Effect of Chinese herbal compound Naofucong () on the inflammatory process induced by high glucose in BV-2 cells.

OBJECTIVE: To determine the effect of medicated serum of Chinese herbal compound Naofucong (, NFC) on the microglia BV-2 cells viability and the transcription and expression of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in microglia BV-2 cells to further explore the mechanisms underlying the protective effect of NFC on inflammatory process induced by high glucose. METHODS: The microglia BV-2 cells incubated in vitro were divided into different groups: the control group (25 mmol/L glucose), the model group (75 mmol/L glucose), high glucose media containing different dose medicated serum of NFC. After being cultured for 24 h, changes in IL-6 and TNF-α were measured by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The expression of surface marker CD11b of activated microglia was measured by confocal laser scanning microscope and Western blot. Nuclear factor-κB (NF-κB) p-p65 expression was analyzed by Western blot. RESULTS: The model group obviously increased the expression of microglial surface marker CD11b and NF-κB p-p65 (all P<0.01), induced a signifificant up-regulation of release and the mRNA expression of IL-6 and TNF-α (P<0.01 or P<0.05). The medicated serum of NFC could obviously down-regulate the transcription and expression of surface marker CD11 b and NF-κB p-p65 (all P<0.01), and inhibit the mRNA and protein expression (P<0.01 or P<0.05) of inflflammatory cytokines, such as IL-6 and TNF-α, in microglia BV-2 cells cultured with high glucose for 24 h. CONCLUSIONS: The inhibition of microglial activation and IL-6 and TNF-α expression induced by high glucose may at least partly explain NFC therapeutic effects on diabetes-associated cognitive decline diseases. Its underlying mechanism could probably be related to the inhibition of NFC on NF-κB phosphorylation.

Neural regeneration: role of traditional Chinese medicine in neurological diseases treatment.

The effects of a single compound and a mixture of traditional Chinese medicine (TCM) on promoting proliferation, differentiation, and migration of neural stem cells and regulating their microenvironment have been observed by Chinese scholars in recent years. These results showed good prospects in improving neural regeneration and repair of neurological disorders such as ischemic brain injury, Alzheimer's disease, Parkinson's disease, and depression. According to the TCM theory, the relationship between life of an individual and the disease was regarded as an entirety, and the theory emphasized the treatment based on syndrome differentiation since ancient times. In this paper, we attempted to introduce these medicines, which belong to natural products and have already been proved to possess clear therapeutic action on human bodies in the clinical setting. We summarized their effects promoting brain neurogenesis and repairing brain injuries in animal models and some mechanisms at the cellular and molecular levels.

Gossypium herbaceam L. extracts ameliorate disequilibrium of IL-1RA/IL-1ß ratio to attenuate inflammatory process induced by amyloid ß in rats.

A chronic inflammatory response possibly mediated by Amyloid ß (Aß) is believed to be a major factor in the pathology of Alzheimer's disease (AD). Studies suggest that the mediators of the inflammatory response, which might contribute to brain damage, involve cytokines, such as IL-1ß. IL-1ß could play an important part in the development of pathologic conditions. There is also an endogenous interleukin-1 receptor antagonist (IL-1RA) in IL-1 family, which could prevent the actions of IL-1ß by competing for receptor binding without inducing any signal transduction. Therefore, the balance of IL-1ß vs IL-1RA is a critical parameter in determining not only whether excessive host inflammation will occur, but also the degree of subsequent host cell damage and associated toxicity. In our previous study, it has been determined that the anti-inflammatory action of Gossypium herbaceam L. extracts (GHE) was involved in its neuroprotection. However, the effects of GHE on IL-1ß and IL-1RA have not been clearly defined in the experimental rat model of AD induced by Aß. Therefore, the current study is performed to evaluate whether GHE could affect the disequilibrium of IL-1RA/IL-1ß ratio in the hippocampus of rats after Aß treatment. Subsequently, we further identify that GHE could efficaciously promote Akt and GSK3ß phosphorylation, and thereby contribute to IL-1ß release decrease as well as a concurrent increase in the level of IL-1RA through NF-κB and MAPK pathways. As a consequence, GHE is potentially beneficial to maintain the endogenous IL-1RA/ IL-1ß balance in the hippocampus of rats and it might be a potential agent to ameliorate inflammatory process in AD.

Gossypium herbaceam extracts attenuate ibotenic acid-induced excitotoxicity in rat hippocampus.

Excitotoxicity is one of the most extensively studied processes of neuronal death and plays an important role in Alzheimer's disease. In the present study, the protective effects of Gossypium herbaceam extracts (GHE) on learning and memory impairment induced by excitatory neurotoxin ibotenic acid were examined in vivo using Morris water maze. Furthermore, neuroprotective effects of GHE were investigated with methods of immunohistochemistry and biochemistry. Our data showed that oral administration with GHE at the doses of 35, 70 and 140 mg/kg exerted an improved effect on the learning and memory impairment in rats induced by intracerebral injection of ibotenic acid. To confirm the precise mechanism of memory improvement by presence of GHE, we further investigated the potential protection on the hippocampus. Our findings suggest that GHE afforded a beneficial inhibition on pro-apoptosis proteins expression following ibotenic acid. Additionally, calcium pump activity and calbindin-D28k expression were dramatically increased after GHE treatment, implicating that the modulation of calcium homeostasis could be involved in the mechanism underlying neuroprotection of GHE against ibotenic acid-induced excitotoxicity. These data suggested that GHE could be a potential agent for preventing or retarding the development or progression of Alzheimer's disease.

Gossypium herbaceam extracts inhibited NF-kappaB activation to attenuate spatial memory impairment and hippocampal neurodegeneration induced by amyloid-beta in rats.

Amyloid-beta (Abeta) is considered to be responsible for the pathogenesis of Alzheimer's disease. In the present study, the protective effect of Gossypium herbaceam extracts (GHE) on learning and memory impairment induced by Abeta were examined in vivo using Morris water maze and step through task. Furthermore, the antioxidant activity and neuroprotective effect of GHE was investigated with methods of histochemistry and biochemistry. These data showed that oral administration with GHE at the doses of 35, 70 and 140 mg/kg exerted an improved effect on the learning and memory impairment in rats induced by intracerebroventricular (i.c.v.) injection of 10 microg of Abeta(25-35). Subsequently, the GHE afforded a beneficial action on promotion on the activity of glutathione peroxidase and catalase, as well as inhibition on the NF-kappaB activation in the hippocampus followed by the presence of Abeta(25-35). Meanwhile, the number of degenerating neurons with an apoptotic feature was dramatically decreased in hippocampus after treatment with GHE, implicating that its antioxidant stress and inhibition of NF-kappaB activation could be involved in the mechanism underlying neuroprotection of GHE against Abeta-induced cell death. These findings suggested that GHE might be a potential agent for treatment of Alzheimer's disease.

Protective effects of phytoestrogen alpha-zearalanol on beta amyloid25-35 induced oxidative damage in cultured rat hippocampal neurons.

Although experimental evidence has shown that the neuroprotective effect from estrogen may benefit postmenopausal women, but the clinical use of estrogen was limited by the risk of increasing the cases of mammary and endometrial cancer. This study was designed to evaluate the neuroprotective effects of a novel phytoestrogen alpha-zearalanol (alpha-ZAL), on the cultured rat hippocampal neurons. Following a 24-h exposure of the cells to amyloid beta-peptide fragment 25-35 (A beta 25-35), a significant reduction in cell survival and activities of total superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as increased of malondialdehyde (MDA) were observed. Preincubation of the cells with alpha-ZAL or 17 beta-estradiol(17 beta-E2) prior to A beta 25-35 exposure elevated the cell survival and SOD and GSH-Px activities, and decreased the level of MDA. These data suggested that the phytoestrogen alpha-ZAL, like estrogen, may effectively antagonize A beta 25-35-induced cell toxicity, which might be beneficial for neurons.

Effects of ning shen ling granule and dehydroepiandrosterone on cognitive function in mice undergoing chronic mild stress.

OBJECTIVE: To investigate the changes of spontaneous and cognitive behavior, and cholinergic M receptors in the brain of mice subjected to chronic mild stress (CMS), and to determine the effect of Ning Shen Ling Granule (NSL) and dehydroepiandrosterone (DHEA) on them. METHODS: CMS model mice were established by applying stress every day for 3 consecutive weeks with 7 kinds of unforeseeable stress sources, and they were medicated for 1 week beginning at the 3rd week of modeling. The changes in behavior were determined by Morris Water Maze and spontaneous movement test, and M-receptor binding activity in cerebral cortex, hippocampus and hypothalamus were measured by radioactive ligand assay with 3H-QNB. RESULTS: (1) The spontaneous movement in CMS model mice was significantly reduced, with the latency for searching platform in Morris Water Maze obviously prolonged (P<0.01), and these abnormal changes in behavior were improved in those treated with NSL and DHEA. (2) The binding ability of M-receptor in cerebral cortex and hippocampus of CMS mice was significantly decreased as compared with those in the control group (P<0.05), but could be restored to the normal level after intervention with NSL or DHEA. CONCLUSION: The decline of spontaneous movement and spatial learning and memory ability could be induced in animals by chronic mild stress, and that may be related to the low activity of central cholinergic M-receptors. Both NSL and DHEA could effectively alleviate the above-mentioned changes.

Treatment with phytoestrogen alpha-zearalanol might protect neurons of hippocampus in ovariectomized rats.

Although neuroprotective effects of estrogen on postmenopausal women have been recognized, an associated increased incidence of uterine and breast tumors has jeopardized the clinical use of estrogen. This study was designed to evaluate the neuroprotective effects of a novel phytoestrogen alpha-zearalanol (alpha-ZAL), on ovariectomized (OVX) rats. Adult Wistar rats were ovariectomized or sham-operated and treatment with equivalent doses of 17beta-estradiol or alpha-ZAL for 5 wk. Uteruses have been weighted and stained by hematoxylin and eosin for morphology analysis. The expression of synaptophysin and parvalbumin in hippocampus were evaluated by immunohistochemistry assays. Our experiments indicated that the synaptophysin and parvalbumin-positive areas were significantly decreased in the OVX group compared to the sham group, alpha-ZAL or 17beta-estradiol administration can reverse the effects. Although alpha-ZAL and 17beta-estradiol treatments reconciled uterus weight loss which was induced by ovariectomy, the effect of alpha-ZAL was less than 17beta-estradiol. This result suggests that alpha-ZAL may effectively abate neurons loss in the hippocampus while slightly promoting weight gain of the uterus.

[Effect of Tujian decoction on protein kinase C activity in renal cortex in diabetic rat].

OBJECTIVE: To investigate influence of administration of Tujian decoction (Chinese herbal medicine) on protein kinase C (PKC) activity, renal function and structure in diabetic rat kidney. METHOD: Experimental diabetic nephropathy model was induced by nephrectomy combined with streptozotocin (STZ) injection in sprague-dawley rat. Tujian decoction (20 g x kg(-1) x d(-1)) and Valsartan (20 mg x kg(-1) x d(-1)) were orally administrated respectively for 12 weeks. PKC activity was measured by [3H]phorbol 12, 13-dibutyrate ([3H]PDBu) binding assay. 24 h urine protein excretion (Upro) and renal pathological changes were observed. RESULT: In 12th week, diabetic nephrectomized rats developed proteinuria, glomerulosclerosis, increased membrane PKC activity (mPKC), decreased cytosol PKC (cPKC), and increased ratio of mPKC and cPKC (M/C). Administration of Tujian decoction or Valsartan led to a reduction in proteinuria, structural injury, mPKC and M/C, and a recovery in cPKC. CONCLUSION: Tujian decoction possesses a renoprotective effect on diabetic nephrectomized rat, at least partially via the inhibition of PKC activation in renal cortex.

[Effects of 7-oxo-DHEA treatment on the immunoreactivity of BALB/c mice subjected to chronic mild stress].

AIM: To determine whether 7-oxo-dehydroepiandrosterone (7-oxo-DHEA) can reverse the hypoimmunity in BALB/c mice exposed to chronic mild stress. METHODS: A chronic mild stress animal model was established by subjecting BALB/c mice to a stressful regimen arranged in an unpredicted manner for 4 consecutive weeks. Immunological function alternations under chronic mild stress were assessed by lymphocytes proliferative response to mitogens and NK cell lysis activity test. RESULTS: The studies showed the correlation between the state of depression and abnormalities in the immune response, such as a decrease of T lymphocytes proliferative response to Con A and suppression of cytotoxic of NK cell. Meanwhile, significant decrease of T3 and T4 levels was also observed. When stressed mice were daily given 7-oxo-DHEA 15 mg.kg-1, lymphocyte proliferative response and the NK cell activity were significantly enhanced and the decreased levels of T3 and T4 were restored in the stressed mice. CONCLUSION: 7-oxo-DHEA can improve the depressive symptoms and hypoimmunity of BALB/c mice induced by chronic mild stress as its parent DHEA.