• 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

• The Journal of Korean Medicine
• /
• v.20 no.1 s.37
• /
• pp.151-160
• /
• 1999

Nitric oxide(NO) is synthesized via the oxidation of L-arginine by a family of nitric oxide synthases(NOS), which are either constitutive(cNOS) or inducible(iNOS). The induction of iNOS in tissues can lead to the sustained production of high concentrations of NO which may exert pro-inflammatory effects including vasodilation. edema, cyototoxicity, and its activity can be mediated by various pro-inflammatory cytokine, including interferon ${\gamma}(INF-{\gamma})$. tumor necrosis factor, IL- 1 and IL-6. The enzyme, iNOS, became a new target for pharmacologcal research with the aim to find new substances for the treatment of chronic inflammatory disorders. Murine macrophages produce large amounts of NO when activated with $TFN-{\gamma}$ plus LPS. The murine macrophage-like cell line, RAW 264.7, is a suitable cell model on which to perform vitro studies regarding the iNOS system. Semen jugrandis is a fatty walnut seed found in Korea. The walnut have been used in foik medicine to improve virility, to relieved asthma, and to relieve constipation. Sesquiterpenelactones were isolated from this plant. In the course of screening for NO inhibitory activity from medicnial plants, the aqueous extract of this plant was found to have a significant activity. The result are summarized as followings. 1. The viability of cells incubated in the presence of semen jugrandis increased mare than non incubated cells. 2. Semen jugrandis suppressed the production of NO in tissues dependent on density. 3. Semen jugrandis suppressed the induction of iNOS in tissues dependent on density can lead to reduced production of NO. 4. Semen jugrandis suppressed the production of superoxide in tissue depend on density. According to the above mentioned results, semen jugrandis could be applied production of NO and superoxide can lead to reduction of chronic inflammatary. And as a depence matter come into a virus of microbe and tumor cells.

• Food Science and Preservation
• /
• v.24 no.1
• /
• pp.116-124
• /
• 2017

In this study, we compared the antioxidant and immuno-modulatory effects of water (HR, HL, HS), 70% ethanol (ER, EL, ES), and 70% methanol (MR, ML, MS) extracts of different parts (root, leaf, and seed) from Glehnia Radix. Yields were 17.40-30.17% for water extract, 11.47-28.67% for 70% ethanol extract, and 10.73-30.57% for 70% methanol extract, respectively. The total polyphenol and flavonoid contents of EL were 10.79 g/100 g and 2.01 g/100 g, respectively. The DPPH and ABTS radical scavenging activities of EL at $1,000{\mu}g/mL$ were 84.70% and 57.64%, respectively. The superoxide radical scavenging and ferric-reducing antioxidant power of EL at $1,000{\mu}g/mL$ were 84.05% and $975.28{\mu}M$, respectively. Moreover, 70% ethanol and 70% methanol extracts of root from Glehnia Radix significantly inhibited production of NO in LPS-stimulated macrophage RAW 264.7 cells without cytotoxicity. These results suggest that 70% ethanol and 70% methanol extracts of Glehnia Radix leaf may be a useful functional food material in the food industry.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.32 no.3
• /
• pp.48-57
• /
• 2019

Objectives : This study examined the inhibitory effects of Wisaengtang(WST) on inflammatory mediators($NF-{\kappa}B$, COX-2, iNOS, IL-6) in cellular inflammatory responses induced by lipopolysaccharide(LPS). Methods : To investigate the cytotoxicity of WST, MTT assay was used. The inhibitory effects of inflammatory mediators were confirmed by real-time PCR and DPPH scavenging activity was measured to confirm the antioxidative effect. Results : When the $NF-{\kappa}B$ mRNA expression was inhibited, the levels of COX-2, iNOS, and IL-6 mRNA in the inflammatory response decreased significantly. iNOS is involved in the production of nitric oxide (NO), and it is confirmed that WST inhibits the expression of iNOS mRNA and thus the production of NO. Conclusions : These results suggest that WST can be a therapeutic substance for oxidation and inflammation through elimination of DPPH free radical and inhibition of $NF-{\kappa}B$ activity.

• The korean journal of orthodontics
• /
• v.25 no.6 s.53
• /
• pp.705-714
• /
• 1995

Due to the great deal of effort that has gone into the study of osteoclastic differentiation and activation over the last few decades, the mechanisms of these two events have been discovered gradually. Nitric oxide($NO^-$), which is produced from arginine by a nitric oxide synthase, opened up a new area of biological research. Recently, it has been reported that $NO^-$ is produced by osteoblasts stimulated by lipopolysaccharide and several other cytokines. In this study, the effect of sodium nitroprusside(SNP), a donor of nitric oxide($NO^-$), on osteoclast-like cell formation and on mature osteoclast function was examined. To determine the mechanism of the inhibitory effects of SNP decreased not only the basal $^{45}Ca$ release but also thee bone resorption induced by PTH and 1,25-dihydroxyvitamin $D_3\;(1,25[OH]_{2}D_3)$. The inhibitory effect of SNP on bone resorption induced by PTH appeared 2 dyas after treatment, whereas SNP effect on inhibiting bone resorption induced by $1,25[OH]_{2}D_3$ appeared at the thhird days. When chicken and rat osteeoclasts were cultured on dentin slices, treatment of $300{\mu}M$ SNP resulted in a significant decrease in dentin resorption by osteoclasts in terms of total resolution area and average individual area. We also examind the effect of SNP on formation of osteoclast-like cells that is TRAP-positive multinucleated cells from chicken and rat bone marrow cells in the presence or absence of $10^{-8}\;M\;1,25[OH]_{2}D_3$. The addition of $300{\mu}M$ SNP inhibiteed the formation of TRAP-positive multinucleated cells. The present data suggest that SNP, possibly as a $NO^-$ donor, inhibits the osteoclastic differentiation and osteoclastic activity.

• Biomolecules & Therapeutics
• /
• v.16 no.3
• /
• pp.277-285
• /
• 2008

Panax ginseng C.A. Mayer (Araliaceae, P. ginseng) has been used for the enhancement of vascular and immune functions in Korea and Japan for a long time. Ginsenoside $Rb_1$ and $Rg_3$ isolated from P. ginseng head-part butanolic extract (PGHB) were investigated for anti-inflammatory activity. Ginsenosides and PGHB did not affect the cell viability within $0\;-\;100\;{\mu}g/ml$ concentration to RAW 264.7 murine macrophage cells. Ginsenosides and PGHB inhibited partly lipopolysaccharide (LPS)-induced nitrite production in a dose-dependent manner. The ginsenosides and PGHB showed partially chemical nitric oxide (NO) quenching (maximum 40%) in the cell-free system. Also, ginsenoside $Rb_1$ and $Rg_3$ inhibited markedly approximately 74 and 54% of inducible nitric oxide synthase (iNOS) mRNA transcription from LPS-induced RAW 264.7 cells. Taken together, the inhibitory effect of ginsenosides and PGHB on NO production did not occur as a result of cell viability, but was caused by both the chemical NO quenching and the regulation of iNOS. Additionally, the ginsenoside $Rb_1$ and PGHB inhibited prostaglandin $E_2$ ($PGE_2$) synthesis in a concentration-dependent manner, showed approximately 70-98% inhibition at $100\;{\mu}g/ml$ concentration. And the treatment with ginsenosides and PGHB attenuated partially LPS-upregulated cyclooxygenase-2 (COX-2) gene transcription. Ginsenoside $Rg_3$ suppressed LPS-stimulated interleukin-6 (IL-6) level to the basal in RAW 264.7 cells. From these results, ginsenoside $Rb_1,\;Rg_3$, and PGHB may be useful for the relief and retardation of immunological inflammatory responses and its action may occur through the reduction of inflammatory mediators, including NO, $PGE_2$, and IL-6 production.

• Journal of Applied Biological Chemistry
• /
• v.66
• /
• pp.29-38
• /
• 2023

Recent studies have highlighted the link between diseases and inflammation across our lifespan. Our sedentary lifestyle, high-calorie diet, chronic stress, chronic infections, and exposure to pollutants and xenobiotics, collectively intensify the course and recurrence of infections and inflammation in our bodies, promoting the prevalence of chronic diseases and aging. Given such phenomena and considering additional factors such as the frequency of prescription, and easy access to over-the-counter drugs, the need for anti-inflammatory therapeutics is ever-increasing. However, the readily available anti-inflammatory treatment option comes with a greater risk of side effects or high cost (biologics). Therefore in this growing competition of discovering and developing new potent anti-inflammatory drugs, we focused on utilizing the established knowledge of traditional medicine to find lead compounds. Since lead optimization is an indispensable step toward drug development, we applied this concept for the production of potent anti-inflammatory compounds achieved by structural modification of flavonoids. The derivative obtained through acetylation of myricetin, 3,3',4',5,5',7-hexaacetate myricetin, showed a greater inhibitory effect in the production of pro-inflammatory mediators such as nitric oxide, Prostaglandin E₂, and pro-inflammatory cytokines like interleukin-6, interleukin1β, in lipopolysaccharide-stimulated RAW264.7 mouse macrophage cells compared to myricetin. The increased potency of inhibition was in conjunction with an increased inhibitory effect on inducible nitric oxide synthase and cyclooxygenase-2 proteins. Through such measures, this study supports lead optimization for well-established lead compounds from traditional medicine using a simpler and greener chemistry approach for the purpose of designing and developing potent anti-inflammatory therapeutics with possibly fewer side effects and increased bioavailability.

• Korean Journal of Plant Resources
• /
• v.28 no.5
• /
• pp.568-573
• /
• 2015

Arabis glabra is a localized common rhizomatous flowering plant, This plant is often used in Korean traditional systems of medicine as a remedy for blood cleaning, detoxification, abscess, gastrospasm, arthritis, contraction and diarrhea. Generally drugs that are used for arthritis have antinociceptive and anti-inflammatory properties. However, validity of the anti-inflammatory activity has not been scientifically investigated so far. Therefore, the aim of this study was to investigate the anti-inflammatory potential of A. glabra using the ethanolic extract and its sub-fractions. To evaluate the anti-inflammatory effects, we examined the inflammatory mediators such as nitric oxide (NO) and prostaglandin E₂ (PGE₂) on RAW 264.7macrophages. Our results indicated that hexane and chloroform fraction significantly inhibited the LPS-induced NO and PGE₂ production in the cells. The hexane fraction inhibitory activity for NO tests with IC₅₀ values showed in 21.0 ㎍/㎖. The chloroform fraction inhibitory activity for PGE₂ tests with IC₅₀ values showed in 18.0 ㎍/㎖. These efficacy are expected to be able to present the potential for the development of health functional food for the prevention inflammatory diseases because it has sufficient preventive medical possibilities. Further, it is determined that it is necessary to further study the mechanism of cytokine and protein expression associated with inflammation.

• Journal of Environmental Science International
• /
• v.28 no.11
• /
• pp.993-1004
• /
• 2019

Chrysanthemum boreale Makino (C. boreale) is widely distributed in Asian countries, and has traditionally been used to treat various inflammatory diseases including bronchitis. In this study, we aimed to isolate biologically active compounds from leaves and stems of C. boreale. Chemical components were purified by column chromatograpy and recyclic HPLC, and characterized from their spectral data (IR, MS, NMR). Biological activity experiments were conducted for Farnesyl-protein transferase (FPTase) activity, apoptosis and nitirc oxide (NO) release. As a results, three sesquiterpene lactones were isolated. Compound 1 (4-methoxy-8-O-acetyl-10-hydroxy-2,11(13)-guaiadiene-12,6-olide) showed strong cytotoxic activities having an average growth inhibition of 50% ($GI_{50}$) value of $1.89{\mu}g/m{\ell}$ against human colon adenocarcinoma cells. Compound 1 also showed a low half maximal inhibitory concentration ($IC_{50}$) value of $10{\mu}g/m{\ell}$ for NO release. In the caspase 3 activity, compound 1 and compound 2 (8-O-(2-carbonyl-2-butyl)-3,10-dihydroxy-4,11(13) -guaiadiene-12,6-olide) exhibited 94% and 90% apoptosis inhibition activity, respectively. Compound 3 (4,8-O-diacetyl -10-hydroxy-2(3),11(13)-guaiadiene-12,6-olide) showed a strong inhibitory effect on FPTase activity with 90% inhibitory activity at a concentration of $100{\mu}g/m{\ell}$. These results clearly show the presence of lactone compounds in the leaves and stems, which may partially contribute to the pharmacological activity of C. boreale.

• Journal of Life Science
• /
• v.21 no.8
• /
• pp.1120-1126
• /
• 2011

Rosa multiflora thunberg belonging to Rosaceae is widely distributed in East Asia including Korea and Japan, and has been reported to have tormentic acid and rosamultin. To develop a new natural anti-inflammatory agent for cosmetics, we investigated the inhibitory effects of inflammation in Rosa multiflora root (R. multiflora root). The biological activity and anti-inflammatory effects were investigated by water, ethanol, methanol and acetone extracts of R. multiflora root. The measurements of polyphenol content from R. multiflora root were highest in water and acetone extracts, at 57.48 ${\pm}$ 0.88 mg/g and 67.05 ${\pm}$ 0.56 mg/g, respectively. The result of DPPH, ABTS and superoxide anion radical scavenging effects showed over 50% efficacy at 50 ${\mu}g/ml$ in ethanol, methanol and acetone extracts. Hyaluronidase inhibition effect showed over 60% efficacy at 500 ${\mu}g/ml$ in ethanol, methanol, and acetone extracts. Nitric oxide radical inhibition effect of R. multiflora root ethanol extracts showed over 30% efficacy at 500 ${\mu}g/ml$. We investigated the effect of R. multiflora root extracts on nitric oxide (NO) production of inducible nitric oxide synthase (iNOS) in LPS-induced RAW 264.7 macrophage cells. The result showed that R. multiflora root extracts have an inhibitory effect on NO production and iNOS expression and also can be used as an anti-inflammatory agent. These antioxidant and anti-inflammatory effects of R. multiflora root show applicant potential application as a functional cosmetic material.