Jakyak-gamcho-tang, a decoction of Paeoniae Radix and Glycyrrhizae Radix et Rhizoma, ameliorates dexamethasone-induced muscle atrophy and muscle dysfunction.

BACKGROUND: Although chronic treatment with glucocorticoids, such as dexamethasone, is frequently associated with muscle atrophy, effective and safe therapeutics for treating muscle atrophy remain elusive. Jakyak-gamcho-tang (JGT), a decoction of Paeoniae Radix and Glycyrrhizae Radix et Rhizoma, has long been used to relieve muscle tension and control muscle cramp-related pain. However, the effects of JGT on glucocorticoid-induced muscle atrophy are yet to be comprehensively clarified. PURPOSE: The objective of the current study was to validate the protective effect of JGT in dexamethasone-induced muscle atrophy models and elucidate its underlying mechanism through integrated in silico - in vitro - in vivo studies. STUDY DESIGN AND METHODS: Differential gene expression was preliminarily analyzed using the RNA-seq data to determine the effects of JGT on C2C12 myotubes. The protective effects of JGT were further validated in dexamethasone-treated C2C12 myotubes by assessing cell viability, myotube integrity, and mitochondrial function or in C57BL/6 N male mice with dexamethasone-induced muscle atrophy by evaluating muscle mass and physical performance. Transcriptomic pathway analysis was also performed to elucidate the underlying mechanism. RESULTS: Based on preliminary gene set enrichment analysis using the RNA-seq data, JGT regulated various pathways related to muscle differentiation and regeneration. Dexamethasone-treated C2C12 myotubes and muscle tissues of atrophic mice displayed substantial muscle protein degradation and muscle loss, respectively, which was efficiently alleviated by JGT treatment. Importantly, JGT-mediated protective effects were associated with observations such as preservation of mitochondrial function, upregulation of myogenic signaling pathways, including protein kinase B/mammalian target of rapamycin/forkhead box O3, inhibition of ubiquitin-mediated muscle protein breakdown, and downregulation of inflammatory and apoptotic pathways induced by dexamethasone. CONCLUSION: To the best of our knowledge, this is the first report to demonstrate that JGT could be a potential pharmaceutical candidate to prevent muscle atrophy induced by chronic glucocorticoid treatment, highlighting its known effects for relieving muscle spasms and pain. Moreover, transcriptomic pathway analysis can be employed as an efficient in silico tool to predict novel pharmacological candidates and elucidate molecular mechanisms underlying the effects of herbal medications comprising diverse biologically active ingredients.

Anti-fatigue potential of Pinus koraiensis leaf extract in an acute exercise-treated mouse model.

Pinus koraiensis leaf (PKL) extract exerts antihyperlipidemic, antidiabetic, and anticancer effects; however, its anti-fatigue properties have not been elucidated to date. In this study, the anti-fatigue properties of PKL were evaluated by assessing the endurance of mice by a weight-loaded forced swimming (WLFS) and rotarod (RR) tests. Subsequently, various behavioral, biochemical, and physiological parameters were measured. Treatment with PKL decreased hepatic and muscular glycogen levels in mice subjected to WLFS and RR test compared to those in acute exercise-treated (AET) mice. Additionally, plasma levels of stress-related biochemical factors (lactate, lactate dehydrogenase, aminotransferase, aspartate aminotransferase, and blood urea nitrogen) decreased significantly (P < 0.05), whereas the levels of superoxide dismutase and glutathione peroxidase increased. Furthermore, PKL potentially improved mental fatigue by decreasing corticosterone and increasing serotonin levels. PKL increased the expression of phosphorylated cyclic adenosine-3',5'-monophosphate response element-binding protein and brain-derived neurotrophic factor in the hippocampus. Collectively, the anti-fatigue effects of PKL could be explained by its antioxidant activity, mediating effects on glycogen synthesis, and control over stress. In conclusion, the findings of the present study suggest that PKL is a potential nutraceutical for improving exercise performance and alleviating fatigue.

Effect of Hibiscus syriacus Linnaeus extract and its active constituent, saponarin, in animal models of stress-induced sleep disturbances and pentobarbital-induced sleep.

Treatment of sleep disorders promotes the long-term use of commercially available sleep inducers that have several adverse effects, including addiction, systemic fatigue, weakness, loss of concentration, headache, and digestive problems. Therefore, we aimed to limit these adverse effects by investigating a natural product, the extract of the Hibiscus syriacus Linnaeus flower (HSF), as an alternative treatment. In the electric footshock model, we measured anxiety and assessed the degree of sleep improvement after administering HSF extract. In the restraint model, we studied the sleep rate using PiezoSleep, a noninvasive assessment system. In the pentobarbital model, we measured sleep improvement and changes in sleep-related factors. Our first model confirmed the desirable effects of HSF extract and its active constituent, saponarin, on anxiolysis and Wake times. HSF extract also increased REM sleep time. Furthermore, HSF extract and saponarin increased the expression of cortical GABAA receptor α1 (GABAAR α1) and c-Fos in the ventrolateral preoptic nucleus (VLPO). In the second model, HSF extract and saponarin restored the sleep rate and the sleep bout duration. In the third model, HSF extract and saponarin increased sleep maintenance time. Moreover, HSF extract and saponarin increased cortical cholecystokinin (CCK) mRNA levels and the expression of VLPO c-Fos. HSF extract also increased GABAAR α1 mRNA level. Our results suggest that HSF extract and saponarin are effective in maintaining sleep and may be used as a novel treatment for sleep disorder. Eventually, we hope to introduce HSF and saponarin as a clinical treatment for sleep disorders in humans.

Antidepressant and Anti-Neuroinflammatory Effects of Bangpungtongsung-San.

Bangpungtongsung-san (BTS) is a traditional Korean medicine consisting of 18 herbs, some which have antidepressant effects. Here, we used an animal model of reserpine-induced depression and lipopolysaccharide (LPS)-stimulated BV2 microglia to assess the antidepressant and anti-neuroinflammatory effects of BTS. Aside from a control group, C57BL/6 mice were administered reserpine (0.5 mg/kg) daily for 10 days via intraperitoneal injection. BTS (100, 300, or 500 mg/kg), vehicle (PBS), or fluoxetine (FXT, 20 mg/kg) was administered orally 1 h before reserpine treatment. Following treatment, a forced swimming test (FST), tail suspension test (TST), and open field test (OFT) were performed, and immobility time and total travel distance were measured. Administration of BTS not only reduced immobility time in the FST and TST but also significantly increased the total travel distance in the OFT. Furthermore, reserpine-treated mice showed significantly elevated serum levels of corticosterone, a stress hormone; however, treatment with BTS significantly reduced corticosterone levels, similar to FXT treatment. Serotonin in reserpine-treated mice was significantly reduced compared to that in control mice, while BTS mice exhibited increased serotonin levels. BTS mice showed increased expression of brain-derived neurotrophic factor (BDNF) and a higher ratio of phosphorylated cAMP response element-binding protein (p-CREB) to CREB (p-CREB/CREB) in the hippocampus. Additionally, reserpine-treated mice exhibited significantly elevated mRNA levels of pro-inflammatory cytokines, but BTS mice showed reduced mRNA levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in the hippocampus. To further demonstrate the anti-neuroinflammatory effects of BTS in vitro, we examined its anti-neuroinflammatory and neuroprotective effects in lipopolysaccharide (LPS)-stimulated BV2 microglia. BTS significantly reduced the levels of NO, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, TNF-α, IL-1ß, and IL-6 in a dose-dependent manner via a decrease in the expression of nuclear factor (NF)-κB p65. Furthermore, the neuroprotective factor heme oxygenase-1 (HO-1) was upregulated via the nuclear factor-E2-related factor 2 (NRF2)/CREB pathway. Taken together, our data suggest that BTS has considerable potential as an anti-neuroinflammation and antidepressant agent, as it has clear effects on depressive behaviors and associated factors caused by reserpine-induced depression.

Analyzing the advantages of subcutaneous over transcutaneous electrical stimulation for activating brainwaves.

Transcranial electrical stimulation (TES) is a widely accepted neuromodulation modality for treating brain disorders. However, its clinical efficacy is fundamentally limited due to the current shunting effect of the scalp and safety issues. A newer electrical stimulation technique called subcutaneous electrical stimulation (SES) promises to overcome the limitations of TES by applying currents directly at the site of the disorder through the skull. While SES seems promising, the electrophysiological effect of SES compared to TES is still unknown, thus limiting its broader application. Here we comprehensively analyze the SES and TES to demonstrate the effectiveness and advantages of SES. Beagles were bilaterally implanted with subdural strips for intracranial electroencephalography and electric field recording. For the intracerebral electric field prediction, we designed a 3D electromagnetic simulation framework and simulated TES and SES. In the beagle model, SES induces three to four-fold larger cerebral electric fields compared to TES, and significant changes in power ratio of brainwaves were observed only in SES. Our prediction framework suggests that the field penetration of SES would be several-fold larger than TES in human brains. These results demonstrate that the SES would significantly enhance the neuromodulatory effects compared to conventional TES and overcome the TES limitations.

Ginsenosides Rg5 and Rk1 Enriched Cultured Wild Ginseng Root Extract Bioconversion of Pediococcus pentosaceus HLJG0702: Effect on Scopolamine-Induced Memory Dysfunction in Mice.

Wild ginseng is known to contain additional physiologically and pharmacologically active substances than common ginseng. The utilization of this herb can be maximized by altering its composition via tissue culture generating adventitious roots. We enriched the content of specific ginsenosides and investigated their role in ameliorating memory impairment. Cultured wild ginseng root was subjected to extraction, steaming, and fermentation using Pediococcus pentosaceus HLJG0702 to enhance the levels of ginsenosides Rg5 /Rk1. The analysis of product, HLJG0701, confirmed target ginsenosides. We analyzed the inhibitory effect of ginsenoside Rg5/Rk1, HLJG0701 and the raw material on acetylcholinesterase. Further, we performed Morris water maze, Y-maze, and passive avoidance tasks with mice exhibiting memory deficit induced by scopolamine, and we analyzed the concentrations of acetylcholinesterase and acetylcholine in their brains. Studies showed that the levels of ginsenosides Rg5 /Rk1, not found in the raw material, were enhanced in HLJG0701. Ginsenosides and HLJG0701 significantly inhibited acetylcholinesterase unlike the raw material. In all behavioral tasks, HLJG0701 showed memory improvement. It reduced acetylcholinesterase, whereas, it preserved acetylcholine in brain. In conclusion, cultured wild ginseng root extract fermented by P. pentosaceus HLJG0702 contains the distinctive ginsenosides Rg5/Rk1, which may ameliorate memory impairment via inhibition of acetylcholinesterase resulting in increased acetylcholine levels in the brain.

Antineuroinflammatory and Neuroprotective Effects of Gyejibokryeong-Hwan in Lipopolysaccharide-Stimulated BV2 Microglia.

Microglia, the central nervous system's innate immune cells, mediate neuroinflammation and are implicated in a variety of neuropathologies. The present study investigated the antineuroinflammatory and neuroprotective effects of Gyejibokryeong-hwan (GBH), a traditional Korean medicine, in lipopolysaccharide- (LPS-) stimulated murine BV2 microglia. BV2 cells were pretreated with GBH, fluoxetine (FXT), or amitriptyline (AMT) for 1 h and then stimulated with LPS (100 ng/mL). The expression levels of nitric oxide (NO), cytokines, and chemokines were determined by the Griess method, ELISA, or real-time PCR. Western blotting was used to measure various transcription factors and mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt activity. GBH significantly reduced the levels of NO, inducible nitric oxide synthase (iNOS), cyclooxygenase- (COX-) 2, tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1ß, IL-6, macrophage inhibitory protein- (MIP-) 1α, macrophage chemoattractant protein- (MCP-) 1, and IFN-γ inducible protein- (IP-) 10, regulated upon activation normal T cell expressed sequence (RANTES) in a dose-dependent manner. Expression of nuclear factor- (NF-) κB p65 was significantly decreased and phosphorylation of extracellular signal-regulated kinase (Erk), c-Jun NH2-terminal kinase (JNK), and PI3K/Akt by GBH, but not p38 MAPK, was decreased. Furthermore, production of anti-inflammatory cytokine IL-10 was increased and Heme oxygenase-1 (HO-1) was upregulated via the nuclear factor-E2-related factor 2 (NRF2)/cAMP response element-binding protein (CREB) pathway, collectively indicating the neuroprotective effects of GBH. We concluded that GBH may suppress neuroinflammatory responses by inhibiting NF-κB activation and upregulating the neuroprotective factor, HO-1. These results suggest that GBH has potential as anti-inflammatory and neuroprotective agents against microglia-mediated neuroinflammatory disorders.

Therapeutic Potential of a Combination of Electroacupuncture and TrkB-Expressing Mesenchymal Stem Cells for Ischemic Stroke.

We prepared and grafted tropomyosin receptor kinase B (TrkB) gene-transfected mesenchymal stem cells (TrkB-MSCs) into the ischemic penumbra and investigated whether electroacupuncture (EA) treatment could promote functional recovery from ischemic stroke. For the behavioral test, TrkB-MSCs+EA resulted in significantly improved motor function compared to that obtained with MSCs+EA or TrkB-MSCs alone. At 30 days after middle cerebral artery occlusion (MCAO), the largest number of grafted MSCs was detected in the TrkB-MSC+EA group. Some differentiation into immature neuroblasts and astrocytes was detected; however, only a few mature neuron-like cells were found. Compared to other treatments, TrkB-MSCs+EA upregulated the expression of mature brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT4) and induced the activation of TrkB receptor and its transcription factor cAMP response element-binding protein (CREB). At 60 days after MCAO, EA highly promoted the differentiation of TrkB-MSCs into mature neuron-like cells compared to the effect in MSCs. A selective TrkB antagonist, ANA-12, reverted the effect of TrkB-MSCs+EA in motor function recovery and survival of grafted MSCs. Our results suggest that EA combined with grafted TrkB-MSCs promotes the expression of BDNF and NT4, induces the differentiation of TrkB-MSCs, and improves motor function. TrkB-MSCs could serve as effective therapeutic agents for ischemic stroke if used in combination with BDNF/NT4-inducing therapeutic approaches.

Antidepressant-Like and Neuroprotective Effects of Ethanol Extract from the Root Bark of Hibiscus syriacus L.

Hibiscus syriacus L. (Malvaceae) is an important ornamental shrub in horticulture and has been widely used as a medical material in Asia. The aim of this study was to assess the antidepressant and neuroprotective effects of a root bark extract of H. syriacus (HSR) and to investigate the underlying molecular mechanisms. Using an animal model of restraint stress, we investigated the effects of HSR on depressive-like behaviors and on the expression levels of serotonin, corticosterone, and neurotrophic factors in the brain. The mice were exposed to restraint stress for 2 h per day over a period of 3 weeks and orally treated with HSR (100, 200, or 400 mg/kg/day). We also examined the neuroprotective effect of HSR using corticosterone-treated human neuroblastoma SK-N-SH cells. The cells were incubated with the extract for 24 h, followed by corticosterone stimulation for 1 h, and then cell viability assay, cellular ATP assay, mitochondrial membrane potential (MMP) assay, cellular reactive oxygen species (ROS) assay, and western blotting were used to investigate the neuroprotective effects of HSR. Administration of HSR not only reduced the immobility times of the restraint-stressed mice in the forced swimming and tail suspension tests, but also significantly increased sucrose preference in the sucrose preference test. In addition, HSR significantly reduced the plasma levels of corticosterone and increased the brain levels of serotonin. The extract also increased the phosphorylation level of cyclic AMP response element-binding (CREB) protein and the expression level of brain-derived neurotrophic factor (BDNF). The in vitro assays showed that HSR pretreatment increased cell viability and ATP levels, recovered MMP, decreased ROS levels, and increased the expression of CREB and BDNF in corticosterone-induced neurotoxicity. Taken together, our data suggest that HSR may have the potential to control neuronal cell damage and depressive behaviors caused by chronic stress.

Antidepressant Effect of Fraxinus rhynchophylla Hance Extract in a Mouse Model of Chronic Stress-Induced Depression.

Prolonged exposure to stress can affect mood and cognition and lead to mood disorders. Research on stress-associated mood disorders is important in modern society as people are increasingly exposed to unavoidable stressors. We used a mouse model with 2 weeks of exposure to electric foot shock and restraint, to determine the effect of Fraxinus rhynchophylla Hance (FX) extract on chronic stress-induced depression. We measured the effect of FX extract using various physiological, behavioral, and biochemical measures. FX extract ameliorated chronic stress-induced body and relative liver weight loss and improved depressive-like behaviors in the open field and forced swim tests. In addition, plasma cortisol and serotonin levels in stress-induced mice following FX treatment were similar to normal mice, and the elevation of proinflammatory cytokines was prevented. Moreover, FX treatment increased the expression of phosphorylated cyclic adenosine-3',5'-monophosphate response element-binding protein (pCREB)/brain-derived neurotrophic factor (BDNF). Further experiments confirmed the efficacy of FX extract by showing similar results using esculin and esculetin, compounds extracted from FX. Taken together, these results indicate that FX extract has an antidepressant effect on chronic stress-induced depression by associating signaling with neuroinflammation and neurogenesis.

Antidepressant-Like Effects of Gyejibokryeong-hwan in a Mouse Model of Reserpine-Induced Depression.

Treatment with the antihypertensive agent reserpine depletes monoamine levels, resulting in depression. In the present study, we evaluated the antidepressant effects of Gyejibokryeong-hwan (GBH), a traditional Korean medicine, in a mouse model of reserpine-induced depression. Mice were treated with reserpine (0.5 mg·kg-1, i.p.) or phosphate-buffered saline (PBS, i.p., normal) once daily for 10 days. GBH (50, 100, 300, and 500 mg·kg-1), PBS (normal, control), fluoxetine (FXT, 20 mg·kg-1), or amitriptyline (AMT, 30 mg·kg-1) was administered orally 1 h prior to reserpine treatment. Mouse behavior was examined in the forced swim test (FST), tail suspension test (TST), and open-field test (OFT) following completion of the treatment protocol. Administration of GBH reduced immobility time in the FST and TST and significantly increased the total distance traveled in the OFT. Plasma serotonin levels were significantly lower in control mice than in normal mice, although these decreases were significantly attenuated to a similar extent by treatment with GBH, FXT, or AMT. Reserpine-induced increases in plasma corticosterone were also attenuated by GBH treatment. Moreover, GBH attenuated reserpine-induced increases in interleukin- (IL-) 1ß, IL-6, and tumor necrosis factor- (TNF-) α mRNA expression in the hippocampus. In addition, GBH mice exhibited increased levels of brain-derived neurotrophic factor (BDNF) and a higher ratio of phosphorylated cAMP response element-binding protein (p-CREB) to CREB (p-CREB/CREB) in the hippocampus. Our results indicated that GBH can ameliorate depressive-like behaviors, affect the concentration of mood-related hormones, and help to regulate immune/endocrine dysfunction in mice with reserpine-induced depression, likely via activation of the BDNF-CREB pathway. Taken together, these findings indicate that GBH may be effective in treating patients with depression.

High-fluence 1064-nm Q-Switched Nd:YAG laser: Safe and effective treatment of café-au-lait macules in Asian patients.

OBJECTIVES: Café-au-lait macules (CALMs) are benign cutaneous hyperpigmentary disorders. Usually, laser therapies for cosmetic concerns result in more severe side effects in the people of Asian descent than that of Caucasians. Unfortunately, there is no gold standard for the laser treatment of CALMs in skin of people of Asian descent. To investigate the efficacy and safety of a high-fluence 1064-nm Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG) laser treatment of CALMs in Asian patients. STUDY DESIGN: The medical records of 35 Korean patients (age range: 1 to 40 years old, mean age: 18.5 years) diagnosed with isolated CALMs were reviewed retrospectively. METHODS: The patients were treated with a 1064-nm Q-switched Nd:YAG laser. The parameters were a spot size of 7 mm, a fluence of 2.2-2.4 J/cm2 with a slow single sliding-stacking pass, and a pulse rate of 10 Hz with a 1-week interval for 20-50 sessions. RESULTS: At the week of the final treatment, all treated CALMs showed considerable pigmentation removal without any permanent side effects, such as scaring, mottled hypopigmentation and postinflammatory hyperpigmentation (PIH). All treated CALMs showed more than 50% clinical improvement. No recurrence was observed in any of the patients after 12 months of follow-up. CONCLUSION: A high-fluence 1064-nm Q-switched Nd:YAG laser treatment of CALMs in Asian patients is a safe and effective method without side effects and recurrence.

Beneficial Effects of Gagam-Palmultang on Scopolamine-Induced Memory Deficits in Mice.

From text mining of Dongeuibogam, the 7 herbs in Palmultang can be considered effective candidates for memory enhancement. We sought to determine whether Gagam-Palmultang, comprising these 7 herbs, ameliorates scopolamine-induced memory impairment in mice, by focusing on the central cholinergic system and memory-related signaling molecules. Behavioral tests were performed after inducing memory impairment by scopolamine administration. The cholinergic system activity and memory-related molecules were examined in the hippocampus by enzyme-linked immunosorbent, western blot, and immunofluorescence assays. Gagam-Palmultang ameliorated scopolamine-induced memory impairment in the Morris water maze test, producing a significant improvement in the mean time required to find the hidden platform. Treatment with Gagam-Palmultang reduced acetylcholinesterase activity and expression in the hippocampus induced by scopolamine. The diminished phosphorylated phosphatidylinositide 3-kinase (PI3K), extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), and mature brain-derived neurotrophic factor (mBDNF) expressions caused by scopolamine administration were attenuated by treatment with Gagam-Palmultang. This treatment also promoted neuronal cell proliferation in the hippocampus. Gagam-Palmultang has beneficial effects against scopolamine-induced memory impairments, which are exerted via modulation of the cholinergic system as well as the PI3K and ERK/CREB/BDNF signaling pathway. Therefore, this multiherb formula may be a useful therapeutic agent for diseases associated with memory impairments.

Potential benefits of mesenchymal stem cells and electroacupuncture on the trophic factors associated with neurogenesis in mice with ischemic stroke.

The beneficial effects of mesenchymal stem cells (MSCs) and electroacupuncture (EA) on neurogenesis and related trophic factors remain unclear. Bone marrow MSCs (mBMSC) were transplanted into the striatum of mice with middle cerebral artery occlusion (MCAO), and EA stimulation was applied at two acupoints, Baihui and Dazhui. EA treatment significantly improved motor function, and a synergistic effect of combined mBMSC and EA treatment was observed. Combined mBMSC and EA treatment reduced prominent atrophic changes in the striatum and led to proliferation of neural progenitor cells in the subventricular zone (SVZ) and the surrounding areas of the striatum (SVZ + striatum) of MCAO mice. The mBMSC and EA treatment markedly enhanced mature brain-derived neurotrophic factor (mBDNF) expression in the SVZ + striatum and hippocampus of mice with MCAO, and combined treatment enhanced neurotrophin-4 (NT4) expression. The number of mBDNF- and NT4-positive neurons in the SVZ + striatum and hippocampus increased following EA treatment. Combined treatment led to an increase in the expression levels of phosphorylated cAMP response element binding protein in the neuroblasts of the striatum. Our results indicate that combined MSC and EA treatment may lead to a better therapeutic effect via co-regulation of neurotrophic factors in the brain, by regulating neurogenesis more than single therapy.

Treatment of café-au-lait macules with a high-fluenced 1064-nm Q-switched neodymium:yttrium aluminum garnet laser.

Café-au-lait macules (CALMs) are light to dark brown macules or patches of increased melanin concentration found along the dermoepidermal junction. Although many attempts to treat CALMs using various kinds of laser/light-based devices have been reported, CALMs remain refractory thereto with high recurrence rates. In this case series, we describe four patients with idiopathic CALMs that were effectively and safely treated with a non-ablative, high-fluenced, Q-switched (QS), 1064-nm neodymium:yttrium aluminum garnet (Nd:YAG) laser. The typical laser parameters for treating CALMs, including a spot size of 7-7.5 mm, a fluence of 2.4-2.5 J/cm2, and one to two passes until the appearance of mild erythema, but not petechiae, were utilized in this study over 12-24 treatment sessions at 2-week intervals. We suggest that high-fluenced QS 1064-nm Nd:YAG laser treatment can be used as an effective and alternative treatment modality for CALMs with minimal risk of side effects.

Electroacupuncture ameliorates memory impairments by enhancing oligodendrocyte regeneration in a mouse model of prolonged cerebral hypoperfusion.

We modeled prolonged cerebral hypoperfusion in mice using bilateral common carotid artery stenosis (BCAS) and electroacupuncture (EA) stimulation was applied at two acupoints, Baihui (GV20) and Dazhui (GV14). In behavioral tests of memory, BCAS produced impairments in spatial and short-term memory in mice that were attenuated by therapeutic EA stimulation. Therapeutic use of EA in BCAS also enhanced oligodendrocyte (OL) differentiation from oligodendrocyte precursor cells (OPCs), in association with white matter improvements in the corpus callosum (CC). In PCR analyses of growth factor gene expression, significant positive changes in 3 genes were observed following EA stimulation in BCAS, and here we highlight alterations in neurotrophin-4/5 (NT4/5). We confirmed EA-mediated positive changes in the expression of NT4/5 and its receptor, tyrosine receptor kinase B (TrkB). Treatment of naïve and BCAS + EA animals with a selective TrkB antagonist, ANA-12, produced losses of myelin and cognitive function that were ameliorated by EA therapy. Moreover, following BCAS we observed an EA-dependent increase in phospho-activated CREB (a downstream mediator of NT4/5-TrkB signaling) in OPCs and OLs of the CC. Our results suggest that EA stimulation promotes the recovery of memory function following white matter injury via a mechanism that promotes oligodendrocyte regeneration and involves NT4/5-TrkB signaling.

Emodin from Polygonum multiflorum ameliorates oxidative toxicity in HT22 cells and deficits in photothrombotic ischemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum Thunb. has been used widely in East Asia in treatment of diseases associated with aging. Emodin, an active component from Polygonum multiflorum Thunb., provides benefits for brain disturbances induced by severe cerebral injury. AIM OF THE STUDY: We investigated the neuroprotective effect of emodin from Polygonum multiflorum Thunb. against glutamate-induced oxidative toxicity and cerebral ischemia. MATERIALS AND METHODS: For examination of neuroprotective effects of emodin, cell viability, cytotoxicity, flow cytometry, and Western blot were performed in HT22 cells and infarct volume, behavioral tests and Western blot in a mouse model of photothrombotic ischemic stroke. RESULTS: Pretreatment with emodin resulted in significantly reduced glutamate-induced apoptotic cell death in HT22 cells. However, blocking of phosphatidylinositol-3 kinase (PI3K) activity with LY294002 resulted in significantly inhibited cell survival by emodin. Exposure of glutamate-treated cells to emodin induced an increase in the level of Bcl-2 expression, whereas the expression of Bax and active caspase-3 proteins was significantly reduced. In addition, treatment with emodin resulted in increased phosphorylation of Akt and cAMP response element binding protein (CREB), and expression of mature brain-derived neurotrophic factor (BDNF). This expression by emodin was also significantly inhibited by blocking of PI3K activity. In a photothrombotic ischemic stroke model, treatment with emodin resulted in significantly reduced infarct volume and improved motor function. We confirmed the critical role of the expression levels of Bcl-2/Bax, active caspase-3, phosphorylated (p)Akt, p-CREB, and mature BDNF for potent neuroprotective effects of emodin in cerebral ischemia. CONCLUSIONS: These results suggest that emodin may afford a significant neuroprotective effect against glutamate-induced apoptosis through activation of the PI3K/Akt signaling pathway, and subsequently enhance behavioral function in cerebral ischemia.

Acupuncture for patients with lumbar spinal stenosis: a randomised pilot trial.

OBJECTIVE: To assess the safety and feasibility of acupuncture for participants with symptomatic lumbar spinal stenosis (LSS) in a pilot study. METHODS: 50 participants with a clinical and radiological diagnosis of LSS were randomised to receive acupuncture combined with usual care (acupuncture group), or usual care alone (control group). Participants in the acupuncture group were offered 12-16 sessions of manual acupuncture±electroacupuncture over 6 weeks and maintained their usual self-management. The control group was provided with physical therapy as required and maintained their usual self-management. The primary outcome was the change in back-specific functional status, as measured by the Oswestry disability index (ODI) at the 3-month follow-up. Secondary outcomes included symptoms and other relevant domains. Outcome assessors were not blinded. RESULTS: 39 participants (78%) completed the trial with 524 treatment visits. There were no significant differences between the two groups in back-specific function (ODI: mean difference -2.5, 95% CI -8.9 to 3.8). Pain in the back and/or leg showed small improvements at 3 months, while there were no significant differences in other secondary outcomes. The total number of adverse events was 61 (12% of 524 treatment visits). All but one were minor and transient. The one severe adverse event was deemed to be unrelated to acupuncture. CONCLUSIONS: The study was feasible. Acupuncture combined with usual care did not confer significant functional improvements over usual care alone. Further randomised trials with adequate sample sizes and outcome assessor blinding are warranted to evaluate the role of acupuncture for LSS. TRIAL REGISTRATION NUMBER: NCT01987622.

Studies on medicinal herbs for cognitive enhancement based on the text mining of Dongeuibogam and preliminary evaluation of its effects.

ETHNOPHARMACOLOGICAL RELEVANCE: In literature on Korean medicine, Dongeuibogam (Treasured Mirror of Eastern Medicine), published in 1613, represents the overall results of the traditional medicines of North-East Asia based on prior medicinal literature of this region. We utilized this medicinal literature by text mining to establish a list of candidate herbs for cognitive enhancement in the elderly and then performed an evaluation of their effects. MATERIALS AND METHODS: Text mining was performed for selection of candidate herbs. Cell viability was determined in HT22 hippocampal cells and immunohistochemistry and behavioral analysis was performed in a kainic acid (KA) mice model in order to observe alterations of hippocampal cells and cognition. RESULTS: Twenty four herbs for cognitive enhancement in the elderly were selected by text mining of Dongeuibogam. In HT22 cells, pretreatment with 3 candidate herbs resulted in significantly reduced glutamate-induced cell death. Panax ginseng was the most neuroprotective herb against glutamate-induced cell death. In the hippocampus of a KA mice model, pretreatment with 11 candidate herbs resulted in suppression of caspase-3 expression. Treatment with 7 candidate herbs resulted in significantly enhanced expression levels of phosphorylated cAMP response element binding protein. Number of proliferated cells indicated by BrdU labeling was increased by treatment with 10 candidate herbs. Schisandra chinensis was the most effective herb against cell death and proliferation of progenitor cells and Rehmannia glutinosa in neuroprotection in the hippocampus of a KA mice model. In a KA mice model, we confirmed improved spatial and short memory by treatment with the 3 most effective candidate herbs and these recovered functions were involved in a higher number of newly formed neurons from progenitor cells in the hippocampus. CONCLUSIONS: These established herbs and their combinations identified by text-mining technique and evaluation for effectiveness may have value in further experimental and clinical applications for cognitive enhancement in the elderly.