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

• IMMUNE NETWORK
• /
• v.7 no.1
• /
• pp.39-47
• /
• 2007

Background: Stromal cell-derived factor (SDF)-1 is a potent chemoattractant for activated T cells into the inflamed Rheumatoid arthritis (RA) synovium. To determine the effect of macrophage migration inhibitory factor (MIF) on the production of SDF-1 in the inflamed RA synovium. Methods: The expression of SDF-1 and MIF in RA and Osteoarthritis (OA) synovium was examined by immunohistochemical staining. The SDF-1 was quantified by RT-PCR and ELISA after RA fibroblast like synoviocyte (FLS) were treated with MIF in the presence and absence of inhibitors of intracellular signal molecules. The synovial fluid (SF) and serum levels of MIF and SDF-1 in RA, OA and healthy control were measured by ELISA. Results: Expression of SDF-1 and MIF in synovium was higher in RA patients than in OA patients. The production of SDF-1 was enhanced in RA FLS by MIF stimulation. Such effect of MIF was blocked by the inhibitors of NF-${\kappa}B$. Concentrations of SDF-1 in the serum and SF were higher in RA patients than in OA patients and healthy control. SDF-1 and MIF was overexpressed in RA FLS, and MIF could up-regulate the production of SDF-1 in RA FLS via NF-${\kappa}B$-mediated pathways. Conclusion: These results suggest that an inhibition of interaction between MIF from T cells and SDF-1 of FLS may provide a new therapeutic approach in the treatment of RA.

• Molecular & Cellular Toxicology
• /
• v.3 no.2
• /
• pp.85-89
• /
• 2007

Efficient gene delivery to specific tissues, such as inflammatory and cancerous tissues, is currently a major concern in disease treatment. The human transferrin receptor (hTR) has been detected in the synovium and fibroblast-like synoviocytes (FLS), which raises the possibility that expression of hTR is associated with the pathogenesis of rheumatoid arthritis (RA). To investigate whether the hTR is a useful target for gene transduction into the FLS of RA patients, recombinant adenoviruses with wildtype fiber (AdLac) and transferrin peptide-tagged fiber (Tf-AdLac) were used. The hTR expression level in FLS was notably increased by basic fibroblast growth factor (bFGF). Gene transduction to FLS was significantly higher by the hTR-targeted adenovirus than by the AdLac adenovirus, and treatment of the FLS with bFGF resulted in increased gene transduction by Tf-AdLac. Taken together, these data support Tf-AdLac as a new strategy for gene transduction in the treatment of RA patients.

• CELLMED
• /
• v.11 no.1
• /
• pp.1.1-1.4
• /
• 2021

Background: Amavata is a disease that occurs as a result of the error of metabolism. Poor dietary habits and faulty Dincharya (daily regimen) and ritucharya (seasonal regimen) leading to deranged metabolism and Agni (metabolic fire) which results in the formation of Ama(undigested product of metabolism). When Amaconceals with Vata(subtle energy associated with movement) and circulates in the body under the influence of Vyana Vayu (omnipresent air)it clogs the srotasas (microchannels) and initiates the inflammatory cascade. Amavata is commonly correlated with rheumatoid arthritis (RA) while other forms of auto-immune disorders can also be included in Amavata.Dysbiosis of the gut microbiota (GM) has been connected to the onset of diverse autoimmune diseases. In this study, it was hypothesized that Panchakarma (bio-purificatory methods) based intervention such as Virechana Karma (therapeutic purgation) may influence microbiota. Materials and Methods: Various Ayurvedic literature were reviewed for the etiopathogenesis of Amavata. Different databases were searched with research papers related to Gut Dysbiosis and autoimmunity and management of RA. A connecting link between Intestinal Dysbiosis with the autoimmune mechanisms was established and it was also found that the bowel cleansing introduced a change to the GM. Conclusion: It was concluded that Virechana karma is effective in gut flora Dysbiosis. This study aims to correlate the ancient Ayurvedic principles related to Agni Bala(metabolic energy) and biopurificatory treatment modalities like Virechana karma (therapeutic purgation)with the modern concept of gut microbiota and its role in the pathogenesis of various autoimmune disorders such as rheumatoid arthritis. The article creates an understanding about principles of Ayurveda and its rationality in today's scientific world and thereby opens newer vistas of research in therapeutics from Ayurveda, which may be helpful in the management of various immune-mediated Diseases through Ayurveda.

• Korean Journal of Acupuncture
• /
• v.24 no.3
• /
• pp.117-137
• /
• 2007

Objectives & Methods : The purpose of this study is to observe the effects of Gentianae macrophyllase Radix herbal-acupuncture solution(GR-HAS) at Joksamni(ST36) on Collagen-induced arthritis(CIA) in DBA/1J mice. The author performed several experimental items to analyze arthritis evaluation, change of weight, spleen size and adhesion rate, change of cytokine level, IgG, IgM and anti-collagen II , change of immunocyte count, histological change of CIA mouse joint related with RA. Results : 1. In the GR-HA group, the arthritis index, the incidence of arthritis and joint edema were significantly decreased. 2. In GR-HA group, there were no weight loss and similarly maintained as normal group. Spleen size, adhesion rate and the edema and transformation of knee joint were low and similarly maintained as normal group. 3. In the GR-HA, cytokine level, IgG, IgM and anti-collagen II were significantly decreased. 4. In the GR-HA, the change of immunocyte count were similarly maintained as normal group. 5. In the histological changes of the CIA mouse joint, the cartilage destruction and synovial cell proliferation were decreased in the GR-HA(Hematoxylin and eosin stain). The collagen fiber expressions in the GR-HA were similar with that of the normal group(Masson's Trichrome stain) Conclusions : These results suggest that GR-HA at ST36 has an effect to control immune reaction and suppress inflammation, synovial cell proliferation and cartilage destruction in rheumatoid arthritis.

• IMMUNE NETWORK
• /
• v.3 no.3
• /
• pp.248-254
• /
• 2003

Oral administration of antigen has long been used in the induction of immune tolerance in various animal models of autoimmune diseases including rheumatoid arthritis (RA). Alleveation of arthritogenic symptoms has been reported from RA patients who received oral administration of type II collagen (CII) without side effects, however its rather inconsistent therapeutic efficacy and variation among patients calls for more detailed investigation on the mechanism of oral tolerance to be settled as regular treatment for RA. In an attempt to understand the immunogenic processes underpinning tolerance induction by orally administered CII, we analyzed changes in the expression of costimulatory molecules and STAT/SOCS signaling messengers in the mouse model of collagen induced arthritis (CIA). We found thatin the spleen of CIA mice, that has been undergone repeated oral feeding of CII prior to the induction of arthritis, showed increased promortion of CTLA4 expressing lymphocytes than in the spleen of PBS fed control. On the other hand, cells expressing CD28 or ICOS were decreased in the spleen of tolerized mice. Tolerance induction by oral CII administration also enhanced the expression of STAT6 in both RNA and protein level, while not affecting the expression of STAT3. The expression of SOCS3, which hasbeen known to transmit STAT-mediated signals from Th2 type cytokines, remained unchanged in the spleen of tolerized mice. Interestingly transcript of SOCS1, which has been associated with Th1 related pathways, was only visible in the spleen of tolerized but not of control mice, suggesting that as in the case of IL-6 signaling, it may exert a feed back inhibition toward the Th1 type stimulation.

• Journal of Acupuncture Research
• /
• v.24 no.3
• /
• pp.127-143
• /
• 2007

Objectives : The purpose of this study was to observe the effects of Chaenomelis Fructus herbal-acupuncture solution (ChF-HAS) at the Joksamni ($ST_{36}$) on arthritis induced by Collagen II in mice. Methods : The author performed several experimental items. The severity of arthritis, changes of mouse weight, size of the spleen and the degree of stenosis, changes of cytokine level, IgG, IgM and anti-collagen II, changes of immunocyte count, histological changes of the CIA mouse joint were analyzed and the conclusions are as follows. Results: 1. In the ChF-HA, the arthritis index, the incidence of arthritis, the degree of joint edema was significantly decreased. 2. In the ChF-HA, weight, spleen size and stenosis rate was low and maintained as the normal group was. 3. In the ChF-HA, cytokine level, IgG, IgM and anti-collagen II were significantly decreased. 4. In the ChF-HA, on changes of immunocyte count were maintained to the levels of normal group. 5. In histological changes of the CIA mouse joint, the cartilage destruction and synovial cell proliferation were decreased. Conclusions: These results suggest that ChF-HA at the $ST_{36}$ has an important role to control the immune reactions and suppress inflammatory response on the collagen induced rheumatoid arthritis. This study can be a significant supporting evidence that ChF-HA is chosen to be the principal therapy for clinical practice of the rheumatoid arthritis in the future.

• Journal of Acupuncture Research
• /
• v.24 no.4
• /
• pp.81-97
• /
• 2007

Objective: The purpose of this study was to observe the effects of Cnidii Rhizoma herbal-acupuncture solution(CR-HAS) at Joksamni($ST_{36}$) on arthritis induced by Collagen II in mice. Methods : The author performed several experimental items. The severity of arthritis, changes of mouse weight, size of the spleen and the degree of stenosis, changes of cytokine level, IgG, IgM and anti-collagen II, changes of immunocyte count, histological changes of the CIA mouse joint were analyzed. Results: 1. In the CR-HA, the arthritis index, the incidence of arthritis, the degree of joint edema was significantly decreased. 2. In the CR-HA, weight, spleen size and stenosis rate was low and maintained as the normal group was. 3. In the CR-HA, cytokine level, IgG, IgM and anti-collagen II were significantly decreased. 4. In the CR-HA, on changes of immunocyte count were maintained to the levels of normal group. 5. In histological changes of the CIA mouse joint, the cartilage destruction and synovial cell proliferation were decreased. Conclusions : These results suggest that CR-HA at the $ST_{36}$ has an important role to control the immune reactions and suppress inflammatory response on the collagen induced rheumatoid arthritis. This study can be a significant supporting evidence that CR-HA will be chosen to be the principal therapy for clinical practice of the rheumatoid arthritis in the future.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2001.11a
• /
• pp.83-83
• /
• 2001

Head of Panax ginseng indicates its growth number of years and it has been widely used for supplying energy to weak person. However, the underlying mechanisms are not sufficiently reported. Thus, we inclined to study head of Panax ginseng in rheumatoid arthritis and inflammation. Rheumatoid arthritis (RA), an organ-specific inflammatory disease of human, is characterized by a chronic and destructive inflammatory reaction and possibly autoimmune in etiology. It is occurred when the synobial membranes of joints and many other tissues of the body is attacked which induces significant health problem in terms of numbers of sufferers (U.S. incidence 23.7/100,000), and the synobial inflammatory is dominated by activated macrophage.

• IMMUNE NETWORK
• /
• v.8 no.1
• /
• pp.29-37
• /
• 2008

Interleukin-23 (IL-23) is a novel pro-inflammatory cytokine which has been implicated to play a pathogenic role in rheumatoid arthritis (RA). This study was undertaken to investigate the IL-23 inductive activity of the proinflammatory cytokine IL-17, $IL-1{\beta}$ and tumor necrosis factor (TNF-${\alpha}$) in RA synovial fluid mononuclear cells (SFMC). Expression of IL-23p19, IL-17, $IL-1{\beta}$ and TNF-${\alpha}$ in joint was examined by immunohistochemistry (IHC) of patients with RA and osteoarthritis (OA). The effects of IL-17 and $IL-1{\beta}$ on expression of IL-23p19 in human SFMC from RA patients were determined by reverse transcriptase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). IL-23p19 was expressed in the RA fibroblast like synoviocyte (FLS), but not from OA FLS. Similar to the protein expression, IL-23p19 mRNA could be detected by RT-PCR in RA SFMC. IL-17 and $IL-1{\beta}$ could induce RA SFMC to produce the IL-23p19. The effects of IL-17 were much stronger than $IL-1{\beta}$ or TNF-${\alpha}$. These responses were observed in a doseresponsive manner. In addition, IL-17 or $IL-1{\beta}$ neutralizing antibody down-regulated the expression of IL-23p19 induced by LPS in RA-SFMC. Our results demonstrate that IL-23p19 is overexpressed in RA synovium and IL-17 and $IL-1{\beta}$ appears to upregulate the expression of IL-23p19 in RA-SFMC.