• Proceedings of the Plant Resources Society of Korea Conference
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• 2022.09a
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• pp.107-107
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• 2022

Scrophularia koraiensis Nakai is widely used to remedy fever, edema, and neuritis. S. koraiensis has harpagoside and angoroside C, these compounds have been reported to alleviate inflammation, rheumatic diseases, and analgesic stimulation. We evaluated the anti-inflammatory effects of the ethanol extract of S. koraiensis (SKE) in lipopolysaccharides (LPS)-induced macrophages. At cellular levels, SKE decreased the production of nitric oxide (NO), the expression of inducible nitric oxide synthase (iNOS), and cytokines (IL-1b, TNF-a, and IL-6) under the LPS stimulation. SKE inhibited the phosphorylation of nuclear transcription factor-kappa B (NF-κB) p65 and its inhibitor (IκB-α). In addition, SKE suppressed the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 in the mitogen-activated protein kinase (MAPK) pathway. In conclusion, SKE could be considered a potential resource for attenuating inflammation response and it may be utilized in the material for cosmetics, food additives, and tea.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.895-902
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• 2002

Monocytes and macrophages playa major role in defense mechanism of the host response to tumor, in part through the secretion of several potent products and macrophage cytokines. Monocytes and tissue macro phages produce at least two groups of protein mediators of inflammation, interleukin 1 (IL-1) and tumor necrosis factor (TNF). Recent studies emphasizes that TNF and IL-1 modulate the inflammatory function of endothelial cells, leukocytes, and fibroblasts. In this study, our work is directed toward studying the in vitro effects of Korean propolis on the ability to induce cellular and secretory responses in murine macrophage cell line, RAW 264.7. It was found that Water Extract of Korean Propolis (WEP) could activate macro phages by producing cytokines. The production of the macrophage cytokines, IL-1 and TNF-$\alpha$, by RAW 264.7 treated with WEP was examined from 2.5 $\mu\textrm{g}$/ml up to 25 $\mu\textrm{g}$/ml with dose dependent manner. Nitric oxide (NO) production was also increased when cells were exposed to combination of LPS and WEP from 2.5 $\mu\textrm{g}$/ml up to 25 $\mu\textrm{g}$/ml. At high dose of WEP (50 to 100 $\mu\textrm{g}$/ml) used to prescribe for anti-inflammatory and analgesic medicine showed inhibition of NO production in LPS-stimulated macrophage. Besides cytokine production, NO release, surface molecule expression and cell morphologic antigen expression were increased in response to the stimulation by WEP. These results suggested WEP may function through macrophage activation.

• Journal of Veterinary Clinics
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• v.16 no.1
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• pp.86-94
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• 1999

To invstigate the available dosage and effects of xylazine as preanesthetics on the propofol anesthesia in the dog, the experimental animals were randomly divided into 3 groups (xylazine 0.55 mg/kg (group 1), 1 mg/kg (group 2) and 2 mg/kg (group 3) were premedicated) and, monitored analgesic and anesthetic effect, body temperature, respiratory rate (breaths/minute), heart rate (beats/minutes). Also, hematological and serum chemical changes were monitored. In all experimental groups, the animals were recumbent just after propofol injection and time difference was not detected. Except vomitting after xylazine injection and insignificant ataxia during recovery, no significant side effects were observed. In group 2, loss of toe-web needle prick response time was slightly longer than group 1 but the response in group 2 and group 3 were similar, In group 2 and 3, the duration of anesthesia was longer than group 1 (2 folds) but there was no difference between group 2 and 3. Recovery time was prolonged in proportion to administration dosage of xylazine. In all experimental groups, the body temperature of animals was decresed gradually according to experimental time but no significant changes were monitored. The heart rate and respiratory rate were significantly (p<0.01, p<0.05) decreased after propofol injection Hematologically, no significant changes were monitored in total leukocye numbers, total erythrocye numbers, MCV, MCH, MCHC, serum GOT and GPT values Significant changes in all groups were not observed except significant increase in BUN, total-protein and abumin values of group 3. On the basis of these result, premedication of xylazine can be helpful in decresing some side effects and the dosage of propofol. 1 mg/kg of xylazine as preanesthetics on the propofol anesthesia in the dog is considered to be available.

• The Korean Journal of Pain
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• v.11 no.1
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• pp.1-6
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• 1998

Background: The role of nitric oxide(NO) in analgesia from opioids is controversial. On the one hand, IV morphine analgesia is enhanced by IV injection of NO synthase inhibitors. On the other hand, IV morphine results in increased release of NO in the spinal cord. There have been no behavioral studies examining the interaction between IV morphine and intrathecal injection of drugs which affect NO synthesis. Method: Rats were prepared with chronic lumbar intrathecal catheters and were tested withdrawal latency on the hot plate after 3~5 days of surgery. Antinociception was determinined in response to a heat stimulus to the hind paw before and after IV injection of morphine, 2.5 mg/kg. Twenty minutes after morphine injection, rats received intrathecal injection of saline or the NO synthase inhibitors, L-NMMA or TRIM, the NO scavenger, PTIO, or the NO synthase substrate, L-Arginine. Intrathecal injections, separated by 15 min, were made in each rats and measurements were obtained every 5 min. Result: Mophine produced a 60~70% maximal antinociceptive response to a heat stimulus in all animals for 60 min in control experiments. Intrathecal injection of idazoxane decreased antinociception of IV morphine. The NO synthase inhibitors and the NO scavenger produced dose-dependent decreases in antinociceptive effect of morphine, whereas saline as a control group and L-Arginine as the NO substrate had no effect on antinociception of morphine. Conclusion: The present study supports the evidences that systemic morphine increase the nitrite in cerebrospinal fluid and dorsal horn. These data suggest that the synthesis of NO in the spinal cord may be important to the analgesic effect of IV morphine and increased NO in spinal cord has different action from the supraspinal NO.

• Journal of Acupuncture Research
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• v.33 no.3
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• pp.1-16
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• 2016

Objectives : The objective of this study was to investigate the effects of Gentianae Macrophyllae Radix pharmacopuncture (GP) at Hwando (GB30) in neuropathic pain induced rats. Methods : Neuropathic pain in rats was induced by tibial and sural nerve transection. The rat subjects were divided into 6 groups : normal (Nor, n = 5), control (Con, n = 5), neuropathic pain- induced injected at GB30 with 1 mg/kg GP (GP-A, n = 5), 5 mg/kg GP (GP-B, n = 5) and 20 mg/kg GP (GP-C, n = 5), and neuropathic pain-induced injected with 1mg/kg Tramadol (Tramadol, n＝5). Injections were administered 2 times a week for a total of 5 treatments. After each treatment plantar withdrawal response was measured and after all 5 treatments were completed c-fos, Bax, Bcl-2, mGlu5 and leukocytes in the blood were analyzed. Results : 1. Groups GP-A, GP-B and GP-C showed a meaningful decrease in the withdrawal response of mechanical allodynia compared to the control group. 2. Groups GP-A, GP-B and GP-C showed a meaningful decrease in the expression of c-fos compared to the control group. 3. Groups GP-A and GP-C showed a meaningful increase in the expression of mGluR5 compared to the control group. 4. Groups GP-A, GP-B and GP-C showed a meaningful decrease in Bax/Bcl-2 ratio compared to the control group. Conclusion : These results suggest that Gentianae Macrophyllae Radix pharmacopuncture at Hwando (GB30) could decrease mechanical allodynia and could have analgesic and neuroprotective effects on the model of neuropathic pain.

• Archives of Pharmacal Research
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• v.28 no.7
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• pp.848-853
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• 2005

Synurus deltoides was previously found to possess significant anti-inflammatory activity especially against chronic inflammation, and strong analgesic activity in vivo. In this study, new anti-inflammatory formulation containing S. deltoides extract as a major ingredient was prepared and in vivo activity was evaluated. The plausible action mechanism was also investigated. The new formulation (SAG) contains 1 part of S. deltoides extract, 0.9 part of Angelica gigas extract and 0.9 part of glucosamine sulfate (w/w). SAG inhibited dose-dependently edematic response of arachidonic acid (AA)- and 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema in mice, which is an animal model of acute inflammation. SAG showed 44.1 % inhibition of AA-induced ear edema at an oral dose of 50 mg/kg. In an animal model of chronic inflammation, SAG clearly reduced the edematic response of 7 -day model of multiple treatment of TPA (38.1 % inhibition at 200 mg/kg/day). Furthermore, SAG (50-800 mg/kg/day) as well as S. deltoides extract (285 mg/kg/day) significantly inhibited prostaglandin $E_2$ production from the skin lesion of the animals of 7-day model. These results were well correlated with in vitro finding that SAG as well as S. deltoides extract reduced cyclooxygenase (COX)-1- and COX-2-induced prostanoid production, measured in mouse bone marrow-derived mast cells. Therefore, these results suggest that SAG possesses anti-inflammatory activity in vivo against acute as well as chronic inflammatory animal models at least in part by inhibition of prostaglandin production through COX-1/COX-2 inhibition. And COX inhibition of SAG is possibly contributed by S. deltoides extract among the ingredients. Although the anti-inflammatory potencies of SAG were less than those of currently used anti-inflammatory drugs, this formulation may have beneficial effect on inflammatory disorders as a neutraceutical.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.2
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• pp.272-278
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• 2002

To investigate the anti-inflammatory and analgesic effects of Herba Chelidoniie, the extracts of Herba Chelidoniie treated in arthritic rat model. Complete Freund,s Adjuvant(CFA) were injected in the subcutaneous tissue of left foot paw of rats to induce arthritis. Herba Chelidonii extracts(HC) was administered immediately into the peritoneal cavity after CFA injection for 12 days. The immunohistochemical stainings for calcitonin gene-related peptide(CGRP) and substance P in the L4, L5 and L6 spinal dorsal horn and ganglia were done, and the paw swelling was measured with a micrometer and the blood leukocytes were counted. The results were as follows : The paw swelling of HC treated group was significantly decreased in 12th day after CFA injection compare to control group. The change of differential leukocytes counts of HC treated group increased the ratio of lymphocytes, and decreased the ratio of neutrophils compare to control group. The extent of CGRP immunoreactive nerve fiber of dorsal horn of HC treated group was weakly stained compare to control group. The number of CGRP immunoreactive neurons of L6 spinal cord of HC treated group was significantly decreased compare to control group. The extent of substance P immunoreactive nerve fiber of dorsal horn of He treated group was weakly stained compare to control group. The number of substance P immunoreactive neurons of L4, L5 and L6 spinal cord of HC treated group was significantly decreased compare to control group. These experimental results suggest that Herba Chelidonii extracts reduce the number of CGRP and substance P immunoreactive neurons and nerve fibers of spinal dorsal horns and ganglia, and decrease paw swelling in arthritic rat model, which may be closely related to analgesic and antiinflammatory effects of Herba Chelidonii.

• The Korean Journal of Pain
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• v.13 no.2
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• pp.149-155
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• 2000

Background: Pulsed radiofrequency (RF) lesioning is a painless procedure and causes no neurodestruction and neuritis-like reaction are common following conventional RF lesioning. There is little data about the effect of pulsed RF especially with regard to its suitability for the treatment of acute pain. The possibility of a placebo effect cannot be ruled out because a double-blind study was not performed in previous studies. There is also no neuropathologic study about pulsed RF. Methods: The rats were anesthetized with sodium pentobarbital (40 mg/kg, i.p.; supplemented as necessary). The common sciatic nerve was exposed by blunt dissection through biceps femoris. Pulsed RF was administered to the common sciatic nerve using a 30 ms/s pulse with for 120 seconds. The temperature reached was no more than $42^{\circ}C$. Analgesia was determined using hot-plate assay shortly and, 3 days and 1 week before, and 2 weeks after operation. Lesions were examined with LM (light microscope) and EM (electron microscope) 2 weeks later. Results: There were no differences in response latencies between the control and experimental group. There were many vacuoles with hyaline bodies in the Schwann cell cytoplasm rather than axon in LM and larger electron dense bodies. No changes were found in the axon or unmyelinated fibers. Only small changes were found in the sheaths of myelinated fibers and Schwann cells. Conclusions: We therefore do think that any analgesic effect of pulsed RF is not a result of block of neural conduction. But rather than it can be attributed to others factors. It was also ineffective as a treatment for acute pain such as that caused by the hot-plate test.

• Journal of Veterinary Clinics
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• v.27 no.4
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• pp.336-342
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• 2010

The purpose of this study was to determine the antagonistic effects of flumazenil on anesthesia induced with tiletamine/zolazepam in dogs. The anesthetic effects (sedation, analgesic, muscle relaxation, posture and auditory response score), vital signs (heart rate, respiratory rate and rectal temperature) and blood biochemistry (glucose (GLU), total protein (TP), alanine aminotransferase (ALT), aspartate aminotransferase (AST)) were examined as indicators of the antagonistic effects. A total of 6 clinically healthy mongrel dogs were used in this study. The dogs in TZ group received administration of tiletamine/zolazepam 10 mg/kg IV. The dogs in TZF group received administration dose of TZ 10 mg/ kg IV followed by the administration of flumazenil 0.1 mg/kg 20 minutes after administering a TZ 10 mg/kg dose. There were significant differences in the recovery of anesthesia between the groups. The GLU level in the TZF group after the administration of flumazenil was significantly higher than that of the TZ group. There was a larger change in the HR in the TZF group than in the TZ group until 30 minutes after flumazenil administration. The sternal recumbency, standing and walking times of the TZF group were faster than those of the TZ group. In conclusion, flumazenil showed antagonistic effect against tiletamine/zolazepam in dogs. When recovering from anesthesia, flumazenil reduced sternal recumbency, standing and walking times.

• The Korean Journal of Pharmacology
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• v.22 no.2
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• pp.88-95
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• 1986

Clinically, subhypnotic doses of barbiturates have been known to elicit hyperalgesia. In this experiment, effect of acute or chronic phenobarital treatment on the response to pain in rat was reevaluated by hot-plate method. To elucidate its mechanism, changes of ${\beta}-endorphin$ contents and [3H]-morphine binding of the rat midbrain as well as functional opiate receptor in vas deferens were also measured. Intraperitoneal injection of sub anesthetic dose phenobarbital induced initial hyperalgesia followed by successive analgesia, while chronic phenobarbital-treatment decreased reactivity to pain. Naloxone (10mg/kg, i.p.) markedly shortened hot plate latency period, and significantly inhibited the analgesic action of phenobarbital. Single dose of phenobarbital did not affect ${\beta}-endorphin$ contents and [3H]-morphine binding in rat mid brain, but in the chronic phenobarbital-treated groups, ${\beta}-endorphin$ contents was increased, while Bmax of opiate receptor binding was decreased. Moreover, very significant correlations among responses to pain, changes of ${\beta}-endorphin$ contents and opiate receptor binding were observed. However, Kd values of opiate receptor bindings were not changed in all preparations. In the chronic phenobarbital-treated vas deferens preparations, ID50 of morphine was increased witb concomittant decrease of maximum effect. But $pA_2 $, value for naloxone was not changed. From these results, it is suggested that phenobarbital can produce analgesia due to changes of ${\beta}-endorphin$ contents as well as functional opiate receptors by receptor regulation.