Efficacy of porcine placental extract on climacteric symptoms in peri- and postmenopausal women.

OBJECTIVES: Injections of human placental extract have long been used to treat menopausal symptoms. Recently, porcine placental extract (PPE), an oral supplement, has been developed for this purpose. The aim of this study was to assess whether PPE has an impact on climacteric symptoms in perimenopausal and postmenopausal women. METHODS: Seventy-six women with climacteric symptoms were enrolled into this open-label, randomized, controlled study. The control group (n = 38) underwent 24 weeks of open treatment with Toki-shakuyaku-san (TJ23), an oral herbal remedy used to alleviate climacteric symptoms. The PPE group (n = 38) received three capsules of PPE/day orally for the initial 12 weeks and six capsules/day for the next 12 weeks. Climacteric symptoms were evaluated in both groups using the Simplified Menopausal Index (SMI) score, Zung's Self-Rating Depression Scale (ZSDS) and the Spielberger State-Trait Anxiety Inventory (STAI) before commencing treatment, after 12 weeks of treatment and on completion of treatment. RESULTS: Treatment with PPE was significantly (p < 0.01) more effective in reducing the SMI, ZSDS and STAI measures at 12 and 24 weeks than TJ23 treatment alone. Treatment with PPE was also significantly effective (p < 0.01) in reducing the subscale scores of the SMI for items such as hot flushes, insomnia, irritability, depression, fatigue and joint pain. PPE treatment had no significant adverse effects. CONCLUSION: Oral PPE treatment is another possible option for treating perimenopausal and postmenopausal women with climacteric symptoms.

Efficacy of porcine placental extracts with hormone therapy for postmenopausal women with knee pain.

OBJECTIVES: Knee pain related to osteoarthritis increases with age and is more common in middle-aged women. Although hormone replacement therapy (HRT) improves knee pain, women unresponsive to HRT need an effective adjunctive therapy. The aim of this study was to assess whether oral porcine placental extracts (PPE) have an impact on patients with knee pain as an adjunctive therapy combined with HRT. METHODS: Forty-eight postmenopausal women with knee pain receiving HRT were enrolled into this open-label, randomized, controlled study. Subjects were randomized into Group 1 (n= 24) or Group 2 (n=24). Subjects in Group 1 were given 3 months open treatment with calcium (260 mg/day) as adjunctive therapy combined with HRT. Group 2 received PPE (9 capsules/day) as adjunctive therapy combined with HRT. Changes in the degree of knee pain were evaluated by the Visual Analog Scale (VAS). RESULTS: Treatment with PPE was significantly effective in reducing the VAS score for knee pain at 4 weeks (p < 0.05), at 8 weeks (p< 0.01) and at 12 weeks (p<0.01), compared with the control group. Interestingly, the effects continued for 4 weeks after cessation of treatment in the PPE group (p< 0.01) compared with the control group. The PPE treatment had no significant adverse effects on blood biochemical and metabolic profiles, especially related to the risk factors for cardiovascular disease. CONCLUSION: PPE is a possible option as an adjunctive oral supplement in the case of HRT-resistant, long-lasting knee pain.

Galantamine improves apomorphine-induced deficits in prepulse inhibition via muscarinic ACh receptors in mice.

BACKGROUND AND PURPOSE: Galantamine, a weak acetylcholine esterase (AChE) inhibitor and allosteric potentiator of nicotinic ACh receptors (nAChRs), improves apomorphine-induced deficits in prepulse inhibition (PPI), sensory information-processing deficits, via a nAChR-independent mechanism. The present study examined the role of muscarinic ACh receptors (mAChRs) in the effect of galantamine, and studied the mechanism of galantamine-induced increases in prefrontal ACh levels in mice. EXPERIMENTAL APPROACH: Apomorphine (1 mg kg(-1)) was administered to male ddY mice (9-10 weeks old) to create a PPI deficit model. Extracellular ACh concentrations in the prefrontal cortex were measured by in vivo microdialysis. KEY RESULTS: Galantamine- and donepezil-mediated improvements in apomorphine-induced PPI deficits were blocked by the preferential M(1) mAChR antagonist telenzepine. The mAChR agonist oxotremorine also improved apomorphine-induced PPI deficits. Galantamine, like donepezil, increased extracellular ACh concentrations in the prefrontal cortex. Galantamine-induced increases in prefrontal ACh levels were partially blocked by the dopamine D(1) receptor antagonist SCH23390, but not by antagonists of mAChRs (telenzepine) and nAChRs (mecamylamine). Galantamine increased dopamine, but not 5-HT, release in the prefrontal cortex. CONCLUSIONS AND IMPLICATIONS: Galantamine improves apomorphine-induced PPI deficits by stimulating mAChRs through increasing brain ACh levels via a dopamine D(1) receptor-dependent mechanism and AChE inhibition.

Ginkgo biloba extract EGb 761 attenuates hippocampal neuronal loss and cognitive dysfunction resulting from chronic restraint stress in ovariectomized rats.

We have recently found that a combination of ovariectomy (OVX) and chronic restraint stress causes cognitive dysfunction and reduces hippocampal CA3 neurons in female rats and that estrogen replacement suppresses the OVX/stress-induced behavioral and morphological changes. In this study, we examined the effect of Ginkgo biloba extract (EGb 761), a popular herbal supplement, on the cognitive dysfunction and neuromorphological change in OVX/stress-subjected rats. Female Fisher 344 rats were randomly divided into three groups: vehicle-treated OVX, EGb 761 (50 mg/kg) -treated OVX and vehicle-treated sham-operated control groups. Two months after ovariectomy, all animals received restraint stress for 21 days (6 h/day), and were then subjected to a novel object recognition test followed by morphological examination by Nissl staining. EGb 761 was orally administered once daily until the behavioral analysis was done. Treatment with EGb 761 improved memory impairment and neuronal loss of hippocampus in the OVX/stress-subjected group in the same ways as 17beta-estradiol. On the other hand, EGb 761 did not affect the loss of bone mineral density and increase in body weight after OVX, although 17beta-estradiol attenuated them. These results have important implications for neuroprotective and cognition enhancing effects of EGb 761 in postmenopausal women and suggest that the effects are mediated by a different mechanism from estrogen.

Increase of noradrenaline release in the hypothalamus of freely moving rat by postsynaptic 5-hydroxytryptamine1A receptor activation.

1. 5-Hydroxytryptamine (5-HT) plays a role in the regulation of noradrenergic neurones in the brain, but the precise mechanism of regulation of noradrenaline (NA) release by 5-HT1A receptors has not been defined. The present study describes the effect of a highly potent and selective 5-HT1A receptor agonist, 5-(3-[[(2S)-1,4-benzodioxan-2-ylmethyl)]amino]propoxy)-1,3-b enzodioxole HC1 (MKC-242), on NA release in the hypothalamus using microdialysis in the freely moving rat. 2. Subcutaneous injection of MKC-242 (0.5 mg kg-1) increased extracellular levels of NA and its metabolite, 3-methoxy-4-hydroxyphenylglycol, in the hypothalamus and hippocampus. 3. The 5-HT1A receptor agonists, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (0.2 mg kg-1) and buspirone (3 mg kg-1) mimicked the effect of MKC-242 in increasing NA release in the hypothalamus. 4. The effects of MKC-242 and 8-OH-DPAT in the hypothalamus were antagonized by pretreatment with WAY100135 (10 mg kg-1), a silent 5-HT1A receptor antagonist. 5. Local administration of 8-OH-DPAT (10-100 microM), citalopram (1 microM), a 5-HT reuptake inhibitor, and MDL72222 (10 microM), a 5-HT3 receptor antagonist, into the hypothalamus, had no effect on NA release. 6. Intracerebroventricular injection with 5,7-dihydroxytryptamine caused a marked reduction in brain 5-HT content, but the treatment affected neither basal NA levels nor the MKC-242-induced increase in NA release. 7. The effect of MKC-242 in increasing NA release was not attenuated by repeated treatment with the drug (0.5 mg kg-1, once a day for 2 weeks). 8. The present results suggest that activation of postsynaptic 5-HT1A receptors increases NA release in the hypothalamus.

Sex difference for tolerance of 5-HT1A receptor-mediated temperature and corticosterone responses in mice.

Repeated treatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) resulted in significant attenuation of 8-OH-DPAT-induced hypothermia and adrenocorticol effect in mice of both sexes, while it did not affect the 8-OH-DPAT-induced decrease in 5-hydroxyindoleacetic acid in the hypothalamus in either sex. The attenuated responses developed more rapidly in female than in male mice, indicating sex differences in the adaptive regulation of the 5-HT1A receptor-mediated responses.