Effect of Ronghuang Granule on serum FGF23, FGFRs and Klotho in non-dialysis patients with CKD-MBD and kidney deficiency and damp-heat syndrome / 南方医科大学学报

OBJECTIVE@#To observe the effect of Ronghuang granule on serum fibroblast growth factor 23 (FGF23), fibroblast growth factor receptor (FGFRs) and Klotho protein levels in non-dialysis patients with chronic kidney disease-mineral and bone disorder (CKD-MBD) and kidney deficiency and damp heat syndrome.@*METHODS@#Seventy non-dialysis CKD-MBD patients with kidney deficiency and dampness-heat syndrome were randomized into control group (=35) and treatment group (=35). All the patients were given routine treatment combined with traditional Chinese medicine retention enema, and the patients in the treatment group received additional Ronghuang granule treatment (3 times a day). After the 12-week treatments, the patients were examined for changes of TCM syndromes. Serum levels of Ca, P, parathyroid hormone (iPTH), FGF23, FGFRs and Klotho proteins were detected before and after treatment. These parameters were also examined in 20 healthy volunteers.@*RESULTS@#Sixty-five patients completed the study, including 33 in the control group and 32 in the treatment group. The patients in the treatment group showed significantly better treatment responses than those in the control group ( < 0.05 or 0.01). At 4, 8, and 12 weeks of treatment, the patients in the treatment group had significantly lowered scores of TCM syndromes compared with the score before treatment ( < 0.05 or 0.01), while in the control group, significant reduction of the scores occurred only at 12 weeks ( < 0.05); at each of the time points, the treatment group had significantly greater reductions in the score than the control group ( < 0.01). Significant improvements in serum Ca, P and iPTH levels were observed at 4, 8, and 12 weeks in the treatment group ( < 0.05) but only at 12 weeks in the control group ( < 0.05). The patients in the control and treatment groups all showed elevated serum levels of FGF23, FGFRs and Klotho protein compared with the normal subjects ( < 0.01); FGF23, FGFRs and Klotho levels were significantly reduced in the treatment group ( < 0.05) but remained unchanged in the control group (>0.05), showing significant differences between the two groups.@*CONCLUSIONS@#Ronghuang granule improves the clinical symptoms of non-dialysis CKD-MBD patients with kidney deficiency and dampness heat syndrome by reducing serum levels of FGF23, FGFRs and Klotho, improving calcium and phosphorus metabolism disorder, and inhibiting secondary hyperparathyroidism.

A study on Qingshen granule for treatment of renal fibrosis in patients with chronic renal failure accompanied by damp-heat syndrome and its mechanism / 中国中西医结合急救杂志

Objective To observe the anti-fibrosis therapeutic effect and mechanism of Qingshen granule for treatment of patients with chronic renal failure (CRF) accompanied by damp-heat syndrome.Methods Sixty-eight patients with CRF accompanied by damp-heat syndrome were randomly divided into a control group and a observation group, and the study was completed only in 61 patients, 31 in the control group and 30 in the observation group. Thirty subjects having taken physical health examination were assigned in a healthy control group. All the patients in both treatment groups were treated with conventional western medical therapy and traditional Chinese medicine (TCM) retention enema, and for patients in observation group, Qingshen granule was given additionally, 1 bag (10 g) thrice a day taken orally. The therapeutic course was 8 weeks. The clinical therapeutic effect, the levels of serum creatinine (SCr), the glomerular filtration rate (eGFR), serum interleukin-17 (IL-17), collagen type Ⅲ (Col-Ⅲ) and nuclear factor-κB p65 (NF-κB p65) in peripheral blood mononuclear cells (PBMC) were measured before and after treatment in the two treatment groups, and the above results were compared with those in healthy control group.Results Clinically, the total effective rates of the disease and of the TCM syndrome in observation group were significantly higher than those in the control group (86.67% vs. 58.06%, 83.33% vs. 45.16%, bothP < 0.01). In the observation group, the level of SCr was obviously lower, and the level of eGFR was markedly higher after treatment, and compared with the control group, the changes in above data after treatment in observation group were more significant [SCr (μmol/L): 250.62±164.97 vs. 393.72±183.64, eGFR (mL·min-1·1.73 m-2): 33.42±17.24 vs. 39.72±23.85, bothP < 0.05]. After treatment, the levels of serum IL-17, Col-Ⅲ and NF-κB p65 in PBMC were obviously lowered in both treatment groups compared with those before treatment, the therapeutic effect in observation group being superior to that in the control group [IL-17 (ng/L): 17.47±8.87 vs. 25.51±16.69, Col-Ⅲ (μg/L): 17.06±8.76 vs. 23.77±10.44, NF-κB p65 (μg/L): 0.58±0.34 vs. 0.83±0.30, allP < 0.05].Conclusion The Qingshen granule can ameliorate the clinical symptoms, improve renal function, decrease the levels of serum IL-17, Col-Ⅲ and NF-κB p65 in PBMC, intervene renal fibrosis in patients with CRF and damp-heat syndrome, ultimately delaying the progress of CRF.

The interference effect of traditional Chinese medicine Qingshen granule on signal transduction pathway of fokal adhesion kinase-rat sarcoma-mitogen activated protein kinase in rats with renal fibrosis / 中国中西医结合急救杂志

Objective To observe the effect of traditional Chinese medicine (TCM) Qingshen granule on signal transduction pathway of fokal adhesion kinase-rat sarcoma-mitogen activated protein kinase (FAK-Ras-MAPK) in renal tissue of rats with renal interstitial fibrosis (RIF). Methods Forty Spargue-Dawley (SD) rats were randomly divided into normal control, model, Bailing capsule and Qingshen granule groups (each, n = 10). The rat model with RIF was reproduced by unilateral ureteral obstruction (UUO) or ligation method. The rats in Bailing capsule group were treated with Bailing capsule dissolved in 4 mL warm water, and the dosage was 0.3 g·kg-1·d-1 for intragastric administration;the rats in Qingshen granule group were treated with Qingshen granule dissolved in 4 mL warm water, its dosage was 6 g·kg-1·d-1 for intragastric administration, and equal volume of normal saline was given to normal control group and model group by gavage. After treatment for 8 weeks, the levels of blood urea nitrogen (BUN), serum creatinine (SCr), fibronectin (FN),α-smooth muscle actin (α-SMA) were determined in each groups. The renal tissue expression levels of FAK, Ras, p38MAPK, FN, α-SMA were determined in various groups by immunohistochemistry staining method. Results Compared with the normal control group, the levels of serum BUN, SCr, FN and α-SMA were significantly increased in the model group. There were no significant differences in the levels of serum BUN and SCr before administration of drugs between Bailing capsule group and Qingshen granule group (both P>0.05). The levels of BUN, SCr, FN, andα-SMA were all significantly lowered in the two treatment groups than those of the model group after administration, the descent in Qingshen granule group being more marked [BUN (mmol/L):13.18±4.91 vs. 18.56±5.59, SCr (μmol/L): 104.80±12.04 vs. 119.02±12.47, FN (mg/L): 29.72±16.75 vs. 46.38±8.63, α-SMA (kU/L):5.49±2.68 vs. 7.13±2.37, all P < 0.05]. The immunohistochemistry staining showed: the kidney tissue expression levels of FAK, Ras, p38MAPK, FN, and α-SMA in the model group were significantly higher than those of normal control group, above indexes were all significantly lower in Bailing capsule group and Qingshen granule group than those of the model group, and the descent in Qingshen granule group was more obvious (FAK: 3.00±1.41 vs. 5.28±2.21, FN: 4.25±1.04 vs. 6.29±2.06, α-SMA: 3.25±1.28 vs. 4.86±1.57, p38MAPK: 2.50±1.31 vs. 4.71±2.50, Ras:3.50±1.41 vs. 4.29±1.38, all P<0.05). Conclusion Qingshen granule can reduce serum BUN and SCr levels in rats with RIF, and inhibit the activation of FAK-Ras-MAPK signal transduction pathway in the kidney, thereby it may reduce the generation of FN andα-SMA and play a role of anti-RIF.

Effects of Qingshen Granule on serum interleukin-8 and -18 levels in patients with a sharp deterioration of chronic renal failure and dampness-heat syndrome: a randomized controlled trial / 中西医结合学报

Background: Dampness-heat syndrome is a major syndrome type in patients with a sharp deterioration of chronic renal failure (CRF). Qingshen Decoction, a compound traditional Chinese herbal medicine, could relieve the clinical symptoms of CRF patients, and was considered to have a certain reversal effect on rapid deterioration of renal function. Objective: To observe the changes of serum interleukin-8 (IL-8) and IL-18 levels in CRF patients with a sharp deterioration and dampness-heat syndrome, and to explore the curative efficacy of Qingshen Granule. Design, setting, participants and interventions: Sixty CRF patients with a sharp deterioration and dampness-heat syndrome from Department of Nephrology, the First Affiliated Hospital of Anhui College of Traditional Chinese Medicine, were randomly divided into treatment group (30 cases) and control group (30 cases), with another 20 healthy individuals as normal control. The patients in the treatment and control groups were all treated with Jiedu Xiezhuo II, a compound traditional Chinese herbal medicine, given as retention enema. Qingshen Granule was additionally administered to the patients in the treatment group with 1 dosage each time and 3 times a day. The treatment course was one month. Main outcome measures: The levels of serum IL-8 and IL-18 in the normal individuals and before and after treatment in the treatment and control groups were detected. Results: The total response rates of treatment group in clinical efficacy assessment and assessment of syndrome of traditional Chinese medicine (86.67% and 86.67%) were higher than those of the control group (56.67% and 60%), and there were significant differences between the two groups (P0.05). After one-month treatment, the levels of serum IL-8 and IL-18 were markedly decreased in the two groups (P<0.01), and the levels of serum IL-8 and IL-18 in the treatment group were markedly lower than those in the control group (P<0.05). There were differences in decreased degrees of IL-8 and IL-18 levels between the two groups (P<0.05). Conclusion: CRF patients with a sharp deterioration and dampness-heat syndrome have high serum IL-8 and IL-18 levels. Qingshen Granule can reduce the levels of serum IL-8 and IL-18, and improve the renal function and ameliorate the clinical symptoms.