• 대한의생명과학회지
• /
• 제19권2호
• /
• pp.168-172
• /
• 2013

Toll-like receptors (TLRs) play an important role for host defense against invading pathogens. TLR4 has been identified as the receptor for lipopolysaccharide (LPS), which is a cell wall component of gram-negative bacteria. The activation of TLR4 signaling by LPS leads to the activation of NF-${\kappa}B$ and the expression of pro-inflammatory gene products such as cytokines, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). To evaluate the therapeutic potential of (E)-1-(2-(2-nitrovinyl)phenyl)pyrrolidine (NVPP), previously synthesized in our laboratory, NF-${\kappa}B$ activation and iNOS and COX-2 expression induced by LPS were examined. NVPP inhibited the activation of NF-${\kappa}B$ induced by LPS. NVPP also suppressed the iNOS expression induced by LPS but it did not suppress COX-2 expression induced by LPS. These results suggest that NVPP has the specific mechanism for anti-inflammatory responses.

• 대한의생명과학회지
• /
• 제24권2호
• /
• pp.102-107
• /
• 2018

Toll-like receptors (TLRs) play an important role for host defense against invading pathogens. The activation of TLRs signaling leads to the activation of $NF-{\kappa}B$ and the expression of pro-inflammatory gene products such as cytokines and inducible nitric oxide synthase (iNOS). To evaluate the therapeutic potential of cardamonin, which is a naturally occurring chalcone from Alpinia species (zingiberaceous plant species), $NF-{\kappa}B$ activation and iNOS expression induced by MALP-2 (TLR2 and TLR6 agonist) or LPS (TLR4 agonist) were examined. Cardamonin inhibited the activation of $NF-{\kappa}B$ induced by MALP-2 or LPS. Cardamonin also suppressed the iNOS expression induced by MALP-2 or LPS. These results suggest that cardamonin has the specific mechanism for anti-inflammatory responses by regulating of TLRs signaling pathway.

• 대한의생명과학회지
• /
• 제23권2호
• /
• pp.104-110
• /
• 2017

Inflammation is a pathophysiological process that is known to be involved in numerous diseases. Microbial infection or tissue injury activates inflammatory responses, resulting in the induction of proinflammatory proteins including inducible nitric oxide synthase (iNOS). Aster yomena is used in traditional Korean remedies. Here, we investigated the effects of ethanol extracts of Aster yomena (EAY) on the expression of iNOS induced by ovalbumin (OVA), one of the major egg allergens, or lipopolysaccharide (LPS), a Toll-like receptor 4 agonist. EAY inhibited OVA- or LPS-induced $NF-{\kappa}B$ activation. EAY also suppressed OVA- or LPS-induced iNOS expression and nitrite production. These results suggest that EAY has the specific mechanism for anti-inflammatory responses and the potential to be developed as a potent anti-inflammatory and anti-allergic drug.

• 대한의생명과학회지
• /
• 제25권1호
• /
• pp.60-65
• /
• 2019

Toll-like receptors (TLRs) are one of the families of pattern recognition receptors (PRR) operating in the innate immunity. TLRs have the ability to recognize relatively conserved microbial components, which are generally referred to as pathogen-associated molecular patterns (PAMPs). The activation of TLRs signaling leads to the activation of $NF-{\kappa}B$ and the expression of pro-inflammatory gene products such as cytokines and inducible nitric oxide synthase (iNOS). To evaluate the therapeutic potential of pristimerin, which is a naturally occurring triterpenoid compound from Celastraceae plants, iNOS expression induced by MALP-2 (TLR2 and TLR6 agonist), Poly[I:C] (TLR3 agonist), or LPS (TLR4 agonist) were examined. Pristimerin suppressed the iNOS expression induced by MALP-2, Poly[I:C], or LPS. These results suggest that pristimerin can modulate TLRs signaling pathways leading to decreased inflammatory gene expression.

• Biomolecules & Therapeutics
• /
• 제16권3호
• /
• pp.231-236
• /
• 2008

The current work was designed to assess novel pharmacological activities of 4-hydroxybenzaldehyde (HD), a major phenolic constituent of various natural products of plant origin, such as Gastrodia elata Blume. HD exhibited a significant inhibition in the chick chorioallantoic membrane (CAM) angiogenesis. HD also displayed an inhibitory effect in acetic acid-induced permeability in mice. Anti-nociceptive activity of HD was convinced using the acetic acid-induced writhing test in mice. HD was able to suppress production of nitric oxide (NO) and induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-activated RAW264.7 macrophages. HD also diminished the reactive oxygen species (ROS) level elevated in the LPS-activated macrophages. In brief, HD exhibits anti-angiogenic, anti-inflammatory and anti-nociceptive activities possibly via down-regulating iNOS and/or COX-2, which may be partly responsible for pharmacological efficacies of various natural products.

• Archives of Pharmacal Research
• /
• 제27권9호
• /
• pp.937-943
• /
• 2004

Recent investigations have shown that certain flavonoids, especially flavone derivatives, inhibit nitric oxide (NO) production by inducible NO synthase (iNOS) in macrophages, which contrib-ute their anti-inflammatory action. For the purpose of finding the optimized chemical structures of flavonoids that inhibit NO production, various A- and B-ring substituted flavones were syn-thesized and evaluated for their inhibitory activity using lipopolysaccharide-treated RAW 264.7 cells. It was found that the optimal chemical structures were A-ring 5,7-dihydroxyflavones hav-ing the B-ring 2＇,3＇-dihydroxy or 3＇,4＇-dihydroxy or 3＇,4＇-hydroxy/methoxy (methoxy/hydroxy) groups. These structurally optimized compounds were revealed to be down-regulators of iNOS induction, but not direct iNOS inhibitors. Of these derivatives that were evaluated, 2＇,3＇,5,7-tet-rahydroxyflavone and 3＇,4＇,5,7-tetrahydroxyflavone (Iuteolin) showed the strongest inhibition. The $IC_{50}$/ values for these compounds were 19.7 and 17.1 11M, respectively. Therefore, these compounds may have a potential as new anti-inflammatory agents.

• 한국약용작물학회지
• /
• 제15권5호
• /
• pp.324-328
• /
• 2007

To search for immunoactive natural products exerting anti-inflammatory activity, we have evaluated the effects of the ethanol extracts of Rubus coreanus Miq. (ERC) on lipopolysaccharide-induced nitric oxide (NO), tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$, and $Interferon-{\gamma}\;(IFN-{\gamma})$ production by RAW 264.7 macrophage cell line. Our data indicate that this extract is a potent inhibitor of NO production and it also significantly decreased $IFN-{\gamma}\;and\;TNF-{\alpha}$ production. Consistent with these results, the protein level of inducible Nitric Oxide Synthase (iNOS) and cyclooxygenase-2 (COX-2) was inhibited by ethanol extracts of ERC in a dose-dependent manner. These results suggest that ERC may exert anti-inflammatory and analgesic effects possibly by suppressing the inducible NO synthase and COX-2 expressions.

• 대한한방내과학회지
• /
• 제34권4호
• /
• pp.339-348
• /
• 2013

Objectives : Danguieumja is a traditional medicinal prescription to treat skin disease. It was commonly used for the treatment of itching, chronic urticaria and atopic dermatitis in Korea by the addition or omission of several herbs. This study investigated the anti-inflammatory potential of Gagam-Danguieumja (GDE) water extract. Methods : We examined the effects of GDE on the lipopolysaccharide (LPS)-induced production of nitric oxide (NO) in a murine macrophage cell line, RAW 264.7 cells. Results : GDE inhibited production of NO in a dose dependent manner and also decreased the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2). As a possible molecular mechanism of anti-inflammatory effect increased phosphorylation of mitogen-activating protein kinases (MAPK) by LPS were blocked by GDE treatment. Conclusions : These results suggest that GDE has an anti-inflammatory therapeutic potential through the inhibition of MAPK phosphorylation, thereby decreasing the expression of pro-inflammatory genes.

• Molecules and Cells
• /
• 제38권7호
• /
• pp.610-615
• /
• 2015

Alveolar epithelial cells have been functionally implicated in Mycobacterium tuberculosis infection. This study investigated the role of ursolic acid (UA)-a triterpenoid carboxylic acid with potent antioxidant, anti-tumor, anti-inflammatory, and anti-tuberculosis properties in mycobacterial infection of alveolar epithelial A549 cells. We observed that M. tuberculosis successfully entered A549 cells. Cytotoxicity was mediated by nitric oxide (NO). A549 toxicity peaked along with NO generation 72 h after infection. The NO generated by mycobacterial infection in A549 cells was insufficient to kill mycobacteria, as made evident by the mycobacteria growth indicator tube time to detect (MGIT TTD) and viable cell count assays. Treatment of mycobacteria-infected cells with UA reduced the expression of inducible nitric oxide synthase, NO generation, and eventually improved cell viability. Moreover, UA was found to quench the translocation of the transcription factor, nuclear factor kappa B (NF-${\kappa}B$), from the cytosol to the nucleus in mycobacteria-infected cells. This study is the first to demonstrate the cytotoxic role of NO in the eradication of mycobacteria and the role of UA in reducing this cytotoxicity in A549 cells.

• Bulletin of the Korean Chemical Society
• /
• 제28권8호
• /
• pp.1289-1293
• /
• 2007

Persicaside has been isolated as a new alkaloid natural compound from a methanol (EtOA)-soluble extract of Prunus persica seed. It was purified by a combination of chromatographic techniques and recrystallization. The structure of Persicaside was determined by extensive NMR experiments and mass ppectroscopic data. It inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) production via suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2 expression in rat osteoblast sarcoma cells (ROS 17/2.8) in concentration-dependent manner whereas it spares the COX-1 enzyme activity.