• Korean Journal of Oriental Medicine
• /
• v.12 no.3 s.18
• /
• pp.59-67
• /
• 2006

Aims: Acupuncture has been used for the treatment of essential hypertension, but the efficacy and the mechanism of acupuncture in prevention of hypertension are still unclear. We tested the hypothesis that electroacupuncture (EA) applied to Baekhoe (GV20) changes NO/NOS system during development of hypertension in spontaneously hypertensive rats (SHR), and thereby causes the delay of development of hypertension in SHR. Methods: The male SHR rats in the developmental stages of hypertension (7-8 weeks) were randomly divided into three groups (control group, GV20 acupuncture group, and tail acupuncture group). And the age matched Wistar Koyto Rats (WKY) were randomly divided into two groups (nagative control, GV20 acupuncture group). EA treatments (10Hz, 1mA, 0.1ms) were carried out for 25 min/day for five consecutive days. The systolic blood pressure (SBP) was determined in conscious rats by the tail-cuff method using automatic BP mornitoring system. We investigated the activations of inducible NO synthase (iNOS) in nuclei of solitary tract (NTS) and rostral ventrolateral medulla (RVLM) of SHR by the western blotting method. Results: The SBP after the termination of EA stimulation applied to the GV20 was stabilized at $169.14{\pm}3.67$ mmHg which is lower value than that of the control group. The SBP of control group was elevated to $178.14{\pm}3.49$ mmHg. In addition, we evaluated NOS activity as well as iNOS protein expression of NTS and RVLM in both of SHR and WKY. The iNOS activity in NTS was significantly higher in SHR than in WKY. Furthermore, the iNOS activity of NTS showed significant decreases in EA groups compare to that of non treated SHR group. Although iNOS expression of RVLM showed non significant changes between SHR and WKY, EA significantly enhanced the iNOS expression in SHR. Our data support the hypothesis that delayed development of hypertension and altered iNOS expression of NTS and RVLM by EA stimulations in SHR rats. Conclusions: The findings demonstrate that acupuncture can change NO/NOS system in NTS and RVLM, and exert beneficial role on development of hypertension.

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

• Biomolecules & Therapeutics
• /
• v.19 no.4
• /
• pp.438-444
• /
• 2011

The mushroom Coriolus versicolor contains biologically active polysaccharides, most of which belong to the ${\beta}$-glucan group. Diverse physicochemical properties, due to different sources and isolated types of ${\beta}$-glucans, can induce distinct biological activities. We investigated the effects of ${\beta}$-glucans from C. versicolor on phagocytic activity, nitric oxide (NO), TNF-${\alpha}$ production, and signaling of dectin-1, a well-known ${\beta}$-glucan receptor, in macrophages. ${\beta}$-Glucans increased phagocytic activity and TNF-${\alpha}$ and NO-iNOS/eNOS production. Laminarin, a specific inhibitor of dectin-1, showed strong inhibitory effects on phagocytosis and subsequent TNF-${\alpha}$, iNOS, and eNOS production increased by ${\beta}$-glucans, indicating that ${\beta}$-glucans reacts with dectin-1 receptors. We examined whether the aforementioned cytokines were involved in the signaling pathway from the dectin-1 receptor to phagocytosis, and found that the inhibition of iNOS, eNOS, and TNF-${\alpha}$ receptors significantly decreased ${\beta}$-glucan-induced phagocytosis. In conclusion, our study showed that dectin-1 signaling, triggered by ${\beta}$-glucans, subsequently elicited TNF-${\alpha}$ and NO-iNOS/eNOS production, and that these molecules seem to act as secondary molecules that cause eventual phagocytosis by macrophages. These findings suggest that C. versicolor could be used as a nutritional medicine that may be useful in the treatment of infectious disease.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1998.11a
• /
• pp.196-196
• /
• 1998

Nitric oxide is involved in various physiological processes. Among isoforms of nitric oxide synthase, iNOS is partly responsible for inflammation and septic shock. During our continual search for anti-inflammatory flavonoids, we have found that flavonoids, especially flavones, possessed the inihibitory activity of NO production by iNOS from LPS-activated RAW 264.7 cell. In this study, flavonoids from Scutellaria radix were investigated for their inhibitory activity of nitric oxide production. It was found that wogonin, among tested flavonoids including baicalein, oroxylin A, skullcapflavone II, showed the strongest inhibition of nitric oxide production (IC$\sub$50/ = 17 uM). And this inhibition was, at least partly, due to down-regulation of iNOS enzyme induction, not due to direct inhibition of iNOS enzyme activity.

• Journal of Life Science
• /
• v.21 no.12
• /
• pp.1689-1697
• /
• 2011

In this study, we investigated the anti-inflammation effect of Persicaria thunbergii (P. thunbergii) on RAW 264.7 murine macrophage cells. The anti-inflammatory activity of P. thunbergii was determined by measuring expression of the LPS-induced inflammatory proteins, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and nuclear factor-${\kappa}B$ (NF-${\kappa}B$), and the production of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$). Methanol extract of P. thunbergii decreased the expression of iNOS, COX-2 and NF-${\kappa}B$, and increased the expression of HO-1 in LPS-stimulated RAW264.7 cells. Methanol extract was fractioned by n-butanol, hexane and ethyl acetate (EtOAc) and each fraction was tested for inhibitory effects on inflammation. Among the sequential solvent fractions, the EtOAc soluble fraction was investigated by the expression of prostaglandin $E_2$ ($PGE_2$), and showed decreasing form to the dose-dependent manner. EtOAc extract showed the most effective inhibitory activity of the expression of iNOS, COX-2 and NF-${\kappa}B$, and the production of NO. The study showed that P. thunbergii has anti-inflammatory activity through the decrease of NO and inhibition of iNOS, COX-2, $PGE_2$ and NF-${\kappa}B$ expression, and by the increase of HO-1 enzyme. This study needs for more investigation to find out the most effective single compound with anti-inflammatory activity.

• BMB Reports
• /
• v.40 no.5
• /
• pp.636-643
• /
• 2007

This study was designed to identify and characterize the mechanism of macrophage activation by AAP, an acidic polysaccharide fraction isolated from the roots of Angelica sinensis (Oliv.) Diels. As a result, AAP significantly enhanced nitric oxide (NO) production and cellular lysosomal enzyme activity in murine peritoneal macrophages in vitro and in vivo. Furthermore, L-NAME, a specific inhibitor of inducible nitric oxide synthase (iNOS), effectively suppressed AAP-induced NO generation in macrophages, indicating that AAP stimulated macrophages to produce NO through the induction of iNOS gene expression and the result was further confirmed by the experiment of the increase of AAP-induced iNOS transcription in a dose-dependent manner. To further investigate, AAP was shown to strongly augment toll-like receptor 4 (TLR4) mRNA expression and the pretreatment of macrophages with anti-TLR4 antibody significantly blocked AAP-induced NO release and the increase of iNOS activity, and tumor necrosis factor-$\alpha$ (TNF-$\alpha$) secretion.

• Culinary science and hospitality research
• /
• v.18 no.4
• /
• pp.233-242
• /
• 2012

Macrophage-derived nitric oxide (NO) plays an important role in immune responses. Overproduction of NO by inducible nitric synthase(iNOS) is known to be closely correlated with the pathology of a variety of diseases and inflammations. This study investigated the inhibitory effect of extract from various mushrooms(Phellinus linteus(PL), Inonotus obliquus(IO), Sarcodon aspratus(SA), Hericium erinacium(HE), and Russula cutefracta(RC)) on NO production and its molecular mechanism in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Among the mushrooms, HE extracts exhibited the strongest NO-inhibition activity. It was also found that HE extract inhibited LPS-induced iNOS and COX-2 expression in RAW264.7 cells. The present results give the understanding of biological activities of mushrooms and encourage their application for supplements and cook.

• Korean Journal of Plant Resources
• /
• v.25 no.3
• /
• pp.317-322
• /
• 2012

In this study we investigated the effects of supplementation with fucoidan from brown alga on the function of natural-killer (NK) cells to evaluate the possibility as an immunomodulator in ovariectomized (OVX) rats. A total of 18 female Wistar rats (six weeks) were used this study and 12 rats were OVX, and the rest of rats were sham-operated. The sham and one OVX group were fed standard diet, and the remaining OVX group received fucoidan (0.05% supplemented diet). After 12 weeks of supplementation, rats were sacrificed to assess the tumoricidal activity of the NK cells and the NO-iNOS regulation from splenocytes. The mass of body and the immune organs such as spleen and thymus were also studied. In OVX rats, body and thymus weights increased, however fucoidan supplementation did not change the body mass and organs weight compared to OVX group. Fucoidan supplementation increased NK cell activity and reduced NO-iNOS production in OVX rats. Ex vivo treatment of fucoidan increased NK cell activity in splenocytes from shame and OVX rats. Ex vivo, we confirmed that fucoidan partially reduced the NK cell activity in the presence of iNOS inhibitors in OVX-splenocytes. These results indicate fucoidan supplementation has a NK cell tumoricidal activity, which are regulated by the iNOS production in OVX rats. This suggests that fucoidan is useful for potential therapeutic strategies as a nutrient in regulating the NK cells in postmenopausal osteoporosis patients.

• YAKHAK HOEJI
• /
• v.47 no.5
• /
• pp.311-318
• /
• 2003

Eurya emarginata (Thunb.) Makino (Theaceae) is distributed in coastal areas of island. The leaves of Eurya are used in the traditional medicine of the coastal areas of jeju island with the aim of diuresis or to treat ulcers. Nevertheless, there are few reports on the biological activity and constituents of E. emarginata. In this study, we investigated the pharmacological activity of the solvent extracts of E. emarginata on the several inflammatory markers (TNF-$\alpha$, IL-1$\beta$, IL-6, NO, iNOS and COX-2). Also we examined the antioxidizing effect of the solvent extracts by determination of DPPH radical-scavenging activity. Among the solvent fractions, EtOAc and BuOH extracts showed potent radical scavenging activity (RC$_{50}$=10.9 and 12.7 respectively). The subtractions of EF 5-4-6-3-2 and BF 1 potentially inhibited the mRNA expression of pro-inflammatory cytokines (IL-1$\beta$, IL-6 and TNF-$\alpha$) at the concentration of 100 $\mu\textrm{g}$/mι. Also the fractions inhibited the mRNA expression of pro-inflammatory cytokines (IL-1$\beta$, IL-6 and TNF-$\alpha$) and protein expression of iNOS and COX-2 at the concentration of 100 $\mu\textrm{g}$/mι. And then, the inhibition of iNOS was correlated with the decrease of nitrite level. These results suggest that E. emarginata may have anti-inflammatory activity through the inhibition of pro-inflammatory cytokines, iNOS and COX-2.2.

• Journal of Life Science
• /
• v.26 no.3
• /
• pp.318-324
• /
• 2016

This study was aimed to verify anti-inflammatory activity of fermented Sargassum siliquanstrum with lactic acid bacteria. Anti-inflammatory activities were compared by measuring the amount of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and suppressive effect on inducible nitric oxide synthase (iNOS) expression in stably transfected RAW 264.7 cells. Inhibitory activities of NO production and iNOS expression were measured after confirmation of NO radical scavenging activities. Fermentation increased NO radical scavenging activities from 7.6% to 15.2% compared to non-fermented condition, and fermentation with Lactobacillus sp. SH-1 was the most efficient. Fermentation without algal debris showed better NO radical scavenging activities than that with debris. Fermentation with Lactobacillus sp. SH-1 also showed the highest NO production inhibitory activity (64.1%) in LPS-stimulated RAW 264.7 cells. LPS-induced iNOS expression was diminished to 28.6, 35.6, 49.4 and 58.5 at 50, 100, 500 and 1,000 μg/ml, respectively, by fermentation with Lactobacillus sp. SH-1. According to MTT assay, fermented S. siliquanstrum did not influence the cell viability at all concentrations tested, meaning no or less cytotoxicity. These results suggest that S. siliquanstrum has NO radical scavenging activity and anti-inflammatory activity. Thus biological activities of S. siliquanstrum were upgraded by fermentation, which could be used for the development of functional foods.