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Effects And Mechanism Of Cordyceps Sinensis And Its Monomeric Components On Treatment Of Osteoporosis In Rats

Posted on:2015-06-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:W QiFull Text:PDF
GTID:1224330422473623Subject:Surgery
Abstract/Summary:PDF Full Text Request
Osteoporosis (OP) is a systemic bone disease characterized by reduction of bone tissuecontent in a unit volume and degeneration of bone microstructure caused by a variety offactors, resulting in increased bone fragility and reduced bone strength, thus tending topresent fracture. Osteoporosis has been more than just a disease, it is a serious socialproblem. The most important symptoms it brings include severe pain, multiple fracturesand breathing difficulties caused by narrowing in the thoracic cavity. Among manypatients suffering pain caused by osteoporosis, postmenopausal women are doublyaffected by aging and hormone level decline. They have become the largest group ofvictims of such disease, accounting for over70%of the overall patients. In addition, withthe increasing number of patients with type2diabetes, particularly the elderly, diabeteshas become one of the important reasons for the formation of osteoporosis clinically atpresent, and it is often neglected by patients because of its latency so that the treatment isusually delayed and the consequences could be disastrous. Currently, drugs for theprevention and treatment of osteoporosis are mainly bone resorption inhibitors, agents forpromoting bone formation and mineralization drugs. All these drugs belong to replacement therapy. In a long-term use of them, they have disadvantages such as largeside effects, low targeting and poor compliance. Therefore, it is necessary to find amedication which is suitable for a wide audience group for the treatment of osteoporosis.The application of traditional Chinese medicine in China has thousands years of historywith a high degree of recognition among people. Meanwhile, Chinese medicine hasadvantages such as systemic conditioning, small side effects and convenient materialdrawing in the treatment of osteoporosis, attracting more and more people’s attention. Inmany traditional Chinese medicines, unique medicinal value of Cordyceps sinensis haslong been favored by people. Therefore, the way to explore the potential of Cordycepssinensis to develop an anti-osteoporosis Chinese medicine with independent intellectualproperty rights becomes the purpose of the study. So, does Cordyceps sinensis have theability to prevent and treat osteoporosis? What is the mechanism it playing an antagonisticeffect on osteoporosis? Does the Cordymin which is the one of the monomer componentsof Cordyceps sinensis can play a important role in anti-osteoporosis? We will commencestudies around these questions.1.The effects and mechanism of strontium-rich Cordyceps sinensis in prevention ofovariectomized rats with osteoporosis(1) Objective: To study effects and related mechanisms of strontium-rich Cordycepssinensis on the prevention of osteoporosis in ovariectomized rats.(2) Methods: Female rats were randomly divided into five groups: sham operationgroup (Sham), ovariectomized group (OVX), Cordyceps sinensis group (CS), strontiumgroup (SR) and strontium-rich Cordyceps sinensis group (CSS). There were10rats ineach group. Ovaries were removed by surgery in four groups (OVX), the remaining groupunderwent sham operation (control). Group1(sham operation) and Group2(OVX) weretreated with10ml saline orally; Group3, Group4and Group5were treated with10mlCSS, CS and SR orally for up to8weeks. Urinary calcium, serum calcium, serumphosphorus, bone mineral density (BMD), bone mineral content (BMC) as well aschanges in the uterus, thymus and body weight of rats were observed; and serum alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), osteocalcin (OC),homocystine, type I collagen cross-linked C-terminal peptide (CTX), estradiol andinterferon-γ (IFN-γ) levels in rats were also examined.(3) Results: both CSS and SR had a positive impact on bone mechanical strength andmineral content in ovariectomized rats with osteoporosis. However, the femoral neck strengthin CSS treatment group was higher than that of SR treatment group. CSS and SR couldsignificantly reduce urinary calcium, serum calcium and phosphorus levels. On the contrary,CS and CSS could significantly increase the weight of the atrophied uterus and body weightand also reduce the quality of the thymus, whereas SR didn’t show any of such effects.Meanwhile, CSS could significantly reduce serum ALP and TRAP levels, promote thesecretion of osteocalcin and reduce CTX levels. In addition, it could significantly reduce thelevel of IFN-γ and significantly increase the level of estradiol in the body.(4) Conclusion: This study demonstrates the value of strontium-rich Cordycepssinensis in the treatment of postmenopausal osteoporosis in humans. CSS can effectivelytreat osteoporosis caused by decreased bone strength and bone mineral content, itsmechanism of action is mainly achieved by the reduction of bone loss in osteoporoticmodel, significantly reducing bone resorption and promoting bone formation and estradiolgeneration in vivo. It also shows that Cordyceps sinensis has the potential to antagonizethe osteoporosis.2. Preventive effect of Cordyceps sinensis extract on rats with disuse osteoporosis(1) Objective: To verify whether Cordyceps sinensis has a preventive effect on rat withdisuse osteoporosis.(2) Methods: Rats were randomly divided into six groups, of which, five groups weretreated with hindlimb suspension (HLS). One HLS group was administered withalendronate (2.0mg/kg/d) orally, another three HLS groups were orally administered withdifferent doses of Cordyceps sinensis (100,300,500mg/kg/d) respectively for continuous8weeks. The remaining HLS group is a control group not administered before and afterHLS. Each group is composed of10males and females. Body weight, serum and urine biochemical markers, bone mineral density (BMD), bone mineral content (BMC),mechanics and bone microstructure were measured.(3) Results: Compared with other HLS groups, higher doses (300and500mg/kg/d) ofCordyceps sinensis or alendronate had a positive effect on body weight, mechanicalstrength, BMD and BMC in treatment group. In HLS rats, Cordyceps sinensis decreasedbone turnover markers in a dose-dependent manner and increased osteocalcin levels.Micro-CT analysis of L-4vertebrae showed that trabecular bone rats in high-doseCordyceps sinensis group (500mg/kg) had been significantly improved in number,thickness and gap compared with HLS group.(4) Conclusion: This study shows that eight weeks of higher doses of Cordycepssinensis can prevent disuse osteoporosis in rats. It means Cordyceps sinensis can be usedas a replacement therapy preventing human disuse-induced osteoporosis.3. Effects of Cordymin on alloxan-induced osteoporosis in diabetic rats(1) Objective: To study the protective effect of Cordymin on alloxan-inducedosteoporosis in diabetic rats and possible mechanisms.(2) Methods: Rats were randomly divided into five groups. Those in four groups wereinjected with alloxan intraperitoneally for the construction of diabetic model. Diabetic ratsin three groups received daily intraperitoneal injection of Cordymin (20,50and100mg/Kg/d) for a total of five weeks. Each of the remaining diabetes control group wascomposed of10male rats. Measurement and evaluation were conducted on blood glucose,glycosylated hemoglobin (HbA1c), serum alkaline phosphatase (ALP), tartrate-resistantacid phosphatase (TRAP), insulin levels, total antioxidant status (TAOS), bone mineraldensity (BMD), bone mineral content (BMC) and pancreatic β cell injury.(3) Results: Cordymin could lower blood glucose, glycosylated hemoglobin (HbA1c), ALPand TRAP levels in blood and increase insulin levels in a dose-dependent manner. Furthermore,by the treatment of Cordymin, pancreatic β cell death and TAOS could be relatively reduced indiabetic rats. Meanwhile, BMC and BMD of them could be increased.(4) Conclusion: Cordymin may have a protective effect on diabetes-induced osteoporosis. In summary, above results show that: Cordyceps sinensis can promote osteogenesis,reduce bone loss and effectively repair the damage of osteoporosis to body functions.Cordymin, as one of the important monomer components of Cordyceps sinensis, caneffectively relieve the symptoms of diabetes, reduce pancreatic β cell damages, antagonizethe activity of the oxidizing agent in the body, increase body weight, promote thedeposition of calcium in bones of the body and even has the potential to treat osteoporosiscaused by diabetes. This major discovery indicates a new direction for the treatment ofosteoporosis for us; and it is expected to expand a new understanding of pharmacologyfunction and anti-osteoporosis effect of Cordyceps sinensis and to lay a solid theoreticalfoundation for the future development of anti-osteoporosis drugs with independentintellectual property rights.
Keywords/Search Tags:Cordyceps sinensis, Cordymin, Strontium, Postmenopausal Osteoporosis, Hindlimb Suspension, Disuse Osteoporosis, Diabetic-induced Osteoporosis, Micro-CT, Biomechanics, Bone turnover
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