Ameliorative effects of Kyung-Ok-Ko and its mixture with Pueraria lobata Ohwi on postmenopausal osteoporosis by promoting phytoestrogenic activity in rats.

Introduction: Kyung-Ok-Ko (KOK) is a popular traditional medicine used as a natural alternative to hormone replacement therapy for treating postmenopausal symptoms in Asia. Pueraria lobata Ohwi (P. lobata) is rich in isoflavones and has been traditionally used in combination with other herbs to produce synergistic and pharmaceutical effects via a multi-target approach for disease treatment. We aimed to investigate the phytoestrogenic effects of KOK extract against postmenopausal symptoms in ovariectomized (OVX) rats and confirm its efficacy by mixing KOK and P. lobata extracts. Methods: OVX rats were daily oral administrated with KOK and KOK + P. lobata mixture extracts (300-400 mg/kg) and their body weight and tail temperature were monitored for 12 weeks. The biochemical parameters, estradiol levels, and bone turnover markers were measured in the serum samples. Moreover, the estrogen receptor, ER-α and ER-ß expression in the uterus and the uterus morphology were evaluated. AMPK, ATG1/ULK1, and mTOR protein expression in the liver were assessed. Results: The 12-week treatment with KOK and KOK + P. lobata mixture extracts did not cause liver damage or hormonal changes in the OVX rats. The treatments reduced the high lipid accumulation-related body weight gain and the tail temperature increase that was induced by ovariectomy. Further, it exhibited protective effects against hyperlipidemia and osteoporosis. No significant difference was observed in uterine weight compared to the OVX-treated group, while endometrial thickness reduction inhibition was observed due to ovariectomy. Bone mineral density (BMD) and serum osteocalcin levels, which decreased in OVX rats, increased with both treatments. Western blotting analysis showed that ER-α and ER-ß were not expressed in the treated rats, whereas these proteins were expressed in Sham-operated rats. No significant differences in the phosphorylation of AMPK were observed; however, the ATG1/ULK1 and mTOR protein phosphorylation levels were upregulated and downregulated in the treated rats compared to those of OVX rats, respectively. Conclusion: This is the first in vivo study observing the efficacy and synergistic effects of the mixture of KOK and P. lobata. Our results suggest the potential of KOK and KOK + P. lobata mixture as an alternative therapy for alleviating menopausal symptoms.

Effects of Artemisia annua L. on postmenopausal syndrome in ovariectomized mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia annua L. (Asteraceae) has been used as an antipyretic and anti-parasitic drug in traditional medicine for more than 2000 years. It has also been prescribed to treat symptoms caused by deficiency of Yin, which might be observed in menopausal state from the point of view of traditional medicine. AIM OF THE STUDY: We hypothesized that A. annua might be useful for treating menopausal disorders with less adverse effects than hormone replacement therapy. Thus, the aim of the present study was to investigate effects of A. annua on postmenopausal symptoms of ovariectomized (OVX) mice. MATERIALS AND METHODS: OVX mice were employed as a model for postmenopausal disorders. Mice were treated with a water extract of A. annua (EAA; 30, 100 or 300 mg/kg, p.o.) or 17ß-estradiol (E2; 0.5 mg/kg, s.c.) for 8 weeks. Open field test (OFT), novel object recognition task (NOR), Y-maze test, elevated plus maze test (EPM), splash test and tail suspension test (TST) were conducted to determine whether EAA could ameliorate postmenopausal symptoms. Phosphorylated levels of extracellular signal-regulated kinase (ERK), protein kinase B (Akt), and glycogen synthase kinase-3ß (GSK-3ß), ß-catenin and expression level of synaptophysin in the cortex and hippocampus were evaluated by Western blot analysis. RESULTS: EAA treatment significantly increased the discrimination index in NOR, decreased the time in closed arm than in open arm in EPM, increased grooming time in splash test, and decreased immobility time in TST, as did E2 treatment. In addition, decreased phosphorylation levels of ERK, Akt, GSK-3ß, and ß-catenin and expression levels of synaptophysin in the cortex and hippocampus after OVX were reversed by administration of EAA and E2. CONCLUSION: These results suggest that A. annua can ameliorate postmenopausal symptoms such as cognitive dysfunction, anxiety, anhedonia, and depression by activating ERK, Akt, and GSK-3ß/ß-catenin signaling pathway and hippocampal synaptic plasticity, and that A. annua would be a novel treatment for postmenopausal symptoms.

Benefits of Black Cohosh (Cimicifuga racemosa) for Women Health: An Up-Close and In-Depth Review.

Women's health is an imminent concern worldwide, but it remains an ignored segment of research in most developing countries, and is yet to take the center stage in even developed nations. Some exclusive female health concerns revolve around both pathological and physiological aspects. These gender-specific maladies include breast, cervical, and ovarian cancers, and physiological concerns such as menopause and osteoporosis, which are often coexistent. Recently, women's health issues, including postmenopausal syndrome, have attracted the attention of researchers and practitioners alike, opening newer pharmaceutical research and clinical avenues. Although not counted as a disease, postmenopausal syndrome (PMS) is a female health phenomenon underpinned by hormonal depletion. Enhanced life expectancy in women has added to their suffering, and pharmacological interventions are needed. Amongst the available treatment modalities, the use of numerous botanicals has emerged as an efficient health management tool for women. Cimicifuga racemosa (CR or Black Cohosh) is a plant/herb which has been traditionally exploited and extensively used by women. This review is an attempt to compile and provide a summary of the importance of CR in complementary and alternative therapies for the improvement of various disorders related to women, such as menopausal syndrome, mammary cancer, and osteoporosis. It aims to systematically highlight the bioactive constituents, pharmacology, pharmacokinetics, therapeutic potentials, quality control processes, chromatographic techniques, and possible mechanisms of action of clinically effective phytomedicine for women's health. Various clinical trials and patents relating to CR and women's health have been collated. Furthermore, the plant and its related products have been considered from a regulatory perspective to reveal its commercial feasibility. The present review summarizes the existing data on CR focusing on women's health, which can help to introduce this traditional phytomedicine to the world and provide some reference for future drug development.

Menopausal Remediation and Quality of Life (QoL) Improvement: Insights and Perspectives.

Cessation of menstruation, widely known as menopause is a significant transition period in women's life. It leads to the arrest of fertility and creates a depletion of the hormones causing physical, mental, sexual, and social problems which lead to a serious decline in their quality of life. The onset of menopause induces certain sudden changes, while others appear in a phasic manner, henceforth demanding an adequate understanding of its progression, adverse impact on life, and exploration of any remedial measures thereof. Menopause, despite being a natural occurrence, brings in significant changes to women's life, almost sometimes leading to severe debilitation. However, it is still not attended and remains an ignored health issue that warrants the immediate attention of researchers, practitioners, and health policymakers. The present review is an attempt to draw attention towards these women-centric health issues and diligently explores the causes, symptoms and also describes the various procedures for the management of menopausal and postmenopausal syndromes. The review tries to summarise the currently available pharmaceutical interventions and also dwells into herbal and complementary remedies which could ameliorate and provide respite from the etiolating menopausal symptoms.

Mitigation of Memory Impairment in Ovariectomized Rats Using Garlic Powder Treated with Subcritical Water.

Women with estrogen deficiency are at the risk of suffering from neurological symptoms such as memory impairment. In the present study, we investigated the effect of garlic, Allium sativum L. (Asparagales: Amaryllidaceae), treated with subcritical water on memory impairment in ovariectomized (OVX) rats. OVX rats were administered garlic powder for 84 d. Hippocampus-dependent spatial memory was assessed using the Morris water maze test. Escape latency of the OVX rats increased compared with that of sham-operated rats. The prolonged escape latency of the OVX rats decreased to the level of that of sham-operated rats upon the administration of garlic powder (0.5% in feed). The weights of the body, uterus, and brain were not affected by the garlic powder administration. These results suggest that garlic powder treated with subcritical water mitigates memory impairment in OVX rats.

To evaluate the efficacy and safety of PLC in perimenopausal or postmenopausal women with Hot Flashes: study protocol for a randomized controlled trial.

BACKGROUND: Hot flashes are the most frequent symptoms of the menopause, with 10-20% of all postmenopausal women reporting nearly intolerable occurrences. Although pharmacopuncture with hominis placenta extract is one of the new acupuncture therapies popular in East Asian medicine with a known efficacy in treating facial flushing, there has been little research on the efficacy and safety of this extract. This study, therefore, aims to evaluate the efficacy and safety of pharmacopuncture with hominis placenta extract (PLC) compared to injections of normal saline, in perimenopausal and postmenopausal women in Korea. METHODS/DESIGN: This study is a randomized placebo-controlled single-blind multi-center parallel-design trial. In total, 128 perimenopausal or postmenopausal women who meet the inclusion criteria will be recruited. The treatment group will receive PLC pharmacopuncture twice a week, for a total of 18 sessions over 9 weeks. The control group will receive injections of normal saline at the same acupoints during the same period. The post-treatment follow-up assessment will occur 4 weeks after the participant has completed the treatment. DISCUSSION: We believe that this trial will provide evidence for the efficacy and safety of PLC pharmacopuncture as a treatment for hot flashes in perimenopausal and postmenopausal women. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), Republic of Korea, ID: KCT0003533 , Registered on 20 February 2019.

Improvement of neurological disorders in postmenopausal model rats by administration of royal jelly.

OBJECTIVE: Royal jelly (RJ) from honeybees (Apis mellifera) has estrogenic activity. Estrogen deficiency after menopause leads to a high risk of memory impairment and depression as well as metabolic syndrome and osteoporosis. We here investigated the effect of RJ on memory impairment and depression-like behaviors in ovariectomized (OVX) rats. METHODS: OVX rats were administered with RJ for 82 days. Hippocampus-dependent spatial memory and depression-like behaviors were assessed by the Morris water maze test and the forced swimming test, respectively. The weights of body, brain and uterus and the contents of protein and myelin galactolipids including galactosylceramide and sulfatide were measured. RESULTS: Memory impairment and depression-like behaviors in OVX rats were recovered to the levels of sham-operated rats by RJ administration. Increased body weight and decreased uterine weight in OVX rats were recovered to the levels of sham-operated rats by 17ß-estradiol (E2) administration but not by RJ administration. In contrast, brain weight was slightly increased by RJ administration but not by E2 administration. The contents of protein and myelin galactolipids were higher in the brains of RJ-administered OVX rats than in the brains of E2-administered OVX rats. CONCLUSION: The results suggest that RJ has a beneficial effect on neurological symptoms of a menopausal disorder.

Postmenopausal syndrome.

Menopause is one of the most significant events in a woman's life and brings in a number of physiological changes that affect the life of a woman permanently. There have been a lot of speculations about the symptoms that appear before, during and after the onset of menopause. These symptoms constitute the postmenopausal syndrome; they are impairing to a great extent to the woman and management of these symptoms has become an important field of research lately. This chapter attempts to understand these symptoms, the underlying pathophysiology and the management options available.

The Effect of Pomegranate on Postmenopausal Syndrome: A Randomized, Double-blind, Placebo-controlled Trial / 대한폐경학회지

OBJECTIVES: To investigate the safety and effect of pomegranate extract on postmenopausal syndrome. METHODS: One hundred twelve women participated in a randomized, double-blind, placebo-controlled trial conducted in a tertiary university hospital in Korea. Women were treated with pomegranate extract or placebo for 12 weeks. The primary end point was menopausal symptoms, which were evaluated based on the Kupperman Index. The secondary end point was the serum estradiol (E2, pg/ml) level. Statistical analysis was performed. RESULTS: Menopausal symptoms as the Kupperman Index were significantly improved in the pomegranate group compared to placebo during the 12 weeks of intervention (P < 0.0001). Melancholia did not differ between the two groups. There was also no difference in serum E2 levels. There were no differences between the two groups in age, body weight, height, systolic and diastolic blood pressures, serum white and red blood cell counts, and fasting blood glucose, hemoglobin, aspartic transaminase, alanine transaminase, total cholesterol, triglycerides, high- and low-density lipoprotein-cholesterol, creatinine, and E2 levels. The side effects of pomegranate extract were negligible. CONCLUSION: Pomegranate extract is safe and effective in the treatment of menopausal symptoms. Further studies on whether or not the beneficial effect of pomegranate extract is due to the estrogen component are needed.

The Effect of Pomegranate on Postmenopausal Syndrome: A Randomized, Double-blind, Placebo-controlled Trial / 대한폐경학회지

OBJECTIVES: To investigate the safety and effect of pomegranate extract on postmenopausal syndrome. METHODS: One hundred twelve women participated in a randomized, double-blind, placebo-controlled trial conducted in a tertiary university hospital in Korea. Women were treated with pomegranate extract or placebo for 12 weeks. The primary end point was menopausal symptoms, which were evaluated based on the Kupperman Index. The secondary end point was the serum estradiol (E2, pg/ml) level. Statistical analysis was performed. RESULTS: Menopausal symptoms as the Kupperman Index were significantly improved in the pomegranate group compared to placebo during the 12 weeks of intervention (P < 0.0001). Melancholia did not differ between the two groups. There was also no difference in serum E2 levels. There were no differences between the two groups in age, body weight, height, systolic and diastolic blood pressures, serum white and red blood cell counts, and fasting blood glucose, hemoglobin, aspartic transaminase, alanine transaminase, total cholesterol, triglycerides, high- and low-density lipoprotein-cholesterol, creatinine, and E2 levels. The side effects of pomegranate extract were negligible. CONCLUSION: Pomegranate extract is safe and effective in the treatment of menopausal symptoms. Further studies on whether or not the beneficial effect of pomegranate extract is due to the estrogen component are needed.

The effect of pomegranate on postmenopausal syndrome in ovariectomized rats / 대한산부인과학회지

OBJECTIVE: To determine whether or not pomegranate extract can affect postmenopausal syndrome in ovariectomized rats. METHODS: Seventy-nine female Sprague-Dawley rats were used: A, no intervention; B, sham operation and distilled water; C, ovariectomy and distilled water; D, ovariectomy and 10% dilute pomegranate; E, ovariectomy and 20% pomegranate; and F, ovariectomy and 40% pomegranate. The study samples were obtained 4 weeks later. The following parameters were investigated for analyses: the thickness of urogenital epithelium, tail skin temperature, serum levels of sex hormones, lipid profile, homocysteine, and thiobarbituric acid reactive substances. RESULTS: 20% pomegranate had a transient thickening effect of bladder epithelial layer. There was an intermittent lowering effect of tail skin temperature of pomegranate extract, however, it was not consistent. There were lowering effect in serum homocysteine and elevating effect in serum high density lipoprotein-cholesterol. Pomegranate did not reverse post-ovariectomy reduced sex hormone levels. CONCLUSION: Pomegranate extract showed a tendency to reverse ovariectomy-related urothelial changes. Also pomegranate had a serum homocysteine-lowering effect.