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Researches of Pueraria Mirifica

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Estradiol Replacement in Ovariectomized Rats Is Antihyperalgesic in the Formalin Test

Authors: Christy A. Mannino,* Samantha M. South,* Vanya Quinones-Jenab,† and Charles E. Inturrisi*
*Department of Pharmacology, Weill Medical College of Cornell University, New York, New York.
†Department of Psychology, Hunter College, City University of New York, New York, New York.

Abstract: A subcutaneous implant of 17β-estradiol or progesterone provides steady-state serum hormone levels from 7 to 24 days after implantation and allows the evaluation of the effects of the replacement with these hormones on phase 1 and phase 2 formalin-induced behaviors in ovariectomized (OVX) rats. Graded doses of 17β-estradiol (5% to 40%) reduce formalin-induced behavior by 35% to 49% during phase 2 but not during phase 1, as measured with an automated formalin apparatus. The maximal response is seen with 20% 17β-estradiol. The antihyperalgesic effect of 20% 17β-estradiol is significant at 8 days after implantation and persists at 21 days. In contrast, graded doses of progesterone have no effect on either phase of formalin. The estrogen receptor antagonist tamoxifen completely prevents the antihyperalgesic effect of the 20% 17β-estradiol implant. Formalin- induced behaviors during phase 2 are significantly less in proestrus females and OVX rats given 20% 17β-estradiol compared with OVX control rats. Also, the formalin-induced increase in serum corticosterone is attenuated in OVX control rats compared with proestrus females and OVX rats given 20% 17β-estradiol. These results indicate that estrogen replacement in OVX rats restores the maximal corticosterone response to tonic pain and, by an estrogen receptor–mediated process, inhibits tonic pain. Perspective: Hormone replacement (HR) therapy remains a widely used modality. We used a pharmacokinetically based rat HR model that results in continuous physiological levels of 17β-estradiol to demonstrate the analgesic (antihyperalgesic) effects of estrogen replacement in an inflammatory pain model (formalin). These results suggest a potentially important consequence of HR therapy.

Published : 17 August 2004
Key words : Pueraria Mirifica, Phytoestrogen, PTH, Calcium, Aged menopausal monkey

Pueraria Mirifica initiative promotes the cellular mechanism of neuronal survival in neuron human neuroblastoma cells.

Authors: Sayan Sawatsri*1, Wanphen Yamkunthong1, Neil Sidell2.
1. Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand;
2. Emory University School of Medicine, GYN-OB Dept., Research Div., Atlanta, GA, USA.

Pueraria Mirifica (PM) or White Kwao Krue (Thai Herb) has been used as a rejuvenator for long time in aging. It contains a variety of phytoestrogens that possess the highest estrogenic activity. In molecular research and epidemiological data show that estrogen replacement therapy (ERT) can decrease the risk of developing Alzheimer's disease. Interestingly, whether the estrogenic effect of PM can prevent neurotrophic from neurotoxic agents e.g. glutamate, H2O2, and beta-amyloid 25-35 in AD model. What a mechanism of PM that prevents neuronal cell death is.

Objectives: The current study investigated the neurotrophic and neuroprotective action of the complex formulation of phytoestrogen from a standardized PM extract compare with 17b-estradiol in AD model in vitro.

Methods: Crude PM was extracted by ethanol and standardized by HPLC. Action of standarize PM was pretreated in human neuroblastoma cell line (LA-N5) in complete media of estrogen deprivation condition with neurotoxic agents; 0.2mM glutamate, 20µM H2O2, and 8 µg/ml beta-amyloid 25-35 by inhibit cell death. By using inverted microscope, morphologic and biochemical analysis were conducted in neuroblastoma cultures to determine the neurotrophic and neuroprotective properties of standardize PM and 17b-estradiol. Using ICI anti-estrogenic activity and estrogen dependent breast cancer cell for demonstrate the inhibition of PM in estrogen receptor pathway in AD model.

Results: the results demonstrated that PM significantly decreased neuronal cell death in a time and dose dependent fashion. Results of neuroprotection studies demonstrated that PM and 10-8 M 17b-estradiol induced highly significant neuroprotection against beta-amyloid, hydrogen peroxide, glutamate-induced toxicity. Inhibi action of PM and 17b-estradiol by estrogen antagonist (ICI164,384) after induce with neurotoxic agents that show significantly increase cell death.

Conclusions: PM shows estrogenic activity similar 17b-estradiol and prevents neurotoxic agents for neuronal dead significantly by may pass estrogen pathway. For clinical application of PM possible to use for intervention in Alzheimer's disease and other neurodegenerative disease in aging in the near future.

Published: 2008
Keywords: Phytoestrogens, Pueraria mirifica, Hippocampal neuron, 17ß-estradiol, Synaptophysin, Synaptic density
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