| Aging is an unavoidable and complex natural law of life, which is a core part of the life process that affects the healthy development of the whole human society. With the improvement of modern living standards, life expectancy begins to be extended. However, with the increase of age, the metabolism of the body and the function of various organs decline gradually, and the appearance of the body and the aging signs of internal organs become more and more obvious. Then, the incidence of heart disease, cerebrovascular disease, osteoporosis, menopausal syndrome and other age-related diseases is increased gradually, along with the aging body’s immune function decline and degradation of degeneration. Although we can not go against the natural laws of aging, we still can effectively reduce the incidence of age-related diseases, by exploring the mechanisms of human aging, using the health measures in a comprehensive way, and paying attention to protection. To this end, the Chinese and foreign scholars have conducted many studies hoping to prolong human life healthily and improve the quality of human aging.There are 300 or more theories and hypotheses about aging, which mainly include radical oxidation theory, immune disorders theory, brain damage decay theory, endocrine dysfunction theory, and so on. Oxidative damage and aging theory considered that the damage of the active oxygen component produced in the life cycle of metabolism can cause aging. With age, free radical defense system function begins to decline, the levels of superoxide dismutase (SOD) decreased and malondialdehyde (MDA) increased gradually, resulting in a large number of unsaturated fatty acid oxidation, causing biofilm damage, extensive DNA mutation, protein denaturation and other cellular degeneration damage, thus resulting in aging. The immune system and aging theory considered that the immune response of the elderly to self-antigens is increased, while the immune response to exogenous antigens is reduced. The aging of the immune system mainly includes the degradation of secrete viability and cell differentiation in thymus and bone marrow stem cells, manifested as cellular and humoral immune dysfunction. Therefore, the regulation of immune function can delay aging. Cell death and senescence theory considered that cell death is an important aspect of aging, including necrosis and apoptosis. Brain cells apoptosis is existed even in early adult mice, while the apoptosis rate is accelerated, and the removal of apoptotic cells is slowed down along with the age increase, especially in older mice. Apoptosis may be an important cause in the nerve cell death of brain aging process. Endocrine dysfunction theory considered that growth, development, maturation and aging have a close relationship with multicellular organism neuroendocrine function. Endocrine levels decrease with age, especially in estrogen, may affect normal cell activity and then cause aging. Supplementary estrogen for postmenopausal women can effectively delay osteoporosis and atherosclerosis. In addition, growth hormone, testosterone and dehydroepiandrosterone sulfate of the body fluids also decline rapidly with age. Muscle strength, bone density and skin elasticity can be improved through short-term hormone supplements.Traditional Chinese medicine (TCM) theory of aging and delaying aging has profound elaboration and rich practice. Su Wen-ancient naive theory clearly pointed out that the born, grow up and aging of the body are regulated by the kidney essence, so the kidney deficiency is the main cause of aging. Senile tinnitus and deafness, backache petrified, nocturia are all the performance of declining kidney. Therefore, tonifying kidney should be focused on under the premise of recuperating health.Osteoporosis is a threat to the health of the elderly, a metabolic disease showed bone component unchanged, skeletal bone density loss, bone tissue fiber structure degradation, and risk of fracture increased. Although the basic theory of traditional Chinese medicine does not mention "osteoporosis" explicitly, the related symptoms such as back pain, length shortened, humpback and fractures changes of the ancient Chinese literature on "Gu Wei", "Gu Ku" and "Gu Bi" are very similar with modern medicine clinical symptoms and signs of osteoporosis, especially in "Gu Wei". TCM theory holds that the main pathogenesis of osteoporosis is kidney deficiency, spleen deficiency and blood stasis. Kidney is the foundation of the birth, the main essence, and the main bone marrow. Kidney deficiency can cause empty marrow, therefore, the growth, development, strong, and weak of bone are all closely related with the kidney essence. The adequate kidney essence makes bones strong and powerful, while deficiency of kidney essence can cause the lack of the bone marrow source, bones dystrophy, bone mineral content loss, bone density decreased, and result in osteoporosis.Learning and memory is one of the advanced functions of the brain. Memory dysfunction is an early symptom of aging animals, so we should pay more attention to brain function in the early aging. Marrow is born from kidney essence, filling in the brain. The brain stores the essence, and it is an odd constant of the internal organs, the sea of marrow, which shows that brain function is closely related with kidney. In Qing dynasty, Chongqing Hall Essay wrote by Wang pointed out that:"Brain is the sea of marrow, known as the house of mental activity. If the marrow is enough, memorization will be strong and not be forgotten. On the contrary, memorization will decline prematurely and become injury. " Therefore, adequate kidney essence can bring marrow overflowing, make mind clear and energetic, hear well and see clearly, respond flexibly, and have a good memory. On the contrary, kidney deficiency can bring marrow empty, body and mind decadence, malaise, lack of energy, respond slowly and memory loss.Menopausal syndrome refers to a series of common syndromes that menopausal women will appear, such as the blood flushes intermittent fever, irritability, insomnia, forgetfulness, backache, osteoporosis, and so on. TCM holds that the basic pathogenesis of menopausal syndrome is on kidney, of which "Tian Kui " exhaustion is the basis. Kidney qi declines gradually in menopausal women, and then deficiency of Chong Ren and "Ting Xie" will cause liver function insufficient, manifested as irritability symptom on menopause patients. Blood and mind are dominated by heart. Kidney deficiency can not nourish the heart, and then consumption of blood, distraught emotion will result in inattention, upset, insomnia and other symptoms on menopause patients.Dendrobium in the south is just like the ginseng in the north. Dendrobium’s property is slightly cold, tastes gan, and belongs to stomach and kidney meridian, which is firstly recorded in the Shen Nong’s herbal classic, as the top grade. Dendrobium can "strong yin essence, make up the five internal organs asthenia, strong bones and muscles, tonify kidney, and prolong lifespan", recorded in Compendium of Materia Medica, which has been beneficial for tonyfying kidney and medical healthcare on all previous dynasties. As early as the Tang Dynasty, Dendrobium, Saus-sureainvolucrate, Ginseng, Polygonum multiflorum aged a hundred and twenty year, Poria cocos aged sixty year, Cistanche salsa, Ganoderma Lucidum Karst in deep mountains, undersea Pearl, and Cordyceps sinensis are known as the nine important Chinese herbal medicine, recorded in Taoist canons, of which Dendrobium ranks first.Our previous study showed that Dendrobium Officinale can enhance antioxidant enzyme activities in blood, promote the proliferation of spleno-lymphocytes, inhibit the release of pro-inflammatory cytokines and inhibit the NF-κB signal pathway to reach the anti-aging effect on ovary in aging female mice. However, the mechanism of Dendrobium Officinale to carry out the extensive effect is not clear yet.Recent studies have confirmed that the regulation of mTOR (mammalian target of rapamycin) pathway is closely related with aging. mTOR can participate in inflammation aging process through the activation of NF-kB and release of proinflammatory cytokines. Mitochondrial dysfunction induces the increase of oxygen free radicals is one of the regulatory mechanism of aging. The decrease in the number of mitochondria and the decline in their function are closely connected with many age-related diseases. The suppression of mTORCl can cause activation on gene with protective function, by limiting mitochondrial respiration to reduce the injury caused by oxygen free radicals, and then to reach the life extension.The previous findings of Dendrobium Officinale on inhibition of NF-κB signal pathway, combined with the participation of mTOR in inflammation aging process, we come up with the hypothesis that, "Dendrobium Officinale may improve reproductive senescence by inhibiting the excessive activation of mTOR signal pathway and regulating the mitochondria-mediated apoptosis pathway, to affect the process of many age-related diseases, and reach the function as tonifying kidney and prolonging life"ObjectiveBased on the "tonify kidney and prolong life" efficacy of Dendrobium officinale, and combined with the theory of traditional Chinese medicine, such as "kidney governing bone, kidney producing marrow, kidney governing reproduction and kidney storing essence", in this study, we constructed ovariectomy-induced osteoporosis mice, D-galactose induced sub-acute aging and natural aging mice, to investigate the effect of Dendrobium officinale on strengthening bone and musculature, reinforcing intelligence, tonifying internal organs and longevity, respectively.Methods1. Based on the "kidney governing bone", to study the effect of Dendrobium officinale on ovariectomy-induced osteoporosis mice.Kunming mice, female, aged 1 month. A month after surgical ovariectomy, the mice were randomly divided into ovariectomized model group, positive control group (estradiol:0.17 mg/kg), Dendrobium officinale juice group (DO: 2 g fresh crude drug/kg, equivalent to 130 mg polysaccharide/kg), Dendrobium officinale polysaccharide group (DOP:140 mg/kg, equivalent to 130 mg polysaccharide/kg). Another 12 mice from the same batch were picked up as the sham operation group. All animals were administered respectively for a month. Detection indicators were as follows:(1) Serum biochemical indexes:calcium (Ca), phosphorus (P), alkaline phosphatase (AKP), superoxide dismutase (SOD) and malondialdehyde (MDA) content. (2) Histopathological examination:uterus tissue. (3) Bone morphology observation:bone histomorphometry study and bone mineral density study.2. Based on the "kidney producing marrow", to study the effect of Dendrobium officinale on brain function in aging female mice.Kunming mice, female, aged 1 month. D-galactose induced sub-acute aging model was established by subcutaneous injection of D-galactose (1 g/kg) for 8 weeks.2 weeks after the model began to establish, the modeling mice were randomly divided into D-galactose model group, positive control group (estradiol:0.17 mg/kg), Dendrobium officinale juice group (DO:2 g fresh crude drug/kg, equivalent to 130 mg polysaccharide/kg), Dendrobium officinale polysaccharide group (DOP:140 mg/kg, equivalent to 130 mg polysaccharide/kg). Another 24 mice from the same batch were picked up as the normal control group. All animals were administered respectively for 3 months. Ovariectomized mice were established by the same way as described in the previous chapter.6 months after surgical ovariectomy, the modeling mice were randomly divided into 4 groups as previously mentioned. All animals were administered respectively for 13 months. Detection indicators were as follows:(1) Behavioral study: Morris water maze test. (2) Histopathological examination:brain tissue.3. Based on the "kidney storing essence", to study the effect of Dendrobium officinale on longevity in aging mice and drosophila.D-galactose induced sub-acute aging mice were from the second quarter of the second chapter, the natural aging mice were divided into aged model group, positive control group (estradiol:0.17 mg/kg), Dendrobium officinale juice group (DO:2 g fresh crude drug/kg, equivalent to 130 mg polysaccharide/kg), Dendrobium officinale polysaccharide group (DOP:140 mg/kg, equivalent to 130 mg polysaccharide/kg). All animals were administered respectively till they died. The wild type Drosophila melanogaster was given by Professor Li (Guangzhou University of Chinese Medicine). Drosophila collected in 8h were randomly divided into control group, Rhodiola group (3%), estradiol group, Dendrobium officinale juice group (1,3,9%), Dendrobium officinale polysaccharide group (0.1,0.3,0.9%). The drugs were dissolved respectively in basic medium, and the medium was changed every 5 days. All Drosophila melanogaster was cultured respectively till they died. Detection indicators were as follows:(1) D-galactose induced sub-acute aging mice:weight, body temperature, histopathological examination for heart, liver, spleen, thymus, lung, kidney, adrenal gland, mitochondrial membrane potential detection in brain, spleen, thymus and ovary tissues. (2) Life span observation on natural aging mice:the average life span, average maximum life span, medial death time and average life span rate. (3) Life span observation on Drosophila melanogaster:the average life span, average maximum life span, medial death time and average life span rate.4. Based on the "kidney governing reproduction", to study the mechanism of Dendrobium officinale on anti-aging effect through delaying reproductive organ senescence.Kunming mice, female, aged 1 month. D-galactose induced sub-acute aging mice were established by the same way as described in the previous chapter. 2 weeks after the model began to establish, the modeling mice were randomly divided into D-galactose model group, positive control group (estradiol:0.17 mg/kg), Dendrobium officinale juice group (DO:2 g fresh crude drug/kg, equivalent to 130 mg polysaccharide/kg), Dendrobium officinale polysaccharide group (DOP:140 mg/kg, equivalent to 130 mg polysaccharide/kg). Another 20 mice from the same batch were picked up as the normal control group. All animals were administered respectively for 4 months. Detection indicators were as follows:(1) Histopathological examination:uterus and ovary tissues. (2) Mitochondrial function detection on uterus and ovary:ATP content, mitochondrial membrane potential and gene expression detection on mitochondria mediated apoptosis pathway and mitochondria fusion protein-2. (3) Gene expression detection on mTOR signal pathway in uterus and ovary tissues.Results1. Based on the "kidney governing bone", to study the effect of Dendrobium officinale on ovariectomy osteoporosis mice.Both Dendrobium officinale juice and Dendrobium officinale polysaccharide could improve the contents of phosphorus (P), calcium (Ca), and alkaline phosphatase (AKP) in serum, which had a certain regulation effect on the balance of calcium and phosphorus. Dendrobium officinale could decrease the content of malondialdehyde (MDA), and increase superoxide dismutase (SOD) activity. Dendrobium officinale also had the effect to improve pathology changes on uterus and bone trabecula, such as thinning of the bone cortex, interrupted morphological structural, and so on. Among them, Dendrobium officinale juice had a marked increase in uterus coefficient, the percentage of bone trabecular area, the number of bone trabecular, and a reduction in the degree of bone trabecular separation. Dendrobium officinale polysaccharide could also improve the above morphology changes on bone trabecular to a certain degree. The above results showed that, Dendrobium can promote bone formation, enhance the antioxidant capacity of the body, improve the metabolism of oxygen free radicals effectively, and then play an important role in anti-osteoporosis.2. Based on the "kidney producing marrow", to study the effect of Dendrobium officinale on brain function in aging female mice.8 weeks after D-galactose modeling, the serum SOD activity decreased, and the content of MDA increased significantly, indicating that the oxidative damage of the body was caused, and D-galactose sub-acute aging model was set up successfully. Compared with young mice, the ability of learning in elderly ovariectomized mice was poorer, while the difference was not obvious when compared with young ovariectomized mice, indicating that ovariectomy could have a certain impact on learning ability of positioning search and space search, which meant estrogen deficiency could lead to learning and memory dysfunction, resulted in brain aging. Compared with D-galactose sub-acute aging mice, Dendrobium officinale juice could significantly shorten the latency period and searching distance, and increase the percentage of swimming time and distance in the target quadrant, indicating that Dendrobium officinale could enhance the learning ability in D-galactose sub-acute aging mice, especially in memory consolidation on space search. In ovariectomized mice, Dendrobium officinale juice could shorten the searching distance in early old aged ovariectomized mice, but did not have obvious effect on elderly ovariectomized mice. The above results showed that Dendrobium officinale could improve learning and memory dysfunction caused by oxidative damage and youth hormone deficient, through scavenging oxygen free radicals, improving the oxidative damage such as the decrease in the number of brain neurons and neurofibrillary tangles phenomenon, promoting the recovery of damaged neurons, so as to improve the vitality of cerebral neuron cell. The effect of Dendrobium officinale in elderly ovariectomized mice suggested that the degree of dysfunction in brain function and memory caused by hormone deficiency and age stimulation were too serious to reverse.3. Based on the "kidney storing essence", to study the effect of Dendrobium officinale on longevity in aging mice and drosophila.Dendrobium officinale polysaccharide could obviously increase the temperature of scapula, back and abdomen in natural aging mice, indicating Dendrobium officinale had a certain enhancement on elderly basal metabolic activities. Dendrobium officinale could improve pathologic changes on important organs. It could also significantly increase the ATP content of brain, spleen and adrenal, mitochondrial membrane potential of spleen and brain, improve the depolarization phenomenon, which had a protective effect on apoptosis and necrosis of the organs. In aging female mice and drosophila, the average life span and medial death time were both extended in Dendrobium officinale group. The above results showed that, Dendrobium officinale had promoting effect on tonifying important organs and longevity.4. Based on the "kidney governing reproduction", to study the mechanism of Dendrobium officinale on anti-aging effect through delaying reproductive organ senescence.Dendrobiumofficinale could significantly increase the uterus coefficient and improve the pathologic changes on uterus and ovary. Dendrobium officinale could increase the ATP content of uterus and ovary, mitochondrial membrane potential by up-regulating Bcl-2 mRNA gene expression in uterus and ovary, down-regulating Bax gene expression in uterus and Mfn-2 mRNA gene expression in ovary, so as to increase the ratio of Bcl-2/Bax mRNA gene expression. Dendrobium officinale also had a down-regulating effect on mTOR in ovary, however the relationship between mTOR signal pathway and mitochondrial apoptosis pathway were still not clear. The above results showed that, Dendrobium officinale could protect reproductive organ from mitochondrial damage, and the mechanism of anti-apoptosis by inhibiting mTOR signal pathway needs to be further studied.ConclusionTo sum up, Dendrobium officinale could improve reproductive function decline, strong bones and muscles, enhance intelligence, and delay age-related diseases process, such as osteoporosis, senile dementia, menopausal syndrome, and so on, so as to extend a certain survival time. The reproductive organ senescence delayed by regulation of mTOR signal pathway and mitochondrial apoptosis pathway might be one of the basic role on overall anti-aging effect for Dendrobium officinale. Our study provided scientific basis for "tonify kidney and prolong life" efficacy of Dendrobium officinale and promoted its development and application of elderly health care products. |
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