• Natural Product Sciences
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• v.25 no.4
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• pp.304-310
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• 2019

The stems of Oplopanax elatus (OE) have long been used to treat inflammatory disorders in herbal medicine, and in the previous investigation, OE was found to possess anti-inflammatory activity in lipopolysaccharide-treated macrophages, RAW 264.7 cell. OE reduces inducible nitric oxide (NO) synthase-induced NO production, and interferes with mitogen-activated protein kinase activation pathways. In the present study, the pharmacological action of the water extract of OE was examined to establish anti-arthritic action, using a rat model of adjuvant-induced arthritis (AIA). The water extract of OE administered orally inhibited AIA-induced arthritis at (100 - 300) mg/kg/day. The paw edema was significantly decreased, in combination with reduced production of pro-inflammatory cytokines. The action mechanism includes an inhibition of MAPKs/nuclear transcription factor-κB activation. These new findings strongly suggest that OE possesses anti-arthritic action, and may be used as a therapeutic agent in inflammation-related disorders, particularly in arthritic condition.

• Journal of Periodontal and Implant Science
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• v.48 no.6
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• pp.347-359
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• 2018

Purpose: Periodontitis and rheumatoid arthritis (RA) share a similar inflammatory pathogenesis. Porphyromonas gingivalis (Pg) can induce anticyclic-citrullinated peptide autoantibodies (anti-CCP antibodies), a key factor in the development of RA. This study aimed at evaluating the relationships between the 2 diseases and identifying the clinical implications thereof, with a focus on periodontal pathogens in Korean adults. Methods: A total of 260 RA patients and 86 age- and sex-matched control patients without arthritis were enrolled in this prospective cross-sectional study. Periodontal indices and the prevalence and amount of periodontal pathogens were compared between the groups. Correlations between periodontal and RA indices were examined, as were correlations between 9 periodontal pathogens and RA indices. Results: The RA group had significantly higher values than the control group for all investigated periodontal indices (P<0.05) except the number of teeth. The gingival index (GI) was correlated with the disease activity score 28 (DAS28) (r=0.125, P=0.049), RA disease duration (r=0.253, P<0.001), erythrocyte sedimentation rate (ESR) (r=0.162, P=0.010), and anti-CCP antibody titer (r=0.205, P=0.004). Probing pocket depth (PPD) was correlated with ESR (r=0.139, P=0.027) and anti-Pg antibody titer (r=0.203, P=0.001). Bleeding on probing (BOP) was correlated with DAS28 (r=0.137, P=0.030), RA disease duration (r=0.202, P=0.001), ESR (r=0.136, P=0.030), anti-Pg antibody titer (r=0.177, P=0.005), and anti-CCP antibody titer (r=0.188, P=0.007). Clinical attachment level (CAL) and periodontitis severity were correlated with anti-Pg antibody titer (the former r=0.201, P=0.002; the latter r=0.175, P=0.006). The quantity of Pg was positively correlated with the serum anti-Pg antibody titer (r=0.148, P=0.020). Conclusions: The GI, BOP, and PPD showed positive relationships with several RA indices. The anti-Pg antibody titer had positive relationships with PPD, BOP, CAL, and periodontitis severity. Thus, increasing values of periodontal indices could be used as a risk indicator of disease development in RA patients, and an increasing anti-Pg antibody titer could be considered as a warning sign in RA patients suffering with periodontitis.

• The Korean Journal of Pharmacology
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• v.26 no.1
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• pp.51-54
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• 1990

Human leukocyte cathepsin-Gs are active participant in the active phase of inflammations like rheumatoid arthritis, emphysema and glomerular injury. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for treatment of these inflammatory diseases. Mechanism of action of NSAIDs for treatment of inflammatory diseases, especially like rheumatoid arthritis, are known as the inhibitors of prostaglandin synthesis. Inhibitions of the activities of human leukocyte cathepsin-Gs by non-steroidal anti-inflammatory drugs, however, were not same as the known pharmacological effects (inhibition of cyclooxygenase) of these drugs. Among them, especially, sulindac, salicylate, phenylbutazone, oxyphenbutazone, and salicyluric acid inhibited human leukocyte cathepsin-Gs effectively. $IC_{50}s$ of each drug were 4.3mM, 14.3mM, 6.5mM, 11mM and 15mM respectively. The drugs which have same chemical structure and same degree of inhibition effect on cyclooxygenase showed different degree or no effect on inhibition of cathepsin G. These inhibition effect might be, beside of inhibition of cyclooxygenase in the prostaglandin synthesis pathway, another benefitial antiinflammatory effect of NSAIDs by direct protection against tissue destruction in inflammatory diseases.

• Journal of Rheumatic Diseases
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• v.24 no.4
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• pp.227-235
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• 2017

Objective. Failure of first-line anti-tumor necrosis factor (TNF) agents in in rheumatoid arthritis patients leads to decisions among second-line biologic agents. To better inform these decisions, the therapeutic effectiveness of rituximab is compared with other second-line biologic agents in this observational study. Methods. Between November 2011 and December 2014, study subjects were observed for 12 month periods. Patients with an inadequate response to initial anti-TNF agent received either rituximab or alternative anti-TNF agents (adalimumab/etanercept/infliximab) based on the preference of patients and physicians. The efficacy end point of this study was the change in 28-joint count Disease Activity Score (DAS28) at six and 12 months from baseline. Safety data were also collected. Results. Ninety patients were enrolled in the study. DAS28 at six months did not change significantly whether the patients were treated with rituximab or alternative anti-TNF agents in intention-to-treat analysis (n=34, $-1.63{\pm}0.30$ vs. n=31, $-2.05{\pm}0.34$) and standard population set analysis (n=31, $-1.51{\pm}0.29$ vs. n=24, $-2.21{\pm}0.34$). Similarly, the change in DAS28 at 12 months did not reach statistical significance ($-1.82{\pm}0.35$ in the rituximab vs. $-2.34{\pm}0.44$ in the alternative anti-TNF agents, p=0.2390). Furthermore, the incidences of adverse events were similar between two groups (23.5% for rituximab group vs. 25.8% for alternative anti-TNF agents group, p=0.7851). Conclusion. Despite the limitations of our study, switching to rituximab or alternative anti-TNF agents after failure of the initial TNF antagonist showed no significant therapeutic difference in DAS28 reduction.

• Journal of Pharmacopuncture
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• v.4 no.1
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• pp.65-84
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• 2001

We recently demonstrated that bee venom (BV) injection into acupoint (i.e. Zusanli) produced more potent anti-inflammatory and antinociciptive effect in Freunds adjuvant induced rheumatoid arthritis (RA) model as compared with that of non-acupoint injection(i.e back). However, the precise components underlying BV-induced antinociceptive and/or anti-inflammatory effects have not been fully understood. Therefore, we further investigated the anti-arthritic effect of BV after extracting the whole BV according to solubility (water soluble: BVA, ethylacetate soluble: BVE). Subcutaneous BVA treatment (0.9 mg/kg/day) into Zusanli acupoint was found to dramatically inhibit paw edema and radiological change (i.e. new bone proliferation and soft tissue swelling) caused by Freunds adjuvant injection. In addition, the increase of serum interleukin-6 by RA induction was normalized by the BVA treatment as similar with that of non-arthritic animals. On the other hand, BVA therapy significantly reduced arthritis induced nociceptive behaviors (i.e., nociceptive score for mechanical hyperalgesia and thermal hyperalgesia). Furthermore, BVA treatment significantly suppressed adjuvant induced Fos expression in the lumbar spinal cord at 3 weeks post-adjuvant injection. However, BVE treatment (0.05 mg/kg/day) has not any anti-inflammatory and anti-nociceptive effect on RA. Based on the present results, we demonstrated that BVA might be a effective fraction in whole BV for long-term treatment of RA-induced pain and inflammation. However, it is clear necessary that further fraction study about BVA was required for elucidating an effective component of BVA.

• Journal of Yeungnam Medical Science
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• v.32 no.2
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• pp.127-131
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• 2015

Churg-Strauss syndrome (CSS) is a necrotizing vasculitis with extra-, peri-vascular eosinophilic infiltration. Chronic symmetric polyarthritis with the presence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody are the mainstay of rheumatoid arthritis (RA) diagnosis. Mononeuritis multiplex is a peripheral neuropathy involving more than 2 separate nerve areas. A 62-year-old male patient was referred for left foot drop and polyarthritis of both hands and feet for 4 months. During evaluation, mononeuritis multiplex was detected on nerve conduction study and electromyography tests: vasculitis with neutrophil, eosinophil, and lymphocyte infiltration on peroneal nerve biopsy. A positive response to methacholin and bronchodilator was observed on the pulmonary function test. Radiologic tests showed peri-articular soft tissue swelling and osteopenia on both hand and foot. Marked peripheral eosinophilia, high RF, and positive perinuclear anti-neutrophil cytoplasmic antibody were detected on blood tests. Here, we report on a patient with overlap syndrome of CSS and RA with review of the relevant literature, from which a few references to overlap syndrome of CSS and RA were available.

• YAKHAK HOEJI
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• v.54 no.6
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• pp.500-506
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• 2010

TNF-${\alpha}$ and VCAM-1 play a pivotal role in the pathogenesis of rheumatoid arthritis, and the development of drugs targeting these molecules has extended the therapeutical approaches to rheumatoid arthritis patients. Bispecific antibodies combine the antigen-binding sites of two antibodies within a single molecule and thus they are able to bind to two different epitopes simultaneously. A specific bispecific antibody format termed "Di-diabody" was made for the efficient approach to anti-inflammation. In this study, the DNA vector construct of Di-diabody was built up against two antigens, VCAM-1 and TNF-${\alpha}$. For evaluating this Di-diabody as a bispecific antibody on the efficacy of anti-inflammation, the proteins were analyzed according to each antigen binding affinity and cell based assay related separate molecules. The 7H/Humira Di-diabody produced in this study interacted with its ligands, VCAM-1 and TNF-${\alpha}$, respectively. Also, this antibody exhibited the similar functional activities as compared to 7H-IgG in respect to inhibition of hVCAM-1-induced cell adhesion and Humira-IgG in respect to inhibition of TNF-${\alpha}$ induced cytotoxicity. Further study to elucidate the pharmacological significance of the Di-diabody is warranted using experimental animals.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.542-547
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• 2008

In order to examine anti-inflammatory effect of Cinnamomi Ramulus (CR) alcohol extract on rheumatoid arthritis, the present study investigated the viability and TNF-${\alpha}$ production in Raw264.7 cells treated with CR and collagen induced arthritis in DBA/1J mice which were orally administered with CR prior to immunization. The results are as follows: CR extract at $20{\mu}g/ml$ inhibited the viability of Raw264.7 by 50%. CR at 15 and $20{\mu}g/ml$ showed a significant decrease in TNF-${\alpha}$ levels from Raw264.7 cells treated with LPS. CR administration decreased arthritic index in DBA/1J mice immunized with bovine collagen type II but it did not reach statistical significance. CR administration significantly decreased spleen weights obtained from mice in 6 weeks after immunization. CR administration significantly decreased serum anti-type II collagen antibody levels compared with control group. CR administration decreased serum IL-6 levels compared with control group but it did not reach statistical significance.

• 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.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.1 no.1
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• pp.15-24
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• 1988

To study the effect of Sopoungwhalwheol-tang and Sopoungwhalwheol-tang with cheon chung on the "Tong poung" "yeouk Geul poung" inoriental medicine (Rheumatoid arthrits) measure cure effect on the Analgesic, Anti-inflammatory anti-phlogistic and concentration of albumin's Test. The results are Summarized as follows, 1. Sopoungwhalwheol-tang liquid reduced significantly the pain by acetic acid in accordance with the increase of double dosages, and Sopoungwhalwheol-tang with cheon chung (which was similar with Aspring Group) was more marked effective. 2. Sopoungwhalwheol-tang with cheon chung reduced the edema by carragenine and at 60 minutes, two groups all reduced the edema and at 180 minutes, Sopoungwhalwheol-tang was recognized some effectiveness and Sopoungwhalwheol-tang with cheon chung was recognized excellent effectiveness. 3. Sopoungwhalwheol-tang with cheon chung has more continued Antiphlogistic effect against the fever by yeast which was fallen after 60 minutes of prescription of medicine than Sopoungwhalwheol-tang. 4. Sopoungwhalwheol-tang with cheon chung was more effective against the concentration of albumin by $1\%$ bovine serum albumin than Sopoungwhalwheol-tang. 5. According to the above experiments. Sopoungwhalwheol-tang with cheon chung has greater anti-inflammatory, antiphlogistic Analgestic effect than Sopoungwhalwheol-tang.