Biomedical subjects
Publications and source records attributed to Insop Shim.
GV01 is one of the most effective acupoints to treat diarrhea in humans and animals. The present study showed that skin on the GV01 acupoint reveals tenderness and neurogenic inflammation in colonic inflammatory states, but not in normal healthy states.
Peripheral nerve injury often results in abnormal neuropathic pain such as allodynia or hyperalgesia. Acupuncture, a traditional Oriental medicine, has been used to relieve pain and related symptoms. However, the efficiency of acupuncture in relieving neuropathic pain is not clear. The aim of this study was to investigate the anti-allodynic effects of acupuncture through behavioral and electrophysiological examinations. Male Sprague-Dawley rats were subjected to neuropathic surgery consisting of a tight ligation and transection of the left tibial and sural nerves, under pentobarbital anesthesia. The acupuncture experiment consisted of four different groups, one treated at each of three different acupoints (Zusanli (ST36), Yinlingquan (SP9), and a sham-acupoint) and a control group. Behavioral tests for mechanical allodynia and cold allodynia were performed for up to two weeks postoperatively. Extracellular electrophysiological recordings were made from the dorsal roots using platinum wire electrodes. Mechanical and cold allodynia were significantly reduced after acupuncture treatment at the Zusanli and Yinlingquan acupoints, respectively. Electrophysiological neural responses to von Frey and acetone tests were also reduced after acupuncture at the same two acupoints. These results suggest that acupuncture may be beneficial in relieving neuropathic pain.
Anti-inflammatory and anti-arthritic effects of water distillates of Ephedra sinica STAPF (ES), in herb-acupuncture, on the inflammatory responses of arthritis was investigated using phorbol 12-myristate 13-acetate (PMA)/lipopolysaccharide (LPS)-induced human macrophage and adjuvant-induced arthritic rat. The luciferase reporter vectors driven by the tumor necrosis factor (TNF)-alpha and cyclooxygenase-2 promoters were transiently transfected into U937 cells, which were then differentiated and stimulated by PMA and LPS, respectively, to develop an in vitro anti-inflammation assay system. The luciferase activities, observed in the activated U937 cells, were significantly inhibited by ES herb-acupuncture, compared to those of PD98509 and berberine. To evaluate ES herb-acupuncture as a novel anti-arthritic therapy, a polyarthritic rat model was developed using heat-killed Mycobacterium tuberculosis, and 50 mul of ES distillate was subcutaneously injected into the ST36 acupoint on each knee joint. While the articular indexes of arthritic rats were evidently decreased by ES herb-acupuncture, their body weights did not regain their initial levels. This may be due to the accelerating effects of ES on weight-loss and fat consumption. The mRNA expressions of TNF-alpha and interleukin (IL)-6 genes, which were closely stimulated in the arthritic rat joints, were found to be restored to the normal levels through the ES treatment. In the case of IL-1beta, the recovery was not significant but substantial. The anti-arthritic effect of ES herb-acupuncture was not found in the ES-treated/non-acupoint group. In conclusion, the ES herb-acupuncture into the ST36 acupoint was found to be effective in alleviating the inflammatory response and thus arthritic symptoms in adjuvant-induced arthritic rats.
The effects of acupuncture and electroacupuncture on an animal model of arthritic pain were examined. Under halothane anesthesia, arthritic pain was induced by the injection of carrageenan into the knee joint cavity of male Sprague-Dawley rats. Behavioral performance was tested before and after the termination of acupuncture or electroacupuncture. Electrophysiologically, the responses of afferents to a movement cycle were recorded before and after acupuncture or electroacupuncture. After the acupuncture procedure, the weight-bearing force of the rats was significantly improved and the neural responses to noxious movement stimulation were reduced. Electroacupuncture significantly improved weight-bearing behavior and inhibited neural responses of articular afferents to noxious stimulation. These results indicate that acupuncture and electroacupuncture may provide a potent strategy in relieving arthritic pain.
The present study investigates the effects of Yukmijihwang-tang Derivatives (YMJd) on learning and memory through the Morris water maze task and the central cholinergic system of rats with excitotoxic medial septum (MS) lesion. In the water maze test, the animals were trained to find a platform in a fixed position for 6 d and then received a 60-s probe trial in which the platform was removed from the pool on the 7th day. Ibotenic lesion of the MS showed the impaired performance in the Morris water maze test and severe cell losses in the MS, as indicated by decreased choline acetyltransferase-immunoreactivity in the medial septum. Daily administrations of YMJd (100 mg/kg, i.p.) for 21 consecutive days produced significant reversals of ibotenic acid-induced deficit in learning and memory. These treatments also reduced the loss of choline acetyltransferase (ChAT) immunoreactivity in the MS induced by ibotenic acid. These results suggest that impairments of spatial learning and memory might be attributable to the degeneration of septohippocampal cholinergic (SHC) neurons and that YMJd treatment ameliorated learning and memory deficits partly due through neuroprotective effects on the central acetylcholine system. Our studies suggest that YMJd might be useful in the treatment of Alzheimer's disease.
Acupoints on the Large Intestine Meridian and specific acupoints related with large intestine have been empirically used to treat large intestinal disease. However, the relationship between acupoints related with large intestine and their functions has not been investigated fully. We investigated whether large intestine-related acupoints affect colonic motility in conscious dogs implanted with electrodes at the proximal colon. Manual acupuncture was applied at the following acupoints: 7 main points on the Large Intestine Meridian (LI1, LI2, LI3, LI4, LI5, LI6, and LI11), ST25, BL25 or GV1. Acupuncture at the Large Intestine Meridian acupoints, ST25 and BL25 had no significant effects on the proximal colonic motility. However, acupuncture at GV1 depressed the proximal colonic motility by decreasing the total duration and the frequency of contractile states, which may contribute to the therapeutic effects of GV1. This study also revealed that there was no clear correlation between Large Intestine Meridian and the proximal colonic motility in conscious dogs.
OBJECT: The purpose of this study was to determine whether subthalamic nucleus (STN) ablation caused by kainic acid can restore dopaminergic neurotransmission and improve motor deficits in a 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian model. METHODS: The authors investigated behavioral changes in rats displaying parkinsonian symptoms (6-OHDA-lesioned rats) after an STN lesion was created using kainic acid. They also measured levels of dopamine and its metabolites following tissue dissection. The results of this study showed that STN ablation led to behavioral improvement in parkinsonian motor deficits. Increased levels of dopamine were also observed in the striatum and globus pallidus externus (GPE). CONCLUSIONS: The results indicate that creation of an STN lesion in this hemiparkinsonian rat model may counteract some of the neurochemical changes within the striatum and GPE caused by the 6-OHDA, and influence striatal dopaminergic metabolism.
Many studies have shown that acupuncture can contribute to the biochemical balance in the central nervous system and maintenance or recovery of homeostasis. It is well known that chronic administration of ethanol may produce depletion or sensitization of extracellular dopamine levels in the nucleus accumbens. The present study was designed to investigate the effects of acupuncture on chronic ethanol-induced changes in extracellular dopamine levels in the nucleus accumbens shell (using in vivo microdialysis in unanesthetized rats). Male Sprague-Dawley rats were treated with 3 g/kg/day of ethanol (20%, w/v) or saline by intraperitoneal injection for 21 days. Following 72 h of ethanol withdrawal, acupuncture was applied at bilateral Shenmen (HT7) points for 1 min. Different group of rats using the same paradigm of ethanol treatment were acupunctured at the same points after the systemic ethanol challenge (3 g/kg, i.p.). Acupuncture at the specific acupoint HT7, but not at control points (PC6 or tail) significantly prevented both a decrease of extracellular dopamine levels in the nucleus accumbens during ethanol withdrawal and an increase in accumbal dopamine levels induced by the ethanol challenge. These results provided strong evidence that stimulation of the specific acupoint HT7 helps to normalize the release of dopamine in the mesolimbic system following chronic ethanol treatment.
Several studies have shown that behavioral hyperactivity induced by psychomotor stimulants is prevented by ginseng saponins. In an attempt to investigate whether the effect of ginseng saponins is through their inhibitory action on the enhanced dopaminergic transmission by psychomotor stimulants, we examined the effects of ginseng total saponin (GTS) presynaptically on nicotine-induced dopamine (DA) release in the striatum of freely moving rats using in vivo microdialysis technique and postsynaptically on the in vitro and in vivo binding of [3H]raclopride to DA D2 receptors. Also, we examined the effects of GTS on nicotine-induced locomotor hyperactivity and on nicotine-induced Fos protein expression in the nucleus accumbens and striatum. Systemic pretreatment with GTS (100 and 400 mg/kg, intraperitoneally (i.p.)) resulted in a dose-dependent inhibition of locomotor hyperactivity induced by nicotine. GTS decreased nicotine-induced DA release in the striatum in a dose-dependent manner. However, GTS had no effects on resting levels of locomotor activity and extracellular DA in the striatum. GTS inhibited the in vitro binding of [3H]raclopride to rat striatal membranes with an IC50 of 5.14+/-1.09 microM. High doses of GTS (400 and 800 mg/kg, i.p.) resulted in decreases in the in vivo binding of [3H]raclopride in the striatum. GTS decreased nicotine-induced Fos protein expression in the nucleus accumbens and striatum, reflecting the inhibition by GTS of nicotine-induced enhancement of dopaminergic transmission. The results of the present study suggest that GTS acts not only on dopaminergic neurons directly or indirectly to prevent nicotine-induced DA release but also postsynaptically by binding to DA D2 receptors. This may explain the blocking effect of GTS on behavioral activation induced by nicotine and conceivably by other psychostimulants. Our data raise the possibility that GTS, by attenuating nicotine-induced enhancement of dopaminergic transmission, may prove to be a useful therapeutic agent for nicotine addiction and warrant further investigation on its effect on nicotine's rewarding property.
Acupuncture as a therapeutic intervention has been used for the treatment of many functional disorders including substance abuse. However, there are still many unanswered question about the basic mechanism underlying acupuncture's effectiveness in the treatment of drug addiction. Repeated injection of psycostimulants or morphine can produce behavioral and neurochemical sensitization and have been used as a model for studying drug addiction. The present study was designed to investigate the effect of acupuncture on repeated morphine-induced changes in extracellular dopamine levels using in vivo microdialysis and repeated morphine-induced behavioral changes. Male Sprague-Dawley rats were treated with saline or increasing doses of morphine (10, 20 and 40 mg/kg, s.c., twice daily for 3 days). Following 15 days of withdrawal, acupuncture was applied at bilateral Shenmen (HT7) points for 1 min after the systemic challenge with morphine HCl (5 mg/kg, s.c.). Results showed that acupuncture at the specific acupoint HT7, but not at control points (TE8 and tail) significantly decreased both dopamine release in the nucleus accumbens and behavioral hyperactivity induced by a systemic morphine challenge. These results suggest that the therapeutic effect of acupuncture on morphine addiction occurs through inhibition of neurochemical and behavioral sensitization to morphine.
Oriental medicine uses acupuncture at the GV01 acupoint with great success to treat diarrhea. It significantly reduced the colonic motility and inflammation in colitic rats. Naloxone pretreatment blocked these effects. The therapeutic effects of acupuncture at GV01 in colitis may involve endogenous opioid pathways.
To investigate the effects of repeated immobilization-stress challenge on HPA axis, genomic transcriptome in the hypothalamus of immobilization-stressed mouse was analyzed by using cDNA microarray. With the 1.5-fold cutoff of arbitrary criteria, the expression levels of 108 genes out of 6016 genes were significantly modulated in the hypothalamus by the stress. Energy metabolism-, lipid metabolism-, and apoptosis- and signal transduction-related genes were activated while DNA repair-, protein biosynthesis-, and structure integrity-related genes were down-regulated in the hypothalamus. Eighteen genes among them were selected for RT-PCR analysis to confirm the change of their expression levels on agarose gels. Besides, dozens of novel genes, which have not been previously reported, were screened to be modulated by the immobilization stress through the transcriptome analysis. These genes are related to apoptosis, tumor-suppression, DNA-binding and protein folding, and thus may be used as potential targets for the development of therapeutics of chronic stress or depressant.
The anti-obesity effects of crude saponin (CS) of Korean red ginseng (KRG) were investigated in the rat fed a high-fat (HF) diet. Male Sprague-Dawley (SD) rats became obese by feeding the HF diet over 5 weeks, while the control rats were fed a normal diet, and then both groups were treated with CS (200 mg/kg, i.p.) for 3 weeks. The body weight, food consumption, adipose tissues, and expression of appetite peptides such as leptin and neuropeptide Y (NPY) were investigated in rats fed normal and HF diet after treatment of CS. Administration of CS reduced body weight, food intake, and fat content in HF diet rats in a manner similar to those of the normal diet fed rats. The hypothalamic NPY expression and serum leptin level were reduced in HF diet rats after CS treatment. Our results suggest that CS may be useful in the treatment of obesity and related disorders as anti-obesity agents.
Through the proteomic analysis using 2-dimensional electrophoresis, the nicotine addiction-associated proteins were extensively screened in the striatum of rat brains. The nicotine addiction was developed by repeated nicotine injection (0.4mg/kg s.c.), twice daily for 7 days, followed by one challenge injection after a 3 day withdrawal period, and then confirmed by observing a 2.3-fold increase in locomoter activity. The 3 up- and 4 down-regulated proteins were selected and identified to be zinc-finger binding protein-89 (ZBP-89), 2'3'-cyclic nucleotide 3'-phosphodiesterase 1, deoxyribonuclease 1-like 3 (DNase1l3), tandem pore domain halothane inhibited K(+) channel (THIK-2), brain-specific hyaluronan-binding protein (BRAL-1), death effector domain-containing DNA binding protein (DEDD), and brain-derived neurotrophic factor (BDNF) by mass spectrophotometric fingerprinting. Among them, the expression patterns of ZEB-89, DNase1l3, THIK-2, DEDD, and BDNF mRNAs were found to be coincident with those of cognate proteins, by using RT-PCR analysis. These proteins could be suggested as drug targets to develop a new therapy for nicotine-associated diseases, as well as the clues to understand the mechanism of nicotine.
Recent studies have suggested that maternally deprived rats exhibit anxiogenic-like behavior when exposed to stress in later life. Neuropeptide Y (NPY) is involved in the regulation of various physiological functions such as the expression of anxiety. Female Wistar rat pups were separated from their mothers for 3h daily from postnatal days 3 (P3) to 14 (P14). Acupuncture groups were treated with acupuncture at Shenmen (HT7) or Zusanli (ST36) on alternate days from P50 to P62. Their anxiety-like behavior was evaluated using an elevated plus-maze at P62, and then NPY immunohistochemistry in the basolateral amygdala (BLA) was performed. Rats exposed to maternal separation (MS) were less likely to explore the open arms of the plus-maze compared to control rats that were not exposed to MS. Among maternally separated groups, the percentage of time spent in the open arms was significantly increased in the HT7 acupuncture group, but not the ST36 acupuncture group, compared to MS group. In accordance with this behavior, the numbers of NPY-immunoreactive cells in the BLA were lower in the MS group compared to the control group. Among maternally separated groups, the numbers of NPY-immunoreactive cells in the BLA were significantly higher in the HT7 acupuncture group, but not higher in the ST36 acupuncture group, compared to MS group. These findings suggest that acupuncture treatment might reduce anxiety-like behavior in adult rats following maternal separation by modulating the NPY system in the amygdala.
Acupuncture as a therapeutic intervention is widely practiced in the treatment of many functional disorders including alcohol abuse. In the present study, the effects of acupuncture on alcohol withdrawal syndrome (AWS) and Fos-like immunoreactivity (FLI) in the striatum and the nucleus accumbens (NAC) of rats were investigated. During 3 days of cessation following chronic administration of ethanol (3 g/kg, i.p. for 3 weeks), rats showed a significant increase in AWS, such as hypermotility, tail rigidity, grooming and tremor, and an increase in FLI in the dopamine terminal areas of the brain. Treatment with acupuncture at zusanli (ST36) or sanyinjiao (SP6) during the withdrawal period inhibited both AWS and FLI of rats undergoing ethanol injection. These results suggest that acupuncture may be useful in the treatment of alcoholism by modulating post-synaptic neural activation in the striatum and NAC.
Depression is associated with a dysfunctional serotonin system. Recently, several lines of evidence have suggested that a very important evoking factor in depression may be a serotonin deficit in the hippocampus. This study assessed the antidepression effects of Nelumbinis Semen (NS) through increasing serotonin concentrations under normal conditions and reversing a decrease in serotonin concentrations in rat hippo-campus with depression-like symptoms induced by chronic mild stress (CMS). Using an in-vivo microdialysis technique, the serotonin-enhancing effect of NS on rat hippocampus was investigated and its effects compared with those of two well-known antidepressants, Hypericum perforatum (St John's wort) and fluoxetine (Prozac). Rats were divided into five groups: saline-treated normal, without CMS; saline-treated stress control; NS-, St John's wort- and fluoxetine-treated rats under CMS for 8 weeks or no stress treatment. NS and fluoxetine significantly increased serotonin in normal conditions and reversed a CMS-induced decrease in serotonin release in the hippocampus (P<0.05 compared with normal group or control group under CMS). These results suggest that NS increases the serotonin levels normally decreased in depression, resulting in an enhancement of central serotonergic transmission and possible therapeutic action in depression. It is suggested that NS may present an antidepressant effect through enhancement of serotonin.
Behavioral sensitization, as evidenced by the progressive enhanced locomotor response to a subsequent injection of the drug, is the major behavioral outcome produced by repeated injections of nicotine, and a model for studying drug addiction. It is putatively regarded that the alteration of extracellular dopamine release in the nucleus accumbens is closely associated with nicotine-induced behavioral sensitization. The present study was performed to evaluate the effects of the essential oil from Angelica gigas NAKAI (on fragrance inhalation) on repeated nicotine-induced locomotor activity and extracellular dopamine levels in the nucleus accumbens of rats using in vivo microdialysis. Rats were given repeated injections of saline or nicotine (0.4 mg/kg s.c., twice a day for 7 d), followed by one challenge injection on the 4th day after the last daily injection. Systemic challenge with nicotine (0.4 mg/kg s.c.) produced a larger increase in locomotor activity in nicotine-pretreated rats than in saline-pretreated rats. A direct local challenge of 3 mM nicotine via a microdialysis probe also induced a larger increase in dopamine release in nicotine-pretreated rats than in saline-pretreated rats. Most importantly, our results showed that inhalation of the essential oils from Angelica gigas NAKAI significantly decreased both dopamine release in the nucleus accumbens and locomotor activity induced by a nicotine challenge. These results suggest that the essential oils from Angelica gigas NAKAI inhibit nicotine-induced behavioral and neurochemical sensitization, and imply that the essential oil from Angelica gigas NAKAI may be effective in treating nicotine addiction, possibly by modulating dopamine release in the nucleus accumbens.