• YAKHAK HOEJI
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• v.44 no.3
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• pp.224-231
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• 2000

$Nokyangbotang^{TM}$ (NYBT) is a kind of powerful food for health and have been drunk at a oral dose of 80 ml (99.5 mg) three times per day: It has not been well studied about the anti-fatigue and hepatoprotective activity. In this experiments, we evaluated pathophysiologically the effect of NYBT on swimming time in mouse and hepatoprotective activity in rats intoxicated with carbon-tetrachloride. NYBT was nontoxic in orally acute toxicity test ($LD_{50}$, 320 ml/60 kg): a nontoxic food in more four times of one-shoot dosage (80 ml) to human. Weight-loaded forced swimming test was carried out to measure the swimming time of mice with a 4% load of body weight in plastic cylinder (diameter $10{\;}cm{\;}{\times}{\;}height{\;}20{\;}cm$) on water bath at $25^{\circ}C$, and the anti-fatigue activity represented the ratio of swimming time of experimental group to that of control group. NYBT had dose-dependent anti-fatigue activity Mice administered NYBT at a dose of 320 ml/60 kg once daily for 5 days could swim about two times more than control. Hepatoprotective activities of NYBT were examined by the determination of malonedialdehyde (MDA) and pathological survey in liver and liver function test of rat intoxicated with $CCl_4$ at i.m. dose of 2 ml/kg once daily for 7days. NYBT decreased dose-dependently thiobarbituric acid reactive substance: Oral administration of NYBT at a dose of 20 ml/60 kg was $38.51{\;}{\pm}{\;}3.02$ nmol MDA/g of tissue, that of 80 ml/60 kg was $33.76{\;}{\pm}{\;} 1.84$ nmol MDA/g of tissue, and that of 320 ml/60 kg was $32.87{\;}{\pm}{\;}1.90$ nmol MDA/g of tissue as compared with control group ($43.61{\;}{\pm}{\;}2.85$ nmol MDA/g of tissue). All rats administered NYBT at a dose of 320 ml/60 kg were survival as compared with 40% survival of control animals, and GPT activity of rats administered NYBT at a dose of 80 ml/60 kg was decreased as compared with control. In histopathological survey, NYBT improved slightly the fatty changes of hepatocytes around centrilobular area. These results suggest that NYBT has anti-fatigue and hepatoprotective activity in rats and mice.

• Korean Journal of Food Science and Technology
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• v.32 no.3
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• pp.726-735
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• 2000

This study was conducted to investigate the biological activities of polysaccharide extracted from the fruit body and cultured mycelia of Phellinus linteus IY001. All fractions were extracted by hot water, in the next, Fr. I, Fr. II, Fr. III and Fr. IV were polysaccharide obtained by ethanol precipitation or ultrafiltration. The highest antitumor activity against sarcoma 180 in ICR mice was observed in Fr. III and Fr. IV at the level 85%, but the antitumor activity had no connection with their anticomplementary activity in vitro, it might probably be due to extraction of hot water. All fractions promoted the production of nitric oxide and $TNF-{\alpha}$ in macrophage, addition of Fr. I and Fr. II resulted in production of nitric oxide$3(5.9{\sim}37.6\;{\mu}M)$ and of the $TNF-{\alpha}$ production($8,696.2{\sim}9,420pg/ml)$. All fractions inhibited the lipid peroxidation induced by $AsA/Fe^{2+}$, $ADP/NADPH/Fe^{3+}\;and\;CCl_4/NADPH$ in rat liver microsomes, and Fr. III showed the electron donating ability stronger than tocopherol in assay system using DPPH. From these results, it is suggested that all fractions contain immunoregulatory components which may protect cellular materials from the oxidative damages by their radical scavenging activities.

• Korean Journal of Medicinal Crop Science
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• v.25 no.5
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• pp.269-281
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• 2017

Background: Small particles increase airway inflammation upon reaching the alveoli. Here, we investigated the protective or therapeutic effects of Salvia plebeia R. Br. (SP_R) extracts on airway inflammation. Methods and Results: To investigate the anti-inflammatory activity of SP_R extracts, we measured their inhibitory effect on the production of reactive oxygen species (ROS) expression of inflammatory mediators, and immune cell infiltration in MH-S alveolar macrophage cells and in the ambient particulate matter (APM)-exposed airway inflammation mice model. The SP_R extracts inhibited the production of ROS and expression of IL-4, IL-10, IL-15, and IL-17A mRNA in APM-stimulated MH-S cells. Oral administration of SP_R extracts suppressed APM-induced inflammatory symptoms, such as high alveolar wall thickness, excess collagen fibers, decreased mRNA expression of chemokines (Ccr9, Ccl5, Ccr3), inflammatory cytokines (IL-15, TNF-${\alpha}$), and IL-4 Th2 cytokine in the lung. The SP_R extracts also inhibited ROS production, granulocyte ($CD11b^+Gr-1^+$) infiltration, IL-17A, TNF-${\alpha}$, macrophage inflammatory protein (Mip-2), and chemokine (C-X-C motif) ligand 1 (Cxcl-1) production in the airway. The specific compounds in the SR-R extracts that mediate the anti-inflammatory effects were identified. Conclusions: In this study, SP_R extracts effectively inhibited airway inflammatory responses, such as ROS production and granulocyte infiltration into the airway, by regulating the expression of chemokines and inflammatory cytokines.

• Journal of Ginseng Research
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• v.47 no.4
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• pp.515-523
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• 2023

Background: 20(S)-protopanaxadiol (PPD), one of the main components of ginseng, has anti-inflammatory, anti-estrogenic, and anti-tumor activities. It is known that activated hepatic stellate cells (HSCs) are the primary producers of extracellular matrix (ECM) in the liver, and the Wnt/β-catenin pathway participates in the activation of HSCs. We aimed to explore whether PPD inhibits liver fibrosis is associated with the Wnt/β-catenin pathway inactivation. Methods: The anti-fibrotic roles of PPD were examined both in vitro and in vivo. We also examined the levels of Wnt inhibitory factor 1 (WIF1), DNA methyltransferase 1 (DNMT1) and WIF1 methylation. Results: PPD obviously ameliorated liver fibrosis in carbon tetrachloride (CCl₄)-treated mice and reduced collagen deposition. PPD also suppressed the activation and proliferation of primary HSCs. Notably, PPD inhibited the Wnt/β-catenin pathway, reduced TCF activity, and increased P-β-catenin and GSK-3β levels. Interestingly, WIF1 was found to mediate the inactivation of the Wnt/β-catenin pathway in PPD-treated HSCs. WIF1 silencing suppressed the inhibitory effects of PPD on HSC activation and also restored α-SMA and type I collagen levels. The downregulation of WIF1 expression was associated with the methylation of its promoter. PPD induced WIF1 demethylation and restored WIF1 expression. Further experiments confirmed that DNMT1 overexpression blocked the effects of PPD on WIF1 expression and demethylation and enhanced HSC activation. Conclusion: PPD up-regulates WIF1 levels and impairs Wnt/β-catenin pathway activation via the downregulation of DNMT1-mediated WIF1 methylation, leading to HSC inactivation. Therefore, PPD may be a promising therapeutic drug for patients with liver fibrosis.

• Journal of Ginseng Research
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• v.47 no.4
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• pp.534-542
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• 2023

Background: Ginsenoside Rg1, a bioactive component of Ginseng, has demonstrated anti-inflammatory, anti-cancer, and hepatoprotective effects. It is known that the epithelial-mesenchymal transition (EMT) plays a key role in the activation of hepatic stellate cells (HSCs). Recently, Rg1 has been shown to reverse liver fibrosis by suppressing EMT, although the mechanism of Rg1-mediated anti-fibrosis effects is still largely unclear. Interestingly, Smad7, a negative regulator of the transforming growth factor β (TGF-β) pathway, is often methylated during liver fibrosis. Whether Smad7 methylation plays a vital role in the effects of Rg1 on liver fibrosis remains unclear. Methods: Anti-fibrosis effects were examined after Rg1 processing in vivo and in vitro. Smad7 expression, Smad7 methylation, and microRNA-152 (miR-152) levels were also analyzed. Results: Rg1 significantly reduced the liver fibrosis caused by carbon tetrachloride, and reduced collagen deposition was also observed. Rg1 also contributed to the suppression of collagenation and HSC reproduction in vitro. Rg1 caused EMT inactivation, reducing Desmin and increasing E-cadherin levels. Notably, the effect of Rg1 on HSC activation was mediated by the TGF-β pathway. Rg1 induced Smad7 expression and demethylation. The over-expression of DNA methyltransferase 1 (DNMT1) blocked the Rg1-mediated inhibition of Smad7 methylation, and miR-152 targeted DNMT1. Further experiments suggested that Rg1 repressed Smad7 methylation via miR-152-mediated DNMT1 inhibition. MiR-152 inhibition reversed the Rg1-induced promotion of Smad7 expression and demethylation. In addition, miR-152 silencing led to the inhibition of the Rg1-induced EMT inactivation. Conclusion: Rg1 inhibits HSC activation by epigenetically modulating Smad7 expression and at least by partly inhibiting EMT.

• IMMUNE NETWORK
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• v.20 no.4
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• pp.32.1-32.15
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• 2020

Influenza virus is the major cause of seasonal and pandemic flu. Currently, oseltamivir, a potent and selective inhibitor of neuraminidase of influenza A and B viruses, is the drug of choice for treating patients with influenza virus infection. However, recent emergence of oseltamivir-resistant influenza viruses has limited its efficacy. Morin hydrate (3,5,7,2',4'-pentahydroxyflavone) is a flavonoid isolated from Morus alba L. It has antioxidant, anti-inflammatory, neuroprotective, and anticancer effects partly by the inhibition of the NF-κB signaling pathway. However, its effects on influenza virus have not been studied. We evaluated the antiviral activity of morin hydrate against influenza A/Puerto Rico/8/1934 (A/PR/8; H1N1) and oseltamivir-resistant A/PR/8 influenza viruses in vitro. To determine its mode of action, we carried out time course experiments, and time of addition, hemolysis inhibition, and hemagglutination assays. The effects of the co-administration of morin hydrate and oseltamivir were assessed using the murine model of A/PR/8 infection. We found that morin hydrate reduced hemagglutination by A/PR/8 in vitro. It alleviated the symptoms of A/PR/8-infection, and reduced the levels of pro-inflammatory cytokines and chemokines, such as TNF-α and CCL2, in infected mice. Co-administration of morin hydrate and oseltamivir phosphate reduced the virus titers and attenuated pulmonary inflammation. Our results suggest that morin hydrate exhibits antiviral activity by inhibiting the entry of the virus.

• International Journal of Stem Cells
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• v.16 no.3
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• pp.342-355
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• 2023

Background and Objectives: Osteoblasts are derived from bone marrow mesenchymal stem cells (BMMSCs) and play important role in bone remodeling. While our previous studies have investigated the cell subtypes and heterogeneity in osteoblasts and BMMSCs separately, cell-to-cell communications between osteoblasts and BMMSCs in vivo in humans have not been characterized. The aim of this study was to investigate the cellular communication between human primary osteoblasts and bone marrow mesenchymal stem cells. Methods and Results: To investigate the cell-to-cell communications between osteoblasts and BMMSCs and identify new cell subtypes, we performed a systematic integration analysis with our single-cell RNA sequencing (scRNA-seq) transcriptomes data from BMMSCs and osteoblasts. We successfully identified a novel preosteoblasts subtype which highly expressed ATF3, CCL2, CXCL2 and IRF1. Biological functional annotations of the transcriptomes suggested that the novel preosteoblasts subtype may inhibit osteoblasts differentiation, maintain cells to a less differentiated status and recruit osteoclasts. Ligand-receptor interaction analysis showed strong interaction between mature osteoblasts and BMMSCs. Meanwhile, we found FZD1 was highly expressed in BMMSCs of osteogenic differentiation direction. WIF1 and SFRP4, which were highly expressed in mature osteoblasts were reported to inhibit osteogenic differentiation. We speculated that WIF1 and sFRP4 expressed in mature osteoblasts inhibited the binding of FZD1 to Wnt ligand in BMMSCs, thereby further inhibiting osteogenic differentiation of BMMSCs. Conclusions: Our study provided a more systematic and comprehensive understanding of the heterogeneity of osteogenic cells. At the single cell level, this study provided insights into the cell-to-cell communications between BMMSCs and osteoblasts and mature osteoblasts may mediate negative feedback regulation of osteogenesis process.

• Animal Bioscience
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• v.37 no.2
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• pp.303-314
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• 2024

Objective: Rutin, also called vitamin P, is a flavonoids from plants. Previous studies have indicated that rutin can alleviate the injury of tissues and cells by inhibiting oxidative stress and ameliorating inflammation. There is no report on the protective effects of rutin on goat rumen epithelial cells (GRECs) at present. Hence, we investigated whether rutin can alleviate lipopolysaccharide (LPS)-induced damage in GRECs. Methods: GRECs were cultured in basal medium or basal medium containing 1 ㎍/mL LPS, or 1 ㎍/mL LPS and 20 ㎍/mL rutin. Six replicates were performed for each group. After 3-h culture, the GRECs were harvested to detect the relevant parameters. Results: Rutin significantly enhanced the cell activity (p<0.05) and transepithelial electrical resistance (TEER) (p<0.01) and significantly reduced the apoptosis rate (p<0.05) of LPS-induced GRECs. Rutin significantly increased superoxide dismutase, glutathione peroxidase, and catalase activity (p<0.01) and significantly decreased lactate dehydrogenase activity and reactive oxygen species and malondialdehyde (MDA) levels in LPS-induced GRECs (p<0.01). The mRNA and protein levels of interleukin 6 (IL-6), IL-1β, and C-X-C motif chemokine ligand 8 (CXCL8) and the mRNA level of tumor necrosis factor-α (TNF-α) and chemokine C-C motif ligand 5 (CCL5) were significantly increased in LPS-induced GRECs (p<0.05 or p<0.01), while rutin supplementation significantly decreased the mRNA and protein levels of IL-6, TNF-α, and CXCL8 in LPS-induced GRECs (p<0.05 or p<0.01). The mRNA level of toll-like receptor 2 (TLR2), and the mRNA and protein levels of TLR4 and nuclear factor κB (NF-κB) was significantly improved in LPS-induced GRECs (p<0.05 or p<0.01), whereas rutin supplementation could significantly reduce the mRNA and protein levels of TLR4 (p<0.05 or p<0.01). In addition, rutin had a tendency of decreasing the protein levels of CXCL6, NF-κB, and inhibitor of nuclear factor kappa-B alpha (0.05

• Herbal Formula Science
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• v.15 no.1
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• pp.163-173
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• 2007

Jeungaektang (JAT) is the herbal formula, has the effect of moistening the dryness by activating lung Qi and by nourishing Yin, has being used for dryness syndromes. Generally the herbal formulae for moistening dryness are used for exogenous or endogenous dryness syndromes. JAT has been clinically used for the treatment of endogenous dryness syndromes. It is composed of Scrophulariae Radix. Rehmanniae Radix and Liriopis Tuber. Recent studies showed that JAT has a protective effect against $CCl_{4}-induced$ hepatotoxicity and anti-inflammatory effects against ear swelling of mouse induced by Crotonis Fructus. However, the effect of JAT on the immunological activity was rarely studied. Therefore, this study evaluated the effects of JAT the regulatory mechanism of nitric oxide (NO) and cytokines in the lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. After the treatment of JAT water extract, cell viability was measured by MTT assay, NO production was monitored by measuring the nitrite content in culture medium. Cyclooxygenase-2 (COX -2) and inducible nitric oxide synthase (iNOS) were determined by immunoblot analysis, and levels of cytokine were analyzed by sandwich immunoassays. Results provided evidence that JAT inhibited the production of nitrite and nitrate ($0.1{\sim}1.0$ mg/ml), iNOS ($0.1{\sim}1.0$ mg/ml), $interleukin-1{\beta}$ ( $0.1{\sim}1.0$ mg/ml) and tumor necrosis $factor-{\alpha}$ ($0.1{\sim}1.0$ mg/ml) in RAW 264.7 cells activated with LPS. Furthermore, JAT inhibited the expression of COX-2 expression and production of prostagladin E2 ($0.1{\sim}1.0$ mg/ml). These findings suggest that JAT can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections.

• Radiation Oncology Journal
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• v.12 no.2
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• pp.129-141
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• 1994

Intracellular ions which have a major role in cellular function have been reported to affect repair of radiation damage. Recently it has been reported that ouabain sensitizes A549 tumor cellls but not CCL-120 normal cells to radiation. Ouabain inhibits the $Na^+-K^+$-pump rapidly thus it increases intracellular Na concentration, Vanadate which is distributed extensively in almost all living organisms is known to be a $Na^+-K^+$-ATPase inhibitors, This study was performed to see any change in radiosensitivity of tumor cell by vanadate and any role of $Na^+-K^+$ATPase in radiosensitization. Experiments have been carried out by pretreatment with vanadate in human cell line(A549, JMG) and mouse cell line(L1210, spleen). For the cell survival MTT assay was performed for A549 and JMC cells and frypan blue dye exclusion test for L120, and spleen cells. Measurements of $Na^+-K^+$-ATPase activity in control, vanadate treated cell, radiation treated cell (9 Gy for A549 and JMG, 2 Gy for L1201, spleen), and combined $10^{-6}M$ vanadate and radiation treated cells were done. The results were summerized as fellows. 1. L1210 cell was most radiosensitive, and spleen cell and JMG cell were intermediate, and A549 cell was least radiosensitive. 2. Mininum or no cytotoxicity was seen with vanadate below concentration of $10^{-6}M$. 3. In A549 cells there was a little change in radiosensitivity with treatment of vanadate. However radiation sensitization was shown in low dose level of radiation i. e. 2- Gy. In JMG cells no change in radiosensitivity was noted. Both L1210 and spleen cell had radiosensitization but change was greater in tumor cell. 4. $Na^+-K^+$-ATPase activity was inhibited significantly in tumor cell by treatment of vanadate. 5. Radiaiton itself inhibited $Na^+-K^+$-ATPase activity of tumor cell with high $Na^+-K^+$-ATPase concention. Increase in radiosensitivity by vanadate was closely associated with orginal $Na^+-K^+$-ATPase contents. From the above results vanadate had little cytotoxicity and it sensitized tumor cells to radiation. Inhibitory effect of vanadate on $Na^+-K^+$-ATPase activity might be one of the contributing factors for radiosensitization to tumor cells which has greater enzyme activity than that of normal cell. It was suggested vanadate could be used as a potential radiosensitizer for tumor cells.