Eun Jin Yang

Bee venom attenuates neuroinflammatory events and extends survival in amyotrophic lateral sclerosis models

BackgroundAmyotrophic lateral sclerosis (ALS) is a disease affecting the central nervous system that is either sporadic or familial origin and causing the death of motor neurons. One of the genetic factors contributing to the etiology of ALS is mutant SOD1 (mtSOD1), which induces vulnerability of motor neurons through protein misfolding, mitochondrial dysfunction, oxidative damage, cytoskeletal abnormalities, defective axonal transport, glutamate excitotoxicity, inadequate growth factor signaling, and neuroinflammation. Bee venom has been used in the practice of Oriental medicine and evidence from the literature indicates that BV plays an anti-inflammatory or anti-nociceptive role against inflammatory reactions associated with arthritis and other inflammatory diseases. The purpose of the present study was to determine whether bee venom suppresses motor neuron loss and microglial cell activation in hSOD1G93A mutant mice.MethodsBee venom (BV) was bilaterally injected (subcutaneously) into a 14-week-old (98 day old) male hSOD1G93A animal model at the Zusanli (ST36) acupoint, which is known to mediate an anti-inflammatory effect. For measurement of motor activity, rotarod test was performed and survival statistics were analyzed by Kaplan-Meier survival curves. The effects of BV treatment on anti-neuroinflammation of hSOD1G93A mice were assessed via immunoreactions using Iba 1 as a microglia marker and TNF-α antibody. Activation of ERK, Akt, p38 MAP Kinase (MAPK), and caspase 3 proteins was evaluated by western blotting.ResultsBV-treated mutant hSOD1 transgenic mice showed a decrease in the expression levels of microglia marker and phospho-p38 MAPK in the spinal cord and brainstem. Interestingly, treatment of BV in symptomatic ALS animals improved motor activity and the median survival of the BV-treated group (139 ± 3.5 days) was 18% greater than control group (117 ± 3.1 days). Furthermore, we found that BV suppressed caspase-3 activity and blocked the defects of mitochondrial structure and cristae morphology in the lumbar spinal cord of hSOD1G93A mice at the symptomatic stage.ConclusionFrom these findings, our research suggests BV could be a potential therapeutic agent for anti-neuroinflammatory effects in an animal model of ALS.

Ginseng for cognitive function in Alzheimer's disease: a systematic review.

The objective of this review is to assess the clinical evidence for or against ginseng as a treatment for Alzheimers disease (AD). We searched 20 databases from their inception to January 2009 and included all randomized clinical trials (RCTs) of any type of Panax ginseng to treat human patients suffering from AD. Methodological quality was assessed using the Jadad score. Two RCTs met all inclusion criteria. They assessed the effectiveness of ginseng as an adjunct to drug therapy on cognitive function compared with conventional drug therapy. Their results suggested significant effect in favor of ginseng on the Mini-Mental Status Examination (n = 174, weight mean difference (WMD), 1.85; 95% confidence intervals, CIs 0.88 to 2.82, P = 0.0002) and on the Alzheimers Disease Assessment Scale (ADAS)-cognitive (n = 174, WMD, 3.09; 95% CIs 1.08 to 5.09, P = 0.003). Both of these studies are burdened with serious methodological limitations. In conclusion, the evidence for ginseng as a treatment of AD is scarce and inconclusive. Further rigorous trials seem warranted.

Bee Venom Reduces Neuroinflammation in the MPTP-Induced Model of Parkinson's Disease

ABSTRACT Aim: This study was designed to investigate the anti-inflammatory effects of bee venom (BV) in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinsons disease (PD). Method: MPTP was administered by intraperitoneal (IP) injection at 2-hr intervals over an 8-hr period. Mice were then subjected to BV subcutaneous injection and sacrificed on days 1 and 3 following the final MPTP injection. The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) was assessed by tyrosine hydroxylase (TH) immunohistochemistry. Microglial activation was measured by immunohistochemistry for macrophage antigen complex-1 (MAC-1) and inducible nitric oxide synthase (iNOS). The staining intensities of MAC-1 and iNOS were quantified with respect to optical density. Result: In animals treated with MPTP, the survival percentages of TH+ cells in the SNpc were 32% on day 1 and 46% on day 3 compared with normal mice. In BV-treated mice, the survival percentages of TH+ cells improved to 70% on day 1 and 78% on day 3 compared with normal mice. BV treatment also resulted in reduced expression of the inflammation markers MAC-1 and iNOS in the SNpc. Conclusion: These data suggest that BV injection may have a neuroprotective effect that attenuates the activation of the microglial response, which has implications for the treatment of PD.

Maca (L. meyenii) for improving sexual function: a systematic review

BackgroundMaca (Lepidium meyenii) is an Andean plant of the brassica (mustard) family. Preparations from maca root have been reported to improve sexual function. The aim of this review was to assess the clinical evidence for or against the effectiveness of the maca plant as a treatment for sexual dysfunction.MethodsWe searched 17 databases from their inception to April 2010 and included all randomised clinical trials (RCTs) of any type of maca compared to a placebo for the treatment of healthy people or human patients with sexual dysfunction. The risk of bias for each study was assessed using Cochrane criteria, and statistical pooling of data was performed where possible. The selection of studies, data extraction, and validations were performed independently by two authors. Discrepancies were resolved through discussion by the two authors.ResultsFour RCTs met all the inclusion criteria. Two RCTs suggested a significant positive effect of maca on sexual dysfunction or sexual desire in healthy menopausal women or healthy adult men, respectively, while the other RCT failed to show any effects in healthy cyclists. The further RCT assessed the effects of maca in patients with erectile dysfunction using the International Index of Erectile Dysfunction-5 and showed significant effects.ConclusionThe results of our systematic review provide limited evidence for the effectiveness of maca in improving sexual function. However, the total number of trials, the total sample size, and the average methodological quality of the primary studies were too limited to draw firm conclusions. More rigorous studies are warranted.

Effects of ginsenoside Re on LPS-induced inflammatory mediators in BV2 microglial cells.

BackgroundMicroglial activation plays an important role in neurodegenerative diseases by producing several pro-inflammatory enzymes and pro-inflammatory cytokines. Lipopolysaccharide (LPS)-induced inflammation leads to the activation of microglial cells in the central nervous system (CNS) and is associated with the pathological mechanisms of neurodegenerative diseases, including PD, AD, and ALS. Ginseng is a natural antioxidant used in herbal medicine and contains ginsenosides (Rb1, Rg1, Rg3, Re, and Rd), which have anti-neoplastic and anti-stress properties.This study demonstrates the involvement of the anti-inflammatory signaling pathway, ginsenoside-Re (G-Re), which is one of the ginsenosides mediated by LPS-induced neuroinflammation in BV2 microglial cells.MethodsBV2 microglial cells were pretreated with 2 μg/ml G-Re and stimulated with 1 μg/ml LPS to induce neuroinflammation. To investigate the effect of G-Re on LPS-induced cell signaling, we performed western blotting and immunofluorescence using specific antibodies, such as phospho-p38, COX2, and iNOS.ResultsPretreatment with 2 μg/ml G-Re was neuroprotective against 1 μg/ml LPS-treated microglial cells. The neuroprotective events induced by G-Re treatment in neuroinflammation occurred via the phospho-p38, iNOS, and COX2 signaling pathways in BV2 cells.ConclusionTaken together, we suggest that G-Re exerts a beneficial effect on neuroinflammatory events in neurodegenerative diseases.

Electroacupuncture Delays Hypertension Development through Enhancing NO/NOS Activity in Spontaneously Hypertensive Rats

Using spontaneously hypertensive rats (SHR), this study investigated whether electroacupuncture (EA) could reduce early stage hypertension by examining nitric oxide (NO) levels in plasma and nitric oxide synthase (NOS) levels in the mesenteric resistance artery. EA was applied to the acupuncture point Governor Vessel 20 (GV20) or to a non-acupuncture point in the tail twice weekly for 3 weeks under anesthesia. In conscious SHR and normotensive Wistar Kyoto (WKY) rats, blood pressure was determined the day after EA treatment by the tail-cuff method. We measured plasma NO concentration, and evaluated endothelial NO syntheses (eNOS) and neuronal NOS (nNOS) protein expression in the mesenteric artery. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were lower after 3 weeks of GV20 treatment than EA at non-acupuncture point and no treatment control in SHR. nNOS expression by EA was significantly different between both WKY and no treatment SHR control, and EA at GV20 in SHR. eNOS expression was significantly high in EA at GV 20 compared with no treatment control. In conclusion, EA could attenuate the blood pressure elevation of SHR, along with enhancing NO/NOS activity in the mesenteric artery in SHR.

Electroacupuncture reduces neuroinflammatory responses in symptomatic amyotrophic lateral sclerosis model

Amyotrophic lateral sclerosis (ALS) is a paralyzing disorder that is characterized by the progressive degeneration and death of motor neurons. Acupuncture or electroacupuncture (EA) has been used for the treatment of various conditions including osteoarthritis, asthma, and other types of chronic pain conditions. It has been hypothesized that acupuncture exerts anti-inflammatory and anti-nociceptive effects on inflammatory reactions processes. The purpose of this study was to determine whether acupuncture at a specific acupoint could produce anti-inflammatory responses and suppress motor neuron loss in the hG93ASOD1 mouse, commonly used as a model for inherited ALS. We delivered EA at the Zusanli (ST36) acupuncture point in the symptomatic hSOD1G93A animal model. The EA-treated mutant hSOD1 transgenic mice showed decreases in microglial cell activity and TNF-alpha expression in the spinal cord and brain stem. Furthermore, EA significantly improved motor activity compared to the control group and reduced neuronal cell loss in hSOD1G93A mice. Our research suggests a potential functional link between EA therapy and anti-neuroinflammatory response in an ALS animal model.

Effects of bee venom on glutamate-induced toxicity in neuronal and glial cells.

Bee venom (BV), which is extracted from honeybees, is used in traditional Korean medical therapy. Several groups have demonstrated the anti-inflammatory effects of BV in osteoarthritis both in vivo and in vitro. Glutamate is the predominant excitatory neurotransmitter in the central nervous system (CNS). Changes in glutamate release and uptake due to alterations in the activity of glutamate transporters have been reported in many neurodegenerative diseases, including Parkinsons disease, Alzheimers disease, and amyotrophic lateral sclerosis. To assess if BV can prevent glutamate-mediated neurotoxicity, we examined cell viability and signal transduction in glutamate-treated neuronal and microglial cells in the presence and absence of BV. We induced glutamatergic toxicity in neuronal cells and microglial cells and found that BV protected against cell death. Furthermore, BV significantly inhibited the cellular toxicity of glutamate, and pretreatment with BV altered MAP kinase activation (e.g., JNK, ERK, and p38) following exposure to glutamate. These findings suggest that treatment with BV may be helpful in reducing glutamatergic cell toxicity in neurodegenerative diseases.

Antiallodynic Effects of Electroacupuncture Combined with MK-801 Treatment through the Regulation of p35/p25 in Experimental Diabetic Neuropathy

The anti-allodynic effect of NMDA receptor antagonist and acupuncture treatments were explored through spinal p35 regulation of diabetic neuropathic rat. We evaluated the change over time of p35/p25 protein levels in the spinal cord compared with behavioral responses to thermal and mechanical stimulation in streptozotocin (STZ)-induced diabetic rats. Additionally, we studied p35 expression when electroacupuncture (EA) and a sub-effective dose of NMDA (N-methyl-D-aspartate) receptor antagonist (MK-801) were used to treat hyperalgesia in the diabetic neuropathic pain (DNP). Thermal paw withdrawal latency (PWL) and mechanical paw withdrawal threshold (PWT) were significantly decreased in the early stage of diabetes in rats. p35 expression after STZ injection gradually decreased from 1 week to 4 weeks compared to normal controls. p25 expression in 4-week diabetic rats was significantly higher than that of 2-week diabetic rats, and thermal PWL in 4-week diabetic rats showed delayed responses to painful thermal stimulation compared with those at 2 weeks. EA applied to the SP-9 point (2 Hz frequency) significantly prevented the thermal and mechanical hyperalgesia in the DNP rat. Additionally, EA combined with MK-801 prolonged anti-hyperalgesia, increased p35 expression, and decreased the cleavage of p35 to p25 during diabetic neuropathic pain. In this study we show EA combined with a sub-effective dose of MK-801 treatment in DNP induced by STZ that is related to p35/p25 expression in spinal cord.

The Effects of Bee Venom Acupuncture on the Central Nervous System and Muscle in an Animal hSOD1G93A Mutant

Amyotrophic lateral sclerosis (ALS) is caused by the degeneration of lower and upper motor neurons, leading to muscle paralysis and respiratory failure. However, there is no effective drug or therapy to treat ALS. Complementary and alternative medicine (CAM), including acupuncture, pharmacopuncture, herbal medicine, and massage is popular due to the significant limitations of conventional therapy. Bee venom acupuncture (BVA), also known as one of pharmacopunctures, has been used in Oriental medicine to treat inflammatory diseases. The purpose of this study is to investigate the effect of BVA on the central nervous system (CNS) and muscle in symptomatic hSOD1G93A transgenic mice, an animal model of ALS. Our findings show that BVA at ST36 enhanced motor function and decreased motor neuron death in the spinal cord compared to that observed in hSOD1G93A transgenic mice injected intraperitoneally (i.p.) with BV. Furthermore, BV treatment at ST36 eliminated signaling downstream of inflammatory proteins such as TLR4 in the spinal cords of symptomatic hSOD1G93A transgenic mice. However, i.p. treatment with BV reduced the levels of TNF-α and Bcl-2 expression in the muscle hSOD1G93A transgenic mice. Taken together, our findings suggest that BV pharmacopuncture into certain acupoints may act as a chemical stimulant to activate those acupoints and subsequently engage the endogenous immune modulatory system in the CNS in an animal model of ALS.