• Journal of Korean Medicine Rehabilitation
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• v.25 no.1
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• pp.27-44
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• 2015

Objectives This study was carried out to find the effects of Gami-cheongyulsaseub-tang (hereinafter referred to GCST) on the inhibition of zymosan-induced pain in rats and collagen II-induced arthritis (CIA) in DBA/1J mouse. Methods As an acute inflammatory pain model, peripheral inflammation was induced by intraplantar injection of zymosan into the right hind paw in rats and then the hyperalgesia and pain regulating factors in spinal cord were analyzed. As a chronic inflammation model, the mixture of collagen II and complete Freund's adjuvant was treated into mice to establish rheumatoid arthritis and then body weight, thickness of hind paw, pathological change of spleen, immunological rheumatoid factor (IgG1, IgG2a, IgG2b, IgM and anti-collagen II), pro-inflammatory cytokines, and bone injury were analyzed. Results In the acute inflammatory pain model, GCST significantly inhibited the thermal and mechanical hyperalgesia and the pain regulating factors, including Fos, CD11b, PKA and PKC, in the spinal cord with a dose-dependent manner. In the chronic rheumatoid arthritis model, GCST administration decreased arthritic index and paw edema as compared with CIA control group. In particular, GCST reduced significantly the serum levels of total IgG2a, IgG2b, IgM, and specific anti-collagen II, but not total IgG1. GCST also resulted in the attenuation of bone injury and spleen enlargement/adhesion in CIA mice. Moreover, the secretion of pro-inflammatory cytokines TNF-${\alpha}$ and IL-$1{\beta}$ in CIA mice was significantly reduced by GCST in a dose-dependent manner. Conclusions Comparison of the results in this study showed that GCST had anti-nociceptive and immunomodulatory effects. These data imply that GCST can be used as an effective drug for not only rheumatoid arthritic pain but also other auto-immune diseases.

• Journal of Dental Anesthesia and Pain Medicine
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• v.22 no.2
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• pp.97-105
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• 2022

Background: The pentadecapeptide BPC-157 has been shown to have anti-inflammatory and wound healing effects on multiple target tissues and organs. Peptides have potent anti-inflammatory effects on periodontal tissues in rats with periodontitis. Few studies have investigated the effect of BPC-157 on pain after dental procedures or oral surgeries. The purpose of the present study was to investigate the antinociceptive effects of BPC-157 on postoperative incisional pain in rats. Methods: Sprague-Dawley rats were randomly divided into five groups: control (saline with the same volume), BPC10 (10 ㎍/kg of BPC-157), BPC20 (20 ㎍/kg of BPC-157), BPC40 (40 ㎍/kg of BPC-157), and morphine (5 mg/kg of morphine). A 1-cm longitudinal incision was made through the skin, fascia, and muscle of the plantar aspect of the hind paw in isoflurane-anesthetised rats. Withdrawal responses were measured using von Frey filaments at 0, 2, 6 h and 4, 7 d after incision. The formalin test was also performed to differentiate its anti-nociceptive effect from an inflammatory reaction or central sensitization. Pain behavior was quantified periodically in phases 1 and 2 by counting the number of flinches in the ipsilateral paw after injection with 30 µL of 5% formalin. Results: The threshold of mechanical allodynia was significantly increased in the BPC10, BPC20, BPC40 and morphine groups compared with that in the control group at 2 h. These increasing thresholds then returned to the levels of the control group. The BPC-157 group showed a much higher threshold at 4 days after incision than the control group. The thresholds of the BPC groups, except the morphine group, were normalized 7 days after incision. The flinching numbers of the BPC10, BPC20, BPC40 and morphine groups were significantly decreased in phase 1, but there was no decrease in the BPC-157 groups except the morphine group in phase 2. Conclusions: BPC-157 was effective only for a short period after incision. It was also effective during phase 1 but not during phase 2, as determined by the formalin test. BPC-157 might have a short antinociceptive effect, even though it has anti-inflammatory and wound healing effects.

• Korean Journal of Plant Resources
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• v.19 no.6
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• pp.660-664
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• 2006

The aerial part of Siegesbeckia pubescens (Compositae) has been used to treat rheumatoid arthritis and hypertension in the Oriental medicine. This crude drug has been used without process (SP-0) or with three times-process of steaming and drying (SP-3) or the nine times of that process (SP-9). To search for the antinociceptive anti-inflammatory components from this crude drug, activity-directed fractionation was performed on this crude drug. Since the $CHCl_3$ extract was shown to have a more potent effect than other extracts, it was subjected to silica gel & ODS column chromatography to yield two diterpene compounds (1). Compound 1 was structurally identified as ent-16 (H, 17-hydroxykauran-19-oic acid, which were tentatively named siegeskaurolic acid A. A main diterpene, siegeskaurolic acid A was tested for the antiiflammatory antinociceptive effects using both hot plate- and writhing anti-nociceptive assays and carrageenan-induced anti-inflammatory assays in mice and rats. Pretreatment with siegeskaurolic acid A (20 and 30mg/kg) significantly reduced the stretching episodes, action time of mice and carrageenan-induced edema. These results support that siegeskaurolic acid is a main diterpene responsible for antinociceptive and antiiflammatory action of S. pubescens. In addition, the assays on SP-0, SP-3 and SP-9 produced the experimental results that SP-9 had more significant effects than other two crude drugs. These results suggest that the processing on the original plant may lead to the higher pharmacological effect.

• Archives of Pharmacal Research
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• v.25 no.4
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• pp.475-479
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• 2002

Capsaicin, a major pungent constituent of red pepper (Capsicum annuum L.) possesses a vast variety of pharmacologic and physiologic activities. Despite its irritant properties, the compound exerts anti-inflammatory and anti-nociceptive effects. Previous studies from this laboratory revealed that capsaicin, when topically applied onto dorsal skin of female ICR mice, strongly attenuated activation of NF-kB and AP-1 induced by the typical tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), which may account for its anti-tumor promoting activity in mouse skin. In the present work, we have found that capsaicin suppresses TPA-stimulated activation of NF-kB through inhibition of $IkB{\alpha}$ degradation and blockade of subsequent nuclear translocation of p65 in human pro myelocytic leukemia HL-60 cells. Methylation of the phenolic hydroxyl group of capsaicin abolished its inhibitory effect on NF-kB DNA binding. Likewise, TPA-induced activation of AP-1 was mitigated by capsaicin treatment.

• Biomolecules & Therapeutics
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• v.22 no.3
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• pp.260-266
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• 2014

This study evaluated the pharmacokinetic profile and therapeutic efficacy of piroxicam (PX), a long acting non-steroidal anti-inflammatory drug for the treatment of arthritis, following intra-articular (IA) injection in comparison to the pharmacokinetic profile and therapeutic efficacy of PX after intramuscular (IM) injection. In the pharmacokinetic study in rats, systemic exposure and pharmacokinetic parameters of PX after a single IA dose were compared with systemic exposure and pharmacokinetic parameters of PX after administration of the same dose IM (0.6 mg/kg). The anti-inflammatory and analgesic effects of IA PX were evaluated simultaneously in a monoiodoacetate-induced osteoarthritis rat model. The plasma PX concentration rapidly rose following IA injection, and it was comparable to the plasma PX concentration following IM injection, suggesting the rapid efflux of the drug molecule from the joint cavity. However, in the efficacy study, the IA PX administration significantly reduced the knee swelling by reducing the level of prostaglandin $E_2$ in the joint, compared to that following administration of IA vehicle and after administration of the IM PX dose. In addition, we found that the anti-inflammatory and anti-nociceptive efficacies of IA PX were synergistically increased upon co-treatment with hyaluronic acid (HA), a potent agent for the treatment of osteoarthritis, at the weight ratio of 1:1 or 1:2, and these effects were more pronounced than those following administration of HA or PX alone. In conclusion, this study demonstrated the efficacy of the IA use of PX alone and/or in combination with HA in osteoarthritis.

• Journal of dental hygiene science
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• v.14 no.2
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• pp.240-247
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• 2014

Acaiberry (Euterpe oleracea Mart.) is widely diffused in amazon and is known that has high antioxidant capacity and potential anti-inflammatory activities. The aim of this study was to evaluate analgesic effects of acaiberry in formalin-induced orofacial pain through p38 mitogen-activated protein kinases (p38 MAPK) and nicotinamide adenine dinucleotide phosphate 4 (NOX4) pathway. Rats were divided into 5 groups (n=6); formalin (5%, $50{\mu}L$), formalin after saline (vehicle) or acaiberry (16, 80, 160 mg/kg, intraperitoneally). The nociceptive response was investigated all of groups, p38 MAPK or NOX4 were analysed at dose of 80 mg/kg of acaiberry in rat's medulla oblongata and adrenal gland. Results indicated that acai berry produced analgesic effect in a dose-dependent manner and significantly reduced formalin-induced nociceptive response at 15~40 min. Acaiberry (80 mg/kg) decreased the increased p38 MAPK activation and NOX4 expression in medulla oblongata and adrenal gland. Based on these results, acaiberry is believed to be useful for modulation of orofacial pain and its treatments because of its anti-inflammatory and antioxidative effects.

• Advances in Traditional Medicine
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• v.8 no.3
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• pp.243-251
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• 2008

The effect of alcoholic extracts of Costus specious (Family: Zingiberaceae) was evaluated in experimental models of pain and inflammation. Oral administration of 100, 200 and 300 mg/kg of C. specious extracts were used for the above study. Crude extracts of C. specious (300 mg/kg dose) showed maximum time needed for the response against thermal stimuli ($7.242\;{\pm}\;0.532\;s$) which is comparable to diclofenac sodium ($8.471\;{\pm}\;0.25\;s$) in the hot plate test. The MPH (Maximum Possible Analgesia) has been found to be 14.285 for 300 mg/kg dose of the crude extract while the MPH for diclofenac was 15.857 after 60 min of administration in the hot tail-flick method. The crude extract at 300 and 200 mg/kg doses showed significant reduction in acetic acid induced writhings in mice with a maximum effect of 59.661% reduction at 300 mg/kg dose which is comparable to standard diclofenac sodium (73.4%). Alcoholic extract of C. specious showed significant inhibition in serotonin and egg albumin induced hind paw oedema in rats at 100, 200 and 300 mg/kg of the crude extracts respectively (Serotonin induced edema 44.22; 53.75; 58.51%; egg albumin induced edema - 41.317; 53.892; 59.880% inhibition after 4 h respectively). The antiinflammatory effects showed by the extract were comparable to that of standard indomethacin 5 mg/kg (Serotonin induced edema 77.56%; egg albumin induced edema 77.844% inhibition after 4 h). These results suggest that the extract possesses both the anti-inflammatory and analgesic activity on mice and rat model.

• Natural Product Sciences
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• v.7 no.3
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• pp.76-82
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• 2001

The pharmacological activities of the acetonitrile (MeCN), hexane extracts and isolated pure terpenoidal compound Lupeol from the leaves of Teclea nobilis, Delile (TN), on inflammation induced by carrageenan an implantation of cotton pellets in rats; the nociceptive response using writhing and tail flick tests and the antipyretic activity in yeast-induced fever were examined in mice. Oral administration of TN extracts at doses of 150 and 300 mg/ks and lupeol 5 and 10 mg/kg showed a significant anti-inflammatory activity in rats. The extracts of TN and lupeol significantly decreased the number of contractions and stretchings induced by acetic acid and heat-induced pain in mice. The antipyretic effect of extracts and lupeol was also found to be significant. The behavioral observation of animals showed that the hexane extract and lupeol caused CNS depressant activity and did not produce any toxic or lethal effects in animals at various dose levels. The results suggest that the Teclea nobilis extracts and lupeol possesses anti-inflammatory, analgesic and antipyretic activities.

• Journal of Acupuncture Research
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• v.24 no.2
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• pp.39-49
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• 2007

목적 : 봉독으로 유발된 통각수용의 강도와 봉독으로 나타나는 항통각수용(통각억제성)의 강도를 쥐의 포르말린 테스트를 통해 상호관련됨을 확인하고 capsaicin과 bradykinin으로 통증 유발된 쥐의 자발적인 통증행동(핥기횟수측정; LN), 꼬리경타시험(TFL)과 열판시험(HPL)을 통해 봉독의 항통각수용(통각억제)작용을 재확인 하고자 하였다. 방법 : 쥐의 뒷다리에 통증유도 물질인 Capsaicin 또는 Bradykinin을 20${\mu}l$를 주사하여 동통을 유발하고 자발적 통증행동인 핥기횟수측정(LN), 꼬리경타기간(TFL)과 열판 위에서의 온도자극에 쥐가 반응하는 시간을 측정(HPL)하는 실험을 봉독을 주입하거나, 몰핀을 주입하거나, 아무것도 주입하지 않고 통증유발만 시킨 이후에 각각 시행하였다. 결과: 1. Capsaicin 또는 Bradykinin으로 동통유발 후 LN은 두드러증가를 보임, HPL은 감소를 TFL은 두드러진 감소를 나타내었다. 2. 봉독이나 몰핀 주입 30분 후에 Capsaicin으로 동통유발 이후 LN은 봉독과 몰핀에서 모두 현격한 감소를, HPL은 봉침은 현격한 증가를, 몰핀에서는 감소를, TFL은 봉침과 몰핀에서 모두 현격한 증가를 나타내었다. 3 봉독과 몰핀주입 30분후에 Bradykinin으로 동통유발 이후 LN은 봉독은 증가 몰핀은 현격한 감소를, HPL은 봉침은 증가 몰핀에서는 현격한 증가를, TFL은 봉침과 볼핀에서 모두 증가를 나타내었다. 결론 : 봉독은 Capsaicin 또는 Bradykinin으로 동통유발된 통각수용행동을 감소시키는 결과를 나타내었는데 이것은 기존의 연구결과들에서의 봉독의 항통각수용(통각억제성)의 효과를 입증하였고 봉약침은 염증의 개선이나 암과 관련된 동통에 유효한 방법임을 시사하는 것이다.

• Biomedical Science Letters
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• v.23 no.4
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• pp.380-387
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• 2017

Berchemia berchemiaefolia (BB) are climbing plants or small to medium-sized trees that live in Africa, Asia and America. We performed the present study to investigate whether oral administration of Berchemia berchemiaefolia extract (BBE) protects SD rats from pain. The SD rat experimental groups were divided into four groups. Two of the animal model groups were fed on BBE (200 mg/kg or 100 mg/kg). We performed oral acute toxicity test to determine the optimal oral dose of BBE. To explore if BBE alleviated pain in the SD rat, we undertook the tail flick latency test and formalin test. Additionally, we conducted the anti-oxidative test. The findings of the present study suggest that Berchemia berchemiaefolia extract exhibits strong antioxidant and analgesic activities.