Several studies have demonstrated that the Chinese herb Gastrodia elata Blume can protect against amyloid beta-peptide (Aβ)-induced cell death. To investigate the possible therapeutic effects of Gastrodia elata Blume on Alzheimer's disease, we established a rat model of Alzheimer's disease by injecting Aβ25-35 into bilateral hippocampi. These rats were intragastrically administered 500 or 1 000 mg/kg Gastrodia elata Blume per day for 52 consecutive days. Morris water maze tests showed that Gastrodia elata Blume treatment significantly improved the spatial memory of Alzheimer's disease rats. Congo red staining revealed that Gastrodia elata Blume significantly reduced the number of amyloid deposits in the hippocampus of these rats. Western blot analysis showed that choline acetyltransferase expression in the medial septum and hippocampus was significantly increased by the treatment of Gastrodia elata Blume, while Ellman method showed significant decrease in the activity of acetylcholinesterase in all three regions (prefrontal cortex, medial septum and hippocampus). These findings suggest that long-term administration of Gastrodia elata Blume has therapeutic potential for Alzheimer's disease.
(1) Intrahippocampal injection of amyloid beta-peptide (25-35) (Aβ25-35) impaired spatial reference memory in rats.
(2) Aβ25-35 had detrimental effects on choline acetyltransferase expression and acetylcholinesterase activity in the brain.
(3) Long-term administration of Gastrodia elata Blume partially reversed these effects in Alzheimer's disease rats.
(4) Gastrodia elata Blume is a potential drug candidate for the treatment of Alzheimer's disease.
Luteolin (3′,4′,5,7-tetrahydroxyflavone) has powerful anti-apoptotic and antioxidant properties. This study aimed to investigate the effects of luteolin on hyperglycemia-mediated apoptosis in the hippocampi of rats with streptozotocin-induced diabetic encephalopathy after injection into the tail veins, and the molecular mechanisms involved. Biochemistry and terminal deoxynucleotidyl transferase mediated dUTP nick end labelling detection results showed that luteolin treatment (given twice daily for 15 days) significantly inhibited hyperglycemia-mediated apoptosis, decreased malondialdehyde levels and increased glutathione levels in the hippocampi of streptozotocin-induced diabetic rats. Western blot analysis revealed that luteolin also inhibited the expression of apoptosis-related factors and cytochrome c release from mitochondria. Luteolin also improved the learning and memory abilities of rats with diabetic encephalopathy in a water maze test. Further western blot analysis revealed that luteolin treatment facilitated neuronal cell survival through activation of the phosphatidylinositol 3-kinase/Akt signaling pathway, an extracellular signal pathway involved in the suppression of cell apoptosis and promotion of cell survival. These experimental findings indicate that luteolin can inhibit apoptosis of hippocampal nerve cells in rats with diabetic encephalopathy, and that this effect is mediated by an indirect antioxidative effect, the inhibition of activation of apoptosis-related factors and the activation of phosphatidylinositol 3-kinase/Akt signal pathway.
(1) Luteolin is a kind of natural flavonoid existing in several plants. It has many kinds of pharmacological activities, with anti-oxidative, anti-inflammatory and anti-apoptosis effects, and can be regarded as a potential natural anti-aging protective agent, even an ideal treatment for neurological impairment.
(2) Luteolin injection via tail veins reduced the amount of streptozotocin-induced apoptosis in hippocampal cells in rats with diabetic encephalopathy, and the molecular mechanism was investigated.
(3) Luteolin could inhibit apoptosis of hippocampal nerve cells in rats with diabetic encephalopathy, and the mechanism of action included an indirect anti-oxidative effect and inhibition of apoptosis-related factors. In addition, luteolin activates the phosphatidylinositol 3-kinase/Akt signaling pathway, and accordingly suppresses apoptosis of hippocampal nerve cells.
Ninety-four patients with lumbar intervertebral disc herniation were enrolled in this study. Of these, 48 were treated with Feng's Spinal Manipulation, hot fomentation, and bed rest (treatment group). The remaining 46 patients were treated with hot fomentation and bed rest only (control group). After 3 weeks of treatment, clinical parameters including the angle of straight-leg raising, visual analogue scale pain score, and Japanese Orthopaedic Association score for low back pain were improved. The treatment group had significantly better improvement in scores than the control group. Magnetic resonance myelography three-dimensional reconstruction imaging of the vertebral canal demonstrated that filling of the compressed nerve root sleeve with cerebrospinal fluid increased significantly in the treatment group. The diameter of the nerve root sleeve was significantly larger in the treatment group than in the control group. However, the sagittal diameter index of the herniated nucleus pulposus and the angle between the nerve root sleeve and the thecal sac did not change significantly in either the treatment or control groups. The effectiveness of Feng's Spinal Manipulation for the treatment of symptoms associated with lumbar intervertebral disc herniation may be attributable to the relief of nerve root compression, without affecting the herniated nucleus pulposus or changing the morphology or position of the nerve root.
(1) The nerve root sleeve is filled with cerebrospinal fluid that acts as a natural pressure receptor. We evaluated changes in the anatomical and biomechanical characteristics of the nerve root sleeve to investigate the mechanisms underlying the curative effect of Feng's Spinal Manipulation.
(2) Magnetic resonance myelography can clearly show nerve root compression, and was used to assess the effectiveness of Feng's Spinal Manipulation for treatment of symptoms associated with lumbar intervertebral disc herniation.
(3) Feng's Spinal Manipulation for treatment of lumbar intervertebral disc herniation reduces compression of the nerve root, but does not reduce disc herniation.
The astrocyte is a critical regulator of neuronal survival after ischemic brain injury. Electroacupuncture may be an effective therapy for cerebral ischemia, as electroacupuncture frequency can affect the structural integrity of astrocytes. In this study, a rat model of middle cerebral artery occlusion established using the modified thread embolism method was treated with electroacupuncture of the bilateral Quchi (LI11) and Zusanli (ST36) at 15, 30, and 100 Hz frequencies. Behavioral testing, immunohistochemistry and electron microscopy were used to explore the effect of these electroacupuncture frequencies used on maintaining the structural integrity of ischemic brain tissue. Compared with the model and 100 Hz electroacupuncture groups, the 15 and 30 Hz electroacupuncture groups displayed decreased neurological deficit scores, as evaluated by the “Longa” method, significantly increased glial fibrillary acidic protein expression, and alleviated ultrastructural damage of astrocytes at the edge of the infarct. Our experimental findings indicate that 15 and 30 Hz electroacupuncture intervention can favorably maintain the structural integrity of astrocytes and play a protective role in cerebral ischemic injury. Astrocyte structural integrity may be the mechanism underlying acupuncture production of ischemic tolerance.
(1) Astrocytes can aggravate ischemic brain damage and therefore determine the survival of ischemic neurons.
(2) Electroacupuncture is an effective treatment of cerebral ischemia, however, the optimal electroacupuncture frequency for the treatment of cerebral ischemia remains unclear.
(3) Electroacupuncture intervention at 15 and 30 Hz frequencies can maintain the structural integrity of astrocytes, showing a protective effect against cerebral ischemic injury. We speculate that maintenance of the structural integrity of astrocytes is one possible way that acupuncture produces ischemic tolerance.
Eleutheroside B or E, the main component of Acanthopanax, can relieve fatigue, enhance memory, and improve human cognition. Numerous studies have confirmed that high doses of acetylcholine significantly attenuate clinical symptoms and delay the progression of Alzheimer's disease. The present study replicated a rat model of aging induced by injecting quinolinic acid into the hippocampal CA1 region. These rats were intraperitoneally injected with low, medium and high doses of eleutheroside B or E (50, 100, 200 mg/kg), and rats injected with Huperzine A or PBS were used as controls. At 4 weeks after administration, behavioral tests showed that the escape latencies and errors in searching for the platform in a Morris water maze were dose-dependently reduced in rats treated with medium and high-dose eleutheroside B or E. Hematoxylin-eosin staining showed that the number of surviving hippocampal neurons was greater and pathological injury was milder in three eleutheroside B or E groups compared with model group. Hippocampal homogenates showed enhanced cholinesterase activity, and dose-dependent increases in acetylcholine content and decreases in choline content following eleutheroside B or E treatment, similar to those seen in the Huperzine A group. These findings indicate that eleutheroside B or E improves learning and memory in aged rats. These effects of eleutheroside B or E may be mediated by activation of cholinesterase or enhanced reuse of choline to accelerate the synthesis of acetylcholine in hippocampal neurons.
(1) Administration of high-dose acanthopanax significantly relieves the symptoms and shortens the course of Alzheimer's disease. However, little is known about eleutheroside B or E treatment for Alzheimer's disease or its related mechanisms.
(2) The results of this study demonstrate that eleutheroside B or E can improve learning and memory deficits in aged rats induced by quinolinic acid, possibly by activating cholinesterase or enhancing choline reuse to accelerate acetylcholine synthesis in hippocampal cells.
The traditional Chinese medicine Jiaweisinisan has antidepressant effects, and can inhibit hypothalamus-pituitary-adrenal gland axis hyperactivity in stress-induced depression. In this study, rat hippocampal neural precursor cells were cultured in serum-free medium in vitro and a stress damage model was established with 120 μM corticosterone. Cells were treated with 10% (v/v) Jiaweisinisan drug-containing serum and the corticosterone antagonist RU38486. Results of the 3-(4,5-dimethylthiazol-2-yl)-3,5-di-phenytetrazoliumromide assay showed that both Jiaweisinisan drug-containing serum and RU38486 promoted the proliferation of neural precursor cells after corticosterone exposure. Immunofluorescence detection showed that after Jiaweisinisan drug-containing serum and RU38486 treatment, the 5-bromo-2-deoxyuridine/terminal deoxynucleotidyl transferase dUTP nick end labeling ratio in hippocampal neural precursor cells significantly increased, and the apoptotic rates of glial cells reduced, and neuron-like cell differentiation from neural precursor cells significantly increased. Our experimental findings indicate that Jiaweisinisan promotes hippocampal neurogenesis after stress damage.
(1) Jiaweisinisan, a traditional Chinese medicine, has been suggested to prevent stress injury.
(2) This study aimed to observe the influence of Jiaweisinisan drug-containing serum on the proliferation and differentiation of hippocampal neural precursor cells following corticosterone-induced damage.
(3) Jiaweisinisan can promote the proliferation of hippocampal neural precursor cells, and inhibit the apoptosis of glial cells and neurons in the presence of high concentrations of corticosterone.
Scutellaria baicalensis stem-leaf total flavonoid might attenuate learning/memory impairment and neuronal loss in rats induced by amyloid beta-peptide. This study aimed to explore the effects of Scutellaria baicalensis stem-leaf total flavonoid on amyloid beta-peptide-induced neuronal apoptosis and the expression of apoptosis-related proteins in the rat hippocampus. Male Wistar rats were given intragastric administration of Scutellaria baicalensis stem-leaf total flavonoid, 50 or 100 mg/kg, once per day. On day 8 after administration, 10 μg amyloid beta-peptide (25-35) was injected into the bilateral hippocampus of rats to induce neuronal apoptosis. On day 20, hippocampal tissue was harvested and probed with the terminal deoxyribonucleotidyl transferase-mediated biotin-16-dUTP nick-end labeling assay. Scutellaria baicalensis stem-leaf total flavonoid at 50 and 100 mg/kg reduced neuronal apoptosis induced by amyloid beta-peptide (25-35) in the rat hippocampus. Immunohistochemistry and western blot assay revealed that expression of the pro-apoptotic protein Bax, cytochrome c and caspase-3 was significantly diminished by 50 and 100 mg/kg Scutellaria baicalensis stem-leaf total flavonoid, while expression of the anti-apoptotic protein Bcl-2 was increased. Moreover, 100 mg/kg Scutellaria baicalensis stem-leaf total flavonoid had a more dramatic effect than the lower dosage. These experimental findings indicate that Scutellaria baicalensis stem-leaf total flavonoid dose-dependently attenuates neuronal apoptosis induced by amyloid beta-peptide in the hippocampus, and it might mediate this by regulating the expression of Bax, cytochrome c, caspase-3 and Bcl-2.
(1) Based on the objective criteria for drug effects described in previous in vivo studies, apoptosis was examined in this study, and the expression of apoptosis-related proteins was qualitatively and semi-quantitatively assayed using immunohistochemistry. Furthermore, western blot analysis was used for quantitating protein expression. Bax, Bcl-2, cytochrome c and caspase-3 were selected for assessment.
(2) Scutellaria baicalensis stem-leaf total flavonoid can attenuate apoptosis in the hippocampus induced by amyloid beta-peptide, reduce the expression of Bax, cytochrome c and caspase-3, and increase the expression of the anti-apoptotic protein Bcl-2.
(3) Scutellaria baicalensis stem-leaf total flavonoid has inhibitory effects against neuronal apoptosis in amyloid beta-peptide (25-35)-treated rats, and the effect is dose-dependent.
We report a case of a 21-year-old man who had severe traumatic brain injury as a result of an accident at the age of 16 years. Two years and 4 months after the trauma, at the age of 19 years, he still had severe right hemiplegia and cognitive dysfunction including aphasia and attention and memory disturbance. Conventional rehabilitation programs could not resolve all of the neuropsychological problems. He started receiving Goshinjo therapy over a period of 22 months. Following the therapy, significant improvements in verbal intelligence quotient (assessed by the Wechsler Adult Intelligence Scale-Third Edition) and attention and concentration function (using the Wechsler Memory Scale-Revised), and remission of traumatic epilepsy were observed. Goshinjo therapy is suspected to be effective in the treatment of cognitive dysfunction in the chronic stage after severe traumatic brain injury.
(1) Goshinjo therapy restores and normalizes the excessive life energy field in the human body.
(2) The present study describes the case of a young man who received Goshinjo therapy after severe traumatic brain injury. Significant improvements in verbal intelligence quotient, attention and concentration were observed.
(3) Goshinjo therapy is suspected to be effective in the treatment of cognitive dysfunction in the chronic stage after severe traumatic brain injury.
Oxygen free radical damage is regarded as a direct or indirect common pathway associated with diabetic neuropathy and is the main cause of complications in peripheral neuropathies. We speculate that Jiaweibugan decoction has a significant effect in treating diabetic peripheral neuropathy through an anti-oxidative stress pathway. In this study, a diabetic rat model was established by intraperitoneal injection of streptozotocin. Rats were treated with Jiaweibugan decoction via intragastric administration. The levels of malondialdehyde and glutathione, which are indirect indexes of oxidative stress, in serum were determined using a colorimetric method. The expression levels of nuclear factor kappa B p65 mRNA and p38 mitogen-activated protein kinase, which are oxidative stress associated factors, in the dorsal root ganglion of spinal S4-6 segments were evaluated by reverse-transcriptase polymerase chain reaction and immunohistochemistry. Results showed that, Jiaweibugan decoction significantly ameliorated motor nerve conduction velocity in diabetic rats, effectively decreased malondialdehyde levels in serum and the expression of nuclear factor kappa B p65 mRNA and p38 mitogen-activated protein kinase mRNA in the dorsal root ganglion, and increased glutathione levels in serum. Therefore, our experimental findings indicate that Jiaweibugan decoction plays an anti-oxidative stress role in the diabetic peripheral neuropathy process, which has a protective effect on peripheral nerve injury.
(1) Jiaweibugan decoction can effectively improve the clinical symptoms of patients with diabetic peripheral nerve injury; however, the protective mechanisms remain unclear.
(2) Jiaweibugan decoction can markedly improve sciatic motor nerve conduction velocity in diabetic rats, decrease serum levels of malondialdehyde and the expression of nuclear factor kappa B p65 and p38 mitogen-activated protein kinase in the dorsal root ganglion, and increase serum levels of glutathione.
(3) Oxidative stress contributes to the process of diabetic peripheral neuropathy. In this study, we show that Jiaweibugan decoction can reduce oxidative stress levels in a rat model of diabetic peripheral neuropathy.
Suspended moxibustion-produced heat can transfer from the acupoint to other sites of the body. The suspended moxibustion should be terminated when clinical propagated sensation disappears, because this implies that the quantity of moxibustion is sufficient. We wanted to investigate if this phenomenon also occurs in experimental animals. In the present study, a rat model of stroke was established and treated with suspended moxibustion at Dazhui (DU14) for 60 minutes. Results showed that the increase in tail temperature began at 15 minutes after suspended moxibustion and decreased gradually at 40 minutes. In addition, neurological function was significantly improved in stroke rats with tail temperature increase following suspended moxibustion, and this effect was associated with significantly reduced tumor necrosis factor α and interleukin 1β mRNA. However, there was no significant difference between 40- and 60-minute suspended moxibustion. The findings indicate that elevated tail temperature began to decrease at 40 minutes after suspended moxibustion, and further suspended moxibustion was not useful in the recovery of stroke rats.
(1) Tail temperature increased after 15-minute suspended moxibustion, but decreased after 40 minutes in stroke rats.
(2) Suspended moxibustion with tail temperature increase improved neurological deficit better than did moxibustion without tail temperature increase.
(3) Continuing suspended moxibustion could not further strengthen its efficacy when tail temperature began to decrease.
(4) This finding is in accordance with the rules of heat-sensitive moxibustion, which states that moxibustion should be terminated when the propagated sensation disappears, as this implies that the quantity of moxibustion is sufficient.