• Journal of Microbiology and Biotechnology
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• 제18권10호
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• pp.1641-1647
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• 2008

Amygdalin is a cyanogenic glycoside plant compound found in the seeds of rosaceous stone fruits. We evaluated the anti-inflammatory and analgesic activities of amygdalin, using an in vitro lipopolysaccharide (LPS)-induced cell line and a rat model with carrageenan-induced ankle arthritis. One mM amygdalin significantly inhibited the expression of TNF-$\alpha$ and IL-l$\beta$ mRNAs in LPS-treated RAW 264.7 cells. Amygdalin (0.005, 0.05, and 0.1 mg/kg) was intramuscularly injected immediately after the induction of carrageenan-induced arthritic pain in rats, and the anti-arthritic effect of amygdalin was assessed by measuring the weight distribution ratio of the bearing forces of both feet and the ankle circumference, and by analyzing the expression levels of three molecular markers of pain and inflammation (c-Fos, TNF-$\alpha$, and IL-l$\beta$) in the spinal cord. The hyperalgesia of the arthritic ankle was alleviated most significantly by the injection of 0.005 mg/kg amygdalin. At this dosage, the expressions of c-Fos, TNF-$\alpha$, and IL-l$\beta$ in the spinal cord were significantly inhibited. However, at dosage greater than 0.005 mg/kg, the pain-relieving effect of amygdalin was not observed. Thus, amygdalin treatment effectively alleviated responses to LPS-treatment in RAW 264.7 cells and carrageenan-induced arthritis in rats, and may serve as an analgesic for relieving inflammatory pain.

• Journal of Acupuncture Research
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• 제24권4호
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• pp.157-166
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• 2007

Objective : The aim of this study was to investigate anti-arthritic effects of Honghwa-ja herbal acupuncture extract through inhibitory MIF activation. Methods: After Rheumatoid arthritis(RA) knee joint was induced by lipopolysaccharide(LPS) in vivo, Honghwa-ja herbal acupuncture solution was applied on $ST_{35}$(犢鼻) and $EX-LE_{202}$(內膝眼) coresponding human body. To research the effect on the expression of MIF, COX-2, MMP-9 mRNA, RT-PCR was performed on LPS-stimulated Raw 264.7 cells. Results: In the Honghwa-ja herbal acupuncture solution treated Raw 264.7 cell, the mRNA expression of cytokines, RA related inflammation factors, such as the MIF, COX-2, and MMP-9 reduced concentration dependently. Positive reaction of RA-related cytokines MIF, $IL-6R-{\alpha}$, STAT3, COX-2, MMP-9 was reduced. Conclusion : Honghwa-ja herbal acupuncture extract has significant protecting ability against acute progressive RA by inhibiting the production of MIF, as a top in cytokines related to inflammation.

• IMMUNE NETWORK
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• 제14권2호
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• pp.116-122
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• 2014

Macrophage death plays a role in several physiological and inflammatory pathologies such as sepsis and arthritis. In our previous work, we showed that simvastatin triggers cell death in LPS-activated RAW 264.7 mouse macrophage cells through both caspase-dependent and independent apoptotic pathways. Here, we show that the nuclear orphan receptor NR4A1 is involved in a caspase-independent apoptotic process induced by LPS and simvastatin. Simvastatin-induced NR4A1 expression in RAW 264.7 macrophages and ectopic expression of a dominant-negative mutant form of NR4A1 effectively suppressed both DNA fragmentation and the disruption of mitochondrial membrane potential (MMP) during LPS- and simvastatin-induced apoptosis. Furthermore, apoptosis was accompanied by Bcl-2-associated X protein (Bax) translocation to the mitochondria. Our findings suggest that NR4A1 expression and mitochondrial translocation of Bax are related to simvastatin-induced apoptosis in LPS-activated RAW 264.7 macrophages.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2022년도 추계학술대회
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• pp.103-103
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• 2022

Ganghwaljetongyeum (GHJTY) is a complex herbal decoction comprising 18 plants; it is used to treat arthritis. In order to develop a new anti-arthritic herbal medication, we selected 5 out of 18 GHJTY plants by using bioinformatics analysis. The new medication, called ChondroT, comprised water extracts of Osterici Radix, Lonicerae Folium, Angelicae Gigantis Radix, Clematidis Radix, and Phellodendri Cortex. This study was designed to investigate its chondroprotective and anti-inflammatory effects to develop an anti-arthritic herb medicine. ChondroT was validated using a convenient and accurate high-performance liquid chromatography. photodiode array (HPLC-PDA) detection method for simultaneous determination of its seven reference components. The concentrations of the seven marker constituents were in the range of 0.81-5.46 mg/g. The chondroprotective effects were evaluated based on SW1353 chondrocytes and matrix metalloproteinase 1 (MMP1) expression. In addition, the anti-inflammatory effects of ChondroT were studied by Western blotting of pro-inflammatory enzymes and by enzyme-linked immunosorbent assay (ELISA) of inflammatory mediators in lipopolysaccharides (LPS)-induced RAW264.7 cells. ChondroT enhanced the growth of SW1353 chondrocytes and also significantly inhibited IL-1β-induced MMP-1 expression. However, ChondroT did not show any effects on the growth of HeLa and RAW264.7 cells. The expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was induced by LPS in RAW264.7 cells, which was significantly decreased by pre-treatment with ChondroT. In addition, ChondroT reduced the activation of NF-κB and production of inflammatory mediators, such as IL-1β, IL-6, PGE2, and nitric oxide (NO) in LPS-induced RAW264.7 cells. These results show that ChondroT exerted a chondroprotective effect and demonstrated multi-target mechanisms related to inflammation and arthritis. In addition, the suppressive effect was greater than that exhibited by GHJTY, suggesting that ChondroT, a new complex herbal medication, has therapeutic potential for the treatment of arthritis.

• 대한의생명과학회지
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• 제18권4호
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• pp.338-344
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• 2012

Mollugin is the active compound of Rubia cordifolia, a well known herb widely used in alternative medicines for the treatment of various inflammatory diseases including arthritis and uteritis. In the present study, we investigated the anti-inflammatory effects of mollugin in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophage cells. Treatment with mollugin significantly inhibited LPS-induced release of nitric oxide, prostaglandin $E_2$, and inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ and interleukin-6. In addition, mollugin suppressed LPS-induced nuclear factor-kappa B (NF-${\kappa}B$) transcriptional activity. These results suggest that mollugin inhibits LPS-induced expression of inflammatory molecules via NF-${\kappa}B$, at least in part, and indicate the potential value of mollugin as a valuable new drug candidate for the treatment of various inflammatory diseases.

• Journal of Microbiology and Biotechnology
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• 제32권2호
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• pp.141-148
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• 2022

Many bone diseases such as osteolysis, osteomyelitis, and septic arthritis are caused by gram-negative bacterial infection, and lipopolysaccharide (LPS), a bacterial product, plays an essential role in this process. Drugs that inhibit LPS-induced osteoclastogenesis are urgently needed to prevent bone destruction in infective bone diseases. Marein, a major bioactive compound of Coreopsis tinctoria, possesses anti-oxidative, anti-inflammatory, anti-hypertensive, anti-hyperlipidemic, and anti-diabetic effects. In this study, we measured the effect of marein on RAW264.7 cells by CCK-8 assay and used TRAP staining to determine osteoclastogenesis. The levels of osteoclast-related genes and NF-κB-related proteins were then analyzed by western blot, and the levels of pro-inflammatory cytokines were quantified by ELISA. Our results showed that marein inhibited LPS-induced osteoclast formation by osteoclast precursor RAW264.7 cells. The effect of marein was related to its inhibitory function on expressions of pro-inflammatory cytokines and osteoclast-related genes containing RANK, TRAF6, MMP-9, CK, and CAII. Additionally, marein leads to markedly inhibited NF-κB signaling pathway activation in LPS-induced RAW264.7 cells. Concurrently, when the NF-κB signaling pathway was inhibited, osteoclast formation and pro-inflammatory cytokine expression were decreased. Collectively, marein could inhibit LPS-induced osteoclast formation in RAW264.7 cells via regulating the NF-κB signaling pathway. Our data demonstrate that marein might be a potential drug for bacteria-induced bone destruction disease. Our findings provide new insights into LPS-induced bone disease.

• Archives of Pharmacal Research
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• 제26권12호
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• pp.1061-1066
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• 2003

The fruit of Actinidia polygama (AP) has long been used as a folk medicine in Korea for treating pain, rheumatic arthritis and inflammation. The present investigation was carried out to determine the in vivo and in vitro anti-inflammatory activity of AP using several animal models of inflammation. The 70% ethanol extract of the fruit of AP significantly inhibited acetic acidinduced, vascular permeability in a dose dependent manner (23%, 38%, and 41 % inhibition at doses of 200 mg/kg, 500 mg/kg and 1000 mg/kg, respectively). This effect was maintained in AP water-soluble fraction (APW). The APW fraction also showed significant inhibitory activity against the rat paw edema induced by a single treatment of carrageenan. In vitro experiments were performed to demonstrate the inhibitory activities of APW (100 $\mu$ g/ml) on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production. The results showed that APW dose-dependently suppressed LPS-induced NO production in RAW 264.7 macrophages without a notable cytotoxic effect and also decreased inducible NO synthase (iNOS) protein expression. APW also showed a significant inhibitory effect in LPS-induced $PGE_2$ production and cyclooxygenase-2 (COX-2) expression.

• 한국약용작물학회지
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• 제22권4호
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• pp.262-269
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• 2014

Complex of mulberry extract (CME) is composed of extracts of mulberry (Morus alba L.) fruit, mulberry leaves and black beans (Glycine max (L.) Merr.). In this study, we investigated prevention effects of CME on degenerative arthritis. The $SC_{50}$ value of DPPH radical scavenging by CME was $158.49{\pm}11.35{\mu}/mL$. We found that CME significantly reduced the production of nitric oxide (NO) and protein expression of cyclooxygenase-2 (COX-2) in RAW 264.7 cells which were activated by LPS. Experiments using animal model of degenerative arthritis showed that CME (400 mg/kg body weight) inhibited the production of TNF-${\alpha}$ (77.5%) and IL-$1{\beta}$ (95.0%). Furthermore, it was observed that CME reduced to 85.9% of paw edema induced by carrageenan. These results suggest that CME could improve degenerative arthritis.

• 대한한의학방제학회지
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• 제18권2호
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• pp.183-199
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• 2010

Rheumatoid arthritis is characterized by the focal loss of cartilage due to an up-regulation of inflammatory pathways, which produce inflammatory mediators, such as interleukin-1beta(IL-$1{\beta}$), IL-6, tumour necrosis factor alpha(TNF-$\alpha$), prostaglandin, and nitric oxide(NO). We investigated the anti-arthritic effects of water extract from FLOS LONICERAE(FLWE) in vitro and in vivo. Extract inhibited the production of inflammatory mediators(NO, IL-$1{\beta}$, TNF-$\alpha$, and prostaglandin $E_2$) and the expression of inducible NO synthase(iNOS) and cyclooxygenase-2(COX-2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in a dose-dependent manner. FLWE also inhibited TNF-$\alpha$, IL-$1{\beta}$, IL-6, and $PGE_2$ production as well as COX activity in collagen-induced mouse arthritis. Moreover, FLWE significantly suppressed collagen-induced mouse arthritis. These results suggest that FLOS LONICERAE may be useful for therapy against inflammatory immune diseases and rheumatoid arthritis, probably by suppressing the production of inflammatory mediators.

• 대한약침학회지
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• 제4권1호
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• pp.5-21
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• 2001

The influence of electroacupuncture (EA), a traditional Chinese medical treatment, on type Ⅱ collagen-induced arthritis (CIA) was examined in DBA/1J mice in vivo. Mice were immunized intradermally twice at the 3-week interval with bovine type Ⅱ collagen(C Ⅱ). EA stimulation, begun on the 21 simultaneously with the second immunization, was applied at the acupoint equivalent to GV4 three times a week for 3 weeks. The results showed that EA delayed the onset, attenuated the severity of arthritis, and reduced the anti-collagen antibody level. Furthermore, we investigated the impact of EA on the productions of endogenous $interleukin-1{\Beta}$ (IL-1 beta) and prostaglandin E2 (PGE2), and the levels of IL-1 beta mRNA in splenocytes and synovial tissues from C Ⅱ immunized mice on the 45 and cyclooxygenase-2 (COX-2) mRNA in lipopolysaccharide (LPS)-stimulated macrophages of normal mice by using reverse transcriptase-polymerase chain reaction (RT-PCR). EA stimulation significant inhibited the concentrations of splenic endogenous IL-1 beta and serum PGE2. The expression of IL-1 beta mRNA in spleen cells was obviously down-regulated and that in synovial tissues was modestly affected by EA. COX-2 mRNA was highly expressed in cultured peritoneal macrophages when stimulated with LPS. Previous treatment with EA also reduced LPS-stimulated induction of COX-2 mRNA. These data suggest that EA has an inhibitory effect on murine CIA, and the partial mechanism of its therapeutic result may be attributed to inhibiting the productions of IL-1 beta and PGE2 by suppression the IL-1 beta and COX-2 gene activations.