• Proceedings of the Plant Resources Society of Korea Conference
• /
• 2018.10a
• /
• pp.98-98
• /
• 2018

In this study, we evaluated the anti-inflammatory effect of extracts of leaves (ST-L) and branches (ST-B) from Sageretia theezans in LPS-stimulated RAW264.7 cells. ST-L and ST-B significantly inhibited the production of the pro-inflammatory mediators such as NO, iNOS, COX-2, $IL-1{\beta}$ and IL-6 in LPS-stimulated RAW264.7 cells. ST-L and ST-B blocked LPS-induced degradation of $I{\kappa}B-{\alpha}$ and nuclear accumulation of p65, which resulted to the inhibition of $NF-{\kappa}B$ activation in RAW264.7 cells. ST-L and ST-B also attenuated the phosphorylation of ERK1/2, p38 and JNK in LPS-stimulated RAW264.7 cells. In addition, ST-L and ST-B increased HO-1 expression in RAW264.7 cells, and the inhibition of HO-1 by ZnPP reduced the inhibitory effect of ST-L and ST-B against LPS-induced NO production in RAW264.7 cells. Inhibition of p38 activation and ROS elimination attenuated HO-1 expression by ST-L and ST-B, and ROS elimination inhibited p38 activation induced by ST-L and ST-B. ST-L and ST-B dramatically induced nuclear accumulation of Nrf2, but this was significantly reversed by the inhibition of p38 activation and ROS elimination. Collectively, our results suggest that ST-L and ST-B exerts potential anti-inflammatory activity by suppressing $NF-{\kappa}B$ and MAPK signaling activation, and activating HO-1 expression through the nuclear accumulation of Nrf2 via ROS-dependent p38 activation. These findings suggest that ST-L and ST-B may have great potential for the development of anti-inflammatory drug to treat acute and chronic inflammatory disorders.

• Biomolecules & Therapeutics
• /
• v.26 no.2
• /
• pp.175-181
• /
• 2018

Carbon monoxide (CO) is well-known as toxic gas and intrinsic signaling molecule such as neurotransmitter and blood vessel relaxant. Recently, it has been reported that low concentration of CO exerts therapeutic actions under various pathological conditions including liver failure, heart failure, gastric cancer, and cardiac arrest. However, little has been known about the effect of CO in neurodegenerative diseases like Parkinson's disease (PD). To test whether CO could exert a beneficial action during oxidative cell death in PD, we examined the effects of CO on 6-hydroxydopamine (6-OHDA)-induced cell death in C6 glioma cells. Treatment of CO-releasing molecule-2 (CORM-2) significantly attenuated 6-OHDA-induced apoptotic cell death in a dose-dependent manner. CORM-2 treatment decreased Bax/Bcl2 ratio and caspase-3 activity, which had been increased by 6-OHDA. CORM-2 increased phosphorylation of NF-E2-related factor 2 (Nrf2) which is a transcription factor regulating antioxidant proteins. Subsequently, CORM-2 also increased the expression of heme oxygenase-1 and superoxide dismutases (CuZnSOD and MnSOD), which were antioxidant enzymes regulated by Nrf2. These results suggest that CO released by CORM-2 treatment may have protective effects against oxidative cell death in PD through the potentiation of cellular adaptive survival responses via activation of Nrf2 and upregulation of heme oxygenase-1, leading to increasing antioxidant defense capacity.

• Journal of Life Science
• /
• v.24 no.7
• /
• pp.713-720
• /
• 2014

In this study, the antioxidative and anti-inflammatory activities of Ardisia arborescens ethanol extract (AAEE) were evaluated using in vitro assays and a cell culture model system. AAEE exhibited potent scavenging activity against 1,1-diphenyl-2-picryl hydrazyl (DPPH), similar to ascorbic acid, which was used as a positive control. Moreover, AAEE effectively suppressed lipopolysaccharide (LPS)- and hydrogen peroxide ($H_2O_2$)-induced reactive oxygen species (ROS) in RAW 264.7 cells. Furthermore, AAEE induced the expression of antioxidative enzymes, heme oxygenase 1 (HO-1), and thioredoxin reductase 1 (TrxR1), in addition to their upstream transcription factor, nuclear factor-E2-related factor 2 (Nrf2), in a dose-dependent manner. The upstream signaling pathways of mitogen-activated protein kinases (MAPKs) might regulate the modulation of HO-1, TrxR1, and Nrf2 expression. On the other hand, AAEE inhibited LPS-induced nitric oxide (NO) formation, without cytotoxicity. Suppression of NO formation was the result of AEEE-induced down-regulation of inducible NO synthase (iNOS). The suppression of NO and iNOS by AAEE might be modulated by their upstream transcription factor, nuclear factor (NF)-${\kappa}B$, and activator protein (AP)-1 pathways. Taken together, these results provide important new insights into the antioxidative and anti-inflammatory activities of A. arborescens. AAAEE might represent a promising material in the field of nutraceuticals.

• Journal of Life Science
• /
• v.24 no.9
• /
• pp.973-980
• /
• 2014

This study was conducted to explore new nutraceutical resources from the plant kingdom possessing biological activities. To fulfill this purpose, the anti-oxidative and anti-inflammatory activities of Decaisnea insignis ethanol extract (DIEE) were evaluated. First, DIEE possessed potent scavenging activity against 1,1-diphenyl-2-picryl hydrazyl (DPPH), similar to ascorbic acid used as a positive control. Moreover, DIEE inhibited lipopolysaccharide (LPS)- and hydrogen peroxide ($H_2O_2$)-induced reactive oxygen species (ROS) in RAW 264.7 cells. Furthermore, DIEE induced the expression of an anti-oxidative enzyme, heme oxygenase 1 (HO-1), and its upstream transcription factor, nuclear factor-E2-related factor 2 (Nrf2), in a dose-dependent manner. The modulation of the HO-1 and Nrf2 expressions might be regulated by mitogen-activated protein kinases (MAPKs) and their upstream signaling pathways. On the other hand, DIEE suppressed LPS-induced nitric oxide (NO) formation without cytotoxicity. The inhibition of the NO formation was the result of the downregulation of inducible NO synthase (iNOS) by DIEE. The suppression of NO and iNOS by DIEE might be modulated by their upstream transcription factors, nuclear factor ${\kappa}B$ ($NF-{\kappa}B$), and activator protein 1 (AP-1) pathways. Taken together, these results provide important new insights that D. insignis possesses anti-oxidative and anti-inflammatory activities. Therefore, it might be utilized as a promising material in the field of nutraceuticals.

• Journal of The Korean Society of Integrative Medicine
• /
• v.12 no.1
• /
• pp.63-71
• /
• 2024

Purpose : Skin is the primary barrier to protect the body from various exogenous factors. Among them, UVB exposure can cause the induction of not only excessive inflammatory responses but also the degradation of extracellular matrix (ECM), including collagen and elastin. This study tried to investigate the ameliorative effect of Persicaria perfoliata ethanol extract (PPEE) on UVB-irradiated photodamage through the regulation of activator protein (AP)-1, phosphoinositide 3-kinase (PI3K)/Akt, and mitogen-activated protein kinase (MAPK) signaling molecules in HaCaT cells. Methods : The cytotoxicity of PPEE on HaCaT cells was evaluated by the WST-1 assay. The 80 mJ/cm² of UVB (312 nm) was irradiated on HaCaT cells to induce the photodamage. Western blot analysis was conducted to investigate the protein expression levels of cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-9, and heme oxygenase (HO)-1 for ameliorative status by PPEE treatment in UVB-exposed HaCaT cells. In addition, the activated status of the inflammatory transcription factor, AP-1, as well as upstream signaling molecules, PI3K/Akt, and MAPK, were also evaluated by Western blot analysis. Results : Any cytotoxic effect was not induced at the concentration up to 200 ㎍/ml by PPEE treatment. Protein expression levels of COX-2 and MMP-9 were significantly down- and up-regulated by PPEE treatment. The inflammatory transcription factor AP-1, stimulated by UVB irradiation, was also significantly attenuated by PPEE treatment. The phosphorylated status of PI3K/Akt and MAPK were mitigated by PPEE treatment in UVB-exposed HaCaT cells. Moreover, PPEE treatment potently accelerated the expression of HO-1 and its transcription factor, nuclear factor-erythroid 2-related factor (Nrf)2, which is known for its anti-inflammatory activity. Conclusion : Consequently, PPEE treatment significantly regulated COX-2 and MMP-9 expressions in UVB-irradiated HaCaT cells. The inflammatory transcription factor AP-1, along with upstream signaling molecules PI3K/Akt and MAPKs, were also attenuated by PPEE treatment in UVB-exposed HaCaT cells. Additionally, PPEE treatment exaggerated HO-1 expression and Nrf2 activation, which might have contributed to the anti-inflammatory activity of PPEE. These results indicate that PPEE could be a candidate for attenuating UVB-induced photodamage in human skin.

• Journal of The Korean Society of Integrative Medicine
• /
• v.11 no.4
• /
• pp.73-82
• /
• 2023

Purpose : Cymbopogon citratus, also known as lemongrass, has widely spread around the world and its essential oil is usually applied in food, perfume, and other industrial purposes. In addition, C. citratus has also been used for the treatment of inflammation, digestive disorders, and diabetes in traditional medicine. In this study, the antioxidative activity of C. citratus ethanol extract (CCEE) was analyzed in RAW 264.7 cells through the induction of one of phase II enzymes, heme oxygenase (HO)-1 by nuclear factor-erythroid 2 p45-related factor (Nrf)2, mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase (PI3K)/Akt. Methods : The antioxidative activity of CCEE against oxidative stress and its underlying molecular mechanisms were analyzed by the cell viability assay, intracellular reactive oxygen species (ROS) formation assay, and Western blot analysis in RAW 264.7 cells. Results : The results exhibited that CCEE potently attenuated tert-butyl hydroperoxide (t-BHP) induced intracellular ROS levels in a dose-dependent manner without any cytotoxicity. CCEE treatment significantly induced the expression of HO-1 which is known for its antioxidative capacity. In addition, CCEE treatment significantly upregulated the expression of Nrf2, a corresponding transcription factor for the regulation of antioxidative enzymes, which was in accordance with the HO-1 overexpression. MAPK and PI3K/Akt were also evaluated for their important roles in the regulation of cellular redox homeostasis against oxidative damage. As a result, the potent HO-1 expression was mediated by not extracellular regulated kinase (ERK), c-Jun NH2 terminal kinase (JNK), p38, but phosphoinositide 3-kinase (PI3K) phosphorylation. To confirm the antioxidative activity of CCEE-induced HO-1 expression, oxidative damage was initiated by t-BHP and attenuated by CCEE treatment, which was identified by HO-1 selective inhibitor and inducer. Conclusion : Consequently, CCEE potently induced the HO-1-mediated antioxidative potential through the modulation of Nrf2 and PI3K/Akt signaling pathways in RAW 264.7 cells. These results suggest that CCEE could be a promising strategy for the mitigation against cellular oxidative damage.

• Journal of Life Science
• /
• v.28 no.2
• /
• pp.207-215
• /
• 2018

Inflammatory response and oxidative stress play critical roles in the development and progression of many human diseases. Therefore, a great deal of attention has been focused on finding functional materials that can control inflammation and oxidative stress simultaneously. The purpose of this study was to investigate the effects of Socheongja and Socheong 2, Korean black seed coat soybean varieties, on the inflammatory and oxidative stress induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages. Our data indicated that the extracts of Socheongja (SCJ) and Socheong 2 (SC2) significantly suppressed LPS-induced production of nitrite oxide (NO) and prostaglandin $E_2$, key pro-inflammatory mediators, by suppressing the expression of inducible NO synthase and cyclooxygenase-2. It was also found that SCJ and SC2 reduced the LPS-induced secretion of pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$, which was concomitant with a decrease in the protein levels. In addition, SCJ and SC2 markedly diminished LPS-stimulated intracellular reactive oxygen species accumulation, and effectively enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase (HO)-1 expression. Furthermore, LPS-induced activation of mitogen-activated protein kinases (MAPKs) was abrogated by SCJ and SC2. Taken together, these data suggest that SCJ and SC2 may offer protective roles against LPS-induced inflammatory and oxidative responses in RAW 264.7 macrophages through attenuating MAPKs pathway, and these effects are mediated, at least in part, through activating Nrf2/HO-1 pathway. Given these results, we propose that SCJ and SC2 have therapeutic potential in the treatment of inflammatory and oxidative disorders caused by over-activation of macrophages.

• The Journal of Internal Korean Medicine
• /
• v.43 no.4
• /
• pp.643-655
• /
• 2022

Objective: To investigate the protective effects of Haeganjeon on a thioacetamide (TAA)-induced liver fibrosis mouse model and to determine the Haegan-jeon signaling pathway. Methods: Mice were randomly divided into 4 groups: Normal group (Nor), TAA-induced liver fibrosis group (Con), TAA-induced liver fibrosis group administered 50 mg/kg silymarin (S50), TAA-induced liver fibrosis group administered 200 mg/kg Haegan-jeon (H200). The liver fibrosis mouse model was established by intraperitoneal injection with TAA three times a week for 8 weeks. During the 8 weeks, mice were orally administered silymarin and Haegan-jeon every day. At the end of the study, serum was collected to measure the levels of AST, ALT, ammonia, and myeloperoxidase (MPO). Liver tissue was harvested and analyzed by western blotting and Masson's trichrome staining. Results: Administration of Haegan-jeon suppressed the increase in serum levels of AST, ALT, ammonia, and MPO due to TAA-induced liver fibrosis. Compared to the Con group, the H200 group showed increases in antioxidant-related factors (Nrf2, HO-1, catalase, and GPx-1/2) and decreases in inflammatory-related factors (NF-κB p65, p-IκB-α, Cox-2, iNOS, TNF-α, and IL-1β) in western blots. The H200 treatment inhibited the expression of α-SMA and Collagen I. Conclusions: Haegan-jeon showed a hepatoprotective effect induced by activation of antioxidant-related factors, such as Nrf2, and it regulated the inflammation response by suppression of NF-κB.

• Environmental Mutagens and Carcinogens
• /
• v.26 no.4
• /
• pp.97-112
• /
• 2006

Heme oxygenase(HO)-1 is an important antioxidant enzyme that plays a pivotal role in cellular adaptation and protection in response to a wide array of noxious stimuli. Thus, HO-1 induction has been associated with prevention or mitigation of pathogenesis of various diseases, including acute inflammation, atherosclerosis, degenerative diseases, and carcinogenesis. Recent progress in our understanding of the function of molecules in the cellular signaling network as key modulators of gene transcription sheds light on the molecular mechanisms underlyuing HO-1 gene expression. A panel of redox-sensitive transcription factors such as activator protein-1, nuclear factor-kB, and nuclear factor E2-related factor-2, and some of the upstream kinases have been identified as prime regulators of HO-1 gene induction. This review summarizes molecular mechanisms underlying HO-1 expression and the significance of targeted induction of HO-1 as a potential chemopreventive or chemoprotective strategy.

• Proceedings of the Plant Resources Society of Korea Conference
• /
• 2018.10a
• /
• pp.103-103
• /
• 2018

Oenothera biennis, commonly known as evening primrose, a potential source of natural bioactive substances: flavonoids, steroids, tannins, fatty acids and terpenoids responsible for a diverse range of pharmacological functions. However, whether extract prepared from aerial part of O. biennis (APOB) protects skin against oxidative stress remains unknown. To investigate the protective effects of APOB against oxidative stress-induced cellular damage and elucidated the underlying mechanisms in the HaCaT human skin keratinocytes. Our results revealed that treatment with APOB prior to hydrogen peroxide ($H_2O_2$) exposure significantly increased viability, and the highest DPPH radical-scavenging activities and reducing power of HaCaT cells. APOB also effectively attenuated H2O2-induced comet tail formation and inhibited the $H_2O_2$-induced phosphorylation levels of the histone ${\gamma}H2AX$, as well as the number of apoptotic bodies and Annexin V-positive cells. In addition, APOB exhibited scavenging activity against intracellular reactive oxygen species (ROS) accumulation and restored the mitochondrial membrane potential loss by $H_2O_2$. Moreover, $H_2O_2$ enhanced the cleavage of caspase-3 and degradation of poly (ADP-ribose)-polymerase (PARP), a typical substrate protein of activated caspase-3, as well as DNA fragmentation; however, these events were almost totally reversed by pretreatment with APOB. Furthermore, APOB increased the levels of heme oxygenase-1 (HO-1), which is a potent antioxidant enzyme, associated with the induction of nuclear factor-erythroid 2-related factor 2 (Nrf2). According to our data, APOB is able to protect HaCaT cells from $H_2O_2$-induced DNA damage and cell death through blocking cellular damage related to oxidative stress through a mechanism that would affect ROS elimination and activating the Nri2/HO-1 signaling pathway.