Purpose: The purpose of this study was to investigate the effect of the intensity of microcurrent stimulation (with currents of 50 ${\mu}A$, 100 ${\mu}A$ and 300 ${\mu}A$ using a pulse frequency of 5 pps) on wound healing in rats. Methods: Sixty male Korean rats were randomly divided into four groups of 15 rats that were subjected to four different treatment protocols (control group, no treatment; experimental groups, treated with currents of 50 ${\mu}A$, 100 ${\mu}A$ or 300 ${\mu}A$). An experimental 20 mm linear wound was made in each animal and all animals in the experimental groups received microcurrent stimulation once a day for 20 minutes until the day of sacrifice on day 1, day 3 and day 6. An optical microscope was used to determine any histological changes. Results: The experimental results were as follows. 1. In an examination with the naked eye, all groups showed similar changes until the first day. However, from the third day, a little intercellular fluid soaked through wound region in the control group rats. In the experimental group animals, little intercellular fluid soaked through wound region, and swelling and redness did not appear, from the third day. 2. In an examination with histological evaluation, more significant changes were observed in all of the experimental group rats than the control group animals. Especially, a stimulation intensity of 50 ${\mu}A$ caused a more significant effect than the use of the other intensities by day 6 of wound healing. In addition, rapid recovery was observed. Conclusion: It was determined that microcurrent stimulation had a positive effect on wound healing. A stimulation intensity of 50 ${\mu}A$ was more effective than the other intensities (100 ${\mu}A$ and 300 ${\mu}A$) utilized for wound healing. Furthermore, low-intensity microcurrent stimulation was more effective for the purpose of wound healing.
Purpose: Scutellaria baicalensis is a herb which has effect of eliminating heat, drying dampness, purging away fire, detoxicating. Clinically, has been used to remove fever and control of inflammation. We have studied in series to investigate the effective traditional oriental medicines of treatment for endometriosis. In this study, the effects of Scutellaria baicalensis administrated orally or rectally on surgically induced endometriosis in rat were investigated. Methods: The endometrial tissues of rats were autografted to their small intestine. Rats with surgically induced endometriosis were administered with Scutellaria baicalensis extracts for 40 days orally or rectally. We observed the tissue size of ectopic uterine implants at the mesenteric with the naked eye and examined the concentration of estradiol, progesterone, $TNF-{\alpha}$ and IL-2, IL-4, IL-6 and IL-10 in serum. Also, we inquired which was more effective between oral administration groups and rectal administration groups. Results: The size of ectopic uterine implants of orally or rectally treated groups was much smaller than those of control groups. The concentrations of estradiol, progesterone, $TNF-{\alpha}$, IL-2 and IL-6 were significantly decreased in oral administration experimental group compared with the control group. The concentrations of progesteron, $TNF-{\alpha}$, IL-2 and IL-6 were significantly decreased in rectal administration experimental group compared with the control group. The efficiency of oral administration group was better than that of rectal administration group at the serum concentration of estradiol and IL-4. Conclusion: Our data suggest that Scutellaria baicalensis inhibit the inflammation induced from ectopic uterine implants at the mesenteric wall and inhibit the growth of ectopic uterine implants. Judging from the above results, it can be suggested that Scutellaria. baicalensis should be a useful agent for inhibiting the inflammation induced from ectopic uterine implants and the proliferation of endometriosis. Maybe, oral administration of Scutellaria baicalensis is more effective than rectal administration.
Yoo, Nam Ho;Kwon, Yongsoo;Chun, Hyeon Soo;An, Kyu Sup;Kim, Hye Jin;Ryu, Hyeon Yeol;Lee, So Min;Song, Kyung Seuk;Park, Byung Jun;Kim, Myong Jo
Korean Journal of Pharmacognosy
/
v.50
no.3
/
pp.205-218
/
2019
This study was conducted to investigate the toxicity symptoms and approximate lethal dose (ALD) of Oplopanax elatus (Nakai) Nakai hydrothermal extract powder by single oral dose toxicity and 4 weeks of repeated oral dose determination. The Sprague-Dawley (SD) male and female rats were treated with 1,250 (low- dosage group), 2,500 (medium- dosage group) and 5,000 (high- dosage group) mg/kg. In the single oral dose toxicity test, no dead animals and toxic symptoms were observed during the experiment. And there were no related with anomalies in normal weight changes and autopsy results. In the four-week repeated oral dose determination test, no death animals and toxicity symptoms were observed during the experiment, and there were no abnormal results in weight changes, feed and negative intake measurements. Results of eye examination, urinalysis, hematological values and serum biochemical values, gross findings and absolute organ were not of singularity. These result demonstrated that no toxic symptoms were observed by the test substance Oplopanax elatus (Nakai) Nakai hydrothermal extract powder under this test condition, and the non-toxic content is determined to be 5,000 mg/kg/day.
Kim, Young Sook;Cho, Yong Wan;Lim, Hye-Won;Sun, Yonghua
Journal of the Korean Applied Science and Technology
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v.39
no.3
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pp.442-453
/
2022
Various animal models have been used to study the efficacy and action mechanisms of human diseases and medicines. Zebrafish (Danio rerio) is increasingly and successfully used as a model in translational research on human diseases. We obtained necessary information from original peer reviewed articles published in scientific 54 journals, such as Pubmed, Google Scholar, Scopus scince their inception until Dec, 2020 using the following terms: zebrafish animal models, herbal medicine, in vivo screening. In this review, we discuss the recent contributions of the various zebrafish disease models to study of herbal medicines. We focused on cancer, eye diseases, vascular diseases, diabetes and its complications, and cosmetic dermatology. We also highlight the molecular action mechanisms of medicines against these disease, demonstrated using zebrafish embryo. Zebrafish can be pivotal in bridging the gap from lab to clinical bedside. It is used as a model to understand human diseases pathogenies with further scope for drug development. Furthermore, zebrafish can reduce rat and mouse animals in biomedical research.
This study was carried out to investigate the teratological potential of azinphos-methyl in the rat fetuses and to establish the nature of the effects on organogenesis and intrauterine development. The Sprague-Dawley female rats (180-210g) without previous litter were used in this study. Azinphos-methyl dosages of 0.094mg/kg, 0.4mg/kg, 1.5mg/kg were selected based on the acute intragastric $LD_{50}$ of 15mg/kg in the rat. Azinphos-methyl in water (Treatment Group), non-treatment control (Negative Control), water control (Sham Control), were administered by oral route and aqueous solution of acetyl salicylic acid (Positive Control) was administered by gavage at rate of 10 ml/kg of body weight from day 6 through 15. The results obtained were summarized as follows. 1. Decreased body weight of dams was observed in animals treated with aspirin and azinphos-methyl 1.5 mg/kg from day 7 through 14. (P<0.01) 2. There was an apparent decrement in the absolute liver weight in the azinphos-methyl 1.5 mg/kg treated group (P<0.05). However, the absolute and relative kidney weight in aspirin group (P<0.05, P<0.01) and the absolute and relative ovary weight in aspirin, azinphos-methyl treatment groups (P<0.01, P<0.05) were increased. 3. Decreased protein contents of dam's liver was observed in the aspirin and high dose azinphos-methyl treated group of animals (P<0.01). 4. The number of male-female ratio per dam increased in azinphos-methyl 1.5 mg/kg group but there was an apparent decrement in the body weight of fetuses in aspirin and high dose azinphos-methyl group (P<0.01, P<0.05). Total immature and resorbed fetuses were increased in aspirin group and the number of dead fetuses were also increased in azinphos-methyl 1.5mg/kg treated group of animals. (P<0.01, P<0.05). 5. In soft tissue defects, diaphragmatic hernia in diaphragm, anophthalmia, enlarged olfactory bulb, hydrocephalus, absence of third and lateral ventricle in skull, hydronephrosis in kidney, atrophy of left ventricle wall, enlarged apex in heart were observed. Especially, defects of diaphragm, heart and eye ball showed peak incidences in the high dose azinphosmethyl and aspirin group. (P<0.01). 6. Variations in the ossification patterns of skull, sternebrae, tail, forelimbs and hindlimbs showed peak incidences in the aspirin and high dose azinphos-methyl group. (P<0.01). 7. In the developmental indices of offspring, the mortality of aspirin and azinphos-methyl 1.5mg/kg treated group was higher than that of negative control. And, there was an apparent decrement in the body weight of fetuses (P<0.01) and considerable differences were obtained in pivoting, development of fur, auditory function, vision, quadrupled muscle development and testes descent in aspirin and azinphos-methyl 1.5mg/kg group. (P<0.01).
Objectives : The purpose of this study is to investigate Acute and Subacute Toxicity, and Anti-cancer Effect of H Herbal-acupuncture on mice and rats. Methods : Balb/c mice were injected intraperitoneally with H Herbal-acupuncture for $LD_{50}$ and acute toxicity test. Sprague-Dawley rats were experimented in the same way for subacute toxicity test. H Herbal-acupuncture was injected into abdomen of mice having S-180 cancer cell line. Result : 1. During the test, $LD_{50}$ could not be counted since there was no expired subjects. 2. In an acute toxicity test, the loss of motility and reflex action was observed, but weight increased in the treatment group, compared with those in the normal group (P<0.05). 3. In an acute toxicity test of serum biochemical values of mice, glucose increased in the treatment group II while total cholesterol was increased in the all treatment groups (P<0.05). 4. In a subacute toxicity test, a little loss of motility and reflex action was observed in the treatment group. Weight of mice in the treatment group decreased on the 28th day. 5. In a subacute toxicity test, liver weight was decreased but lung weight of mice increased in the all treatment groups (P<0.05). 6. As a result of measuring Complete Blood Count test (CBC) of rat, HCT was decreased in treatments even though it was not significant, compared with the normal group (P<0.05). 7. In a serum biochemical value test of subacute toxicity, total protein and albumin decreased in the all treatment groups. Creatinine, glucose, GOT increased in the treatment group I compared with the control group. Alkaline phos-phatase decreased in treatment II group, compared with the control group (P<0.05). 8. Median survival time that was measured in the rats treated with sarcoma-180 cancer cell Median decreased in the treatment group, compared with the control group (P<0.05). 9. Natural killer cell activity showed significant reduction at 100:1 and 10:1 E/T ratio while it increased at 50:1 E/T ratio. It is inferred that there was an error in the experiment (P<0.05). 10. In an interleukin-2 productivity test, even though it decreased in lung cancer, and increased in abdomen cancer, but it was only a small difference (P<0.005). 11. After injecting B16F10 cell into a capillary vessel of C57BL/6 mice and generating metastasized lung cancer, the lung was examined with the naked eye. It was not possible to see metastasized cancer in the all groups on the seventh day but the cancer was viewed on the fourteenth day. The number and volume of metastasized cancer in the treatment group enlarged in the treatment group, compared with the control group. Conclusion : According to the results, H herbal-acupuncture took no effects in cancer.
Lee, Jin Ho;Ha, In Hyuk;Kim, Me Riong;Kim, Min Jeong;Lee, Jae Woong;Lee, In Hee;Chung, Hwa Jin;Kim, Eun Jee
Journal of Acupuncture Research
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v.32
no.4
/
pp.77-89
/
2015
Objectives : To evaluate the safety of multiple-dose intramuscular Shinbaro Pharmacopuncture in male and female Sprague-Dawley(SD) rats over a period of 4 weeks(12 sessions). Methods : In order to test the safety of multiple-dose intramuscular Shinbaro Pharmacopuncture we used 40 healthy male and female 6-week old SD rats(male weight 171.79~196.37 g, female weight 127.93~146.43 g). Shinbaro Pharmacopuncture was administered intramuscularly to male and female SD rats at doses of 4.6 (low dose group, n=10), 9.2 (moderate dose group, n=10), and 18.5 mg/kg(high dose group, n=10), respectively. General symptoms, body weight changes, blood tests, biochemical testing, necropsy, organ weight and histopathogical findings were examined over a 4-week period. Results : 1. No mortalities or adverse effects were caused by the investigational substance were observed during the study period. 2. There was no significant difference in body weight caused by the the investigational substance across all groups. 3. No significant between-group difference was found to be caused by the investigational substance in blood tests and biochemical testing. 4. No abnormalities were detected by a necropsy examination with the unaided eye at the macro level after treatment with the investigational substance. 5. Difference in organ weight between groups caused by the investigational substance was not found. 6. All groups did not exhibit pathological findings caused by the investigational substance in histopathogical examination. Conclusions : According to these results, Shinbaro Pharmacopuncture has no systemic or organ toxicity with multiple-dose intramuscular administrations in male and female SD rats over a 4-week period (12 sessions). These results imply that no adverse effects are observed at a level (NOAEL) of Shinbaro Pharmacopuncture of 18.5 mg/kg.
DA-6034, a eupatilin derivative of flavonoid, has shown potent effects on the protection of gastric mucosa and induced the increases in fluid and glycoprotein secretion in human and rat corneal and conjunctival cells, suggesting that it might be considered as a drug for the treatment of dry eye. However, whether DA-6034 induces $Ca^{2+}$ signaling and its underlying mechanism in epithelial cells are not known. In the present study, we investigated the mechanism for actions of DA-6034 in $Ca^{2+}$ signaling pathways of the epithelial cells (conjunctival and corneal cells) from human donor eyes and mouse salivary gland epithelial cells. DA-6034 activated $Ca^{2+}$-activated $Cl^-$ channels (CaCCs) and increased intracellular calcium concentrations ($[Ca^{2+}]_i$) in primary cultured human conjunctival cells. DA-6034 also increased $[Ca^{2+}]_i$ in mouse salivary gland cells and human corneal epithelial cells. $[Ca^{2+}]_i$ increase of DA-6034 was dependent on the $Ca^{2+}$ entry from extracellular and $Ca^{2+}$ release from internal $Ca^{2+}$ stores. Interestingly, these effects of DA-6034 were related to ryanodine receptors (RyRs) but not phospholipase C/inositol 1,4,5-triphosphate ($IP_3$) pathway and lysosomal $Ca^{2+}$ stores. These results suggest that DA-6034 induces $Ca^{2+}$ signaling via extracellular $Ca^{2+}$ entry and RyRs-sensitive $Ca^{2+}$ release from internal $Ca^{2+}$ stores in epithelial cells.
The organ distribution and pharmacokinetics of DWP401, a recombinant human epidermal growth factor (rhEGF), were compared after single and repeated subcutaneous administration ( 50${\mu}$/kg, 10${\mu}g$Ci/kg of $^{125}I$-DWP401, twice a day for 7 consecutive days) to rats. The pharmacokinetic parameters such as AUC and terminal half-life were similar between two different administration. During repeated administration, the plasma concentration of DWP401 seemed to be constant when the plasma was collected at 15 min after each dosing. The TCA-precipitated radioactivities in thyroid, liver, kidney, and stomach were higher than those of other organs studied after both single and repeated administration. The TCA-precipitated radioactivities after repeated administration in several organs, such as thyroid, stomach, prostate, adrenal, eye ball, and testis were higher than those after single administration. But, according to the observations using gel filtration chromatography and antibody binding assay, the radioactivities in thyroid and stomach were not primarily due to the intact DWP401 or its metabolites but due to the $^{125}I$-thyroxine binding protein. In conclusion, it can be suggested that DWP401 is metabolized to each amino acid or small polypeptides, and there was no significant changes in pharmacokinetics or any indications for accumulation of DWP401 in rat plasma and organs after repeated treatment.
Kim Eui tae;Oh Seung jae;Baac Hyoung won;Kim Sung june
Journal of Biomedical Engineering Research
/
v.25
no.6
/
pp.611-615
/
2004
A neural prostheses can be designed to permit stimulation of specific sites in the nervous system to restore their functions, lost due to disease or trauma. This study focuses on the feasibility of optoelecronic stimulation into nervous system. Optoelectronic stimulation supplies, power and signal into the implanted optical detector inside the body by optics. It can be effective strategy especially on the retinal prosthesis, because it enables the non-invasive connection between the external source and internal detector through natural optical window 'eye'. Therefore, we designed an effective neural stimulating setup by optically based stimulation. Stimulating on the sciatic nerve of a rat with proper depth probe through optical stimulation needs higher ratio of current spreading through the neural surface, because of high impedance of neural interface. To increase the insertion current spreading into the neuron, we used a parallel low resistance compared to load resistance organic interface and calculated the optimized outer parallel resistance for maximum insertion current with the assumption of limited current by photodiode. Optimized outer parallel resistance was at a range of 500Ω-700Ω and a current was at a level between 580uA and 650uA. Stimulating current efficiency from initial photodiode induced current was between 47.5 and 59.7%. Various amplitude and frequency of the optical stimulation on the sciatic nerve showed the reliable visual tremble, and the action potential was also recorded near the stimulating area. These result demonstrate that optoelectronic stimulation with no bias can be applied to the retinal prosthesis and other neuroprosthetic area.
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