Effect of Shenqi Pills （肾气丸） on Cognitive Function and Hippocampal Glucose Energy Metabolism in Type 2 Diabetes Mellitus Model Mice / 中医杂志

ObjectiveTo explore the effect and possible mechanism of Shenqi Pills （肾气丸） on cognitive impairment and hippocampal glucose energy metabolism in type 2 diabetes mellitus （T2DM）. MethodsSixty C57BL/6 mice were randomly divided into control group， model group， rosiglitazone group and Shenqi Pills low-， medium- and high-dose groups， with 10 mice in each group. T2DM model was induced by a high-fat diet combined with intraperitoneal injection of streptozotocin in all the groups except for the control group. After successful modeling， the high-， medium-， and low-dose Shenqi Pills groups were given 2.08， 1.04， and 0.52 g/（kg·d） of Shenqi Pills granules by gavage respectively， while the rosiglitazone group was given 3 mg/（kg·d） of rosiglitazone tablets by gavage， and the control group and model group were gavaged with 10 ml/（kg·d） of distilled water， all for 8 consecutive weeks. The body weight and fasting blood glucose （FBG） level were recorded every two weeks. The Morris water maze test was performed on the 8th week of medication. After 8-week medication， oral glucose tolerance test （OGTT） and fasting insulin level were measured， hippocampal glucose energy metabolism-related products were quantitatively detected by liquid chromatography tandem mass spectrometry， and KEGG annotation analysis was performed. ResultsCompared to those measured at the same timepoints in the control group， the body mass on week 6 and 8， as well as the FBG level on week 2， 4， 6 and 8 in the model group increased； the blood glucose level at 0， 30， 60 and 120 minutes of the OGTT test increased， while fasting insulin level after 8-week medication decreased. The escape latency of the model group was significantly prolonged on the 3rd and 4th days， and the escape latency time increased， while the total swimming distance， platform quadrant residence time and the number of platform crossings decreased （P＜0.05 or P＜0.01）. Compared to those measured at the same timepoints in the model group， the body mass on week 6 in the low-dose Shenqi Pills group， on week 6 and 8 in the medium- and high-dose groups， and on week 8 in the rosiglitazone group were significantly reduced； the FBG levels in all the Shenqi Pills groups and rosiglitazone group on week 6 and 8 decreased， while fasting insulin levels increased. In the OGTT test， blood glucose in the medium-dose group of Shenqi Pills at all timepoints decreased； in the Morris water maze test， the escape latency period of the medium- and high-dose Shenqi Pills groups was shortened on the 3rd and 4th days， while the escape latency time was reduced， and the total swimming distance， platform quadrant residence time， and number of platform crossings increased in the medium-dose Shenqi Pills group （P＜0.05 or P＜0.01）.The medium-dose Shenqi Pills showed best effect， therefore it was selected for the targeted quantitative detection of metabolites. The medium-dose Shenqi Pills group could regulate the disorder of glucose metabolism in the hippocampus of T2DM mice， and 13 differential metabolites were found，up-regulating α-ketoglutarate and 3-phosphoglyceric acid， and down-regulating fumaric acid， glutamatic acid， lactatic acid， inosine， malic acid， adenine， fructose 1,6-diphosphate and others. KEGG annotation of differential metabolites suggested that Shenqi Pills was closely related to the regulation of glucose metabolism disorder and insulin resistance in the hippocampus region of T2DM model mice， as well as neurodegenerative diseases and ABC transport， hypoxia-inducible factor 1 （HIF）， forkhead transcription factor （FoXO） and cyclic adenosine monophosphate （cAMP） signaling pathways. ConclusionShenqi Pills can improve learning and memory abilities and cognitive impairment in T2DM mice， and may act its role by regulating glucose energy metabolism in the hippocampus of T2DM.

Connotation of Shenqi Pills based on severe cases in cardiovascular care unit and modern pathophysiological mechanism and application of Shenqi Pills for heart failure, renal failure, cardiorenal syndrome, and diuretic resistance in critical care medicine / 中国中药杂志

Shenqi Pills, first recorded in Essentials from the Golden Cabinet(Jin Kui Yao Lue) from ZHANG Zhong-jing in Han dynasty, have the effect of warming and tonifying the kidney Qi and are mainly used for the treatment of insufficiency of kidney Qi and kidney Yang. According to modern medicine, kidney Qi involves heart function, kidney function, immune function, and so on. The clinical indications of Shenqi Pills include kidney deficiency, abnormal fluid, and abnormal urination, and the last one is classified into little urine, much urine, and dysuria. In clinical settings, Shenqi Pills can be applied for the treatment of heart failure, renal failure, cardiorenal syndrome, and diuretic resistance, as well as endocrine, urological, orthopedic, and other chronic degenerative diseases. Shenqi Pills are ideal prescriptions for the weak constitution and emergency treatment. It is of great value and significance to carry out in-depth research on the connotation of the classic articles by integrating TCM and western medicine based on "pathogenesis combined with pathology and drug properties combined with pharmacology".

Inhibitory Effect of Jinkui Shenqi Pills on Glucocorticoid-Enhanced Axial Length Elongation in Experimentally Myopic Guinea Pigs / 中国结合医学杂志

OBJECTIVE@#To explore the underlying mechanism of inhibition by Jinkui Shenqi Pills (JKSQP) on glucocorticoid-enhanced axial length elongation in experimental lens-induced myopia (LIM) guinea pigs.@*METHODS@#Sixty 2-week old male guinea pigs were randomly divided into 4 groups with 15 guinea pigs in each group, according to the random numbers generated by SPSS software: control, LIM, saline and JKSQP groups. The control group includes animals with no treatment, while the guinea pigs in the other 3 groups received lens-induced myopization on the right eyes throughout the experiment (for 8 weeks). The saline and JKSQP groups were given daily intraperitoneal injections of 10 mg/kg hydrocortisone for 2 consecutive weeks at the same time, and then orally administered either saline or JKSQP [13.5 g/(kg•d) for 6 consecutive weeks. Body weight, anal temperature and animal appearance were observed and recorded to evaluate the GC-associated symptoms. The ocular parameters, including refraction and axial length, were measured by streak retinoscopy and A-scan ultrasonography, respectively. The levels of plasma hormones associated with the hypothalamic-pituitary-adrenal axis (HPAA), including free triiodothyronine, free thyroxine, estradiol and testosterone, were measured by radioimmunoassay, and cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate were measured by enzyme-linked immunosorbent assay. In addition, the mRNA and protein expressions of retinal amphiregulin (AREG) was measured by quantitative real-time polymerase chain reaction and Western blotting, respectively.@*RESULTS@#JKSQP effectively increased body weight and anal temperature, improved animal appearance and suppressed axial length elongation in glucocorticoid-enhanced myopic guinea pigs with normalization of 4 HPAA-associated plasma hormones (all P<0.05). The plasma level of cAMP was significantly increased, whereas the plasma level of cGMP and the mRNA and protein expressions of retinal AREG were decreased after treatment with JKSQP (all P<0.05).@*CONCLUSION@#JKSQP exhibited a significant inhibitory effect on axial length elongation with decreased expression of AREG in the retina, and normalized 4 HPAA-associated plasma hormones and the expression of cAMP and cGMP in GC-enhanced myopic guinea pigs.

Intervention effects of Jinkui shenqi pills on renal fibrosis model rats and its mechanism / 中国药房

OBJECTIVE To investigate th e intervention effect of Jinkui shenqi pills on renal fibrosis （RF）model rats and its mechanism based on transforming growth factor β1/Smads（TGF-β1/Smads）and TGF-β1/extracellular signal regulated kinase （ERK） signaling pathway. METHODS Male SD rats were given adenine suspension （250 mg/kg）to induce RF model. After modeling ， they were randomly divided into model group ，Colchicine tablet group （positive control ，0.45 mg/kg）and Jinkui shenqi pills low-dose，medium-dose and high-dose groups （0.5，1，2 g/kg），with 10 rats in each group. Other 10 healthy rats were selected as normal group. The rats in administration groups were given the corresponding drugs intragastrically ；normal group and model group were given 0.1％ sodium carboxymethyl cellulose solution ，once a day ，for consecutive 30 d. After last medication ，the serum levels of creatinine （Cr）and blood urea nitrogen （BUN），renal weight and body weight were detected. The ratio of BUN/Cr and renal coefficient were calculated. The pathological morphology of renal tissue in rats were observed. The protein and mRNA expressions of TGF-β1，Smad2，Smad3，ERK1 and ERK 2 were detected. RESULTS Compared with normal group ，serum levels of Cr and BUN and renal coefficient were all increased significantly in model group （P＜0.05），while the ratio of BUN/Cr was decreased significantly （P＜0.05）. The volume of the kidney was significantly increased ，and the surface was seriously granulated. Mesangial hyperplasia ，dilation or atrophy of renal tubules ，accompanied by large-area collagen deposition，could be found. Protein and mRNA expressions of TGF-β 1，Smad2，Smad3，ERK1 and ERK 2 were increased significantly in renal tissue （P＜0.05）. Compared with model group ，above indexes of Jinkui shenqi pills groups were all reversed significantly （P＜0.05）；dilation or atrophy of renal tubules was relieved ，and collagen deposition was reduced to different extents. CONCLUSIONS Jinkui shenqi pills can improve renal function of RF model rats ，the mechanism of which may be associated with inhibiting TGF-β1/Smads and TGF-β1/ERK signaling pathway.

Comparative proteomic profiling of hippocampi in mice treated with Jingui Shenqi Pills and Liuwei Dihuang Pills / 中国中药杂志

The effects of Jingui Shenqi Pills(Jingui) and Liuwei Dihuang Pills(Liuwei) which respectively tonify kidney Yang and kidney Yin on brain function have attracted great attention, while the differences of protein expression regulated by Jingui and Liuwei remain to be studied. This study explored the difference of protein expression profiles in the hippocampi of mice orally administrated with the two drugs for 7 days. The protein expression was quantified using LC-MS/MS. The results showed that among the 5 860 proteins tested, 151, 282 and 75 proteins responded to Jingui alone, Liuwei alone, and both drugs, respectively. The ratio of up-regulated proteins to down-regulated proteins was 1.627 in Jingui group while only 0.56 in Liuwei group. The proteins up-regulated by Jingui were mainly involved in membrane transport, synaptic vesicle cycle, serotonergic synapse, dopaminergic synapse and so on, suggesting that Jingui may play a role in promoting the transport of neurotransmitter in the nervous system. The proteins down-regulated by Liuwei were mainly involved in membrane transport, synapse, ion transport(potassium and sodium transport), neurotransmitter transport, innate and acquired immune responses, complement activation, inflammatory response, etc. In particular, Liuwei showed obvious down-regulation effect on the members of solute carrier(SLC) superfamily, which suggested that Liuwei had potential inhibitory effect on membrane excitation and transport. Finally, consistent results were obtained in the normal mouse and the mouse model with corticosterone-induced depressive-like behavior. This study provides an experimental basis for understanding the effect of Jingui and Liuwei on brain function from protein network.

Mechanism of anti-diabetes of Shenqi Pills based on network pharmacology / 中草药

Objective: The active ingredients and core targets of Shenqi Pills were screened using network pharmacology to explore the underlying mechanism of Shenqi Pills with anti-diabetic activity. Methods: The active compounds and targets of Shenqi Pills were obtained by literature, TCMSP database, Swiss Target Prediction database, and TTD database. Then the target dataset was established, OMIM database and DrugBank database were used to screen the diabetes-related targets, and the interactive target of Shenqi Pills and diabetes was constructed using PPI database. In addition, the “component-target-disease” interactive network map was constructed by Cytoscape software. The target gene function and signaling pathway were analyzed by ClueGO and the molecules and core targets were docked using Autodock software. Results: The results showed that 100 active constituents of Shenqi Pills were screened. Network analysis indicated that the active components of Shenqi Pills involved 58 targets, including low-density lipoprotein receptor-related protein 6, insulin receptor substrate 1, SHC-transforming protein 1, etc. Targets were involved in biological processes such as transcription, apoptosis, cell proliferation, and insulin receptors. Shenqi Pills had anti-diabetic activity by regulating many signaling pathways such as insulin resistance, TNF signaling pathway, type II diabetes mellitus, and insulin signaling pathway. Conclusion: This study demonstrates the characteristics of Shenqi Pills with multi-component-multi-target-multi-pathway to treat diabetes, and provides new ideas and targets for further research on the anti-diabetic activity and the underlying mechanism of Shenqi Pills.

Correlation between In Vitro and In Vivo Metabolism of Total Glycosides of Jinkui Shenqi Pills Based on HPLC-ESI/MSn Technique / 中国药学杂志

OBJECTIVE: To study the metabolic differences of the effective fractions of total glycosides of Jinkui Shenqi Pills in liver homogenate and blood by high performance liquid chromatography-electrospray ion trap mass spectrometry (HPLC-ESI/MSn). METHODS: The in vitro metabolism of the glycosides was studied using rat liver homogenate and the in vivo metabolism was investigated in rats. The metabolites were detected by HPLC-ESI/MS/MS. According to the molecular ion peak in negative ion mode, the molecular weight information of the compound was obtained. RESULTS: A total of 13 chemical components were detected in the rat liver homogenate after incubation for 20 min. Eight prototype components were detected in both liver homogenate and plasma while pentagalloylglucose was only found in the liver homogenate. A total of nine metabolites were detected in plasma, and only four metabolites were found in the liver, which were shared by those in plasma. CONCLUSION: The four common metabolites are produced through liver metabolism of the total glycosides. The RESULTS of this study have important implications for revealing the metabolic mechanisms of the total glycoside constituents in vitro and in vivo.

Systematic Review of Jinkui Shenqi Pills on Hypertension / 中国中医药信息杂志

Objective To evaluate the efficacy and safety of Jinkui Shenqi Pills on hypertension through Meta-analysis and systematic review. Methods Articles about intervention of modified Jinkui Shenqi Pills in hypertensive clinical randomized controlled trials were retrieved from CNKI, Wanfang database, VIP, Cochrane Library, PubMed, and Embase. They were all searched from inception to June 2016. Cochrane system evaluation manual bias risk assessment method was used to evaluate the quality of the articles, and RevMan5.3 software was used for Meta-analysis. Results Nine articles involving 776 cases were included in the study. Meta-analysis showed that the total effective rate of modified Jinkui Shenqi Pills was better than that of conventional Western medicine treatment [OR=2.67, 95%CI (1.73, 4.11), P＜0.000 01], and combination therapy was superior to conventional Western medicine alone [OR=3.27, 95%CI (1.99, 5.39), P＜0.000 01]. However, the efficacy of modified Jinkui Shenqi Pills alone was equivalent to the conventional Western medicine alone [OR=1.16, 95%CI (0.43, 3.09), P=0.77). Conclusion Modified Jinkui Shenqi Pills can improve the clinical symptoms of the patients with hypertension, and combination treatment can improve the antihypertensive effect. However, the quality of the included research literature is too low, yet more large-scale, multi-center, high-quality clinical randomized controlled trials are needed to further verify.

Fingerprint chromatograms and characteristic peaks of Jisheng Shenqi Pills by HPLC / 国际药学研究杂志

Objective: To establish the chromatogrphic fingerprint of Jisheng Shenqi Pills by HPLC method for evaluating the quality of the preparation. Methods: The mobile phase was acetonitrile-0.3% acetic acid solution in a gradient elution mode.The flow rate was 1.0 ml/min and the UV detection wavelength was 240 nm. The similarity of 7 batches of samples was evaluated by using Similarity Calculation Software of TCM Chromatogrphic Fingerprint (2004A edition). Results: Nine common peaks were identified in 7 batches of samples and found belonging to their single medicinal material. The similarity of fingerprint was all higher than 0.797. Conclusion: The method is simple and accurate, reproducible for quality control of the preparation.

Effects ofJingui Shenqi Pills on Expressions of Testicular TGF-β1 and CYP19 in Kidney-yang-deficiency Rats / 中国中医药信息杂志

Objective To observe the effects ofJingui Shenqi Pills on the expressions of TGF-β1, CYP19, sex hormone level and sperm quality;To discuss its mechanism for the treatment of male sterility.Methods Forty adult male SD rats were randomly divided into normal group, model group, retardant group andJingui Shenqi Pills group, 10 rats in each group. Except for the normal group, adenine was used to induce healthy rats to kidney yang deficiency and sterility model rats. Normal group was given normal saline for gavage;retardant group was injected with testicular mesenchyme TGF-β1;Jingui Shenqi Pills group was givenJingui Shenqi Decoction for gavage. Blood was taken through caudal vein. Immunohistochemical, radioimmunoassay and electron microscopy observation were used to detect the expressions of TGF-β1, CYP19, sex hormone level, sperm density and motility rate and testicular morphological changes.Results Compared with normal group, the expression of TGF-β1 in the model group increased and CYP19 decreased (P<0.05). Compared with model group, the expression of TGF-β1 decreased and the expression of CYP19 increased (P<0.05). Compared with normal group, the number of sperm quantity was small and paramorphia in model group (P<0.05). Compared with model group, T, E2, sperm density and motility rate increased significantly inJingui Shenqi Pills group and retardant group (P<0.05). There was no statistical significance among indexes in retardant group andJingui Shenqi Pills group.ConclusionJingui Shenqi Pills can improve sperm quality and sex hormone level of model rats with kidney-yang-deficiency, which mechanism is probably realized by inhibiting the expression of TGF-β1R and promoting the expression of CYP19 in testis to effect development and proliferation of sperm.

Observation of the clinical effects of modified treatment with sijunzi decoction and shenqi pills for primary hypothyroidism / 中国基层医药

Objective To observe the clinical curative effect of sijunzi decoction composite with shenqi pills in the treatment of spleen and kidney yang deficiency syndrome in patients with primary hypothyroidism(hypothyroid-ism).Methods 62 spleen kidney yang deficiency patients with hypothyroidism were randomly divided into 30 cases in the control group and 32 cases in the treatment group.Patients in the control group were given L-thyroxine tablets orally,once a day;patients in the treatment group were given sijunzi decoction combined with shenqi pills for decoc-tion,daily 1 agent,3 times a day orally,on the basis of the control treatment group.Two groups treatment cycle were 4 months,and the clinical efficacy of the two groups were observed.Results The treatment group total effective rate was 96.9%,which was higher than that in the control group 80.0%(χ2 =4.402,P<0.05);before and after treat-ment,TCMsyndrome scores were significantly decreased in the two groups (t=21.40,25.40,all P<0.01)and treatment group decreased more significantly(t=4.30,P<0.01 ).Before and after treatment,TSH,FT3,FT4 in the two groups were significantly improved (control group:t=5.31,1.14,4.13,treatment group:t=6.27,1.85,6.08,all P<0.01),and the degree of improvement in treatment group was more obvious compared with the control group (t=1.33,0.67,278,all P<0.05).Conclusion Sijunzi decoction and shenqi pills can significantly improve the clinical symptoms of primary hypothyroidism of spleen-kidney yang deficiency type in addition to thyroid function and blood lipid,indicating that this method is capable of achieving satisfactory clinical effects in treating primary hypothyroidism of spleen-kidney yang deficiency type.

Fingerprint chromatograms and characteristic peaks of Jisheng Shenqi Pills by HPLC / 国际药学研究杂志

Objective To establ ish the chromatogrphic fingerprint of Jisheng Shenqi Pills by HPLC method for evaluating the quality of the preparation. Methods The mobile phase was acetonitrile-0.3%acetic acid solution in a gradient elution mode.The flow rate was 1.0 ml/min and the UV detection wavelength was 240 nm. The similarity of 7 batches of samples was evaluated by using Similarity Calculation Software of TCM Chromatogrphic Fingerprint (2004A edition). Results Nine common peaks were identified in 7 batches of samples and found belonging to their single medicinal material. The similarity of fingerprint was all higher than 0.797. Conclusion The method is simple and accurate,reproducible for quality control of the preparation.

Research on Shenqi Pills in treating miscellaneous diseases / 中华中医药杂志

Shenqi Pills is a formula used to reinforce kidney yin and kidney yang and harmonize yin and yang, and also works toward strengthening the bones and the muscle and transforming qi and activating water. It also enhances metabolic activity. Thus, Shenqi Pills is known to be effective on any kind of kidney deficiency regardless of the patient's age or sex, and they are effective even when taken without a personal prescription. Not only is Shenqi Pills effective on pain in the lower back due to kidney deficiency,it is also effective for diabetes mellitus, hypertension, osteoporosis, lubar intervertebral disc protrusion, cervical vertebral-related disorders, ankylosing myelitis, and even menopausal disorders in the gynecology area.

Effects of different TCM prescriptions of JinKuiYaoLve on the levels of Noradrenaline(NE),Dopamine(DA) and 5-hydroxytryptamine(5-HT) in lung and brain tissues of pulmonary fibrosis in the early stages / 中华中医药杂志

Objective:To observe the effect of different TCM prescriptions of JinKuiYaoLve on levels of noradrenaline(NE), dopamine(DA) and 5-hydroxytryptamine(5-HT) in lung and brain tissues of pulmonary fibrosis in the early stages. To investigate the effect and mechanism of TCM prescriptions and the nature of prescription-syndrome. Methods: The wistar rats were divided into groups randomly. Pulmonary fibrosis was induced by bleomycin A5 in all groups except normal group. Rats in drug group were killed after 7 days' treatment. The levels of NE, DA and 5-HT in the lung and brain tissues were detected. Results: The level of NE in the lung tissue of model group was higher than that of normal group, Gualouxiebai decoction(GLXB) group and prednisone group. The level of 5-HT of model group was lower than that of Shenqi Pills(SQW) group and prednisone group. The level of DA of SQW group was lower than that of GLXB group. The level of NE in the brain tissue of model group was higher than that of normal group, but the level of DA was lower than that of normal group, GLXB group and Maimendong decoction(MMD) group. The level of 5-HT of Dahuangzhechong pills (DHZCW) group was higher than that of other groups(P