scholarly journals Low-dose brain estrogen prevents menopausal syndrome while maintaining the diversity of the gut microbiomes in estrogen-deficient rats

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

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

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

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


2001 ◽  
Vol 46 (No. 1) ◽  
pp. 17-23 ◽  
Author(s):  
V. Kummer ◽  
J. Mašková ◽  
J. Čanderle ◽  
Z. Zralý ◽  
J. Neča ◽  
...  

The objective of this study was to test whether silymarin induces changes indicative of estrogenic effects in gonadal organs of ovariectomized (OVX) rats. Silymarin was administered in two experimental groups of OVX rats (n&nbsp;= 7 + 7) for 30 days at the doses of 25 or 50 mg per animal per day. OVX rats (n&nbsp;= 7) receiving 5&nbsp;&micro;g of 17b-estradiol (E2) for the last three days before killing and untreated OVX rats (n&nbsp;= 7) were used as the positive and the negative controls, respectively. Uterine and blood samples were collected immediately after killing. Compared with the negative controls, total and normalized uterine weights were significantly higher in the two experimental groups (P&nbsp;&lt; 0.01 and&nbsp;P&nbsp;&lt;&nbsp;0.05, respectively). Uterotrophic effects of silymarin were also evident from increased heights of the luminal epithelium (P&nbsp;&lt; 0.01) and the endometrium (P&nbsp;&lt; 0.05). The response was dose-independent within the tested range. The strongest uterine response was observed in the OVX rats treated with E2. A highly significant decrease in mean density of estrogen receptor (ERa) immunostaining in the luminal and the glandular endometrial epithelia (P&nbsp;&lt; 0.01) and a stronger ERa immunostaining in stromal cells were observed in the two experimental and the positive control groups. The activities of alkaline and acid phosphatases were significantly increased in the luminal (P&nbsp;&lt; 0.05) and the glandular (P&nbsp;&lt; 0.01) epithelia only in the rats treated with E2. Both silymarin and E2&nbsp;induced an increase in thyroid hormone concentrations in blood serum. The rises of free T3&nbsp;and T4&nbsp;were significant (P&nbsp;&lt; 0.05) in the group receiving 50 mg of silymarin per day. Hepatic oxidative metabolism of steroids was assumed to be another target of the action of silymarin. The mitochondrial cytochrome&nbsp;P450-dependent testosterone hydroxylase activity and the cytochrome&nbsp;P4501A-dependent 7-ethoxyresorufin O-deethylase activity were significantly increased (P&nbsp;&lt; 0.05) in the group receiving 50&nbsp;mg of silymarin per day and in the E2-treated control group, respectively. However, the modulations of the CYP enzymes played only a minor role in the overall estrogenic effect of silymarin. Histological and functional alterations in the OVX rats treated orally with silymarin for 30 days were consistent with those seen in E2-treated rats and were indicative of estrogenic effects of silymarin.


2016 ◽  
Vol 242 (6) ◽  
pp. 593-605 ◽  
Author(s):  
Jin Ah Ryuk ◽  
Byoung-Seob Ko ◽  
Hye Won Lee ◽  
Da Sol Kim ◽  
Suna Kang ◽  
...  

Tetragonia tetragonioides (Pall.) Kuntze (TTK) and JakYakGamCho-Tang (JGT) have been used for improving women’s health and treating inflammatory diseases. We determined that the long-term consumption of these herbal extracts alleviates the progression of postmenopausal symptoms in high-fat-diet fed ovariectomized (OVX) rats, and further explored the mechanisms involved. Five groups of OVX rats were fed high fat diets that were supplemented with either 2% dextrin (control), 2% TTK (70% ethanol extract), 2% JGT (water extract), 1% JGT + 1% TTK (JGTT), or 30 µg/kg body weight/day of 17β-estradiol (positive control). After eight weeks of dietary intervention, the herbal treatments did not change the serum concentrations of 17β-estradiol or uterine weight in control rats, but they were higher in the positive-control group. TTK rats exhibited higher daily energy expenditure, particularly fat oxidation, without modifying the energy intake than the controls. TTK lowered the fat mass but lean body mass of the abdomen and leg were increased. JGT decreased periuterine fat mass and lean body mass more than the control but the decrease was not as much as TTK. TTK resulted in substantially lower serum concentrations of the proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1, than the control and JGT had lesser effect than TTK. Insulin resistance, determined by homeostasis model assessment estimate for assessing insulin resistance (HOMA-IR) and insulin tolerance test, was reduced in the decreasing order of control, JGT, JGTT, and TTK and the HOMA-IR of TTK was similar to the positive control. TTK, but not JGT, enhanced glucose tolerance compared with the control, although the serum insulin levels in TTK were lower compared to the control. Interestingly, the β-cell masses were much greater in the TTK and JGTT groups than in the control, and they were comparable to the positive control. The increases in β-cell masses in TTK and JGTT groups were associated with enhanced β-cell proliferation and suppressed apoptosis, which was related to the decreased TNF-α and interleukin-1β expressions. In conclusion, JGTT did not improve menopausal symptoms better than TTK itself. TTK itself prevented the OVX-induced impairments in energy, lipid, and glucose metabolism, similar to the positive control, without changing serum 17β-estradiol levels and potentiating insulin signaling and decreasing proinflammatory cytokines. TTK may be a useful intervention to alleviate some menopausal symptoms similar to selective estrogen receptor modulators and should be investigated with further human study. Impact statement Menopause decreases the quality of life in middle-aged women and herbal remedies are sometimes used as alternatives for hormone replacement therapy, which may have detrimental side effects. Although several herbal extracts have been studied, no remedies improve all the menopausal symptoms. In this study, the 70% ethanol extract of Tetragonia tetragonioides (Pall.) Kuntze (TTK) reduced the symptoms of hot flushes and improved energy, glucose, and lipid metabolism in estrogen-deficient animals without increasing serum 17β-estradiol levels. This extract acts like a selective estrogen receptor modulator and it may be a useful intervention for alleviating menopausal symptoms. This is the first study to show that the 70% ethanol extract of TTK has the potential to treat menopause-associated symptoms and metabolic disturbances. It may be a useful intervention for alleviating the symptoms of menopause in women if its efficacy can be confirmed in human studies.


Nutrients ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 948 ◽  
Author(s):  
Hye Yang ◽  
Min Kim ◽  
Dae Kwon ◽  
Da Kim ◽  
Ting Zhang ◽  
...  

The combination of freeze-dried aronia, red ginseng, ultraviolet-irradiated shiitake mushroom and nattokinase (AGM; 3.4:4.1:2.4:0.1) was examined to evaluate its effects on insulin resistance, insulin secretion and the gut microbiome in a non-obese type 2 diabetic animal model. Pancreatectomized (Px) rats were provided high fat diets supplemented with either (1) 0.5 g AGM (AGM-L), (2) 1 g AGM (AGM-H), (3) 1 g dextrin (control), or (4) 1 g dextrin with 120 mg metformin (positive-control) per kg body weight for 12 weeks. AGM (1 g) contained 6.22 mg cyanidin-3-galactose, 2.5 mg ginsenoside Rg3 and 244 mg β-glucan. Px rats had decreased bone mineral density in the lumbar spine and femur and lean body mass in the hip and leg compared to the normal-control and AGM-L and AGM-H prevented the decrease. Visceral fat mass was lower in the control group than the normal-control group and its decrease was smaller with AGM-L and AGM-H. HOMA-IR was lower in descending order of the control, positive-control, AGM-L, AGM-H and normal-control groups. Glucose tolerance deteriorated in the control group and was improved by AGM-L and AGM-H more than in the positive-control group. Glucose tolerance is associated with insulin resistance and insulin secretion. Insulin tolerance indicated insulin resistance was highly impaired in diabetic rats, but it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Insulin secretion capacity, measured by hyperglycemic clamp, was much lower in the control group than the normal-control group and it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Diabetes modulated the composition of the gut microbiome and AGM prevented the modulation of gut microbiome. In conclusion, AGM improved glucose metabolism by potentiating insulin secretion and reducing insulin resistance in insulin deficient type 2 diabetic rats. The improvement of diabetic status alleviated body composition changes and prevented changes of gut microbiome composition.


Author(s):  
Hye Jeong Yang ◽  
Min Jung Kim ◽  
Dae Young Kwon ◽  
Da Sol Kim ◽  
Ting Zhang ◽  
...  

The combination of freeze-dried aronia, red ginseng, ultraviolet-irradiated shiitake mushroom and natokinase (AGM; 3.4: 4.1: 2.4: 0.1) was examined to evaluate its effects on insulin resistance, insulin secretion and gut microbiome in a non-obese type 2 diabetic animal model. Pancreatectomized (Px) rats were provided high fat diets supplemented with either of 1) 0.5 g AGM (AGM-L), 2) 1 g AGM (AGM-H), 3) 1 g dextrin (control), or 4) 1g dextrin with 120 mg metformin (positive-control) per kg body weight for 12 weeks. AGM (1 g) contained 6.22 mg cyanidin-3-galactose, 2.5 mg ginsenoside Rg3 and 0.6 mg &beta;-glucan. Px rats had decreased bone mineral density in the lumbar spine and femur and lean body mass in the hip and leg compared to the normal-control and AGM-L and AGM-H prevented the decrease. Visceral fat mass was lower in the control group than the normal-control group and its decrease was smaller by AGM-L and AGM-H. HOMA-IR was lower in descending order of the control, positive-control, AGM-L, AGM-H and normal-control groups. Glucose tolerance was deteriorated in the control group and it was improved by AGM-L and AGM-H more than in the positive-control group. Glucose tolerance is associated with insulin resistance and insulin secretion. Insulin tolerance indicated insulin resistance was highly impaired in diabetic rats, but it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Insulin secretion capacity, measured by hyperglycemic clamp, was much lower in the control group than the normal-control group and it was improved in the ascending order of the positive-control, AGM-L and AGM-H. Diabetes modulated the composition of gut microbiome and AMG prevented the modulation of gut microbiome. In conclusion, AGM improved glucose metabolism by potentiating insulin secretion and reducing insulin resistance in insulin deficient type 2 diabetic rats. The improvement of diabetic status alleviated body composition changes and prevented changes of gut microbiome composition.&nbsp;&nbsp;


2017 ◽  
Vol 2017 ◽  
pp. 1-15
Author(s):  
Hye Won Lee ◽  
Byung-Seob Ko ◽  
Suna Kang ◽  
Jin Ah Ryuk ◽  
Min Joo Kim ◽  
...  

We investigated whether dangguijakyak-san (DJY) and dangguijihwang-tang (DJH), oriental medicines traditionally used for inflammatory diseases, could prevent and/or delay the progression of postmenopausal symptoms and osteoarthritis in osteoarthritis-induced estrogen-deficient rats. Treated ovariectomized (OVX) rats consumed either 1% DJY or 1% DJH in the diets. Positive-control rats were given 30 μg/kg bw 17β-estradiol and control rats were given 1% fat as were the normal-control rats. All rats received high-fat diets for 8 weeks. At the 9th week, OVX rats received articular injections of monoiodoacetate (MIA) or saline (normal control) into the right knee. At 3 weeks after MIA injection, DJY reduced visceral-fat mass and improved glucose metabolism by reducing insulin resistance, whereas DJH increased BMD and decreased insulin resistance. DJH improved weight distribution in the right knee and maximum running velocity on a treadmill at days 14 and 21 as much as those of the positive control. TNF-α, IL-1β, and IL-6 levels in articular cartilage were much higher in the control than the positive control, whereas both DJY and DJH reduced the levels to those of the positive control. The histological analysis assessed articular cartilage damage near the tidemark and proteoglycan loss in the control versus the positive control; DJY and DJH prevented this damage and proteoglycan loss. In conclusion, DJY may provide an effective treatment for improving glucose tolerance, and DJH may be appropriate for preventing osteoarthritis.


2020 ◽  
Vol 18 (1) ◽  
pp. 47
Author(s):  
FERIZAL NEGERI SAMUDRA ◽  
RETNO BUDIARTI ◽  
IRMAWATI IRMAWATI

<p><strong>ABSTRACT</strong></p><p><strong>Background</strong>; In Indonesia, most diarrhea disease in 1995 to 2001 are caused by Shigella spp. Shigella spp infection can cause various symptom dan complication. Generally, the treatment by using antibiotic can cause antibiotic resistance. Sea cucumber (Holoturia scabra) is an herb that known, available, and easy to consume by society and has an antibacterial effect. Therefore, further research to study the effect of Holoturia Scabra on <em>Shigella Dysentriae</em> growth in vitro is needed.</p><p><strong>Objectives</strong>: The goal of this research is demonstrate the effect of sea cucumber (Holoturia scabra) to the growth of the <em>Shigella dysentriae</em> bacteria in vitro.</p><p><strong>Method</strong>: The method in this research is Posttest Only Control Group. There are 6 groups, 4 types of and 2 control groups. The concentration of the treatment group is 100%,50%, 25%, and, 12.5% while for positive control tests using chloramphenicol and aquadest as a negative control.</p><p><strong>Result</strong>: The result showed there is an influence on the intake of sand cucumber to the growth of the Shigella dysenteriae.</p><p><strong>Conclusion</strong>: Sea cucumber (<em>Holoturia scabra</em>) inhibit the growth of <em>Shigella dysenteriae</em>.</p><p><strong>Key words</strong>: <em>Shigella dysenteriae</em>, sea cucumber (<em>Holoturia scabra</em>), antibacterial</p>


2017 ◽  
Vol 14 (4) ◽  
pp. 4561 ◽  
Author(s):  
Hamza Albayrak ◽  
Paşa Yalçın ◽  
Sema Altun Yalçın

In this research, it was aimed to determine the effect of learning stations designed for astronomy subjects on the academic achievement of students and give an alternative method for teaching astronomy in the literature. The mixed approach in which mixed quantitative and qualitative methods were used together was preferred in the study. Among the quantitative methods, the pre-test and post-test model of the semi-experimental method was used; in addition, the protocols were applied about the method, which was used. The research was carried out with 98 seventh class students, who were under education in a secondary school located in the Eastern Anatolia Region of Turkey in the education year of 2015-2016. The quantitative data were analysed via the Astronomy Achievement Test (AAT) developed by the researchers and had 0,795 Cronbach Alpha reliability coefficient. The astronomy subjects in science lesson of the seventh class were studied with the experimental group through the learning stations; on the other hand, they were studied with the students in the control group through the activities stated in the textbook prepared by the Ministry of Education. The AAT was applied for the experimental, control groups using the pre- and post-tests, and data were analysed with the t-test. Meaningful difference was determined in AAT pre-test average scores of experimental and control groups; on the other hand, a meaningful difference was determined between the groups according to the independent samples t-test results applied with the average scores of the post-test(p<0.05). As a result of the analysis of the data gathered with the Station Observation Form (SOF), developed for the research, it was found out that the students recognise the learning stations as a technique of useful, entertaining, engaging, and easy-to-learn that enable them to learn astronomy topics effectively.Extended English abstract is in the end of Full Text PDF (TURKISH) file. ÖzetBu araştırmada, astronomi konuları için tasarlanan öğrenme istasyonlarının öğrencilerin akademik başarılarına etkisini belirlemek ve literatüre astronomi öğretimi için alternatif bir yöntem sunmak amaçlanmıştır.  Araştırmada karma nicel ve nitel yöntemlerin birlikte kullanıldığı karma yaklaşım tercih edilmiştir. Nicel yöntemlerden yarı deneysel yöntemin ön test- son test modeli kullanılmış olup ayrıca uygulanan yöntem hakkında öğrenci görüşmeleri yapılmıştır. Araştırma 2015- 2016 eğitim öğretim döneminde Doğu Anadolu Bölgesinde yer alan bir ortaokulda öğretim gören 98 yedinci sınıf öğrenci ile yürütülmüştür.  Nicel veriler için araştırmacılar tarafından geliştirilen ve cronbac’h alpha güvenlik katsayısı 0.795 olan Astronomi Başarı Testi (ABT) kullanılmıştır.  Yedinci sınıf fen bilimleri dersi içerisindeki astronomi konuları deney grubu ile öğrenme istasyonları yardımıyla, kontrol grubundaki öğrencilerle MEB’in ön gördüğü ders kitabında yer alan etkinlikler takip edilerek işlenmiştir. ABT deney ve kontrol gruplarına ön test- son test olarak uygulanarak t testi ile analiz edilmiştir. Araştırmada deney ve kontrol gruplarının ABT ön test ortalama puanları arasında anlamlı bir farklılık belirlenmişken, son test puan ortalamaları ile yapılan bağımsız örnekler t testi sonuçlarına göre gruplar arasında anlamlı bir farklılık belirlenmiştir (p<0.05). Araştırma için geliştirilen İstasyon Gözlem Formu (İGF) ile elde edilen verilerinin analizi sonucunda öğrenciler öğrenme istasyonlarını, astronomi konuları için etkili öğrenmeyi sağlayan, faydalı, eğlenceli, ilgi çekici ve kolay öğrenmeyi destekleyen bir teknik olarak gördükleri bulunmuştur.


Author(s):  
Tayo Micheal Anjuwon ◽  
Oluwafemi Abiodun Adepoju ◽  
Olufemi Adewale Adeniran

This study evaluated the antiplasmodial, hepatic and nephritic effects of fractions of Glyphaea brevis methanol leaf extract in P. berghei infected mice. Mice weighing between 15-30 g were infested intraperitoneally with 0.2ml plasmodium infected blood and left for 3 hours before treatment. Infected test groups were treated via oral route of administration with varying doses (200, 300 and 400 mg/kg body weight) of ethylacetate, N-butanol and residual aqueous portion fractions of the Glyphaea brevis methanol extract and Artemisinin (5 mg/kg b.wt) for four days. N-butanol fraction showed the highest antiplasmodial activity (76.64%), followed by residual aqueous portion (73.25%) and ethylacetate (72.99%); Artemisinin has 86.13%. Serum bilirubin (total and conjugated) concentrations of the untreated group (0.82 ± 0.20, 0.51 ± 0.12) were significantly lower (P<0.05) than those in the infected group treated with 300 mg/kg of the residual aqueous portion (1.36 ± 0.20, 0.76 ± 0.05) respectively. Serum albumin levels showed significant (P<0.05) increase in all the groups treated compared to the positive control. Serum total protein, urea and creatinine levels of test groups were not significantly (P>0.05) different from the positive control group. Conclusively, Glyphaea brevis has substantial antiplasmodial activity and could provide a lead for new antimalarial drug development.


Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 311 ◽  
Author(s):  
Sunmin Park ◽  
Ting Zhang ◽  
Jing Yi Qiu ◽  
Xuangao Wu ◽  
Jeong-Yong Lee ◽  
...  

Silk fibroin hydrolysates have been reported to reduce hyperglycemia, but the mechanism has not been determined in Asian type 2 diabetes (T2DM). We hypothesized that the consumption of acid hydrolyzed silk peptides (SPs) alleviates hyperglycemia by improving insulin sensitivity and subsequently normalizing glucose-stimulated insulin secretion in T2DM. We investigated this hypothesis in a partial pancreatectomized (Px) rat model. Px rats was assigned randomly to the following six groups and fed assigned diet for 8 weeks: the Px-control (0.5 g/kg/day dextrin), the SP-L (0.05 g/kg/day), the SP-M (0.1 g/kg/day), the SP-H (0.5 g/kg/day), the positive-control (40 mg/kg/day metformin), or the normal-control (sham-operated rats; 0.5 g/kg/day dextrin). SPs contained high levels of glycine, alanine, and serine. We found SPs dose-dependently increased food efficiency and body weight gain in Px rats. Animals in the Px-control group rats exhibited lower glucose metabolism, as evidenced by impaired glucose-stimulated insulin secretion coupled with impaired insulin sensitivity, and reduced bone mineral density (BMD) and lean body mass (LBM), compared to the normal-control. SPs and metformin similarly partially protected against Px-induced BMD loss in the lumbar spine and femur. Px-induced decreases in LBM were dose-dependently prevented by SPs, and muscle forces in the SP-M and SP-H groups were maintained at the normal-control level. Glucose tolerance was dose-dependently improved by SPs as determined by oral glucose tolerance and oral maltose tolerance tests, and glucose tolerances were similar in the SP-H and positive-control groups. Insulin tolerance, an index of insulin sensitivity, was dose-dependently enhanced by SPs, and the SP-H group exhibited better insulin tolerance than the positive-control group as determined by intraperitoneal insulin sensitivity testing. Insulin secretory capacity assessed using a hyperglycemic clamp improved in the following order: Px-control <SA-L <SA-M <positive-control <SA-H <normal-control. SP-M prevented gut microbiota dysbiosis. In conclusion, SPs administered at 0.1–0.5 g/kg/day improved glucose regulation by potentiating both insulin secretion and insulin sensitivity in non-obese T2DM rats.


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