| Marine shellfish resources are abundant in China,and the amount of processed waste(especially shells)is huge.At present,the value of traditional utilization method of shellfish processing waste is relatively low,which is easy to cause resource waste.Based on our former work in studying the preparation of calcium L-pyroglutamate(CAP),we have studied the anti-osteoporosis effect,neuroprotective effect and anti-fatigue effect of CAP,so as to provide theoretical support for the application of CAP in the present study.Firstly,by constructing the osteoporosis model of ovariectomized female SD rats,postmenopausal osteoporosis was simulated for exploring the anti-osteoporosis effect and mechanism of CAP.The effect of CAP on promoting calcium absorption was evaluated based on the contents of serum 25-OH-VD and bone calcium content of rats.The mechanism of anti-osteoporosis action of CAP was investigated by using bone conversion index alkaline phosphatase(ALP)content,osteogenesis related pathways and bone resorption pathways.The treatment of CAP significantly improved the decreased serum25-OH-VD content and bone calcium content of ovariectomized(OVX)rats,which indicated that CAP promoted the calcium utilization in bone.The femur bone mineral density(BMD),bone wall thickness and femur trabecular micro-architecture of the OVX rats were both significantly improved,which suggested that the bone was improved by the CAP treatment.Meanwhile,the serum ALP activity of OVX rats was reduced by CAP,which means that CAP can suppress the high bone turnover induced by the ovariectomy.The OPG expression was increased and the RANKL expression was correlated reduced by the CAP,which indicated that CAP could suppress the proliferation and differentiation of osteoclasts by influencing the OPG/RANKL/RANK signaling pathway.Moreover,CAP reduced the content of DKK1 and increased the content of ?-catenin in femur,which suggested that CAP promotes the proliferation and activation of osteoblasts by influencing Wnt/?-catenin signaling pathway.We found that CAP was an ideal calcium supplement for the treatment of osteoporosis.Secondly,the effects of CAP on neuroprotection,ameliorating memory and cognitive impairment were investigated in a scopolamine induced memory impairment mice model.The cognitive function and spatial memory of mice were tested by the Morris water maze test and Y-maze test;the inflammatory indexes,oxidative stress indexes and the cholinergic indexes in hippocampus of mice were detected to investigate the mechanism of neuroprotective effect of CAP.In the behavioral test,CAP decreasedthe escape latency of mice in the place navigation test,increased the number of crossing the region placed platform in the spatial probe test,and increased the exploring period in the novel arm of Y-maze in the spatial identification test,all the changes were statistically significant.In addition,the hippocampus acetyl cholinesterase(AChE)activity and malondiadehyde(MDA)content were significantly decreased while the activity of superoxide dismutase(SOD)were significantly improved by CAP,which indicated CAP can fix the cholinergic system and enhance the anti-oxidant activity of mice.In the determination of inflammatory factors,it was found that the IL-1? and TNF-? levels were significantly reduced by CAP,while the level of IL-10 was significantly increased.The results supports the finding that CAP improved the cognitive impairment of mice by fixing the cholinergic system and enhancing the anti-oxidant ability as well as anti-inflammatory ability of mice.Finally,the anti-fatigue effect of CAP were studied in a weigh-loaded forced swimming test(FST)combined with lopopolysaccharide intraperitoneal injection mice model.The swimming period was recorded for the evaluating the exercise tolerance of mice,and the oxidant stress indexes,inflammatory indexes as well as biochemical indexes of energy metabolism were detected to primarily investigate the mechanism of CAP on reducing fatigue.The FST results showed CAP significantly prolonged the swimming time of mice in the weigh-loaded FST.The hepatic glycogen and muscle glycogen content were significantly increased while the serum lactic acid content was significantly decreased by CAP.In addition,the content of MDA in muscle was decreased while the muscle SOD activity of mice was enhanced.The levels of proinflammatory factor,such as IL-1? and TNF-? in serum of mice,were significantly down-regulated while the anti-inflammatory factors such as IL-10 were up-regulated.In total,the results demonstrated that CAP can increase the energy reserve,accelerate the blood lactic acid clearance,enhance the anti-oxidant ability and anti-inflammatory ability,so as to improve the fatigue tolerance of mice.In this paper,we have preliminary studied the effects and related mechanisms of CAP on anti-postmenopausal osteoporosis,anti-AD and anti-fatigue effects in vivo.The experimental results showed that the absorption of CAP in vivo was good,which could effectively treat the postmenopausal osteoporosis,improve the cognitive impairment induced by scopolamine,and present a good anti-fatigue effect.This research provides the basic data for the high-value utilization of Marine shellfish,and also provide feasible drugs for the treatment of postmenopausal osteoporosis and Alzheimer's disease,as well as ideal health care drugs for the elimination or delay of fatigue state. |
PDF Full Text Request