Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice.

Oxaliplatin, a chemotherapeutic drug for colorectal cancer, induces severe peripheral neuropathy. Bee venom acupuncture (BVA) has been used to attenuate pain, and its effect is known to be mediated by spinal noradrenergic and serotonergic receptors. Morphine is a well-known opioid used to treat different types of pain. Here, we investigated whether treatment with a combination of these two agents has an additive effect on oxaliplatin-induced neuropathic pain in mice. To assess cold and mechanical allodynia, acetone and von Frey filament tests were used, respectively. Significant allodynia signs were observed three days after an oxaliplatin injection (6 mg/kg, i.p.). BVA (0.25, 1, and 2.5 mg/kg, s.c., ST36) or morphine (0.5, 2, and 5 mg/kg, i.p.) alone showed dose-dependent anti-allodynic effects. The combination of BVA and morphine at intermediate doses showed a greater and longer effect than either BVA or morphine alone at the highest dose. Intrathecal pretreatment with the opioidergic (naloxone, 20 µg) or 5-HT3 (MDL-72222, 15 µg) receptor antagonist, but not with α2 adrenergic (idazoxan, 10 µg) receptor antagonist, blocked this additive effect. Therefore, we suggest that the combination effect of BVA and morphine is mediated by spinal opioidergic and 5-HT3 receptors and this combination has a robust and enduring analgesic action against oxaliplatin-induced neuropathic pain.

Traditional herbal medicine as adjunctive therapy for breast cancer: A systematic review.

OBJECTIVES: To assess the effectiveness of traditional herbal medicine (THM) as adjunctive therapy for breast cancer as evidenced by randomized controlled trials (RCTs). METHODS: Five electronic English and Chinese databases were systematically searched up to February, 2014. All RCTs involving THM in combination with conventional cancer therapy for breast cancer were included. RESULTS: Eight RCTs involving 798 breast cancer patients were systematically reviewed. Three studies reported a significant difference in the improvement of quality of life (QOL) compared to the control group. Two studies reported an increase in the white blood cell count after treatment. Data on hot flashes and sleep quality were evaluated. However, no significant differences in immediate tumor response were observed. CONCLUSION: THM combined with conventional therapy in the treatment of breast cancer is efficacious in improving QOL and in decreasing the number of hot flashes per day. More research and well-designed, rigorous, large clinical trials are necessary to further address these issues.

Traditional herbal medicine for cancer pain: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of traditional herbal medicine (THM) as an adjunctive therapy for cancer pain is unclear. OBJECTIVE: To assess the effectiveness of THM as an adjunctive therapy for cancer pain using randomized controlled trials (RCTs). METHODS: Five electronic databases, including those from the UK and China, were systematically searched for the period before September 2013. All RCTs involving the use of THM in combination with conventional cancer therapy for cancer pain were included. RESULTS: Twenty-four RCTs involving 4889 patients with cancer pain were systematically reviewed. Among them, nine studies of 952 patients reported a significant decrease in the number of patients with cancer pain in the treatment group. Four studies of 1696 patients reported a significant decrease in the degree of pain in the treatment group. CONCLUSION: The results of these studies suggest that THM combined with conventional therapy is efficacious as an adjunctive therapy for patients with cancer pain. However, more research, including well-designed, rigorous, and larger clinical trials, are necessary to address these issues.

Traditional herbal medicine as adjunctive therapy for nasopharyngeal cancer: a systematic review and meta-analysis.

The effectiveness of traditional herbal medicine (THM) as treatment for nasopharyngeal cancer (NPC) has not been clearly demonstrated. The aim of this study is to assess the effectiveness of THM as adjunctive therapies for NPC using the results of randomized controlled trials (RCTs). Five electronic databases, including English and Chinese databases, were systematically searched up to February 2014. All RCTs involving traditional herbal medicine in combination with conventional cancer therapy for NPC were included. Twenty-two RCTs involving 2,298 NPC patients were systematically reviewed. Of these 22 studies, 15 on 1482 patients reported a significant increase in the number surviving patients with survivals of more than 1, 3, or 5 years. Seven studies on 595 patients reported a significant increase in immediate tumor response, and three studies on 505 patients reported a significant decrease in distant metastasis. This meta-analysis of 22 studies suggests that THM combined with conventional therapy can provide an effective adjunctive therapy for NPC. More research and well-designed, rigorous, large clinical trials are required to address these issues.

Serotonergic mechanism of the relieving effect of bee venom acupuncture on oxaliplatin-induced neuropathic cold allodynia in rats.

BACKGROUND: Oxaliplatin, an important chemotherapy drug for advanced colorectal cancer, often induces peripheral neuropathy, especially cold allodynia. Our previous study showed that bee venom acupuncture (BVA), which has been traditionally used in Korea to treat various pain symptoms, potently relieves oxaliplatin-induced cold allodynia in rats. However, the mechanism for this anti-allodynic effect of BVA remains poorly understood. We investigated whether and how the central serotonergic system, a well-known pathway for acupuncture analgesia, mediates the relieving effect of BVA on cold allodynia in oxaliplatin-injected rats. METHODS: The behavioral signs of cold allodynia in Sprague-Dawley (SD) rats were induced by a single injection of oxaliplatin (6 mg/kg, i.p.). Before and after BVA treatment, the cold allodynia signs were evaluated by immersing the rat's tail into cold water (4°C) and measuring the withdrawal latency. For BVA treatment, a diluted BV (0.25 mg/kg) was subcutaneously administered into Yaoyangguan (GV3) acupoint, which is located between the spinous processes of the fourth and the fifth lumbar vertebra. Serotonin was depleted by a daily injection of DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.) for 3 days. The amount of serotonin in the spinal cord was measured by ELISA. Serotonergic receptor antagonists were administered intraperitoneally or intrathecally before BVA treatment. RESULTS: The serotonin levels in the spinal cord were significantly increased by BVA treatment and such increase was significantly reduced by PCPA. This PCPA pretreatment abolished the relieving effect of BVA on oxaliplatin-induced cold allodynia. Either of methysergide (mixed 5-HT1/5-HT2 receptor antagonist, 1 mg/kg, i.p.) or MDL-72222 (5-HT3 receptor antagonist, 1 mg/kg, i.p) blocked the anti-allodynic effect of BVA. Further, an intrathecal injection of MDL-72222 (12 µg) completely blocked the BVA-induced anti-allodynic action, whereas NAN-190 (5-HT1A receptor antagonist, 15 µg, i.t.) or ketanserin (5-HT2A receptor antagonist, 30 µg, i.t.) did not. CONCLUSIONS: These results suggest that BVA treatment alleviates oxaliplatin-induced acute cold allodynia in rats via activation of the serotonergic system, especially spinal 5-HT3 receptors. Thus, our findings may provide a clinically useful evidence for the application of BVA as an alternative therapeutic option for the management of peripheral neuropathy, a dose-limiting side effect that occurs after an administration of oxaliplatin.

Gyejigachulbu-Tang Relieves Oxaliplatin-Induced Neuropathic Cold and Mechanical Hypersensitivity in Rats via the Suppression of Spinal Glial Activation.

Activation of spinal glial cells plays a crucial role in the pathogenesis of neuropathic pain. An administration of oxaliplatin, an important anticancer drug, often induces acute neuropathic cold hypersensitivity and/or mechanical hypersensitivity in patients. Gyejigachulbu-tang (GBT), a herbal formula comprising Cinnamomi Cortex, Paeoniae Radix, Atractylodis Lanceae Rhizoma, Zizyphi Fructus, Glycyrrhizae Radix, Zingiberis Rhizoma, and Aconiti Tuber, has been used in East Asia to treat various pain symptoms, especially in cold patients. This study investigated whether and how GBT alleviates oxaliplatin-induced cold and mechanical hypersensitivity in rats. The behavioral signs of cold and mechanical hypersensitivity were evaluated by a tail immersion test in cold water (4°C) and a von Frey hair test, respectively. The significant cold and mechanical hypersensitivity were observed 3 days after an oxaliplatin injection (6 mg/kg, i.p.). Daily oral administration of GBT (200, 400, and 600 mg/kg) for 5 days markedly attenuated cold and mechanical hypersensitivity. Immunoreactivities of glial fibrillary acidic protein (GFAP, astrocyte marker) and OX-42 (microglia marker) in the spinal dorsal horn were significantly increased by an oxaliplatin injection, which were restored by GBT administration. These results indicate that GBT relieves oxaliplatin-induced cold and mechanical hypersensitivity in rats possibly through the suppression of spinal glial activation.

Efficacy of acupuncture in reducing preoperative anxiety: a meta-analysis.

Background. Acupuncture has been shown to reduce preoperative anxiety in several previous randomized controlled trials (RCTs). In order to assess the preoperative anxiolytic efficacy of acupuncture therapy, this study conducted a meta-analysis of an array of appropriate studies. Methods. Four electronic databases (MEDLINE, EMBASE, CENTRAL, and CINAHL) were searched up to February 2014. In the meta-analysis data were included from RCT studies in which groups receiving preoperative acupuncture treatment were compared with control groups receiving a placebo for anxiety. Results. Fourteen publications (N = 1,034) were included. Six publications, using the State-Trait Anxiety Inventory-State (STAI-S), reported that acupuncture interventions led to greater reductions in preoperative anxiety relative to sham acupuncture (mean difference = 5.63, P < .00001, 95% CI [4.14, 7.11]). Further eight publications, employing visual analogue scales (VAS), also indicated significant differences in preoperative anxiety amelioration between acupuncture and sham acupuncture (mean difference = 19.23, P < .00001, 95% CI [16.34, 22.12]). Conclusions. Acupuncture therapy aiming at reducing preoperative anxiety has a statistically significant effect relative to placebo or nontreatment conditions. Well-designed and rigorous studies that employ large sample sizes are necessary to corroborate this finding.

Expression levels of the hypothalamic AMPK gene determines the responsiveness of the rats to electroacupuncture-induced analgesia.

BACKGROUND: Although electroacupuncture (EA) relieves various types of pain, individual differences in the sensitivity to EA analgesia have been reported, causing experimental and clinical difficulties. Our functional genomic study using cDNA microarray identified that 5'-AMP-activated protein kinase (AMPK), a well-known factor in the regulation of energy homeostasis, is the most highly expressed gene in the hypothalamus of the rats that were sensitive to EA analgesia ("responder"), as compared to the rats that were insensitive to EA analgesia ("non-responder"). In this study, we investigated the causal relationship between the hypothalamic AMPK and the individual variation in EA analgesia. METHODS: Sprague-Dawley (SD) rats were divided into the responder and the non-responder groups, based on EA-induced analgesic effects in the tail flick latency (TFL) test, which measures the latency of the tail flick response elicited by radiant heat applied to the tail. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to quantify the expression levels of AMPK mRNA in the hypothalamus of the responder and non-responder rats. Further, we examined whether viral manipulation of the AMPK expression in the hypothalamus modulates EA analgesia in rats. RESULTS: The real-time RT-PCR analysis showed that mRNA expression levels of AMPK in the hypothalamus of the responder rats are significantly higher than those of the non-responder rats, validating the previous microarray results. Microinjection of dominant negative (DN) AMPK adenovirus, which inhibits AMPK activity, into the rat hypothalamus significantly attenuates EA analgesia (p < 0.05), whereas wild type (WT) AMPK virus did not affect EA analgesia (p > 0.05). CONCLUSIONS: The present results demonstrated that levels of AMPK gene expression in the rat hypothalamus determine the individual differences in the sensitivity to EA analgesia. Thus, our findings provide a clinically useful evidence for the application of acupuncture or EA for analgesia.

The effects of the standardized herbal formula PM014 on pulmonary inflammation and airway responsiveness in a murine model of cockroach allergen-induced asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: PM014 is a modified form of the Chung-Sang-Bo-Ha-Tang (CSBHT) herbal formula that has been used to treat chronic pulmonary diseases in Korea for centuries. Previously, we developed a formulation of PM014 based on a series of in vitro and in vivo screening efforts that comprises seven herbal extracts. The PM014 formula includes the root of Rehmannia glutinosa, the cortex of Paeonia suffruticosa, the fruit of Schizandra chinensis, the root of Asparagus cochinchinensis, seeds of Prunus armeniaca, the root of Scutellaria baicalensis and the root of Stemona sessilifolia. Asthma is a chronic inflammatory disease of the lungs that is characterized by wheezing, bronchial contraction, and chest tightness. In addition, the airway becomes hypersensitive and narrows through an inflammatory reaction mediated by Th2 cells. The present study was conducted to evaluate the ability of PM014 to prevent allergic airway inflammation and to attenuate airway responses in a cockroach allergen-induced mouse model. MATERIALS AND METHODS: Mice sensitized to and challenged with cockroach allergen were treated with oral administration of PM014. Airway resistance was determined by whole body plethysmography. In addition, Th2 cytokines and immune cell profiles of bronchoalveolar lavage (BAL) fluid and inflammatory mediators in serum were analyzed by ELISA. A series of histological examinations were also conducted to demonstrate the effects of PM014 on airway remodeling, goblet cell hyperplasia and inflammatory responses in the lung. RESULTS: PM014 significantly inhibited the number of total cells, eosinophils, neutrophils, macrophages and lymphocytes in the BAL fluid of mice that were challenged with cockroach allergen. In addition, PM014 reduced the levels of Th2 cytokines (IL-4, IL-5 and IL-13) in the BAL fluid and inflammatory mediators such as IgE in the serum, as measured by enzyme-linked immunosorbent assay (ELISA). Histopathological analysis also showed that PM014 substantially inhibited eosinophil infiltration into the airway, goblet cell hyperplasia and smooth muscle hypertrophy. CONCLUSIONS: In this study, our results indicate that PM014 has significant effects on allergic airway inflammation upon exposure to cockroach allergen in a mouse model. According to these outcomes, PM014 may have therapeutic potential as a treatment for allergic asthma.

Effect of Achyranthes bidentata Blume on 3T3-L1 Adipogenesis and Rats Fed with a High-Fat Diet.

The present study investigated the antiobesity effect of Achyranthes bidentata Blume root water extract in a 3T3-L1 adipocyte differentiation model and rats fed with a high-fat diet. To investigate the effect of Achyranthes bidentata Blume on adipogenesis in vitro, differentiating 3T3-L1 cells in adipocyte-induction media were treated every two days with Achyranthes bidentata Blume at various concentrations (1 to 25 µ g/mL) for eight days. We found that Achyranthes bidentata Blume root inhibited 3T3-L1 adipocyte differentiation without affecting cell viability, and Western blot analysis revealed that phospho-Akt expression was markedly decreased, whereas there was no significant change in perilipin expression. Furthermore, administration of Achyranthes bidentata Blume root (0.5 g/kg body weight for six weeks) to rats fed with a high-fat diet significantly reduced body weight gain without affecting food intake, and the level of triglyceride was significantly decreased when compared to those in rats fed with only a high-fat diet. These results suggest that Achyranthes bidentata Blume root water extract could have a beneficial effect on inhibition of adipogenesis and controlling body weight in rats fed with a high-fat diet.

Treatment with pyranopyran-1, 8-dione attenuates airway responses in cockroach allergen sensitized asthma in mice.

Chronic allergic asthma is characterized by Th2-typed inflammation, and contributes to airway remodeling and the deterioration of lung function. Viticis Fructus (VF) has long been used in China and Korea as a traditional herbal remedy for treating various inflammatory diseases. Previously, we have isolated a novel phytochemical, pyranopyran-1, 8-dione (PPY), from VF. This study was conducted to evaluate the ability of PPY to prevent airway inflammation and to attenuate airway responses in a cockroach allergen-induced asthma model in mice. The mice sensitized to and challenged with cockroach allergen were treated with oral administration of PPY. The infiltration of total cells, eosinophils and lymphocytes into the BAL fluid was significantly inhibited in cockroach allergen-induced asthma mice treated with PPY (1, 2, or 10 mg/kg). Th2 cytokines and chemokine, such as IL-4, IL-5, IL-13 and eotaxin in BAL fluid were also reduced to normal levels following treatment with PPY. In addition, the levels of IgE were also markedly suppressed after PPY treatment. Histopathological examination demonstrated that PPY substantially inhibited eosinophil infiltration into the airway, goblet cell hyperplasia and smooth muscle hypertrophy. Taken together, these results demonstrate that PPY possesses a potent efficacy on controlling allergic asthma response such as airway inflammation and remodeling.

Effects of electroacupuncture on oxaliplatin-induced neuropathic cold hypersensitivity in rats.

This study investigated whether and how electroacupuncture (EA) attenuates cold hypersensitivity (allodynia) in a rat model of oxaliplatin-induced neuropathic pain. Cold allodynia [evaluated by immersing the tail into cold water (4 °C) and measuring the withdrawal latency] was induced 3 days after an oxaliplatin administration (6 mg/kg, i.p.). EA stimulation (2/100 Hz, 0.3-ms pulse duration, 0.2-0.3 mA) was delivered to ST36 acupoint or non-acupoint for 20 min. Low-frequency (2 Hz) EA at ST36 relieved cold allodynia more effectively than high-frequency EA at ST36 or low-frequency EA at non-acupoint. Naloxone (opioid antagonist, 2 mg/kg, i.p.) completely blocked such EA-induced anti-allodynia, whereas phentolamine (α-adrenergic antagonist, 2 mg/kg, i.p.) did not. Moreover, plasma ß-endorphin levels significantly increased right after the end of EA and subsequently decreased. These results indicate that low-frequency EA at ST36 in rats has a marked relieving effect on oxaliplatin-induced cold allodynia that is mediated by the endogenous opioid, but not noradrenergic, system.

Effect of bee venom acupuncture on oxaliplatin-induced cold allodynia in rats.

Oxaliplatin, a chemotherapy drug, often leads to neuropathic cold allodynia after a single administration. Bee venom acupuncture (BVA) has been used in Korea to relieve various pain symptoms and is shown to have a potent antiallodynic effect in nerve-injured rats. We examined whether BVA relieves oxaliplatin-induced cold allodynia and which endogenous analgesic system is implicated. The cold allodynia induced by an oxaliplatin injection (6 mg/kg, i.p.) was evaluated by immersing the rat's tail into cold water (4°C) and measuring the withdrawal latency. BVA (1.0 mg/kg, s.c.) at Yaoyangguan (GV3), Quchi (LI11), or Zusanli (ST36) acupoints significantly reduced cold allodynia with the longest effect being shown in the GV3 group. Conversely, a high dose of BVA (2.5 mg/kg) at GV3 did not show a significant antiallodynic effect. Phentolamine ( α -adrenergic antagonist, 2 mg/kg, i.p.) partially blocked the relieving effect of BVA on allodynia, whereas naloxone (opioid antagonist, 2 mg/kg, i.p.) did not. We further confirmed that an intrathecal administration of idazoxan ( α 2-adrenergic antagonist, 50 µ g) blocked the BVA-induced anti-allodynic effect. These results indicate that BVA alleviates oxaliplatin-induced cold allodynia in rats, at least partly, through activation of the noradrenergic system. Thus, BVA might be a potential therapeutic option in oxaliplatin-induced neuropathy.

Mechanisms of electroacupuncture-induced analgesia on neuropathic pain in animal model.

Neuropathic pain remains as one of the most difficult clinical pain syndromes to treat. Electroacupuncture (EA), involving endogenous opioids and neurotransmitters in the central nervous system (CNS), is reported to be clinically efficacious in various fields of pain. Although multiple experimental articles were conducted to assess the effect of EA-induced analgesia, no review has been published to assess the efficacy and clarify the mechanism of EA on neuropathic pain. To this aim, this study was firstly designed to evaluate the EA-induced analgesic effect on neuropathic pain and secondly to guide and help future efforts to advance the neuropathic pain treatment. For this purpose, articles referring to the analgesic effect of acupuncture on neuropathic pain and particularly the work performed in our own laboratory were analyzed. Based on the articles reviewed, the role of spinal opioidergic, adrenergic, serotonergic, cholinergic, and GABAergic receptors in the mechanism of EA-induced analgesia was studied. The results of this research demonstrate that µ and δ opioid receptors, α 2-adrenoreceptors, 5-HT1A and 5-HT3 serotonergic receptors, M1 muscarinic receptors, and GABAA and GABAB GABAergic receptors are involved in the mechanisms of EA-induced analgesia on neuropathic pain.

Acupuncture for gouty arthritis: a concise report of a systematic and meta-analysis approach.

OBJECTIVE: To assess the effectiveness of acupuncture as complementary therapy for gouty arthritis from randomized controlled trials (RCTs). METHODS: Five electronic databases, including English and Chinese, were systematically searched until August 2012. All RCTs involving acupuncture in combination with conventional therapy for gouty arthritis were included. RESULTS: Ten RCTs involving 852 gouty arthritis patients were systematically reviewed. Among them six studies of 512 patients reported a significant decrease in uric acid in the treatment group compared with a control group, while two studies of 120 patients reported no significant decrease in uric acid in the treatment group compared with the control group. The remaining four studies of 380 patients reported a significant decrease in visual analogue scale score in the treatment group. CONCLUSION: The results of the studies included here suggest that acupuncture is efficacious as complementary therapy for gouty arthritis patients. More research and well-designed, rigorous and large clinical trials are necessary to address these issues.

Complementary and alternative medicine in the undergraduate medical curriculum: a survey of Korean medical schools.

BACKGROUND: The current status of complementary and alternative medicine (CAM) education in Korean medical schools is still largely unknown, despite a growing need for a CAM component in medical education. The prevalence, scope, and diversity of CAM courses in Korean medical school education were evaluated. DESIGN: Participants included academic or curriculum deans and faculty at each of the 41 Korean medical schools. A mail survey was conducted from 2007 to 2010. Replies were received from all 41 schools. RESULTS: CAM was officially taught at 35 schools (85.4%), and 32 schools (91.4%) provided academic credit for CAM courses. The most common courses were introduction to CAM or integrative medicine (88.6%), traditional Korean medicine (57.1%), homeopathy and naturopathy (31.4%), and acupuncture (28.6%). Educational formats included lectures by professors and lectures and/or demonstrations by practitioners. The value order of core competencies was attitude (40/41), knowledge (32/41), and skill (6/41). Reasons for not initiating a CAM curriculum were a non-evidence-based approach in assessing the efficacy of CAM, insufficiently reliable reference resources, and insufficient time to educate students in CAM. CONCLUSIONS: This survey reveals heterogeneity in the content, format, and requirements among CAM courses at Korean medical schools. Korean medical school students should be instructed in CAM with a more consistent educational approach to help patients who participate in or demand CAM.

Placebo effect was influenced by publication year in three-armed acupuncture trials.

OBJECTIVES: We investigated the relationship between the placebo effect and the trial or patient characteristics. DATA SOURCES: We identified randomized clinical trials with acupuncture, sham and no-treatment groups in which no-treatment or conventional therapy was applied to the no-treatment group. Thirty-one trials in which no treatment was applied in the no-treatment group were categorised as 'strict' trials. Thirty-nine trials in which no-treatment or conventional therapy was applied to the no-treatment group were categorised as 'less strict' trials. We calculated the treatment effect, defined as the difference in the effect size between the acupuncture and no-treatment groups, and the placebo effect, defined as the difference in the effect size between the sham and no-treatment groups. Then, a random effect meta-regression analysis was performed on the two effects with respect to trial or patient characteristics. RESULTS: The treatment effect was not found to be associated with any factors in both the strict and less strict trials. However, the placebo effect was found to be associated with the publication year in both the strict and less strict trials (P=0.009 and 0.005, respectively). The placebo effect increased by 0.05 in effect size per year in trials that were published more recently. CONCLUSION: While the treatment effect was not influenced by any trial or patient characteristics, the placebo effect was associated with the publication year.

Electroacupuncture attenuates mechanical and warm allodynia through suppression of spinal glial activation in a rat model of neuropathic pain.

Neuropathic pain remains one of the most difficult clinical pain syndromes to treat. It is traditionally viewed as being mediated solely by neurons; however, glial cells have recently been implicated as powerful modulators of pain. It is known that the analgesic effects of electroacupuncture (EA) are mediated by descending pain inhibitory systems, which mainly involve spinal opioid, adrenergic, dopaminergic, serotonergic, and cholinergic receptors. However, studies investigating the suppressive effects of EA on spinal glial activation are rare. In the present study, we assessed the cumulative analgesic effects of EA on mechanical and warm allodynia in a rat model of neuropathic pain. We investigated the clinical efficacy of EA as long-term therapy and examined its effects on spinal glia, matrix metalloproteinase (MMP)-9/MMP-2, proinflammatory cytokines and serum immunoglobulin G (IgG) concentration. Rats were randomly divided into four groups as follows: the operation group (OP), operation with EA-non acupoint (EA-NA), operation with EA-ST36 acupoint (EA-ST36), and sham operation (shamOP). Following neuropathic or sham surgery, repeated EA was performed every other day after the behavioral test. On day 53 after the behavioral test, rats were perfused for immunohistochemistry and Western blot analysis to observe quantitative changes in spinal glial markers such as OX-42, astrocytic glial fibrillary acidic protein (GFAP), MMP-9/MMP-2, and proinflammatory cytokines. Allodynia and OX-42/GFAP/MMP-9/MMP-2/tumor necrosis factor (TNF)-α/interleukin (IL)-1ß activity in the EA-ST36 group was significantly reduced, compared to the OP and EA-NA groups, and IgG in EA-ST36 rats significantly increased. Our results suggest that the analgesic effect of EA may be partly mediated via inhibition of inflammation and glial activation and repeated EA stimulation may be useful for treating chronic pain clinically.

Gene Expression Profile of the Hypothalamus in DNP-KLH Immunized Mice Following Electroacupuncture Stimulation.

Clinical evidence indicates that electroacupuncture (EA) is effective for allergic disorder. Recent animal studies have shown that EA treatment reduces levels of IgE and Th2 cytokines in BALB/c mice immunized with 2,4-dinitrophenylated keyhole limpet protein (DNP-KLH). The hypothalamus, a brain center of the neural-immune system, is known to be activated by EA stimulation. This study was performed to identify and characterize the differentially expressed genes in the hypothalamus of DNP-KLH immunized mice that were stimulated with EA or only restrained. To this aim, we conducted a microarray analysis to evaluate the global gene expression profiles, using the hypothalamic RNA samples taken from three groups of mice: (i) normal control group (no treatments); (ii) IMH group (DNP-KLH immunization + restraint); and (iii) IMEA group (immunization + EA stimulation). The microarray analysis revealed that total 39 genes were altered in their expression levels by EA treatment. Ten genes, including T-cell receptor alpha variable region family 13 subfamily 1 (Tcra-V13.1), heat shock protein 1B (Hspa1b) and 2'-5' oligoadenylate synthetase 1F (Oas1f), were up-regulated in the IMEA group when compared with the IMH group. In contrast, 29 genes, including decay accelerating factor 2 (Daf2), NAD(P)H dehydrogenase, quinone 1 (Nqo1) and programmed cell death 1 ligand 2 (Pdcd1lg2) were down-regulated in the IMEA group as compared with the IMH group. These results suggest that EA treatment can modulate immune response in DNP-KLH immunized mice by regulating expression levels of genes that are associated with innate immune, cellular defense and/or other kinds of immune system in the hypothalamus.

Effects of Atractylodes macrocephala Koidzumi rhizome on 3T3-L1 adipogenesis and an animal model of obesity.

ETHNOPHARMACOLOGICAL RELEVANCE: Atractylodes macrocephala Koidzumi (AMK) is an herbal medicine traditionally used for treatment of abdominal pain, gastrointestinal disease, obesity, and related complications. AIM OF THE STUDY: We investigated the effects and molecular mechanism of AMK rhizome water extract on 3T3-L1 adipogenesis and an animal model of obesity. MATERIALS AND METHODS: To study the effect of AMK on adipogenesis in vitro, differentiating 3T3-L1 cells were treated every two days with AMK at various concentrations (1-25µg/ml) for eight days. Oil Red O staining was performed to determine the lipid accumulation in 3T3-L1 cells. To elucidate the inhibitory mechanism of AMK on adipogenesis, phosphorylation levels of Akt and expression of perilipin, were analyzed by Western blotting. AMK was administered orally to high fat diet (HFD)-induced obese rats to confirm its effect in vivo. RESULTS: AMK inhibited 3T3-L1 adipocyte differentiation in a dose-dependent manner without cellular toxicity. Phospho-Akt expression was highly decreased by AMK treatment, whereas there was no significant change in perilipin expression. AMK administration significantly reduced the body weight of rats fed a HFD. Plasma triglyceride levels were significantly lower in the AMK-treated HFD group than those in the HFD control group or normal diet (ND) group, although serum total, HDL- and LDL-cholesterol levels did not differ between the groups. CONCLUSION: These results demonstrate an inhibitory effect of AMK on adipogenesis through reduction of an adipogenic factor, phospho-Akt. AMK had a beneficial effect, reducing body weight gain in a HFD-induced animal model of obesity.