• Biomedical Science Letters
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• v.28 no.2
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• pp.137-144
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• 2022

Poria cocos is a natural substance known to have anticancer, antioxidant and anti-inflammatory effects. The aim of this study is to investigate the analgesic effects of Poria cocos extract (PCE). We evaluated the analgesic effects of PCE using adjuvant induced arthritis rat model. Male SD rats were administered intra-orally with PCE according to prescribed dosage, during 6 days. After 6 days later, serum TNF-α, IL-1β, and IL-6 levels were measured by ELISA. In our experiment, administration of PCE decreased TNF-α, IL-1β, IL-6 and PGE2 level in serum. Furthermore, it was confirmed that allodynia was relieved in evaluation of pain behavior. It was confirmed that administration of PCE reduces nociceptive pain by reducing nociceptive stimuli by acting as an anti-inflammatory drug.

• 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.

• Journal of Acupuncture Research
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• v.32 no.2
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• pp.65-75
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• 2015

Objectives : The purpose of this study was to investigate the effects of warm needling at $GB_{30}{\cdot}GB_{34}$ on Complete Freund's Adjuvant(CFA)-induced rheumatoid arthritis in rats. Methods : Arthritis was induced by injecting CFA subcutaneously into the left knee joint and paw. Acupuncture(AT) and warm needling(W-AT0.5, W-AT1.0) were injected at $GB_{30}{\cdot}GB_{34}$, every other day for a total of 5 times beginning on day 10 after the CFA injection. Thereafter, external shape, paw edema, serum aminotransferase and anti-inflammatory factors were assessed, and hematological and histological observations were made. Results : In paw edema volume all 3 groups(AT, W-AT0.5, W-AT1.0) showed significant decrease compared to the CFA control group. In TNF-${\alpha}$ and IL-6, all 3 groups showed significant decrease compared to CFA control group. In AST and ALT all 3 groups showed no significant change. In IL-$1{\beta}$, W-AT0.5 and W-AT1.0, groups showed significant decrease compared to the CFA control group. Leucocyte, erythrocyte and thrombocyte, all 3 groups showed no significant change. In histological observations, all 3 groups were similar to the intact group in terms of synoviocyte, cartilage lacuna and cartilage cells. Conclusions : The results suggest that warm needling at $GB_{30}{\cdot}GB_{34}$, has the effect of suppressing inflammation of CFA-induced rheumatoid arthritis in rats.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.1
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• pp.79-95
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• 2011

Objectives : This study was to investigate the antiarthritic effect of Hwallak-dan(Huoluo-dan) on the complete freund's adjuvant(CFA)-induced arthritis in Lewis rats. Methods : Arthritis was induced by intradermal injection of CFA into base of tail. Experimental groups divided into normal(n=10), control(n=10) and treated(n=10) group. Animals of control group received normal saline for twenty days, treated group received extracts Hwallak-dan(Huoluo-dan) for same duration, light mineral oil only injected non-arthritic rats were served as normal group. The incidence of arthritis and arthritic index were observed after treatment. Body weight, paw edema volume and thickness of ankle joint were measured at 0, 11, 14, 17, 20 days after treatment. White blood cell(WBC) counts in blood were analysed at 20 days after treatment and tumor necrosis $factor-{\alpha}(TNF-{\alpha})$, $interleukin-1{\beta}(IL-1{\beta}$), IL-6 contents in paw exudate were analysed by ELISA at 20 days after treatment. Histopathology on the ankle joint were performed at 20 days after treatment. Results : 1. Incidence of arthritis of treated group was 60% and control group was 100% at 20 days after treatment. 2. Arthritic index of treated group was significantly decreased compared with control group at 20 days after treatment. 3. Paw edema volume and thickness of ankle joint of treated group was significantly decreased compared with control group at 20 days after treatment. 4. Total WBC of treated group was significantly decreased compared with control group at 20 days after treatment. 5. Neutrophils of treated group was significantly decreased compared with control group at 20 days after treatment. 6. $TNF-{\alpha}$ content in paw exudate of treated group was significantly decreased compared with control group at 20 days after treatment. 7. $IL-1{\beta}$ content content in paw exudate of treated group was significantly decreased compared with control group at 20 days after treatment. 8. IL-6 content content in paw exudate of treated group was significantly decreased compared with control group at 20 days after treatment. 9. Histopathological arthritic index of treated group was significantly decreased compared with control group at 20 days after treatment. Conclusions : These results indicate that Hwallak-dan(Huoluo-dan) has inhibitory effect on the development and progression of CFA-induced arthritis in rats.

• Advances in Traditional Medicine
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• v.8 no.4
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• pp.416-422
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• 2008

This study evaluated the anti-inflammatory potential of the crude alkaloidal fraction (CAF) of methanol extract of Solanum trilobatum Linn. (Solanacea) root in animal models of inflammation. Crude alkaloidal fraction at doses of 25, 50 and 100 mg/kg significantly (p < 0.01) reduced carrageenan induced rat paw volume at 3 h after carrageenan challenge as compared to control group of animals. CAF (25, 50 and 100 mg/kg) significantly (p < 0.01) and dose dependently suppressed cotton pellet induced granuloma formation. Topical application of CAF (1, 5 and 10 mg/ear) markedly inhibited multiple application of TPA in mice. CAF elicited pronounced inhibitory effects on formaldehyde and adjuvant induced arthritis in rats. These results indicate that CAF of methanol extract of the Solanum trilobatum has anti-inflammatory activity in acute and chronic inflammation.

• Journal of Acupuncture Research
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• v.17 no.1
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• pp.153-168
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• 2000

To investigate effects of Paeonia Radix Rubra aqua-acupuncture on Adjuvant Athritis in rats, the edema rate, the number of WBC, the quantity of total protein, albumin and globuline in the blood serum were measured and histological test of the muscular tissue were done in the arthritis part. 1. After arthritis of Sprague dawley(SD) rats was induced by injecting Freund's complete adjuvant for 2 weeks, normal saline was injected for the Control group and Paeonia Radix Rubra acua-acupuncture was injected for the Exp. group during 30 days. Selected point was $D{\acute{u}}bf(ST_{35})$ in both groups. And then the inframmator volume of plantar were checked. The volume of the plantar was $0.84{\pm}0.14mm$ in Control group and $0.57{\pm}0.09mm$ in Exp. group, the swelling of plantar was restricted significanily in Exp, group(P<0.05). 2. The number of WBC was $10.34{\pm}0.14(10^3/ml)$ in normal group and $37.47{\pm}5.46(10^3/ml)$ in Control group. It was $25.21{\pm}3.45(10^3/ml)$ in Exp. group. This fact showed that Exp group. with Paeonia Radix Rubra acua-acupuncture was more effective than Control group in the treatment of arthritis(P<0.05). 3. The content of total protein in the blood serum were $6.14{\pm}0.43g/d{\ell}$ in normal group, $7.95{\pm}0.94g/d{\ell}$ in Control group, and $6.82{\pm}1.23g/d{\ell}$ in Exp. group. There was no significance in total protein between Exp. group and Control group from the statistical analysis. 4. The contents of albumin in the blood serum were $2.94{\pm}0.13g/d{\ell}$ in normal group, $2.01{\pm}0.48g/d{\ell}$ in Control group and $2.75{\pm}0.14g/d{\ell}$ in Exp, group. This fact showed that Exp. group had significant increase in the serum albumin from the statistical analysis, in comparison with Control group(P<0.05). 5. The contents of globulin in the blood serum were $3.19{\pm}0.48g/d{\ell}$ in normal group, $4.70{\pm}1.26g/d{\ell}$ in Control group and $3.58{\pm}0.73g/d{\ell}$ in Exp. group. There was no significance in the serum globulin between Exp. group and Control group from the statistical analysis. 6. In histological examinadon, because inflammatory reaction was active, remarkably irregular tissue and large amount of inflammatory cells were found in Control. group. But Exp. group showed that tissues were in some degree recovered, the number of inflamed cells was decreased and inflammation was restrained. From these results, it is shown Paeonia Radix Rubra aqua-acupuncture restrained inflammatory reaction and muscular tissue necrosis in SD rat's plantar was restrained by Freund's complete adjuvant.

• Journal of Pharmacopuncture
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• v.5 no.1 s.8
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• pp.91-103
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• 2002

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. characterized by leukocyte infiltration, a chronic inflammation of the joint, a pannus formation and the extensive destruction of the 3Iticular caJ1ilage and bone. Several proinflammatory cytokines such as tumor necrosis factor-${\alpa}$(TNF-${\alpa}$), interleukin-1${\beta}$ (IL-1${\beta}$) and interleukin 6 (IL-6) have been implicated in the pathological mechanisms of synovial tissue proliferation, joint destruction and programmed cell death in rheumatoid joint. In the Korean traditional medicine, Hominis placenta (HP) as an herbal solution of herb-acupuncture has been widely used to treat the inflammatory diseases including RA. In order to study the medicinal effect of HP herb-acupuncture on rheumatoid joint, an adjuvant-induced arthritis (AlA) was generated by the injection of 1.5 mg uf Mycobactelium tuberculusis. emulsified in squalene, 10 the base of the tail of Sprague-Dawley(SD) rats. After onset stage of polyarthritis, HP was daily injected to the Zusanti (ST36) acupuncture points in both of rat lags and the expression pattems of cytokines such as TNF-{\alpa}$, IL-1${\beta}$, and 1L-6 at the knee joint were analyzed using immunostaining and RT-PCR. The HP herb-acupuncture was found to be effective to alleviate the arthritic symptums in adjuvant-induced arthritic rats as regards the joint appearance and the expression profiles of inflammatory cytokines. In conclusion, therapeutic effects of HP herb-acupuncture on the rat with AlA might be related to anti inflammatory activities of the hurb-acupuncture.

• Journal of Life Science
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• v.31 no.8
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• pp.736-744
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• 2021

Artemisia princeps Pampanini is an herbal medicine widely used to immune function-related diseases, such as anti-oxidative, anti-inflammatory, and antibacterial agents. In this study, we investigated the anti-inflammatory effects of AP extract and underlying mechanisms were evaluated in RAW 264.7 cells. The effects of AP extract were also studied in a complete Freund's adjuvant (CFA)-induced arthritis and lipopolysaccharide (LPS)-induced inflammation mouse model. In RAW 264.7 cells, AP extracts significantly inhibited the LPS-induced nitric oxide (NO) production and inducible NO synthase and cyclooxygenase-2 protein expression. The LPS-induced phosphorylation of mitogen-activated protein kinases and nuclear factor-κB was also significantly blocked by AP extract in RAW 264.7 cells. Oral administration of AP extract suppressed the increase in mouse paw edema and spleen index compared to CFA-treated mice group. Histologically, the infiltration of inflammatory cells was increased in cartilage and synovium in the CFA-treated mouse group, whereas it was suppressed in the AP extract-administered group. Furthermore, AP extract treatment significantly reduced the inflammatory cytokine, tumor necrosis factor-α, levels in CFA and LPS-treated mouse. In conclusion, the anti-inflammatory and anti-arthritis effect of AP extract was confirmed in both in vitro and in vivo models, suggesting that Artemisia princeps Pampanini may be a candidate material for arthritis treatment.

• The Journal of Korean Medicine
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• v.21 no.3
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• pp.77-87
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• 2000

Objectives : To investigate effects of Achyranthis Radix aqua-acupuncture on adjuvant arthritis in rats. Methods : After eliciting arthritis in Sprague dawley(SD) rats by injection of Freund's complete adjuvant for 2 weeks, normal saline was injected for the Exp. I group and Achyranthis Radix aqua-acupuncture was injected for the Exp. II group during 30days. The selected point was Dokbi (ST35) in both groups. Then the edema rate, the number of WBC, the quantity of total protein, albumin and globuline in the blood serum, and histological test of the muscular tissue were measured in the arthritis stricken areas. Results : I) The volume of the paws were checked. The volume of the paws was $0.84{\pm}0.l4mm$ in the Exp. I group and $0.47{\pm}0.14mm$ in the Exp. IIgroup. The swelling of the paws was restricted significantly in the Exp. II group(P<0.05). 2) The number of WBC was $10.34{\pm}0.14(l03/ml)$ in the normal group and $37.47{\pm}5.46(103/ml)$ in the Exp. I group. It was $21.24{\pm}2.58(103/ml)$ in the Exp. II group. This fact showed that treatment with Achyranthis Radix aqua-acupuncture adminstered to the Exp. II group was more effective than the Exp. I group in the treatment of arthritis(P<0.05). 3) The content of the total protein in the blood serum was $6.14{\pm}43g/dl$ in the normal group, $7.95{\pm}0.94g/dl$ in the Exp. I group, and $6.41{\pm}0.68g/dl$ in the Exp. II group. There was no significance in total protein between the Exp. II group and the Exp. I group from the statistical analysis. 4) The content of albumin in the blood serum was $2.94{\pm}0.l3g/dl$ in the normal group, $2.01{\pm}0.48g/dl$ in the Exp. I group and $3.15{\pm}0.27g/dl$ in the Exp. II group, which revealed a significant increase in the serum albumin from the statistical analysis of the Exp. II group compared with the Exp. I group. 5) The content of the globulin in the blood serum was $3.19{\pm}$0.48g/dl in the normal group, $4.70{\pm}1.26g/dl$ in the Exp. I group and $3.26{\pm}0.57g/dl$ in the Exp. II group. There was no significance in the serum globulin between the Exp. II group and Exp. I group from the statistical analysis. 6) In histological findings, because of severe inflammatory reaction, remarkably irregular tissue and large amount of inflammatory cells were found in the Exp. I group. But the Exp. II group showed a small amount of inflammatory cells, the refrained inflammatory state and even recovering state. Conclusions : These results show that Achyranthis Radix aqua-acupuncture reduces the inflammatory reaction and muscular tissue necrosis in SD rat's paws induced by Freund's complete adjuvant.

• IMMUNE NETWORK
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• v.11 no.5
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• pp.258-267
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• 2011

Background: Current management strategies attempt to diagnose rheumatoid arthritis (RA) at an early stage. Transcription profiling is applied in the search for biomarkers for detecting early-stage disease. Even though gene profiling has been reported using several animal models of RA, most studies were performed after the development of active arthritis, and conducted only on the peripheral blood and joint. Therefore, we investigated gene expression during the initial phase of collagen-induced arthritis (CIA) before the arthritic features developed in the thymus in addition to the peripheral blood and synovium. Methods: For gene expression analysis using cDNA microarray technology, samples of thymus, blood, and synovium were collected from CIA, rats immunized only with type II collagen (Cll), rats immunized only with adjuvant, and unimmunized rats on days 4 and 9 after the first immunization. Arrays were scanned with an Illumina bead array. Results: Of the 21,910 genes in the array, 1,243 genes were differentially expressed at least 2-fold change in various organs of CIA compared to controls. Among the 1,243 genes, 8 encode T-cell receptors (TCRs), including CD3${\zeta}$, CD3${\delta}$, CD3${\varepsilon}$, CD8${\alpha}$, and CD8${\beta}$ genes, which were down-regulated in CIA. The synovium was the organ in which the genes were differentially expressed between CIA and control group, and no difference were found in the thymus and blood. Further, we determined that the differential expression was affected by adjuvant more than Cll. The differential expression of genes as revealed by real-time RT-PCR, was in agreement with the microarray data. Conclusion: This study provides evidence that the genes encoding TCRs including CD3${\zeta}$, CD3${\delta}$, CD3${\varepsilon}$, CD8${\alpha}$, and CD8${\beta}$ genes were down-regulated during the initial phase of CIA in the synovium of CIA. In addition, adjuvant played a greater role in the down-regulation of the CD3 complex compared to CII. Therefore, the down-regulation of TCR gene expression occurred dominantly by adjuvant could be involved in the pathogenesis of the early stage at CIA.