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.

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.

[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.