• Archives of Pharmacal Research
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• 제24권2호
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• pp.150-158
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• 2001

The activity of nonsteroidal antiinflammatory drugs (NSAIDs) in rheumatoid arthritis is not only due to the inhibition of the production of prostaglandins, which can even have beneficial immunosuppressive effects in chronic inflammatory processes. Since we speculated that these drugs could also act by protecting endogenous proteins against denaturation, we evaluated their effect on heat-induced denaturation human serum albumin (HSA) in comparison with several fatty acids which are known to be potent stabilizers of this protein. By the Mizushimas assay and a recently developed HPLC assays we observed that NSAIDs were slightly less active [$EC_{50}~10^{-5}-10^{-4}$ M] than FA and that the HPLC method was less sensitive but more selective than the turbidimetric assay, i.e. it was capable of distinguishing true antiaggregant agents like FA and NSAIDs from substances capable of inhibiting the precipitation of denatured protein aggregates. In conclusion, this survey could be useful for the development of more effective agents in protein condensation diseases like rheumatic disorders, cataract and Alzheimers disease.

• 대한한의학회지
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• 제30권1호
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• pp.150-162
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• 2009

Objectives: Inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 ($PGE_2$) and pro-inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ playa critical role in inflammatory immune response. Therefore, intervention of inflammatory mediator production promises therapeutic benefit for treatment of many chronic inflammatory diseases, such as allergic asthma, rheumatoid arthritis, multiple sclerosis, septic shock and neurodegenerative diseases. In this study, the pharmacological effects of the flower MeOH extract Panax notoginseng (Notoginseng Flos; NF) on inflammation were investigated to address potential therapeutic or toxic effects. Methods: RA W264.7 cells were treated with different concentrations of NF methanol (NF-M) extract in the presence or absence of LPS ($1{\mu}g/m{\ell}$). Results: NF-M extract significantly inhibited LPS-induced production of NO, $PGE_2$ and pro-inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ in a dose-dependent manner. In addition, NF-M extract suppressed mRNA expressions and protein levels of iNOS, COX-2 and pro-inflammatory cytokines in LPS-stimulated RA W264.7 cells. Conclusion: These results indicated that NF-M extract inhibits LPS-induced production of inflammatory mediators in macrophages and demonstrated that NF-M extract possesses anti-inflammatory properties in vitro.

• Journal of Acupuncture Research
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• 제23권2호
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• pp.113-123
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• 2006

Objectives : Deer antler Herbal-Acupuncture (DHA) solution represents one of the most commonly used medicine to treat rheumatoid arthritis. But, mechanisms of its antiarthritic activities are still poorly understood. Identification of common DHA aqua-acupuncture capable of affording protection or modulating the onset and severity of arthritis may have important human health implications. Results : We determined if DHA could prevent the binding of $IL-1{\beta}$ to its cellular receptors. DHA addition to rat chondrocytes treated with $IL-1{\beta}$ or with reactive oxygen species(ROS) prevents the activation of proteoglycan synthesis. After treatment with $IL-1{\beta}$, DHA increased the expression of mRNA encoding the type II $IL-1{\beta}$ receptor. These results emphasize the potential role of two regulating proteins of the $IL-1{\beta}$ signaling pathway that could account for the beneficial effect of DHA in osteRArthritis. The present study also identifies a novel mechanism of DHA-mediated anti-inflammatory activity. Conclusion : It is shown that DHA inhibits both $IL-1{\beta}-$ and $TNF-{\alpha}-induced$ NO production in normal human articular chondrocytes. The observed suppression of IL-1-induced NO production is associated with inhibition of inducible NO synthase(iNOS) mRNA and protein expression. In addition, DHA also suppresses the production of IL-1-induced cyclooxygenase-2 and IL-6. The constitutively expressed cyclooxygenase-1, however, was not affected by the sugar. These results demonstrate that DHA expresses a unique range of activities and identifies a novel mechanism for the inhibition of inflammatory processes.

• Journal of Acupuncture Research
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• 제23권2호
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• pp.125-137
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• 2006

Objectives : The effect of water extract of the pilose antler of Cervus korean TEMMINCK var. mantchuricus Swinhoe (Nokyong), a traditional immuno-suppressive and immuno-activating Korean oriental medicine, on collagen-induced arthritis (CIA) mice model was studied. Identification of common Nokyong capable of affording protection or modulating the onset and severity of arthritis may have important human health implications. Methods : Nokyong has shown to possess anti-inflammatory and anticarcinogenic properties in experimental animals. In this study we determined the effect of DAE on collagen-induced arthritis in mice. Results : In three independent experiments mice given DAE in water exhibited significantly reduced incidence of arthritis (33% to 50%) as compared with mice given no DAE in water (84% to 100%). The arthritis index also was significantly lower in DAE-fed animals. Western blot analysis showed a marked reduction in the expression of inflammatory mediators such as cyclooxygenase 2 (Cox-2), $Interferon-{\gamma}\;(INF-{\gamma})$, and tumor necrosis factor ${\alpha}\;(TNF-{\alpha})$ in arthritic joints of DAE-fed mice. The neutral endopeptidase (NEP) activity was approximately 6-fold higher in arthritic joints of non-DAE-fed mice in comparison to nonarthritic joints of nonimmunized mice whereas it was only 2-fold higher in the arthritic joints of DAE-fed mice. Additionally, total IgG and type II collagen-specific IgG levels were lower in the arthritic joints of DAE-fed mice. Conclusion : Taken together our studies suggest that DAE may be useful in the prevention of onset and severity of arthritis.

• Journal of Ginseng Research
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• 제33권2호
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• pp.149-154
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• 2009

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and progressive cartilage and bone erosion. Korean red ginseng (KRG) has been shown to have an anti-inflammatory effect by inhibiting the secretion of inflammatory cytokines like $TNF-{\alpha}$, IL-1, -6, and -8, and $IPN-{\gamma}$. In this study, whether KRG extract has an inhibitory effect on the collagen-inducible development of arthritis in DBA/1J mice was investigated. To induce arthritis, type II collagen emulsified in Complete Freund's Adjuvant was intradermally injected into the base of the tails of mice. Three weeks after the initial injection, a booster injection of type II collagen emulsified in Incomplete Freund's Adjuvant was administered. The oral administration of KRG extract for 8${\sim}$10 weeks at the dose of 300 mg/kg (three days a week) inhibited the development of arthritis in the experimental group, compared to the control group which was given saline. While the administration of KRG extract three times a week demonstrated both preventive and inhibitory effects, the administration of KRG extract once a week had little inhibitory effect. In other studies, the regimen of KRG administration has been shown to decrease the plasma level of inflammatory cytokines like IL-8 and TNF-${\alpha}$, but the plasma levels of these cytokines were not decreased in the present study. The results of the present study suggest that KRG has preventive and inhibitory effects on collagen-induced arthritis.

• Journal of Acupuncture Research
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• 제22권2호
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• pp.33-41
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• 2005

Objective : The effect of Ulmus davidiana Planch(UD), which has long been known to have anti-inflammation and protective effects on damaged tissue, inflammation and bone among other functions, on the development of type II collagen (CII)-induced arthritis (CIA) in rats was studied. Methods : Male rats were immunized with an emulsion of $200\;{\mu}g$ of CII and complete Freund's adjuvant (CFA). The rats were then given intraperitoneal stimulation of Ulmus davidiana Planch herbal acupuncture(UDHA)or saline during the experiment. When compared with rats treated with saline as control, UDHA at doses of more than $20{\mu}g/100\;g$ rat once a day for 7 days inhibited the ability of inguinal lymph node cells to produce T cell cytokines interleukin-2, interleukin-6, $IFN-{\gamma}$ when the cells were obtained from rats 14 days after immunization and cultured in vitro with CII. Results : When rats were injected intraperitoneally, UD -treated group and control group rats did not differ significantly when low doses of UD was given to rats. Conclusion : The recommended dose of UD in the management and treatment of rat CIA will be more than $20{\mu}g/100\;g$, which is two-firth of human therapeutic dose. From the results, it was concluded that the effect of UDHA is dependent of dosage.

• 동의생리병리학회지
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• 제21권5호
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• pp.1278-1284
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• 2007

Solanum Iyratum Thunb (Solanaceae) has multiple applications in korean traditional medicine because of its cytotoxic, immunological and anti-inflammatory activities. However, no study on the anti-arthritic activity of Solanum Iyratum Thunb has been reported in vivo. Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which ultimately leads to the destruction of cartilage and bone. Cytokine production were assessed during CIA(collagen-induced arthritis) model mice in lymph node (LN), in knee joint and spleen, using ELISA. DBA/1j mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with Solanum Iyratum Thunb (SLT) orally at 400, 200 mg/kg once a day for 4 weeks. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. SLT significantly suppressed the progression of CIA and inhibited the production of TNF-alpha and IFN-gamma in serum and spleen cell culture supernatant. The erosion of cartilage was dramatically reduced in mouse knees after treatment with SLT. In conclusion, our results demonstrates that SLT significantly suppressed the progression of CIA. This action was characterized by suppression of arthritis index, cartilage erosion and synovial cell infiltration and the decreased production of $TNF-{\alpha}$, $IFN-{\gamma}$, CD4+, CD19+, CD3+/CD69+ cells (in lymph node), CD11b+/Gr-1 + (in knee joint).

• Journal of Acupuncture Research
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• 제34권4호
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• pp.153-158
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• 2017

Background: Hominis placenta (HP) is used in Korean medicine to tonify qi and blood, and enrich yin and tonify yang. HP has been reported to have therapeutic effects. Methods: A survey of international and Korean electronic databases was conducted using the search terms "hominis placenta pharmacopuncture" and "hominis placenta extract". The search was limited to material published up to May 31, 2017. Results: A total of 83 studies were included in this systematic review: 50 were clinical studies, 25 were basic studies, and 8 were other types of study. Among clinical studies, the most frequently treated disease groups were musculoskeletal diseases and nervous system diseases. In vitro studies were conducted mainly on anti-inflammatory, analgesic, and anti-cell necrosis models. Most of the in vivo studies were performed in rheumatoid arthritis or diabetic complications models. Conclusion: HP pharmacopuncture has effects in the treatment of various diseases. Further large-scale randomized controlled trials are needed to improve the level of evidence for HP pharmacopuncture. It would be helpful if future in vitro and in vivo studies could identify the mechanism of action of HP pharmacopuncture.

• Journal of Acupuncture Research
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• 제32권3호
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• pp.1-13
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• 2015

Purpose : This research was conducted to investigate the effect of sweet bee venom pharmacopuncture and low level laser acupuncture on paw edema, pain index, anti-inflammatory factor, AST, ALT and complete blood cell count of a rat model with Complete Freund's Adjuvant-induced arthritis. Methods : Five experimental groups were formed with each consisting of six rats: normal group, control group, sweet bee venom pharmacopuncture group, lower level laser acupuncture group, and sweet bee venom pharmacopuncture, lower level laser acupuncture group. The experimental model of arthritis was induced by two injections of Freund's adjuvant into the left knee joint of Sprague Dawley(SD) rats. The second injection of Freund's adjuvant was given ten days after the first one. Ten days later, sweet bee venom pharmacopuncture and low level laser acupuncture were administered separately or together by assigned groups at $GB_{34}$ and $GB_{39}$ of rats twice a week for a total of six times. Thereafter, edema rate, pain index, tumor necrosis factor-${\alpha}$, interleukin-6, aspartate aminortansferase, alanine aminotransferase and complete blood cell count were measured. Results : We noticed synergic effects of sweet bee venom pharmacopuncture and low level laser acupuncture according to the results of the paw edema and Von Frey pain index. The sweet bee venom pharmacopuncture(BVA) and sweet bee venom pharmacopuncture+ low level laser acupuncture(BVA+LLA) groups experienced a more significant effect when compared with the control group. Conclusions : These results suggest that Sweet Bee Venom Pharmacopuncture and low level laser acupuncture at GB34 and GB39 have a significant anti-inflammatory effect on Freund's adjuvant arthritis in rats.

• 생약학회지
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• 제36권4호통권143호
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• pp.318-323
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• 2005

The leaves (KPL) of Kalopanax pictus (KP) are used as a vegetable or a functional food in Korean society. The stem bark (Kalopanacis Cortex, KPS) has been traditionally used to treat neurotic pain, rheumatoid arthritis and diabetic disease. This research was undertaken to demonstrate that the leaf extract of KP (KPL) has also the antinociceptive and antiinflammatory effects like the extract (KPS) of Kalopanacis Cortex and to compare the activity levels of several extracts obtained from KP. Antinociceptive and antiinflammatory effects were measured against the extracts described as followings; KPL-1 (the MeOH extract obtained from the leaf shoot of KP collected on May), KPL-2 (the MeOH extract from KP collected on June), KPL-3 (the MeOH ectract from KP with no thorns), KPS-1 (MeOH extract from KPS of a Korean habitat), KPS-2 (MeOH extract from KPS of a Chinese habitat). The antimociceptive test undertaken by acetic acid-induced writhing, hot plate-, and tail-flick methods using mice. The anti-inflammatory test was also undertaken by measuring the edema in the carrageenan-induced test. The order of activity potency in the antinociceptive and antiinflammatory assays was commonly shown as followings: KPL-3>KPS>1>KPS-2>KPL-1>KPL-2. This order was also observed in acetic acid-induced vascular permeability test. The antiinflammatory activity in carrageenan-induced assay was also observed as the following order: KPL-3>KPS- 1>PS-2>KPL-1>KPL-2. In addition, adjuvant-induced rats were used for a model to assess the oxidative stress. Treatment of the rat with the extracts reduced serum thiobarbituric acid-reactive substances (TBARS), hydroxy radical(OH) and superoxide dismutase(SOD) activity caused by FCA together together with the inhibition of hepatic TBARS level and lipofuscin content. The above finding suggests that the leaf extract has the antinociceptive and antinflammatory activity. It is also suggested that KPL-3 with more potent activity than other tested extracts could be developed for a new available biomaterial.