• YAKHAK HOEJI
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• v.56 no.1
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• pp.20-25
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• 2012

In Northeast Asia, Paeoniae Radix has been used in treatments of inflammation-causing diseases such as arthritis for many centuries. Paeoniflorin, one of the principle bioactive monoterpene glucosides from the paeony root, is reported to be mostly responsible for the effectiveness of the treatments. However, the anti-inflammatory effect of a monoterpene, paeoniflorigenone (PFG) which partially has the moiety of paeoniflorin minus a glucose structure is unknown. Thus, the aim of this work was to investigate anti-inflammatory activity of PFG. For the investigation, PFG activity on the NO (nitric oxide) production from LPS-stimulated macrophages, and the anti-inflammatory effect was tested in the animal model of septic arthritis caused by Candida albicans, a major etiological agent for septic arthritis. For induction of the arthritis, mice were administered with an emulsion of C. albicans cell wall (CACW) mixed with Complete Freund's Adjuvant (CFA) via footpad-injection (Day 0); PFG at a dose of 0.5 or 1 mg/mouse (25 or 50 mg/kg of body-weight) was given to the animals on Day 3, 6, and 9; footpads were scored for arthritis. Moreover, the PFG effect on proliferation of T-lymphocyte that causes aggravation of arthritis was additionally tested. Data resulting from those tests showed that PFG inhibited the NO production from the stimulated macrophage in a dose dependent manner (P<0.05), indicating that PFG is an anti-inflammatory. To confirm the in-vitro results, anti-inflammatory activity of PFG was determined against C. albicans-caused septic arthritis. Data showed that PFG-treatment reduced footpad-swelling which indicates that PFG has anti-arthritic effect (P<0.05), which is therapeutic. The anti-arthritic effect appeared to be mediated by PFG suppression of T-cell proliferation. Ultimately, PFG, a monoterpene component, has anti-inflammatory activity analogous to paeoniflorin. The anti-inflammatory activity treats the septic arthritis due to a pathogenic fungus C. albicans.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.7-13
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• 2001

Arthritis may be broadly classified as degenerative - related to defects in cartilage and other joint constituents, often age-associated - or inflammatory disease. Inflammatory arthritis called as rheumatoid arthritis (RA) is a chronic inflammatory arthropathy and characterized by a destructive arthritis. RA encompasses infectious arthritis, arthritis caused by intra-articular deposits of crystalline material (gout), syndromes associated with genetic defects (familial Mediterranean fever), and the immune-mediated inflammatory arthropathy. Degenerative arthritis called as osteoarthritis (OA), which is most frequently occurring, causes degenerative figures of knee, waist and knuckle, and accompanies severe pain around the cartilage. Also, it may cause morning stiffness, gelling effect, tenderness, bone swelling, crepitus, and motion disorders.

• The Journal of Korean Medicine
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• v.32 no.6
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• pp.18-29
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• 2011

Objectives: To investigate anti-inflammatory and anti-arthritic effects of Gyulpidaehwangbakcho-tang (GDBT) extract in a murine model of rheumatoid arthritis. Methods: The mice received $100{\mu}g$ of bovine type II collagen in Freund's complete adjuvant by intradermal injection at the base of the tail on day 0 and a booster injection on day 21. The mice were orally administered with GDBT (200 or 50mg/kg dissolved in distilled water) daily from day 1 to day 21 after arthritis incidence, and monitored for disease incidence and the severity of arthritis up to day 21. In order to evaluate the effect of GDBT on disease progression, we examined pro-inflammatory cytokines including IL-$1{\beta}$, IL-6, TNF-${\alpha}$, COX-2 and NOS-II. Results: GDBT produced a significant and dose dependent inhibition of arthritis and inflammation during the entire duration of the study. This action was characterized by the decreased production of IL-$1{\beta}$, IL-6, TNF-${\alpha}$, COX-2, and NOS-II in vivo. Conclusion: We believe that the anti-arthritic activity of GDBT is due to its modulatory effect on the expression of pro-inflammatory cytokine in the synovium. Our results contribute towards validation of the traditional use of GDBT in the treatment of RA and other inflammatory joint disorders.

• The Journal of Korean Academy of Orthopedic Manual Physical Therapy
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• v.14 no.2
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• pp.16-24
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• 2008

Anatomy: Advanced knowledges of cellular and molecular biology led to the development of therapies of rheumatoid arthritis(RA). Rheumatoid arthritis (RA) is a chronic, recurrent, systemic inflammatory disease and results in major deformity or dysfunction of joints. Etiology: Rheumatoid arthritis is now concevied as autoimmune disease. There have been many trials to define the immunological changes in rheumatoid arthritis. But now pathogenesis and significance of immunoglobulin complement and rheumatoid factor are not full accepted. Syndrome: Joints are characteristically involved with early inflammatory changes in the synovial membrane, peripheral portions of the articular cartilage, and lation tissue(pannus) forms, covers, and erodes the articular cartilage, bone and ligaments within the jiont capsule. Inflammatory changes also occur in tendon sheaths(tenosynovitis), and if subjected to a lot of friction, the tendons may fray or rupture. Extra-articular pathological changes sometimes occur, these include rheumatoid nodules, atrophy and fibrosis of muscles, and mild cardiac changes. Treatment: Tumor necrosis factor(TNF) inhibitor for the treatment of rheumatoid arthritis(RA) induces not only significant improvement of symptoms and signs of RA but also substantial inhibition of progressive joint damage.

• Korean Journal of Pharmacognosy
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• v.27 no.3
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• pp.184-189
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• 1996

Ohyaksungisan, combined preparation of crude drugs, has been used for hemiplegia, arthralgia and paralysis in traditional Korean medicine. The anti-inflammatory activity of the aqueous extract from Ohyaksungisan(OSSE) was investigated on acetic acid-induced edema and adjuvant arthritis in rats. Acute toxicity and analgesic action in mice were also examined. Its anti-inflammatory activity on 5% acetic acid-induced edema and adjuvant arthritis was observed with oral administration. The acute toxicity showed 10% mortality at 2400 mg/kg (p.o), but was not showed at 1200 mg/kg (i.p). OSSE was showed to have significant analgesic action (P<0.05) at 150 mg/kg and this action was strengthened at 300, 600 mg/kg. The anti-inflammatory effect was showed significant preventive effect on the hind paw edema from 90 min. and the adjuvant arthritis, when orally administered for 19 days. showed significant inhibitory effect on the hind paw edema from the 5th day.

• Herbal Formula Science
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• v.18 no.2
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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.

• Journal of Korean Medicine Rehabilitation
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• v.23 no.2
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• pp.49-61
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• 2013

Objectives : This study was conducted to determine whether or not Kangwhaldoche-tang(Qianghuodaozhi-tang) (KDT) aqueous extracts can protect articular cartilage losses on the Freund's complete adjuvant(FCA)-induced rat rheumatoid arthritis. Methods : 520, 260 or 130 mg/kg of KDT were orally administered once a day for 14 days from 14 days after FCA treatments, and 15 mg/kg of dexamethasone was intraperitoneally administered as reference drug in this experiment. Changes on the body weight, knee circumferences, gross arthritis score, inflammatory tissue prostaglandin(PG) $E_2$ levels were monitored with cartilage collagen components and glucosaminoglycans(GAGs) compositions - chondroitin sulphate, heparin sulphate and hyaluronic acid in the present study. Results : As results of FCA treatment, classic rheumatoid arthritis featuring dramatic decreases of the body weights, cartilage collagen and GAGs contents with increases of the knee circumferences, gross arthritis scores and inflammatory tissue $PGE_2$ levels, were demonstrated in the present study. However, these changes from FCA - induced rheumatoid arthritis were clearly inhibited by treatment of dexamethasone and all three different dosages of KDT. Although overall anti-inflammatory effects of KDT 520 mg/kg were lowered than those of dexamethasone 15 mg/kg treated rats, KDT 520 mg/kg showed more favorable preserve effects on the cartilage GAGs and KDT 260 mg/kg treated rats showed similar preserve effects as compared with dexamethasone 15 mg/kg in this experiment. Conclusions : The present results supported that over 75 mg/kg of KDT showed favorable anti-arthritic effects on the FCA-induced arthritis mediated by suppression of $PGE_2$, representative inflammatory mediator, and may help improve rheumatoid arthritis.

• Advances in Traditional Medicine
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• v.9 no.2
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• pp.164-173
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• 2009

The anti-inflammatory effect of Spirulina fusiformis on monosodium urate crystal-induced inflammation in mice has been investigated and compared with the non-steroidal anti-inflammatory drug Indomethacin. The paw volume, lysosomal enzyme activities, lipid peroxidation, anti-oxidant status and inflammatory mediator tumour necrosis factor-$\alpha$ were studied in control and monosodium urate crystal-induced mice after oral administration of Spirulina platensis in an experimental model for gouty arthritis. In the induced mice, the levels of lysosomal enzymes, inflammatory mediator tumour necrosis factor-$\alpha$, lipid peroxidation and the paw volume increased significantly, whereas the antioxidant status decreased when compared to control mice. $\beta$-glucuronidase and lactate dehydrogenase level were also found to be increased in untreated monosodium urate crystal-incubated polymorphonuclear leucocytes. After the oral administration of Spirulina fusiformis, the physical and biochemical changes observed in monosodium urate crystal-induced animals were significantly restored to near normal levels. The results clearly indicated the anti-inflammatory role of Spirulina fusiformis, a promising drug for gouty arthritis.

• IMMUNE NETWORK
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• v.19 no.1
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• pp.2.1-2.13
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• 2019

The enhanced differentiation and activation of osteoclasts (OCs) in the inflammatory arthritis such as rheumatoid arthritis (RA) and gout causes not only local bone erosion, but also systemic osteoporosis, leading to functional disabilities and morbidity. The induction and amplification of NFATc1, a master regulator of OC differentiation, is mainly regulated by receptor activator of NF-κB (RANK) ligand-RANK and calcium signaling which are amplified in the inflammatory milieu, as well as by inflammatory cytokines such as TNFα, IL-1β and IL-6. Moreover, the predominance of CD4⁺ T cell subsets, which varies depending on the condition of inflammatory diseases, can determine the fate of OC differentiation. Anti-citrullinated peptide antibodies which are critical in the pathogenesis of RA can bind to the citrullinated vimentin on the surface of OC precursors, and in turn promote OC differentiation and function via IL-8. In addition to adaptive immunity, the activation of innate immune system including the nucleotide oligomerization domain leucine rich repeat with a pyrin domain 3 inflammasome and TLRs can regulate OC maturation. The emerging perspectives about the diverse and close interactions between the immune cells and OCs in inflammatory milieu can have a significant impact on the future direction of drug development.

• Korean Journal of Veterinary Research
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• v.39 no.4
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• pp.715-723
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• 1999

Bee venom (BV) has been traditionally applied to relieve pain and to cure inflammatory diseases such as rheumatoid arthritis (RA) and neuritis. While several investigators have evaluated the anti-inflammatory effect of BV treatment, the anti-nociceptive effect of BV treatment on inflammatory pain is not reported. Therefore, we decided to evaluate the analgesic effect of BV treatment using Freund's adjuvant induced chronic arthritis model. Freund's adjuvant-induced arthritis has been used as an experimental animal model for RA in humans to assess the efficacy of the anti-inflammatory/analgesic drugs. In this study, subcutaneous BV treatment (1mg/kg/day) produced significantly reductions of symptoms related to arthritic pain (i.e. mechanical hyperalgesia and thermal hyperalgesia). The anti-nociceptive effect of BV was observed from at least 12 days after BV treatment. Furthermore, BV treatment significantly suppressed adjuvant induced Fos expression in lumbar spinal cord. We also found that local injection of BV into near the inflammatory site (especially Zusanli-acupoint) showed more potent analgesic effect on arthritic pain rather than distant injection of BV from inflammatory site (arbitrary side of back). The present study demonstrates that BV treatment has anti-nociceptive effect on arthritis induced inflammatory pain. The analgesic effect of BV on RA is probably mediated by the effect of BV itself or possible other mechanism such as counter-irritation. Furthermore, it is possible that BV acupuncture is one of the promising candidates for long-term therapy of RA.