• Journal of Ginseng Research
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• v.46 no.1
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• pp.62-70
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• 2022

Background: Maternal Toxoplasma gondii (T. gondii) infection during pregnancy has been associated with various mental illnesses in the offspring. Ginsenoside Rh2 (GRh2) is a major bioactive compound obtained from ginseng that has an anti-T. gondii effect and attenuates microglial activation through toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. GRh2 also alleviated tumor-associated or lipopolysaccharide-induced depression. However, the effects and potential mechanisms of GRh2 on depression-like behavior in mouse offspring caused by maternal T. gondii infection during pregnancy have not been investigated. Methods: We examined GRh2 effects on the depression-like behavior in mouse offspring, caused by maternal T. gondii infection during pregnancy, by measuring depression-like behaviors and assaying parameters at the neuronal and molecular level. Results: We showed that GRh2 significantly improved behavioral measures: sucrose consumption, forced swim time and tail suspended immobility time of their offspring. These corresponded with increased tissue concentrations of 5-hydroxytryptamine and dopamine, and attenuated indoleamine 2,3-dioxygenase or enhanced tyrosine hydroxylase expression in the prefrontal cortex. GRh2 ameliorated neuronal damage in the prefrontal cortex. Molecular docking results revealed that GRh2 binds strongly to both TLR4 and high mobility group box 1 (HMGB1). Conclusion: This study demonstrated that GRh2 ameliorated the depression-like behavior in mouse offspring of maternal T. gondii infection during pregnancy by attenuating the excessive activation of microglia and neuroinflammation through the HMGB1/TLR4/NF-κB signaling pathway. It suggests that GRh2 could be considered a potential therapy in preventing and treating psychiatric disorders in the offspring mice of mothers with prenatal exposure to T. gondii infection.

• Nutrition Research and Practice
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• v.17 no.5
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• pp.899-916
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• 2023

BACKGROUND/OBJECTIVES: Oxidative stress is a fundamental neurodegenerative disease trigger that damages and decimates nerve cells. Neurodegenerative diseases are chronic central nervous system disorders that progress and result from neuronal degradation and loss. Recent studies have extensively focused on neurodegenerative disease treatment and prevention using dietary compounds. Heseperetin is an aglycone hesperidin form with various physiological activities, such as anti-inflammation, antioxidant, and antitumor. However, few studies have considered hesperetin's neuroprotective effects and mechanisms; thus, our study investigated this in hydrogen peroxide (H₂O₂)-treated SH-SY5Y cells. MATERIALS/METHODS: SH-SY5Y cells were treated with H₂O₂ (400 µM) in hesperetin absence or presence (10-40 µM) for 24 h. Three-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability, and 4',6-diamidino-2-phenylindole staining allowed us to observe nuclear morphology changes such as chromatin condensation and apoptotic nuclei. Reactive oxygen species (ROS) detection assays measured intracellular ROS production; Griess reaction assays assessed nitric oxide (NO) production. Western blotting and quantitative polymerase chain reactions quantified corresponding mRNA and proteins. RESULTS: Subsequent experiments utilized various non-toxic hesperetin concentrations, establishing that hesperetin notably decreased intracellular ROS and NO production in H₂O₂-treated SH-SY5Y cells (P < 0.05). Furthermore, hesperetin inhibited H₂O₂-induced inflammation-related gene expression, including interluekin-6, tumor necrosis factor-α, and nuclear factor kappa B (NF-κB) p65 activation. In addition, hesperetin inhibited NF-κB translocation into H₂O₂-treated SH-SY5Y cell nuclei and suppressed mitogen-activated protein kinase protein expression, an essential apoptotic cell death regulator. Various apoptosis hallmarks, including shrinkage and nuclear condensation in H₂O₂-treated cells, were suppressed dose-dependently. Additionally, hesperetin treatment down-regulated Bax/Bcl-2 expression ratios and activated AMP-activated protein kinase-mammalian target of rapamycin autophagy pathways. CONCLUSION: These results substantiate that hesperetin activates autophagy and inhibits apoptosis and inflammation. Hesperetin is a potentially potent dietary agent that reduces neurodegenerative disease onset, progression, and prevention.

• The Journal of Internal Korean Medicine
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• v.27 no.4
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• pp.864-878
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• 2006

Purpose : Panax ginseng(PG) is considered to have salutary effects and stimulant actions on physical capacity. However, the effects of PG on the inflammatory cytokine secretion and hypoxia condition are still not understood. This study wasto elucidate the effect of PG on inflammatory cytokine secretion such as interleukin (IL)-1, IL-6, granulocyte macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor $(TNF)-{\alpha}$. Also, the effects on the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) were measured. Methods : The water extract of PG was administrated to HMC-1 cells before phorbol myristate acetate (PMA)+A23187 treatment. $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, GM-CSF, and VEGF secretion were measured by a modified enzyme-linked immunosorbent assay (ELISA). HIF-1 activation was measured by transcription factor enzyme-linked immunoassay (TF-EIA) Results : PG significantly decreased secretion of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, and GM-CSF in PMA+A23187-induced HMC-1 cells. VEGF secretion was not changed but HIF-1 activation was decreased by the treatment of PG. Conclusions : PG inhibited the secretion of inflammatory cytokines, which impliesPG might contribute to treatment of mast cell-mediated inflammatory disease. Also, PG inhibited PMA+A23187-induced $HIF -1{\alpha}activation}$ and DNA-binding activity for HIF-1. Therefore, these data demonstrate that PG modulates inflammatory cytokines through inhibition of $HIF-1{\alpha}activation}$ activation.

• Journal of Veterinary Clinics
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• v.29 no.4
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• pp.283-296
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• 2012

Allergic contact dermatitis (ACD) is an inflammatory skin disease and regarded as a prototype of T-cell mediated delayed-type hypersensitivity reactions. Poly-${\gamma}$-glutamic acid (PGA) is a biodegradable polymer that is produced by Bacillus subtilis. This study was performed to assess the effects of PGA in a canine model of ACD. ACD was induced on the back of dogs induced by sensitization and repeated application by 2,4-dinitro-1-chlorobenzene (DNCB). Topical treatment of PGA was applied once a day for 12 days and skin biophysical parameters including transepidermal water loss (TEWL), skin hydration, skin pH, skin thickness and erythema index, were measured every two days during experimental periods. Histopathology and immunohistochemistry were performed to evaluate the antiinflammatory effect. In skin biophysical parameters, TEWL, skin hydration, skin thickness and erythema index were significantly increased, with a maximum increase appeared on day 2 (p < 0.05). On the other hand, skin pH was significantly decreased, with a maximum decrease appeared on day 2 (p < 0.01). After the completion of PGA treatment, skin biophysical parameters were significantly reached those of baseline in a time-dependent manner (p < 0.05). In histopathology, marked increases of epidermal thicknesses were induced after DNCB challenge with numerous inflammatory cell infiltrations and edematous changes, decreases of connective tissue occupied regions in dermis. In addition, marked increases of cytokine - tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interferon-${\gamma}$ (IFN-${\gamma}$)-immunoreactivities in the dermis and of apoptotic markers - caspase-3 and PARP-immunoreactivities in the epidermis were observed in DNCB-PBS control as compared with intact control, respectively (p < 0.01). It means, the ACD and related apoptotic changes were induced by DNCB in the present study. However, these ACD induced by DNCB and related apoptosis in epidermis were significantly inhibited by treatment of PGA treated skin, the decreases of infiltrated inflammatory cells and related decreases of pro-inflammatory cytokine immunoreactivities were also observed (p < 0.01). Based on these findings, PGA may have anti-inflammatory and alleviatory effects in the allergic contact dermatitis.

• Journal of Life Science
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• v.26 no.1
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• pp.50-58
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• 2016

The root bark of Ulmus macrocarpa has been used in traditional medicine for the treatment of various diseases such as edema, infection and inflammation. Nevertheless, the biological activities and underlying mechanisms of the immunomodulatory effects remain unclear. In this study, as part of our ongoing screening program to evaluate the immunomodulatory potential of new compounds from traditional medicinal resources, we investigated the effects of U. macrocarpa water extract (UME) on immune modulation in a murine RAW 264.7 macrophage model. As immune response parameters, the productions of as nitric oxide (NO) and cytokines such tumor necrotic factor (TNF)-α, interleukin (IL)-1β and IL-10 were evaluated. Although the release of IL-1β remained unchanged in UME-treated RAW 264.7 macrophages, the productions of NO, TNF-α and IL-10 were significantly increased, along with the increased expression of inducible NO synthase, TNF-α and IL-10 expression at concentrations with no cytotoxicity. UME treatment also induced the nuclear translocation of nuclear factor κB (NF-κB), and phosphorylation of Akt and mitogen-activated protein kinases (MAPKs) indicating that UME activated macrophages through the activation of NF-κB, phosphoinositide-3-kinase (PI3K)/Akt and MAPKs signaling pathways in RAW 264.7 macrophages. Furthermore, pre-treatment with UME significantly attenuated the production of NO, but not TNF-α, IL-1β and IL-10, in lipopolysaccharide-stimulated RAW 264.7 cells suggesting that UME may be useful in preventing inflammatory diseases mediated by excessive production of NO. These findings suggest that the beneficial therapeutic effects of UME may be attributed partly to its ability to modulate immune functions in macrophages.

• Korean Journal of Plant Resources
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• v.34 no.1
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• pp.23-30
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• 2021

Hemistepta lyrata Bunge (HL) has been used as a folk remedy to treat cancer, inflammation, bleeding, hemorrhoids and fever, and leaves and young shoots have been used as famine food. Nevertheless, the biological activities and underlying mechanisms of the anti-inflammatory effects remain unclear. In this study, it was undertaken to explore the functions of the aerial part of HL as a suppressor of inflammation by using RAW 264.7 cells. As immune response parameters, the productions of as nitric oxide (NO) and prostaglandin E2 (PGE2), cytokines such tumor necrotic factor (TNF)-α and interleukin (IL)-6 were evaluated. Although the release of TNF-α remained unchanged in HL-treated RAW 264.7 cells, the productions of NO, PGE2 and IL-6 were significantly increased at concentrations with no cytotoxicity. Furthermore, HL significantly attenuated the mitogen-activated protein kinases (MAPK) pathway including decreasing the phosphorylation of the extracellular signal-regulated kinase (ERK1/2) and p38 mitogen-activated protein kinases. Collectively, this study provides evidence that HL inhibits the production of major pro-inflammatory molecules in LPS-stimulated RAW 264.7 cells via suppression of ERK and P38 MAPK signaling pathways. These findings suggest that the beneficial therapeutic effects of HL may be attributed partly to its ability to modulate immune functions in macrophages.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.4
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• pp.23-40
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• 2011

Objectives: This study was designed to examine the effects of extracts of Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) on the lipid lowering, anti-oxidation and concentration of proinflammatory cytokines and was investigated on hyperlipidemic rats. Methods: Male rats weighing $182.39{\pm}4.71g$ were fed high fat diet for 8 weeks and 36 rats(above 400 g) were divided into 4 groups. Each of 9 rats was divided a control group and experimental groups. We fed a control group of rats a basal diet and administered normal saline(100 mg/kg, 1 time/1 day) for 4 weeks. And we fed each experimental group of rats basal diet and administered an extract of Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) extracts(100 mg/kg, 200mg/kg, 300 mg/kg, 300 mg/kg, 1 time/1 day) for 4 weeks. At the end of the experiment, the rats were sacrificed to determine their chemical composition. We measured lipid of plasma and liver, concentration of proinflmmatory cytokines, anti-oxidative activity and $TNF-{\alpha}$, Apo-B, Apo-E and leptin gene expression. Results: 1. Concentration of plasma free fatty(FFA) showed no significant difference in all the treatment groups. Concentration of plasma triglyceride(TG) showed a significant decrement in the 300 mg/kg in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups than that of control group. 2. Concentration of plasma total cholesterol showed a significant decrement in the 200 and 300 mg/kg in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups than that of control group. Concentration of plasma low density lipoprotein(LDL)-cholesterol showed a Significant decrement in the 300 mg/kg in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups than that of control group. Concentration of plasma high density lipoprotein(HDL)-cholesterol showed a significant increment in the 300 mg/kg in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) group. 3. Concentration of liver total cholesterol showed a tendence to decrease in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups. Concentration of liver TG showed a significant decrement in all Ojeoksangamibang groups than that of control group. 4. Concentration of plasma and liver thiobarbituric acid reactive substance(TBARS) showed a tendence to decrease in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups. 5. The values of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and catalase(CAT) activity showed a significant increment in all Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups than that of control group. 6. The values of plasma aspartate aminotransferase(AST) and alanine aminotransferase(ALT) activity showed no significant different in all treatment group. 7. Concentration of plasma $interleukin(IL)-1{beta}$ showed no significant difference in all the treatment groups. Concentration of plasma IL-6 showed a significant decrement in the 300 mg/kg in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) group than that of control group. Concentration of plasma tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ a siginifant decrement in the 200 and 300 mg/kg in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) group than that of control group. However the concentration of plasma IL-10 in the 300 mg/kg Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups showed a significant increment than that of control group. 9. In the analysis of reverse transcription-polymerase chain reaction(RT-PCR), gene expression of $TNF-{\alpha}$, Apo-B and Apo-E in the Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups showed a lower expression than that of control group. However the gene expression of leptin showed no difference in the treatment groups. 10. The ratio of $TNF-{\alpha}$, Apo-B, and Apo-E per ${\beta}-actin$ expression in the Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups showed a significant decrement than that of control group. However The ratio of leptin expression per ${\beta}-actin$ expression showed no significant difference among all the treatment groups. Conclusions: According to above results, in lowering lipid effect, anti-oxidation and control of pro-inflammatory cytokines production, Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) gives effect.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.2
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• pp.253-261
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• 2004

Ginsenosides and green tea extracts show a variety of biomedical efficacies such as anti-aging, anti-oxidation and anti-tumor-promotion effects. (-)-Epigallocatechin-3-gallate (EGCG) has been reported to inhibit the UVB-induced apoptosis by increasing the Bcl-2-to-Bax ratio. We have previously shown that ginsenoside Fl protects human HaCaT cells from ultraviolet-B (UVB)-induced apoptosis by maintaining constant levels of Bcl-2 and Brn-3a. Here, we investigate the combined effect of ginsenoside Fl and EGCG on the protection of human HaCaT keratinocyte against UVB-induced apoptosis. When treated individually, although 5 ${\mu}$M ginsenoside Fl and 50${\mu}$M EGCG protected cells from UVB-induced apoptosis, 2${\mu}$M ginsenoside Fl or 10${\mu}$M EGCG treatment showed very little protection effect. However, cotreatement of 2${\mu}$M ginsenoside Fl and 10${\mu}$M EGCG successfully protected HaCaT cells from UVB-induced cell death. As expected, combining ginsenoside Fl and EGCG efficiently prevented UVB-induced decrease of Bcl-2 and Brn-3a expression. In addition, cotreatment with ginsenoside F1 and EGCG prevented the dephosphorylation of Rb, whereas individual treatment with ginsenoside Fl or EGCG failed to prevent the dephosphorylation of Rb even at high concentrations.

• Korean Journal of Food Science and Technology
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• v.40 no.2
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• pp.207-214
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• 2008

In Asia Saussurea lappa (SL) has been used as a traditional herbal medicine to treat abdominal pain and tenesmus. Recently, in vitro cell culture studies have shown that SL has anti-ulcer, anti-inflammatory, and anti-tumor properties. To explore its potential chemopreventive and chemotherapeutic effects in colon cancer, we examined whether the hexane extract of SL (HESL) could inhibit the growth of HT-29 human colon cancer cells, and investigated the mechanisms for this effect. The cells were cultured with various concentrations (0-5 ${\mu}g/mL$) of HESL. The results indicated that HESL markedly decreased the numbers of viable HT-29 cells; whereas at the concentration of 5 ${\mu}g/mL$, HESL slightly decreased the viable cell numbers of CCD 1108Sk human skin normal fibroblasts at 72 hr. HESL substantially increased the numbers of cells in the sub G1 phase, and dose-dependently increased apoptotic cell numbers. Western blot analysis of the total cell lysates revealed that HESL increased Bax protein levels, but did not affect Bcl-2 levels. HESL induced the cleavage of poly (ADP-ribose) polymerase and caspases 8, 9, 7, and 3. This study demonstrated that HESL inhibits cell growth and induces apoptosis in HT-29 cells, which may be mediated by its ability to increase Bax levels and activate the caspase pathway. These findings may lead to the development of new therapeutic strategies for colon cancer treatment.

• Journal of Mushroom
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• v.19 no.3
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• pp.225-233
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• 2021

In this study, we evaluated the anti-inflammatory effect of extract from Cudrania tricuspidata twig sawdust fermented with Ganoderma lucidum mycelium. Fermented Cudrania tricuspidata twig sawdust extracted with 70% ethanol and elucidated the potential signaling pathway in lipopolysaccharide (LPS)-induced RAW264.7 cells. Fermented Cudrania tricuspidata twig sawdust inhibits LPS-stimulated nitric oxide (NO) production without affecting cell viability in a dose-dependent manner and production of LPS-induced pro-inflammatory cytokines such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α and prostaglandin2 (PGE₂). Fermented Cudrania tricuspidata twig sawdust also suppressed the expression of the pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW264.7 cells. Moreover, Fermented Cudrania tricuspidata twig sawdust significantly attenuated LPS-induced IkappaB (IκB) degradation and suppressed nuclear factor kappa B (NF-κB) nuclear translocation. These results suggest that fermented Cudrania tricuspidata twig sawdust may have great potential for the development of anti-inflammatory agent.