scholarly journals A Novel, Stable, Estradiol-Stimulating, Osteogenic Yam Protein with Potential for the Treatment of Menopausal Syndrome

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Kam Lok Wong ◽  
Yau Ming Lai ◽  
Ka Wan Li ◽  
Kai Fai Lee ◽  
Tzi Bun Ng ◽  
...  

Abstract A novel protein, designated as DOI, isolated from the Chinese yam (Dioscorea opposita Thunb.) could be the first protein drug for the treatment of menopausal syndrome and an alternative to hormone replacement therapy (HRT), which is known to have undesirable side effects. DOI is an acid- and thermo-stable protein with a distinctive N-terminal sequence Gly-Ile-Gly-Lys-Ile-Thr-Thr-Tyr-Trp-Gly-Gln-Tyr-Ser-Asp-Glu-Pro-Ser-Leu-Thr-Glu. DOI was found to stimulate estradiol biosynthesis in rat ovarian granulosa cells; induce estradiol and progesterone secretion in 16- to 18-month-old female Sprague Dawley rats by upregulating expressions of follicle-stimulating hormone receptor and ovarian aromatase; counteract the progression of osteoporosis and augment bone mineral density; and improve cognitive functioning by upregulating protein expressions of brain-derived neurotrophic factor and TrkB receptors in the prefrontal cortex. Furthermore, DOI did not stimulate the proliferation of breast cancer and ovarian cancer cells, which suggest it could be a more efficacious and safer alternative to HRT.


1991 ◽  
Vol 260 (4) ◽  
pp. E608-E612
Author(s):  
M. Michalkiewicz ◽  
J. M. Connors ◽  
L. J. Huffman ◽  
Z. Pietrzyk ◽  
G. A. Hedge

It has been shown that the compensatory growth of the thyroid gland and the compensatory increase in hormone secretion that occur after hemithyroidectomy are preceded by a dramatic increase in thyroid blood flow (BF). These alterations in the thyroid remnant may be due to the concomitant increase in plasma thyrotropin (TSH) concentrations. It has been suggested, however, that the compensatory thyroid growth may also involve a neural reflex. In this study we have investigated the role of TSH in mediating the compensatory alterations in thyroid BF and mass after subtotal thyroidectomy. Male Sprague-Dawley rats were anesthetized with ether for surgical or sham hemithyroidectomy. One-half of the hemithyroidectomized rats (HTX) received no further treatment; in the other one-half of the HTX rats (Clamp), plasma TSH levels were maintained at levels comparable with those in sham-operated animals by initiating constant thyroid hormone replacement beginning at the time of hemithyroidectomy. Plasma samples for TSH, 3,5,3'-triiodothyronine, and thyroxine radioimmunoassays were obtained 2, 7, 14, and 21 days after surgery. Thyroid BF was determined at 1, 2, and 3 wk after surgery by the reference sample version of the radioactive microsphere technique (141Ce, 15 microns diameter). Plasma TSH levels and thyroid lobe weight were significantly elevated in HTX rats but not in Clamp rats. Thyroid BF was markedly increased in HTX rats. Thyroid BF was also significantly increased in Clamp rats despite the suppression of the rise in plasma TSH concentration, but this increase was less than that in HTX rats. Neither hemithyroidectomy nor Clamp treatments had any effect on arterial blood pressure or BF to other tissues (e.g., kidney).(ABSTRACT TRUNCATED AT 250 WORDS)



2004 ◽  
Vol 287 (1) ◽  
pp. H165-H171 ◽  
Author(s):  
Yi Xu ◽  
Stephen J. Armstrong ◽  
Ivan A. Arenas ◽  
Daniel J. Pehowich ◽  
Sandra T. Davidge

Aging and estrogen deficiency increase the risk for developing cardiovascular disease (CVD). Oxidative stress has also been implicated in the pathophysiology of CVD and in ischemia-reperfusion (I/R) injury. We tested the hypothesis that chronic in vivo estrogen treatment or superoxide inhibition with the SOD mimetic EUK-8 improves cardiac functional recovery after I/R in the aged female rat. Sprague-Dawley rats (12–14 mo) were used as follows: intact ( n = 6), ovariectomized + placebo (OVX, n = 6), OVX + EUK-8 (EUK-8, 3 mg/kg, n = 6), and OVX + estrogen (1.5 mg/pellet, 60 days release, n = 6). Perfused isolated hearts were subjected to global ischemia (25 min) followed by reperfusion (40 min). Functional recovery after I/R and myocardial protein expression of NADPH oxidase (p22, p67, and gp91 phox), inducible nitric oxide synthase (NOS), endothelial NOS, and SOD1, as well as nitrotyrosine levels (as a marker for peroxynitrite), were assessed. Compared with OVX, EUK-8 and estrogen markedly improved functional recovery after I/R, which was associated with a decrease in NADPH oxidase expression and nitrotyrosine staining. However, estrogen increased inducible NOS expression, whereas EUK-8 had little effect. There were no significant changes in endothelial NOS and SOD1 expression among the groups. These results indicate that EUK-8 and estrogen improved cardiac recovery after I/R. Given the controversy surrounding hormone replacement therapy, EUK-8 may be an alternative to estrogen in protecting those at risk for myocardial ischemia in the aging population.



2009 ◽  
Vol 37 (03) ◽  
pp. 519-529 ◽  
Author(s):  
Dan Su ◽  
Han-Yi Li ◽  
Hao-Ran Yan ◽  
Peng-Fei Liu ◽  
Liu Zhang ◽  
...  

The traditional Chinese medical herb Astragalus, the dried root of Astragalus membranaceus (Fisch.) Bge., has been widely applied to treat patients with cardiovascular disease in China and has profound cardioprotective effects. This study investigated the effect of Astragalus on hemodynamic changes in adriamycin (ADR)-injured rat hearts and its underlying molecular mechanism. Sprague-Dawley rats were divided into four groups: control, ADR only, ADR + low dose of Astragalus and ADR + high dose of Astragalus. Rats were injected intraperitoneally with 6 equal doses of ADR (cumulative dose, 12 mg/kg) over a period of 2 weeks. Treatment of Astragalus began 1 day before the onset of ADR injection and was given orally once a day for 50 days (3.3 or 10 g/kg/day). Five weeks after the final injection of ADR, rats treated with ADR only showed a significant inhibition of cardiac diastolic function accompanied by the presence of ascites, a remarkable reduction in body weight and heart weight as well as survival rate compared to the controls. Moreover, SERCA2a mRNA and protein expressions in hearts were obviously downregulated by ADR. However, this impaired cardiac function was significantly improved in both doses of Astragalus feeding groups. The amount of ascites was also reduced in a similar extent in these 2 groups. Only the high dose treatment of Astragalus significantly attenuated the changes of SERCA2a expression in injured hearts and improved survival. These results indicated that Astragalus could improve cardiac function of ADR-injured rat hearts, which was partly mediated by upregulation of SERCA2a expression.



2008 ◽  
Vol 101 (7) ◽  
pp. 1031-1039 ◽  
Author(s):  
Sun-Hye Lim ◽  
Tae-Youl Ha ◽  
Sung-Ran Kim ◽  
Jiyun Ahn ◽  
Hyun Jin Park ◽  
...  

The aim of the present study was to investigate whether ethanol extracts of Psoralea corylifolia L. (PCE) and its active component protect against bone loss in ovariectomised rats. We screened oestrogenic activities of the main extract fractions using in vitro assays and identified bakuchiol as the most active oestrogenic component by HPLC and LC/MS, and then demonstrated that bakuchiol had strong binding affinity for oestrogen receptor (ER) α. Seventy female Sprague–Dawley rats were assigned to either a sham-operated group (n 10) or an ovariectomised group (n 60). The ovariectomised group was subdivided into six groups, each containing ten rats: vehicle group, two bakuchiol-treated groups (dose of 15 mg/kg per d or 30 mg/kg per d; ten rats for each group), two PCE-supplemented groups (0·25 % or 0·5 % extracts of diets; ten rats for each group) and a 17β-oestradiol (E2)-treated group (20 μg/kg per d). We recorded weight and feed intake every week, and killed all animals after 6 weeks. Blood was collected, and the uterus, kidneys and livers were removed. Bakuchiol has a three-fold higher binding affinity for ERα than for ERβ. Bakuchiol and PCE treatments had no uterotrophic activity even though they demonstrated oestrogenic activity in the in vitro assays. Bakuchiol and PCE treatments reduced postmenopausal bone loss by increasing alkaline phosphatase, Ca concentrations, serum E2 concentration and bone mineral density, and by decreasing the inorganic P level. The present study indicated that bakuchiol and PCE treatments could protect against bone loss.



Endocrinology ◽  
2007 ◽  
Vol 149 (4) ◽  
pp. 1987-1993 ◽  
Author(s):  
Stephanie T. Page ◽  
Brett T. Marck ◽  
James M. Tolliver ◽  
Alvin M. Matsumoto

Stimulation of prostate growth is a major concern with testosterone therapy in older hypogonadal men. As a result, nonsteroidal selective androgen receptor modulators with anabolic activity but less prostate stimulation are being developed. Anabolic steroids might exhibit similar tissue selectivity. We hypothesized the anabolic steroid 19-nor-4-androstenediol-3β,17β-diol (3β,19-NA) would increase muscle, lean body mass (LBM), and bone mineral density (BMD) with little stimulation of prostate growth. Male Sprague Dawley rats were implanted with SILASTIC brand (Dow Corning, Midland, MI) capsules containing 3β,19-NA (4, 8, or 16 cm), dihydrotestosterone (DHT) (8 cm), 19-nortestosterone (16 cm), or four empty capsules after undergoing either a sham operation (intact) or orchidectomy (ORX). Serum gonadotropins, measured after 4, 8, or 24 wk of treatment, were significantly lower in 3β,19-NA-treated vs. untreated, intact, and ORX rats (P < 0.05), and testosterone was lowered by 3β,19-NA-treatment of intact animals. LBM and BMD were assessed after 20 wk, and 4 wk later, rats were killed for levator ani muscle and prostate weights. Compared with ORX rats, 3β,19-NA-treated rats had dose-dependent higher levator ani muscle weights, LBM, and BMD, which were similar to intact and DHT-treated rats at the highest 3β,19-NA dose. In contrast, prostate weights in all 3β,19-NA-treated groups were similar to ORX rats and lower than intact and DHT- and 19-nortestosterone-treated rats even at the highest 3β,19-NA dose. In summary, 3β,19-NA increases muscle and bone mass without significant stimulation of prostate growth, suggesting it may have some properties of a steroidal selective androgen receptor modulator. Anabolic steroids such as 3β,19-NA should be studied further to determine their mechanisms of tissue selectivity and effects in men.



2021 ◽  
Author(s):  
Mariam Alawadhia ◽  
Farah Al Shammari ◽  
Fatemah Mulla Ali ◽  
Rama Almatar ◽  
Ayat Al-Duwaikhi ◽  
...  

Abstract BackgroundDexamethasone (DEX) induces intrauterine growth restriction (IUGR) in pregnant rats. IUGR can occur due to apoptosis of trophoblasts, which is believed to be inhibited by progesterone (P4). A group of genes called MTAs play a role in proliferation and apoptosis. MTA1 upregulates trophoblasts proliferation and differentiation, while MTA3 downregulates proliferation and induces apoptosis. Hence, we hypothesized that during IUGR, placental MTA1 decreases and MTA3 increases and this is reversed by P4 treatment. MethodsPregnant Sprague-Dawley rats were divided into 4 groups based on daily intraperitoneal injections: control (C, saline), DEX (DEX, 0.2 mg/kg/day), DEX and P4 (DEX + P4, DEX: 0.2 mg/kg/day, P4: 5 mg/kg/day) and P4-treated (P4, 5 mg/kg/day) groups. Injections were started on 15 dg until the day of dissection (19 or 21 dg). Gene and protein expressions of MTA1 and MTA3 were studied in the labyrinth (LZ) and basal (BZ) zones using real-time PCR and Western blotting, respectively. ResultsDEX treatment induced 18% reduction in fetal body weight (p<0.001) and 30% reduction in placental weight (p<0.01). Maternal P4 level was also significantly lower in DEX treated groups (p<0.05). MTA1 expression was decreased in the LZ (gene, p< 0.001) and BZ (protein p<0.01), while MTA3 protein expression was upregulated in the LZ with DEX treatment (p<0.001). These changes were reversed with P4 treatment. ConclusionThe findings of the present study indicate that DEX induces IUGR through changing the expression of placental MTA1 and MTA3 antigens and P4 improved pregnancy outcome by preventing the changes in MTAs expression.



2007 ◽  
Vol 48 (5) ◽  
pp. 531-539 ◽  
Author(s):  
Z. F. Sheng ◽  
R. C. Dai ◽  
X. P. Wu ◽  
L. N. Fang ◽  
H. J. Fan ◽  
...  

Background: Bone mineral density (BMD) and microstructural variations have been extensively investigated in recent years; however, the compensation for bone loss between different regions is still unclear. Purpose: To fully characterize regional variations in bone mineral density (BMD) as well as the microstructure and dynamic changes of rat tibial trabeculae that occur with bone loss associated with estrogen deficiency. Material and Methods: Female Sprague-Dawley rats were ovariectomized (OVX), sham-operated (sham), or left unoperated (baseline control). The left tibiae were harvested at baseline, and at postoperative weeks 3 and 15. High-resolution micro-computed tomography (µCT) was used to identify the densitometric and microstructural properties of trabeculae in the proximal ends of the rat tibia, specifically the epiphysis and metaphysis. Results: Volumetric BMDs at the organ (organ BMD) and tissue (tissue BMD) levels were significantly higher for trabeculae at the epiphysis than metaphysis. Moreover, trabeculae at the epiphysis were thicker, and fewer in number and connectivity than those at the metaphysis, which were more rod like. Trabeculae at the metaphysis were more susceptible to bone loss induced by estrogen deprivation than at the epiphysis, and the regions varied greatly in their adaptation to this loss. At the metaphysis, trabecular tissue BMD and thickness were unexpectedly higher at postoperative week 15 than week 3 or baseline. In contrast, at the epiphysis, tissue BMD did not change with time, but trabecular thickness significantly increased at week 15 compared to baseline and was also greater in OVX compared to sham rats. Conclusion: Metaphyseal and epiphyseal trabeculae show regionally specific variations in BMD and microstructure. The former are more susceptible to bone loss induced by estrogen deficiency and would be strengthened by either hypertrophy or hypermineralization, while epiphyseal trabeculae are mainly strengthened by thickening.



2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Buyanbileg Sodnom-Ish ◽  
Mi Young Eo ◽  
Ji Hye Oh ◽  
Mi Hyun Seo ◽  
Hoon Joo Yang ◽  
...  

AbstractOsteomyelitis (OM) of the jaw is usually caused by a chronic odontogenic infection. Decompression is the release the intraluminal pressure in the cystic cavity allowing gradual bone growth from the periphery. The aim of this study was to analyze the effectiveness of decompression in an OM jaw model. A 4-mm-diameter defect was made on mandibles of fourteen Sprague–Dawley rats and inoculated with S. aureus (20 μl of 1 × 107 CFU/ml) injection. Two weeks later, four groups were made as non-treatment (C1), only curettage (C2), curettage and decompression (E1), and curettage and decompression with normal saline irrigation (E2). After four weeks, each group was analyzed. Most micro-CT parameters, including bone mineral density [0.87 (± 0.08) g/cm3] with bone volume [0.73 (± 0.08) mm3] was higher in E2 group than that of C1 group (p = 0.04, p = 0.05, respectively). E2 group in histology showed the highest number of osteocytes than those of control groups, 91.00 (± 9.90) (p = 0.002). OPN were expressed strongly in the E1 (“5”: 76–100%) that those of other groups. Decompression drains induced advanced bone healing compared to that of curettage alone. Therefore, it could be recommended to use decompressive drain for enhancing the jaw OM management.



2021 ◽  
Vol 8 ◽  
Author(s):  
Michael D. McAlpine ◽  
Jenalyn L. Yumol ◽  
Wendy E. Ward

During pregnancy and lactation, maternal bone mineral density (BMD) is reduced as calcium is mobilized to support offspring bone development. In humans, BMD returns to pre-pregnancy levels shortly after delivery, shifting from a high rate of bone resorption during pregnancy and lactation, into a rapid phase of bone formation post-lactation. This rapid change in bone turnover may provide an opportunity to stimulate a greater gain in BMD and stronger trabecular and cortical structure than present pre-pregnancy. Providing polyphenols present in red rooibos herbal tea may promote such an effect. In vitro, red rooibos polyphenols stimulate osteoblast activity, reduce osteoclastic resorption, and increase mineral production. The study objective was to determine if consuming red rooibos from pre-pregnancy through to 4 months post-lactation resulted in a higher BMD and improved trabecular and cortical bone structure in a commonly used rat model. Female Sprague-Dawley rats (n = 42) were randomized to one of the following groups: PREG TEA (pregnant, received supplemental level of red rooibos in water: ~2.6 g /kg body weight/day in water), PREG WATER (pregnant, received water), or NONPREG CON (age-matched, non-pregnant control, received water) from 2 weeks pre-pregnancy (age 8 weeks) through to 4 months post-lactation. Rats were fed AIN-93G (pre-pregnancy through to the end of lactation) and AIN-93M (post-lactation onwards). BMD and trabecular structure (bone volume fraction, trabecular number, trabecular separation) were improved (p &lt; 0.05) by 1- or 2-months post-lactation when comparing PREG TEA to PREG CON, though neither group recovered to the level of NONPREG CON. Cortical outcomes (cortical area fraction, cortical thickness, tissue mineral density) for PREG TEA and PREG CON were reduced (p &lt; 0.05) following lactation but returned to the level of NONPREG CON by 2-months post-lactation, with the exception of cortical thickness. The lack of recovery of BMD and key outcomes of trabecular bone structure was unexpected. While consumption of red rooibos did not result in stronger bone post-lactation, red rooibos did support the partial recovery of trabecular BMD and bone structure following pregnancy and lactation. The findings also provide insight into the timing and dose of polyphenols to study in future interventions.



2021 ◽  
Author(s):  
Buyanbileg Sodnom-Ish ◽  
Mi Young Eo ◽  
Ji Hye Oh ◽  
Mi Hyun Seo ◽  
Hoon Joo Yang ◽  
...  

Abstract Background: Osteomyelitis (OM) of the jaw is usually caused by a chronic odontogenic infection. Decompression is the release the intraluminal pressure in the cystic cavity allowing gradual bone growth from the periphery. The aim of this study was to analyze the effectiveness of decompression in an OM jaw model.Methods: A 4-mm-diameter defect was made on mandibles of fourteen Sprague-Dawley rats and inoculated with S. aureus (20 μl of 1x107 CFU/ml) injection. Two weeks later, four groups were made as non-treatment (C1), only curettage (C2), curettage and decompression (E1), and curettage and decompression with normal saline irrigation (E2). After four weeks, each group was analyzed.Results: Most micro-CT parameters of C1 and C2 were significantly lower, and bone mineral density with bone volume was enhanced in E2. E1 and E2 groups in histology showed prominent bone healing with a significantly high number of osteocytes, E2 had the weakest expression of IL-6 compared to that of C1. TNF-α and OPN were expressed strongly in the E1.Conclusion: Decompression drains induced advanced bone healing compared to that of curettage alone in an OM jaw model. Therefore, it could be recommended to use decompressive drain for the enhancement of jaw OM management.



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