The present study aimed at investigating the effects of Puerarin(PR), a major isoflavonoid isolated from the Chinese medicinal herb Puerariae radix, on bone metabolism and the underlying mechanism of action. The in vi...The present study aimed at investigating the effects of Puerarin(PR), a major isoflavonoid isolated from the Chinese medicinal herb Puerariae radix, on bone metabolism and the underlying mechanism of action. The in vivo assay, female mice were ovariectomized(OVX), and the OVX mice were fed with a diet containing low, middle, and high doses of PR(2, 4, and 8 mg·d^(-1), respectively) or 17β-estradiol(E_2, 0.03 μg·d^(-1)) for 4 weeks. In OVX mice, the uterine weight declined, and intake of PR at any dose did not affect uterine weight, compared with the control. The total femoral bone mineral density(BMD) was significantly reduced by OVX, which was reversed by intake of the diet with PR at any dose, especially at the low dose. In the in vitro assay, RAW264.7 cells were used for studying the direct effect of PR on the formation of osteoclasts. PR reduced the formation of tartrate resistant acid phosphatase(TRAP)-positive multi-nucleated cells in the RAW 264.7 cells induced by receptor activator for nuclear factor-κB Ligand(RANKL). MC3T3-E1 cells were used for studying the effects of PR on the expression of osteoprotegerin(OPG) and RANKL m RNA expression in osteoblasts. The expression of OPG m RNA and RANKL m RNA was detected by RT-PCR on Days of 5, 7, 10, and 12 after PR exposure. PR time-dependently enhanced the expression of OPG m RNA and reduced the expression of RANKL m RNA in MC3T3-E1 cells. In conclusion, our results suggest that PR can effectively prevent bone loss in OVX mice without any hyperplastic effect on the uterus, and the antiosteoporosis activity of PR may be related to its effects on the formation of osteoclasts and the expression of RANKL OPG in osteoblasts.展开更多
Recent studies have shown that a 9-hour fast in mice reduces the amount of time spent immobile in the forced swimming test.Howeve r,whether 9-hour fasting has therapeutic effects in female mice with depressive symptom...Recent studies have shown that a 9-hour fast in mice reduces the amount of time spent immobile in the forced swimming test.Howeve r,whether 9-hour fasting has therapeutic effects in female mice with depressive symptoms has not been established.Therefore,in this study,we simulated perimenopausal depression via an ovariectomy in mice,and subjected them to a single 9-hour fasting 7 days later.We found that the ovariectomy increased the time spent immobile in the forced swimming test,inhibited expression of the mammalian target of rapamycin complex 1 signaling pathway in the hippocampus and prefro ntal cortex,and decreased the density of dendritic spines in the hippocampus.The 9-hour acute fasting alleviated the above-mentioned phenomena.Furthermore,all of the antidepressant-like effects of 9-hour fasting were reve rsed by an inhibitor of the mammalian to rget of rapamycin complex 1.Electrophysiology data showed a remarkable increase in long-term potentiation in the hippocampal CA1 of the ovariectomized mice subjected to fasting compared with the findings in the ovariectomized mice not subjected to fasting.These findings show that the antidepressant-like effects of 9-hour fasting may be related to the activation of the mammalian target of the rapamycin complex 1 signaling pathway and synaptic plasticity in the mammalian hippocampus.Thus,fasting may be a potential treatment for depression.展开更多
Objective:The roles of gonadal hormones and nitric oxide(NO) on the analgesic effects of morphine,tolerance to morphine,and their interactions have been widely investigated.In the present study,the effect of L-arginin...Objective:The roles of gonadal hormones and nitric oxide(NO) on the analgesic effects of morphine,tolerance to morphine,and their interactions have been widely investigated.In the present study,the effect of L-arginine(an NO precursor) on morphine tolerance in sham and ovariectomized(OVX) female mice was investigated.Methods:Forty mice were divided into sham and OVX groups.On the first day,a hot plate test((55±0.2) °C;cut-off 30 s) was carried out as a base record 15 min before injection of morphine(10 mg/kg,subcutaneously(s.c.)) and was repeated every 15 min after injection.The sham group was then divided into two subgroups:sham-tolerance-L-arginine(Sham-Tol-LA) and sham-tolerance-saline(Sham-Tol-Sal) which received either L-arginine 50 mg/kg(intraperitoneally(i.p.)) or saline 10 ml/kg(i.p.),respectively,three times in a day for three consecutive days.Morphine tolerance was induced in animals by injecting 30 mg/kg morphine(s.c.) three times/day for three days.This treatment was also used for OVX subgroups.On the fifth day,the hot plate test was repeated.The analgesic effect of morphine was calculated as the maximal percent effect(MPE).The results were compared using repeated measure analysis of variance(ANOVA).Results:There was no significant difference in MPE between the OVX and sham groups.The MPEs in both the Sham-Tol-Sal and OVX-Tol-Sal groups were lower than those in both the sham and OVX groups(P<0.01).The MPE in the OVX-Tol-Sal group was greater than that in the Sham-Tol-Sal group(P<0.01).The MPE in the Sham-Tol-LA group was higher than that in the Sham-Tol-Sal group(P<0.01).However,there was no significant difference between the Sham-Tol-LA and sham groups or between the OVX-Tol-LA and OVX-Tol-Sal groups.Conclusions:The results of the present study showed that repeated administration of morphine causes tolerance to the analgesic effect of morphine.L-Arginine could prevent tolerance to morphine but its effect was different in the presence of ovarian hormones.展开更多
基金supported by a grant from the National Natural Science Foundation of China(No.30873290)
文摘The present study aimed at investigating the effects of Puerarin(PR), a major isoflavonoid isolated from the Chinese medicinal herb Puerariae radix, on bone metabolism and the underlying mechanism of action. The in vivo assay, female mice were ovariectomized(OVX), and the OVX mice were fed with a diet containing low, middle, and high doses of PR(2, 4, and 8 mg·d^(-1), respectively) or 17β-estradiol(E_2, 0.03 μg·d^(-1)) for 4 weeks. In OVX mice, the uterine weight declined, and intake of PR at any dose did not affect uterine weight, compared with the control. The total femoral bone mineral density(BMD) was significantly reduced by OVX, which was reversed by intake of the diet with PR at any dose, especially at the low dose. In the in vitro assay, RAW264.7 cells were used for studying the direct effect of PR on the formation of osteoclasts. PR reduced the formation of tartrate resistant acid phosphatase(TRAP)-positive multi-nucleated cells in the RAW 264.7 cells induced by receptor activator for nuclear factor-κB Ligand(RANKL). MC3T3-E1 cells were used for studying the effects of PR on the expression of osteoprotegerin(OPG) and RANKL m RNA expression in osteoblasts. The expression of OPG m RNA and RANKL m RNA was detected by RT-PCR on Days of 5, 7, 10, and 12 after PR exposure. PR time-dependently enhanced the expression of OPG m RNA and reduced the expression of RANKL m RNA in MC3T3-E1 cells. In conclusion, our results suggest that PR can effectively prevent bone loss in OVX mice without any hyperplastic effect on the uterus, and the antiosteoporosis activity of PR may be related to its effects on the formation of osteoclasts and the expression of RANKL OPG in osteoblasts.
基金supported by the National Natural Science Foundation of China,No.81871070Jilin Province Medical and Health Talents,No.2020SCZT021Changchun City Science and Technology Development Plan Key Project,No.21ZGY16 (all to BJL)。
文摘Recent studies have shown that a 9-hour fast in mice reduces the amount of time spent immobile in the forced swimming test.Howeve r,whether 9-hour fasting has therapeutic effects in female mice with depressive symptoms has not been established.Therefore,in this study,we simulated perimenopausal depression via an ovariectomy in mice,and subjected them to a single 9-hour fasting 7 days later.We found that the ovariectomy increased the time spent immobile in the forced swimming test,inhibited expression of the mammalian target of rapamycin complex 1 signaling pathway in the hippocampus and prefro ntal cortex,and decreased the density of dendritic spines in the hippocampus.The 9-hour acute fasting alleviated the above-mentioned phenomena.Furthermore,all of the antidepressant-like effects of 9-hour fasting were reve rsed by an inhibitor of the mammalian to rget of rapamycin complex 1.Electrophysiology data showed a remarkable increase in long-term potentiation in the hippocampal CA1 of the ovariectomized mice subjected to fasting compared with the findings in the ovariectomized mice not subjected to fasting.These findings show that the antidepressant-like effects of 9-hour fasting may be related to the activation of the mammalian target of the rapamycin complex 1 signaling pathway and synaptic plasticity in the mammalian hippocampus.Thus,fasting may be a potential treatment for depression.
基金Project supported by the Vice Presidency of Research of Mashhad University of Medical Sciences,Iran
文摘Objective:The roles of gonadal hormones and nitric oxide(NO) on the analgesic effects of morphine,tolerance to morphine,and their interactions have been widely investigated.In the present study,the effect of L-arginine(an NO precursor) on morphine tolerance in sham and ovariectomized(OVX) female mice was investigated.Methods:Forty mice were divided into sham and OVX groups.On the first day,a hot plate test((55±0.2) °C;cut-off 30 s) was carried out as a base record 15 min before injection of morphine(10 mg/kg,subcutaneously(s.c.)) and was repeated every 15 min after injection.The sham group was then divided into two subgroups:sham-tolerance-L-arginine(Sham-Tol-LA) and sham-tolerance-saline(Sham-Tol-Sal) which received either L-arginine 50 mg/kg(intraperitoneally(i.p.)) or saline 10 ml/kg(i.p.),respectively,three times in a day for three consecutive days.Morphine tolerance was induced in animals by injecting 30 mg/kg morphine(s.c.) three times/day for three days.This treatment was also used for OVX subgroups.On the fifth day,the hot plate test was repeated.The analgesic effect of morphine was calculated as the maximal percent effect(MPE).The results were compared using repeated measure analysis of variance(ANOVA).Results:There was no significant difference in MPE between the OVX and sham groups.The MPEs in both the Sham-Tol-Sal and OVX-Tol-Sal groups were lower than those in both the sham and OVX groups(P<0.01).The MPE in the OVX-Tol-Sal group was greater than that in the Sham-Tol-Sal group(P<0.01).The MPE in the Sham-Tol-LA group was higher than that in the Sham-Tol-Sal group(P<0.01).However,there was no significant difference between the Sham-Tol-LA and sham groups or between the OVX-Tol-LA and OVX-Tol-Sal groups.Conclusions:The results of the present study showed that repeated administration of morphine causes tolerance to the analgesic effect of morphine.L-Arginine could prevent tolerance to morphine but its effect was different in the presence of ovarian hormones.
