• Journal of Acupuncture Research
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• v.22 no.5
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• pp.67-77
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• 2005

Objectives : The purpose of this study is to examine if Bee Venom Acupuncture may be effective to the neuropathic pain(mechanical allodynia, cold allodynia) in a rat model of neuropathic pain. Methods : To produce the model of neuropathic pain, under isoflurane 2.5% anesthesia, tibial nerve and sural nerve was resected. After the neuropathic surgery, the author examined if the animals exhibited the behavioral signs of alloynia. The allodynia was assessed by stimulating the medial malleolus with von Frey filament and acetone. Three weeks after the neuropathic surgery, Bee Venom Acupuncture was injected at Hwando(GB30) one time a day for one week. After that, the author examined the withdrawl response of neuropathic rats' legs by yon Frey filament and acetone stimulation. And also the author examined c-Fos in the midbrain central gray of neuropathic rats and the change of WBC count in the blood of neuropathic rats. Results : The Bee Venom Acupuncture injected Hwando(GB30) decreased the withdrawl response of mechanical allodynia in BV-2, BV-3 group as compared with control group. The Bee Venom Acupuncture injected Hwando(GB30) decreased the withdrawl response of chemical allodynia(cold allodynia) in BV-2, BV-3 group as compared with control group. The Bee Venom Acupuncture injected Hwando(GB30) showed the significant difference between control group and BV-2 group, control group and BV-3 group in the c-Fos expression and U count. Conclusion : We have noticed that Bee Venom Acupuncture at Hwando(GB30) decreased mechanical allodynia and cold allodynia in the model of neuropathic pain compared with the control group. C-Fos expression in the central gray of that group was also decreased compared with the control group. Psin control using Bee Venom Acupuncture was accumulated as time goes by. This study can be used as a basic resource on a study and a treatment of pain.

• Journal of Acupuncture Research
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• v.32 no.3
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• pp.69-81
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• 2015

Purpose : The first purpose of this study is to find out whether the water extract of Rehmanniae Radix Preparat(RRP), Cuscutae Semen(CS) and their combination(Ssangbohwan, SBH) have the effect of suppressing Receptor activator of nuclear factor kappa-B ligand(RANKL)-induced osteoclast differentiation. The second purpose of this study is to find out whether the water extract of RRP, CS and SBH have the effect of inhibiting osteoporosis in an osteoporosis model induced by lipopolysaccharide(LPS). Methods : After promoting differentiation of osteoclasts by treating the RANKL, we observed the effect by the administration of RRP, CS and SBH. In addition, by means of Reverse transcription polymerase chain reaction(RT-PCR), we assayed mRNA expression levels of NFATc1, c-Fos, TRAP and GAPDHS(Glyceraldehyde-3-phosphate dehydrogenase, spermatogeni) from bone marrow macrophages(BMMs). Similarly, the protein expression levels of NFATc1 (Nuclear factor of activated T-cells, cytoplasmic1), C-Fos, MAPKs(Mitogen-activated protein kinases) and ${\beta}$-actin in cell lysates were analyzed by means of Western Blotting. Finally, we determined the anti-osteoporotic effects of RRP, CS and SBH, through the use of Lipopolysaccharide-induced bone-loss mouse. Results : RRP, CS and SBH showed remarkable inhibitive effect on RANKL-treated osteoclast differentiation without cytotoxicity. SBH inhibited the phosphorylation of p38, Jun N-terminal kinases(JNK), and I-${\kappa}B$ and down-regulated the induction of c-Fos and NFATc1 by RANKL. RRP, CS suppressed degradation of I-${\kappa}B$, but it did not affect c-Fos and NFATc1 by RANKL. Lastly, in vivo data showed that RRP and SBH prevented bone erosion by LPS treatment. Conclusions : These results demonstrate SBH can be effective remedy for bone-loss diseases such as osteoporosis.

• Korean Journal of Acupuncture
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• v.28 no.2
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• pp.37-47
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• 2011

Objectives : We have studied the effects of GaAlAs (808 nm) low level laser therapy (LLLT) and acupuncture at BL40 on neuropathic pain in rats induced by lumbar spinal nerve 5 ligation. Methods : To produce the model of neuropathic pain, under isoflurane 2.5% anesthesia, the lumbar spinal nerve 5 was ligated by 6-0 silk thread. After neuropathic surgery, we examined if the animals exhibited the behavioral sign of allodynia. The allodynia was assessed by stimulating the medial malleolus with von Frey filament and acetone. Three weeks after the neuropathic surgery, GaAlAs (808 nm) low level laser and acupuncture was inserted at BL40 once a day for 6 days. We examined the withdrawal response of neuropathic rats' legs by von Frey filament and acetone stimulation. And also the author examined c-Fos, nociceptin and nociceptin receptor in the midbrain central gray of neuropathic rats. Results : The GaAlAs (808 nm) low level laser therapy and acupuncture at BL40 decreased the withdrawal response of mechanical allodynia that assessed with von Frey filament in LLLT group on 5 and 6 times and with acetone in AT group and LLLT on 6times. The LLLT and acupuncture at BL40 decreased the c-Fos protein expression in AT and LLLT groups. The 808 nm LLLT and acupuncture at BL40 decreased the nociceptin protein and nociceptin receptor protein in LLLT group. Conclusions : We have noticed that GaAlAs (808 nm) LLLT and acupuncture at BL40 decreased mechanical allodynia in the model of neuropathic pain. c-Fos, nociceptin and nociceptin receptor expression in the central gray of that group was also decreased. This study can be used as a basic resource on a study and a treatment of pain.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.2
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• pp.159-170
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• 2011

Objectives : We have studied to know analgesic effects of the combination of Aconitum Cilliare Tuber with honey in the models of peripheral neuropathic pain. Methods : Neuropathic pain model was made by ligating left 5th lumbar spinal nerve. After 3 days, combination of Aconitum Ciliare Tuber and honey extract was administrated each alternate day. Administration was divided three groups, that is NP-OA1(0.06 mg/ml), NP-OA2(0.24 mg/ml), and NO-OA3(0.96 mg/ml). After that, we examined the withdrawl response of neuropathic rats legs by von Frey filament and acetone stimulation. And also we examined c-Fos, glutamic oxaloacetic transaminase(GOT), glutamate-pyruvate transaminase(GPT) and change of weight. Results : Mechanical allodynia in NP-OA1 groups were significantly decreased compared with the control group. Cold allodynia in all experimental groups were no significant differences with the control group. c-Fos protein expression on the central grey, all experimental groups were lower than that of control groups. But, there were no statistically significant differences. Change of weight in all experimental groups were significantly increased compare with the control group. In blood serum GOT in NP-OA1, NP-OA2 groups were significantly decreased compare with the control group. In blood serum GPT in all experimental groups were no significant difference with the control group. Conclusions : We had noticed that the combination of Aconitum Ciliare Tuber and honey decreased mechanical allodynia in the model of neuropathic pain compared with the control group and it has not efficacy in elevation of GOT, GPT and weight loss etc., the element of which becomes damage to liver. This study can be proposed that Aconitum Ciliare with Honey may be applicable to neuropathic pain in clinic. But it is reliability not that cold allodynia and c-Fos expression have effectively to control pain. Therefore we have to follow up about that.

• Journal of Korean Medicine Rehabilitation
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• v.20 no.2
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• pp.1-15
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• 2010

Objectives : This study was performed to evaluate the effects of root of Cibotii rhizoma(CR) ethanol extract on the tissue and neuronal damage of the spinal cord injury(SCI). Methods : SCI was induced by mechanical contusion following laminectomy of 10th thoracic vertebra in Sprague-Dawley rats. CR was orally given once a day for 7 days after SCI. Tissue damage and nerve fiber degeneration were examined with cresyl violet and luxol fast blue(LFS) histochemistry. HSP72(as neuronal damage marker), MAP2(as nerve fiber degeneration marker), c-Fos(immediate early gene), and Bax(pro-apoptotic molecule) expressions were examined using immuno-histochemistry. Individual immuno-positive cells expressing HSP72, MAP2, c-Fos and Bax were observed on the damaged level and the upper thoracic and lower lumbar spinal segments. Results : 1. CR reduced degeneration of nerve fibers and motor neuron shrinkage in the ventral horn of the lower lumbar spinal segment, but generally it did not seem to ameliorate the tissue injury following SCI. 2. CR reduced demyelination in the ventral and lateral funiculus of the lower lumbar spinal segment. 3. CR reduced HSP72 expression on the neurons in the peri-central canal gray matter adjacent to the damaged region. 4. CR strengthened MAP2 expression on the motor neurons in the ventral horn and on nerve fibers in the lateral funiculus of the lower lumbar spinal segment. 5. CR reduced c-Fos positive cells in the peri-lesion and the dorsal horn of the damaged level and in the ventral horn of the lower lumbar spinal segment. 6. CR reduced Bax positive cells in the peri-lesion and the dorsal horn of the damaged level and in the ventral horn of the lower lumbar spinal segment. Conclusions : These results suggest that CR plays an inhibitory role against secondary neuronal damage and nerve fiber degeneration. following SCI.

• The Journal of Internal Korean Medicine
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• v.25 no.4
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• pp.324-336
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• 2004

Objectives : The purpose of this investigation is to evaluate the effects of Scutellaria baicalensis GEORGI on alteration in gene expression in a hypoxia model using cultured rat cortical cells. Methods : E18 rat cortical cells were grown in a Neurobasal medium containing B27 supplement. On 12 DIV, Scutellaria baicalensis GEORGI(20 ug/ml) was added to the culture media and left for 24 hrs. On 11 DIV, cells were given a hypoxic insult $(2%\;O_2/5%\;CO_2,\;37^{\circ}C,\;3\;hrs)$, returned to normoxia and cultured for another 24 hrs. Total RNA was prepared from Scutellaria baicalensis GEORGI-untreated (control) and -treated cultures and alteration in gene expression was analysed by microarray using rat 5K-TwinChips. Results : For most of the genes altered in expression, the Global M values were between -0.5 to +0.5. Among these, 1143 genes increased in their expression by more than Global M +0.1, while 1161 genes decreased by more than Global M -0.1. Effects on some of the genes whose functions are implicated in neural viability are as follows: 1) The expression of apoptosis-related genes such as Bad (Global M = 0.39), programmed cell death-2(Pdcd2) (Global M = 0.20) increased, while Purinergic receptor P2X(P2rxl) Global M = -0.22), Bc12-like1(Bc1211)(Global M = -0.19) decreased. 2) The expression of 'response to stress-related genes such as antioxidation-related AMP-activated protein kinase subunit gamma 1 gene (Prkag1) (Global M = 0.14), catalase gene (Global M = 0.14) and Heme Oxygenase(Hmoxl) increased. 3) The expression of Fos like antigen 2 (Fos12) expressed in neurons that survive ischemic insult increased (Global M = 0.97). Conclusions : these data suggest that Scutellaria baicalensis GEORGI increases the expression of antiapoptosis- and antioxidation- related genes in a way that can not yet be explained.

• Journal of Physiology & Pathology in Korean Medicine
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• v.32 no.1
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• pp.35-42
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• 2018

TRPA1 and TRPV1 are members of the TRP superfamily of structurally related, nonselective cation channels. TRPA1 and TRPV1 are often co-expressed in sensory neurons and play an important role in mechanical hyperalgesia and allodynia during neuropathic pain. Scutellariae Radix was reported to possess anti-inflammation properties and similar patterns of therapeutic action against different diseases. also Baicalin(a known principal constituent of Scutellaria Radix) was shown to down-regulate the mRNA expression levels of TRPV1. In this study, we observed the effects of Scutellariae Radix extract(SRE) in neuropathic pain induced SD rats via modulation of TRPV1 and TRPA1. Oral administration of a Scutellaria Radix extract(in doses of 300mg/kg, SRE(300)) showed a meaningful increase in the withdrawal threshold of mechanical allodynia and showed a meaningful decrease in the expression of c-fos compared to the control group. SRE(100) and SRE(300) showed a meaningful decrease in the expression of TRPV1 level compared to the control group. These results suggest that Scutellariae Radix extract could decrease mechanical allodynia by down-regulate the TRPV1 on the model of neuropathic pain.

• Korean Journal of Acupuncture
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• v.23 no.3
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• pp.55-71
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• 2006

Objectives : The present study was investigated the effect and pathway of heterotopic electroacupuncture (EA) on pain induced by formalin in rats. Methods : Acupoints in the right forepaws, $HT_7$ and $PC_7$, were stimulated with 3 mA, 2 ms, and 10 Hz before subcutaneously formalin injection (5%, $50{\mu}l$) to the left hind paw. Moreover, it was investigated whether the dorsolateral funiculus (DLF), as known to the descending inhibition, mediates analgesia of the heterotopic EA, and an administration of naltrexone blocks the effect of EA. Results : In the immunohistochemistry of cFos-like protein (cFL), there were inhibitory effects of EA on the increased expression of cFL in the lumbar spinal dorsal horn neurons following formalin injection. Especially, EA inhibited the expression of cFL on the superficial laminae than that on the deep laminae at 1 hr after, but that on the deep laminae than that on the superficial laminae at 2 hr after. Also, EA suppressed the increased expression of nitric oxide (NO) and neuronal nitric oxide synthase (nNOS) in the lumbosacral spinal cord after formalin injection, but not Sham-EA. Suppressed expressions of cFL, NO and nNOS in the spinal cord were eliminated after transection of the ipsilateral DLF at $T_{10}{\sim}T_{11}$ levels. However, pretreatment of naltrexone could not prevent the suppressive expressions of cFL, NO and nNOS at the spinal cord. Conclusions : These results suggest that the analgesia of heterotopic EA may be modulated through the DLF constituting the descending inhibition.

• Journal of Physiology & Pathology in Korean Medicine
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• v.29 no.1
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• pp.51-57
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• 2015

Bone destruction is a pathological symptom of some chronic inflammatory diseases, such as rheumatoid arthritis and periodontitis. Inflammation-induced bone loss of these diseases results from increased number and activity of osteoclasts. Paeoniae Radix Alba has been used in korean traditional medicine to treat disease including inflammation, gynecopathy and various pain. However, these effects have not been tested on osteoclasts, the bone resorbing cells that regulate bone metabolism. Here, we investigated the effects of Paeoniae Radix Alba ethanol extract (PRAE) on receptor activator of nuclear factor-kappa B ligand (RANKL)-mediated osteoclast differentiation and formation. Osteoclast differentiation and formation were measured by tartrate resistant acidic phosphatase (TRAP) staining and TRAP solution assay. The treatment of PRAE on bone marrow derived macrophages (BMMs), which is known as osteoclast precursor cells, inhibited osteoclast differentiation and formation in a dose-dependent manner. In addition, the expression of osteoclast differentiation marker genes was suppressed by PRAE treatment. This inhibitory effect of PRAE resulted from significant repression of c-Fos expression, and subsequent reduction of NFATc1 expression which was previously reported as a master transcription factor for osteoclastogenesis in vitro and in vivo. These results demonstrate that PRAE negatively regulates osteoclast differentiation and formation and suggest that PRAE can be used as a potent preventive or therapeutic candidate for various bone diseases, such as postmenopausal osteoporosis, periodontitis and rheumatoid arthritis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.11
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• pp.1648-1657
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• 2014

In this study, the hepatic lipid-lowering effects and related mechanism of action of sujeonggwa were examined in hypercholesterolemia-induced apoprotein E knockout (apo E ko) mice. Sujeonggwa drink was prepared with cinnamon, ginger, and sugar by modifying the traditional recipe of sujeonggwa. Sugar was partially substituted with either stevia or short chain fructooligosaccharide (scFOS) in order to reduce the calorie content of sujeonggwa, which was measured by descriptive analysis. Apo E ko mice (n=42) were induced to have hypercholesterolemia (plasma total cholesterol concentration >1,000 mg/dL) by administration of a high cholesterol diet for 4 weeks, followed by division into six groups. Experimental groups were orally administered water as a vehicle (normal group), sugar solution (control group), commercially available 'V' sujeonggwa drink (positive control group), or three different types of sujeonggwa drinks (S-sugar, S-stevia, and S-scFOS group) for 6 weeks while high cholesterol diet was provided to all animals. Compared to the control group, concentrations of hepatic triglycerides, total cholesterol, thiobarbituric acid reactive substances, and reactive oxygen species in S-sugar, S-stevia, S-scFOS were significantly reduced (P<0.05), indicating that sujeonggwa had inhibitory effects on hepatic lipid accumulation. Protein expression levels of fatty acid synthase (FAS) and its transcription factor, sterol regulatory element-binding protein (SREBP)-1 responsible for triglyceride synthesis, as well as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and its transcription factor, SREBP-2 responsible for cholesterol synthesis, were also reduced in S-sugar, S-stevia, and S-scFOS groups (P<0.05). These benefits of sujeonggwa were even greater in S-stevia and S-scFOS compared to S-sugar. The beneficial effects of S-stevia on regulation of hepatic lipid metabolism were slightly greater than those of S-scFOS although the differences were not significant. In conclusion, sujeonggwa drinks, especially functional sujeonggwa drinks in which sugar was partially substituted with stevia or scFOS, inhibited hepatic lipid accumulation via suppressing FAS and HMGCR protein expression through down-regulation of SREBP-1 and 2.