• Korean Journal of Veterinary Research
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• v.59 no.2
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• pp.59-67
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• 2019

We investigated whether ${\beta}$-carotene (${\beta}-CA$) or ellagic acid (EA), originating from various fruits and vegetables, has a preventive effect against male infertility induced by exogenous scrotal hyperthermia. ICR adult mice were intraperitoneally treated with 10 mg/kg of ${\beta}-CA$ or EA daily for 13 days consecutively. During this time, mice were subjected to transient scrotal heat stress in a water bath at $43^{\circ}C$ for 20 min on day 7, and their testes and blood were obtained on day 14 for histopathologic and biochemical analyses. Heat stress induced significant testicular weight reduction, germ cell loss and degeneration, as well as abnormal localization of phospholipid hydroperoxide glutathione peroxidase (PHGPx) and manganese superoxide dismutase (MnSOD) in spermatogenic and Leydig cells. Heat stress also altered the levels of oxidative stress (lipid peroxidation, SOD activity, and PHGPx, MnSOD, and $HIF-1{\alpha}$ mRNAs), apoptosis (Bax, Bcl-xL, caspase 3, $NF-{\kappa}B$, and $TGF-{\beta}1$ mRNAs), and androgen biosynthesis (serological testosterone concentration and $3{\beta}$-hydroxysteroid dehydrogenase mRNA) in testes. These changes were all improved significantly by ${\beta}-CA$ treatment, but only slightly improved by EA treatment. These findings indicate that ${\beta}-CA$, through modulations of oxidative stress, apoptosis, and androgen biosynthesis, is a potent preventive agent against testicular injuries induced by scrotal hyperthermia.

• The Korea Journal of Herbology
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• v.32 no.2
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• pp.65-75
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• 2017

Objectives : This study aimed to evaluate the protective effect of Orostachydis Herba (OH) and Fermented OH (OHF) against the acute liver injury by lipopolysaccharide (LPS). Methods : OHF by 4 lactic bacteria such as (Lactobacillus hilgardii (OHF1), Leuconostoc mesenteroides (OHF2), Pediococcus acidilactici (OHF3), Saccharomyces cerevisiae (OHF4)) were prepared. Samples were selected to OHF0, OHF2, OHF3 based on UPLC analysis, DPPH, ABTS radical scavenging activities. To evaluate the protective effect of OHF on liver injury mice, ICR mice were divided into 5 groups: Normal mice (Nor), LPS (20 mg/kg) treated mice (Veh), administrated OHF0, OHF2 OHF3 200 mg/kg body weight during 8 days before LPS injection. Serum and liver were collected 24 hours after LPS injection. Results : The activity was high in order of OHF0 and OHF3 in DPPH and ABTS radical scavenging activities. The quercetin contents for bioactive ingredient of OH was 5.39, kaempferol contents was 9.94 by UPLC analysis. The LPS-treated vehicle group significantly increased liver weight, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in serum. In contrast, administrated OHF3 group decreased liver weight, AST, ALT. In addition, OHF3 groups reduced the elevated levels of reactive oxygen species (ROS) in serum and tissues. Moreover, AP-1, iNOS and COX-2 were significantly decreased in OHF2 and OHF3. But $NF-{\kappa}B$ p65 and $TNF-{\alpha}$ only showed a significant reduction in OHF3. Conclusions : Therefore, these results suggest that fermented Orostachydis Herba might be protective effect on liver injury through anti-oxidant effect.

• The Journal of Korean Medicine
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• v.43 no.3
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• pp.1-15
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• 2022

Objectives: Myrrh have been used as a traditional remedy to treat infectious and inflammatory diseases. However, it is largely unknown whether myrrh ethanol extract could exhibit the inhibitory activities against particulate matter (PM)-induced skin injury on human keratinocytes, HaCaT cells. Therefore, this study was aimed to investigate the inhibitory activity of myrrh ethanol extract on PM-induced skin injury in HaCaT cells. Methods: To investigate the inhibitory effects of myrrh ethanol extract in HaCaT cells, the skin injury model of HaCaT cells was established under PM treatment. HaCaT keratinocyte cells were pre-treated with myrrh ethanol extract for 1 h, and then stimulated with PM. Then, the cells were harvested to measure the cell viability, reactive oxygen species (ROS), pro-inflammatory cytokines including interleukin (IL) 1-beta, IL-6, and tumor necrosis factor (TNF)-𝛼, hyaluronidase, collagen, MMPs. In addition, we examined the mitogen activated protein kinases (MAPKs) and inhibitory kappa B alpha (I𝜅-B𝛼) as inhibitory mechanisms of myrrh ethanol extract. Results: The treatment of myrrh ethanol extract inhibited the PM-induced cell death and ROS production in HaCaT cells. In addition, myrrh ethanol extract treatment inhibited the PM-induced elevation of IL-1beta, IL-6, and TNF-𝛼. Also, myrrh ethanol extract treatment inhibited the increase of hyaluronidase, MMP and decrease of collagen. Furthermore, myrrh ethanol extract treatment inhibited the activation of MAPKs and the degradation of I𝜅-B𝛼. Conclusions: Our result suggest that treatment of myrrh ethanol extract could inhibit the PM-induced skin injury via deactivation of MAPKs and nuclear factor (NF)-𝜅B in HaCaT cells. This study could suggest that myrrh ethanol extract could be a beneficial agent to prevent skin damage or inflammation.

• Journal of Korean Medicine Rehabilitation
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• v.32 no.4
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• pp.9-18
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• 2022

Objectives This study was conducted to confirm the anti-inflammatory effect of Naetakbaekryeom-san (NTB), and whether it could be another treatment for inflammatory diseases. Methods The NTB water extract was extracted with hot water at 100℃ for 2 hours, concentrated at 80℃ under reduced pressure, and used. After 2 hours of pretreatment with NTB and positive control Bay11-7082, nitric oxide (NO), inducible NO synthase (iNOS), interleukin (IL)-6, IL-1𝛽, tumor necrosis factor alpha (TNF-𝛼) were measured in RAW264.7 cells activated with lipopolysaccharides (LPS) 500 ng/mL. After 2 hours of pretreatment with NTB, the anti-inflammatory effect of NTB was evaluated by measuring nuclear factor kappa-light-chain-enhancer of activated B cells (NF-𝜅B) in RAW264.7 cells and 293T cells activated with phorbol 12-myristate 13-acetic acid (PMA) 30 ng/mL. Results In RAW264.7 cells activated with LPS, NTB at concentrations of 0.1, 0.3, and 1.0 mg/mL showed no cytotoxicity, significantly inhibited NO production and inhibition of iNOS expression. TNF-𝛼 cytokine levels was not regulated, but NTB at each concentration inhibited the production of IL-1𝛽 and IL-6, and the effect was higher than that of the positive control Bay11-7082 (20 𝜇M). In PMA-activated RAW264.7 cells and 293T cells, each concentration of NBT decreased the NF-𝜅B transcriptional activity, with the greatest decrease at 1 mg/mL. Conclusions These results demonstrated the anti-inflammatory effect of NTB water extracts, but further studies such as comparison of anti-inflammatory effects and antioxidant effects by NTB component, comparison of effects according to extraction solvents, and clinical studies are needed.

• IMMUNE NETWORK
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• v.11 no.1
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• pp.79-94
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• 2011

Background: Dendritic cell (DC)-based vaccines are currently being evaluated as a novel strategy for tumor vaccination and immunotherapy. However, inducing long-term regression in established tumor-implanted mice is difficult. Here, we show that deoxypohophyllotoxin (DPT) induces maturation and activation of bone marrow-derived DCs via Toll-like receptor (TLR) 4 activation of MAPK and NF-${\kappa}B$. Methods: The phenotypic and functional maturation of DPT-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. DPT-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity and for tumor regression against melanoma. Results: DPT promoted the activation of $CD8^+$ T cells and the Th1 immune response by inducing IL-12 production in DCs. In a B16F10 melanoma-implanted mouse model, we demonstrated that DPT-treated DCs (DPT-DCs) enhance immune priming and regression of an established tumor in vivo. Furthermore, migration of DPT-DCs to the draining lymph nodes was induced via CCR7 upregulation. Mice that received DPT-DCs displayed enhanced antitumor therapeutic efficacy, which was associated with increased IFN-${\gamma}$ production and induction of cytotoxic T lymphocyte activity. Conclusion: These findings strongly suggest that the adjuvant effect of DPT in DC vaccination is associated with the polarization of T effector cells toward a Th1 phenotype and provides a potential therapeutic antitumor immunity.

• Journal of Life Science
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• v.30 no.9
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• pp.804-812
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• 2020

The giant mealworm beetle, Zophobas atratus (Coleoptera: Tenebrionidae) has been used as a protein source for small pets and mammals. Recently, it was temporarily registered in the list of the Food Code. We previously performed an in silico analysis of the Zophobas atratus transcriptome to identify putative antimicrobial peptides and identified several antimicrobial peptide candidates. Among them, we assessed the antimicrobial and anti-inflammatory activities of zophobacin 1 that was selected bio-informatically based on its physicochemical properties against microorganisms and mouse macrophage Raw264.7 cells. Zophobacin 1 showed antimicrobial activities against microorganisms without inducing hemolysis and decreased the nitric oxide production of the lipopolysaccharide-induced Raw264.7 cells. Moreover, ELISA and Western blot analysis revealed that zophobacin 1 reduced expression levels of pro-inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). We also investigated expression of pro-inflammatory cytokines (interleukin-6 and interleukin-1β) production through quantitative real time-PCR and ELISA. Zophobacin 1 markedly reduced the expression level of cytokines through the regulation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling. We confirmed that zophobacin 1 bound to bacterial cell membranes via a specific interaction with lipopolysaccharides. These data suggest that zophobacin 1 could be promising molecules for development as antimicrobial and anti-inflammatory therapeutic agents.

• Microbiology and Biotechnology Letters
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• v.42 no.2
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• pp.170-176
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• 2014

In this study, the anti-oxidative and anti-inflammatory activities of Euptelea pleiosperma ethanol extract (EPEE) were evaluated using in vitro assays and cell culture model systems. EPEE possessed a more potent scavenging activity against 1,1-diphenyl-2-picryl hydrazyl than the ascorbic acid used as a positive control. EPEE effectively suppressed lipopolysaccharide (LPS), in addition to hydrogen peroxide induced reactive oxygen species on RAW 264.7 cells. Furthermore, EPEE induced the expression of the anti-oxidative enzyme heme oxygenase 1 (HO-1) and its upstream transcription factor, nuclear factor-E2-related factor 2 (Nrf2), dose and time dependently. The modulation of HO-1 and Nrf2 expression might be regulated by mitogen-activated protein kinases and phosphatidyl inositol 3 kinase/Akt as their upstream signaling pathways. On the other hand, EPEE inhibited LPS induced nitric oxide (NO) formation without cytotoxicity. Suppression of NO formation was the result of the down regulation of inducible NO synthase (iNOS) by EPEE. Suppression of NO and iNOS by EPEE may be modulated by their upstream transcription factor, nuclear factor ${\kappa}B$, and AP-1 pathways. Taken together, these results provide important new insights into E. pleiosperma, namely that it possesses anti-oxidative and anti-inflammatory activities, indicating that it could be utilized as a promising material in the field of nutraceuticals.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.6
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• pp.911-917
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• 2016

Lespedeza cuneata G. Don is an edible perennial herb used in traditional Korean medicine. We investigated the anti-proliferative properties and mechanism of L. cuneata extract. The ethanolic extract of L. cuneata dose-and time-dependently inhibited human colorectal cancer cell proliferation. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to test the effect of the extract on proliferation of HT-29 colorectal cancer cells. The extract inhibited HT-29 cell proliferation with an $IC_{50}$ value of $554.26{\pm}8.81{\mu}g/mL$. L. cuneata extract suppressed production of pro-inflammatory cytokines interleukin-6 and tumor necrosis $factor-{\alpha}$. Apoptosis was evaluated by analysis of DNA fragmentation, poly(ADP-ribose) polymerase cleavage, caspase-3 activity, and protein expression of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2). Our results demonstrated that the extract induced DNA fragmentation and characteristic morphological changes associated with apoptosis in HT-29 colorectal cancer cells. The extract also time- and dose-dependently up-regulated expression of the Bax and down-regulated expression of the Bcl-2. Furthermore, the extract dose- and time-dependently enhanced caspase-3 activity. Our findings provide evidence that L. cuneata extract may mediate its anti-proliferative effect via modulation of apoptosis.

• Journal of Nutrition and Health
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• v.41 no.3
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• pp.224-231
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• 2008

We examined the effect of indole-3-carbinol (I3C, $C_9H_9NO$), an autolysis product of a glucosinolate and a glucobrassicin in vegetables, on MMP-2, -9 activities and TIMP-l and -2 inductions via microtubule-associated protein kinase (MAPK) signaling pathway in prostate cancer cell line, PC3 cells. Our results indicated that I3C inhibited cell growth of PC3 cells in dose (0,50, 100 ,${\mu}M$) and time (0,24,48 and 72 h) dependent manners. Using gelatin zymography for MMP activity, we demonstrated that I3C significantly decrease MMP-2 and -9 activities in PC3 cells. We also observed that I3C decreased the proteins and mRNA levels of MMP-2 and -9 in PC3 cells as well. Inversely, expressions of TIMP-l and -2 protein and mRNA in PC3 cells were increased by I3C in a dose dependent manner. In another experiment, we showed that I3C inhibited PC3 cells invasiveness by using marigel invasion assay and we also found that I3C suppressed MMP transcriptional activity by MAPK signaling pathways. Taken together, our results suggest that I3C may contribute to the potential beneficial food component to prevent the cancer metastasis in prostate cancer cells. (KoreanJNutr2008; 41(3): 224~23I)

• Korean Journal of Acupuncture
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• v.24 no.3
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• pp.149-164
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• 2007

Objectives : Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disease in the gastrointestinal tract. The sources and pathologic mechanisms of IBD are still unknown. Moreover conventional therapies for IBD are not always effective, and they often have serious side effects. The purpose of this study is to examine the effect of Moxi-tar herbal acupuncture in IBD affected mice. Methods : Mice were treated with 5 % 2, 4, 6 - trinitrobenzenesulfonic acid (TNBS) on day 1 and day 7. To assume the preemptive effect and therapeutic effect, herbal acupuncture was practiced with Moxi-tar at BL25 (Daejangsu) on day 0, day 3, and day 6. The end of day in treatment with Moxi-tar herbal acupuncture, the mortality and the inflammatory factors of the colon were measured by the various methods. Results TNBS induced high mortality but herbal acupuncture with Moxi-tar at BL25 sup-pressed the mortality caused by TNBS. TNBS induced infiltration of immune cells in all layers of the colon and increased myeloperoxygenase (MPO) activity, while the treatment with Moxi-tar herbal acupuncture at BL25 suppressed the infiltration of immune cells and the increase of MPO activity caused by TNBS to normal levels, Herbal acupuncture with Moxi-tar regulated $NF-{\kappa}B$ activity, which is an important factor for the pathogenesis of chronic colitis, and reduced the expressions of $TNF-{\alpha}$, $IL-1{\beta}$, and ICAM-1 in the colons of TNBS treated mice. Furthermore herbal acupuncture suppressed macro- and micro- colonic damages caused by TNBS. Conclusions : This study demonstrates that herbal acupuncture with Moxi-tar at BL25 isa potential preemptive and/or therapeutic method targeting the chronic IBD.