• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.467-473
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• 2024

In this study, we investigated the potential protective effects of (+)-afzelechin (AZC), a natural compound that is derived from Bergenia ligulata, on lipopolysaccharide (LPS)-induced inflammatory responses. AZC is known to have antioxidant, anticancer, antimicrobial, and cardiovascular protective properties. However, knowledge regarding the therapeutic potential of AZC against LPS-induced inflammatory responses is limited. Thus, we investigated the protective attributes of AZC against inflammatory damage caused by LPS exposure. We examined the effects of AZC on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in LPS-activated human umbilical vein endothelial cells (HUVECs). In addition, the effects of AZC on the expression of iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β were analyzed in the lung tissues of LPS-injected mice. Data revealed that AZC promoted the production of HO-1, inhibited the interaction between luciferase and nuclear factor (NF)-κB, and reduced the levels of COX-2/PGE2 and iNOS/NO, thereby leading to a decrease in the signal transducer and activator of transcription (STAT)-1 phosphorylation. Moreover, AZC facilitated the nuclear translocation of Nrf2, increased the binding activity between Nrf2 and the antioxidant response elements (AREs), and lowered the expression of IL-1β in the LPS-treated HUVECs. In the animal model, AZC significantly reduced the expression of iNOS in the lung tissue structure and the TNF-α level in the bronchoalveolar lavage fluid. These findings demonstrate that AZC possesses anti-inflammatory properties that regulate iNOS through the inhibition of both NF-κB expression and p-STAT-1. Consequently, AZC has potential as a future candidate for the development of new clinical substances for the treatment of pathological inflammation.

• BMB Reports
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• v.42 no.12
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• pp.794-799
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• 2009

The inhibition of nitric oxide (NO) and cyclooxygenase-2 (COX-2) production is considered to be a promising approach to the treatment of various diseases, including inflammation and cancer. In this study, we examined the effects of the Agrocybe chaxingu $\beta$-glucan (polysaccharide) on lipopolysaccaride (LPS)-induced nitric oxide (NO) and cyclooxygenase-2 (COX-2) expression in murine macrophage Raw 264.7 cells as well as 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema in mice. The polysaccharide significantly inhibited (P < 0.01) LPS-induced iNOS and COX-2 expression levels in the cells. Furthermore, topical application of polysaccharide resulted in markedly inhibited (P < 0.01) TPA-induced ear edema in mice. These results suggest that this polysaccharide may be used for NO- and COX-2-related disorders such as inflammation and cancer.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.46-52
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• 2023

The most abundant flavanone of grapefruits, naringenin (NN), is well known for its hepatoprotective, anti-lipid peroxidation and anti-carcinogenic effects. We generated three derivatives from NN using this technique in previous studies. Among them, it was confirmed that naringenin-7-O-phosphate (N7P), whose biological and physicochemical properties were not reported, showed a water solubility 45 times higher than that of NN. Therefore, in this study, the anti-inflammatory activity was evaluated in RAW 264.7 cells to investigate the potential physiological activity of N7P. As a result, N7P showed nitric oxide (NO) inhibitory activity at concentrations that did not show toxicity. In addition, prostaglandin E₂ (PGE₂) showed significant inhibitory activity from the lowest concentration of 12.5 μM and showed increased inhibitory activity compared to NN. In addition, as a result of western blot, N7P showed increased cyclooxygenase-2 (COX-2) inhibitory activity than NN, and effectively inhibited NO and PGE₂ by significantly inhibiting their expression pathways. N7P also inhibited inflammatory cytokines, including tumor necrosis factor-α, interleukin-6. Based on these results, we propose that N7P can be used as a potent antiinflammatory agent.

• Korean Journal of Pharmacognosy
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• v.39 no.2
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• pp.95-103
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• 2008

In the present study, we investigated the anti-inflammatory effects by kaempferol-3-O-${\beta}$-D-sophoroside (KS) isolated from Sophora japonica (Leguminosae) on the lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin ($PGE_2$) production by RAW 264.7 cell line compared with kaempferol. KS significantly inhibited the LPS-induced NO and $PGE_2$ production. Consistent with these observations, KS reduced the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels in a concentration-dependent manner. In addition, the release and the mRNA expression levels of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) and interleukin-6 (IL-6) were also reduced by KS. Moreover, KS attenuated the LPS-induced activation of nuclear factor-kappa B ($NF{-\kappa}B$), a transcription factor necessary for pro-inflammatory mediators, iNOS, COX-2, $TNF-{\alpha}$ and IL-6 expression. These results suggest that the down regulation of iNOS, COX-2, $TNF-{\alpha}$, and IL-6 expression by KS are achieved by the downregulation of $NF{-\kappa}B$ activity, and that is also responsible for its anti-inflammatory effects.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.3
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• pp.463-469
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• 2010

This research is performed to obtain positive evidences of Mori cortex, a kind of oriental medicinal herbs, in the cellular levels. The extracts of M. cortex have shown anti-inflammatory effects against cutaneous inflammation and clinical effects on pulmonary asthma and congestion in oriental medicine. Thus BV2 cells were chosen because microglia are considered as the main immunocompetent cells in the central nervous system. Lipopolysaccharide (LPS)-induced microglial activation of cultured BV2 cells and subsequent release of nitric oxide (NO) and Prostaglandin E2 (PGE2) were effectively suppressed by methylene chloride extract of Morus alba L. (MEMA). From the inflammation-mediated mRNA and protein analyses, we showed that inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-$1{\beta}$ (IL-$1{\beta}$) and tumor necrosis alpha (TNF-${\alpha}$) induced by LPS were markedly decreased by MEMA treatment. From the observation of nuclear factor-kB (NF-${\kappa}B$) which is controlling and mediating inflammation through COX-2 and iNOS, there showed that p65, a subunit of NF-${\kappa}B$, was increased in nuclear and $I{\kappa}B$, a competitor of NF-${\kappa}B$, was recovered in cytosol after MEMA treatment. These are corresponding with results of iNOS, COX-2, IL-$1{\kappa}$ and TNF-${\alpha}$, and confirm some suppressive effect against transcriptional activation of NF-${\kappa}B$. In conclusion, the anti-inflammatory action of M. cortex against BV2 microglia cells is expected to protect nerve tissues through suppression of neuronal inflammation in various neurodegenerative diseases.

• YAKHAK HOEJI
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• v.47 no.5
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• pp.311-318
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• 2003

Eurya emarginata (Thunb.) Makino (Theaceae) is distributed in coastal areas of island. The leaves of Eurya are used in the traditional medicine of the coastal areas of jeju island with the aim of diuresis or to treat ulcers. Nevertheless, there are few reports on the biological activity and constituents of E. emarginata. In this study, we investigated the pharmacological activity of the solvent extracts of E. emarginata on the several inflammatory markers (TNF-$\alpha$, IL-1$\beta$, IL-6, NO, iNOS and COX-2). Also we examined the antioxidizing effect of the solvent extracts by determination of DPPH radical-scavenging activity. Among the solvent fractions, EtOAc and BuOH extracts showed potent radical scavenging activity (RC$_{50}$=10.9 and 12.7 respectively). The subtractions of EF 5-4-6-3-2 and BF 1 potentially inhibited the mRNA expression of pro-inflammatory cytokines (IL-1$\beta$, IL-6 and TNF-$\alpha$) at the concentration of 100 $\mu\textrm{g}$/mι. Also the fractions inhibited the mRNA expression of pro-inflammatory cytokines (IL-1$\beta$, IL-6 and TNF-$\alpha$) and protein expression of iNOS and COX-2 at the concentration of 100 $\mu\textrm{g}$/mι. And then, the inhibition of iNOS was correlated with the decrease of nitrite level. These results suggest that E. emarginata may have anti-inflammatory activity through the inhibition of pro-inflammatory cytokines, iNOS and COX-2.2.

• Biomolecules & Therapeutics
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• v.16 no.2
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• pp.132-136
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• 2008

The current study aimed to assess some novel pharmacological activities of vanillin. Vanillin inhibited the chick chorioallantoic membrane (CAM) angiogenesis. Vanillin had anti-inflammatory activity using the acetic acid-induced permeability model in mice. Anti-nociceptive activity of vanillin was shown using the acetic acid-induced writhing test in mice. Vanillin inhibited production of nitric oxide (NO) and induction of inducible nitric oxide synthase (iNOS) but not cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Vanillin decreased the level of iNOS mRNA in the LPS-activated macrophages. Taken together, these results suggest that vanillin can have anti-angiogenic, anti-inflammatory and anti-nociceptive activities in ICR Mice.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.1
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• pp.54-61
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• 2007

The study was designed to investigate the effects of Mixture of Yukgunja-tang and Bambusae Caulis in Liquamen (YTBCL) on the change of regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in rats, and further to determine the mechanism of action of YTBCL. The results in rats were as follows ; YTBCL 25 ${\mu}l$ significantly decreased rCBF and MABP compared with basal condition. YTBCL 100 ${\mu}l$ significantly increased rCBF compared with basal condition, but decreased MABP compared with basal condition. YTBCL 50 ${\mu}l$ significantly increased rCBF compared with basal condition, but MABP was somewhat decreased compared with basal condition. The VTBCL 50 ${\mu}l$-induced increase in rCBF was significantly inhibited by pretreatment with methylene blue (10 ${\mu}g$/kg, i.p.), an inhibitor of guanylate cyclase and indomethacin (1 mg/kg, i.p.), an inhibitor of cyclooxygenase. The YTBCL 50 ${\mu}l$-induced decreased MABP significantly increased by pretreatment with methylene blue but was inhibited by indomethacin. This results were suggested that the mechanism of YTBCL was mediated Dy guanylate cyclase.

• Korean Journal of Plant Resources
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• v.32 no.6
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• pp.669-676
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• 2019

Zanthoxylum piperitum D.C. (ZP) peels has been used as a natural spice and herb medicine for hypertension reduction, for strokes, and for its anti-bacterial and anti-oxidant activity. However, the anti-inflammatory mechanisms employed by ZP have yet to be completely understood. In this study, we elucidate the anti-inflammatory mechanism of ZP in lipopolysaccharide (LPS)-induced RAW264.7 cells. We evaluated the effects of ZP in LPS-induced levels of inflammatory cytokines, prostaglandin E₂ (PGE₂), and caspase-1 using ELISA. The expression levels of inflammatory-related genes, including cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS), were assayed by Western blot analysis. We elucidated the effect of ZP on nuclear factor (NF)-κB activation by means of a luciferase activity assay. The findings of this study demonstrated that ZP inhibited the production of inflammatory cytokine and PGE₂ and inhibited the increased levels of COX-2 and iNOS caused by LPS. Additionally, we showed that the anti-inflammatory effect of ZP arises by suppressing the activation of NF-κB and caspase-1 in LPS- induced RAW264.7 cells. These results provide novel insights into the pharmacological actions of ZP as a potential candidate for development of new drugs to treat inflammatory diseases.

• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.379-387
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• 2009

We have previously reported that N-ethylmaleimide (NEM) induces apoptosis through activation of $K^+$, $Cl^-$-cotransport (KCC) in HepG2 human hepatoblastoma cells. In this study we investigated the possible role of phospholipase $A_2$ ($PLA_2$)-arachidonic acid (AA) signals in the mechanism of the NEM-induced apoptosis. In these experiments we used arachidonyl trifluoromethylketone ($AACOCF_3$), bromoenol lactone (BEL) and p-bromophenacyl bromide (BPB) as inhibitors of the calcium-dependent cytosolic $PLA_2$ ($cPLA_2$), the calcium-independent $PLA_2$ ($iPLA_2$) and the secretory $PLA_2$ ($sPLA_2$), respectively. BEL significantly inhibited the NEM-induced apoptosis, whereas $AACOCF_3$ and BPB did not. NEM increased AA liberation in a dose-dependent manner, which was markedly prevented only by BEL. In addition AA by itself induced $K^+$ efflux, a hallmark of KCC activation, which was comparable to that of NEM. The NEM-induced apoptosis was not significantly altered by treatment with indomethacin (Indo) and nordihydroguaiaretic acid (NDGA), selective inhibitors of cyclooxygenase (COX) and lipoxygenase (LOX), respectively. Treatment with AA or 5,8,11,14-eicosatetraynoic acid (ETYA), a non-metabolizable analogue of AA, significantly induced apoptosis. Collectively, these results suggest that AA liberated through activation of $iPLA_2$ may mediate the NEMinduced apoptosis in HepG2 cells.