• Biomedical Science Letters
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• v.28 no.3
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• pp.170-177
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• 2022

In mountainous regions, wild herbs which can also be edible in nature for humans and animals possess a wide array of biologically diversified properties. It is because of the fact that due to the cold weather of mountains; they are enriched in certain kinds of phytochemicals such as anti-oxidants, anti-inflammatory and many more. One such kind of an herb is Aster scaber (AS) in Korean. It is a widely cultivated culinary herb in Korean peninsula and used as a side dish in Korean culinary cuisine. In view of its extensive use in cuisine, we geared to unravel the anti-oxidant and anti-inflammatory effects of AS in murine alveolar macrophage cell line (MH-S). 2,2'-Azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assays revealed a dose dependent (7.8~1,000 ㎍/mL) inhibition of oxidation by AS 70% ethanol (ASE) extract as compared to Trolox and Ascorbic acid respectively. Nitric oxide assay (NO) showed a dose dependent decrease (5~40 ㎍/mL) in MH-S cells with ASE when stimulated with Coal Fly Ash (CFA). Moreover, this dose for NO reduction was also found to be least cytotoxic for cells as determined by cellular viability (MTT) assay. The gene expression of pro-inflammatory mediators (iNOS and COX-2) and cytokines (IL-6 and IL-1β) and were also dose dependently inhibited by ASE in MH-S cells through RT-PCR. Therefore, in light of these findings, AS exhibited a strong anti-oxidant and anti-inflammatory agent. These results also justify the extensive use of this mountainous herb in culinary practices for beneficial effects on human health.

• International Journal of Oral Biology
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• v.35 no.1
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• pp.27-33
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• 2010

Periodontal disease is a major oral disorder and comprises a group of infections that lead to inflammation of the gingiva and the destruction of periodontal tissues. $PPAR{\gamma}$ plays an important role in the regulation of several metabolic pathways and has recently been implicated in inflammatory response pathways. However, its effects on periodontal inflammation have yet to be clarified. In our current study, we evaluated the anti-inflammatory effects of $PPAR{\gamma}$ on periodontal disease. Human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS) showed high levels of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), matrix metalloproteinase-2 (MMP-2), and -9 (MMP-9). Moreover, these cells also showed upregulated activities for extracellular signal regulated kinase (ERK1/2), inducible nitric oxide synthase (iNOS) and cyclooxygnase-2. However, cells treated with Ad/$PPAR{\gamma}$ and rosiglitazone in same culture system showed reduced ICAM-1, VCAM-1, MMP-2, -9 and COX-2. Finally, the anti-inflammatory effects of $PPAR{\gamma}$ appear to be mediated via the suppression of the ERK1/2 pathway and consequent inhibition of NF-kB translocation. Our present findings thus suggest that $PPAR{\gamma}$ indeed has a pivotal role in gingival inflammation and may be a putative molecular target for future therapeutic strategies to control chronic periodontal disease.

• Korean Journal of Korean Medical Institute of Dermatology and Aesthetics
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• v.1 no.1
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• pp.53-90
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• 2005

Purpose: Contents of astragaloside I, II and IV, cytotoxicity, anticancer activity, immunomodulatory activity and antioxidant capacity were to be compared as a function of the cultivated years as one, three, five and seven years. Method: Major components of Astragali membranacei Radix were separated as astragaloside I, astragaloside II, astragaloside IV by HPLC analysis. Cytotoxicity and anticancer activities were measured by MTT and SRB assay. For immunomodulatory activity, the secretion of IL -6 and $TNF-{\alpha}$, NK cell activation and macrophage activation were observed as well as kinetics of responding to human T cells by a microphysiometer. In vitro antioxidant activities were measured by several radical scavenging activities of superoxide anion radican, DPPH, LDL and linoleic acid. For in vivo activity, the activation of SOD, GSH-px, catalase, ALDH and ADH was measured as well the relative weight of liver. Result : 1. For HPLC analysis, the contents of all of astragaloside I, astragaloside II, astragaloside IV were in order of three, five, one and seven years. 2. The cytotoxicity of normal human lung cell line, HEL299 showed lower than 18% in adding 0.25 mg/ml, and 28.9% in adding 1.0 mg/ml of water extract of seven year root. For methanol extracts, three year root showed highest cytotoxicity as 35.2 % and there was no difference between the cultivated years. 3. For anticancer activities, methanol extracts of one and three year roots showed relatively high inhibition of human stomach cancer cells, AGS, breast cancer cells, MCF-7, lung cancer cells, A549 and liver cancer cell, Hep3B as well as high selectivities. 4. The water extract of seven year root could yield high secretion of IL-6 from both human Band T cells while the methanol extracts of three and five year roots secreted high amounts of IL-6 and $TNF-{\alpha}$ from both Band T cells. 5. As a result of in vitro antioxidant activities, both water and methanol extracts from five and seven year roots showed high activities for superoxide anion radical scavenging activity, inhibiting linoleic acid peroxide and contents of total phenols. 6. For in vivo tests, Mn-SOD and GSH-px activities and weight of liver were better in adding seven year root. For ALDH activity one year root was better and for ADH activity five year root. Overall speaking, seven year root showed relatively better antioxidant activities. Conclusion:There was difference of the contents of astragaloside I, astragaloside II, astragaloside IV according to cultivation year. Methanol extract showed better activities of anticancer and immune activation rather than water extract Interestingly enough, for methanol extracts, overall activities were improved as the cultivation year increased. There might be further investigation required for the clinical uses of the results as several biological activities varied according to the cultivated year of Astragali membranacei Radix.

• Nutrition Research and Practice
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• v.17 no.6
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• pp.1084-1098
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• 2023

BACKGROUND/OBJECTIVES: Previous research has shown maternal betaine supplementation alleviates fetal-derived hepatic steatosis. Therefore, this study examined the anti-inflammatory effect of maternal betaine intake in offspring mice and its mechanism. MATERIALS/METHODS: Female C57BL/6J mice and their offspring were randomly divided into 3 groups according to the treatment received during gestation and lactation: control diet (CD), fatty liver disease (FLD), and fatty liver disease + 1% betaine (FLD-BET). The FLD group was given a high-fat diet and streptozotocin (HFD + STZ), and the FLD-BET group was treated with HFD + STZ + 1% betaine. After weaning, the offspring mice were given a normal diet for 5 weeks and then dissected to measure the relevant indexes. RESULTS: Compared to the CD group, the offspring mice in the FLD group revealed obvious hepatic steatosis and increased serum levels of alanine aminotransferase, interleukin (IL)-6, and tumor necrosis factor (TNF)-α; maternal betaine supplementation reversed these changes. The hepatic mRNA expression levels of IL-6, IL-18, and Caspase-1 were significantly higher in the FLD group than in the CD group. Maternal betaine supplementation reduced the expression of IL-1β, IL-6, IL-18, and apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (ASC). Maternal betaine supplementation also reversed the increasing protein expressions of nitric oxide dioxygenase-like receptor family pyrin domain containing 3 (NLRP3), ASC, Caspase-1, IL-1β, and IL-18 in offspring mice exposed to HFD + STZ. Maternal betaine supplementation decreased the homocysteine (Hcy) and s-adenosine homocysteine (SAH) levels significantly in the livers. Furthermore, the hepatic Hcy concentrations showed significant inverse relationships with the mRNA expression of TNF-α, NLRP3, ASC, and IL-18. The hepatic SAH concentration was inversely associated with the IL-1β mRNA expression. CONCLUSIONS: The lipotropic and anti-inflammatory effect of maternal betaine supplementation may be associated with the inhibition of NLRP3 inflammasome in the livers of the offspring mice.

• Food Science and Biotechnology
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• v.18 no.5
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• pp.1204-1211
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• 2009

Hericium erinaceus is an edible mushroom used as a medicinal food in Asian countries. In this study, the chemopreventive effects of H. erinaceus mycelia hot water extract (HEW) were evaluated. HEW remarkably induced the luciferase activity of the antioxidant response element (ARE), located in the promoter region of phase 2 and antioxidant genes and regulated by nuclear factor E2-related factor 2 (Nrf2). The up-regulation of ARE activity by HEW corresponded with the induction of Nrf2 and the antioxidant enzyme, hemeoxygenase-1. The inhibition of cyclooxygenase-2 (COX-2) activity is a promising effective approach in cancer chemoprevention, and HEW prominently suppressed COX-2 protein expression in HepG2 cells. Furthermore, HEW showed anti-inflammatory activity by modulating inflammatory mediators such as nitric oxide (NO), inducible NO synthase, tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, and the transcription factor, nuclear factor-${\kappa}B$, in lipopolysaccharide-stimulated RAW 264.7 cells. These results suggest that H. erinaceus possessed anti-tumor and anti-inflammatory effects via the modulation of Nrf2/ARE and inflammatory signaling pathways, and may therefore have potential use as a natural chemopreventive agent.

• Journal of Ginseng Research
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• v.36 no.2
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• pp.135-145
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• 2012

Previously, we reported that Helicobacter pylori-associated gastritis and gastric cancer are closely associated with increased levels of hydrogen sulfide ($H_2S$) and that Korean red ginseng significantly reduced the severity of H. pylori-associated gastric diseases by attenuating $H_2S$ generation. Because the incubation of endothelial cells with $H_2S$ has been known to enhance their angiogenic activities, we hypothesized that the amelioration of $H_2S$-induced gastric inflammation or angiogenesis in human umbilical vascular endothelial cells (HUVECs) might explain the preventive effect of Korean red ginseng on H. pylori-associated carcinogenesis. The expression of inflammatory mediators, angiogenic growth factors, and angiogenic activities in the absence or presence of Korean red ginseng extracts (KRGE) were evaluated in HUVECs stimulated with the $H_2S$ generator sodium hydrogen sulfide (NaHS). KRGE efficiently decreased the expression of cystathionine ${\beta}$-synthase and cystathionine ${\gamma}$-lyase, enzymes that are essential for $H_2S$ synthesis. Concomitantly, a significant decrease in the expression of inflammatory mediators, including cyclooxygenase-2 and inducible nitric oxide synthase, and several angiogenic factors, including interleukin (IL)-8, hypoxia inducible factor-1a, vascular endothelial growth factor, IL-6, and matrix metalloproteinases, was observed; all of these factors are normally induced after NaHS. An in vitro angiogenesis assay demonstrated that NaHS significantly increased tube formation in endothelial cells, whereas KRGE pretreatment significantly attenuated tube formation. NaHS activated p38 and Akt, increasing the expression of angiogenic factors and the proliferation of HUVECs, whereas KRGE effectively abrogated this $H_2S$-activated angiogenesis and the increase in inflammatory mediators in vascular endothelial cells. In conclusion, KRGE was able to mitigate $H_2S$-induced angiogenesis, implying that antagonistic action against $H_2S$-induced angiogenesis may be the mechanism underlying the gastric cancer preventive effects of KRGE in H. pylori infection.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.6
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• pp.629-639
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• 2016

The present study was designed to investigate the characteristics of gintonin, one of components isolated from Korean Ginseng on secretion of catecholamines (CA) from the isolated perfused model of rat adrenal gland and to clarify its mechanism of action. Gintonin (1 to $30{\mu}g/ml$), perfused into an adrenal vein, markedly increased the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. The gintonin-evoked CA secretion was greatly inhibited in the presence of chlorisondamine ($1{\mu}M$, an autonomic ganglionic bloker), pirenzepine ($2{\mu}M$, a muscarinic $M_1$ receptor antagonist), Ki14625 ($10{\mu}M$, an $LPA_{1/3}$ receptor antagonist), amiloride (1 mM, an inhibitor of $Na^+/Ca^{2+}$ exchanger), a nicardipine ($1{\mu}M$, a voltage-dependent $Ca^{2+}$ channel blocker), TMB-8 ($1{\mu}M$, an intracellular $Ca^{2+}$ antagonist), and perfusion of $Ca^{2+}$-free Krebs solution with 5mM EGTA (a $Ca^{2+}$chelater), while was not affected by sodium nitroprusside ($100{\mu}M$, a nitrosovasodialtor). Interestingly, LPA ($0.3{\sim}3{\mu}M$, an LPA receptor agonist) also dose-dependently enhanced the CA secretion from the adrenal medulla, but this facilitatory effect of LPA was greatly inhibited in the presence of Ki 14625 ($10{\mu}M$). Moreover, acetylcholine (AC)-evoked CA secretion was greatly potentiated during the perfusion of gintonin ($3{\mu}g/ml$). Taken together, these results demonstrate the first evidence that gintonin increases the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. This facilitatory effect of gintonin seems to be associated with activation of LPA- and cholinergic-receptors, which are relevant to the cytoplasmic $Ca^{2+}$ increase by stimulation of the $Ca^{2+}$ influx as well as by the inhibition of $Ca^{2+}$ uptake into the cytoplasmic $Ca^{2+}$ stores, without the increased nitric oxide (NO). Based on these results, it is thought that gintonin, one of ginseng components, can elevate the CA secretion from adrenal medulla by regulating the $Ca^{2+}$ mobilization for exocytosis, suggesting facilitation of cardiovascular system. Also, these findings show that gintonin might be at least one of ginseng-induced hypertensive components.

• Journal of Ginseng Research
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• v.44 no.6
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• pp.790-798
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• 2020

Background: Beneficial effects of Korean Red Ginseng (KRG) on polycystic ovarian syndrome (PCOS) remains unclear. Methods: We examined whether pretreatment (daily from 2 hours before PCOS induction) with KRG extract in water (KRGE; 75 and 150 mg/kg/day, p.o.) could exert a favorable effect in a dehydroepian-drosterone (DHEA)-induced PCOS rat model. Results: Pretreatment with KRGE significantly inhibited the elevation of body and ovary weights, the increase in number and size of ovarian cysts, and the elevation of serum testosterone and estradiol levels induced by DHEA. Pretreatment with KRGE also inhibited macrophage infiltration and enhanced mRNA expression levels of chemokines [interleukin (IL)-8, monocyte chemoattractant protein-1), proinflammatory cytokines (IL-1β, IL-6), and inducible nitric oxide synthase in ovaries induced by DHEA. It also prevented the reduction in mRNA expression of growth factors (epidermal growth factor, transforming growth factor-beta (EGF, TGF-β)) related to inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cell pathway and stimulation of the nuclear factor erythroid-derived 2-related factor 2 pathway. Interestingly, KRGE or representative ginsenosides (Rb1, Rg1, and Rg3(s)) inhibited the activity of inflammatory enzymes cyclooxygenase-2 and iNOS, cytosolic p-IκB, and nuclear p-nuclear factor kappa-light-chain-enhancer of activated B in lipopolysaccharide-induced RAW264.7 cells, whereas they increased nuclear factor erythroid-derived 2-related factor 2 nuclear translocation. Conclusion: These results provide that KRGE could prevent DHEA-induced PCOS via antiinflammatory and antioxidant activities. Thus, KRGE may be used in preventive and therapeutic strategies for PCOS-like symptoms.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.3-3
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• 2018

For centuries, Panax ginseng Meyer (Korean ginseng) has been widely used as a medicinal herb in Korea, China, and Japan. Ginsenosides are a class of triterpene saponins and recognized as the bioactive components in Korean ginseng. Ginsenosides, which can be classified broadly as protopanaxadiols (PPD), protopanaxatriols (PPT), and oleanolic acids, have been shown to flaunt a vast array of pharmacological activities such as immune-modulatory, anti-inflammatory, anti-tumor, anti-diabetic, and antioxidant effects. In recent years, a number of ginseng and ginsenoside researches have increasingly gained wide attention owing to its unique pharmacological properties. Although good efficacies of ginsenosides have been reported, lack of target specific delivery into tumor sites, low solubility, and low bioavailability due to modifications in gastro-intestinal environments limit their biomedical application in clinical trials. As a result to this major challenge, nanotechnology and drug delivery techniques play a significant role to solve this problematic issue. Thus, we reported the preparation of poly-ethylene glycol (PEG) and glycol chitosan (GC) functionalized to ginsenoside (Compound K and PPD) conjugates via hydrolysable ester bonds with improved aqueous solubility and pH-dependent drug release. In vitro cytotoxicity assays revealed that PEG-CK, and PPD-CK conjugates exhibited lower cytotoxicity compared to bare CK and PPD in HT29 cells. However, GC-CK conjugates exhibited higher and similar cytotoxicity in HT29 and HepG2 cells. Furthermore, GC-CK-treated RAW264.7 cells did not exhibit significant cell death at higher concentration of treatment which supports the biocompatibility of the polymer conjugates. They also inhibited nitric oxide production in lipopolysaccharide (LPS)-induced RAW64.7 cells. In addition to polymer-ginsenoside conjugates, silver (AgNps) and gold nanoparticles (AuNps) have been successfully synthesized by green chemistry using different m. The biosynthesized nanoparticles demonstrated antimicrobial efficacy, anticancer, anti-inflammatory, antioxidant activity, biofilm inhibition, and anticoagulant effect. Special interest on the effective delivery methods of ginsenoside to treatment sites is the focus of metal nanoparticle research.In short, nano-sizing of ginsenoside results in an increased water solubility and bioavailability. The use of nano-sized ginsenoside and P. ginseng mediated metallic nanoparticles is expected to be effective on medical platform against various diseases in the future.

• KSBB Journal
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• v.30 no.4
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• pp.148-154
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• 2015

Onion (Allium cepa) is one of the flavonoids-rich materials in human diet and onion peel, which is the onion by-products, contains over 20 times more quercetin than the flesh. In this study, to examine the anti-inflammatory effects of onion peel hot water extract (OPHWE), the cell viability, nitric oxide (NO), pro-inflammatory cytokines, such as interluekin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and IL-$1{\beta}$, were measured using the murine macrophage cell line RAW 264.7 cells. The Balb/c mice were used for an in vivo acute toxicity test and ICR mice were used for measurement of inhibition effects of croton oil-induced mouse ear edema. As a result, NO levels decreased in a dose-dependent manner. The production of IL-6, TNF-${\alpha}$, and IL-$1{\beta}$ was suppressed by 38%, 41%, and 34% respectively, compared with that of the LPS only group, without any cytotoxicity. The edema formation in the ICR mouse ear was also reduced compared to that in control. Moreover, there were no mortalities occurred in mice administered 5,000 mg/kg body weight of OPHWE. These results suggest that OPHWE has considerable anti-inflammatory activities and can be regarded as a potent candidate material to treat inflammatory diseases.