• Korean Journal of Biological Psychiatry
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• v.13 no.1
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• pp.19-25
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• 2006

Background : Some reports have suggested that decreased nitric oxide metabolites($NO_x$) and activity of nitric oxide synthase could be related to the pathophysiology of depression. We evaluated plasma levels of $NO_x$ in pregnant women with and without postpartum depression at prenatal and postnatal period. Methods : The plasma concentrations of $NO_x$ were measured in 104 pregnant women in the third trimester and at 6 weeks postpartum and in 64 normal controls. The severity of depression and anxiety was measured with the Edinburgh Postnatal Depression Scale(EPDS), Beck Depression Inventory(BDI), and Beck Anxiety Scale(BAI). Results : Plasma $NO_x$ levels at 6 weeks postpartum were significantly lower in cases of postpartum major depression(EDPS scores${\geq}$13 points) than in cases without depression(EDPS scores${\leq}$9 points). Plasma $NO_x$ levels had significantly negative correlation with EPDS scores at 6 weeks postpartum. Conclusion : We demonstrate that decreased plasma $NO_x$ is associated with postpartum depression. Further studies are required to determine whether individual serum concentration of plasma $NO_x$ alone could predict maternal depression.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.3
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• pp.305-310
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• 2007

This study was designed to investigate the effects of KH-305 on erectile dysfunction in young rats, via nitric oxide (NO)-cGMP pathways. After oral administration of the KH-305 mixture (50, 100, 200, 300 mg/kg) to young rats for 10 days, NOS and SOD protein expressions in penile tissue and testosterone in plasma were measured. cGMP degradation was also investigated using bovine vascular smooth muscle cells pretreated with an NO donor, S-nitroso-N-Acetylpenicillamine (SNAP). The penile expression levels of nNOS and eNOS-dependent NOS activities as well as SOD preventing oxidative stress by overproduction of NO were increased significantly. Also, the concentration of testosterone in the plasma was increased. In vitro, cGMP concen-trations were decreased dose dependently in the KH-305. These results suggest that KH-305 may be useful in erectile dysfunction.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.6
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• pp.1284-1290
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• 2002

Scrophularia buergeriana Miquel (Scrophulariaceae) has been used as an anti-inflammatory drug in the folk medicine recipe and been proved its anti-inflammatory effect in the oriental medicine. Since nitric oxide (NO) and superoxide anion (O/sub 2//sup -/) are ones of the major inflammatory parameters, we studied the effect of aqueous extracts of Scrophularia buergeriana (SB) on NO and O/sub 2//sup -/ production in lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages. NO, O/sub 2//sup -/production and inducible NO synthase (iNOS) level were significantly reduced in LPS-activated macrophages by SB compared to those without. Electrophoretic mobility shift assay (EMSA) indicated that SB blocked the activation of NF-kB, which was considered to be a potential transcription factor for the iNOS expression. SB also blocked degradation of IkBα. Furthermore, IkB kinase alpha (IKKα), which phosphorylates serine residues of IkB directly, is inhibited by SB. These results suggest that SB could exert its anti-inflammatory actions by suppressing the activation of NF-kB through inhibition of IKK activity.

• The Journal of Internal Korean Medicine
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• v.34 no.1
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• pp.31-45
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• 2013

Objectives : Gokgisaeng (Korean mistletoe) is used for the treatment of inflammatory and cancer diseases in traditional Korean medicine and its major component lectins have been reported to induce nitric oxide (NO) in RAW 264.7 macrophages, and also induce apoptosis of various types of cancer cells, although its modulatory effects on cancer cell migration and macrophage activation is poorly understood. The aim of this study is to clarify molecular mechanisms of action responsible for the anti-inflammatory and antitumor migration potentials of Korean mistletoe extract (KME). Methods : We investigated the anti-inflammatory activity of KME on NO production and inducible nitric oxide synthase (iNOS) expression by lipopolysaccharide (LPS) in both RAW 264.7 macrophages and rat C6 glioma cells, and also evaluated inhibitory efficacy on glioma cell growth and migration. For assessment, XTT assay, nitrite assay, RT-PCR, scratch-wound and Boyden chamber assay, and western blot analysis were performed. Results : Previously reported, unlike the efficacy of Gokgisaeng lectin, KME inhibited NO production and iNOS expression, and suppressed pro-inflammatory mediators including IL-$1{\beta}$, IL-6, COX-2, iNOS in LPS-stimulated RAW 264.7 cells. Furthermore, KME suppressed tumor cell growth and migration, and it also inhibited LPS-induced NO release and iNOS activation by down-regulating expression of protein kinase C (PKC) and phosphorylation of ERK in C6 glioma cells. Conclusions : Our research findings provide evidence that KME can play a significant role in blocking pro-inflammatory reaction and malignant progression of tumors through the suppression of NO/iNOS by down-regulating of inflammatory signaling pathways, PKC/ERK.

• BMB Reports
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• v.50 no.7
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• pp.384-389
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• 2017

The Nogo-B receptor (NgBR) is necessary for not only Nogo-B-mediated angiogenesis but also vascular endothelial growth factor (VEGF) -induced angiogenesis. However, the molecular mechanisms underlying the regulatory role of the VEGF-NgBR axis in angiogenesis are not fully understood. Here, we report that miR-26a serves as a critical regulator of VEGF-mediated angiogenesis through directly targeting NgBR in endothelial cells (ECs). Stimulation of ECs by VEGF increased the expression of NgBR and decreased the expression of miR-26a. In addition, miR-26a decreased the VEGF-induced migration and proliferation of ECs. Moreover, miR-26a overexpression in ECs decreased the VEGF-induced phosphorylation of the endothelial nitric oxide synthase (eNOS) and the production of nitric oxide, which is important for angiogenesis. Overall, these data suggest that miR-26a plays a key role in VEGF-mediated angiogenesis through the modulation of eNOS activity, which is mediated by its ability to regulate NgBR expression by directly targeting the NgBR 3'-UTR.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.29-38
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• 2023

Recent studies have highlighted the link between diseases and inflammation across our lifespan. Our sedentary lifestyle, high-calorie diet, chronic stress, chronic infections, and exposure to pollutants and xenobiotics, collectively intensify the course and recurrence of infections and inflammation in our bodies, promoting the prevalence of chronic diseases and aging. Given such phenomena and considering additional factors such as the frequency of prescription, and easy access to over-the-counter drugs, the need for anti-inflammatory therapeutics is ever-increasing. However, the readily available anti-inflammatory treatment option comes with a greater risk of side effects or high cost (biologics). Therefore in this growing competition of discovering and developing new potent anti-inflammatory drugs, we focused on utilizing the established knowledge of traditional medicine to find lead compounds. Since lead optimization is an indispensable step toward drug development, we applied this concept for the production of potent anti-inflammatory compounds achieved by structural modification of flavonoids. The derivative obtained through acetylation of myricetin, 3,3',4',5,5',7-hexaacetate myricetin, showed a greater inhibitory effect in the production of pro-inflammatory mediators such as nitric oxide, Prostaglandin E₂, and pro-inflammatory cytokines like interleukin-6, interleukin1β, in lipopolysaccharide-stimulated RAW264.7 mouse macrophage cells compared to myricetin. The increased potency of inhibition was in conjunction with an increased inhibitory effect on inducible nitric oxide synthase and cyclooxygenase-2 proteins. Through such measures, this study supports lead optimization for well-established lead compounds from traditional medicine using a simpler and greener chemistry approach for the purpose of designing and developing potent anti-inflammatory therapeutics with possibly fewer side effects and increased bioavailability.

• Mycobiology
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• v.44 no.4
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• pp.291-301
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• 2016

Culinary mushroom Pleurotus pulmonarius has been popular in Asian countries. In this study, the anti-oxidant, cholinesterase, and inflammation inhibitory activities of methanol extract (ME) of fruiting bodies of P. pulmonarius were evaluted. The 1,1-diphenyl-2-picryl-hydrazy free radical scavenging activity of ME at 2.0 mg/mL was comparable to that of butylated hydroxytoluene, the standard reference. The ME exhibited significantly higher hydroxyl radical scavenging activity than butylated hydroxytoluene. ME showed slightly lower but moderate inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase than galantamine, a standard AChE inhibitor. It also exhibited protective effect against cytotoxicity to PC-12 cells induced by glutamate ($10{\sim}100{\mu}g/mL$), inhibitory effect on nitric oxide (NO) production and inducible nitric oxide synthase protein expression in lipopolysaccharide-stimulated RAW 264.7 macrophages, and carrageenan-induced paw edema in a rat model. High-performance liquid chromatography analysis revealed the ME of P. pulmonarius contained at least 10 phenolic compounds and some of them were identified by the comparison with known standard phenolics. Taken together, our results demonstrate that fruiting bodies of P. pulmonarius possess antioxidant, anti-cholinesterase, and inflammation inhibitory activities.

• Natural Product Sciences
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• v.27 no.3
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• pp.176-182
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• 2021

The phytochemical investigation of Broussonetia kazinoki roots led to the isolation of ten compounds, including six flavonoids (1-6), two lignans (7 and 8), and two coumarins (9 and 10) by comparing their ¹H and ¹³C NMR spectra with reference values. To the best of our knowledge, compounds 9 and 10 were isolated from this plant for the first time. Among the ten isolates, compounds 2, 4, and 6 exhibited inhibitory effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW264.7 cells with IC₅₀ values of 11.98, 10.16, and 24.06 μM, respectively. Furthermore, compounds 2, 4, and 6 reduced LPS-induced inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. Pre-incubation of cells with these compounds also significantly suppressed LPS-induced COX-2 protein expression. Compounds 2, 4, and 6 also showed cytotoxic activity against HL-60 cells with IC₅₀ values ranging between 46.43 and 94.06 μM.

• ALGAE
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• v.37 no.3
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• pp.239-247
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• 2022

Enzyme-assisted hydrolysis is frequently used as a cost-effective and efficient method to obtain functional ingredients from bioresources. This study involved the enzyme-assisted hydrolyzation and purification of fucoidan from Ecklonia maxima stipe and the investigation of its anti-inflammatory activity in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Fucoidans of Viscozyme-assisted hydrolysate from E. maxima (EMSFs) harvested in Jeju, Korea. Structural and chemical characterizations were performed using fourier transform infrared spectroscopy, scanning electron microscope, and monosaccharide analysis. Among fucoidans, EMSF6 was rich in fucose and sulfate and had a similar structural character to commercial fucoidan. EMSF6 showed a strong inhibitory effect on nitric oxide generation in LPS-induced RAW 264.7 cells and significantly decreased the production of LPS-induced pro-inflammatory cytokines, including interleukin-6, interleukin-1β, and tumor necrosis factor α. The anti-inflammatory potential of EMSF6 was mediated through the downregulation of inducible nitric oxide synthase and cyclooxygenase-2 expression. Thus, fucoidans from E. maxima stipe are promising candidates for functional food products.

• Journal of Plant Biotechnology
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• v.50
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• pp.27-33
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• 2023

Zizyphus jujube is a plant in the buckthorn family (Rhamnaceae) that has been the subject of research into antibacterial, antifungal and anti-inflammatory properties of its fruit and seed. However, few studies have investigated its leaves. In this study, the anti-inflammatory activity of ZJL (an extract of Z. jujube leaf) was evaluated to verify its potential as an anti-inflammatory agent and SARS-CoV-2 medicine, using nitric oxide (NO) assay, RT-PCR, SDSPAGE, Western blotting, and UHPLC/TOFHRMS analysis. We found that ZJL suppresed pro-inflammatory mediators such as NO, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor α (TNF-α) in lipopolysaccharide (LPS)-induced RAW264.7 cells. ZJL acted by inhibiting NF-KB and MAPK signaling pathway activity. We also confirmed that ZJL contains a phenol compound and flavonoids with anti-inflammatory activity such as trehalose, maleate, epigallocatechin, hyperoside, catechin, 3-O-coumaroylquinic acid, rhoifolin, gossypin, kaempferol 3-neohesperidoside, rutin, myricitrin, guaiaverin, quercitrin, quercetin, ursolic acid, and pheophorbide a. These findings suggest that ZJL may have great potential for the development of anti-inflammatory drugs and vaccines via inhibition of NF-κB and MAPK signaling in LPS-induced RAW264.7 cells.