Mechanism of yougui yin for steroid-induced femoral head necrosis based on network pharmacology / 中国组织工程研究

BACKGROUND: Existing cell experiments, animal experiments and clinical experiments have found that Yougui Yin can play a positive role in steroid-induced femoral head necrosis, but the specific pharmacological mechanism of Yougui Yin is not described. OBJECTIVE: To explore the mechanism of Yougui Yin in the treatment of steroid-induced femoral head necrosis based on network pharmacology, and to provide a theoretical basis for the clinical application of Yougui Yin in the treatment of steroid-induced femoral head necrosis. METHODS: The Chinese Medicine Computing System Pharmacology Analysis Platform (TCMSP) was used, with oral bioavailability and drug-like properties as the limiting conditions, to retrieve the main active ingredients of six kinds of traditional Chinese medicines including Monkshood, Cinnamon, Rehmannia glutinosa, Cornus officinalis, stir-baked rhizoma dioscoreae, wolfberry in Yougui Yin and predict key target genes. Target genes related to steroid-induced femoral head necrosis were searched in OMIM and GeneCards databases, and the intersection target genes of Yougui Yin and steroid-induced femoral head necrosis were obtained through R language, followed by drawing the Wayne diagram. Using Cytoscape 3.6.1 software, we drew a “component-disease-target” Chinese medicine regulatory network, and then established a protein-protein interaction network with the help of the STRING platform. Finally, the R language and Bioconductor platform were used to perform gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on the intersection genes. RESULTS AND CONCLUSION: There were 43 main effective components in Yougui Yin, including quercetin, glycotein, diosgenin, karanjin, stigmasterol, etc. and 102 key target genes, including ESR1, AKT1, NCOA1, PTGS1, JUN, etc. Gene ontology enrichment analysis revealed 137 molecular functions, 2 119 biological processes and 41 cell components. KEGG pathway analysis yielded 153 signal pathways. To conclude, Yougui Yin may play an anti-osteoporosis and anti-inflammatory role by regulating steroid hormone receptor, phosphatase binding and other molecular functions, participating in biological processes such as active oxygen metabolism and steroid hormone response, affecting cell composition such as membrane raft and RNA polymerase II transcription factor complex, so as to treat steroid-induced femoral head necrosis with the help of endocrine resistance and other signal pathways.

Analysis of blood components of Yougui Yin in normal rats and rats with kidney deficiency caused by adenine based on UPLC-MS technology / 中国中药杂志

Based on the serum medicinal method, this study aims to investigate the migrating components of Yougui Yin in the blood after intragastric administration, and to provide reference for the basic research of its pharmacodynamics. The kidney deficiency rat model was replicated by adenine method. Normal rats and model rats were administered orally for a single gavage of Yougui Yin. The components in blood were rapidly analyzed and identified by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and multiple reaction monitoring(MRM), and the migrating components in blood of Yougui Yin were explored by multivariate statistical analysis. The results showed that there were 42 characteristic peaks in the plasma of normal rats by UPLC-Q-TOF-MS technology and 13 chemical components were identified, including 6 alkaloids, 2 flavonoids, 2 triterpenoid saponins, 1 iridoid, 1 phenylpropanoid and 1 monoterpenoid. There were 22 characteristic peaks in the plasma of kidney-deficiency rats, and 12 chemical components were identified, including 2 iridoids, 6 alkaloids, 2 flavonoids, 1 monoterpenoid and 1 triterpenoid saponin. Verbascoside, isoacteoside, acteoside, pinoresinoldiglucoside, loganin and morroniside were identified by MRM both in the plasma of normal rats and kidney-deficiency rats. Compared with 85 monomer components in Yougui Yin, 17 common prototype components were found by UPLC-MS in the plasma of normal rats and kidney deficiency rats, including verbascoside, isoacteoside, acteoside, rehmapicrogenin derived from Rehmanniae Radix Praeparata, pinoresinol diglucoside and geniposidic acid from Eucommiea Cortex, loganin and morroniside derived from Corni Fructus, mesaconine, benzoylmesaconine, benzoylaconitine, benzoylhypacoitine, mesaconitine, aconitine derived from Aconiti Lateralis Radix Praeparata, liquiritin, isoliquiritin and glycyrrhizic acid derived from Glycyrrhizae Radix et Rhizoma. Thirty-one metabolites of medicinal ingredients not found in the plasma of adenine-induced kidney deficiency rats were also detected in the plasma of normal rats. Twelve metabolites of medicinal materials not found in the plasma of normal rats were detected in the plasma of kidney deficiency rats. The results of the study provide reference for explaining the material basis and mechanism of Yougui Yin in the treatment of kidney deficiency.

Changes of EPO in rats with chronic renal failure and low immunity and reversal effects of Yougui Yin and exogenous EPO / 中国中药杂志

The aim of this paper was to observe the changes of EPO in rats with chronic renal failure and low immunity induced by adenine and to investigate the reversal effect of Yougui Yin(YGY)and exogenous EPO.SD rats were randomly divided into normal control group(n=20)and adenine-model group(n=90).The adenine-model group rats were given with adenine 150 mg·kg~(-1)for 14days by gavage administration,and then randomly divided into 8 groups as follows:model group(n=20),YGY groups(10,20,40 g·kg~(-1),10 in each group),rh EPO group(500,1 000,1 500 IU·kg~(-1),10 in each group),and Guilu Erxian Gao 10 g·kg~(-1)group(positive control group,n=10).From the 15th day,every group except normal control group received 150 mg·kg~(-1)adenine by gavage administration once every two days to maintain the model.Meanwhile,the rats in each YGY group and Guilu Erxian Gao group received corresponding drugs by gavage administration once a day for 30 days.The rats in rh EPO groups were subcutaneously injected with rh E-PO once every 3 days for 30 days.On day 46,rats were anesthetized to take blood and then sacrificed.The serum levels of creatinine,urea,glandular hormone,immunoglobulin,complement and interleukin,the proportion of T cells in the spleen,the killing rate of NKcells and the proliferative capacity of spleen cells were measured.Western blot was used to detect the key proteins in JAK2-STAT5 and NF-κB pathways mediated by EPO in kidney and spleen.As compared with the normal control group,the serum levels of CREA and UREA were increased significantly and the serum levels of ACTH,T and T3 were decreased significantly in the model group rats,indicating that the functions of kidney,adrenal gland,gonad and thyroid in rats were decreased.At the same time,the serum levels of Ig A,Ig G,Ig M,C3,C4,IL-2 and IL-6 were significantly decreased,the proportion of CD4~+,CD4~+/CD8~+T cell subsets,the killing rate of NK cell and the proliferation ability of spleen lymphocyte in spleen of the model group rats were significantly declined,indicating that the immune function of model group rats was decreased,and the model of kidney deficiency immunodeficiency was successfully constructed.As compared with the model group,both YGY and rh EPO significantly reduced serum levels of CREA and UREA,significantly increased serum levels of ACTH,T,T3,T4,Ig A,Ig G,Ig M,C3,C4,IL-2,and IL-6,increased the proportion of CD4~+,CD4~+/CD8~+T cell subsets,the killing rate of NK cell and the proliferation ability of spleen lymphocyte in spleen.YGY could significantly increase the content of EPO in serum.Both YGY and rh EPO could regulate the expression of EPOR,p-JAK2/JAK2,STAT5,NF-κB p50,NF-κB p65 and NF-κB IκB of EPO-mediated JAK2-STAT5 and NF-κB pathways in kidney and spleen.EPO is an important factor in the chronic renal failure and low immunity induced by adenine in rats.Exogenous EPO and YGY have significant reversal effects for the model rats.The mechanism of YGY may be related to the up-regulation of EPO in serum and regulating the expression of key proteins in EPO-mediated JAK2-STAT5 and NF-κB pathways in kidney and spleen.The mechanism of exogenous EPO may be related to regulating the expression of the key proteins in EPO-mediated JAK2-STAT5 and NF-κB pathways in kidney and spleen.

Changes of differentiation and proliferation of neural stem cells in rats treated with corticosterone / 第三军医大学学报

Objective To explore the changes of differentiation and proliferation of neural stem cells in rats treated with corticosterone (CORT). Methods Adult SD rats were administered with CORT (10 mg?kg -1 ?d -1 ) by consecutive subcutaneous injection for 14 days. Single and double immunohistochemical stainings were used to identify the neural stem cells and differentiated neural cells in adult rats. Results Compared with that in the normal control group, the number of BrdU immunohistofluorescence positive cells and BrdU+NF200, BrdU+NeuroD, BrdU+GFAP double immunostaining positive cells in the cerebral cortex, hippocampus, and hypothalamus were markedly decreased ( P

Effect of Sijunzi Tang and Yougui Yin on Learning-Memory Ability and Free Radicals in Aging Rat Model / 中药新药与临床药理

Objective To compare the effect of Sijunzi Tang and Yougui Yin on learning-memory ability and free radicals in aging rat model.Methods The aging rat model was induced by intraperitoneal injection of D-galactose.The swimming time and error times in water maze test were observed and the free radicals SOD,MDA,NO,NOS in rat brain tissue were measured.Results Sijunzi Tang could shorten the rat swimming time in water maze test.Yougui Yin could increase SOD level and decrease MDA level in brain tissue of model rat,while Sijunzi Tang could decrease NO and NOS level.Conclusion Sijunzi Tang could improve the rat spatial learning and memory ability,and Yougui Yin could relieve the damage of free radical in brain tissue of the aging rat model.