• Archives of Pharmacal Research
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• 제25권3호
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• pp.336-342
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• 2002

MeOH extract of Kochia scoparia was fractionated into $CHCl_3-$, EtOAc- and BuOH extracts and the last fraction were hydrolyzed by 3%-NaOH ($MeOH-H_2O$) to compare the bioactivities on antinociceptive and anti-inflammatory effects. Silica gel column chromatography of BuOH fraction afforded a large amount of $3-Ο-{\beta}-D-xylopyranosyl {\;}(1{\rightarrow}3)-{\beta}-D-glucuronopyranosyl$ oleanolic acid (momordin Ic, 4) and that of acid hydrolysate of BuOH fraction gave $3-Ο-{\beta}-D-glucuronopyranosyl oleanolic$ acid (momordin Ib, 3), its 6'-Ο-methyl ester (2) and oleanolic acid (1). Silica gel column chromatography of alkaline hydrolysate afforded a large amount of 4. MeOH extract and both EtOAc- and BuOH fractions were active in the rheumatoidal rat induced Freund's complete adjuvant reagent (FCA) whereas $CHCl_3$ fraction was inactive. Compound 1 and 4 showed significant activities in the same assay but oleanolic acid 3-Ο-glucuronopyranoside (3) showed no activity. These fashions were also observed in carrageenan-induced edema of the rat and in the antinociceptive activity tests undertaken in hot plate- and writhing methods. These results suggest that momordin Ic and its aglycone, oleanolic acid, could be active principles for rheumatoid arthritis.

• The Korean Journal of Physiology and Pharmacology
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• 제7권5호
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• pp.251-254
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• 2003

The present study was designed to examine whether the co-application of morphine with $Ca^{2+}$ channel antagonist $(Mn^{2+},\;verapamil)$, N-methyl-D-aspartate (NMDA) receptor antagonist (2-amino-5-phosphonopentanoic acid$[AP_5]$, $Mg^{2+}$) or protein kinase C inhibitor (H-7) causes the potentiation of morphine-induced antinociceptive action by using an in vivo electrophysiological technique. A single iontophoretic application of morphine or an antagonist alone induced weak inhibition of wide dynamic range (WDR) cell responses to iontophoretically applied NMDA and C-fiber stimulation. Although there was a little difference in the potentiating effects, the antinociceptive action of morphine was potentiated when morphine was iontophoretically applied together with $Mn^{2+}$, verapamil, $AP_5$, $Mg^{2+}$ or H-7. However, the potentiating action between morphine and each antagonist was not apparent, when the antinociceptive action evoked by morphine or the antagonist alone was too strong. These results suggest that the potentiating effect can be caused by the interaction between morphine and each antagonist in the spinal dorsal horn.

• International Journal of Oral Biology
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• 제37권1호
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• pp.1-7
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• 2012

Opioid receptors have been pharmacologically classified as ${\mu}$, ${\delta}$, ${\kappa}$ and ${\varepsilon}$. We have recently reported that the antinociceptive effect of morphine (a ${\mu}$-opioid receptor agonist), but not that of ${\beta}$-endorphin (a novel ${\mu}/{\varepsilon}$-opioid receptor agonist), is attenuated by whole body irradiation (WBI). It is unclear at present whether WBI has differential effects on the antinociceptive effects of ${\mu}-$, ${\delta}-$, ${\kappa}-$ and ${\varepsilon}$-opioid receptor agonists. In our current experiments, male ICR mice were exposed to WBI (5Gy) from a $^{60}Co$ gamma-source and the antinociceptive effects of opioid receptor agonists were assessed two hours later using the hot water ($52^{\circ}C$) tail-immersion test. Morphine and $D-Ala^2$, $N-Me-Phe^4$, Gly-olenkephalin (DAMGO), [$D-Pen^2-D-Pen^5$] enkephalin (DPDPE), trans-3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide (U50,488H), and ${\beta}$-endorphin were tested as agonists for ${\mu}$, ${\delta}$, ${\kappa}$, and ${\varepsilon}$-opioid receptors, respectively. WBI significantly attenuated the antinociceptive effects of morphine and DAMGO, but increased those of ${\beta}$-endorphin. The antinociceptive effects of DPDPE and U50,488H were not affected by WBI. In addition, to more preciously understand the differential effects of WBI on ${\mu}-$ and ${\varepsilon}$-opioid receptor agonists, we assessed pretreatment effects of ${\beta}$-funaltrexamine (${\beta}$-FNA, a ${\mu}$-opioid receptor antagonist) or ${\beta}$-$endorphin_{1-27}$ (${\beta}$-$EP_{1-27}$, an ${\varepsilon}$-opioid receptor antagonist), and found that pretreatment with ${\beta}$-FNA significantly attenuated the antinociceptive effects of morphine and ${\beta}$-endorphin by WBI. ${\beta}$-$EP_{1-27}$ significantly reversed the attenuation of morphine by WBI and significantly attenuated the increased effects of ${\beta}$-endorphin by WBI. The results demonstrate differential sensitivities of opioid receptors to WBI, especially for ${\mu}-$ and ${\varepsilon}$-opioid receptors.

• Biomolecules & Therapeutics
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• 제18권2호
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• pp.159-165
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• 2010

Alpinia katsumadai has been widely used in traditional Chinese and Korean medicine to treat a variety of conditions including emesis and gastric disorders such as gastric pain and distended abdomen. To investigate the antinociceptive potential and mechanism of A. katsumadai, ethanolic extracts of A. katsumadai were assayed on cyclooxygenase-2 and evaluated for analgesic activity based on phenylbenzoquinone (PBQ)-induced writhing and carrageenan-induced hyperalgesia tests. A. katsumadai extracts inhibited the cyclooxygenase-2 enzyme activity in a dose-dependent fashion at an $IC_{50}$ value of 0.044 ${\mu}g$/ml. A. katsumadai extract (30-300 mg/kg, orally (p.o.) administered) significantly inhibited PBQ-induced writhing. This inhibition was judged not to be a false positive because a Rota-rod test revealed no difference in muscular coordination when compared to the controls. With regard to the carrageenan-induced hyperalgesia, A. katsumadai extract (30-300 mg/kg, p.o.) produced a significant, dose-dependent increase in the withdrawal response latencies. Naloxone did not reverse the analgesic effect of A. katsumadai extract in the carrageenan-induced hyperalgesia. Taken together, these results suggest that the antinociceptive activity of A. katsumadai is not related to the opioid receptor. A. katsumadai extract has remarkable, non-opioidreceptor-mediated analgesic effects on PBQ-induced writhing and carrageenan-induced hyperalgesia that occur via cyclooxygenase-2 inhibition.

• 생약학회지
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• 제42권4호
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• pp.317-322
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• 2011

Traditionally, the thorns of Gleditsia sinensis LAM. (GS) have been used for the treatment of various types of cancer and heart, skin, vascular and inflammatory diseases. However, there have been no reports on the antinociceptive or antiinflammatory properties of the thorn of GS. The present study was carried out to evaluate the anti-inflammatory and antinociceptive effects of the ethanolic extract of GS (EEGS) and its sub-fractions. The administration of EEGS (500 mg/kg) or its butanolic fraction (50 and 100 mg/kg) reduced the frequency of the acetic acid-induced writhing reflex in mice. In addition, the administration of the butanolic fraction of EEGS (50 and 100 mg/kg) prolonged the latency of reaction at the hot plate in mice. The butanolic fraction of EEGS also inhibited lipopolysaccharide-induced nitric oxide, prostaglandin $E_2$, and tumor necrosis factor-$\acute{a}$ production in the RAW 264.7 cell line. These results suggest that EEGS has anti-inflammatory and analgesic properties and is a potential therapeutic for inflammation and nociception.

• 약학회지
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• 제51권1호
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• pp.56-62
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• 2007

Twelve epoxy and hydroxydiosgenin derivatives (DI-1${\sim}$DI-12) were synthesized from diosgenin (25(R)-5-spirosten-3${\beta}$-ol). Diosgenin was epoxidized with m-chloroperoxybenzoic acid (mCPBA) to oxidize 25(R)-4${\alpha}$,5${\alpha}$-epoxyspirostane (DI-1). Diosgenin was reacted with DDQ to form 25(R)-1,4,6-spirostatrien-3-one (DI-2), which was treated with 30% H$_2$O$_2$ to give 25(R)-1${\alpha}$,2${\alpha}$-epoxy-4,6-spirostadien-3-one (DI-3) and treated with mCPBA to form 25(R)-6${\alpha}$,7${\alpha}$-epoxy-1,4-spirostadien-3-one (DI-7), respectively. DI-3 was reduced with NaBH$_4$ to afford 25(R) -1${\alpha}$,2 ${\alpha}$-epoxy-4,6-spirostadien-3${\beta}$-ol(DI-4) and reacted with Li metal in absolute ethanol to form 25(R)-2-ethoxy-1,4,6-spirostatrien-3-one (DI-5). DI-7 was reduced with NaBH$_4$ to produce 25(R)-3${\beta}$,7${\alpha}$-dihydroxy-4-spirostene (DI-8) and treated with Li metal in liquid ammonia to produce 25(R)-7${\alpha}$-hydroxy-4-spirosten-3-one (DI-9). DI-2 was reduced with NaBH$_4$ to form 25(R) -4,6-spirestadien-3${\beta}$-ol(DI-10), which was stirred with 30% H$_2$O$_2$ to synthesize 25(R)-4,6-spirostadien-3-one (DI-11) and reacted with mCPBA to give 25(R)-4${\beta}$,5${\beta}$ -epoxy-6-spirosten-3${\beta}$-ol (DI-12), respectively. The antinociceptive effects of synthesiz ed compounds were measured by hot plate method and compound DI-7 signifcantly exhibited antinociceptive effect. DI-2 decreased the serum triglyceride and total cholesterol levels in poloxamer P-407 injected rat.

• 약학회지
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• 제43권3호
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• pp.404-410
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• 1999

Administration of capsaicin produces acute pain and subsequent long-lasting antinociception. The antinociceptive action site of capsaicin is primarily small afferent nerve fibers. However, the effect of capsaicin on the neural activity of dorsal horn neurons are not well understood. The goal of the present experiment was to study the action of capsaicin on activity of dorsal horn neurons using c-fos immunoreactivity in the spinal cord. Intradermal injection of formalin in the hindpaw produced inflammation in the foot pad and increased the number of cells exhibiting Fos-like immunoreactivity (FLI) in the dorsal horn of the spinal cord, suggesting the hyperalgesia because of the apparent inflammation. Intradermal injection of capsaicin prior to formalin injection significantly reduced the number of cells exhibiting FLI induced by formalin and increased the paw-withdrawal latency, suggesting the hypoalgesic effect of capsaicin. Coadministeration with capsaicin of capsazepine and ruthenium red, antagonists of capsaicin receptor reversed the reduction of formalin-induced FLI by capsaicin. he antagonists also partially antagonized the antinociceptive effect of capsaicin in the paw-withdrawal test. These results further suggest that capsaicin reduces prsponses of dorsal horn neurons to the inflammatory nociceptive stimuli in the periphery. Thus, the reduction of FLI subserves the neural mechanisms underlying analgesia produced by capsaicin.

• Archives of Pharmacal Research
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• 제28권2호
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• pp.209-215
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• 2005

The antinociceptive effect of nicotine administered intracereboventricularly (i.c.v.) or intrathecally (i.t) in several pain models was examined in the present study. We found that i.t. treatment with nicotine (from 5 to 20 g) dose-dependently blocked pain behavior revealed during the second phase, but not during the first phase in the formalin test. In addition, i.c.v. treatment with nicotine (from 0.1 to $10\;{\mu}g$) dose-dependently attenuated pain behavior revealed during both the first and second phases. In addition to the formalin test, nicotine administered i.c.v. or i.t. attenuated acetic acid-induced writhing response. Furthermore, i.c.v. or i.t. administration of nicotine did not cause licking, scratching and biting responses induced by substance P, glutamate, TNF-${\alpha}$(100 pg), IL-$1{\beta}$(100 pg) and INF-${\gamma}$ (100 pg) injectied i.t. The antinociception induced by supraspinally-administered nicotine appears to be more effective than that resulting from spinally administered nicotine. Our results suggest that nicotine administration induces antinociception by acting on the central nervous system and has differing antinociceptive profiles according to the various pain models.

• 대한한의학회지
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• 제29권1호
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• pp.39-46
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• 2008

Background : Acupuncture has been used as a clinical treatment in Oriental medicine for various diseases including pain relief. The descending pain control system of periaqueductal gray (PAG) is a powerful pain control system in mammalians. Expression of c-Fos is used as a marker for stimuli-induced metabolic changes of neurons. Objective : In the present study, the effects of acupuncture on analgesic effect in visceral pain were investigated through the writhing reflex and c-Fos expression in ventrolateral PAG (vlPAG) area using immunohistochemistry in mice. Method : For the writhing test, mice were divided into five groups. Immediately after finishing the behavioral test, the animals were weighed and overdosed with Zoletil. After a complete lack of response was observed, the brains of the mice were dissected into serial coronal sections, and c-Fos immunohistochemistry was performed. Statistical analysis of all data was performed using one-way ANOVA. Result : The present results showed that acupuncture affected the writhing reflex and that Choksamni (zusnali) acupoint and aspirin significantlysuppressed acetic acid treatment-induced increased writhing reflex, and the expression of c-Fos in vlPAG was significantly increased in the acupunctured group. Conclusion : The present study suggests that acupuncture has an antinociceptive effect on acetic acid-induced visceral pain by increase of c-Fos expression in mice. Aspirin also showed analgesic effect, however the mechanism is different from the acupuncture.

• Advances in Traditional Medicine
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• 제7권4호
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• pp.390-394
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• 2007

The present study was conducted to evaluate the analgesic activity of ethanolic extract of Andrographis paniculata (AP) in mice. The analgesic investigations were carried out using the acetic acid-induced abdominal writhing and the hot-plate tests. It was demonstrated that intraperitoneal (i.p.) administration of the extract at a dose of 30, 100, 300, 500 mg/kg, produced significant inhibition of abdominal constriction induced with 0.6% (v/v) acetic acid in dosedependent manner. It also demonstrated that the extract produced significant dose-dependent increase in the time of latency to a discomfort reaction in the hot-plate model. In addition, the analgesic effect of the ethanolic extract of AP was significantly reversed by a non-specific opioid receptor antagonist, naloxone. These results indicate that AP has an analgesic effect that was mediated through opioid receptors.