Shenqi Dihuang Decoction inhibits high-glucose induced ferroptosis of renal tubular epithelial cells via Nrf2/HO-1/GPX4 pathway / 中国中药杂志

This study aims to explore the effects of Shenqi Dihuang Decoction on high-glucose induced ferroptosis and the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4) axis in human renal tubular epithelial cells(HK-2) and to clarify the underlying mechanism. The cell injury model was established by exposing HK-2 to high glucose, and the Shenqi Dihuang Decoction-medicated serum was prepared. The optimal concentration and intervention time of Shenqi Dihuang Decoction were determined. HK-2 were divided into normal, high glucose, and low-, medium-, and high-dose Shenqi Dihuang Decoction groups. After interventions, the cell proliferation rate in each group was determined and the cell morphology and mitochondrial ultrastructure were observed. Then, the levels of intracellular reactive oxygen species(ROS), ferrous ion(Fe~(2+)), glutathione(GSH), and malondialdehyde(MDA) and the protein levels of Nrf2, HO-1, GPX4, and xCT were measured. The optimal concentration and intervention time of Shenqi Dihuang Decoction-medicated serum were determined to be 10% and 24 h, respectively. Compared with the high glucose group, high-dose Shenqi Dihuang Decoction promoted the proliferation of HK-2. The cells in the low-, medium-, and high-dose Shenqi Dihuang Decoction groups presented tight arrangement, an increased cell count, improved morphology from a spindle-fiber shape to a cobblestone shape, and improved morphology and structure of mitochondrial membrane and cristae, compared with those in the high glucose group. Meanwhile, all the doses of Shenqi Dihuang Decoction inhibited ROS elevation to mitigate the peroxidation damage, lowered the Fe~(2+) and MDA levels and elevated the GSH level to inhibit lipid peroxidation, and activated the antioxidant pathway to upregulate the protein levels of Nrf2, HO-1, xCT, and GPX4. In conclusion, Shenqi Dihuang Decoction-medicated serum can inhibit high-glucose induced ferroptosis of HK-2 in vitro, which involves the antioxidant effect and the activation of the Nrf2/HO-1/GPX4 pathway.

Clinical study of Shenqi Dihuang Decoction and Xiaochengqi Decoction combined with hemodialysis in the treatment of the patients with CKD stage 5 and Qi and Yin deficiency and turbid poison inherent pattern / 国际中医中药杂志

Objective:To investigate the clinical effect of Shenqi Dihuang Decoction and Xiaochengqi Decoction enema combined with hemodialysis in the treatment of qi deficiency, blood stasis and dampness and turbidity in chronic kidney disease (CKD) stage 5.Methods:Randomized controlled trial. A total of 102 elderly CKD stage 5 patients with Qi and Yin deficiency and turbid poison inherent type were selected from May 2021 to January 2022 of the Beijing Longfu Hospital. The patients were divided into two groups by random number table method. Control group (51 cases) received hemodialysis treatment for 4 weeks, and the observation group (51 cases) received Shenqi Dihuang Decoction and Xiaochengqi Decoction enema combined with hemodialysis treatment for 4 weeks. The levels of BUN, SCr and β2-microglobulin (β2-MG), and K +, Ca 2+, P 3- content, hemoglobin were detected by automatic blood cell analyzer, and serum CRP and IL-6 levels were detected by latex enhanced immune scattering turbidimetry. The adverse reactions during the treatment and evaluate the clinical efficacy were observed and recorded. Results:During the treatment, 2 patients in the observation group withdrew from the study due to severe diarrhea, and other patients completed the study. There were significant differences in total response rate between observation group and control group [91.84%(45/49) vs. 74.51%(38/51); χ2=5.32, P=0.002]. After treatment, scores of lumbar and knee acerbity, tiredness and fatigue, edema, dizziness and tinnitus, fear of cold and warm, yellow face, dry stool and total score in observation group were significantly lower than those in the control group ( t=8.38, 13.44, 15.14, 13.09, 7.12, 7.73, 11.16, 11.45, P<0.01); the scores of SF-12-PCS and SF-12-MCS were significantly higher than those in the control group ( t=3.24, 4.22, P<0.01). After treatment, levels of serum BUN [(15.02±2.35)mmoL/L vs. (18.02±3.65)mmoL/L, t=4.87], SCr[(155.26±23.65) μmol/L vs. (184.49±35.49) μmol/L, t=4.83], β2-MG[(7.12±1.27)mg/L vs. (9.56±2.14)mg/L, t=6.90] and P 3-[(1.51±0.10) mmol/L vs. (2.02±0.19) mmol/L, t=16.70], K +[(3.65±0.54) mmol/L vs. (4.21±0.63)mmol/L, t=4.76] in observation group were significantly lower than those in the control group ( P<0.01); Ca 2+[(1.86±0.36)mmol/L vs. (2.35±0.42)mmol/L, t=6.25] was significantly higher than that of the control group ( P<0.01). No adverse reactions occurred during the treatment in the two groups ( P>0.05). Conclusion:Shenqi Dihuang Decoction and Xiaochengqi Decoction enema and hemodialysis can improve renal function, correct electrolyte disorder, reduce the level of inflammatory factors, improve the quality of life, and improve the therapeutic effect of the patients with CKD stage 5 and Qi and Yin deficiency and turbid poison inherent pattern.

Clinical research on Shenqi Dihuang Decoction combined with conventional western medicine in the treatment of stage Ⅲ diabetic nephropathy / 国际中医中药杂志

Objective:To observe the clinical efficacy of Shenqi Dihuang Decoction combined with conventional western medicine in the treatment of stage Ⅲ Diabetic Nephropathy (DN).Methods:A total of 96 patients with stage Ⅲ diabetic nephropathy with syndrome of deficiency of qi and yin in our hospital, from January 2019 to January 2021, who met the inclusion criteria, were divided into 2 groups by random number table method, 48 in each group. The control group was given the conventional western treatment. The observation group was given Shenqi Dihuang Decoction on the basic of the control group treatment. Both groups treatment lasted for 3 months. Before and after the treatment, the changes of TCM Syndrome Scores were observed. The levels of soluble intercellular adhesion molecular-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1) were detected by double antibody sandwich ELISA. The levels of BUN, SCr, SOD and Hcy were detected by automatic biochemical analyzer, collect 24-hour urine, 24-hour urine total protein quantity (24 UTP) was detected by immunoturbidimetry, and eGFR was calculated by CKD-EPI formula to evaluate the clinical efficacy.Results:After the treatment, the total effective rate in the observation group was 83.3% (40/48), and the control group was 66.7% (32/40) and the difference was statistically significant ( χ2=3.56, P=0.049). After the treatment, TCM Syndrome Scores in the observation group was significantly better than that of the control group ( t=4.05, P<0.01). After treatment, the systolic blood pressure in the observation group was significantly lower than that of the control group ( t=4.29， P<0.01). After treatment, the levels of 24 hUTP [(1.43 ± 0.54) g vs. (1.86 ± 0.50) g, t=4.05], serum sICAM-1[(396.07 ± 50.61)μg/L vs. (480.11 ± 63.01)μg/L, t=7.20], Hcy [(27.41 ± 3.42) μmol/L vs. (29.76 ± 5.80) μmol/L, t=2.42] in the observation group were significantly lower than those in the control group ( P<0.05), and the levels of SOD [(168.32 ± 41.26) U/ml vs. (143.11 ± 37.02) U/ml, t=3.15] was significantly higher than that of the control group ( P<0.01). Conclusions:Shenqi Dihuang Decoction combined with conventional western medicine can reduce 24 hUTP quantity and kidney damage, delay the development of Ⅲ DN, improve clinical effect and protect the kidney function, and sICAM-1 for the Ⅲ DN patients with the syndrome of qi and yin deficiency combined with blood stasis.

Analysis of chemical ingredients of modified Shenqi Dihuang decoction by UPLC-LTQ-Orbitrap-MS / 药学实践杂志

Objective To analyze the chemical compounds of Shenqi Dihuang decoction by the ultraperformance liquid chromatography coupled with linear quadrupole ion trap-orbitrap mass spectrometry (UPLC-LTQ-Orbitrap-MS). Methods Warters ACQUITY UPLC HSS T3 (2.1 mm ×100 mm, 1.8 μm) was used as chromatographic column with mobile phase: 0.1% formic acid water (A)-0.1% formic acid acetonitrile (B) with gradient elution, and flow rate was 0.3 ml/min. Electrospray ion source (ESI) and an electrostatic field orbital ion trap mass analyzer were adopted, which was used to collect mass spectrometry fragment information with positive and negative ion modes, by comparing with the relative retention time of the reference substance. In addition, the fragment information of the mass spectrum was used to identify the compounds. The accurate identification of the chemical components in Shenqi Dihuang decoction was confirmed with literature. Results The study found that UPLC-LTQ-Orbitrap-MS technology could be used to identify 62 chemical components, including 13 aromatic acids, 9 flavonoids, 8 saponins, and 5 aromatic amines, 3 keto acids, 2 phenols, 1 aromatic quinone and other ingredients in Shenqi Dihuang decoction. Conclusion The identification analysis method in this study was efficient and accurate, which could be applied to the identification and analysis of chemical components in Shenqi Dihuang decoction and provided the important experimental data for the research on the material basis and mechanism.

Modified Shenqi Dihuang Decoction in the Treatment of Chronic Glomerular Nephritis:A Meta-analysis and Trial Sequential Analysis / 中国药房

OBJECTIVE:To systematically evaluate therapeutic efficacy of modified Shenqi dihuang decoction in the treatment of chronic glomerular nephritis. METHODS:Retrieved from Wanfang database,CNKI,VIP,CBM,Cochrane Library,Medline, EMBase and PubMed,randomized controlled trials(RCTs)about modified Shenqi dihuang decoction combined with conventional therapy and (or) other Chinese patent medicine (trial group) vs. conventional therapy and (or) other Chinese patent medicine (control group)in the treatment of chronic glomerular nephritis were collected. Meta-analysis was carried out by using Rev Man 5.3 software after literature scanning,data extraction and quality evaluation. Stata 14.0 software was used to conduct Egger test to evaluate publication bias. If publication bias existed,the effect of publication bias on outcome was further evaluated by scissor compensation. TSA v0.9 software was used for trial sequential analysis(TSA)of total efficency. RESULTS:A total of 10 RCTs were included,involving 707 patients. The results of Meta-analysis showed that total response rate of trial group [RR＝1.40,95%CI(1.22, 1.61),P＜0.001] was significantly higher than that of control group; the level of urine protein [SMD＝－1.97,95%CI(－2.92,－1.03),P＜0.001] and Scr [MD＝－28.41,95%CI(－38.95,－17.87),P＜0.001] in trial group were significantly lower than control group,with statistical significance. Publication bias test of total response rate was conducted,and results of it showed that there was publication bias,but bias did not affect the results of this study. TSA analysis showed that the evidence of Meta-analysis was false positive. CONCLUSIONS:Therapeutic efficacy of modified Shenqi dihuang decoction for chronic glomerular nephritis need to be proved by more stringent RCTs.

Effect of Shenqi Dihuang decoction on inflammatory factor, renal function and microcirculation in patients with early diabetic nephropathy / 中国中药杂志

To study the effect of Shenqi Dihuang decoction on inflammatory factor, renal function and microcirculation in patients with early diabetic nephropathy. A total of 205 cases of patient with early diabetic nephropathy treated in our hospital from March 2014 to April 2016 were selected and divided into two groups according to the admitted order, with 103 cases in clinical group and 102 in control group. Patients in control group were treated with melbine and captopril, which may be adjusted according to the clinical symptom. The clinical group was given Shenqi Dihuang decoction. Then the clinical efficady, inflammatory factors, renal function, endothelial function and hemorheology index were compared. Compared with 77.45% in the control group, the total effective rate of the clinical group was 92.23%. There was a significant increase (<0.05). The comparison of the values of IL-6, IL-8, TNF-α and CRP between the two groups before and after treatment showed significant differences. The values of inflammatory factors in treatment group were lower than in control group (<0.05). The comparison of the values of β2-MG, Cys-C and urine m-ALB between the two groups before and after treatment showed significant differences. The values of renal function in treatment group were lower than those in control group (<0.05). Compared with before treatment, ET-1 of the two groups after treatment decreased, while NO increased (<0.05). Compared with the control group, the value of ET-1 in patients of the experimental group was lower after treatment, while NO was higher (<0.05). The comparison of the values of whole blood viscosity, plasma viscosity, whole blood reduction viscosity, platelet aggregation rate and fibrinogen between the two groups before and after treatment showed significant differences. The value of hemorheology index in treatment group was lower than that in control group (<0.05). Shenqi Dihuang decoction has a better effect on patients with early diabetic nephropathy. It can significantly intervene with inflammatory response, reduce proteinuria, protect the renal function of patients, and improve the patient's vascular endothelial function and blood rheology, so as to make microcirculation to recover to the normal level.

Experimental Study on Protective Function of Shenqi Dihuang Decoction on Diabetic Rats'Kidney / 国际中医中药杂志

Objective To study the protective function and the mechanism of Shenqi Dihuang decoction on the kidney of type 2 diabetes melltuds rats. Methods Type 2 diabetes mellitus rat models were set up by injection of small dose of streptozotocin (STZ). The SD rats were randomized into a control group, a model group and a treatment group. The treatment group was given Shenqi Dihuang decoction. The control group and the model group were given the same amount of water. After 24 weeks, renal morphology examination and biochemical indicator were examined. The levels of Ang-Ⅱ and endothelin (ET) in senum were tested by radioimmunoassay and the level of transforming growth factorβ1 (TGF-β1) in renal cortex were determined by immunohistochemistry. Results The kidney function and kidney lesions were significantly improved in the treatment group than in the model group. Ang-Ⅱ And ET levels in serum and renal cortex was reduced, and the expression of TGF-β1 in the treatment group was decreased. Conclusion Shenqi Dihuang Decoction has protective effect on the kidney of diabetic rats, the mechanism may be related to its inhibition on the over expression of Ang- Ⅱ, ET and TGF-β1.