• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.6
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• pp.1470-1476
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• 2007

In the present study, the anti-inflammatory effect of Jungcheonhwadamgangki-tang(定喘化痰降氣湯) water extract was tested in formalin-injection mouse hind paw chronic inflammation model. The test articles were dosed once a day for 10 days, and changes on the body weight, paw weights were observed with histopathology of induced paw dorsum pedis. In addition, histomorphometry was also monitored at sacrifice. The increases of absolute and relative hind paw weight detected in vehicle control compared to that of sham, were significantly and dose-dependently inhibited by Jungcheonhwadamgangki-tang in the present study. A classic acute inflammatory histological changes such as subcutaneous edema, hypertrophy and infiltration of inflammatory cells, was detected in vehicle control. However, these histological changes were significantly and dose-dependently inhibited by Jungcheonhwadamgangki-tang. In addition, the increases of hind paw weight detected in the vehicle control, were also dose-dependently decreased in the all Jungcheonhwadamgangki-tang-dosing groups. Base on these aforementioned results, it is concluded that Jungcheonhwadamgangki-tang have clear anti-inflammatory effect on the chronic inflammation induced by formalin-injection.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.4
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• pp.849-855
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• 2008

In the present study, the anti-inflammatory effect of Jungcheonhwadamgangki-tang plus antler water extract was tested in formalin-injected chronic inflammation model in mouse hind paw. The test articles were dosed once a day for 10 days, and changes on the body weight, paw weights were observed with histopathology of induced paw dorsum pedis. In addition, histomorphometry was also monitored at sacrifice. 15 mg/kg/10 mL of dexamethasone (DEXA) and diclofenac (DICLO) intraperitoneally dosed groups were used as reference groups. A significantly decrease of both absolute and relative paw weights were observed in all dosing groups including DEXA and DICLO groups compared to that of control, and a significantly decrease of the differences between intact and induced paw weights were also observed Jungcheonhwadamgangki-tang plus antler dosing groups compared to that of control. These histological signs-hypertrophy of paw dorsum pedis tissues were detected results from edematous changes on the cutaneous and subcutaneous tissues with severe infiltration of chronic inflammatory cells-were dramatically decreased in all dosing groups including DEXA and DICLO dosing groups compared to that of control. Especially, dose dependently decreases were detected in Jungcheonhwadamgangki-tang plus antler dosing groups compared to that of control. Base on these aforementioned results, it is concluded that Jungcheonhwadam- gangki-tang plus antler have clear anti-inflammatory effect on the chronic inflammation induced by formalin injection.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.612-618
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• 2008

In the present study, the anti-inflammatory effect of Haepyoejin-tang plus antler water extract was tested in formalin-injected chronic inflammation model in mouse hind paw. The test articles-100, 250, 500 mg/kg- were dosed once a day for 10 days, and changes on the body weight, paw weights were observed with histopathology of induced paw dorsum pedis. In addition, histomorphometry was also monitored at sacrifice. 15 mg/kg/10 mL of dexamethasone (DEXA) and diclofenac (DICLO) intraperitoneally dosed groups were used as reference groups. A significantly decrease of both absolute and relative paw weights were observed in all dosing groups including DEXA and DICLO groups compared to that of control, and a significantly decrease of the differences between intact and induced paw weights were also observed Haepyoejin-tang plus antler dosing groups compared to that of control. These histological signs-hypertrophy of paw dorsum pedis tissues were detected results from edematous changes on the cutaneous and subcutaneous tissues with severe infiltration of chronic inflammatory cells-were dramatically decreased in all dosing groups including DEXA and DICLO dosing groups compared to that of control. Especially, dose dependently decreases were detected in Haepyoejin-tang plus antler dosing groups compared to that of control. Base on these aforementioned results, it is concluded that Haepyoejin-tang plus antler have clear anti-inflammatory effect on the chronic inflammation induced by formalin injection.

• Archives of Pharmacal Research
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• v.28 no.2
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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.

• The Korean Journal of Pain
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• v.35 no.2
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• pp.173-182
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• 2022

Background: Neurokinin-1 (NK1) and calcitonin gene-related peptide (CGRP) play a vital role in pain pathogenesis, and these proteins' antagonists have attracted attention as promising pharmaceutical candidates. The authors investigated the anti-nociceptive effect of co-administration of the CGRP antagonist and an NK1 antagonist on pain models compared to conventional single regimens. Methods: C57Bl/6J mice underwent sciatic nerve ligation for the neuropathic pain model and were injected with 4% formalin into the hind paw for the inflammatory pain model. Each model was divided into four groups: vehicle, NK1 antagonist, CGRP antagonist, and combination treatment groups. The NK1 antagonist aprepitant (BIBN4096, 1 mg/kg) or the CGRP antagonist olcegepant (MK-0869, 10 mg/kg) was injected intraperitoneally. Mechanical allodynia, thermal hypersensitivity, and anxiety-related behaviors were assessed using the von Frey, hot plate, and elevated plus-maze tests. The flinching and licking responses were also evaluated after formalin injection. Results: Co-administration of aprepitant and olcegepant more significantly alleviated pain behaviors than administration of single agents or vehicle, increasing the mechanical threshold and improving the response latency. Anxiety-related behaviors were also markedly improved after dual treatment compared with either naive mice or the neuropathic pain model in the dual treatment group. Flinching frequency and licking response after formalin injection decreased significantly in the dual treatment group. Isobolographic analysis showed a meaningful additive effect between the two compounds. Conclusions: A combination pharmacological therapy comprised of multiple neuropeptide antagonists could be a more effective therapeutic strategy for alleviating neuropathic or inflammatory pain.

• Applied Microscopy
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• v.39 no.3
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• pp.205-218
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• 2009

This experiment was performed to evaluate the morphological responses of the gastric epithelial cells of the mouse, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of BCG. Healthy adult ICR mice weighing 25 gm each were divided into normal and experimental groups (tumor control group and BCG-treated group). In the experimental groups, each mouse was inoculated with $1{\times}10^7$ Ehrlich carcinoma cells subcutaneously in the inguinal area. From next day after inoculations, 0.2 mL of saline or BCG (0.5 mL/25 g B.W.: $0.03{\times}10^8{\sim}0.32{\times}10^8$ CFU) were injected subcutaneously to the animals every other day, respectively. The day following the 7th injection of saline or BCG, each mouse was injected with a single dose of 0.7 ${\mu}Ci/g$ of methyl-$^3H$-thymidine (25 Ci/mmol, Amersham Lab., England) through tail vein. Seventy minutes after the thymidine injection, animals were sacrificed, and gastric tissues were taken and fixed in 10% neutral formalin. Deparaffinized sections were coated with autoradiographic emulsion EM-1 (Amersham Lab., England) in a dark room. The number of labeled epithelial cells in the gastric mucosae (mean number of labeled epithelial cells per 3.5 mm length of mucosa) were observed and calculated. And for electron microscopic observation, gastric tissues were prefixed with 2.5% glutaraldehyde-1.5% paraformaldehyde solution, followed by post-fixation with 1% osmium tetroxide solution. On the light microscopic study, gastric mucosae had no morphological changes following the injection of BCG. On the electron microscopic study, in the BCG-treated mice, myelin figures and multivesicular bodies within the gastric epithelial cells were observed more frequently than in those of the normal control ones. On the autoradiographic study, number of the labeled cells of normal control, tumor control and BCG-treated mice were 380.2 (${\pm}31.35$), 426.1 (${\pm}28.43$) and 301.8 (${\pm}34.63$), respectively. In the BCG-treated mice, poorly-labeled cells containing only a few silver grains of 3H-thymidine were observed more frequently as compared in those of the normal control and tumor control ones. From the above results, BCG may suppress the DNA synthesis of the gastric epithelial cells, but does not results severe fine structural defect on the gastric epithelial cells. These results suggest that BCG is expected as one of the effective supplemental anticancer drugs.

• Journal of Radiation Protection and Research
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• v.23 no.2
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• pp.89-96
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• 1998

To assess the radioprotective effects of follicle stimulating hormone (FSH) on ovarian follicles, 3 week-old female mice were irradiated with 8.33 Gy of ${\gamma}$-ray (group R) and followed by 5 IU ip-injection of FSH (group RF). For control groups, 5 IU of saline (group C) or 5 IU of FSH (group F) was ip-injected. Ovaries were collected 0h, 6h, 12h, 14, 2d, 4d, and 8d after irradiation or saline/FSH injection, and followed by fixation in neutral buffered formalin for routine histochemistry. Immunohistochemistry was used to assess the status of follicles and DNA fragmentation was analyzed by agarose gel electrophoresis for total DNA. Staining specific for apoptotic follicles showed high intensity at 6h and 12h in group R and RF On the other hand, staining specific for proliferating follicles showed noticeably high intensity at 8d in group R and Rf. DNA fragmentation of 185bp increased with time in all experimental groups. Especially 370bp appeared at 6h in group R, then disappeared after 1d. In case of group RF, it appeared at 12h and disappeared after 1d. From the above results, the irradiated antral follicles become completely disappeared from 4d to 8d, and then new follicles started to grow again at 8d. FSH had delaying or suppressing effects on follicular atresia after irradiation. In addition, it became clear that radiation-induced follicular atresia was mediated by granulosa cell apoptosis.

• Applied Microscopy
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• v.40 no.4
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• pp.193-200
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• 2010

This experiment was performed to evaluate the morphological responses of the duodenal epithelial cells of the mouse, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of Bacillus Calmette-Guerin (BCG). In the experimental groups, each mouse was inoculated with $1{\times}10^7$ Ehrlich carcinoma cells subcutaneously in the inguinal area. From next day after inoculations, 0.2 mL of saline or BCG (0.5 mL/25 g B.W.: $0.03{\times}10^8\sim0.32{\times}10^8$ CFU) were injected subcutaneously to the animals every other day, respectively. The day following the 7th injection of saline or BCG, each mouse was injected with a single dose of $0.7{\mu}Ci$/g of methyl-$^3H$-thymidine (25 Ci/mmol, Amersham Lab, England) through tail vein. Seventy minutes after the thymidine injection, animals were sacrificed, and duodenal tissues were taken and fixed in 10% neutral formalin. Deparaffinized sections were coated with autoradiographic emulsion EM-1 (Amersham Lab, England) in a dark room and dried and were placed in a light-tight box. The number of labeled epithelial cells in the duodenal mucosae (mean number of labeled epithelial cells per 3.5 mm length of mucosa) were observed and calculated. On the light microscopic study, duodenal mucosae had no severe morphological changes following the injection of BCG. In the tumor control and BCG treated groups, a number of small lymphocytes and eosinophile leucocytes are slightly increased as compared with those of the normal control ones. On the autoradiographic study, number of the labeled cells of normal control, tumor control and BCG-treated mice were 632.3 (${\pm}14.47$), 761.7 (${\pm}27.65$) and 505.0 (${\pm}17.09$) respectively. From the above results, BCG may suppress the DNA synthesis of the duodenal epithelial cells, but does not results severe structural defect on the duodenal mucosae. And it is suggested that BCG may greatly improve the anticancer therapy on certain kind of cancer.