Combination of Fushengong decoction with Western medicine on patients with chronic renal failure: An observational study.

Chronic renal failure (CRF) causes a reduction in glomerular filtration rate and damage to renal parenchyma. Fushengong decoction (FSGD) showed improvement in renal function in CRF rats. This study aims to analyze the differentially expressed proteins in CRF patients treated with Western medicine alone or in combination with FSGD. Sixty patients with CRF recruited from Yongchuan Traditional Chinese Medicine Hospital affiliated to Chongqing Medical University were randomly assigned into control (treated with Western medicine alone) and observation groups (received additional FSGD treatment thrice daily for 8 weeks). The clinical efficacy and changes in serum Bun, serum creatinine, Cystatin C, and transforming growth factor beta 1 (TGF-ß1) before and after treatment were observed. We employed isotope relative labeling absolute quantification labeling and liquid chromatography-mass spectrometry to identify differentially expressed proteins and carried out bioinformatics Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Patients in the observation group showed greater clinical improvement and lower levels of serum Bun, serum creatinine, Cyc-c, and TGF-ß1 than the control group. We identified 32 differentially up-regulated and 52 down-regulated proteins in the observation group. These proteins are involved in the blood coagulation system, protein serine/threonine kinase activity, and TGF-ß, which are closely related to the pathogenesis of CRF. Protein-protein-interaction network analysis indicated that candidate proteins fibronectin 1, fibrinogen alpha chain, vitronectin, and Serpin Family C Member 1 were in the key nodes. This study provided an experimental basis suggesting that FSGD combined with Western medicine could significantly improve renal function and renal fibrosis of CRF patients, which may be through the regulation of fibronectin 1, fibrinogen alpha chain, vitronectin, Serpin Family C Member 1, TGF-ß, and the complement coagulation pathway (see Graphical abstract S1, Supplemental Digital Content, http://links.lww.com/MD/L947).

Metabolomics combined with network pharmacology to explore the mechanisms of modified Guishen pill to ameliorate polycystic ovary syndrome.

BACKGROUND: The modified Guishen pill (MGP) has a prominent therapeutic effect on polycystic ovary syndrome (PCOS). However, its mechanism is still unclear. This study aimed to uncover the mechanism of MGP for PCOS treatment through a comprehensive strategy integrating metabolomics and network pharmacology. METHODS: A letrozole-induced PCOS model was used to evaluate ovarian function in rats. Plasma metabolomics was used to authenticate differential metabolites and enriched related pathways using the MetaboAnalyst platform. Network pharmacology was utilized to explore the endogenous targets of MGP treatment for PCOS. Finally, the potential targets and related biological functions were verified experimentally. RESULTS: MGP improved PCOS symptoms by regulating abnormal levels of sex hormones and alleviating ovarian pathological changes in rats; fifty-four potential differential metabolites involved in MGP treatment for PCOS, and the hub genes derived from network pharmacology were consistent with the metabolomic analysis results to varying degrees. The comprehensive analysis identified that a key novel target for endothelial nitric oxide synthase (eNOS/NOS3), five key metabolites (ornithine, citrulline, l-glutamic acid, acetylornithine, and hydroxyproline), and one pathway (arginine and proline metabolism) were related to the therapy of PCOS with MGP. Subsequently, we verified the localization and expression of eNOS in the ovaries, and it significantly improved insulin resistance, apoptosis, and oxidative stress in letrozole-induced PCOS rats. CONCLUSION: Our work reveals the complex mechanism of MGP therapy for PCOS. This study is a successful paradigm for elucidating the pharmacological mechanism of the traditional Chinese medicine compound.

Effect of Fushengong Decoction on PTEN/PI3K/AKT/NF-κB Pathway in Rats With Chronic Renal Failure via Dual-Dimension Network Pharmacology Strategy.

Overview: The treatment of chronic renal failure (CRF) with traditional Chinese medicine has attracted much attention, but its mechanism is not clear. Network pharmacology is an effective strategy for exploring the interaction mechanisms between Chinese herbs and diseases, however, it still needs to be validated in cell and/or animal experiments due to its virtual screening characteristics. Herein, the anti-CRF mechanism of the Fushengong decoction (FSGD) was investigated using a dual-dimension network pharmacological strategy combined with in vivo experiment. Methods: The traditional Chinese medicine systems pharmacology (TCMSP) database (https://tcmspw.com) and UHPLC-MS/MS technology were used to identify the effective compounds of FSGD in theory and practice, such as quercetin, formononetin, and pachymic acid. The putative targets of FSGD and CRF were obtained from the Swisstarget prediction platform and the Genecards database, respectively. The common target pathways between FSGD and CRF were got from the dual-dimension network pharmacology analysis, which integrated the cross-common targets from the TCMSP components-Swisstarget-Genecards-Venn platform analysis in theory, and the UHPLC-MS/MS identified effective ingredients-Swisstarget screening, such as TNF and PI3K/AKT. Furthermore, system molecular determinations were used to prove the dual-dimension network pharmacology study through CRF rat models, which were constructed using adenine and treated with FSGD for 4 weeks. Results: A total of 121 and 9 effective compounds were obtained from the TCMSP database and UHPLC-MS/MS, respectively. After dual-dimension network pharmacology analysis, the possible mechanism of PTEN/PI3K/AKT/NF-κB pathway was found for FSGD in CRF. In vivo experiments indicated that FSGD can play a role in protecting renal function and reducing fibrosis by regulating the PTEN/PI3K/AKT/NF-κB pathway. These findings provide a reference for FSGD in CRF. Conclusion: Based on the theoretical and practical dual-dimension network pharmacology analysis for FSGD in CRF, the possible molecular mechanism of PTEN/PI3K/AKT/NF-κB was successfully predicted, and these results were verified by in vivo experiments. In this study, the dual-dimension network pharmacology was used to interpret the key signal pathway for FSGD in CRF, which also proved to be a smart strategy for the study of effective substances and pharmacology in FSGD.

iTRAQ-Based Proteomics of Chronic Renal Failure Rats after FuShengong Decoction Treatment Reveals Haptoglobin and Alpha-1-Antitrypsin as Potential Biomarkers.

Background. Chronic renal failure (CRF) has become a global health problem and bears a huge economic burden. FuShengong Decoction (FSGD) as traditional Chinese medicine has multiple pharmacological effects. Objectives. To understand the underlying molecular mechanism and signaling pathway involved in the FSGD treatment of CRF and screen differentially expressed proteins in rats with CRF treated with FSGD. Methods. Thirty-three male Sprague-Dawley rats were randomly divided into control group, CRF group, and FSGD group. Differentially expressed proteins were screened by iTRAQ coupled with nanoLC-MS/MS, and these identified proteins were later analyzed by GO, KEGG, and STRING. Additionally, haptoglobin (HP) and alpha-1-antitrypsin (AAT) were finally verified by ELISA, Western blot, and real time PCR. Results. A total of 417 proteins were identified. Nineteen differentially expressed proteins were identified in the FSGD group compared with the model group, of which 3 proteins were upregulated and 16 proteins were downregulated. Cluster analysis indicated that inflammatory response was associated with these proteins and complement and coagulation cascade pathways were predominantly involved. The validation methods further confirmed that the levels of HP and AAT were significantly increased. Conclusions. HP and AAT may be the important biomarkers in the pathogenesis of CRF and FSGD therapy.

[Effect of Fushengong Decoction on the Expression of Nephrin mRNA in Kidney of Rats with Chronic Renal Failure].

OBJECTIVE: To investigate the effect of Fushengong Decoction on the expression of nephrin mRNA in renal tissue of rats with chronic renal failure (CRF). METHODS: Fifty five male SD rats were randomly divided into five groups: control group, CRF model group, and low, medium and high Fushengong Decoction dose groups. Rats in control group were fed with standard chow, while the other four groups were fed with adenine to make CRF. The rats in control group received intra-gastric normal saline (NS) of 20 mL/(kg · d) for 30 d, while those in low, medium and high Fushengong Decoction dose groups received Fushengong Decoction at the dose of 4 g/kg, 8 g/kg and 16 g/kg respectively, once a day for 30 d. After that, 24 h urinary protein in urine was measured, blood urea nitrogen (BUN) and serum creatinine (SCr) were detected. Histomorphology of glomerulus were studied by HE staining, and the expression of nephrin were detected by immunohistochemistry and RT-PCR. RESULTS: Compared to the control group, the levels of 24 h urinary protein, BUN and SCr increased significantly (P < 0.05) and the expression of nephrin protein and mRNA decreased significantly (P < 0.05) in CRF model group. The renal interstitium showed fibrotic lesions in model group. The levels of 24 h urinary protein, BUN and SCr decreased significantly after the treatment of Fushengong Decoction (P < 0.05), while the expression of nephrin protein and mRNA increased significantly (P < 0.05). CONCLUSION: Fushengong Decoction could reduce urinary protein and relieve renal damage in rats with CRF by improving the expression of nephrin and reducing the injury of podocytes.

[Effects of electro-acupuncture on expression of triggering receptor expressed on myeloid cells 1 in ankle joint synovial tissue of acute gouty arthritis rats].

OBJECTIVE: To investigate the effects of electro-acupuncture (EA) on the expression of triggering receptor expressed on myeloid cell (TREM)l in ankle joint synovial tissue of acute gouty arthritis (AGA) rats. METHODS: Forty male SD rats were randomly divided into 4 groups: normal, AGA, medication and EA group, 10 rats in each group. AGA model was established by induced monosodium urate (MSU) method, except the normal group. Tow days before AGA model was established, normal and AGA groups were lavaged with normal saline (20 ml/kg), medication group was lavaged with colchicine solution (20 ml/kg), EA(1.5-2 Hz, D.-D.wave, 9v; 1-3 rnA) was applied to "Sanyinjiao" (SP6), "jiexi" (ST41) and "Kunlun" (BL60) for 20 min, once daily;continuously for 9 days. Then observed the changes in dysfunction, and the content of TNF-α and IL-lß detected by ELISA, the expression of TREM-l detected by immunohistochemistry and western blot. RESULTS: Compared to the normal group, the AGA group of the dysfunction index increased significantly (P<0.01), the content of TNF-α and IL-lß increased significantly (P<0.05), the expression of TREM-l in synovial tissue increased significantly (P<0.05); the medication and EA groups compared to the AGA group, the dysfunction index decreased significantly (P<0.01), the content of TNF-α and IL-lß decreased significantly (P<0.05), the expression of TREM-l in synovial tissue decreased significantly (P<0.05); there were not statistically significant between the medication and EA group (P>0.05). CONCLUSION: EA treating AGA may be through down-regulating the expression of TREM -1 in synovial tissue.

[Effect of electroacupuncture intervention on renal function and expression of renal beta-catenin in rats with chronic renal failure].

OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention on renal function and expression of renal beta-catenin in rats with chronic renal failure (CRF), so as to reveal its mechanism underlying improvement of CRF. METHODS: Male SD rats were randomly divided into normal, model and EA groups, with 10 rats in each group. CRF model was induced by feeding the rats with 0.5% Adenine(100 mg/d, in forage) for 21 days. EA (1-3 mA, 1.5-2 Hz) was applied to bilateral "San-yinjiao" (SP 6), "Taixi" (KI 3) and "Shenshu" (BL 23) for 20 min, once daily for 30 days. Serum creatinine (Scr) and blood urine nitrogen (BUN) contents were assayed by enzymatic method and deoxy enzymatic method, respectively, and the expression of p-catenin protein in the renal tissue was determined by Western blot. RESULTS: Following modeling, serum Scr and BUN contents and renal p-catenin protein expression level were significantly increased in the model group in comparison with those of the normal group (P<0.05). After EA intervention, serum Scr and BUN contents and the expression of beta-catenin in the renal tissue were all significantly decreased in the EA group compared to the model group (P<0.05). In addition, the animals' body weight values of both model and EA groups were apparently lower than those of the normal group before EA treatment (P<0.05). After EA intervention, the body weight values of the EA group were markedly higher than those of the model group in spite of being still lower than normal rats (P<0.05). CONCLUSION: EA can effectively suppress CRF-induced increase of serum Scr and BUN contents and renal beta-catenin protein expression in CRF rats, suggesting an improvement of the renal function after EA intervention by reducing the expression of beta-catenin in the renal tissue.

[Reflection of dysmenorrhea in acupoint sanyinjiao (SP 6) region].

OBJECTIVE: To observe the reflection of dysmenorrhea in acupoint Sanyinjiao (SP 6) region (body surface) so as to verify the relationship between the acupoint and uterus. METHODS: A total of 60 women (15-35 years in age) including 30 primary dysmenorrhea patients (test group) and 30 healthy subjects (control group) were enrolled in the present study. The visual analog scale (VAS) score and mechanical pain threshold of bilateral Sanyinjiao (SP 6) regions were detected to assess changes of skin sensitivity in subjects undergoing menstrual pain and in the non-menstrual period. RESULTS: The VAS value in the menstrual period of test group was significantly higher than that in the non-menstrual period of the same one group and that in the menstrual period of the control group (P<0.01), and the pain threshold in the menstrual period of test group was significantly lower than that in the non-menstrual period of same one group and that in the menstrual period of the control group (P<0.01). No significant differences of both VAS value and pain threshold were found between the two groups in the non-menstrual period (P>0.05). CONCLUSION: An obvious tenderness at Sanyinjiao (SP 6) exists in women undergoing primary dysmenorrhea, sug- gesting a close correlation between Sanyinjiao (SP 6) and uterus.

[Observation on therapeutic effects of acupoint injection of metoclopramide for postsurgical gastroparesis syndrome].

OBJECTIVE: To observe the clinical effects of acupoint injection of metoclopramide for postsurgical gastroparesis syndrome (PGS). METHODS: A total of 46 patients with PGS(from abdominal surgery) were randomly divided into control and acupoint injection groups (n=23 in each group). Patients of the acupoint injection group were treated by injection of Metoclopramide (5 mg+ normal saline) into bilateral Zusanli (ST 36) and Weishu (BL 21) alternatively, while patients of the control group treated by injection of 10 mg of Metoclopramide into the deltoid muscle and gluteus maximus muscle alternatively. The treatment of both groups was conducted once daily for 14 days. A 3-point scale of clinical symptoms (abdominal distension, belching, nausea-vomiting, upper-abdominal distending pain, sour regurgitation and gastric burning sensation) was used to evaluate the therapeutic effect. RESULTS: There were no statistical differences between two groups in clinical symptom scores before the treatment (P>0.05). Following treatment, the clinical symptom scores of both groups were significantly decreased in comparison with pre-treatment (P<0.05) and the scores of the acupoint injection group were significantly lower than those of the control group (P<0.05). Of the 23 PGS patients in the control group and acupoint injection group, 0 and 2 were cured, 5 and 10 were significantly improved, 10 and 9 were improved, 8 and 2 failed, with the effective rates being 65.22% and 91.30%, respectively. CONCLUSION: Acupoint injection of Metoclopramide is effective for improving clinical symptoms of PGS patients.

[Analysis on Cheng Dan-an's educational thought in his book Chinese acupuncturology].

Mr. CHENG Dan-an, a famous acupuncture master, is the beginner of "Chengjiang Acupuncturological School" in China. This school of thought has a far-reaching impact on current acupunturological education,and its educational thought and teaching features chiefly reflect in CHENG's works. In the present paper, the authors analyze the influence of contemporary historical factors and sum up Mr. CHENG's educational thought on the basis of the written foundation, style and contents of his book Chinese Acupuncturology from four aspects (1) the role of education, (2) the process of education, (3) the teacher's and students' relationship in educational activities,and (4) the compilation of teaching materials about acupuncture and moxibustion.

[Our considerations about basic research and clinical translation based on experimental studies on acupuncture-induced blood-pressure reduction].

Basic research is an important component of acupuncture medicine, and is also the driving force for improving clinical practice. Acupuncture therapy has been used to treat hypertension for many years in China, and its underlying mechanism has also been progressively and partially explored, but its therapeutic effect remains controversial. Authors of the present paper summarize the current state of experimental researches on acupuncture treatment of hypertension from the establishment of hypertension model, acupoint selection, stimulation parameters, and related action mechanisms, and simultaneously found a disassocia- tion between the basic research and clinical practice, particularly in the selection of acupoints and stimulation parameters. Therefore, to establish a bridge for better translation from many achievements of experimental studies to clinical application is of great practical significance. The authors hold that the existing problems of clinical practice should be the foothold of basic research, while successful transformation from basic research achievements to clinical practice is our ultimate target. Only in this way, can we incessantly achieve the goal of improving clinical therapeutic effect of acupuncture therapy from the phase of effectiveness verification, and promote the healthy development of acupuncturology.

[Effect of electroacupuncture stimulation of back-shu points on expression of TNF-alpha and lipid peroxidation reaction in the liver tissue in non-alcoholic fatty liver disease rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation (EAS) of back-shu acupoints on expression of tumor necrosis factor-alpha (TNF-alpha) and lipid peroxidase reaction in the liver in non-alcoholic fatty liver disease (NAFLD) rats. METHODS: Wistar rats were randomly divided into normal group (n = 1), model group (n = 10), EAS group (n = 10) and medication group (n = 10). The NAFLD model was established by feeding the animals with high fat diet for 8 weeks. EAS was applied to bilateral "Pishu" (BL 20), "Geshu" (BL 17) and "Shenshu" (BL 23) for 20 min, once daily for 4 weeks. Rats of the medication group were treated by 1% Dongbao Gantai suspension (0.28 g/kg, 20 mL/kg) once daily for 4 weeks. Pathological changes of the liver tissue were observed by microscope after H. E. staining. Hepatic free fatty acid (FFA) content was assayed by using an automatic biochemistry analyzer, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were detected by penthiobarbituric acid colorimetric method and xanthine oxidase colorimetric method, respectively. The expression of liver TNF-alpha was detected by immunohistochemistry. RESULTS: Compared with the normal group, rats of the model group showed a moderate to severe fatty degeneration of liver cells, significant up-regulation of hepatic TNF-alpha expression, FFA and MDA contents (P < 0.01), and marked down-regulation of SOD activity (P < 0.01). Following 4 weeks' treatment, compared with the model group, liver fatty degeneration was reduced at different degrees in both EAS and medication groups; liver FFA and MDA contents and TNF-alpha expression were significantly down-regulated (P < 0.01, P < 0.05), and hepatic SOD activity was notably increased (P < 0.01, P < 0.05) in both EAS and medication groups, suggesting a reduction of hepatic lipid peroxidation. No significant differences between the EAS and medication groups in the liver FFA and MDA contents, SOD activity and TNF-alpha expression (P > 0.05). CONCLUSION: EA intervention can improve liver fatty degeneration, inhibit high fat induced up-regulation of hepatic TNF-a expression, FFA and MDA contents and down-regulation of SOD activity in non-alcohol fatty liver model rats, which may contribute to its effect in improving NAFLD.

[The effects of electro-acupuncture on the signaling pathway of TLR/MYD88 in ankle joint synovial tissue of acute gouty arthritis rats].

OBJECTIVE: To investigate the effects of electro-acupuncture ( EA) on the related protein expression of the signaling pathway of the toll-like receptor2 (TLR2)/myeloid differentiation factor (MYD) 88 in ankle joint synovial tissue of acute gouty arthritis (AGA) rats. METHODS: Fifty male SD rats were randomly divided into 5 groups: normal group, SMD group, AGA model group, medication group and EA group, 10 rats in each group. SMD group established model by inducing SMD, other groups established AGA model by inducing monosodium urate, except the normal group. Two days before model was established, normal and SMD and AGA model groups were lavaged with normal saline (20 mL/kg), medication group was lavaged with colchicine solution (1 mg/kg), EA (1. 5-2 Hz, D.-D. wave, 9 V, 1-3 mA) was applied to"Sanyinjiao" (SP6),"Jiexi"(ST41) and "kunlun" (BL60) for 20 min, once daily, continuously for 9 days. Then the join sewlling index was observed periodically, the protein expression of TLR2 and MYD88 was determined by immunohistochemistry. RESULTS: Compared to the normal group, the join sewlling of the SMD group in test join increased significantly (P<0. 05) and the protein expression of TLR2 and MYD88 in synovial tissue has not statistically significant (P>0.05), the oin sewlling and protein expression of TLR2 and MYD88 in synovial tissue of model group increased significantly P<0. 05); The medication and EA group compared to the model group, the protein expression of TLR2 and MYD88 in synovial tissue decreased significantly (P <0. 05), the join sewlling in test join decreased significantly P<1. 05); There were not statistically significant between the EA group and the medication group (P>0.05). CONCLUSION: EA can alleviate the symptoms of AGA, which may be related to regulation of the protein expression Y TRI and MYD88 in the TLR/MYD88 signaling pathway.

[Effect of electroacupuncture of "Hegu" (LI 4)-"Taichong" (LR 3) on colonic nitric oxide synthase and glutathione peroxidase activity and nitric oxide content in depression rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the activity of inducible nitric oxide synthase (iNOS), glutathione peroxidase (GSH-Px) and the content of nitric oxide (NO) in colon tissue of depression rats, so as to reveal its mechanism in protecting colonic tissue under depression. METHODS: Forty male SD rats were equally randomized into normal, model, medication and EA groups. Depression model was established by using chronic unpredictable mild stress stimulation (forced ice-water swimming, electric shock, tail-clamping, etc) combined with lonely raising for 21 days. At the same time of modeling, Fluoxetine (1.8 mg/kg, intragastric perfusion) was given to the rats of medication group, once daily for 21 days. EA (1.5-2 Hz, 1-3 mA) was applied to bilateral "Hegu" (LI 4) and "Taichong" (LR 3) for 20 min, once daily for 21 days. The activity of iNOS, GSH-Px and the content of NO in colon tissue were detected by ultraviolet spectrophotometer method. RESULTS: In comparison with normal control group, iNOS activity and NO content in colon tissue increased significantly (P<0.05), and GSH-Px activity decreased considerably (P<0.05) in model group. Whereas compared with model group, iNOS activity and NO content decreased significantly (P<0.05), and GSH-Px activity increased significantly in EA and medication groups. No significant differences were found between EA group and medication group in these 3 indexes (P>0.05). CONCLUSION: EA of "Hegu" (LI 4) and "Taichong" (LR 3) can reduce stress induced increase of both iNOS activity and NO content, and decrease of GSH-Px activity in colon tissue in depression rats, which may contribute to its effect in protecting the digestive tract from injury under depression.

[The point of view of moxibustion in the book, A General Survey of Moxibustion].

OBJECTIVE: To study on academic point of view of the book, A General Survey of Moribustion. METHODS: Study academic thought of the book and clarify academic origin and characteristics of the book. CONCLUSION: Processing of argyi leaf, manufacture of mugwort floss and size of moxa cone have a certain technique standards in the book. The book indicates that small cones should be used with more times of moxibustion. and the properties of mugwort floss are not dry and heat, but are warm and moist and mild, moxibustion not only can be used to treat cold syndrome but also can be used to treat heat syndrome; the body can response to the external moxibustion. The above points of view have still guiding significance in nowadays.