[Effect of Qingshen Granules on inflammation/hepcidin axis and iron metabolism in patients with renal anemia: a single-center, randomized controlled trial].

OBJECTIVE: To evaluate the therapeutic effect of Qingshen Granules on renal anemia in patients with damp-heat syndrome and explore the mechanisms in light of inflammation/hepcidin axis and iron metabolism. METHODS: Sixty patients with renal anemia and dampness-heat syndrome were randomized into control group (n=30) and treatment group (n=30). All the patients were given routine treatment, and the patients in the treatment group received additional treatment with Qingshen Granules (3 times a day). After 12 weeks of treatments, the patients were examined for changes in the integral value of TCM syndrome, serum creatinine (Scr), glomerular filtration rate (eGFR), hemoglobin (HGB), hematocrit (HCT), red blood cell (RBC) count, interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP), ferritin, growth differentiation factor-15 (GDF-15), serum iron (SI), total iron binding capacity (TIBC), transferrin saturation (TAST), soluble transferrin receptor (sTfR) and ferritin levels. RESULTS: After the treatment, the scores of TCM syndrome were significantly improved in the treatment group and were better than those in the control group (P=0.000). Scr and eGFR were improved in both groups after the treatment. The levels of HGB, HCT and RBC were all improved in the two groups after treatment, and the improvements were more obvious in the treatment group (P=0.002, 0.002, and 0.017, respectively). The levels of IL-6, hs-CRP, hepcidine and GDF-15 were all lowered in the two groups after the treatment, and they were all significantly lower in the treatment group than in the control group (all P=0.000). The treatments increased the levels of SI and TAST in both of the groups, and compared with those in control group, the levels of TIBC, sTfR and ferritin were significantly lowered in the treatment group after the 12-week treatment (P=0.000). CONCLUSIONS: Qingshen granules can effectively improve renal anemia in patients with damp-heat syndrome possibly by improving iron metabolism through alleviation of inflammation and reduction of hepcidine level.

Therapeutic Role of Tangshenkang Granule () in Rat Model with Diabetic Nephropathy.

OBJECTIVE: To evaluate the renal protective effect of Tangshenkang Granule () in a rat model of diabetic nephropathy (DN). METHODS: Forty male Sprague-Dawley rats were randomly divided into control, DN, Tangshenkang and benazepril groups. DN model was established in the rats of DN, Tangshenkang and benazepril groups. Tangshenkang Granule solution and benazepril hydrochloride solution were intragastrically administered daily to the rats in the Tangshenkang and benazepril groups for 8 weeks, respectively. Urinary albumin and creatinine were detected. The albumin/creatinine (ACR) was calculated in addition to 24 h urinary protein (24-h UPr), serum creatinine (Scr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and creatinine clearance rate (Ccr). Right kidneys were harvested for pathological observation using periodic acid-silver methenamine-Masson staining. The average glomerular diameter (DG), average glomerular (AG) and mesangial areas (AM) were measured. The thickness of glomerular basement membrane (TGBM) was detected using transmission electron microscope. RESULTS: Compared with rats in the control group, rats in the DN group showed significantly decreased body weight, increased hypertrophy index, 24-h urinary volume, 24-h UPr, ACR, Scr, BUN, Ccr, blood lipids as well as renal pathological indices including DG, AG, AM, AM/AG and TGBM (P <0.05). Compared with the DN group, the weights of rats in the Tangshenkang and benazepril groups were significantly increased, and the renal hypertrophy indices were significantly decreased (P <0.05). The 24-h urinary volumes, ACR, 24-h UPr, Scr, BUN, Ccr, LDL, DG, AG, AM and TGBM were obviously decreased (P <0.05). Compared with the benazepril group, the Tangshenkang group showed significantly decreased levels of ACR, 24-h UPr, AG and AM (P <0.05). CONCLUSIONS: Tangshenkang Granule decreased the urinary protein, attenuated the high glomerular filtration rate and improved lipid metabolism in DN rats, and prevented further injury induced by diabetic nephropathy.

[Effect of Ronghuang Granule on serum FGF23, FGFRs and Klotho in non-dialysis patients with CKD-MBD and kidney deficiency and damp-heat syndrome].

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 (n=35) and treatment group (n=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 (P < 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 (P < 0.05 or 0.01), while in the control group, significant reduction of the scores occurred only at 12 weeks (P < 0.05); at each of the time points, the treatment group had significantly greater reductions in the score than the control group (P < 0.01). Significant improvements in serum Ca, P and iPTH levels were observed at 4, 8, and 12 weeks in the treatment group (P < 0.05) but only at 12 weeks in the control group (P < 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 (P < 0.01); FGF23, FGFRs and Klotho levels were significantly reduced in the treatment group (P < 0.05) but remained unchanged in the control group (P>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.

[Intervention of Qingshen Granule on NF-KB Signal Pathway of Chronic Renal Failure Patients with Damp-heat Syndrome].

Objective To observe the effect of Qingshen Granule (QG) on expressions of nucle- ar factors-κB p65 (NF-κB p65) and phosphonated inhibitor of nuclear factor-κB (p-lκBα) in peripheral blood NF-κB signal transduction pathway of chronic renal failure (CRF) patients with damp-heat syn- drome (DHS) , and to study possible mechanism. Methods Totally 68 CRF patients with DHS were as- signed to the control group and the treatment group by random digit table, 34 in each group. Actually 63 patients completed, 32 in the treatment group and 31 in the control group. A normal group (20 cases) was set up. All patients received basic treatment of Western medicine (WM) and retention enema of Chi- nese medicine (CM). Patients in the treatment group additionally took QG, 1 package each time, 3 times per day. The therapeutic course for all was 8 weeks. The clinical efficacy, level of serum creatinine (SCr), estimated glomerular filtration rate (eGFR), the levels of NF-κB p65 and p-IκBα in peripheral blood were observed and measured before and after treatment. They were also compared with those of the normal group. Results The clinical efficacy and the total effective rate of CM syndrome were 84. 38% (27/32)and 81. 25% (26/32), superior to those of the control group [54. 84%(17/31), 51. 61% (1631) ; P <0. 01 ]. Compared with before treatment, the level of SCr was obviously lower, and eGFR was obviously higher in the treatment group after treatment (P <0. 01). They were better than those of the control group after treatment (P <0. 05). Compared with the normal group, the levels of NF-κB p65 and p-IκBα were significantly higher in the treatment group and the control group before treatment (P < 0. 01). Compared with before treatment, the levels of NF-κB p65 and p-IκBα were obviously lowered in the treatment group after treatment (P <0. 01). They were also better than those of the control group after treatment (P <0. 05). Conclusions QG could improve clinical symptoms of CRF patients with DHS, de- crease SCr level, and increase eGFR level. It could protect renal function. Its mechanism might possibly be related with reducing peripheral blood levels of NF-κB p65 and p-IκBα.

Renoprotective effect of total glucosides of paeony (TGP) and its mechanism in experimental diabetes.

Total glucosides of paeony (TGP), extracted from the root of Paeonia lactiflora pall, has been shown to have ant-inflammatory and antioxidative actions. The aims of this study were to elucidate the renoprotective effect of TGP and its mechanism in experimental diabetes. Streptozotocin-induced diabetic rats were treated with TGP for 8 weeks. Treatment with TGP at 50, 100, and 200 mg/kg significantly lowered 24-h urinary albumin excretion rate in diabetic rats. TGP treatment in all doses markedly attenuated glomerular volume, and treatment with TGP at 100 and 200 mg/kg markedly reduced indices for tubulointerstitial injury in diabetic rats. Western blot analysis showed that the expressions of 1 alpha (IV) collagen, intercellular adhesion molecule (ICAM)-1, interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, NF-kappaB p65, and 3-nitrotyrosine (3-NT) protein were increased in the kidneys of diabetic rats; the increases in these proteins were all dose-dependently and significantly inhibited by TGP treatment. The expression of nephrin protein was significantly reduced in the kidneys from diabetic rats and markedly increased by TGP treatment. The expression of transforming growth factor (TGF)-beta1 protein in the kidney was also significantly increased in diabetic rats, which was significantly inhibited by treatment with TGP at all doses. Our data suggest that TGP treatment ameliorates early renal injury via the inhibition of expression of ICAM-1, IL-1, TNF-alpha, and 3-NT in the kidneys of diabetic rats.