• Korean Journal of Pharmacognosy
• /
• v.34 no.1 s.132
• /
• pp.109-117
• /
• 2003

Arachidonic acid(AA), which is stored in membrane glycerophospholipids, is liberated by phospholipase $A_2(PLA_2)$ enzymes and is sequentially converted to cyclooxygenase (COX) and lipoxygenase (LOX) then to various bioactive prostaglandins (PGs,) and leukotrienes (LTs). In order to find the specific inhibitors of AA metabolism enzymes such as $PLA_2$, COX-2, 5-LO and lyso PAF acetyltransferase. 195 Korean indigenous plant extracts were evaluated for their inhibitory activity on $PGD_2,\;LTC_4$ production from cytokine-induced mouse bone marrow-derived mast cells (BMMC) and arachidonic acid released from phospholipid and PAF production from lyso PAF. From this screening procedure, methanol extract of eight plants such as Saururus chinensis, Aster tataricus, Chrysanthemum cinerariaefolium, Reynoutria japonica, Disocorea nipponica, Epimedium koreanum, impatiens textori, Veronica rotunda var. subintegra were found to inhibit production of inflammatory mediators in vitro assay system.

• The Journal of Internal Korean Medicine
• /
• v.38 no.6
• /
• pp.891-901
• /
• 2017

Objectives: The aim of the study was to evaluate the anti-asthmatic effect of alismatis rhizoma and alisol acetate B combination therapy in a murine asthma model. Methods: C57BL/6 mice were sensitized to and challenged with a mixture of ragweed, dust mite, and aspergillus to induce an asthma animal model. Alismatis rhizoma extract and alisol acetate B combination therapy was co-administered only in the experimental group. To evaluate the anti-asthmatic effect of the combination therapy, inflammatory cell counts in bronchoalveolar lavage (BAL) fluid were determined, and tissue was examined histologically with hematoxylin and eosin (H & E) and periodic acid-Schiff (PAS) stains, by enzyme-linked immunosorbent assay (ELISA) of IgE, IL-4, and IL-5, and with reverse transcription polymerase chain reaction (RT-PCR) of IL-5, IL-33, MUC5AC. Results: Alismatis rhizoma and alisol acetate B combination therapy reduced the number of inflammatory cells, alleviated histologic features, and down-regulated all the investigated asthma mediators, IgE, IL-4, IL-5, IL-33, and MUC5AC. Conclusions: According to the above results, alismatis rhizoma and alisol acetate B combination therapy may have therapeutic potential for asthma.

• The Korean Journal of Pain
• /
• v.26 no.4
• /
• pp.356-360
• /
• 2013

Background: Nerve injury sometimes leads to chronic neuropathic pain associated with neuroinflammation in the nervous system. In the case of chronic neuropathic pain, the inflammatory and algesic mediators become predominant and result in pain hypersensitivity following nervous system damage. It is well known that urinary trypsin inhibitor (ulinastatin, UTI) has an anti-inflammatory activity. Recently, the neuroprotective action of UTI on the nervous system after ischemic injury has been reported. Thus, we evaluated the neuroprotective effect of ulinastatin in a rat model of neuropathic pain. Methods: Neuropathic pain was induced with L5 spinal nerve ligation (SNL) in male Sprague-Dawley rats weighing 100-120 g. The rats were divided into 3 groups, with n = 8 in each group. The rats in the control group (group 1) were administered normal saline and those in group 2 were administered UTI (50,000 U/kg) intravenously through the tail vein for 3 days from the day of SNL. Rats in group 3 were administered UTI (50,000 U/kg) intravenously from the $5^{th}$ day after SNL. The paw withdrawal threshold was measured using the von Frey test for 3 days starting from the $5^{th}$ day after SNL. Results: The paw withdrawal thresholds were significantly increased in the rats of group 2 compared to the other groups (P < 0.05). Conclusions: Ulinastatin, which was administered for 3 days after SNL, increased the paw withdrawal threshold and it could have a neuroprotective effect in the rat model of neuropathic pain.

• Journal of Korean Neurosurgical Society
• /
• v.55 no.5
• /
• pp.237-243
• /
• 2014

Objective : Symptomatic disc degeneration develops from inflammatory reactions in the annulus fibrosus (AF). Although inflammatory mediators during annular inflammation have been studied, the roles of matrix metalloproteinases (MMPs) and their inhibitors have not been fully elucidated. In this study, we evaluated the production of MMPs and tissue inhibitors of metalloproteinase (TIMPs) during annular inflammation using an in vitro co-culture system. We also examined the effect of notochordal cells on annular inflammation. Methods : Human AF (hAF) pellet was co-cultured for 48 hours with phorbol myristate acetate-stimulated macrophage-like THP-1 cells. hAF pellet and conditioned media (CM) from co-cultured cells were assayed for MMPs, TIMPs, and insulin-like growth factor (IGF)-1 levels using real-time reverse-transcriptase polymerase chain reaction and enzyem-linked immunosorbent assay. To evaluate whether notochordal cells affected MMPs or TIMPs production on annular inflammation, hAF co-cultured with notochordal cells from adult New Zealand White rabbits, were assayed. Results : MMP-1, -3, -9; and TIMP-1 levels were significantly increased in CM of hAF co-cultured with macrophage-like cells compared with hAF alone, whereas TIMP-2 and IGF-1 levels were significantly decreased (p<0.05). After macrophage exposure, hAF produced significantly more MMP-1 and -3 and less TIMP-1 and -2. Interleukin-$1{\beta}$ stimulation enhanced MMP-1 and -3 levels, and significantly diminished TIMP-2 levels. Co-culturing with rabbit notochordal cells did not significantly influence MMPs and TIMPs production or COL1A2 gene expression. Conclusion : Our results indicate that macrophage-like cells evoke annular degeneration through the regulation of major degradative enzymes and their inhibitors, produced by hAF, suggesting that the selective regulation of these enzymes provides future targets for symptomatic disc degeneration therapy.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.355.3-356
• /
• 2002

Prostaglandins are synthesized by the enzyme cyclooxygenase (COX). Both constitutive (COX-1) and inducible (COX-2) isoforms have been identified. COX-2 expression is stimulated by inflammatory mediators such as growth factors and cytokines. Most non-steroidal anti-inflammatory drugs (NSAIDS) inhibit both isoforms of COX. Recent evidence suggests that selective inhibitors of COX-2 may possess diminished side effects reletive to common NSAIDS. Novel isothiazoles and isoxazoles were identified as selective inhibitiors of cycloxygenase-2(COX-2). (omitted)

• Archives of Pharmacal Research
• /
• v.27 no.9
• /
• pp.923-929
• /
• 2004

Stylopine is a major component of the leaf of Chelidonium majus L. (Papaveraceae), which has been used for the removal of warts, papillomas and condylomas, as well as the treatment of liver disease, in oriental countries. Stylopine per se had no cytotoxic effect in unstimulated RAW 264.7 cells, but concentration-dependently reduced nitric oxide (NO), prostaglandin E$_2$ (PGE$_2$), tumor necrosis factor-a (TNF-$\alpha$) and interleukin-1$\beta$(IL-1$\beta$), and the IL-6 production and cyclooxygenase-2 (COX-2) activity caused by the LPS stimulation. The levels of inducible nitric oxide synthase (iNOS) and COX-2 protein expressions were markedly suppressed by stylopine in a concentration dependent manner. These results suggest that stylopine suppress the NO and PGE$_2$ production in macrophages by inhibiting the iNOS and COX-2 expressions. These biological activities of stylopine may contribute to the anti-inflammatory activity of Cheli-donium majus.

• Journal of Periodontal and Implant Science
• /
• v.34 no.2
• /
• pp.345-356
• /
• 2004

The triclosan was shown to have anti-microbial and anti-inflammatory effect with inhibition of inflammatory mediators such as prostaglandin $E_2(PGE_2)$. The purpose of this study was to elucidate whether and how $PGE_2$ could be inhibited by triclosan in human gingival fibroblast. Human gingival fibroblast-1 cells (ATCC CRL2014) were pre-treated for 1 hour with triclosan (0.001 ${\mu}/ml{\sim}10$ ${\mu}/ml$) and then stimulated with $TNF-{\alpha}$ (1.0 ng/ml). $PGE_2$ synthesis was evaluated by ELISA and gene expression of COX-1 and COX-2 was evaluated by RT-PCR after $TNF-{\alpha}$, triclosan, and NS-398 (COX-2 inhibitor, 5, ${\mu}M$) and/ or cycloheximide (protein synthesis inhibitor, 2 ${\mu}g/ml$). Triclosan was cytotoxic to human gingival fibroblasts in the concentration higher than 1.0 ${\mu}g/ml$ for longer than 24 hours in tissue culture. The $PGE_2$ synthesis was inhibited by triclosan in dose-dependent manner. Greater COX-2 mRNA suppression was observed with triclosan (0.1 ${\mu}g/ml$) than with $TNF-{\alpha}$ alone, without change in COX-1 gene expression. Inhibitory effects of triclosan on $PGE_2$ synthesis disappeared in presence of cycloheximide. This study suggests that triclosan inhibit prostaglandin $E_2$ at the level of COX-2 gene regulation and require de novo protein synthesis.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2003.11a
• /
• pp.101-101
• /
• 2003

Prostaglandins (PGs) and nitric oxide (NO) produced by inducible cyclooygenase (COX-2) and nitric oxide synthase (iNOS), respectively, have been implicated as important mediators in the process of inflammation and carcinogenesis. On this line, the potential COX-2 or iNOS inhibitors have been considered as anti-inflammatory and cancer chemopreventive agents. In our continuing efforts of searching for novel cancer chemopreventive agents from natural products, we isolated natural sesquiterpenoids as potential COX-2 and iNOS inhibitors in cultured lipopolysaccharide (LPS)-activated mouse macrophage RAW 264.7 cells. Alantolactone, a natural eudesmane-type sesquiterpenoid, exhibited a potent inhibition of COX-2 (IC50 = 0.4 $\mu\textrm{g}$/$m\ell$) and iNOS activity (IC50 = 0.08 $\mu\textrm{g}$/$m\ell$) in the assay system determined by PGE2 and NO accumulation, respectively. The inhibitory potential of alantolactone on the PGE2 and NO production was well coincided with the suppression of COX-2 and iNOS protein and mRNA expression in LPS-induced macrophages. Furthermore, alantolactone inhibited NF-kB but not AP-l binding activity on nuclear extracts evoked by LPS-stimulated macrophage cells, suggesting the possible involvement of NF-kB in the regulation of COX-2 and iNOS expression. In further study with COX-2-expressing human colon HT-29 cells, alantolactone inhibited the cell proliferation, down-regulated COX-2, and inhibited the ERK phosphorylation in the early time. These results suggest that a natural sesquiterpenoid alantolactone might be a potential lead candidate for further developing COX-2 or iNOS inhibitor possessing cancer chemopreventive or anti-inflammatory activity

• Journal of Ginseng Research
• /
• v.36 no.3
• /
• pp.263-269
• /
• 2012

Korean red ginseng has shown therapeutic effects for a number of disease conditions. However, little is known about the anti-inflammatory effect of Korean red ginseng saponin fraction (RGSF) in vitro and in vivo. Therefore, in this study, we showed that RGSF containing 20(S)-protopanaxadiol type saponins inhibited nitric oxide production and attenuated the release of tumor necrotic factor (TNF)-${\alpha}$, interleukin (IL)-6, granulocyte monocyte colony stimulating factor (GMCSF), and macrophage chemo-attractant protein-1 in lipopolysaccharide (LPS) stimulated murine macrophage RAW264.7 cells. Moreover, RGSF down-regulated the mRNA expressions of inducible nitric oxide synthase, cyclooxyginase-2, IL-$1{\beta}$, TNF-${\alpha}$, GMCSF, and IL-6. Furthermore, RGSF reduced the level of TNF-${\alpha}$ in the serum and protected mice against LPS mediated endotoxic shock. In conclusion, these results indicated that ginsenosides from RGSF and their metabolites could be potential sources of therapeutic agents against inflammation.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.17 no.1
• /
• pp.55-65
• /
• 2004

Allergic rhinitis is an inflammation of the nasal mucosa which is triggered by an allergic reaction. When exposed to certain allergens, the IgE covered mast cells degranulate releasing inflammatory mediators and cytokines which results in a local inflammatory reaction. In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis and new therapeutic targets of allergic rhinitis. This experimental study was done to research effects of Sochungryong-tang. We have studied effect of mice on OVA-induced production of IL-4, IL-5, IFN-${\gamma}$ by murine splenocytes and effect of OVA-induced total IgE and OVA-specific IgE. The results were as follows; 1. In IL-4 study, Sochungryong-tang treated group was proved significant inhibitory effect(p〈0.005). 2. In IL-5 study, Sochungryong-tang treated group was proved significant inhibitory effect(p〈0.05). 3. In JFN-${\gamma}$ study, Sochungryong-tang treated group was proved significant inhibitory effect(p〈0.000001). 4. In Total IgE, Sochungryong-tang treated group was proved significant inhibitory effect(p〈0.000001). 5. In OVA-specific IgE, Sochungryong-tang treated group didn't showed significant inhibitory effect. Depending upon above results, it is considered that Sochungryong-tang has the inhibitory effect on the allergic rhinitis of mice and suggested that it could be used in relieving patients of the symptoms which are caused by allergic rhinitis.