Shen-Jing as a Chinese Medicine Concept Might Be a Counterpart of Stem Cells in Regenerative Medicine / 中国结合医学杂志

As the epitome of the modern regenerative medicine, stem cells were proposed in the basic sense no more than 200 years ago. However, the concept of "stem cells" existed long before the modern medical description. The hypothesis that all things, including our sentient body, were generated from a small origin was shared between Western and Chinese people. The ancient Chinese philosophers considered Jing (also known as essence) as the origin of life. In Chinese medicine (CM), Jing is mainly stored in Kidney (Shen) and the so-called Shen-Jing (Kidney essence). Here, we propose that Shen-Jing is the CM term used to express the meaning of "origin and regeneration". This theoretical discovery has at least two applications. First, the actions underlying causing Shen-Jing deficiency, such as excess sexual intercourse, chronic diseases, and aging, might damage the function of stem cells. Second, a large number of Chinese herbs with Shen-Jing-nourishing efficacy had been proven to affect stem cell proliferation and differentiation. Therefore, if Shen-Jing in CM is equivalent with stem cells in regenerative medicine, higher effective modulators for regulating stem-cell behaviors from Kidney-tonifying herbs would be expected.

Effect of compound bushen recipe on chronic fatigue syndrome in C. elegans: an experimental study / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the effect of compound bushen recipe (CBR) in improving the survival state of stress and the overall life span in C. elegans by simulating chronic fatigue syndrome (CFS) under various stress states.</p><p><b>METHODS</b>The tolerance and the average survival time of adult larvae against heat stress (35 degrees C), oxidative stress (250 microg/mL juglone), and in vivo Abeta protein toxicity (Abeta(1-42) transgenic mutant CL4176) under the intervention of the high (500 mg/L), middle (250 mg/L), and low (100 mg/L) dose CBR were observed. The effect of CBR on the average live time (at 25 degrees C), movement distance in 20 seconds, the frequency of pharyngeal pump in 30 seconds, and the reproductive capability were assessed.</p><p><b>RESULTS</b>Compared with the control group, the survival time of heat stressed C. elegans could be significantly increased in each CBR group (P < 0.01). The survival time of heat stressed C. elegans could be elongated, the protein toxicity be attenuated, and the live time prolonged in the high and middle dose CBR groups (P < 0.01, P < 0.05).The movement distance and the frequency of pharyngeal pump could also be increased in the high dose CBR group (P < 0.01). There was no statistical difference in the reproductive capability among all groups (P > 0.05).</p><p><b>CONCLUSIONS</b>CBR could significantly enhance the stress capacity of C. elegans against internal and external environment, and prolong their lifespan. It did not interfere their normal production, and also could improve the quality of life, thus laying a foundation for further mechanism studies and pharmacological researches on CBR in preventing and treating CFS.</p>

Icariin promotes self-renewal of neural stem cells: an involvement of extracellular regulated kinase signaling pathway / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects and underlying molecular mechanisms of icariin (ICA) on self-renewal and differentiation of neural stem cells (NSCs).</p><p><b>METHODS</b>NSCs were derived from forebrains of mice embryos by mechanical dissociation into single cell suspension. The self-renewal of NSCs was measured by neurosphere formation assay. The proliferation of NSCs was detected by water-soluble tetrazolium (WST) and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay. Protein expression of neuron-specific marker tubulin-βIII(TuJ1) and astrocyte-specific marker glial fibrillary acidic protein (GFAP) were measured by immunofluorescence and Western blotting. Using microarray, the differentially expressed genes (DEGs) were screened between NSCs with or without ICA treatment. The signaling pathways enriched by these DEGs and their role in mediating effects of ICA were analyzed.</p><p><b>RESULTS</b>ICA significantly promoted neurosphere formation of NSCs cultured in growth protocol in a dose-dependent manner and achieved the maximum effects at 100 nmol/L. ICA also increased optical absorbance value and EdU incorporation into nuclei of NSCs. ICA had no significant effects on the percentage of TuJ1 or GFAP-positive cells, and TuJ1 or GFAP protein expression in NSCs cultured in differentiation protocol. A total of 478 genes were found to be differentially regulated. Among signaling pathways significantly enriched by DEGs, mitogen activated protein kinase (MAPK) pathway was of interest. Blockade of extracellular signal-regulated kinase (ERK)/MAPK, other than p38/MAPK subfamily pathway partially abolished effects of ICA on neurosphere formation and EdU incorporation of NSCs.</p><p><b>CONCLUSION</b>ICA can promote the selfrenewal of NSCs at least partially through ERK/MAPK signaling pathway.</p>

From "different patterns in the same disease" to "analogous patterns in the same disease" / 中国中西医结合杂志

The relationship between disease in Western medicine (WM) and pattern in Chinese medicine (CM) is a key scientific issue in integrative medicine (IM). The theory of "different patterns in the same disease" has greatly promoted the development of IM and the modernization of CM. However, this concept is frequently misinterpreted in the clinical practice. The individual difference was overemphasized, while common changes among patients suffering from the same disease were neglected. As a result, the identification and treatment of common changes based patterns were weakened. The theory of "analogous patterns in the same disease" combines the concept of "different patterns in the same disease" and "microcosmic identification of patterns", which reveals the core mechanism of CM from the pathogenesis, and identifies the major pattern by analyses of manifestations and pathologic changes. And under the guidance of the theory of "formula corresponding to pattern", the major formula can be set for the major pattern. For those differences among individuals suffering from the same disease, they can be identified as different analogous patterns (subtypes) within a same major pattern, and can be treated with analogous formulae deriving from modified major formula. The theory of "analogous patterns in the same disease" clarifies the intrinsic relationship between the disease and pattern, perfects and develops the theory of "different patterns in the same disease", and it is an important innovation in thinking ways and research methods of IM.

Characteristics of lymphocyte nuclear factor-κB signal transduction kinase expression in aging process and regulatory effect of epimedium flavonoids / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the characteristics of lymphocyte nuclear factor kappa B (NF-κB) signal transduction kinase-related molecular mRNA differential expressions at various month age segments in aging process and the intervening effect of Epimedium flavonoids (EF) on it.</p><p><b>METHODS</b>Sixty SD rats were divided into six groups, according to animals' age, i.e., the 3 days (d) group, the 4 months (m) group, the 10 m group, the 18 m group, the 27 m group, and the 27 m+EF group. RNA was extracted from separated splenic lymphocytes. Adopting NF-κB signal path functional genome oligonucleotide gene-chip (128 related genes), the integral characteristics and differences of NF-κB signal transduction kinase-related mRNA expressions were determined, and the intervening effect of EF was examined.</p><p><b>RESULTS</b>The mean level of the NF-κB signal transduction kinase-related mRNA expressions in rats' splenic lymphocytes lowered with aging; the highest expression was presented at 3 d after birth, and then, it lowered gradually, with the lowest level at 18 m or 27 m. After EF intervention, the expression level was raised to the 10-18 m level in the aged rats.</p><p><b>CONCLUSION</b>The changing rules of lymphocyte NF-κB-signal-transduction-kinase-related mRNA expressions in various stages of aging are helpful for selecting the well time for preventing and intervening aging, and will also give a hint to the molecular index for assessment of senility retarding researches.</p>

Activating effect and mechanism of epimedium on endogenous stem cells / 中国中西医结合杂志

Stem cells are the cells with capacities of self-renovation, multiplication and differentiation. By activating endogenous stem cells to promote regeneration response has provided a new thinking for the treatment of degenerative diseases. The authors found that epimedium flavonoids (EF) can promote the proliferation and migration of adrenocortical stem cells in corticosterone-treated rats (as a model of Shen-yang deficiency); and through gene-chip test it was showed that EF could significantly up-regulate the growth hormone (GH), growth hormone releasing hormone (GHRH) and other growth factors such as insulin-like growth factor binding protein (IGFBP) and nerve growth factor (NGF) in the model rats. In natural aging rats (as model for Shen deficiency), EF could make the gene expression of multiple tissues youthening, and up-regulate the lowered expressions of GH, GHRH, IGFBP and NGF, etc. Further study on the in vitro isolated and cultivated neuro-stem cells proved that EF and its components have direct promoting actions on stem cell proliferation. All the above-mentioned outcomes indicated that the actions of EF and its extracts on stem cells are possibly the cytological basis for their effects on counteracting the suppression of glucocorticoids on hypothalamus-pituitary-adrenal (HPA) axis and retarding aging; also illustrated that TCM could treat diseases by a way of activating endogenous stem cells through mobilizing and elevating hormones and cytokines levels, and bringing the reserved potential of organism into full play.

Transition of studying on Shen deficiency syndrome and aging from holistic concept to systematic biologic viewpoint / 中国中西医结合杂志

Holistic concept is a characteristic contribution of Chinese medicine to medical science. Based on holistic concept, we investigated the correlation of Shenyang deficiency syndrome with the hypothalamus-pituitary-target gland axis; and revealed by gene chip technique the molecular network regulatory rule of intervention with Chinese drugs on hypothalamus-pituitary-adrenal-thymus axis in aged rats as a model for Shen deficiency syndrome; also the two major gene regulation pathways, namely, the neuro-endocrine-immune pathway and the neuro-endocrine-bone metabolic pathway, in hypothalamus, pituitary, adrenal, lymphocytes, kidney, liver, bone of aged rats, so as to advance the holistic research on Chinese medicine syndromes. Recently, based on the dynamic, intervention and multi-layer integration requirement of systematic biology, the common rule of aging was found at three different levels, the whole genomic transcription level, the metabolic level and the single ageing signaling pathway level. Meanwhile, it was demonstrated that the temporal and spatial association of genes will be weakened gradually along with aging. And Epimedium Flavonoids (EF), an extracts from Epimedium have been proved to be capable of effectively reversing both of these systemic changes. Thus, the transition of study from holistic concept to systematic biologic viewpoint could surely promote the progression of Chinese medicine to modern life science.

Establishment of a quantitative mathematical model of Shen-deficiency syndrome based on whole-genome transcriptional profiles / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To establish a quantitative mathematical model of Shen-deficiency syndrome of TCM by utilizing whole-genome transcriptional profiles.</p><p><b>METHODS</b>The 4, 10, 18, 24 months old SD rats were used, 24-months aged rats intervened by Epimedium Flavonoids (EF) were adopted in the experiment. Rats' hypothalamus, pituitary, adrenal, lymphocytes, bone, liver, and kidney, and spleen were taken for determining whole-genome mRNA expression with gene chip, and a quantitative nerve network model was established by utilizing the gene expression profile of different aged rats, then the model was used to evaluate the effects of EF on Shen-deficiency syndrome.</p><p><b>RESULTS</b>Totally 199 genes showing age-dependent characteristics were screened out from the 7 kinds of tissue, most of them were neuro-endocrine immune related genes. Evaluation based on the mathematical model showed the age of hypothalamus, pituitary, adrenal, liver, kidney, bone, and spleen in the 24-months rats after EF intervention was 12.64, 10.87, 8.10, 12.70, 11.93, 13.14, and 10.13 months, respectively.</p><p><b>CONCLUSION</b>A quantitative mathematical model can be established based on the gene expression profile, it is suitable for estimating the efficacy of Shen-tonifying drugs. EF can make the gene expression of elder close to the young state, suggesting that EF has action in improving Shen-deficiency syndrome and delaying senescence.</p>

Study on changes of protein phosphorylation of p65, IkappaBalpha and IkappaBepsilon in lymphocytes of rats in progress of aging and interventional effect of Epimedium flavonoids / 中国中药杂志

<p><b>OBJECTIVE</b>To study the characteristics of protein phosphorylation of p65, IkappaBalpha and IkappaBepsilon in lymphocytes of rats in the progress of aging and the the interventional effect of Epimedium flavonoids (EF).</p><p><b>METHOD</b>We chose the lymphocytes derived from SD rat spleen. We divided the SD rats into five groups i. e. 4 months (4 m), 27 months (27 m), the 27 m EF treated group (27 m + EF), and we also observed the whole interventional effect of PDTC (a NF-kappaB inhibitor) on old rat groups (27 m PDTC, 27 m PDTC + EF ) when IkappaBepsilon, IkappaBalpha were detected. Through the western-blotting analyses, we studied the entire characteristics and distinctions of phosphorylation expression in molecules related to NF-kappaB signal transduction pathway p65, IkappaBepsilon and IkappaBalpha in lymphocytes across the age spectrum of rats in aging. We also observed the whole interventional effect of EF on lymphocytes of old rats.</p><p><b>RESULT</b>With the increasing of age, the mean level of phosphorylation expressions of p65, IkappaBalpha and IkappaBepsilon in rat spleen lymphocytes decreased obviously, When inhibited NF-kappaB by PDTC, there was decreased evidently, while PDTC + EF can active NF-kappaB family and the above molecules were increased to a certain extent.</p><p><b>CONCLUSION</b>The phosphorylation expressions of p65, IkappaBalpha and IkappaBepsilon in rat spleen lymphocytes were not enouphe, EF have a strong effect to upregulated the expression of them during aging.</p>

Effect and mechanism of Epimedium flavanoids for aging retardation from viewpoint of transcriptomics and metabonomics / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect and its mechanism of Epimedium flavanoids (EF) in retarding aging with different systematic viewpoints.</p><p><b>METHODS</b>Hypothalamus, pituitary, adrenal and lymphocytes taken from 4-, 10-, 18-, 24-month old rats and from EF treated 24-month old rats were used to measure whole genome mRNA expression by gene array. Serum samples were used for metabonomic assay with high performance liquid chromatography. Using specific gene chip for NF-kappaB signaling pathway to detect the gene expression of the molecule related to that pathway in lymphocytes. Then, a neural network (NN) model was established upon the data obtained to quantitatively evaluate the degree of aging and the efficacy of drug intervention.</p><p><b>RESULTS</b>Gene expression of 199 genes showedan age-dependent pattern, most of which were reversed by EF, and the output of NN model showed that EF made the transcriptomics of 24-month old rats to 8-13 months. Seventeen metabolites among the 1,885 peaks detected were identified to have significant age-depending changes, and EF intervention reset the level of metabolites to a younger (18-month) level. The integral level of gene expression for NF-kappaB signaling pathway decreased significantly along with the increasing of age, and was significantly elevated by EF, NN model showed it approached to 10.5-month old.</p><p><b>CONCLUSION</b>Phenotype of aging at different levels demonstrates a common age-dependent trend; EF can reverse this age-dependent change at different levels in a synchronous manner.</p>

Comparison of gene expression profiles between rats of Shen deficiency syndrome and Shen-yang deficiency syndrome differentiated according to therapeutic efficacy of drugs used / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore similarity and difference of connotation between Shen deficiency syndrome (SDS) and Shen-yang deficiency syndrome (SYDS) on the molecular level.</p><p><b>METHODS</b>The senescent SD rats and corticosterone-treated rats were adopted for models of SDS and SYDS respectively, their syndrome was differentiated according to the therapeutic efficacy of treatment with epimedium flavonoids (EF). The gene expression profiles of hypothalamas, pituitary, adrenal gland and lymphocytes (HPAT axis) were detected before and after EF treatment using gene chip provided by Affymetrix company.</p><p><b>RESULTS</b>As compared with the young rats, the ageing rats and corticosterone-treated rats showed a significant down-regulation in highly consistent pattern, of various neurotransmitters of HPAT axis firstly, followed with that of growth and sex hormone related genes. EF could reverse the above genes expression in both models, and for SYDS model rats, it could also significantly up-regulate the gene expressions of heat shock protein, cytochrome P450 and thyroid stimulating hormone (TSH).</p><p><b>CONCLUSION</b>Both SDS and SYDS model rats show connotation of Shen deficiency, and the substantial base of Shen-yang deficiency syndrome resides in the process of oxidative phosphorylation of energy metabolism accelerated by thyroid hormone.</p>

Important action of improving adrenocortical function for certain diseases recovery / 中国中西医结合杂志

It has been found that the hypofunction status of hypothalamus-pituitary-adrenal (HPA) axis exists in patients with Shen-yang deficiency syndrome of TCM, also presents in most asthma patients. Seasonal attack of asthma can be prevented with Shen-tonifying drugs by improving adrenocortical function. Since patients subject to long-term glucocorticoids display hypofunction condition of HPA axis, Shen-tonifying drugs should be helpful to gluocorticoid withdrawal for getting higher success rate. Basic researches also indicated that the activating of adrenocortical stem cells and promoting regeneration of adrenal cortex is one of the mechanisms underlying improvement of adrenocortical function. Series of research showed that hypofunction of adrenocortex is the general pathological change in some diseases, so, Shen-tonifying drugs act a part in unitarily modulating the adrenocortical function, to get the therapeutic effect of both regulating the whole and improving the local.

An outstanding feature of traditional Chinese medicine: improving local pathology by regulating holistic function / 中国中西医结合杂志

Holistic conception reflects that "Syndrome" summarizes all aspects and conditions related to occurrence of disease referring to different constitutions. "Treatment according to syndrome differentiation" improves local pathological changes through regulating holistic function, which is the practical application of holistic conception and an outstanding feature of TCM. According to syndrome differentiation, treatment shows favorable effects on local pathological changes as restenosis after coronary artery intervention therapy, excessive inflammation, vascular endothelial injury in coronary artery disease and hypoadrenocortical function with drugs for promoting blood to remove blood stasis, clearing heat and detoxifying toxin, and warming Shen-yang, and aromatic drugs for warming meridian to dredge obstruction.

Syndrome differentiation through drug effects in mapping the two regulatory pathways of gene networks in Shen deficiency syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the regulatory pathways and rules of the gene networks in Shen deficiency syndrome.</p><p><b>METHODS</b>Tissues of hypothalamus, pituitary, adrenal, lymphocyte, bone, liver and kidney were taken as samples from 4 months' and 24 months' old SD rats and rats after treatment with Epimedium flavonoids (EF), differences of gene expression profile in Shen deficiency syndrome were studied repeatedly with gene chip rat expression set U230 2.0 array from Affymetrix Co.</p><p><b>RESULTS</b>Gene expressions in the aged rats all decreased including neurotransmitter of gamma-aminobutyric acid (gammaGABA), gonadotropin releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), thyroid stimulating hormone (TSH), growth hormone-releasing hormone receptor (GHRH), insulin-like growth factor (IGF) and binding proteins (IGFBP) in hypothalamus, pituitary and adrenal (HPA axis), cell growth-related gene, growth factor related protein, and immune regulatory genes such as interferon gamma (IFN-gamma), interleukin 4 (IL-4) and interleukin 6 (IL-6) in lymphocytes, parathyroid hormone (PTH), calcitonin, procollagen, collagen, connective tissue growth factor in bone, and oxidative phosphorylation genes such as cytochrome P450 and NADH dehydrogenase, glutamate dehydrogenase related with protein metabolism, and glucose-6-phosphatase related with glucose metabolism in liver, most of which were up-regulated after treatment with EF as well as genes related with ageing and cell cycle, such as cyclin B, metabolism related genes and proteins of sodium and chloride channel in kidney.</p><p><b>CONCLUSION</b>Dysfunction of the two regulatory pathways of gene networks as nerve-endocrine-immunity and nerve-endocrine-bone metabolism exists in Shen deficiency syndrome differentiated by effects of drugs, which could be improved by strengthening Shen therapy.</p>

Exploration on molecular mechanism of Epimediun flavonoids in regulating adrenocortical regeneration in rats with inhibited hypothalamic-pituitary-adrenal axis using oligonucleotide microarrays / 中国中西医结合杂志

<p><b>UNLABELLED</b>To investigate the regulatory effects of epimedium flavonoids (EF) on adrenocortical regeneration in rats with inhibited hypothalamic-pituitary-adrenal (HPA) axis.</p><p><b>METHODS</b>Cell distribution in cell cycle and cell apoptotic rate were measured with PI stain and flow-cytometry; apoptosis cells were showed by in situ terminal-deoxynucleotidyl transferase-mediated deoxy-uridine triphosphate-fluorescene nick end labeling assay (TUNEL), and the genome-wide gene mRNA expression was detected by oligonucleotide microarrays.</p><p><b>RESULTS</b>Compared to the normal control, adrenal cells isolated from the HPA axis inhibited model group were arrested in Go/GI phase, and showed a higher apoptotic rate (P < 0.05). After treated with EF, cells in G0/G1 phase decreased and those in G2/M phase increased (P < 0.01), and the elevated apoptotic rate reduced significantly (P < 0.05). TUNEL assay showed the number of apoptotic cells per section was 4.67 1.53 in the normal control group, 70.67 +/- 9.29 in the model group, and 18.67 +/- 7.64 in the EF-treated group respectively (n=3). Gene expressions in adrenal were mostly restrained in the model group, including 7 cytocycle promoting genes, including V-ras, V-jun, etc., while after treatment with EF, 6 cytocycle promoting genes, 1 anti-apoptotic gene, and genes that closely related with adrenocortical regeneration as IGF-II and FGF7 and their receptors, as well as 7 steroid biosynthesis participated genes were all up-regulated. Conclusion EF can accelerate adrenocortical cell proliferation, inhibit its apoptosis, and promote steroid biosynthesis so as to enhance adrenocortical regeneration in HPA axis inhibited rats, which may contribute to the beneficial effects of EF in protecting adrenocortical function during glucocorticoid withdrawal.</p>

Mechanism of epimedium flavonoids in regulating immuno-senescence via nuclear factor-kappa B related signal transduction pathway / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the mechanism of epimedium flavonoids (EF) in regulating immunosenescence via nuclear factor-kappa B (NF-kappaB) related signal transduction pathway.</p><p><b>METHODS</b>(1) The apoptosis index (AI) of splenic lymphocyte in aged rats was monitored by flow cytometry, that of young rats was taken as control. (2) The differential expression profile of NF-kappaB related signals in aged rats allocated in the control group (aged rats, group A), the EF treated group (group B), the PDTC (a NF-kappaB inhibitor) treated group (group C) and the PDTC plus EF treated group (group D), was determined and the main significant molecules in them were analyzed with gene microarray of 96 genes related to NF-kappaB signal pathway.</p><p><b>RESULTS</b>Excessive apoptosis of T lymphocyte cell was seen in aged rats, and it was significantly suppressed in group B and D. In group B, 73 genes were up-regulated to different extent, including 10 of the NF-kappaB/Rel/IB gene family, transduction signal molecule member of NIK/IKK/I B/Rel/NF-kappaB, NF-kappaB regulatory target genes, trans-membrane receptors, transcription factors, and receptor protein, etc. But the up-regulation on NF-kappaB gene family could not be seen in group C and that on others were also alleviated, while in the group D, the NF-kappaB gene family and its related transduction pathway were still activated to some extent. The NF-kappaB gene family showed a markedly common feature after EF intervention, either used alone or in combination with PDTC, i.e. the significant upregulated NF-kappaB1, NF-kappaB2, Rel B and I Bepsilon, and activated NIK/IKK/I B/Rel/NF-kappaB pathway.</p><p><b>CONCLUSION</b>EF can suppress the excessive apoptosis of splenic lymphocyte in aged rats and activate Rel/NF-kappaB/ I B/IKK and their signal transduction pathway to up-regulate NF-kappaB through adjusting I Bepsilon and I Balpha, which may be the essential mechanism of EF in rebuilding the immune homeostasis of T lymphocyte apoptosis and retarding immunosenescence.</p>

Studies of gene networks and singal transduction of kidney deficiency syndrome by syndrome differentiation through drug effects / 中国中西医结合杂志

Three kinds of networks were summarily described in this review including the small intracellular molecular networks, the middle-scale networks of hypothalamus-pituitary-adrenal-thymus (HPAT) axis and the large network, neuroendocrine-immune (NEI) network, covering the whole organism and linking multiple systems together. The hypothesis was expressed that the "disease" or "syndrome" formed in the human body by the intervention from outside world is based on the changes of multi-molecular network. In this paper, the pattern and ability of signal transduction channel and the methods of studying changes in it were also described, and raised, herefrom, "to determine syndrome by drug effects (DSDE)" is the intervention means for studying syndrome in the light of systemic biological methods. We found Kidney-yang deficiency syndrome covered the NEI network and the regulating center located in hypothamus with Compound Bushen Recipe (CBR, Kidney-tonifying recipe). By intervention with EF, an effective component of CBR, it was found that EF can activate the immune system and the three networks, including growth axis, sex hormone axis and lymphocyte apoptosis network in HPAT axis through the downward pathway of NEI network to play its efficiency of molecular network. There are many regulation patterns of EF on networks. For example, in the network mechanism of lymphocyte apoptosis and proliferation, EF can reconstruct the balance of the opposite apoptosis related genes and proliferation related genes; EF can assemble and integrate co-stimulating molecules, transform growth factors (TGF), and several oncogenes to form an upstream factor network for initiating the proliferation and anti-apoptosis promotion; EF can simultaneously up-regulate the two opposite genes expression of IkappaB and NFkappaB in NIK/IKK/IkappaB/Rel/NFkappaB signal transduction channel, which could not only control the rising of NFkappaB in a moderate range, but also guarantee its predominant status to exert its hinge role in molecule regulating network, by which gene network regulation atlas in HPAT axis of Kidney-deficiency syndrome was observed.

Study on the regulative rule of reinforcing shen principle on sexual precocity and senescence at the molecular level / 中国中西医结合杂志

The imbalance of Shen-yin and Shen-yang is a common pathological basis of sexual precocity and senescence. Senescence can be regarded as physiological Shen-deficiency, which is mainly the deficiency of Shen-Yang, while the essence of sexual precocity is hyperactivity of Fire due to Yin-deficiency, and deficiency of Shen-Yin is the predominance in the imbalance. The process of growth, development, maturing and aging led by Shen-qi, is mainly involving the hypothalamus-pituitary-growth hormone axis and sexual gland axis. Early initiation of these two axes appears in sexual premature children, manifesting syndrome of Fire hyperactivity due to Yin-deficiency, while in senescence, the decline of the axes appears ahead of time and manifests syndrome of Yang qi consumption. It has been shown in experimental and clinical researches that significantly good effects could be obtained by applying Chinese recipe for warmly reinforcing Shen-Yang to postpone senescence and recipe for nourishing Yin and removing Fire to inhibit sexual precocity. It also been proved by determining syndrome and speculating the damaged site according to the effects of drug that the pathologic damage of sexual precocity and senescence is sited on the hypothalamus or higher center.

Molecular mechanism of epimedium flavonoids in immune homeostasis remodeling in aged rats revealed by lymphocyte gene expression profile / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To elucidate the gene regulatory pattern of Epimedium flavonoids (EF) in immune homeostasis remodeling in the aged rats.</p><p><b>METHODS</b>(1) To quantitatively analyse the apoptosis percentage of lymphocyte in spleen of aged, young and EF treated rats using flow cytometry. (2) To analyse the lymphocyte gene expression profiles of different groups using gene chips (Rat Genome U34A).</p><p><b>RESULTS</b>(1) Detection of lymphocyte apoptosis percentage showed that there was significant difference in comparing between aged group and young group, between EF treated group and aged group (P < 0.01). (2) As compared with that in the young group, in the aged group, 116 genes were up-regulated and 215 down-regulated. As compared with that in the old group, in the EF treated group, 447 genes were up-regulated and 456 down-regulated, which involved the aspects as cell apoptosis and cell proliferation regulation, etc.</p><p><b>CONCLUSION</b>(1) The expression pattern characterized by up-regulation of apoptosis promoting genes expression and down-regulation of apoptosis inhibiting genes expression, is the important gene background of immuno-homeostasis imbalance in the aged. (2) The role of EF is to reverse the abnormal changes of gene expressions with opposite functions, i.e. the apoptosis promoting and inhibiting, proliferation enhancing and antagonizing genes, to reconstruct a beneficial equilibrium of gene expression and thus to further remodel the immuno-homeostasis in the aged.</p>

Experimental study on effect of epimedium flavonoids in protecting telomere length of senescence cells HU / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of senescence delay of human diploid fibroblast (2BS) and protecting telomere length by epimedium flavonoids (EF).</p><p><b>METHODS</b>The drug sera of EF were used to treat the 2BS. The population doublings of 2BS cells were observed, the mRNA expression of p16 gene were determined by fluorescence real-time quantitative RT-PCR, the telomerase activation of 2BS cells were determined by TRAP-Hyb, the total retinoblastoma (Rb) and phosphorated Rb protein content were detected by ELISA, the telomere length of 2BS cells were determined by telomere restriction fragment (TRF) Southern blot assay.</p><p><b>RESULTS</b>EF could significantly extend the population doublings of 2BS cells, the expression of p16 mRNA was decreased and the content of phosphorated Rb protein were increased by EF. The telomere lengthening of 2BS cells were improved by EF, but the telomerase was not activated.</p><p><b>CONCLUSION</b>In senescence human fibroblasts 2BS cells, p16 gene mRNA expression increased, content of phosphorated Rb protein decreased and the telomere length of 2BS shortened, EF might delay the aging of cells through inhibiting the p16 gene expression, promoting the production of phosphorated Rb protein and to protect the length of telomere, but not activating the telomerase.</p>