica-gel column chromatography. These subfractions exhibited dose-dependent inhibition against iNOS activity in the range of $2.59-5.6\;{\mu}g/ml$ except for fraction No. 3, 4, 5, 6, 8, 9, and 16. Our study shows that Chrysanthemum sibiricum has the strongest inhibitory effect against iNOS activity and has similar effect to curcumin. Therefore, further studies for the identification of active principles from Chrysanthemum sibiricum and investigation for the mechanism of the inhibition of iNOS by active principles will be performed.

• The Journal of Internal Korean Medicine
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• v.35 no.3
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• pp.262-273
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• 2014

Objectives: This study was carried out to investigate the protective effect of Coptidis Rhizoma steamed with rice wine (CR) against gastroduodenal mucosal injury through inhibiting inducible nitric oxide synthase (iNOS) activation. Methods: In in vitro experiment, LPS-induced RAW 264.7 macrophages were treated with CR(0.4, 0.6, 0.8, 1.0 mg/ml) and iNOS mRNA expression and nitric oxide (NO) production were measured. In in vivo experiment normal group mice were treated with neither ethanol nor CR. Both control and sample group mice were orally administrated with ethanol. Five hours after ethanol administration control group mice were orally administrated with distilled water, sample group mice were orally administrated with CR. After three days administration, gastroduodenal mucosa of mice was observed histopathologically and iNOS, nuclear factor-kappa B (NF-${\kappa}B$) activation were observed immunohistochemically. Results: In in vitro experiment iNOS mRNA expression and NO production in LPS-induced RAW 264.7 macrophages were decreased by CR dose-dependently. In in vivo experiment, gastroduodenal mucosal injury was repaired by CR and iNOS, NF-${\kappa}B$ activation in gastroduodenal mucosa were decreased by CR. Conclusions: Coptidis Rhizoma steamed with rice wine has a protective effect against gastroduodenal mucosal injury through inhibiting iNOS activation.

• Korean Journal of Food Science and Technology
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• v.44 no.6
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• pp.759-762
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• 2012

Egg allergies have been reported as one of the most prevalent food hypersensitivities in the pediatric population. One of the major egg allergens is ovalbumin (OVA), which is the major protein in the egg whites. Phenethyl isothiocyanate (PEIC) from cruciferous vegetables has an effect on anti-inflammatory therapy. In the present report, we show that PEIC inhibits the nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activation induced by OVA. PEIC also inhibits the OVA-induced inducible nitric oxide synthase (iNOS) expression and nitrite production. However, PEIC did not suppress the cyclooxygenase-2 (COX-2) expression induced by OVA. These results suggest that PEIC has the specific mechanism for anti-inflammatory responses and efficient anti-allergic activities.

• The Journal of Korean Medicine
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• v.30 no.3
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• pp.39-50
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• 2009

Objective : The aim of this study was to evaluate the effects of Aconiti ciliare tuber on the descending pain and the recovery of locomotor function that results from sciatic crushed nerve injury in rats. Method : In order to assess the effects of the aqueous extract of Aconiti ciliare tuber on the recovery rate of locomotor function, we investigated the walking track analysis, and for the effects on the pain control we investigated brain-derived neurotrophic factor (BDNF) and inducible nitric oxide synthase (iNOS) expression in the sciatic nerve and on the expressions of c-Fos in the ventrolateral periaqueductal gray (vlPAG) region resulting from the sciatic crushed nerve injury in rats. Result : Treatment with Aconiti ciliare tuber significantly enhanced the SFIvalue, enhanced BDNF expression, decreased iNOS expression, and suppressed c-Fos expression. The present results showed that Aconiti ciliare tuber facilitated functional recovery following sciatic crushed nerve injury in rats. The recovery mechanisms of SFI by Aconiti ciliare tuber might be ascribed to the increase of BDNF expression for nerve regeneration and reinnervation and to the suppression of iNOS expression for inhibiting nerve inflammation. Conclusion : In this process it has been shown that Aconiti ciliare tuber can be used for pain control and functional recovery from peripheral nerve injury.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.145-145
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• 1998

In the present study, we have demonstrated that taurine could stimulate the production of nitric oxide and the activity of ERK2 (extracellular signal regulated protein kinase or pp42 MAP kinase). Nitric oxide(NO), the product of inducible nitric oxide synthase(iNOS), is known to be implicated in the metabolism of bone. ERK cascade plays a key role in the gene expression of iNOS in osteoblastic cell. We investigated whether taurine (l-20mM) could stimulate ERK2 activity, nitric oxide production, and inducible nitric oxide synthase in osteoblast-like UMR-106 cells. Nitric oxide was measured spectophotometrically as nitrite and the activation of ERK2 and iNOS was studied using Western 145 blot analysis. Taurine increased the production of nitric oxide in a dose-dependent manner and the effect was reached to a maximum at 10 mM. The activation of iNOS were consistent with NO levels. The tyrosine phosphorylation of ERK2 was increased by taurine in a time-dependent manner. The these result suggest that taurine might stimulate the production of nitric oxide in osteoblast-like cells by the activation of ERK2 and could regulate the metabolism of bone via nitric oxide.

• Journal of Microbiology and Biotechnology
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• v.28 no.8
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• pp.1310-1317
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• 2018

The stems of Dendrobium moniliforme have been used in traditional herbal medicine for the treatment of fever and lack of body fluid in Korea. In this study, we investigated anti-inflammatory effects of the aqueous extract of D. moniliforme stems (DM) in response to lipoteichoic acid (LTA), a major constituent of the cell wall of Gram-positive bacteria. DM inhibited LTA-induced expression of a pro-inflammatory mediator inducible nitric oxide synthase (iNOS) in the murine macrophages. And DM induced expression of heme oxygenase-1 (HO-1) at the transcriptional level. Conversely, the knockdown of HO-1 expression by siRNA markedly reversed the inhibitory effects of DM on LTA-induced iNOS expression. We also demonstrated that nuclear translocation of Nrf2 was increased following treatment with DM. In addition, DM-mediated Nrf2 activation and HO-1 expression were suppressed by PI3K/Akt and p38 inhibitors; treatment with DM also resulted in phosphorylation of Akt and p38. These results suggest that DM inhibits the expression of iNOS in LTA-stimulated macrophages, and that these effects are mediated by the upregulation of HO-1 expression via PI3K/Akt/p38-Nrf2 signaling.

• Biomedical Science Letters
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• v.25 no.3
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• pp.267-274
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• 2019

Toll-like receptors (TLRs) are one of the families of pattern recognition receptors (PRR) to recognize pathogen-associated molecular patterns (PAMPs). PAMPs stimulate TLRs to initiate specific immunoactivity. The activation of TLRs signaling leads to the expression of pro-inflammatory gene products such as cytokines and inducible nitric oxide synthase (iNOS). To evaluate the therapeutic potential of dehydrocostus lactone (DHL), which is a natural sesquiterpene lactone derived from various medicinal plants, iNOS expression induced by LPS (TLR4 agonist), MALP-2 (TLR2 and TLR6 agonist), or Poly[I:C] (TLR3 agonist) were examined. DHL suppressed the iNOS expression induced by LPS, MALP-2, or Poly[I:C]. DHL also inhibited nitrite production induced by LPS, MALP-2, or Poly[I:C]. These results suggest that DHL can modulate TLRs signaling pathways resulting in anti-inflammatory effect.

• BMB Reports
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• v.43 no.9
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• pp.629-634
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• 2010

Endotoxin including lipopolysaccharide (LPS) confers organ tolerance against subsequent challenge by ischemia and reperfusion (I/R) insult. The mechanisms underlying this powerful adaptive defense remain to be defined. Therefore, in this study we attempted to determine whether nitric oxide (NO) and its associated enzymes, inducible NOS (iNOS) and endothelial NOS (eNOS, a constitutive NOS), are associated with LPS-induced renal tolerance against I/R injury, using iNOS (iNOS knock-out) or eNOS (eNOS knock-out) gene-deleted mice. A systemic low dose of LPS pretreatment protected kidney against I/R injury. LPS treatment increased the activity and expression of iNOS, but not eNOS, in kidney tissue. LPS pretreatment in iNOS, but not eNOS, knock-out mice did not protect kidney against I/R injury. In conclusion, the kidney tolerance to I/R injury conferred by pretreatment with LPS is mediated by increased expression and activation of iNOS.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.101-101
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• 2003

Prostaglandins (PGs) and nitric oxide (NO) produced by inducible cyclooygenase (COX-2) and nitric oxide synthase (iNOS), respectively, have been implicated as important mediators in the process of inflammation and carcinogenesis. On this line, the potential COX-2 or iNOS inhibitors have been considered as anti-inflammatory and cancer chemopreventive agents. In our continuing efforts of searching for novel cancer chemopreventive agents from natural products, we isolated natural sesquiterpenoids as potential COX-2 and iNOS inhibitors in cultured lipopolysaccharide (LPS)-activated mouse macrophage RAW 264.7 cells. Alantolactone, a natural eudesmane-type sesquiterpenoid, exhibited a potent inhibition of COX-2 (IC50 = 0.4 $\mu\textrm{g}$/$m\ell$) and iNOS activity (IC50 = 0.08 $\mu\textrm{g}$/$m\ell$) in the assay system determined by PGE2 and NO accumulation, respectively. The inhibitory potential of alantolactone on the PGE2 and NO production was well coincided with the suppression of COX-2 and iNOS protein and mRNA expression in LPS-induced macrophages. Furthermore, alantolactone inhibited NF-kB but not AP-l binding activity on nuclear extracts evoked by LPS-stimulated macrophage cells, suggesting the possible involvement of NF-kB in the regulation of COX-2 and iNOS expression. In further study with COX-2-expressing human colon HT-29 cells, alantolactone inhibited the cell proliferation, down-regulated COX-2, and inhibited the ERK phosphorylation in the early time. These results suggest that a natural sesquiterpenoid alantolactone might be a potential lead candidate for further developing COX-2 or iNOS inhibitor possessing cancer chemopreventive or anti-inflammatory activity