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To observing the inhibitory effect of sodium alendronate on bone loss in ovariectomized rats and to explore the mechanism of its inhibitory effect on bone loss. Methods Forty female Wistar rats were randomly divided into sham surgery group (10) and modeling group (30), Rats in the modeling group underwent minimally invasive abdominal resection of bilateral ovaries. Rats in the sham surgery group underwent excision of equal volume of adipose tissue. Three days later, rats in the modeling group of were randomly divided into three groups; the model group (OVX), the positive drug ethinylestradiol group (EE), and the alendronate sodium group. Rats of each group received medication or distilled water by gavage with the prescribed dosage. After significant differences in overall bone mineral density among the groups of rats were observed, all rats were euthanized. After dissection, each organ of the rats was weighed and the organ coefficients were calculated. Dual energy X-ray absorptiometry was used to detect the bone mineral density of the rat femur and the vertebral bone AG-IS universal testing machine was used to detect the biomechanics of the rat femur. VG staining method was used for bone morphometric analysis. Blood was collected from the abdominal aorta of rats and serum was separated. ELISA kit was used to analyze osteocalcin (OC) and tartaric acid phosphatase (TRACP 5b) levels in rat serum. Results Compared with the sham group, there was no significant change in the body weight of the other groups of rats. The organ index result showed that compared with the sham group, there were no significant changes in the liver, lung, spleen, and kidney indices of each group of rats, while the uterine index of the model group rats reduced significantly compared to the control group. After intervention with ethinylestradiol or alendronate sodium, the uterine index of the model group rats increased significantly. The bone mineral density result showed that after modeling, the bone mineral density of the whole body, femur, and vertebrae in rats significantly decreased. However, after intervention with alendronate sodium, bone mineral density significantly increased, but it could not return to normal state. In biomechanical experiments, the maximum load on the femur and vertebrae showed a trend similar to bone mineral density. There was no significant change in the elastic modulus values among the groups before and after administration. The result of bone morphometry showed a significant increase in the number and density of bone trabeculae in the EE group and the alendronate sodium group. In ovariectomized rats, serum levels of osteocalcin (OC) reduced significantly and levels of TRACP 5b increased significantly. However, after administration of ethinylestradiol or alendronate sodium, the OC level in the EE group increased and the TRACP 5b content significantly decreased. The OC level in the alendronate sodium group continued to decrease and TRACP 5h content also significantly decreased. The difference was statistically significant. Conclusion Alendronate sodium increases bone mineral density and bone mass and inhibits bone loss in ovariectomized rats. Its main mechanism of action may be achieved by inhibiting bone resorption by osteoclasts, with a weak effect on bone formation. [ABSTRACT FROM AUTHOR]

Objective To study whether oral sheep placenta powder canprevent postmenopausal osteoporosis. Methods: Established an osteoporosis model and randomly divide it into sham surgery group (Sham), model group (OVX), sheep fetal disc powder low (L), medium (M), high-dose group (H), and ethinylestradiol group (EE). The whole body bone density is measured every two weeks. After 1.5 months, weighed and calculated the main organ coefficients, detected the in vitro BMD and serum bone metabolism indexes, and performed Micro-CT scanning to observe the changes of bone tissue morphology. Results After 6 weeks, the overall bone density of the OVX group rats was significantly lower than that of the Sham group (P<0.01), but there was no significant decrease in the EE group. The three groups of sheep fetal discs were significantly higher than those of the OVX group (P<0.01). The changes in bone mineral density of the isolated femur showed a similar trend, but there was no significant difference between the Low group and OVX (P>0.05).Micro-CT scan analysis showed that among the three groups of sheep placenta, only the parameters of group M weresimilar to those of Sham group and EE group, and HE staining of histomatological sections of femur after decalcification showed similar results to those of Micro-CT. The three-point bending test of the femur found that the maximum load and strength of the M group were significantly higher than those of the OVX group (P<0.01, P<0.05). In serum bone metabolism indicators, the bone formation indicators BAP and PINP in the M group were significantly higher than those in the OVX group, while the bone resorption indicators CTX-I and TRACP were significantly lower than those in the OVX group. During the experiment, there were no significant differences in body weight among all groups, no obvious abnormalities in the appearance of the heart, liver, spleen, lung, kidney and other major organs, no significant differences in organ coefficients except the uterus of the ethoestradiol group, and no significant abnormalities were found in pathological examination except the uterus of the ethoestradiol group. Conclusion Oral administration of sheep placenta powder [300 mg/(kg?d)] can prevent osteoporosis in ovaries excised rats. The dual activities of promoting bone formation and inhibiting bone absorption may be an important mechanism of anti-osteoporosis, and sheep placenta powder has no side effect of thickening endometrium. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine Gu Sui Bu (Drynaria fortunei J. Smith), has the effect of tonifying the kidneys and strengthening bone. There are many modern studies on the anti-osteoporosis pharmacological mechanism of Gu Sui Bu (Drynaria fortunei J. Smith) but no reports on the pharmacological mechanism of Gu Sui Bu (Drynaria fortunei J. Smith) improving cell pyroptosis and anti-osteoporosis have been found. Aim: This study aims to verify the changes in cellular standard indicators in postmenopausal osteoporosis, thereby revealing the participating mechanism of pyroptosis and the intervention effect of Gu Sui Bu (Drynaria fortunei J. Smith) . Methods: Gu Sui Bu (Drynaria fortunei J. Smith) subjected to UHPLC-Q-Orbitrap-MS/MS analysis, and the OVX rat model was constructed in vivo as the research object. It was divided into sham operation group (SHAM), ovariectomized osteoporosis model group (OVX) and Gu Sui Bu (Drynaria fortunei J. Smith) group (TFRD-L, TFRD-H). After 3 months of modeling, the medication group was treated with Gu Sui Bu (Drynaria fortunei J. Smith) and the samples were collected after 12 weeks of intervention. ELISA was used to detect the levels of Caspase-1, NLRP3, GSDMD, IL-1β, and IL-18 in rat serum; the right femur was taken for Micro-CT large bone microstructure scanning and femoral BMD detection; the femur was subjected to rat histopathology HE, TRAP staining; immunohistochemistry and immunofluorescence staining of rat histopathology were performed. WB and PCR were used to observe the expression of Osteoblasts and pyroptosis-related indicators Caspase-1, NLRP3, GSDMD and RUNX2, IL-1β, and IL-18. Results: UHPLC-Q-Orbitrap-MS/MS analysis the main compounds in Gu Sui Bu (Drynaria fortunei J. Smith) samples were identified. These 9 chemical components are Palmitic acid, Fisetin, Caffeic acid, Naringin, Rutin, Uridine, Cafestol, Astilbin . Rat Micro-CT, The results of HE staining and TRAP showed that compared with the rats in the OVX group, the number of bone trabeculae in the rats in the Gu Sui Bu (Drynaria fortunei J. Smith) medication group (TFRD-L, TFRD-H) increased, became wider and thicker, and the bone density increased. Continuity increases and bone lacunae decrease. Rat serum ELISA, femoral tissue immunohistochemistry, immunofluorescence staining and WB, PCR showed that compared with the OVX group, Caspase-1, NLRP3, The expression levels of GSDMD and inflammation were reduced (p

Osteoporosis represents a prevalent disease that involves the degeneration of bone. The development of potent therapies is desired because the current clinical treatments are not able to provide a satisfying therapeutic effect. Recently, gold (Au) nanomaterials and chondroitin sulfate (CS) have been attracted a lot of attention in the field of drug delivery. The purpose of this research was to investigate exactly CS-AuNP function and its positive influences on anti-osteoporosis in ovariectomized (OVX) rats. The outcome of the OVX rats experimental results revealed effective anti-osteoporosis molecular targets of developed CS-AuNP formulation and their influence on the gut microbiota. Importantly, CS-AuNPs significantly improved lipid profiles, bone microstructure, metabolism markers, and bone mineral density. The findings provide more evidence that CS-AuNPs have effective therapeutic potential in anti-osteoporotic treatment by the MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Urinary incontinence is the major sign of menopause genitourinary syndrome and is usually related to the sexual dysfunctions. Fifty percent of menopausal women have menopausal urinary tract. Menopause genitourinary syndrome is a hypoestrogenic condition with external sexual, urological, and genital implications. The production of estrogen decline after menopause is an important parameter for urinary incontinence. Recently, nanotechnology has been applied as a remedial option for the genitourinary disease treatment. Silver nanoparticles were mediated by the Silybum marianum aqueous extract for the menopausal urinary incontinence treatment in ovariectomized rats in the current experiment. The green-formulated AgNPs@Silybum marianum were characterized by FT-IR, TEM, SEM, and UV–Vis. The SEM findings prove the spherical morphology with size of 15–60 nm. The ovariectomized rats were treated by AgNPs@Silybum marianum (5 and 20 µg/kg/day) for 56 days. According to the results, AgNPs@Silybum marianum increased the urinary bladder weight and reduced the body weights in comparison with the untreated rats. AgNPs@Silybum marianum rats indicated a dose-dependent amelioration for the acetylcholine contraction index. AgNPs@Silybum marianum also ameliorated the levels of serum 17β-estradiol, urinary bladder hydroxyproline, triglyceride, cholesterol, LDL, HDL, ALP, AST, and ALT in the ovariectomized rats. Based on the experiment results, the recent formulation may be applied for the menopausal urinary incontinence treatment in humans after performing the clinical research.

Bone broth has recently gained worldwide recognition as a superfood that supplements several nutrients lacking in modern human diets; however, little is known of its efficacy on osteoporosis. Therefore, we aimed to identify the components of chicken–vegetable bone broth (CVBB) that are associated with osteoporosis prevention and verified the efficacy of these components using in vivo studies. In biochemical and cell biological experiments, CVBB was fractionated using ion exchange chromatography (IEC), and the effect of each IEC fraction on osteoclast differentiation was evaluated based on tartrate‐resistant acid phosphatase (TRAP) activity, TRAP staining, and quantitative polymerase chain reaction analysis using mouse macrophage‐like cells (RAW264 cell). In animal experiments, an ovariectomized (OVX) rat model was generated, followed by whole bone broth (OVX/CVBB) or IEC fraction (OVX/CVBB‐Ext) administration and bone structural parameter characterization of OVX rat tibia based on micro‐CT. Four CVBB fractions were obtained using IEC, and the fraction containing both hyaluronan and chondroitin sulfate (CVBB‐Ext) led to the maximum inhibition of RAW264 cell differentiation. CVBB‐Ext downregulated the expression of osteoclast differentiation marker genes. In animal experiments, the OVX group showed a clear decrease in bone density compared to that in the Sham operation group. The OVX/CVBB and OVX/CVBB‐Ext groups showed increased bone mineral density and bone volume/tissue volume values compared to those in the OVX/control group. These results suggested that CVBB and CVBB‐Ext slowed osteoporosis progression. Therefore, we conclude that hyaluronan and chondroitin sulfate in CVBB are key substances that impede osteoporosis progression. Practical Application: This study provides practical information on the effects of bone broth ingredients on osteoporosis to expand the current knowledge on the efficacy of bone broth, which is a widely consumed food. These results may help in the future development of bone broth as a dietary supplement for managing osteoporosis. [ABSTRACT FROM AUTHOR]

Objective To investigate the therapeutic effect of ganoderma lucidum spores on ovariectomy-induced osteoporosis in rats. Methods Thirty-nine female Sprague-Dawley rats were randomly selected and ovariectomized to establish osteoporotic rat model, and the other 20 rats were performed sham surgery. Then all 59 rats were fed normally for 16 weeks. After successful modeling, 10 rats were randomly selected from the sham surgery group as blank control group (C group). Then 30 ovariectomized rats were randomly divided into three groups: model group (M group), low-dose ganoderma lucidum spores group (BL group, 400 mg/kg), and high-dose ganoderma lucidum spores group (BH group, 1 600 mg/kg). All rats were treated with gavage once a day for 10 weeks. Body weight changes, organ index, femoral bone mineral density, microstructural images of trabecular bone, trabecular bone parameters, bone biomechanical properties, and the serum content of bone metabolites were compared among the groups. Results There was no significant difference in body weight changes among the groups (P＞0.05). There were no statistical differences in organ index of the liver, spleen, and thymus among the groups (P＞0.05). Compared to that in C group, uterine index in M group decreased significantly (P＜0.01). However, uterine index in BL and BH groups was significantly higher than that in M group (P＜0.05). Compared to those in M group, the following indicators: femoral bone mineral density (BMD), bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), maximum load, bending strength, elastic modulus, and estradiol (E2) content in serum in BL and BH groups increased significantly (P＜0.05). However, the level of trabecular separation (Tb.Sp), osteocalcin (OC) content, bone alkaline phosphatase (BALP) content, and tartrate-resistant acid phosphatase 5b (TRACP-5b) content in serum in BL and BH groups decreased significantly (P＜0.01). Micro-CT images of the bone showed a decrease in density in trabecular bone of M group, while other micro-CT images of the bone showed a increase in density in trabecular bone of BL and BH groups. Conclusion Ganoderma lucidum spores have a certain therapeutic effect on osteoporosis in ovariectomized rats. It may be due to that ganoderma lucidum spores keep a balance of bone resorption and bone formation by improving endocrine function and estrogen level, thereby improving bone quality and increasing bone strength and bone mineral density. [ABSTRACT FROM AUTHOR]

Abstract Purpose In osteoporosis, the balance between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) is disrupted. The osteogenic differentiation of bone marrow MSCs (BMSCs) is important for improving osteoporosis. The aim of this study was to explore the role and molecular mechanism of miR-210 in the balance of osteogenic/adipogenic differentiation of BMSCs in postmenopausal osteoporosis. Methods Postmenopausal osteoporosis rat models were constructed by ovariectomy (OVX). BMSCs were isolated from the femur in rats of Sham and OVX groups. MiR-210 was overexpressed and suppressed by miR-210 mimics and inhibitor, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative mRNA expression of miR-210, ephrin type-A receptor 2 (EPHA2), alkaline phosphatase (ALP), osterix (OSX), osteocalcin (Bglap), Runt-related transcription factor 2 (Runx2), peroxisome proliferator activated receptor gamma, and fatty acid binding protein 4 (FABP4) in each group of rat femoral tissues or BMSCs. Western blot was applied to detect the protein expression level of EPHA2 in rat femoral tissues and cells. Alizarin red S staining and oil red O staining were performed to assess the osteogenic and adipogenic differentiation of BMSCs, respectively. In addition, the targeting relationship between miR-210 and EPHA2 was verified by a dual luciferase gene reporter assay. Results The expression of miR-210 was significantly reduced in femoral tissues and BMSCs of OVX rats, and its low expression was associated with reduced bone formation. The osteogenic differentiation was enhanced in OVX rats treated with miR-210 mimic. Overexpression of miR-210 in transfected BMSCs was also found to significantly promote osteogenic differentiation and even inhibit adipogenic differentiation in BMSCs, while knockdown of miR-210 did the opposite. Further mechanistic studies showed that miR-210 could target and inhibit the expression of EPHA2 in BMSCs, thus promoting osteogenic differentiation and inhibiting adipogenic differentiation of BMSCs. Conclusion MiR-210 promotes osteogenic differentiation and inhibits adipogenic differentiation of BMSCs by down-regulating EPHA2 expression. As it plays an important role in the osteogenic/adipogenic differentiation of osteoporosis, miR-210 can serve as a potential miRNA biomarker for osteoporosis.

Objective To investigate the effect of the strong bone and muscle form ula on bone mineral density ( BMD ) and IL-17 level in ovariectomized ra ts. Methods Thirty SPF grade 6-month-old female SD rats were divided into Sham group ( 11 = 9) and model group ( n = 21) according to random number table. After 12 weeks, 3 rats were respectively se lected from the Sham group and OVX group for lumbar vertebrae BMD test to verify the success of modeling. Rats in the model group were divided into OVX group ( n = 6), ZGQJ group ( n = 6 ), and Alen group ( n = 6 ). Rats in ZGQJ group received the strong bone and muscle formu la. Rats in Alen group received alendronate sodium. After 12 weeks of the treatment, the rats were sacrificed. BMD of the lumbar vertebrae was detected with DEXA. The microstructure of the tibia was detected with micro-CT. The structure of the femur and spleen was observed with HE staining. Serum level of IL-17 was detected with ELISA. The level of IL-17 in the tibia was detected with immunofluorescent staining. The level of IL-17 in the spleen was detected with immunohistochemistry. Results Compared to that in OVX group, the lumbar vertebrae BMD in ZGQJ and Alen group increased significantly ( P

Objective To explore the effect of ginseng polysaccharide on relieving osteoporosis and Wnt3/B-catenin/Runx2 signaling pathway in ovariectomized rats. Methods Rats were divided into five groups, sham operation group, model group, low-dose and high-dose ginseng polysaccharide groups (100 and 200 mg/kg), and alendronate sodium vitamin D3 group (6.25 mg/kg), with 10 rats in each group. Osteoporosis model was established using ovariectomy. After continuous intervention for 12 weeks, body mass was recorded. The histopathologic morphology of the bone was observed. Bone mineral density, bone biomechanical indexes, serum bone metabolism, and biochemical indexes were detected. Expressions of Wnt3, B-catenin, and Runx2 in the bone tissue were measured. Results Compared to those in the model group, the body mass of rats in low-dose and high-dose ginseng polysaccharide groups decreased significantly P < 0.01 ), the histopathologic morphology of bone was alleviated, P < 0.01 ) and bone mineral density, stiffness, and maximum stress and maximum load increased significantly ( P < 0.05, . Serum TRAP-5b content decreased significantly P < 0.05 P < 0.01 ) . The contents of BALP, OC, OPG, P3+, and Ca2+ increased significantly (P<0.05. P < 0.01 ) . The expressions of Wnt3, B-catenin, and Runx2 in the bone tissue increased significantly (P< 0.05, P < 0.01 ) . Conclusion Ginseng polysaccharide relieves osteoporosis in ovariectomized rats. Its mechanism may be related to the activation of Wnt3/B-catenin/Runx2 signaling pathway. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate the pathological changes in cardiac function, blood pressure, blood lipids and bone metabolism in ovariectomized (OVX) rats, as well as the intervention effect of Guizhi Longgu Muli decoction (GZLM). Bilateral oophorectomy was used to establish an OVX menopausal model. Four groups of rats were randomly selected: Sham surgery group, OVX group, estradiol (0.018g/L) and GZLM group (20g/kg). Cardiac function was assessed using ultrasound, blood pressure was measured using the tail cuff method. The oxidase method was used to determine the total cholesterol (TC) and triglycerides in serum. Direct measurement of high-density lipoprotein and lowdensity lipoprotein levels (LDL-C). Hematoxylin eosin staining and electron microscopy examination of myocardial structure. Microscopic CT was used to determine the bone microstructure. GZLM improved pathological cardiac changes and reduced the LVIDs, LVVols and LVVold. There was a decrease in systolic pressure, diastolic pressure and mean blood pressure in GZLM group. A decrease in serum TC and LDL-C levels was observed in the GZLM group. The BMD, BV/TV, Tb. Th, Tb.N of GZLM group raised, while Tb.SP and SMI significantly decreased or decreased. GZLM may have the effect of improving abnormal cardiac structure and function, promoting bone metabolism in OVX rats. [ABSTRACT FROM AUTHOR]

Purpose: In osteoporosis, the balance between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) is disrupted. The osteogenic differentiation of bone marrow MSCs (BMSCs) is important for improving osteoporosis. The aim of this study was to explore the role and molecular mechanism of miR-210 in the balance of osteogenic/adipogenic differentiation of BMSCs in postmenopausal osteoporosis. Methods: Postmenopausal osteoporosis rat models were constructed by ovariectomy (OVX). BMSCs were isolated from the femur in rats of Sham and OVX groups. MiR-210 was overexpressed and suppressed by miR-210 mimics and inhibitor, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative mRNA expression of miR-210, ephrin type-A receptor 2 (EPHA2), alkaline phosphatase (ALP), osterix (OSX), osteocalcin (Bglap), Runt-related transcription factor 2 (Runx2), peroxisome proliferator activated receptor gamma, and fatty acid binding protein 4 (FABP4) in each group of rat femoral tissues or BMSCs. Western blot was applied to detect the protein expression level of EPHA2 in rat femoral tissues and cells. Alizarin red S staining and oil red O staining were performed to assess the osteogenic and adipogenic differentiation of BMSCs, respectively. In addition, the targeting relationship between miR-210 and EPHA2 was verified by a dual luciferase gene reporter assay. Results: The expression of miR-210 was significantly reduced in femoral tissues and BMSCs of OVX rats, and its low expression was associated with reduced bone formation. The osteogenic differentiation was enhanced in OVX rats treated with miR-210 mimic. Overexpression of miR-210 in transfected BMSCs was also found to significantly promote osteogenic differentiation and even inhibit adipogenic differentiation in BMSCs, while knockdown of miR-210 did the opposite. Further mechanistic studies showed that miR-210 could target and inhibit the expression of EPHA2 in BMSCs, thus promoting osteogenic differentiation and inhibiting adipogenic differentiation of BMSCs. Conclusion: MiR-210 promotes osteogenic differentiation and inhibits adipogenic differentiation of BMSCs by down-regulating EPHA2 expression. As it plays an important role in the osteogenic/adipogenic differentiation of osteoporosis, miR-210 can serve as a potential miRNA biomarker for osteoporosis. [ABSTRACT FROM AUTHOR]

Objective To observe the protective effect of visceral adipose tissue derived serine protease inhibitor (vaspin) on osteoporosis in ovariectomized rats, and to explore the potential mechanism. Methods Thirty female SD rats were randomly divided into sham group (Sham), OVX group (OVX), and OVX+vaspin group, with 10 rats in each group. Rats in OVX group and OVX+vaspin group were performed ovariectomy to construct postmenopausal osteoporosis model. Rats in OVX+vaspin group received intraperitoneal injection of 1μg/kg vaspin every day, while rats in Sham and OVX groups received intraperitoneal injection of the same amount of normal saline. After 12 weeks of intervention, serum concentrations of type 1 collagen pron-terminal propeptide (P1NP), osteocalcin (OCN), tartrate-resistant acid phosphatase (TRAP), type 1 collagen C-terminal peptide (CTX), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were detected. Then histological examination, biomechanical analysis, and micro-CT examination were performed to evaluate bone microstructure and bone strength. The effects of vaspin on mRNA and protein expressions of OPG and RANKL in the bone tissue were detected using qRT-PCR and Western blotting. Results After 12 weeks of vaspin intervention, compared those in OVX group, serum P1NP and OCN in OVX+vaspin group increased significantly, while serum TRAP, CTX, IL-1β, and TNF-α decreased significantly (P<0.05). The mRNA and protein expression levels of OPG and RANKL in the bone tissue of the OVX group were respectively up-regulated and down-regulated compared to those in OVX group. Conclusion Vaspin may regulate bone metabolism in OVX rats by up-regulating the expression of OPG and down-regulating the expression of RANKL. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of trichostatin A (TSA) on titanium implant (TI) osseointegration in ovariectomized rats. Methods 3-Month-old female Sprague-Dawley rats (n=30) were randomly divided into Sham group (n=5) and OVX group (n=25). After 3 months of normal feeding, 5 rats in each group were randomly selected and were sacrificed. The distal femurs were harvested for evaluation with high-resolution micro-CT. HE staining was used to verify the establishment of osteoporosis model. TI was inserted bilaterally in the femoral metaphyseal region of remaining rats in OVX group. All the TI implanted rats were randomly divided into 2 groups: Control group (n=10) and TSA group (n=10). The rats in TSA group were intraperitoneally injected trichostatin A for 4 weeks. The rats in Control group were intraperitoneally injected the same amount of normal saline. All the rats were sacrificed after the drug treatment and the distal femurs were harvested for evaluation with high-resolution micro-CT, HE staining, and Masson staining. The serum of the rats was examined using ELISA. Results Compared with those in Sham group, micro-CT results showed that bone mineral density (BMD), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and connective density (Conn.D) in OVX group decreased (P<0.05), and trabecular separation (Tb.Sp) and structure model index (SMI) increased (P<0.05) in OVX group. HE staining results showed that Tb.N in OVX group significantly decreased. Compared with those in the Control group, BMD, BV/TV, Tb.Th, and Tb.N increased in TSA group (P<0.05), and Tb.Sp and SMI decreased (P<0.05). HE staining and Masson staining results showed that Tb.N and new bone increased in TSA group. ELISA results showed that bone morphogenesis-related proteins bone morphogenetic protein-2 (BMP2) and serum osteocalcin (OCN) increased in TSA group. Conclusion TSA improves TI implant osseointegration by promoting bone trabecular formation in OVX rats by up-regulating the key proteins of bone formation OCN and BMP2. [ABSTRACT FROM AUTHOR]

The study was designed in order the effect of one class of lipophilic statins (Atorvastatin) in some biomarkers of bone formation (Alkaline phosphatase (ALP), 1,25 (OH)2 D3, calcium, and phosphorous) in serum of ovariectomized female rats. Thirty adult female rats (2.5-3) months, weighing (200-220) gm were housed at conditions of controlled temperature (22-25°C), cycle (12h light - 12h dark) in the house of animals of Veterinary Medicine College of Mosul University. The animals were divided into three equal groups, sham group, ovariectomized (ovx) group, and ovx treatment orally with 20mg/kg/d of atorvastatin. After 60 days of treatment, blood from all groups was collected for ALP activity, 1,25 (OH)2 D3, calcium, and phosphorous estimation, and left femur bones were excised for histological examination. The results showed that the serum ALP, calcium, and phosphorus were significantly elevated, and a significant reduction in 1,25 (OH)2D3 was noticed in the ovx group. However, treatment with atorvastatin caused a significant reduction in ALP with a non-significant elevation in 1,25 (OH)2D3. Histological results showed a low density and thin trabecular bone, a few blood vessels, high numbers of osteoclast, with low numbers of osteoblasts in the ovx group. However, the treated ovx with atorvastatin increases the thickness of trabecular bone, medium developed osteogenic tissue, and a low number of osteoblasts. In conclusion, atorvastatin has a moderate effect on bone of ovx, affecting bone formation more than bone resorption.

The study was planned to explore the influence of one type of hydrophilic statins (rosuvastatin) on the level of serum osteocalcin, N-telopeptide of type 1 collagen (NTx), calcium, and phosphorus. In addition to calcium, phosphorus, and magnesium in femur bone ash of female ovariectomized rats. Thirty female rats aged 2.5-3 months were divided as follows, sham group, ovariectomized (ovx) group as a model of osteoporosis, and (ovx) group treated with 20mg /kg of rosuvastatin for 60 days. Blood samples were collected after 30 and 60 days of the experiment for biochemical analysis. Besides, after 60 days of the treatment, right femur bones were excised and ashed to estimate calcium, phosphorus, and magnesium. The results showed a significant elevation in serum osteocalcin, (NTx), calcium, and phosphorus, in addition to elevation in osteoclasts number and deceased osteoblasts and thickness of trabecular bone in the (ovx) group compared to the sham, while treatment with rosuvastatin caused a significant reduction in osteocalcin, (NTx), calcium and phosphorus after 60 days. Also, the results revealed a significant reduction in the percentage of (Ca, P and Mg) content in bone ash of the (ovx) group compared to the sham group. However, rosuvastatin treatment led to a significant elevation in the percentage of calcium and inorganic phosphate in bone ash and increased the thickness of trabecular bone and development in osteocytes compared with ovariectomized rats. The conclusion of the present study, rosuvastatin has a positive effect on the bone of ovariectomized rats.

Context Studies using experimental models have demonstrated that prebiotics are involved in antiosteoporotic mechanisms. Objective This study was conducted to determine the impact of supplementation with prebiotics in the basal diet of ovariectomized rats with induced osteoporosis as a preclinical model. Methods A comprehensive systematic search was carried out in the electronic databases PubMed, Science Direct, Web of Science, Scielo, and Google through March 2022 for studies that investigated the impact of prebiotics on bone mineral density (BMD), bone mineral content (BMC), and bone biomechanics. Results The search returned 844 complete articles, abstracts, or book chapters. After detailed screening, 8 studies met the inclusion criteria. Rats (n = 206), were randomly divided between control and treatment groups. Weighted mean differences (WMDs) with the 95%CIs were used to estimate the combined effect size. Compared with the control group, dietary intake of prebiotics significantly increased bone density in the BMD subgroups, with WMDs as follows: 0.03 g/cm3, 95%CI, 0.01–0.05, P  < 0.00001, n = 46; and 0.00 g/cm2, 95%CI, 0.00–0.02, P  < 0.00001, n = 81; total BMD: WMD, 0.01, 95%CI, 0.01–0.02, P  < 0.00001, n = 127; bone content in BMC: WMD, 0.02 g, 95%CI, 0.00–0.04, P  = 0.05, n = 107; and the 3-point-bend test: WMD, 15.20 N, 95%CI, 5.92–24.47, P  = 0.00001, n = 120. Conclusion Prebiotics improve indicators of osteoporosis, BMD, BMC, and bone biomechanics in ovariectomized rats. More studies are needed to increase the level of evidence. Systemic Review Registration Systematic Review Protocol for Animal Intervention Studies [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of Zhuanggu Qiangji Decoction on skeletal muscle morphology and function in ovariectomized rats. Methods Thirty-two 3-month-old female Sprague-Dawley（SD） rats were routinely fed for three months, and then randomly divided into sham operation group（n=8） and model group（n=24）. In the sham operation group, part of the adipose tissue around the ovaries was removed, while the rats in the model group underwent bilateral ovariectomy. After 12 weeks of postoperative feeding, the model group was equally divided into three groups, including model control group, Zhuanggu Qiangji decoction group and allenphosphate sodium group. Two rats were selected from each group to verify the success of ovariectomy model. Finally, according to the equivalent dose conversion formula, the rats in each group were treated by gavage for 12 weeks. After the end of gavage, the limb grip strength of the rats was measured. The gastrocnemius and soleus muscles were weighed and the skeletal muscle mass index was calculated. The morphological structure of muscle fibers was observed by HE staining, and the cross-sectional area of muscle fibers was measured. Results The limb grip strength, gastrocnemius index and triceps calves index of rats in the sham operation group, Zhuanggu Qiangji decoction group and alendronate sodium group were significantly higher than those in the model group（P＜0.05）. The mean cross-sectional area of gastrocnemius muscle fiber in the sham operation group and the Zhuanggu Qiangji decoction group was significantly higher than that in the model group（P＜0.05）, while there was no significant difference between the alendronate sodium group and the model group（P＞0.05）. Besides, there was no significant difference among the sham operation group, Zhuanggu Qiangji decoction group and alendronate sodium group（P＞0.05）. The morphological structure of skeletal muscle fibers in the three groups was also better than that in the model control group under HE staining. Conclusion Zhuanggu Qiangji decoction can significantly improve the morphology and function of skeletal muscle in ovariectomized rats. [ABSTRACT FROM AUTHOR]

Introduction:Artemisia argyi polysaccharide (AAP) has a beneficial effect on menstruation-related symptoms and the potential regulation of lipid metabolism. It is expected to be a safe and effective ingredient for estrogen deficiency and lipid metabolic disorders. Here, we investigate the effect of AAP on body weight gain, estrogen level, and blood lipid changes in ovariectomized (OVX) rats. Methods: Thirty-six female Wistar rats were randomly divided into six treatment groups, including a sham-operated (Sham) group, OVX group, estrogen replacement (OVX + E2) group, and AAP treatment (OVX + 125, 250, 500 mg/kg AAP) group. The body weight and feed intake were recorded every week. The level of estrogen and blood lipid was determined. The gene expressions and protein expressions of estrogen receptors (ERs), fatty acid synthetase (FAS), acetyl CoA carboxylase 2 (ACC2), and 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) were determined. Results: AAP treatment significantly decreased the body weight gain and average daily food intake of rats in the OVX group. Treatment with AAP significantly increased the relative weight of the uterus, plasma estrogen level, and the gene expression and protein expression of ER-α in the uterus. For blood lipids, plasma levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol were significantly reduced by AAP treatment in OVX rats. AAP treatment decreased the expression of FAS and HMGR in the liver of OVX rats. Furthermore, AAP treatment significantly increased the gene expression of ACC2, the protein expression of P-ACC2, and the ratio of P-ACC2/ACC2. Conclusion: In summary, AAP treatment exerts beneficial effects on body weight gain and lipid metabolism disorder induced by ovariectomy through increasing estrogen levels, inhibiting FAS, and promoting fatty acid oxidation. [ABSTRACT FROM AUTHOR]

Abstract Background Fragility fracture is one of the most serious consequences of female aging, which can increase the risk of death. Therefore, paying attention to the pathogenesis of postmenopausal osteoporosis (PMOP) is very important for elderly women. Methods and materials Forty 12-week-old female rats were divided into two groups including the ovariectomy (OVX) group and the control group. Four rats in each group were selected at 1, 4, 8, 12 and 16 weeks after operation. Vertebral bones and femurs were dissected completely for micro-Computed Tomography (micro-CT) scanning, biological modulus detection and histomorphological observation. Results In OVX group, bone volume/total volume (BV/TV), bone trabecular connection density (Conn.D) and trabecular bone number (Tb.N) decreased significantly with time (P 0.05). Over time, the tartrate resistant acid phosphatase (TRAP), osteocalcin (BGP), type I procollagen amino terminal propeptide (PINP) and type I collagen carboxy terminal peptide (CTX-I) in OVX group increased significantly (P

Abstract: Objective To investigate the mechanism of Jingangwan in the treatment of postmenopausal osteoporosis based on serum metabolomics by gas chromatography-mass spectrometry. Methods The rat model of postmenopausal osteoporosis was replicated by bilateral ovariectomy, and SD female rats were randomly divided into blank group ( Blank), sham operation group ( Sham), model group ( OVX), Jingangwan group (JGW, 3. 6 g/kg) and estradiol valerate group ( E2, 9 mg/kg), 6 rats in each group; and the drugs were given by intragastric administration once a day. After 12 weeks of administration, the right femurs of the rats were taken for hematoxylin-eosin staining ( H&E ) and bone mineral density ( BMD ) determination, The Enzyme-Linked ImmunoSorbent Assay ( ELISE) method was used to detect bone metabolism indicators alkaline phosphatase ( ALP), osteocalcin ( OCN), serum tartrate resistant acid phosphatase 5b ( TRAP5b), and biochemical method to detect total cholesterol ( TC), total triglycerides ( TG), low-density lipoprotein cholesterol ( LDL-C), high-density lipoprotein cholesterol ( HDL-C) content. After pre-treatment, serum samples were metabolically examined, principal component analysis and orthogonal partial least square discriminant analysis were combined to identify and screen serum metabolites, and related metabolic pathways were enriched through MetaboAnalyst. Results H&E staining result showed that the morphology of bone trabecular bone in JGW group was significantly improved compared with that in model group. Compared with Sham group, BMD and HDL-C levels in OVX group were decreased ( P

Research shows that the consumption of soybean foods can reduce the incidence rate of bone fractures in women after menopause. The aim of this study was to investigate the effects of different complex of soy β‐conglycinin (7S) and isoflavones (7S‐ISO) on osteoporosis in ovariectomized rats. All treatments were administrated intragastrically to the groups every afternoon for 3 months. The treatments were administrated at 1 mL·(100 g)−1, the animals were given 50 mg·kg−1·d−1 ISO, and the concentration of protein was about 2 wt. %. The bone mineral density (BMD) and the bone biomechanics results of left tibia' maximum load in the 7S‐ISO group is significantly higher than in the ovariectomized group and the 7S group (p <.05). Otherwise, the serum tartrate‐resistant acid phosphatase (s‐TRACP), serum osteocalcin (s‐BGP), and serum estradiol (s‐E2) levels in 7S‐ISO were all significantly different from the OVX, OVX + casein, and the OVX + 7S group (p <.05). The serum calcium (s‐Ca) level was not significantly different among all the groups. 7S‐ISO may exhibit moderate estrogenic activities and as compared to 7S and ISO in osteoporosis (OP) of ovariectomized rats. Practical applications: The effects of soy proteins on the health of females have always been a concern. It has been extensively reported soy 7S globulin (7S) as a type of trimer glycoprotein can depress blood fats. The aim of this study was to investigate the effects of different complex of soy β‐conglycinin and isoflavones (ISO), the main storage proteins and polyphenols in soy, on osteoporosis in ovariectomized rats. [ABSTRACT FROM AUTHOR]

Bone health is vital through all life stages and has become a growing public health concern. The role of rhizoma drynariae (RD) as a traditional Chinese medicine for bone injury recovery has been widely investigated. Still, there is little research related to RD as a functional component in food to improve calcium bioavailability and bone health. Milk powder is a daily vital food source of dietary calcium. The present study aimed to investigate and compare the effects of a functional milk powder reinforced with RD extracts (RDE) or vitamin D, vitamin K2, and calcium, or both, using Sprague-Dawley rats, with both low calcium growing rat model and low calcium ovariectomized (OVX) rat model. For growing rats, RDE increased bone mineral density (BMD) and improved the microstructure of bone trabecula in the femur and lumbar vertebrae. The levels of serum bone turnover markers CTX-I, PINP, and BGP were increased with RDE supplementation. The tartrate-resistant acid phosphatase staining suggested a decrease in the number of osteoclasts in the femur. Immunohistochemistry showed that the osteoclast-related protein RANKL was downregulated, and the osteogenic-associated proteins RUNX2 and OSX significantly increased in the lumbar vertebrae. Similarly, in OVX rats, RDE improved BMD and microstructure in lumbar vertebrae, and the levels of CTX-I, PINP, and BGP were also increased. In conclusion, the novel functional milk powder supplemented with RDE facilitated osteogenesis and inhibited osteoclast in rats at both stages, especially with lumbar vertebrae in growing rats. Our findings provide new prospects and a more precise target for enhancing bone health by incorporating RDE as a functional component in milk powder., (© 2025, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

ObjectivesThis study aimed to identify the key proteins in the bone mass of ovariectomized (OVX) rats after a period of regular moderate-intensity treadmill exercise and to investigate their effects using tag mass spectrometry and quantitative proteomics with a view to improving the understanding and treatment of postmenopausal osteoporosis.MethodsSixty three-month-old female Sprague-Dawley tats of specific-pathogen-free grade were randomly and equally divided into a sham operation group, ovariectomized group (OVX) and ovariectomized combined exercise (OVX + EX) group, and the latter took moderate-intensity treadmill exercise for 17 weeks. After this period of time, body composition and bone density were measured using dual-energy x-ray absorptiometry, and serum bone metabolism indicators were measured using an enzyme immunoassay. In addition, the bone microstructure was examined using micro-computed tomography and scanning of the femur, and femur proteins were subject to proteomic analysis.ResultsCompared with the rats in the OVX group, the bone metabolism indicators in the OVX + EX group decreased significantly, femur bone density increased significantly, the number of the trabeculae increased, and continuity was higher. In the OVX + EX group, 17 proteins were significantly upregulated and 33 significantly downregulated. The main gene ontology and signaling pathways enriched by the proteins were identified as the tumor necrosis factor-mediated signaling pathways. The protein-protein interaction network identified the key proteins, and the correlation analysis of these proteins and the bone parameters found histone deacetylase 8(HDAC8) and leucine-rich transmembrane and O-methyltransferase domain containing (LRTOMT) and trimethylguanosine synthase 1(TGS1) and ankyrin repeat domain 46(ANKRD46) to be the key targets of exercise in relation to postmenopausal osteoporosis.ConclusionModerate-intensity treadmill exercise significantly improved the bone mass of OVX rats, and differentially expressed proteins, such as HDAC8 and LRTOMT and TGS1 and ANKRD46, could be the target of moderate-intensity treadmill exercise.

Background. Calcium (Ca) and magnesium (Mg) are important components of bones, whose homeostasis is disturbed during menopause. Calcium and magnesium metabolism are closely related, so it is important to study the interactions between them. This study aimed to determine the effect of Ca-enriched pumpkin on the Mg content in tissues in an animal model of postmenopausal osteoporosis. Material and methods. 70 female Wistar rats divided into seven groups. One group was fed a standard diet (C), whereas the other six groups were ovariectomized and fed a standard diet (OVX), a calcium-deficient diet (DEF), a calcium lactate diet (CaL), calcium-lactate-enriched pumpkin (P_CaL), calcium lactate and alendronate (CaL_B), or calcium-lactate-enriched pumpkin and alendronate (P_CaL_B). This nutritional intervention was followed for 12 weeks, and then the rats were euthanized. Tissue samples were collected, and their magnesium content was assessed. Results. The Mg content in bones was lower in the OVX group (3.15 ±0.19 mg/g) but higher in the DEF group (3.76 ±0.16 mg/g) in comparison with the control group (3.45 ±0.15 mg/g). The Mg content in the muscles and the liver was higher in the P_CaL group (1025.24 ±47.22 µg/g and 2102.09 ±83.35 µg/g) compared with the control group (842.51 ±19.13 µg/g and 1486.15 ±97.12 µg/g). However, the CaL_B and P_CaL_B groups showed a high Mg content in the kidneys (about 156% of the control group). Conclusion. Ovariectomy and intervention diets revealed various new observations regarding the effect of innovative calcium-rich foods on the Mg content. These results showed that (i) ovariectomy decreases the status of Mg content; (ii) deficiency of Ca in the diet and Ca-enriched pumpkin with alendronate improve the Mg content in bones; and (iii) alendronate promotes the accumulation of Mg in the kidneys. In postmenopausal women, both those treated and untreated with drugs and diet, magnesium status should be monitored. [ABSTRACT FROM AUTHOR]

Calcitriol supplementation in ovariectomized rats for 8 weeks reduce osteoporosis risk and safe for kidney depend a proper dose. The objective of the research was to study the efectivity of high dose calcitriol for osteoporosis prevention and safe for kidney in ovariectomized Wistar rats. Fifteen female Wistar rats at 8 weeks of age were randomly divided into three groups of five which were sham operated rats (KN), ovariectomized rats (KOV), and ovariectomized rats+calcitriol supplementation 200ng/day (OVD200). After 8 weeks of treatment, blood samples were taken from plexus orbitalis medialis for estrogen analysis. All rats were then euthanized, left tibia and left kidney were taken for histopathological examination using hematoxylin and eosin stain. Immunohistochemistry using anti TRAP5b monoclonal antibody was also done for left tibia by streptavidin-biotin. The results showed that estradiol level of KOV was significantly decreased compared with KN (P

The primary focus of bisphosphonate medications is on targeting human farnesyl pyrophosphate synthase (hFPPS), an essential regulator of mammalian isoprenoids. Yet, these drugs encounter limitations due to their restricted "druglike" properties and their effectiveness primarily in treating skeletal disorders. In this study, we synthesized novel non-bisphosphonate compounds, using 4,4'-(ethane-1,2-diylbis(oxy))bis(3-methoxybenzaldehyde) (1) as a starting compound, with the aim of targeting hFPPS through a mixed binding approach. Among the various compounds tested, compounds 4a and 4b exhibited significant inhibition of hFPPS activity, with IC 50 values of 1.108 and 1.24 μM, respectively. Docking studies further revealed that both compounds bound within the allylic binding site and near the isopentenyl diphosphate (IPP) site within the hFPPS pocket. Molecular dynamic simulations were performed on the best docking pose of the most potent compound 4a to confirm the formation of a stable complex with hFPPS. In an in vivo study conducted on ovariectomized rats, various biochemical markers including osteocalcin, estradiol, osteoprotegerin, bone mineral content, and density were negatively impacted, while levels of bone specific alkaline phosphatase, receptor activator of nuclear factor kappa-Β ligand, serum/urinary calcium, and phosphate increased. Notably, compound 4a exhibited antiresorptive properties similar to zoledronate, effectively restoring most of the perturbed biochemical estimations. These findings suggest the potential of compound 4a , a non-bisphosphonate compound, as alternative therapeutic agents for combating osteoporosis. [Display omitted] • Synthesis of novel non-bisphosphonate compounds targeting hFPPS through a mixed binding approach. • Compounds 4a and 4b exhibited significant inhibition of hFPPS activity, with IC 50 values of 1.108 and 1.24 μM, respectively. • Docking studies further revealed that both compounds bound within the allylic binding site and near the isopentenyl diphosphate (IPP) site within the hFPPS pocket. • Molecular dynamic simulations were performed on the best docking pose of the most potent compound 4a to confirm the formation of a stable complex with hFPPS. • In vivo studies, compound 4a exhibited antiresorptive properties similar to zoledronate, the findings suggest that compound 4a is a non-bisphosphonate compound, as alternative therapeutic agents for combating osteoporosis. [ABSTRACT FROM AUTHOR]

Objective To study the curative effect of bionic tiger‐bone powder on osteoporosis in ovariectomized rats and investigate its mechanism. Methods Overall, a 120 female Wistar rats were randomly divided into Sham (sham‐operated group), ovariectomy (OVX, ovariectomized group), TB (bionic tiger‐bone powder treatment group after ovariectomy) and TB + VD groups (bionic tiger‐bone powder + vitamin D treatment group after ovariectomy). The osteoporotic rat model was established 3 months after ovariectomy, and rats were intragastrically administrated with the corresponding drugs. Serum and bone tissue samples were collected from 10 rats in each group at weeks 4, 12 and 24 after intragastric administration. The bone microstructure of L6 vertebrae was analyzed by MicroCT, the biomechanical strength of left femurs was measured by the three‐point bending test, and serum bone metabolism markers (P1NP and CTX) were detected by ELISA. Changes in bone collagen were analyzed by Masson's trichrome staining and hydroxyproline detection, and members of the BMP2/SMAD/RUNX2 and OPG/RANKL/RANK signal pathways were detected by immunoblotting. Results Compared with the OVX group, the serum level of P1NP in the TB and TB + VD groups was higher (P

Background Amlodipine as a calcium channel blocker has anti-inflammatory effect through overaugmentation of nitric oxide production and antioxidant effect by reduced superoxide radicals and increased level of superoxide dismutase. l-carnitine has anti-inflammatory action through reaction with acyl group that is accumulated in anoxic cells and antioxidant effect through decreasing the superoxide anion production. Aim The aim was to evaluate the possible ameliorating effect of amlodipine (AML) and L-Carnitine (L-C) combination on osteoporotic bony changes in ovariectomized (OVX) rats versus each drug separately. A total of 50 adult female albino rats (weighting 100–125 g) of local strain were chosen as an animal model for this study. The animals were randomly divided into five groups. Each group comprised ten rats: group 1, negative control; group 2, OVX rats, positive control; group 3, AML-treated OVX rats; group 4, L-C-treated OVX rats, and group 5, AML and L-C-treated OVX rats. Bony changes were examined through evaluating markers of bone turnover, such as alkaline phosphatase and osteocalcin; femoral metaphyseal histomorphology; and serum proinflammatory cytokines, such as tumor necrosis factor-α, expression. Results alkaline phosphatase, osteocalcin, and tumor necrosis factor-α were significantly elevated in positive control group, which was associated with marked deterioration of bone microarchitecture. Treatment with AML and L-C combination significantly mitigated inflammation and histopathological osteoporotic changes compared with each of AML and L-C drugs separately. Conclusion AML and L-C combination could have a synergistic role in management of radical osteoporosis in OVX rats over each drug separately.

To explore the effect and mechanism of aralia taibaiensis on osteoporosis through Wnt/β-catenin catenin signaling pathway in ovariectomized rats. Methods Forty female SD rats were randomly divided into sham operation group, model group, Xianlinggubao capsule group ( 0.3 g/kg), aralia taibaiensis low-dose group ( 0.4 g/kg), and aralia taibaiensis high-dose group ( 0.8 g/ kg ) . There were 8 rats in each group. Except for rats in the sham operation group, rats in other groups underwent ovariectomy. Corresponding drugs were intragastrically administered for 12 weeks after operation. Bone biomechanical properties were measured using three-point bending test. Bone mineral density and microstructure were detected with micro-CT. Serum bone metabolism indexes were detected with ELISA. Morphological changes of bone tissue was observed with HE staining. The expression of proteins in Wnt/β-catenin in signaling pathway in bone tissue was detected by Western blotting. Results Compared to the model group, after 12 weeks of high-dose aralia taibaiensis treatment, the maximum load, stiffness, maximum stress and bone mineral density increased significantly ( P

Background: Fragility fracture is one of the most serious consequences of female aging, which can increase the risk of death. Therefore, paying attention to the pathogenesis of postmenopausal osteoporosis (PMOP) is very important for elderly women.Methods and Materials: Forty 12-week-old female rats were divided into two groups including the ovariectomy (OVX) group and the control group. Four rats in each group were selected at 1, 4, 8, 12 and 16 weeks after operation. Vertebral bones and femurs were dissected completely for micro-Computed Tomography (micro-CT) scanning, biological modulus detection and histomorphological observation.Results: In OVX group, bone volume/total volume (BV/TV), bone trabecular connection density (Conn.D) and trabecular bone number (Tb.N) decreased significantly with time (P < 0.05). The elastic modulus of femur in OVX group was lower than that in control group, but there was no significant difference between them (P > 0.05). Over time, the tartrate resistant acid phosphatase (TRAP), osteocalcin (BGP), type I procollagen amino terminal propeptide (PINP) and type I collagen carboxy terminal peptide (CTX-I) in OVX group increased significantly (P < 0.05). The micrographs of the OVX group showed sparse loss of the trabecular interconnectivity and widening intertrabecular spaces with time.Conclusion: The bone loss patterns of vertebral body and femur were different in the early stage of estrogen deficiency. The bone turnover rate of OVX rats increased, however the changes of biomechanical properties weren't obvious. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of sesamin on the changes of bone structure and the expression of osteocalcin and type I collagen in the rat model. Methods Ovariectomized (OVX) rat model was established. Rats received sesamin (80 mg/kg) by intragastric administration as an intervention and a control group was established at the same time. The femur of rats was analyzed using micro-computed tomography (micro-CT). The content of osteocalcin (OCN) and the expression of type I collagen in the femur were detected with immunohistochemistry and immunofluorescence. Results Compared to those in the OVX group, bone mineral density (BMD) of OVX+S increased and the trabecular spacing (Tb.Sp) decreased in the experimental group. At the same time, the expressions of osteocalcin and type I collagen in the intervention group was significantly higher than those in the intervention group (P<0.05). Conclusion Sesamin effectively promotes the remodeling of bone structure in ovariectomized rats and has a positive effect on the treatment and prevention of osteoporosis in rats. [ABSTRACT FROM AUTHOR]

Abstract Background Depression is a serious and common psychiatric disorder generally affecting more women than men. A woman’s risk of developing depression increases steadily with age, and higher incidence is associated with the onset of menopause. Here we evaluated the antidepressant properties of Asparagus cochinchinensis (AC) extract and investigated its underlying mechanisms in a rat menopausal depression model. Methods To model this menopausal depression, we induced a menopause-like state in rats via ovariectomy and exposed them to chronic unpredictable mild stress (CUMS) for 6 weeks, which promotes the development of depression-like symptoms. During the final 4 weeks of CUMS, rats were treated with either AC extract (1000 or 2000 mg/kg, PO), which has been reported to provide antidepressant effects, or with the tricyclic antidepressant imipramine (10 mg/kg, IP). Results We report that CUMS promotes depression-like behavior and significantly increases serum corticosterone and inflammatory cytokine levels in the serum of ovariectomized (OVX) rats. We also found that CUMS decreases the expression of brain-derived neurotrophic factor (BDNF) and its primary receptor, tropomyosin receptor kinase B (TrkB), in OVX rats, and treatment with AC extract rescues both BDNF and TrkB expression levels. Conclusion These results suggest that AC extract exerts antidepressant effects, possibly via modulation of the BDNF-TrkB pathway, in a rat model of menopausal depression.

Abstract Background The prevalence of hypertension in young women is lower than that in age-matched men while the prevalence of hypertension in women is significantly increased after the age of 50 (menopause) and is greater than that in men. It is already known that sphingosine-1-phosphate (S1P) and ceramide regulate vascular tone with opposing effects. This study aimed to explore the effects of ovariectomy and estrogen supplementation on the ceramide/S1P rheostat of the aorta in rats, and to explore a potential mechanism for perimenopausal hypertension and a brand-new target for menopausal hormone therapy to protect vessels. Methods In total, 30 female adult SD rats were randomly divided into three groups: The sham operation group (SHAM), ovariectomy group (OVX) and ovariectomy plus estrogen group (OVX + E). After 4 weeks of treatment, the blood pressure (BP) of the rats was monitored by a noninvasive system; the sphingolipid content (e.g., ceramide and S1P) was detected by liquid chromatography-mass spectrometry (LC-MS); the expression of the key enzymes involved in ceramide anabolism and catabolism was measured by real-time fluorescence quantitative polymerase chain reaction (qPCR); and the expression of key enzymes and proteins in the sphingosine kinase 1/2 (SphK1/2)-S1P-S1P receptor 1/2/3 (S1P1/2/3) signaling pathway was detected by qPCR and western blotting. Results In the OVX group compared with the SHAM group, the systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) increased significantly, especially the SBP and PP (P 0.05). Conclusions Ovariectomy resulted in the imbalance of the aortic ceramide/S1P rheostat in rats, which may be a potential mechanism underlying the increase in SBP and PP among perimenopausal women. Besides, the ceramide/S1P rheostat may be a novel mechanism by which estrogen protects vessels.

This research was planned to verify the influence of saponin, that extracted from Glycyrrihiza glabra in activity of hepatic enzymes and some biochemical parameters of serum ovariectomized adult female rats. 15 adult female rats were randomly divided into three groups, which included sham-operated (sham), ovariectomized (ovx), and ovariectomized rats treated orally with (250 mg/kg/day) of saponin extract for (25) days. The results revealed, that ovx rats showed a significant elevation in alkaline phosphatase (ALP) activity, Calcium level, a significant reduction in activities of creatine kinase (CK), aspartate amino transferase (AST), γ-Glutamyl transferase (GGT), and level of albumin, creatinine without any significant change in alanine amino transferase (ALT) activity and magnesium level comparison with sham -operated rats. Treatment ovx rats with 250 mg/kg of saponin caused a significant reduction in ALT and CK activities, and elevation in albumin and creatinine levels, and AST, GGT activities. In conclusion, the present results revealed that, saponin extracted of Glycyrrihiza glabra have an effect in hepatic enzyme activity and some biochemical parameters in ovariectomized female rats with osteoporosis results from reduction in estrogen level.

Weight-bearing training, as one of resistance exercises, is beneficial to bone health. Myostatin (MSTN) is a negative regulator of skeletal muscle growth and development. Animals lacking MSTN show increased bone mineral density (BMD). The aim of this study was to investigate the preventive effect of weight-bearing training on bone loss in ovariectomized rats and whether it was related to MSTN. In this study, the rats were randomly assigned to three group: Sham-ovariectomized (Sham), ovariectomized (OVX), ovariectomized and weight-bearing training (OWT). The rats in the OWT group ran at 20-m/min bearing with 35% of their body weight for 6 days/week. After 10 weeks, compared with the OVX group, weight-bearing training increased the BMD of total femur and trabecular bone by 8.13% and 57.44%, respectively. The OVX-induced destruction of bone microarchitecture including the thickness and number of trabeculae and bone volume fraction was all significantly improved (9.26%, 47.68%, 63.03%) in the OWT group. The OVX-induced degradation of bone mechanical properties was significantly enhanced in the OWT group (maximum load increased by 35.46%, stiffness increased by 89.19%, energy absorption increased by 53.4%; elastic modulus increased by 26.3%). Ten-week weight-bearing training also significantly upregulated the mRNA and protein expression of Wnt1 and β-catenin, which is crucial in bone development. Compared with the Sham group, MSTN in serum and muscle increased in the OVX group, but it decreased in the OWT group compared with the OVX group. Its receptor ActRIIB and downstream molecules Smad2/3 in the OVX group were downregulated in bone by weight-bearing training. The results indicated that MSTN is an important myokine for weight-bearing training to attenuate bone loss in ovariectomized rats. [ABSTRACT FROM AUTHOR]

The study examined the skin histomorphology and biochemistry in mature ovariectomized rats treated and not treated with estrogen. Biochemical parameters (superoxide dismutase, malondialdehyde, and hydroxyproline content) were measured in dorsal skin samples collected in 50 days after surgery. The morphology of dorsal skin was analyzed under a microscope. In ovariectomized rats, the skin levels of superoxide dismutase and hydroxyproline were significantly lower, while the superoxide dismutase content was significantly higher than in shamoperated animals (p<0.05). Estrogen therapy significantly increased the levels of superoxide dismutase and hydroxyproline and reduced superoxide dismutase level in ovariectomized rats in comparison with the corresponding parameters in untreated ovariectomized animals (p<0.05). Histomorphological analysis of the skin from non-treated ovariectomized rats revealed reduced vascularization and lower density of papillary capillaries in comparison with these parameters in sham-operated controls; estrogen treatment prevented these changes. We concluded that ovariectomized rats can be employed as a model of aging skin in menopause [ABSTRACT FROM AUTHOR]

Objective To investigate the mechanism of Jiangu Granule in the treatment of postmenopausal osteoporosis by metabonomics. Methods Sixty rats were randomly divided into normal group, model group and Jiangu Granule group.The Jiangu granule group was given Jiangu granule solution by gavage, and the others were given the same capacity saline by gavage. After 6 week or 12 week, the femur, tibia and lumbar vertebrae were used for the test of bone mineral density(BMD) and biomechanics. The blood of abdominal aorta was analyzed by liquid chromatography-mass spectrometry (LC-MS). After univariate statistics and multivariate statistics analysis, the potential metabolites were selected. Results Compared with the normal group, the BMD and maximum load of model group decreased significantly, while the Jiangu Granule group tended to return to normal level. It was indicated that the model was successful and the rat body was tended to return to normal. The serum metabolic spectrum of the model group and the normal group were completely separated. Jiangu Granule group was close to the normal group. 27 different metabolites, such as pantothenate, stearic acid and corticosterone, were screened out, which were related to the biosynthesis of pantothenate and CoA, unsaturated fatty acids and steroid hormones, respectively. These metabolites were involved in lipid metabolism, nucleic acid metabolism, amino acid metabolism and so on. Conclusion Jiangu granule may treat postmenopausal osteoporosis by regulated multiple metabolic pathways. [ABSTRACT FROM AUTHOR]

Background: Evidences are beginning to accrue that flavonoids, particularly phytoestrogens, could have beneficial effects against several age-related diseases linked to estrogen deficiency including postmenopausal osteoporosis. Methods: In this study, the effect of chrysin on selected bone-remodeling markers in ovariectomized rats and its estrogen-like activity in silico were investigated. Results: The data indicated that administration of chrysin at 50 mg/kg and 100 mg/kg for 6 weeks to OVX rats significantly (p < 0.05) prevented body weight gain and partially reverse uterine weight loss. In addition, treatment of OVX rats significantly (p < 0.01) increased femur dry weight, femur ash weight, bone ash calcium, and phosphorous levels in a dose-dependent manner. However, there was significant (p < 0.001) decline in serum estradiol level in all OVX rats compared to the sham-operated group. Interestingly, administration of chrysin significantly (p < 0.05) reversed the reduction of estradiol induced by ovariectomy compared to untreated OVX rats. Moreover, administration of chrysin to OVX rats significantly (p < 0.05) suppressed excessive elevation of bone-remodeling markers expression compared to untreated OVX rats. Similarly, molecular docking analysis revealed that chrysin interacts with both α and β estrogen receptors with exothermic binding energies of −229.83 kcal/Mol and −252.72 kcal/Mol, respectively, and also fits perfectly into the active site of both α and β estrogen receptors. Conclusion: This study demonstrated that chrysin exhibits potential antiosteoporotic effects against bone loss in OVX rats through enhanced bone mineral contents and preventing excessive elevation of bone-remodeling markers and bone-resorbing cytokine. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effects of chicken eggshell powder rich in calcium and the inorganic form of calcium carbonate on osteoporotic bone structure using an animal model of ovariectomized rats. Animals were divided into four groups: sham-operated rats (SHAM group); ovariectomized rats untreated (OVX group); OVX rats treated with eggshell powder (Biomin H®; OVX + ECa group; total Ca content 1.5%); and OVX rats receiving inorganic calcium carbonate (calcium carbonate precipitated, total Ca content 1.5%; OVX + ICa group) during 8 weeks. Ovariectomy increased total body weight, plasma alkaline phosphatase activity, cortical bone thickness, periosteal bone apposition, and considerably worsened the trabecular bone microarchitecture. Calcium supplementation in both OVX + ECa and OVX + ICa groups elevated blood supply in the cortical bone when compared to OVX rats. Treatment with eggshell powder, unlike the OVX + ICa group, significantly lowered bone resorption, increased plasma calcium level, relative volume of trabecular bone, and secondary osteon population density, which together contributes to the enhanced bone strength. In addition, sizes of Haversian canals and secondary osteons in OVX + ECa group reached the values of SHAM group. Our results suggest that chicken eggshell powder more effectively ameliorates bone loss in ovariectomized rats than precipitated calcium carbonate. [ABSTRACT FROM AUTHOR]

Objective: Using RNA-sequencing technology to screen the effect of moderate-intensity treadmill exercise on the sensitive genes that affect bone mass in the peripheral blood mononuclear cells (PBMCs) of ovariectomized (OVX) rats.Methods: Three-month-old female Sprague-Dawley rats of Specific Pathogen Free (SPF) grade were randomly divided into the sham operation (SHAM) group, OVX group, and OVX combined exercise (OVX + EX) group. The OVX + EX group performed moderate-intensity treadmill exercise for 17 weeks. Then, the body composition and bone mineral density (BMD) were measured, and the bone microstructure of the femur was observed. PBMCs were collected from the abdominal aorta, and the differential genes were analyzed by transcriptome sequencing to further screen sensitive genes.Results: (1) In the OVX group, the body weight and body fat content were significantly higher than in the SHAM group while the muscle content and BMD were significantly lower than the SHAM group. (2) The trabecular bone parameters in the OVX group were significantly lower than in the SHAM group, and they were significantly higher in the OVX + EX group than in the OVX group. When compared with the SHAM group, the microstructure of the distal femur trabecular in the OVX group was severely damaged, suggest that the morphological structure of trabecular bone is severely damaged, the number of trabecular bones is reduced, and the thickness becomes thinner, which lead to the widening of the trabecular bone space and the appearance of osteoporosis. The number and continuity of the trabecular bones were higher in the OVX + EX group than in the OVX group. (3) A Venn diagram showed that there were 58 common differential genes, and the differential genes were mainly enriched in the PI3K-Akt signaling pathway. Five sensitive genes were screened including CCL2, Nos3, Tgfb3, ITGb4, and LpL. The expression of CCL2, Nos3, and Tgfb3 genes was closely related to multiple bone parameters.Conclusion: Moderate-intensity treadmill exercise may improve the body composition and bone mass of the OVX group by upregulating CCL2 and other genes of the PBMC. The PBMCs in the peripheral blood can be a useful tool for monitoring the effect of exercise on bone health in postmenopausal osteoporosis.

BACKGROUND: Paeonol can inhibit inflammation and relieve the clinical symptoms of chronic osteoarthritis. As a natural drug component with less side effects and more safety, it is of great clinical significance to explore the treatment of osteoporosis. OBJECTIVE: To investigate the effects of paeonol on the signal pathway of forkhead box O3a/Wnt and the density of vertebrae in ovariectomized osteoporosis (OVX-OP) rats. METHODS: Female Sprague-Dawley rats were randomly divided six groups (n=10 per group). Rats in the sham operation only underwent removal of adipose tissue adjacent to the ovary, and the other 50 rats were used to make OVX-OP rat models by bilateral ovariectomy. The rat models were randomly divided into OVX-OP group, estrogen group (ethinylestradiol 10 μg/kg/d), low- (paeonol 125 mg/kg/d), medium- (paeonol 250 mg/kg/d), and high-dose (paeonol 500 mg/kg/d) groups. The rats were administered by gavage. Sham operation group and OVX-OP group were given the same amount of normal saline. The intervention lasted for 12 weeks. The levels of serum estrogen, osteoprotegerin and osteocalcin were measured by enzyme-linked immunosorbent assay. Bone mineral density of the femur and vertebrae was measured by dual energy X-ray animal bone mineral density meter. The biomechanical indexes of the femur and vertebrae, elastic modulus, maximum load and yield load, were measured by orthopedic biomechanical tester. The expression levels of forkhead box O3a and Wnt2 mRNA were detected by real-time fluorescence quantitative PCR. The expression levels of forkhead box O3a, Wnt2 and nucleus β-catenin proteins were detected by western blot. RESULTS AND CONCLUSION: After the treatment, the bone mineral density, elastic modulus, maximum load, and yield load in the 4th and 5th lumbar vertebrae, serum estradiol and osteoprotegerin levels, Wnt2 mRNA and protein levels, and nucleus β-catenin protein level were significantly lower in the OVX-OP group than the sham operation group (P < 0.05), while serum osteocalcin and vertebral forkhead box O3a mRNA and protein levels were significantly higher in the OVX-OP group (P < 0.05). Compared with the OVX-OP group, low-, medium, and high-dose paeonol significantly increased the bone mineral density, elastic modulus, maximum load, and yield load in the 4th and 5th lumbar vertebrae, serum estradiol and osteoprotegerin levels, Wnt2 mRNA and protein levels in the vertebrae (P < 0.05), and decreased the levels of serum osteocalcin and vertebral FOXO3a mRNA and protein (P < 0.05). Moreover, the above-mentioned indexes were better in the high-dose paeonol group than the estrogen group (P < 0.05). To conclude, paeonol can increase bone mineral density of the vertebrae, improve the biomechanical condition, and relieve osteoporosis in OVX-OP rats, which may be related to the inhibition of forkhead box O3a and the promotion of Wnt2/β-catenin pathway activation. [ABSTRACT FROM AUTHOR]

Introduction: The objectives of the present study were to determine whether simvastatin (SIM) could reverse the harmful effects on titanium rod osseointegration in ovariectomized rats fed high-fat diet (HFD). Materials and Methods: Ovariectomized female Sprague–Dawley rats were randomly allocated to three groups and received SIM treatment plus HFD for 12 weeks. We then evaluated the microstructure parameters, histological parameters, biomechanical parameters, bone turnover, and blood lipid level. Results: After 12 weeks of treatment, SIM can significantly improve bone formation around the titanium rod and osseointegration including higher values of maximum push-out force, bone area ratio (BAR), bone-to-implant contact (BIC), bone mineral density (BMD), bone volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), mean connective density (Conn.D) when compared with the HFD group. In addition, system administration of SIM showed positive effects on collagen type 1 cross-linked C-telopeptide (CTX-1), procollagen I N-terminal propeptide (PINP), total cholesterol (TC), triglycerides (TGL), low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol. Compared with the HFD group, lower values of CTX-1, P1NP, TC, TGL and LDL were observed in the SIM+HFD group (P < 0.05). Conclusion: Our findings revealed that HFD may have an adverse effect on osseointegration in osteoporotic conditions, and the harmful effect of HFD on osseointegration could be reversed by SIM. [ABSTRACT FROM AUTHOR]

Objective: Using RNA-sequencing technology to screen the effect of moderate-intensity treadmill exercise on the sensitive genes that affect bone mass in the peripheral blood mononuclear cells (PBMCs) of ovariectomized (OVX) rats. Methods: Three-month-old female Sprague-Dawley rats of Specific Pathogen Free (SPF) grade were randomly divided into the sham operation (SHAM) group, OVX group, and OVX combined exercise (OVX + EX) group. The OVX + EX group performed moderate-intensity treadmill exercise for 17 weeks. Then, the body composition and bone mineral density (BMD) were measured, and the bone microstructure of the femur was observed. PBMCs were collected from the abdominal aorta, and the differential genes were analyzed by transcriptome sequencing to further screen sensitive genes. Results: (1) In the OVX group, the body weight and body fat content were significantly higher than in the SHAM group while the muscle content and BMD were significantly lower than the SHAM group. (2) The trabecular bone parameters in the OVX group were significantly lower than in the SHAM group, and they were significantly higher in the OVX + EX group than in the OVX group. When compared with the SHAM group, the microstructure of the distal femur trabecular in the OVX group was severely damaged, suggest that the morphological structure of trabecular bone is severely damaged, the number of trabecular bones is reduced, and the thickness becomes thinner, which lead to the widening of the trabecular bone space and the appearance of osteoporosis. The number and continuity of the trabecular bones were higher in the OVX + EX group than in the OVX group. (3) A Venn diagram showed that there were 58 common differential genes, and the differential genes were mainly enriched in the PI3K-Akt signaling pathway. Five sensitive genes were screened including CCL2, Nos3, Tgfb3, ITGb4, and LpL. The expression of CCL2, Nos3, and Tgfb3 genes was closely related to multiple bone parameters. Conclusion: Moderate-intensity treadmill exercise may improve the body composition and bone mass of the OVX group by upregulating CCL2 and other genes of the PBMC. The PBMCs in the peripheral blood can be a useful tool for monitoring the effect of exercise on bone health in postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

Genistein seems to have a protective and therapeutic effect on conditions associated with neovascular growth in the retina. This study investigated the angiogenesis, antioxidant, and anti-inflammatory effect of genistein on the retinas in ovariectomized diabetic rats. In this study, 40 female albino Wistar rats were divided into four groups (n = 8 per group): sham, ovariectomized group (OVX), OVX + diabetes (OVX.D), and OVX.D + genistein (OVX.D.G). OVX induced by removal of bilateral ovaries and then high-fat diet (HFD) and a low dose of streptozotocin (STZ) (1 mg/kg; intraperitoneal (IP) injection) was used for diabetes induction (OVX.D) with 8 weeks of genistein treatment (OVX.D.G). At the end of 8 weeks, the retina was removed under anesthesia. The samples were used to measure extracellular signal-regulated kinase (ERK), matrix metalloproteinase 2 (MMP-2), vascular endothelial growth factor (VEGF), and nuclear factor NF-kappa-B (NF-κB) by western blotting and inflammatory factors ELISA and oxidative stress. Measurements of glutathione (GSH) and malondialdehyde (MDA) showed that OVX and especially OVX.D significantly decreased GSH and increased MDA level in the retina, but genistein reversed these effects in OVX.D.G groups. Also, OVX and OVX.D significantly increased VEGF, MMP-2, p-ERK, NF-κB, interleukin-1beta (IL-1β), and tumor necrosis factor alpha (TNFα) expression in the retina of OVX and OVX.D groups in comparison to the sham group (p < 0.05). However, a significant reduction of these proteins was observed in the genistein-treated group (p < 0.05). In conclusion, bilateral ovariectomy and subsequently estrogen deficiency caused the development of inflammation, neovascularization, and then retinopathy in STZ-induced diabetic ovariectomized rats. On the basis of the results, genistein administration may be a practical approach for improving symptoms and complications of ovariectomized diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Purpose: Cardioprotective effect of carbon monoxide, a gasotransmitter against myocardial ischemia–reperfusion injury (I/R), is well established in preclinical studies with male rats. However, its ischemic tolerance in post-menopausal animals has not been examined due to functional perturbations at the cellular level. Methods: The protective role of carbon monoxide releasing molecule-2 (CORM-2) on myocardial I/R was studied in female Wistar rats using the Langendorff apparatus. The animals were randomly divided into normal and ovariectomized (Ovx) female rats and were maintained 2 months post-surgery. Each group was further divided into 4 subgroups (n = 6/subgroup): normal, I/R, CORM-2-control (20 μmol/L), and CORM-2-I/R. The cardiac injury was estimated via myocardial infarct size, lactate dehydrogenase, and creatine kinase levels in coronary effluent and cardiac hemodynamic indices. Mitochondrial functional activity was assessed by measuring mitochondrial electron transport chain enzyme activities, swelling behavior, mitochondrial membrane potential, and oxidative stress. Results: Hemodynamic indices were significantly lower in ovariectomized rat hearts than in normal rat hearts. Sixty minutes of reperfusion of ischemic heart exhibited deteriorated cardiac physiological recovery in both ovariectomized and normal groups, where prominent decline was observed in ovariectomized rat. However, preconditioning the isolated heart with CORM-2 improved hemodynamics parameters significantly in both ovariectomized and normal rat hearts challenged with I/R, but with a limited degree of protection in ovariectomized rat hearts. The protective effect of CORM-2 was further confirmed via a reduction in cardiac injury, preservation of mitochondrial enzymes, and reduction in oxidative stress in all groups. Conclusion: CORM-2 administration significantly attenuated myocardial I/R injury in ovariectomized rat hearts by attenuating I/R-associated mitochondrial perturbations and reducing oxidative stress. [ABSTRACT FROM AUTHOR]

Objective: To assess the estrogenic activity of hydroalcoholic extract of Clitoria ternatea leaves in female Wistar rats. Methods: Hydroalcoholic extract of C. ternatea leaves prepared by using cold maceration method was tested for estrogenic activity. An acute toxicity study was conducted to estimate the safe dose using OECD 423 guidelines. For estrogenic activity, ovariectomized female rats were divided into four groups, with 6 rats in each group. The control and standard groups were administered with 1% carboxymethyl cellulose orally and estradiol valerate at 1 μg/rat/day subcutaneously, respectively. The third group was administered with hydroalcoholic extract of C. ternatea at the dose 500 mg/kg body weight orally and the fourth group was administered with hydroalcoholic extract of C. ternatea at the dose 500 mg/kg body weight orally along with estradiol valerate at dose 1 μg/rat/day subcutaneously. All treatments lasted for 7 consecutive days and estrogenic activity was assessed by observing vaginal cornfication. On day 8, all animals were sacrificed and uterine horns were dissected out. Utrine weight was measured and blood serum was further processed for the estimation of biochemical parameters like cholesterol, total proteins, alkaline phosphatase and estrogen by autoanylser. Histological studies of uterus were also carried out. Results: Acute toxicity studies indicated the hydroalcoholic extract of C. ternatea leave was found to be safe up to the dose level of 2 000 mg/kg. Oral administration of C. ternatea extract at the dose 500 mg/kg body weight and and estradiol valerate (1 μg/rat/day) caused morphological changes i.e. increase in uterine weight, vaginal opening and cornification of cells; biochemical changes i.e. increase in cholesterol, total protein, alkaline phosphatase and estrogen contents; histological changes i.e. increase in uterine diameter, thickness and height of endometrium. Simultaneous administration of C. ternatea extract with estradiol valerate showed a synergistic effect. Histological investigations further confirmed the strong estrogenic nature of C. ternatea extract. Conclusions: C. ternatea extract (500 mg/kg) showed a significant estrogenic activity which is also supported by biochemical and histological studies. So, on the basis of these findings, it can be concluded that C. ternatea can be used as an alternative to synthetic oral contraceptives.