Simiao pill inhibits epithelial mesenchymal transition in a mouse model of chronic hyperuricemic nephropathy by inhibiting NLRP3 inflammasome activation.

BACKGROUND: Simiao pill module (SMM), a traditional Chinese medicine formula, has been widely used to treat gout and gouty arthritis. The goal of this study was to investigate the effects of SMM on epithelial-mesenchymal transition (EMT) and activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome in a mouse model of potassium oxonate (PO)-induced chronic hyperuricemic nephropathy (HN). METHODS: Mice were randomly divided into the following four groups: control, HN model (PO), febuxostat (FEB)-treated (PO + FEB), and SMM-treated (PO + SMM) groups. Following 6 weeks of treatment, blood samples were collected and mice were sacrificed to collect kidney samples to study the biochemical parameters associated with renal function and histopathological changes associated with HN, respectively. The samples were analyzed for the expression of markers of EMT (collagen type 3, α-smooth muscle actin [α-SMA], fibronectin, vimentin and E-cadherin) and activation of NLRP3 inflammasome (NLRP3, apoptosis-associated speck-like protein [ASC], caspase-1, interleukin [IL]-1ß, and IL-18). RESULTS: Our results showed that hyperuricemia, impaired kidney function, and renal pathological characteristics induced by PO treatment were improved following treatment with SMM and FEB. Additionally, treatment with SMM and FEB decreased the expression of vimentin, collagen 3, fibronectin, and α-SMA, and increased the expression of E-cadherin. Moreover, NLRP3 inflammasome activation, as assessed by the increased expression of NLRP3, ASC, and caspase-1, and secretion of IL-1ß and IL-18, was inhibited by treatment with SMM and FEB. CONCLUSION: These results suggest that SMM inhibited EMT and NLRP3 inflammasome activation in chronic HN mice, and the beneficial effect of SMM was compared with a standard drug, FEB.

Icariin attenuates renal fibrosis in vivo and in vitro by inhibiting the Notch2/Hes-1 pathway.

Chinese herbs were widely proposed as a novel approach for renal fibrosis. Icariin has been reported to be involved in a variety of diseases. Unilateral ureteral obstruction (UUO) is a popular experimental model of renal injury, which is often used in the study of renal fibrosis. A UUO mouse model was successfully constructed, and tubular injury and renal fibrosis were observed. Icariin treatment attenuated tubular injury and renal fibrosis in UUO mice. In addition, treatment with Icariin reduced the fibronectin, type I collagen and α-SMA levels in UUO mice. Furthermore, in a transforming growth factor (TGF)-ß1-induced renal fibrosis cell model, icariin treatment also decreased fibronectin, type I collagen and α-SMA expression. Icariin treatment also reversed the enhanced migration of TGF-ß1-induced HK-2 cells. These data indicated that icariin suppressed renal fibrosis in vivo and in vitro. Additionally, icariin treatment suppressed the Notch2/Hes-1 pathway in UUO mice and TGF-ß1-treated HK-2 cells. In summary, this study found that icariin reduced renal fibrosis in vivo and in vitro by inhibiting the Notch2/Hes-1 pathway, which might help to improve therapies for renal fibrosis.

Protective Effects of Ligustroflavone, an Active Compound from Ligustrum lucidum, on Diabetes-Induced Osteoporosis in Mice: A Potential Candidate as Calcium-Sensing Receptor Antagonist.

Ligustroflavone is one major compound contained in active fraction from Fructus Ligustri Lucidi (the fruit of Ligustrum lucidum), which could regulate parathyroid hormone (PTH) levels and improve calcium balance by acting on calcium-sensing receptors (CaSR). This study aimed to explore the potency of ligustroflavone as a CaSR antagonist and its protective effects against diabetic osteoporosis in mice. LF interacted well with the allosteric site of CaSR shown by molecular docking analysis, increased PTH release of primary parathyroid gland cells and suppressed extracellular calcium influx in HEK-293 cells. The serum level of PTH attained peak value at 2 h and maintained high during the period of 1 h and 3 h than that before treatment in mice after a single dose of LF. Treatment of diabetic mice with LF inhibited the decrease in calcium level of serum and bone and the enhancement in urinary calcium excretion as well as elevated circulating PTH levels. Trabecular bone mineral density and micro-architecture were markedly improved in diabetic mice upon to LF treatment for 8 weeks. LF reduced CaSR mRNA and protein expression in the kidneys of diabetic mice. Taken together, ligustroflavone could transiently increase PTH level and regulate calcium metabolism as well as prevent osteoporosis in diabetic mice, suggesting that ligustroflavone might be an effective antagonist on CaSR.

Clinical study on Yishen Qufeng Shengshi Recipe () for glomerular proteinuria patients: A randomized controlled trial.

OBJECTIVE: To explore the therapeutic effect of Yishen Qufeng Shengshi Recipe (, YQSR) in patients with glomerular proteinuria METHODS: A total of 145 patients with glomerular proteinuria were selected and randomly assigned to the treatment group (108 cases) and the control group (37 cases) according to a random number table in a ratio of 3:1. All patients received conventional and symptomatic treatment. In addition, patients in the treatment and control groups were given YQSR (200 mL, twice per day, orally) and losartan (50 mg/d orally), respectively for 6 months. The 24-h urine protein quantity, blood urea nitrogen, and serum creatinine in the two groups were measured at multiple time points before and after treatment. RESULTS: At the end of the study, 5 cases were lost to follow-up in the treatment group and 1 in the control group. Finally, the statistical data included 103 cases in the treatment group and 36 cases in the control group. The total effectiveness after 2, 4, and 6 months was 81.6% (84/103), 87.4% (90/103), and 92.2% (95/103), respectively, in the treatment group and 47.2% (17/36), 55.6% (20/36), and 61.1% (22/36), respectively, in the control group, with significant difference between the two groups (P<0.01 at all observation points). In the treatment group, the curative effect after 6 months was better than that after 2 months (P<0.05). The 24-h urine protein quantity was significantly lower in the treatment group at 3, 4, 5, and 6 months than that in the control group (P<0.05 or P<0.01, respectively) CONCLUSION: YQSR could significantly reduce the amount of glomerular proteinuria in the early stage.

[Treatment of Proteinuria in Chronic Glomerular Disease Patients with Pi-Shen Deficiency Complicated Damp-Heat Syndrome by Yishen Qingre Huashi Recipe: a Clinical Study].

OBJECTIVE: To observe the therapeutic effect of Yishen Qingre Huashi Recipe (YQHR) in treating proteinuria of chronic glomerular disease patients with Pi-Shen deficiency complicated damp-heat syndrome (PSDCDHS). METHODS: Totally 121 stage 1 -2 primary chronic glomerular disease patients with PSDCDHS were randomly assigned to the treated group (85 cases) and the control group (36 cases) according to 2:1. All patients received conventional and symptomatic treatment. Patients in the treated group took YQHR additionally, while those in the control group took Losartan Potassium Tablet (50 mg each time, once per day) additionally. The therapeutic course for all was 6 months. Changes of 24 h urine protein, blood urea nitrogen (BUN), serum creatinine(SCr), and estimated glomerular filtration rate (eGFR) were observed at different time points. And the difference in therapeutic effects were compared between the two groups. RESULTS: Compared with the control group after 6 months of treatment, 24 h urine protein obviously decreased in the treated group (P <0. 05). There was no statistical difference in SCr, BUN, or eGFR between the two groups after 6 months of treatment (P >0. 05). The total effective rate after 2, 4, and 6 months of treatment in the treated group was 77. 6% (66/85 cases), 82. 4% (70/85 cases), and 89. 4% (76/85 cases), respectively. They were 47. 2% (17/36 cases), 55. 6% (20/36 cases), and 61. 1% (22/36 cases) in the control group, respectively. Compared with before treatment in the treated group, the total effective effect after 6 months of treatment was higher than that after 2 months of treatment (χ2=4. 28, P <0. 01). Compared with the control group at the same time points, the total effective rate in the treated group after 2, 4, and 6 months of treatment was higher (χ2=10. 87, 9. 53, 13.16, P <0. 01). CONCLUSION: YQHR could significantly lower proteinuria in chronic glomerular disease patients with PSDCDHS, improve the clinical effect, thereby providing clinical evidence for treating chronic glomerular disease proteinuria from resolving dampness and clearing heat.

[Multi-center randomized control study on the effects of syndrome differentiated traditional Chinese medicine therapy on CKD 1-2 with chronic nephritis proteinuria].

OBJECTIVE: To determine the effects of Syndrome Differentiated Chinese Medicine (TCM) Therapy on (CKD) 1-2 stage chronic kidney disease with proteinuria. METHODS: A prospective randomized control study was undertaken in 11 centers. A total of 396 chronic nephritis patients were divided into a treatment group (n=297) and a control group (n=99). Their TCM syndrome was classified as "Qi and Yin Deficiency of spleen and kidney" or "Qi and Yang Deficiency of spleen and kidney", with accompanying syndromes showing as "water and dampness", "damp-heat", and "blood stasis". Patients in the treatment group took a dose of Chinese medicine daily in response to their syndromes, while the controls took 50 mg/d losartan. The course of treatment was 24 weeks. Changes of 24-hour urinary protein excretion and glomerular filtration rate (eGFR) before and after treatments (4, 8, 12, 16, 20, 24 weeks), as well as clinical efficacy (after 4, 16, 24 weeks treatments) were measured. RESULTS: 361 patients were included in the final program participants comply analysis (PPS). Patients in the treatment group showed gradual decreased 24-hour urinary protein excretion, whereas the controls remained unchanged. Significant differences in 24-hour urinary protein excretion appeared between the experimental and control group at week 20 and 24 (P<0.05). eGFR decreased in all of the patients after treatments (P=0.0014). At three follow-up points, patients in the treatment group had higher eGFR than the controls, but without statistical significance (P>0.05). Significant differences in clinical remission rate, marked effect rate and total effective rate were observed between the treatment and control groups at week 24 (P<0.001). CONCLUSION: Syndrome differentiated TCM therapy can reduce the level of proteinuria in CKD 1-2 nephritis patients, promoting clinical effectiveness and protecting renal functions.

[Syndrome differentiation-based treatment with traditional Chinese medicine for proteinuria in patients with chronic kidney disease: a randomized multicenter trial].

OBJECTIVE: To evaluate the clinical efficacy of syndrome differentiation-based treatment with traditional Chinese medicine (TCM) versus losartan therapy in addition to basic treatment for management of proteinuria in patients with chronic kidney disease. METHODS: This multicenter, randomized, and case-controlled clinical trial was conducted among 81 consecutive patients meeting the inclusion criteria. The patients were randomized consecutively to receive TCM treatments according to the syndrome patterns in TCM (spleen and kidney Qi and Yin deficiency, and spleen and kidney Qi and Yang deficiency, n=60) or oral losartan therapy (50 mg/day, n=21) in addition to the basic treatments. All the patients were followed up for 24 weeks to observe the clinical effects. RESULTS: The patients in TCM group showed a significantly higher overall response rate (93.33%) than those in losartan group (76.20%, P<0.05). The TCM score in the two groups were all decreased at week 24 as compared with baseline (P<0.01 or P<0.05). The TCM scores in both groups decreased significantly after the treatments as compared with the baseline scores (P<0.05). After a 8-week-long treatment, Scr, eGFR and Cys-C, U-Pro/24 h, and MA/Cr all decreased significantly in TCM group (P<0.05) but showed no significant changes in losartan group (P>0.05). CONCLUSION: Syndrome differentiation-based TCM treatment in addition to basic treatments can produce satisfactory therapeutic effects on proteinuria in patients with chronic kidney disease by improving the clinical symptoms, reducing TCM symptom scores and proteinuria, and protecting the renal functions.