scholarly journals Rheum rhaponticum Root Extract Improves Vasomotor Menopausal Symptoms and Estrogen-Regulated Targets in Ovariectomized Rat Model

2021 ◽  
Vol 22 (3) ◽  
pp. 1032
Author(s):  
Mickey Wilson ◽  
Veera Konda ◽  
Kathryn Heidt ◽  
Thirumurugan Rathinasabapathy ◽  
Anuradha Desai ◽  
...  

Ovarian insufficiency and ovariectomy are characterized by deregulated heat loss mechanisms. Unlike hormone therapy, ERr 731 (a standardized botanical extract of Siberian rhubarb Rheum rhaponticum L. high in rhaponticin) acts like a selective estrogen receptor modulator for ERβ receptors and may offer a higher degree of safety while maintaining the desired efficacy profile. In this study, we examined the relationship between oral administration of ERr 731 and the underlying components of skin vasomotion responses in an ovariectomized (OVX) rat model. ERr 731 dose-dependently reduced tail skin temperature (Tskin) values by an average of 1 °C. The rapid onset of this effect was observed in 1 and 3 mg/kg/day ERr 731 groups as early as day 2 of administration, and remained in place for the duration of the treatment (2 weeks). Substituting ERr 731 after E2 withdrawal helped maintain body temperature similarly to E2 alone, suggesting the usefulness of ERr 731 for replacing existing hormonal therapy in humans. ERr 731 also acted as a highly selective agonist for ERβ in the hypothalamus of OVX rats, as well as in ERα/β cell-based reporter assays. These data validate the OVX/Tskin rat model as a suitable screening platform to evaluate botanical and pharmaceutical treatments of menopause, while providing further evidence for the efficacy of ERr 731 towards alleviating vasomotor menopausal symptoms and improving wellbeing during the menopausal transition.

2021 ◽  
Vol 12 (2) ◽  
pp. 108
Author(s):  
Jignesh Shah ◽  
Sonia Chandanani ◽  
Jayanthi Reddy ◽  
Hepzibah Kirubamani ◽  
ArunMadhab Boruah ◽  
...  

2019 ◽  
Vol 244 (3) ◽  
pp. 193-206 ◽  
Author(s):  
Byoung-Seob Ko ◽  
Jin Ah Ryuk ◽  
Joo Tae Hwang ◽  
Ting Zhang ◽  
Xuangao Wu ◽  
...  

The different ojayeonjonghwan remedies all contain five fruit and seed water extracts, and they have been used for reproductive health in men and women. We hypothesized that the two OJa remedies would differently improve the early menopause-related vasomotor and neurological symptoms in estrogen-deficient animals. Ovariectomized (OVX) rats had either 0.5% dextrin (OVX-control), conjugated equine estrogen (150 μg/kg body weight; positive-control), 0.5% ojayeonjonghwan remedy-1 (OJa1), or 0.5% ojayeonjonghwan remedy-2(OJa2) in high-fat diet for 12 weeks. Normal-control rats (sham operation) were fed the same high-fat diet as OVX-control rats. Tail skin temperature, depressiveness, memory function, and body composition were determined. The mRNA expressions of hippocampal serotonin receptor (5HT)1A and 5HT2A and brain-derived neurotrophic factor(BDNF) were measured. OJa1 and OJa2 groups had lower tail skin temperatures than OVX-control. Bone mineral density (BMD) and lean body mass (LBM) measured by DEXA increased only in OJa2, and were similar to the positive- and normal-controls ( P < 0.05). In the forced swim test immobile time, an index of depressiveness was much lower in OJa1 and OJa2 than the control group. Memory as measured by passive avoidance, water maze, and Y maze tests was impaired in the OVX-control group, compared to the normal-control ( P < 0.05), but normalized in OJa1 comparable to the positive- and normal-control groups. The neurological impairments were associated with serum serotonin levels and 5HT2A mRNA expression in the midbrain, and decreased hippocampal BDNF mRNA and protein expressions in the OVX-control group compared to normal-controls ( P < 0.05). OJa1 increased serum serotonin levels and 5HT2A expression in the midbrain, and hippocampal BDNF expression to similar levels as normal-controls ( P < 0.05). In conclusion, OJa1 and OJa2 improved hot flashes and depression and maintained BMD and LBM. OJa2 prevented the impairment of memory function in OVX rats. OJa1 and OJa2 have the potential to be effective therapies for postmenopausal vasomotor and neurological symptoms. Impact statement Menopausal symptoms impair the quality of life of many women, and although conventional treatments are often effective, their use is limited by adverse effects. Ojayeonjonghwan, OJa, is a traditional Oriental medicine that is used for both male and female reproductive health and has a long history of safe use. We evaluated the effectiveness of two variations of OJa (OJa1 and OJa2) for treating menopausal symptoms in ovariectomized (OVX) rats. Both OJa preparations were effective for relieving indicators of hot flashes and depression, and for preventing loss of bone mineral density and lean body mass. Only OJa 2 prevented memory dysfunction. These results show that the traditional Oriental medicine, Ojayeonjonghwan, has the potential to relieve menopausal symptoms in women and should be further evaluated in human clinical trials as an alternative to convention therapies in women for whom conventional therapies are not indicated or found to be ineffective.


2018 ◽  
Vol 9 (4) ◽  
pp. 2480-2489 ◽  
Author(s):  
Jun Yeon Park ◽  
Hwayoung Yun ◽  
Jeyun Jo ◽  
Ji Yun Baek ◽  
Sang Cheon Lee ◽  
...  

Cirsium japonicum var. maackii exerted beneficial effects in a rat model of menopause.


2008 ◽  
Vol 3 ◽  
pp. 117863370800300 ◽  
Author(s):  
Rachel L. Ruhlen ◽  
Grace Y. Sun ◽  
Edward R. Sauter

The Women's Health Initiative found that combination estrogen and progesterone hormone replacement therapy increases breast cancer and cardiovascular disease risk, which compelled many women to seek herbal alternatives such as black cohosh extract (BCE) to relieve their menopausal symptoms. While several clinical trials document the efficacy of BCE in alleviating menopausal symptoms, preclinical studies to determine how BCE works have yielded conflicting results. Part of this is because there is not a universally accepted method to standardize the dose of black cohosh triterpenes, the presumed active ingredients in the extract. Although the mechanism by which BCE relieves symptoms is unknown, several hypotheses have been proposed: it acts 1) as a selective estrogen receptor modulator, 2) through serotonergic pathways, 3) as an antioxidant, or 4) on inflammatory pathways. We found that while the most prominent triterpene in BCE, 23-epi-26-deoxyactein, suppresses cytokine-induced nitric oxide production in brain microglial cells, the whole BCE extract actually enhanced this pathway. A variety of activities have been reported for black cohosh and its compounds, but the absorption and tissue distribution of these compounds is unknown.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Jia Yang ◽  
Li-juan Xiong ◽  
Fei Xu ◽  
Xiang Zhao ◽  
Bo Liu ◽  
...  

Objective.To study the effects of estrogen on colon polyp formation, proliferation, and angiogenesis on a rat model of colon cancer induced by dimethylhydrazine (DMH).Methods.Thirty-six female ovariectomized (OVX) rats were randomly divided into 3 groups: (I) control group (administrated with vehicles weekly), (II) DMH group (administrated with DMH weekly), and (III) DMH + E2group (administrated with DMH and 17β-estradiol weekly). The incidence, volumes, and multiplicity of colon polyps in each group were evaluated. The microvessel density (MVD), the expressions of Proliferating Cell Nuclear Antigen (PCNA), and the expressions of HIF-1αand VEGF in polyps were detected in each group.Results.Estrogen reduced the multiplicity, volumes, and the PCNA expressions of DMH-induced colon polyps. The MVD in DMH + E2group was significantly lower than that in DMH group. Estrogen treatment decreased the HIF-1αand VEGF expressions at both mRNA and protein level.Conclusion.Estrogen replacement was protective for ovariectomized rats from DMH-induced carcinogenesis, and one of the mechanisms for this was due to estrogen’s inhibitive effects on blood vessel formation by downregulating VEGF and HIF-1αexpressions.


2018 ◽  
Vol 315 (1) ◽  
pp. E99-E109 ◽  
Author(s):  
Sunmin Park ◽  
Da Sol Kim ◽  
Eun Seon Kang ◽  
Da Bin Kim ◽  
Suna Kang

We evaluated the effects of intracerebroventricular administration (ICV) of brain estrogen and progesterone on menopausal symptoms and their effects on the secretion of follicle-stimulating hormone(FSH) and luteinizing hormone (LH) in estrogen-deficient rats. Three weeks after ovariectomy (OVX) or sham operation, OVX rats were given ICV infusions of either 17β-estradiol (4 μg/day; ICV-E), progesterone(0.8 μg/day; ICV-P), or vehicle (control) for 4 wk. OVX rats in the positive-control group were orally provided 150 μg 17β-estradiol·kg body wt−1·day−1. Sham rats had ICV vehicle infusion (normal-control). Serum 17β-estradiol levels of ICV-E and ICV-P groups were higher than the control group but much lower than the normal- and positive-control groups. Tail skin temperature was higher in the control group than the other groups. Serum FSH and LH levels were much higher in the control group than positive- and normal-control groups, but ICV-E and ICV-P lowered the levels similar to the normal-control treatment. ICV-E and ICV-P prevented the decreased energy expenditure in OVX rats. Homeostasis model assessment estimate of insulin resistance was lowered in the descending order of the control, positive-control, ICV-P, ICV-E, and normal-control treatments. The decreased bone mineral density was prevented by the positive-control, ICV-E, and ICV-P treatments. The control group exhibited decreased short-term memory and spatial memory compared with the other groups. Surprisingly, the control group exhibited a decreased richness of the gut microbiome compared with normal-control group, and ICV-E protected against the decrease the most. In conclusion, small amounts of brain estrogen and, to some extent, progesterone improved menopausal symptoms by decreasing serum FSH levels and maintaining the diversity of the gut microbiome in estrogen-deficient rats.


2005 ◽  
Vol 184 (1) ◽  
pp. 59-68 ◽  
Author(s):  
J E Sánchez-Criado ◽  
J Martín de las Mulas ◽  
C Bellido ◽  
R Aguilar ◽  
J C Garrido-Gracia

The selective oestrogen receptor modulator (SERM) tamoxifen (TX) has agonist/antagonist actions on LH secretion in the rat. Whereas in the absence of oestrogens TX elicits progesterone receptor (PR)-dependent GnRH self-priming, it antagonizes oestrogen-stimulatory action on LH secretion. The aim of these experiments was to explore whether TX treatment-induced differential expression of oestrogen receptor (ER)α and ERβ in the gonadotrope may determine its agonist effect on LH secretion. In the first experiment, basal LH secretion, GnRH-stimulated LH secretion and PR-dependent GnRH self-priming were determined in incubated pituitaries from ovariectomized (OVX) rats treated with oestradiol benzoate (EB), TX or raloxifene (RX). Cycling rats in metoestrus or pro-oestrus were used as basic controls. As in pro-oestrus, pituitaries from OVX rats treated with EB exhibited GnRH-stimulated LH secretion, immunohistochemical PR expression and GnRH self-priming. While RX had no effect on these parameters, TX induced PR expression and GnRH self-priming. GnRH self-priming was absent in pituitaries incubated with the antiprogestin ZK299. In the second experiment, we evaluated the immunohistochemical expression of ERα and ERβ in gonadotropes of cycling rats and OVX rats treated with EB, TX or RX. We found that while ERα expression was similar in all six groups, ERα expression was oestrous cycle dependent. Moreover, ERα expression in gonadotropes of TX-treated rats was as high as that found in pro-oestrus, while ERα expression in the gonadotropes of RX-treated rats was lower than in metoestrous or pro-oestrous pituitaries. These results suggest that, in the absence of the cognate ligand, TX, unlike RX, may regulate LH secretion through the ERα subtype in gonadotropes.


2019 ◽  
Vol 70 (2) ◽  
pp. 1541
Author(s):  
C. PASSALI ◽  
A. PATSAKI ◽  
P. LELOVAS ◽  
N. ALIGIANNIS ◽  
M. MAKROPOULOU ◽  
...  

The aim of this study was to examine the effect of Red Wine Polyphenols (RWPs) extract on bone mineral density (BMD) in the ovariectomized (OVX) rat model. Thirty-five 10-month-old Wistar rats were separated into controls (CTRL), OVX and OVX plus RWPs in their drinking water (dose, 50 mg/kg body weight per day), starting immediately after OVX for 6 months. Βody and uterine weight, BMD of the tibia at baseline, 3 and 6 months post-OVX, and 3-pointing bending of the femur, were examined. Statistical comparison of the total tibia BMD within groups during the study period showed a significant reduction in the OVX and OVX+RWPs groups both from baseline to 3 and 6 months and from 3 to 6 months, whereas in the CTRL group, there was no significant change. For the proximal tibial metaphysis, comparison of BMD percentage changes from baseline to 3 months and 6 months and from 3 to 6 months revealed highly statistical differences between OVX and OVX+RWPs groups (P = 0.000). OVX induced a significant reduction of biomechanical parameters as expected; the 3-point bending test showed that the maximum force before fracture, energy absorption and fracture stress significantly increased in the OVX group treated with RWPs compared with the nontreated OVX rats (P = 0.048, P = 0.002 and P = 0.003, respectively). Dietary intake of RWPs for 6 months significantly prevented trabecular bone loss and improved bone strength in estrogen-deficient ovariectomized rats.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 330-330
Author(s):  
Eun Young Kang ◽  
Hyun Kyung Kim ◽  
Gwang-woong Go

Abstract Objectives Menopause causes ovarian hormone decline, followed by symptoms including weight gain, bone loss, hot flashes, and menopausal depression. We had a purpose that a combination of Leonurus japonicus Houtt, Eclipta prostrata L., and Pueraria lobata Ohwi (LEPE) would alleviate menopausal symptoms in an ovariectomized menopausal rat model. Methods Female rat underwent surgery to resect bilateral ovarian and were randomly assigned to five groups: (1) Sham, (2) Vehicle, negative control, (3) LEPE (100 mg/kg bw), (4) LEPE (200 mg/kg bw), and (5) Estradiol (E2, 3 μg/kg bw). LEPE was orally gavaged daily for 12 weeks. Results There is no effect on growth performance, including body weight and feed intake, or body composition, including lean mass and fat in tissue. LEPE did not cause hepatotoxicity (aspartate aminotransferase and alanine aminotransferase) and endocrine disturbance (estradiol, follicle-stimulating hormone levels, and uterine weight). Despite decreasing type I collagen (CTX-1), LEPE did not affect bone mineral density and osteocalcin. LEPE supplement reduced the tail temperature and increased the rectal temperature, improving menopause-associated vasomotor symptoms such as hot flashes and night sweat. Furthermore, LEPE relieved behavior related to menopausal depression, including in forced swimming and tail suspension tests. Conclusions These findings suggest that LEPE ameliorates menopausal symptoms via improving menopause-associated vasomotor symptoms and depression behavior in a female rat model of surgical menopause. Funding Sources This research was funded by Nong Shim.


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