• Natural Product Sciences
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• 제27권2호
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• pp.115-121
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• 2021

Lentinus edodes contains functional metabolites such as polysaccharopeptides, lectins, and secondary metabolites. Fermented soybean paste is representative fermented materials in Korea, and is gradually increasing due to various biological activities. In the present study, ethanol extracts of fermented products with/without L. edodes were designated as SPL and SP, and prepared to develop safer and therapeutic functional foods with antioxidant and anti-inflammatory activities for treatment of inflammatory disorders. SP and SPL extracts exhibited antioxidant effects via inhibiting radical activities. Inflammatory mediators, nitric oxide (NO), prostaglandin E₂ (PGE₂), interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) production and nuclear factor-kappa B (NF-κB) activation were down-regulated by two extracts. SPL extract more strongly enhanced the antioxidant and anti-inflammatory activities than SP extract. Its' activities shown more longer fermentation period and more strong inhibitory effects. Taken together, our results suggested that fermented product with medicinal plant has synergic effect and SPL can be a potential candidate for treatment of inflammatory bowel diseases.

• 한국식품저장유통학회지
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• 제30권1호
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• pp.65-77
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• 2023

In this study, we investigated the immunological properties of six strains of Acetobacter pasteurianus through nuclear factor-kappa B/activator protein-1 (NF-κB/AP-1) transcription factor activation and nitric oxide (NO) and cytokine production in macrophages. We found that the six A. pasteurianus strains had no significant inhibitory effect on the cell viability of RAW-Blue^TM cells at the concentration of (25, 50, 100 CFU/macrophage). The production of NO and cytokines (TNF-α, IL-1β, and IL-6) showed different abilities of immune activation for each strain, and it was 0.7 to 0.9 times higher than that of the LPS (100 ng/mL, v/v) positive control and 7 to 8 times superior to that of the negative control group. To explore the underlying mechanism, we evaluated the mRNA expression of pro-inflammatory genes. Consequently, we found that inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression including genes expression of cytokines were elevated by the six A. pasteurianus treatment. These results suggested that the six strains of A. pasteurianus have an excellent industrial application value as a functional material for the purpose of enhancing immune function.

• 생명과학회지
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• 제31권8호
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• pp.736-744
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• 2021

강화사자발쑥(Artemisia princeps Pampanini)은 항산화, 항염증 및 항균제와 같은 면역 기능 관련 질병에 널리 사용되는 약초이다. 이 연구에서 우리는 RAW 264.7 세포에서 AP 추출물의 항염증 효과를 조사하고 관련 메커니즘을 평가하였다. AP 추출물의 효과는 complete Freund's adjuvant (CFA) 유도 관절염 및 lipopolysaccharide(LPS) 유도 마우스 모델에서도 평가되었다. RAW 264.7 세포에서 AP 추출물은 LPS에 의해 유도 된 산화질소(NO) 생성과 inducible NO synthase 및 cyclooxygenase-2 단백질 발현을 현저하게 억제했다. RAW 264.7 세포에서 LPS로 유도된 mitogen-activated protein kinase 와 nuclear factor-κB의 인산화 또한 AP 추출물에 의해 유의하게 억제되었다. AP 추출물의 경구 투여는 CFA 처리 마우스 그룹에 비해 발의 부종 및 비장 지수 증가를 억제하였다. 조직학적으로 CFA 처리 마우스 군에서는 cartilage와 synovium에서 염증 세포의 침윤이 증가한 반면 AP 추출물 투여군에서는 억제되었다. 더욱이, AP 추출물은 염증성 사이토카인으로 알려진 tumor necrosis factor-α 수준을 CFA 및 LPS 처리 마우스 모델에서 현저하게 감소시켰다. 결론적으로, AP 추출물의 항염증 및 항 관절염 효과는 in vitro 및 in vivo 모델 모두에서 확인되었으며, 이는 Artemisia princeps Pampanini가 관절염 치료의 후보 물질이 될 수 있음을 시사한다.

• Journal of Microbiology and Biotechnology
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• 제30권4호
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• pp.583-590
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• 2020

Deinococcus actinosclerus BM2^T (GenBank: KT448814) is a radio-resistant bacterium that is newly isolated from the soil of a rocky hillside in Seoul. As an extremophile, D. actinosclerus BM2^T may possess anti-inflammatory properties that may be beneficial to human health. In this study, we evaluated the anti-inflammatory effects of BM2U, an aqueous extract of D. actinosclerus BM2^T, on lipopolysaccharide (LPS)-mediated inflammatory responses in RAW264.7 macrophage cells. BM2U showed antioxidant capacity, as determined by the DPPH radical scavenging (IC₅₀ = 349.3 ㎍/ml) and ORAC (IC₅₀ = 50.24 ㎍/ml) assays. At 20 ㎍/ml, BM2U induced a significant increase in heme oxygenase-1 (HO-1) expression (p < 0.05). BM2U treatment (0.2-20 ㎍/ml) significantly suppressed LPS-induced increase in the mRNA expression of proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 (p < 0.05). BM2U treatment also suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which are involved in the production of inflammatory mediators. BM2U treatment also inhibited the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs): JNK, ERK, and p-38 (p < 0.05). Collectively, BM2U exhibited anti-inflammatory potential that can be exploited in attenuating inflammatory responses.

• 대한본초학회지
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• 제31권5호
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• pp.79-84
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• 2016

Objective : Nypa fruticans Wurmb. Fruit (NF) has been used as a conventional medicine to treat inflammatory peridontal diseases in Myanmar and Eastern Asia. However, the anti-inflammatory effect of NF aqueous extract on lipopolysaccharide (LPS)-induced inflammatory responses was not well-investigated. Therefore, this study was aimed to investigate the anti-inflammatory effect of NF on LPS-induced inflammatory responses on RAW 264.7 cells.Methods : To induce inflammation on the macrophage cell line, RAW 264.7 cells were treated with 500 ng/mL of LPS. Water extracts of NF was treated 1 h prior to treatment of LPS. Cell viability was measured by MTT assay. Production of nitrite was measured with Griess assay and pro-inflammatory cytokines such as interleukine (IL)-1β and IL-6, and tumor necrosis factor (TNF)-α was measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR). In addition, we examined the inhibitory mechanisms of NF by western blot and immunocytochemistry.Result : Water Extract from NF itself did not have any cytotoxic effect at the concentration of 200 ㎍/ml in RAW 264.7 cells. Treatment of NF inhibited the production of nitrite, and pro-inflammatory cytokines inlcuding IL-1β, IL-6 and TNF-α in a dose dependant. In addition, NF treatment inhibited the LPS-induced activation and translocation of nuclear factor (NF)-κB.Conclusion : In summary, our result suggest that treatment of NF could reduce the LPS-induced inflammatory responses via deactivation of NF-κB. This study could suggest that NF could be a beneficial drug or agent to prevent inflammation.

• 대한한방부인과학회지
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• 제34권2호
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• pp.1-15
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• 2021

Objectives: This study was designed to examine immuno-modulatory effects of Evodia Rutaecarpine by activating innate immune system and inhibiting inflammation. Methods: First, Cell cytotoxicity was examined with 4T1 breast carcinoma and TG-induced macrophage. To investigate activating innate immune system of Evodiamine Rutacarpine Extract (ERE) on macrophage, we tested tumor necrosis factor-alpha (TNF-α), interleukin-12 (IL-12), and interleukin-6 (IL-6). In addition, TNF-α and nitric oxide (NO) induced by lipopolysaccharide (LPS) were measured after treating with ERE to observe innate immune modulating effect of ERE on RAW 264.7 cell. Also, mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) were examined by western blot analysis. Results: In cytotoxicity analysis, ERE significantly affected tumor cell growth above specific concentration. Also, ERE significantly affected macrophage growth above specific concetration. As compared with the control group, the production of TNF-α, IL-12 and IL-6 were increased in TG-induced macrophage. As compared with the control group, TNF-α and IL-6 were significantly up-regulated in RAW 264.7 cell. The expression of TNF-α and NO induced by LPS after treating ERE was significantly decreased compared with control group. In addition, We observed ERE inhibited the phosphorylation levels of p-extracellular signal-regulated kinase (p-ERK), p-Jun N-terminal kinase (p-JNK), and p-p38 in western blotting by treating ERE on RAW 264.7 cell. Conclusions: ERE seems to have considerable impact on the anti-cancer effect by activation of innate immune system and inflammation control.

• 대한한방부인과학회지
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• 제34권3호
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• pp.15-28
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• 2021

Objectives: This study was designed to examine the anti-cancer activity by innate immunomodulating and anti-inflammatory effects of liriopis tuber water extract (LPE). Methods: Cell cytotoxicity was tested with 4T1 mouse mammary carcinoma cells, spleen cells, macrophage, and RAW264.7 cells. To investigate innate immunomodulating effects of LPE on macrophage, we measured tumor necrosis factor-alpha (TNF-α), interleukin-12 (IL-12), and interleukin-10 (IL-10). To investigate innate immunomodulating effects of LPE on RAW264.7 cell, we measured TNF-α, interleukin-6 (IL-6). In addition, TNF-α and nitric oxide (NO) induced by lipopolysaccharide (LPS) were measured after treating with LPE to observe innate immunomodulating effect of LPE on RAW264.7 cell. Also, mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) were examined by western blot analysis. Results: In an in vitro cytotoxicity analysis, LPE affected tumor cell growth above specific concentration. As compared with the control group, the production of TNF-α, IL-12, and IL-10 were increased in macrophage. As compared with the control group, the production of TNF-α and IL-6 were increased in RAW 264.7 cell. The expression of TNF-α and NO induced by LPS after treating LPE was decreased. In addition, treatment of RAW 264.7 cell with LPE increased the phosphorylation levels of p-extracellular signal-regulated kinase (p-ERK), p-Jun N-terminal kinase (p-JNK), and p-p38. Conclusions: LPE might have impact on the anti-cancer effect by activation of innate immune system and inflammation control.

• Nutrition Research and Practice
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• 제17권5호
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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.

• Journal of Applied Biological Chemistry
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• 제62권1호
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• pp.57-66
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• 2019

The ethyl acetate fraction of Bat Faeces (Ye Ming Sha: natural products used in Chinese Medicine) after fermentation (EFBF-AF) showed enhanced anti-oxidative effects in 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt assays. Fermentation of the Bat Faeces by using the crude enzyme extract from Aspergillus kawachii, significantly increased the anti-inflammatory effects. Fermented Bat Faeces markedly inhibited nitric oxide production, inducible nitric oxide synthase, and cyclooxygenase-2 expression in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The EFBF-AF reduced the nuclear translocation of nuclear factor kappa B ($NF-{\kappa}B$) via $IKK{\alpha}$ and $I{\kappa}B{\alpha}$ phosphorylation, and decreased the phosphorylated the extracellular signal-regulated kinases (ERK) and p38 expression in LPS-treated RAW 264.7 macrophages. In addition, the EFBF-AF suppressed the expression of pro-inflammatory genes, such as interleukin-$1{\beta}$, interleukin-6, and tumor necrosis $factor-{\alpha}$. These results suggest that fermented Bat Faeces may suppress pro-inflammatory responses in LPS-stimulated RAW 264.7 macrophages cells via ERK, p38 mitogen-activated protein kinase and $NF-{\kappa}B$ signaling pathways.

• Journal of Microbiology and Biotechnology
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• 제29권7호
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• pp.1022-1032
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• 2019

Probiotics are known to provide the host with immune-modulatory effects and are therefore of remarkable interest for therapeutic and prophylactic applications against various disorders, including inflammatory diseases. Weissella cibaria JW15 (JW15) has been reported to possess probiotic and antioxidant properties. However, the effect of JW15 on inflammatory responses has not yet been reported. Therefore, the objective of the current study was to evaluate the anti-inflammatory potential of JW15 against lipopolysaccharide (LPS) stimulation. The production of pro-inflammatory factors and the cellular signaling pathways following treatment with heat-killed JW15 was examined in LPS-induced RAW 264.7 cells. Treatment with heat-killed JW15 decreased nitric oxide and prostaglandin $E_2$ production via down-regulation of the inducible nitric oxide synthase and cyclooxygenase-2. In addition, treatment with heat-killed JW15 suppressed the expression of pro-inflammatory cytokines, interleukin $(IL)-1{\beta}$, IL-6, and tumor necrosis factor-${\alpha}$. The anti-inflammatory properties of treating with heat-killed JW15 were associated with mitogen-activated protein kinase signaling pathway-mediated suppression of nuclear factor-${\kappa}B$. These results indicated that JW15 possesses anti-inflammatory potential and provide a molecular basis regarding the development of functional probiotic products.