• The Korean Journal of Physiology and Pharmacology
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• v.25 no.3
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• pp.207-216
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• 2021

Several studies have previously reported that exposure to stress provokes behavioral changes, including antinociception, in rodents. In the present study, we studied the effect of acute cold-water (4℃) swimming stress (CWSS) on nociception and the possible changes in several signal molecules in male ICR mice. Here, we show that 3 min of CWSS was sufficient to produce antinociception in tail-flick, hot-plate, von-Frey, writhing, and formalin-induced pain models. Significantly, CWSS strongly reduced nociceptive behavior in the first phase, but not in the second phase, of the formalin-induced pain model. We further examined some signal molecules' expressions in the dorsal root ganglia (DRG) and spinal cord to delineate the possible molecular mechanism involved in the antinociceptive effect under CWSS. CWSS reduced p-ERK, p-AMPKα1, p-AMPKα2, p-Tyk2, and p-STAT3 expression both in the spinal cord and DRG. However, the phosphorylation of mTOR was activated after CWSS in the spinal cord and DRG. Moreover, p-JNK and p-CREB activation were significantly increased by CWSS in the spinal cord, whereas CWSS alleviated JNK and CREB phosphorylation levels in DRG. Our results suggest that the antinociception induced by CWSS may be mediated by several molecules, such as ERK, JNK, CREB, AMPKα1, AMPKα2, mTOR, Tyk2, and STAT3 located in the spinal cord and DRG.

• Korean Journal of Pharmacognosy
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• v.54 no.2
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• pp.61-65
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• 2023

Clerodendrum trichotomum has been widely used as a traditional medicine for the treatment of numerous diseases, including pain management. However, there have been extremely limited pharmacological and phytochemical studies on Clerodendrum trichotomum up to now. In this study, we investigated the effects of the methanolic extract of Clerodendrum trichotomum (MCT) on nociceptive pain in mice. Our finding demonstrate that MCT treatment significantly extended the latency time in both the tail-immersion test and hot-plate test. Additionally, MCT treatment reduced acetic acid-induced writhing motions. These results suggest that MCT possesses strong anti-nociceptive activities against thermal and chemical nociception. In the formalin test, mice fed with MCT exhibited reduced licking time during both the early and late phases, thereby confirming the therapeutic potential of MCT in central and peripheral nociception. Furthermore, in combination tests using naloxone, the MCT-mediated anti-nociception was slightly reduced, indicating that MCT might act as a partial opioid receptor agonist. Based on these results, MCT may be a valuable candidate for the development of anti-nociceptive agents.

• The Journal of Korean Obstetrics and Gynecology
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• v.37 no.1
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• pp.23-39
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• 2024

Objectives: Primary dysmenorrhea (PD) is defined as abdominal pain during menstruation period in the absence of an identifiable pathological lesion. Corydalis tuber (CT) is an herbal medicine that has an excellent effect in relieving pain and convulsions. The purpose of this study is to observe the effect of Corydalis tuber aqueous extracts (CTe) on primary dysmenorrhea. Methods: The rats were injected with estradiol benzoate subcutaneously for 10 days (2.5 mg/kg on the first and 10th days, and 1 mg/kg from the 2~9th day). Oxytocin 1 U/kg was treated by peritoneal injection 1 hour after the last 10th injection of estradiol benzoate. CTe 400, 200 and 100 mg/kg were administered orally, once a day for 10 days at 30 minutes after each estradiol benzoate treatment. The results of CTe were compared to those of IND 5 mg/kg orally treated rats. Results: As results of estradiol benzoate and oxytocin administration, noticeable decreases of body weights and gains, uterus weights were observed with congestion and enlargement of the uterus at gross inspections, and increases of abdominal writhing responses, uterus MDA levels, GSH contents, SOD and CAT activities. However, these oxidative stress mediated PD signs were dose-dependently decreased by 10 consecutive days of oral administration of three different doses of CTe 400, 200 and 100 mg/kg as comparable to those of IND 5 mg/kg in CTe 200 mg/kg. Conclusions: CTe had a significant improvement effect on primary dysmenorrhea in the PD rat model induced by estrogen benzoate and oxytocin.

• The Korean Journal of Pain
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• v.37 no.2
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• pp.151-163
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• 2024

Background: Galangin, commonly employed in traditional Chinese medicine for its diverse medicinal properties, exhibits potential in treating inflammatory pain. Nevertheless, its mechanism of action remains unclear. Methods: Mice were randomly divided into 4 groups for 7 days: a normal control group, a galangin-treated (25 and 50 mg/kg), and a positive control celecoxib (20 mg/kg). Analgesic and anti-inflammatory effects were evaluated using a hot plate test, acetic acid-induced writhing test, acetic acid-induced vascular permeability test, formalin-induced paw licking test, and carrageenan-induced paw swelling test. The interplay between galangin, transient receptor potential vanilloid 1 (TRPV1), NF-κB, COX-2, and TNF-α proteins was evaluated via molecular docking. COX-2, PGE2, IL-1β, IL-6, and TNF-α levels in serum were measured using ELISA after capsaicin administration (200 nmol/L). TRPV1 expression in the dorsal root ganglion was analyzed by Western blot. The quantities of substance P (SP) and calcitonin gene-related peptide (CGRP) were assessed using qPCR. Results: Galangin reduced hot plate-induced licking latency, acetic acid-induced contortions, carrageenan-triggered foot inflammation, and capillary permeability in mice. It exhibited favorable affinity towards TRPV1, NF-κB, COX-2, and TNF-α, resulting in decreased levels of COX-2, PGE2, IL-1β, IL-6, and TNF-α in serum following capsaicin stimulation. Galangin effectively suppressed the upregulation of TRPV1 protein and associated receptor neuropeptides CGRP and SP mRNA, while concurrently inhibiting the expression of NF-κB, TNF-α, COX-2, and PGE2 mRNA. Conclusions: Galangin exerts its anti-inflammatory pain effects by inhibiting TRPV1 activation and regulating COX-2, NF-κB/TNF-α expression, providing evidence for the use of galangin in the management of inflammatory pain.

• Journal of Korean Medicine Rehabilitation
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• v.15 no.1
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• pp.127-141
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• 2005

Objectives : This study was performed to investigate the effects of Gamichangbaek-san(Jiaweichangbai-san) on anti-inflammatory, analgesic, anti-febrile and immune response on the arthritis of carrageenan-induced animals. Methods and Materials : Rats were classified into control and sample groups which are 7 individuals each for the experiments about anti-inflammatory and anti-febrile. Each of the 7 mice were classified into normal, control, sample groups for the analgesic experiments. Gamichangbai-san(Jiaweichangbai-san) was administered to sample group and normal saline was administered to normal and control groups. Arthritis was induced by injection of 1% carrageenan $0.1m{\ell}$ and Gamichangbaek-san(Jiaweichangbai-san) was administered after 30 minutes. The change of edema in Carrageenan-induced Arthritic Rats' Paws was measured after 1 hour and 5 hours from the injection of carraqeenan with Plethysmometer(7150, UGO BASILE, ltaly) by Winter' method. WBC, Lymphocyte and ESR were measured by heart puncture and CD4+ T cell, CD8+ T cell and CD4+/CD8+ T cell ratio were measured from the spleen tissue. Writhing syndrom was measured with Tail flick unit(UGO BASILE, Italy) in the experiments conducted to check the analgesic activity. The temperature of the paws of carrageenan-induced arthritic rats was measured by Laser thermometer. Rectal temperature was measured by Yeast's method in anti-febrile experiments. Immune response was measured by CD4+, CD8+ T cell ratio and CD4+/CD8+ T cell ratio. Results : 1. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) decreased the increase rate of Paw Edema effectively with statistical significance. 2. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) decreased WBC, Lymphocyte and ESR with statistically high significance. 3. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) did not show significant analgesic effect, but the Pressure pain threshold of the paws was increased with statistical significance. 4. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) decreased rectal temperature effectively and had an anti-febrile effect about the febrile of a joint with statistical significance. 5. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) increased CD4+ T cell ratio with statistically high significance and increased CD+8 T cell ratio with statistical non significance but increased CD4+/CD8+ T cell ratio effectively with statistical significance, too. Conclusions : According to the above results, it can be concluded Gamichangbaek-san(Jiaweichangbai-san) showed the treatment effects on the artificial arthritis resulted from carageenan in rats and it is suggested that more interest and study in the security for the clinical use were needed.

• The Korea Journal of Herbology
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• v.29 no.6
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• pp.165-173
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• 2014

Objectives : Platycodon Root is frequently used in traditional medicine to treat inflammatory diseases of the throat. The purpose of this study was to characterize the effect of the EtOH extract of fermented Platycodon grandiflorum on the ameliorative effects on the Antipruritic Effect of atopic dermatitis mouse model induced by compound 48/80 and ovalbumin (OVA)-induced allergic responses in mice. Methods : In the present study, we examined the anti allergic effect of Platycodon grandiflorum (PR) and its fermented production (FPR) in several mouse model. We measured acute ear edema in a mouse model caused by TPA and consecutively histological change of Ear tissue was observed by hematoxylin and eosin (H&E) staining. and also Scratching behaviors by compound 48/80 was investigated. The levels of allergic mediators such as immunoglobulin (Ig) E, and anti-oxidant markers such as SOD and MDA in the sera of OVA induced allergic mice were measured by enzyme-linked immunosorbent assay. Results : FPR inhibited compoud 48/80-induced scratching behavior in mice, as well as acetic acid-induced writhing in mice. The anti-scratching behavioral effect of FPR was more potent than PR. FPR extract significantly decreased the serum levels of IgE and MDA compared with those of OVA control group. Conclusions : These results indicate that Anti allergic effect of Platycodon grandiflorum is enhanced by fermentation with Saccharomyces cerevisae and FPR may be useful for protection from the itching reactions, which are IgE-mediated representative skin allergic diseases.

• The Journal of Internal Korean Medicine
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• v.36 no.3
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• pp.236-251
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• 2015

Objectives: To investigate the anti-inflammatory, analgesic, anti-pyretic and anti-histamine activities of 20 herbal medicines to test their efficacy in common cold treatment. Methods: For all experiments, the herbal medicines were extracted with 80% ethanol and freeze-dried. To determine the anti-oxidative properties, we tested DPPH-free radical-scavenging activity and xanthine oxidase inhibitory activity. To determine anti-inflammatory and analgesic potential, we investigated acetic acid-induced vascular permeability and writhing test in ICR mice. For anti-pyretic activities, an LPS-induced pyrexia study was conducted in rabbits. To evaluate the anti-histamine activity, we examined compound 48/80-induced systemic anaphylaxis in ICR mice and the release of β-hexosaminidase on rat basophilic leukemia (RBL-2H3) cells. Results: Ephedrae herba, Forsythiae fructus, Cinnamomi ramulus, and Cimicifugae rhizome showed potent free-radical scavenging activities. Gentianae macrophyllae radix inhibited acetic acid-induced vascular permeability. Schizonepetae spica and Cimicifugae rhizome inhibited acetic acid. Cinnamomi ramulus and Angelicae decursivae radix inhibited LPS-induced pyrexia. Angeliace dahuricae radix and Asari radix inhibited compound 48/80. Scutellariae radix, Cinnamomi ramulus, Ephedrae herba, and Zingiberis rhizoma crudus potently inhibited the release of β-hexosaminidase. Conclusions: We examined the anti-inflammatory, analgesic, anti-pyretic and anti-histamine activities of 20 herbal medicines;We examined the anti-inflammatory, analgesic, anti-pyretic and anti-histamine activities of 20 herbal medicines Codonopsis pilosulae radix, Zingiberis rhizoma crudus, and Cinnamomi ramulus showed novel efficacy. These results suggest that some of herbal medicines may be very effective in treating common cold.

• Journal of Veterinary Clinics
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• v.27 no.6
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• pp.663-667
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• 2010

Experiments were undertaken to assess the antinociceptive effect of bee venom (BV) in rodent animal models. Comparison of antinociceptive efficacy between Korean BV and commercially available American BV was the primary interest of the study. Korean BV was collected using BV collector devices in which an electrical impulse is used to stimulate the worker bee (Apis mellfera L.) to sting and release venom. After collection, whole BV was evaporated until dry using the BV collector. Commercially available dried American BV was purchased from Sigma Company in USA. Korean and American sourced BVs were diluted and amounts of 6 mg/kg body weight (BW), 0.6 mg/kg BW and 0.06 mg/kg BW were tested. BV was subcutaneously injected to produce an antinociceptive effect and the antinociceptive efficacy was evaluated using a writhing test in mice and a formalin test in rats. The antinociceptive effects of the two BVs tested were similar in mice for visceral pain and showed a dose-dependent response. The antinociceptive effect of Korean BV was not significantly different compare to American BV. These results suggest that Korean BV may be used to achieve an antinociceptive effect for use in medical therapies.

• Journal of Acupuncture Research
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• v.15 no.2
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• pp.1-15
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• 1998

Purpose : The study for changes in components and acitvities of Artemisiae Herba at various processing temperature is generally regarded as a foundation in setting the optimum heat-processing temperature and for getting the maximum activities for medical usage of this herb. Methods: Therefore some experiments were performed either in vitro or in vivo and various changes were observed - the changes in the weitht of Artemisiae Herba, the changes in the relative amount of three kinds of extracts from Artemisiae Herba ( diluted ethanol extract, water extract, ether extract ), the TLC pattern of essential oil at various processing temperature, the existance of inhibitory effects both on ${\beta}$-Glucuronidase activities, and on heat-induced hemolysis, the effects on increased vascular permeability. The valid results derived from the experiments are as follows. Results: 1. The weight of Artemisiae Herba prominently decreased at 240^{\circ}C$. 2. The contents of diluted ether extract were maximum in the unprocessing condition. Those of water extract were maximum at 180^{\circ}C$ and at 210^{\circ}C$. and the changes of diluted ethanol extract at 150^{\circ}C$. 3. The TLC pattern of essential oil in Artemisiae Herba at various processing temperature showed that a component began to increase at Rf 0.56 and another component began to decrease at Rf 0.86. 4. The contents of Eupatilin in Artemisiae Herba at various processing temperature continued to decreased in proportion to the temperature rise, the extent of which was prominent at 210^{\circ}C$, and was unnoticeable at 270^{\circ}C$. 5. Inhibitory effects on ${\beta}$-Glucuronidase activities, trypsin activities and heat-induced hemolysis increased in proportion to the density of Artemisiae Herba. Inhibitory effects on ${\beta}$-Glucuronidase activities and trypsin activities were relatively high at 180^{\circ}C$ while on the writhing syndrome and inhibitory effects on increased vascular permeability induced by acetic acid were maximum at 240^{\circ}C$. those on heat-induced hemolysis were relatively high at 240^{\circ}C$. 6. In vivo, both analgesic effects Conclusions: To maximize of the effectiveness of Artemmisiae Herba, the ideal heating temperature is in the range of 180^{\circ}C{\sim}240^{\circ}C$.

• The Journal of Internal Korean Medicine
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• v.29 no.3
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• pp.554-566
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• 2008

Objectives : Modified Gamgil-tang is a prescription commonly used for respiratory diseases. This thesis was carried out to check the treatment effects and diversity of drug formulation by comparing extraction method of ethanol and water of modified Gamgil-tang. Methods : All experiments were carried out with water and 50% ethanol extraction for comparison. In vivo experiment, hyaluronidase inhibitory effects and trypsin inhibitory effects were tested to measure the anti-inflammatory effects activity. Scavenging effects of DPPH free radical, xanthine oxidase inhibitory effects and inhibition on TBA-RS formation were experimented to measure anti-oxidative effects. With the in vivo experiment, ICR group mice and SD group rats were used as experimental animals. An anti-inflammatory effects experiment were carried out to measure the action on carrageenin-induced hind paw edema: analgesic effects were measured using writhing syndrome induced by 0.7% acetic acid in mice: antipyretic effect was measured using endotoxin, and inhibitory effects of increase vascular permeability induced by 0.5% histamine were measured. Results : For extraction of glycyrrhizin contents, ethanol extract was extracted 2 times of that of water extract. Anti-inflammatory effects showed high in ethanol extract. Anti-oxidative effects measured high in ethanol extract. No significant result was found in inhibition on TBA-RS formation. Analgesic effects were found to be similar in water and ethanol extract. Antipyretic effects were found to be stronger in water extract. Inhibitory effects of increase vascular permeability induced by 0.5% histamine showed stronger in ethanol extract. Conclusion : By measuring anti-inflammatory effects, analgesic effects, antipyretic effects, anti-oxidative effects, and histamine permeation inhibition effects both in water extract and ethanol extract after adding agents such as Mentha Herba, Gardenias Fructus, and propolis to existing Gamgil-Tang, ethanol extract was found to be more effective in anti-inflammatory effects, analgesic effects, anti-oxidative effects, and histamine permeation inhibition effects. The converse was found for antipyretic effect.