• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.1 no.1
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• pp.167-190
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• 1995

Bikiwhan is one of the oriental medicines that have been used for the treatment of tumors since ancient times. However, the mechanism of the drug action is not closely surved. This study was made to investigate the effects of Bikiwhan on the innate immunity were analysed by measuring the functions of phagocytes, and those of specific immunity were analysed by measuring T and B cells activities. The followings are the results obtained from this study : 1. Bikiwhan has direct cytotoxic effects against human lymphoma cell lines (K562) in a dose dependent manner. 2. An administration of Bikiwhan increased allogenic immune response in the mouse. 3. An administration of Bikiwhan increased the antibodies formation against SRBC. 4. An administration of Bikiwhan enhanced the apperance of rosette forming cells in the spleen. 5. An administration of Bikiwhan decreased the delayed-type hypersensitivity against dinitrofluorobenzene. 6. An administration of Bikiwhan has no effect on natural killer cells. 7. Bikiwhan increased the phagocyte activity of peritoneal macrophages in vitro and in in vivo as well. 8. Bikiwhan depressed the formation of reactive oxygen intermediated in vitro and in vivo as well. 9. Bikiwhan has the capacity to make peritoneal macrophages secrete nitric oxide. The above results demonstrate that Bikiwhan has enhancing effects of immune responses against tumors by decreasing tissue demages caused by immune responses.

• Journal of Korean Medicine Rehabilitation
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• v.29 no.2
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• pp.135-147
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• 2019

Objectives This study was performed to evaluate the effect of Pyrola japonica extract (NJ) and its principal constituent, homoarbutin (HA) on osteoclast differentiation and gene expression and bone resorption. The osteoclastogenesis and gene expression were determined in receptor activator of nuclear factor kappa B ligand (RANKL)-stimulated RAW264.7 cell. Methods In order to evaluate the effect of HA extracted from NJ on bone resorption, osteoclasts were used to be differentiated and formed by stimulating RAW264.7 cells with RANKL. Tartarate-resistant acid phosphatase (TRAP) (+) polynuclear osteoclast formation ability was evaluated, and differentiation control genes including cathepsin K, matrix metalloproteinases-9 (MMP-9), and TRAP in osteoclast differentiation were analyzed by real-time polymerase chain reaction (PCR). Immunoblotting was performed to measure the effect of mitogen-activated protein kinase (MAPK) factors on bone resorption, and the effect of osteoclasts on osteoclast differentiation was measured. Results Both NJ and high concentration of HA blocked RANKL-stimulated differentiation from RAW264.7 cell to TRAP-positive multinucleated cells. NJ reduced RANKL-induced expression of TRAP, cathepsin K. Both NJ and high concentration of HA inhibited RANKL-mediated expression of MMP-9, nuclear factor of activated T-cells, cytoplasmic 1, and cellular Jun-fos. NJ suppressed RANKL-stimulated expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase, tumor necrosis factor-alpha, and levels of interleukins. Both NJ and HA decreased bone resorption in osteoclast-induced bone pit formation model. Conclusions These results suggest that NJ and HA blocked bone resorption by decreasing RANKL-mediated osteoclastogenesis through down-regulation of genes for osteoclast differentiation.

• Microbiology and Biotechnology Letters
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• v.49 no.4
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• pp.543-551
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• 2021

Nocardiopsis species produce bioactive compounds, such as antimicrobial and anti-cancer agents and toxins. However, no reports have described their anti-inflammatory and anti-fibrotic effects during nasal polyp (NP) formation. In this study, we investigated whether marine-derived bacterial Nocardiopsis sp. 13G027 exerts anti-inflammatory and anti-fibrotic effects on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and transforming growth factor (TGF)-β1-induced NP-derived fibroblasts (NPDFs). Nitric oxide (NO) and prostaglandin E₂ (PGE₂) levels were analyzed. Extract from Nocardiopsis sp. 13G027 significantly inhibited the upregulation of NO and PGE₂ in LPS-activated RAW 264.7 macrophages. The expression of mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt/PKB) in LPS-induced RAW 264.7 macrophages was evaluated; smooth muscle alpha-actin (α-SMA), collagen type I (Col-1), and fibronectin also phosphorylated small mothers against decapentaplegic (SMAD) 2 and 3 in TGF-β1-stimulated NPDFs. The Nocardiopsis sp. 13G027 extract suppressed the phosphorylation of MAPKs and Akt and the DNA-binding activity of activator protein 1 (AP-1). The expression of pro-fibrotic components such as α-SMA, Col-1, fibronectin, and SMAD2/3 was inhibited in TGF-β1-exposed NPDFs. These findings suggest that Nocardiopsis sp. 13G027 has the potential to treat inflammatory disorders, such as NP formation.

• Journal of Ginseng Research
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• v.47 no.1
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• pp.144-154
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• 2023

Background: As the major pathophysiological feature of obstructive sleep apnea (OSA), chronic intermittent hypoxia (CIH) is vital for the occurrence of cardiovascular complications. The activation of calpain-1 mediates the production of endothelial reactive oxygen species (ROS) and impairs nitric oxide (NO) bioavailability, resulting in vascular endothelial dysfunction (VED). Ginsenoside Rg1 is thought to against endothelial cell dysfunction, but the potential mechanism of CIH-induced VED remains unclear. Methods: C57BL/6 mice and human coronary artery endothelial cells (HCAECs) were exposed to CIH following knockout or overexpression of calpain-1. The effect of ginsenoside Rg1 on VED, oxidative stress, mitochondrial dysfunction, and the expression levels of calpain-1, PP2A and p-eNOS were detected both in vivo and in vitro. Results: CIH promoted VED, oxidative stress and mitochondrial dysfunction accompanied by enhanced levels of calpain-1 and PP2A and reduced levels of p-eNOS in mice and cellular levels. Ginsenoside Rg1, calpain-1 knockout, OKA, NAC and TEMPOL treatment protected against CIH-induced VED, oxidative stress and mitochondrial dysfunction, which is likely concomitant with the downregulated protein expression of calpain-1 and PP2A and the upregulation of p-eNOS in mice and cellular levels. Calpain-1 overexpression increased the expression of PP2A, reduced the level of p-eNOS, and accelerated the occurrence and development of VED, oxidative stress and mitochondrial dysfunction in HCAECs exposed to CIH. Moreover, scavengers of O₂^·-, H₂O₂, complex I or mitoKATP abolished CIH-induced impairment in endothelial-dependent relaxation. Conclusion: Ginsenoside Rg1 may alleviate CIH-induced vascular endothelial dysfunction by suppressing the formation of mitochondrial reactive oxygen species through the calpain-1 pathway.

• Molecules and Cells
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• v.40 no.2
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• pp.133-142
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• 2017

Previous studies have shown that bone marrow mesenchymal stromal cell (MSC) transplantation significantly improves the recovery of neurological function in a rat model of intracerebral hemorrhage. Potential repair mechanisms involve anti-inflammation, anti-apoptosis and angiogenesis. However, few studies have focused on the effects of MSCs on inducible nitric oxide synthase (iNOS) expression and subsequent peroxynitrite formation after hypertensive intracerebral hemorrhage (HICH). In this study, MSCs were transplanted intracerebrally into rats 6 hours after HICH. The modified neurological severity score and the modified limb placing test were used to measure behavioral outcomes. Blood-brain barrier disruption and neuronal loss were measured by zonula occludens-1 (ZO-1) and neuronal nucleus (NeuN) expression, respectively. Concomitant edema formation was evaluated by H&E staining and brain water content. The effect of MSCs treatment on neuroinflammation was analyzed by immunohistochemical analysis or polymerase chain reaction of CD68, Iba1, iNOS expression and subsequent peroxynitrite formation, and by an enzyme-linked immunosorbent assay of pro-inflammatory factors (IL-$1{\beta}$ and TNF-${\alpha}$). The MSCs-treated HICH group showed better performance on behavioral scores and lower brain water content compared to controls. Moreover, the MSC injection increased NeuN and ZO-1 expression measured by immunochemistry/immunofluorescence. Furthermore, MSCs reduced not only levels of CD68, Iba1 and pro-inflammatory factors, but it also inhibited iNOS expression and peroxynitrite formation in perihematomal regions. The results suggest that intracerebral administration of MSCs accelerates neurological function recovery in HICH rats. This may result from the ability of MSCs to suppress inflammation, at least in part, by inhibiting iNOS expression and subsequent peroxynitrite formation.

• Nutrition Research and Practice
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• v.18 no.5
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• pp.617-632
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• 2024

BACKGROUND/OBJECTIVES: Atherosclerosis particularly due to high circulating level of low-density lipoprotein is a major cause of cardiovascular diseases. Ellagic acid is a natural polyphenolic compound rich in pomegranates and berries. Our previous study showed that ellagic acid improved functionality of reverse cholesterol transport in murine model of atherosclerosis. The aim of this study is to investigate whether ellagic acid inhibited inflammation-associated atherosclerotic plaque formation in cholesterol-fed apolipoprotein E (apoE)-knockout (KO) mice. MATERIALS/METHODS: Wild type mice and apoE-KO mice were fed a cholesterol-rich Paigen diet for 10 weeks to induce severe atherosclerosis. Concurrently, 10 mg/kg ellagic acid was orally administered to the apoE-KO mice. Plaque lesion formation and lipid deposition were examined by staining with hematoxylin and eosin, Sudan IV and oil red O. RESULTS: The plasma leukocyte profile of cholesterol-fed mice was not altered by apoE deficiency. Oral administration of ellagic acid attenuated plaque lesion formation and lipid deposition in the aorta tree of apoE-KO mice. Ellagic acid substantially reduced plasma levels of soluble vascular cell adhesion molecule and interferon-γ in Paigen diet-fed apoE-KO mice. When 10 mg/kg ellagic acid was administered to cholesterol-fed apoE-KO mice, the levels of CD68 and MCP-1 were strongly reduced in aorta vessels. The protein expression level of nitric oxide synthase-2 (NOS2) in the aorta was highly enhanced by supplementation of ellagic acid to apoE-KO mice, but the expression level of heme oxygenase-1 (HO-1) in the aorta was reduced. Furthermore, ellagic acid diminished the increased aorta expression of the inflammatory adhesion molecules in cholesterol-fed apoE-KO mice. The treatment of ellagic acid inhibited the scavenger receptor-B1 expression in the aorta of apoE-KO mice, while the cholesterol efflux-related transporters were not significantly changed. CONCLUSION: These results suggest that ellagic acid may be an atheroprotective compound by attenuating apoE deficiency-induced vascular inflammation and reducing atherosclerotic plaque lesion formation.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.32 no.1 s.55
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• pp.59-64
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• 2006

Crinum asiaticum Linne var. japonicum has long been used as a rheumatic remedy, an anti-pyretic, an anti-ulcer treatment, and for the alleviation of local pain and fever in Korea and Malaysia. In order to investigate the possibility of Crinum asiaticum Linne var. japonicum extract as a cosmetic ingredient, we measured its anti-inflammatory effect by inhibition of iNOS (inducible nitric oxide synthase), and the release of PGE2, IL-6, and IL-8. HPLC experiment after extraction with 95% ethanol at pH 3.5 showed that Crinum asiaticum Linne var. japonicum was mainly composed of lycorine (up to 1%), a well-known immunosuppressant. The content of lycorine varied depending on the type of tissue analyzed and the extraction method. In anti-inflammatory assay for inhibition of nitric oxide formation on lipopolysaccharide (LPS)- activated mouse macrophage RAW 264.7 cells, the ethanolic extract of Crinum asiaticum showed inhibitory activity of NO production in dose-dependent manner ($IC_{50} = 83.5 {\mu}g/mL$). Additional study by RT-PCR demonstrated that the extract of Crinum asiaticum significantly suppressed the expression of the iNOS gene. Moreover, the extract of Crinum asiaticum did not show my cytotoxicity, but did show cell proliferation effect against LPS ($10{\sim}60%$ increase of tell viability). In an assay to determine inhibition of the $H_2O_2$-activated release of PGE2, IL-6, and IL-8 in human normal fibroblast cell lines, the release of PGE2 and IL-6 was almost completely inhibited above concentrations of 0.05% and 1%, respectively. Moreover, the release of IL-8 was completely inhibited over the entire range of concentrations (> 0.0025%). The result showed that the extract of Crinum asiaticum Linne var. japonicum has sufficient anti-inflammatory effect. There-fore, Crinum asiaticum Linne var. japonicum extract may be useful as an ingredient of cosmetic products.

• Childhood Kidney Diseases
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• v.11 no.1
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• pp.24-31
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• 2007

Purpose : Nitric oxide(NO) is a very potent vasodilator synthesized from L-arginine by endothelial cells. We investigated whether urinary NO excretion was altered in various renal diseases in children and whether urinary NO excretion could be used in predicting pathologic causes and fibrosis in renal diseases in children. Methods : We recruited 48 patients(32 minimal change nephrotic syndrome[MCNS] and 16 vesicoureteral reflux[VUR] patients from the pediatric renal clinic in Korea University Guro Hospital. We measured the concentration of nitrite$(NO_2)$ and nitrate$(NO_3)$ by Griess reaction and that of creatinine(Cr) by Jaffe method in randomized spot urines. We then analyzed the urinary$(NO_2+NO_3)/Cr$ ratios and compared the values between each patient group. Urinary $(NO_2+NO_3)/Cr$ ratios were also evaluated according to the recurrence and the degree of proteinuria at sampling in the MCNS group and compared according to the presence of renal scarring and the grade of reflux in the VUR group. Results : The ratios of urinary$(NO_2+NO_3)/Cr$ were significantly increased in the VUR and MCNS groups, as compared to the control group. In the MCNS group, a higher level of urine $(NO_2+NO_3)/Cr$ was observed In frequent relapse patients(relapse over four times within one year after first diagnosis) and the patients with severe proteinuria at sampling, respectively. The VUR group with renal scars also showed a higher level of urinary$(NO_2+NO_3)/Cr$ compared to that without scars. Conclusions : In summary, VUR may play a role in the pathogenesis of VUR and MCNS. NO also seems to affect proteinuria and renal scar formation. (J Korean Soc Pediatr Nephrol 2007;11:24-31)

• Korean Journal of Fisheries and Aquatic Sciences
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• v.32 no.6
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• pp.764-769
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• 1999

This study was designed to investigate the effects of sea tangle (Laminaria japonica) extract (Dasi-Ex group: dry base $4.0\%$) and fucoidan-added (Fuco-I, II, III group: fucoidan of $1,0\%,\;2.0\%,\;3.0\%$ added to Dasi-Ex) drinks on the formation of oxygen radicals and scavenger enzyme activities of stressed mice. ICR male mice (20 $\pm$2 g) were fed experimental diets and these drinks instead of water for 18 days including 4 days of sociopsychological stress. Dasi-Ex and Fuco-I, II and III groups resulted in a marked decreases $20\~40\%$ in basal oxygen radical (BOR) formation, and $15\~25\%$ in induced oxygen radical (IOR) formation compared with control group. Hydroxyl radical formations were significantly inhibited about $10\%$ in Dasi-Ex group, while remarkably inhibited $30\~40\%$ in Fuco-I, II and III groups. lipid peroxide (ISO) levels in Dasi-Ex group were not significantly different from those of control group, tut Fuco-I, II and III groups resulted in a significant decreases about $10\%$ in LPO levels compared with control group, Dasi-Ex, Fuco-I, II and III groups resulted in a marked decreases ($31\%,\;36\%,\;39\%$ and $42\%$, respectively) in oxidized protein levels through production of carbonyl group. Significant differences in nitric oxide (NO) levels in Dasi-Ex group were not obtained, but NO levels were slightly inhibited about $7\%$ in Fuco-I and II groups and $20\%$ in Fuco-III group compared with control group. Significant differences in superoxide dismutase (SOD) and catalase (CAT) activities in Dasi-Ex and Fuco-I groups were not obtained, but Fuco-II and III groups resulted in a significant increases $25\~40\%$ in SOD activities, and about $10\%$ in CAT activities compared with control group. These results suggest that the sociopsychological stress and aging process could be effectively inhibited by biological activity of sea tangle and fucoidan components.

• Journal of the Korean Society of Marine Environment & Safety
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• v.21 no.2
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• pp.188-193
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• 2015

It has been generally recognized that $N_2O$(Nitrous Oxide) emission from marine diesel engines has a close correlation with $SO_2$(Sulfur Dioxide) emission, and diversity of fuel elements using ships affects characteristics of the $N_2O$ emission. According to recent reports, in case of existence of an enough large NO(Nitric Oxide) generated as fuel combustion, effect of the $SO_2$ emission in exhaust gas on the $N_2O$ formation is more vast than effect of the NO. Therefore, $N_2O$ formation due to the $SO_2$ element operates on a important factor in EGR(Exhaust Gas Recirculation) systems for NOx reduction. An aim of this experimental study is to investigate that intake gas of the diesel engine with increasing of $SO_2$ flow rate affects $N_2O$ emission in exhaust gas. A test engine using this experiment was a 4-stroke direct injection diesel engine with maximum output of 12 kW at 2600rpm, and operating condition was set up at a 75% load. A standard $SO_2$ gas with 0.499%($m^3/m^3$) was used for changing of $SO_2$ concentration in intake gas. In conclusion, the diesel fuel included out sulfur elements did mot emit the $SO_2$ emission, and the $SO_2$ emission in exhaust gas according as increment of the $SO_2$ standard gas had almost the same ratio compared with $SO_2$ rate in mixture inlet gas. Furthermore, the $N_2O$ element in exhaust gas was formed as $SO_2$ mixture in intake gas because increment of $SO_2$ flow rate in intake gas increased $N_2O$ emission. Hence, diesel fuels included sulfur compounds were combined into $SO_2$ in combustion, and $N_2O$ in exhaust gas should be generated to react with NO and $SO_2$ which exist in a combustion chamber.