acteoside and Proteinuria

The existing therapies of IgA nephropathy are unsatisfying. Acteoside, the main component of Rehmannia glutinosa with anti-inflammatory and anti-immune effects, can improve urinary protein excretion and immune disorder. Th22 cell is involved in IgA nephropathy progression. This study was determined to explore the effect of acteoside on mesangial injury underlying Th22 cell disorder in IgA nephropathy. Serum Th22 cells and urine total protein of patients with IgA nephropathy were measured before and after six months treatment of Rehmannia glutinosa acteoside or valsartan. Chemotactic assay and co-culture assay were performed to investigate the effect of acteoside on Th22 cell chemotaxis and differentiation. The expression of CCL20, CCL22 and CCL27 were analyzed. To explore the effect of acteoside on mesangial cell injury induced by inflammation, IL-1, IL-6, TNF-α and TGF-β1 were tested. Results showed that the proteinuria and Th22 lymphocytosis of patients with IgA nephropathy significantly improved after combination treatment of Rehmannia glutinosa acteoside and valsartan, compared with valsartan monotherapy. In vitro study further demonstrated that acteoside inhibit Th22 cell chemotaxis by suppressing the production of Th22 cell attractive chemokines, i.e., CCL20, CCL22 and CCL27. In addition, acteoside inhibited the Th22 cell proliferation. Co-culture assay proved that acteoside could relieve the overexpression of pro-inflammatory cytokines, and prevent the synthesis of TGF-β1. TGF-β1 level in mesangial cells was positively correlated with the Th22 cell. This research demonstrated that acteoside can alleviate mesangial cell inflammatory injury by modulating Th22 lymphocytes chemotaxis and proliferation.

Topics: Adult; Biopsy; Cell Line; Cell Proliferation; Chemokine CCL20; Chemokine CCL22; Chemokine CCL27; Chemotaxis; Coculture Techniques; Disease Progression; Drug Therapy, Combination; Female; Glomerulonephritis, IGA; Glucosides; Humans; Immunosuppressive Agents; Male; Mesangial Cells; Middle Aged; Phenols; Proteinuria; Rehmannia; T-Lymphocytes, Helper-Inducer; Transforming Growth Factor beta1; Treatment Outcome; Valsartan; Young Adult

This study aims to assess the efficacy and safety of Rehmannia glutinosa acteosides used in combination with the angiotensin receptor blocker irbesartan to treat primary chronic glomerulonephritis. A total of 479 patients diagnosed with primary chronic glomerulonephritis were recruited from outpatient clinics and were randomly assigned to the treatment group (Rehmannia glutinosa acteosides, two 200-mg capsules, bid; and irbesartan, one 150-mg tablet, qd) or the control group (irbesartan, one 150-mg tablet, qd). The primary outcome was 24-h urinary protein. Secondary outcome measures included blood pressure, estimated glomerular filtration rate, erythrocyturia, serum alanine aminotransferase, aspartate transaminase and electrolytes. After 8 weeks of treatment, the treatment group showed a mean reduction in 24-h proteinuria of 36.42% compared to baseline, which was significantly higher than the mean reduction from baseline of 27.97% in the control group (P = 0.0278).Adverse drug reactions occurred at a similarly low rate in the treatment group (0.4%) and control group (1.2%, P = 0.3724). In the treatment of chronic glomerulonephritis, the combination of Rehmannia glutinosa acteosides and irbesartan can reduce proteinuria more effectively than irbesartan alone.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Biphenyl Compounds; Blood Pressure; Female; Glomerulonephritis; Glucosides; Humans; Irbesartan; Male; Middle Aged; Phenols; Proteinuria; Rehmannia; Tetrazoles

The objective of the study was to investigate the effectiveness and efficacy of the randomized, parallel, and controlled trial of Traditional Chinese Medicine, general acteoside of Rehmanniae leaves, compared with piperazine ferulate in the treatment of primary chronic glomerulonephritis. Rehmanniae leaves and piperazine ferulate can reduce proteinuria and erythrocyturia effectively in the treatment of primary chronic glomerulonephritis. A total of 400 patients diagnosed with primary chronic glomerulonephritis were recruited from outpatient clinics and were randomly assigned to the treatment group (general acteoside of Rehmanniae leaves, two 200mg tablets, bid) or the control group (piperazine ferulate, four 50-mg tablets, bid ). The primary outcome was 24-h urinary protein. Secondary outcome measures included estimated glomerular filtration rate (eGFR), erythrocyturia, and electrolytes. After 8 weeks of treatment, the treatment group and the control group showed a mean reduction in 24-h proteinuria of 34.81% and 37.66%. The 95% CI of difference of the mean reduction in 24-h proteinuria between the two groups was [-11.50%, 5.80%]. No significant differences were found between the two groups in the erythrocyturia reduction. Neither group showed obvious changes between baseline and 8 weeks in eGFR or electrolytes. Adverse events occurred at a similarly low rate in the treatment group (1.5%) and control group (2.5%, P = 0.7238). Both general acteoside of Rehmanniae leaves and piperazine ferulate can reduce proteinuria and erythrocyturia effectively in the treatment of primary chronic glomerulonephritis.

Topics: Adult; Chronic Disease; Electrolytes; Erythrocytes; Female; Glomerular Filtration Rate; Glomerulonephritis; Glucosides; Humans; Male; Medicine, Chinese Traditional; Phenols; Phytotherapy; Piperazine; Piperazines; Plant Extracts; Plant Leaves; Proteinuria; Rehmannia

Effects of acetoside (ACT) on crescentic-type anti-GBM nephritis in rats were investigated. When rats were treated with ACT from the 1st day after i.v. injection of anti-GBM serum, ACT inhibited the elevation of protein excretion into urine. In the ACT-treated rats, cholesterol and creatinine contents and antibody production against rabbit gamma-globulin in the plasmas were lower than those of the nephritic control rats. Histological observation demonstrated that this agent suppressed hypercellularity and the incidence of crescent formation, adhesion of capillary wall to Bowman's capsule and fibrinoid necrosis in the glomeruli. Furthermore, rat-IgG and C3 deposits on the GBM were significantly less in the ACT-treated group than in the control nephritic group. When the treatment was started from the 20th day after i.v. injection of anti-GBM serum, by which the disease had been established, ACT resulted in a similar effect on the nephritic rats as stated above. These results suggest that ACT may be a useful medicine against rapidly progressive glomerulonephritis, which is characterized by severe glomerular lesions with diffuse crescents.

Topics: Analysis of Variance; Animals; Antibody Formation; Cholesterol; Complement C3; Complement Hemolytic Activity Assay; Creatinine; Disease Models, Animal; Drug Evaluation, Preclinical; gamma-Globulins; Glomerulonephritis; Glucosides; Immunohistochemistry; Immunosuppressive Agents; Kidney Glomerulus; Male; Phenols; Plant Extracts; Proliferating Cell Nuclear Antigen; Proteinuria; Rats; Rats, Sprague-Dawley

We investigated the effect of acteoside in comparison with that of cyclosporin A on leukocyte accumulation in the glomeruli of rats with crescentic-type anti-glomerular basement membrane (GBM) nephritis. Acteoside given p.o. at a dose of 30 mg/kg once a day for 15 consecutive days after treatment with anti-GBM serum markedly suppressed the urinary protein as well as glomerular histological changes. Acteoside given p.o. for 5 or 15 consecutive days markedly suppressed the accumulation of total leukocytes, ED-1-positive cells (monocytes/macrophages), CD4-positive cells, CD8-positive cells, interleukin-2-receptor-positive cells (activated T cells) and Ia-positive cells in the glomeruli. These effects of cyclosporin A (20 mg/kg/day, p.o.) were also as potent as those of acteoside (30 mg/kg/day, p.o.). Cyclosporin A also strongly suppressed the elevation of plasma antibody level against rabbit gamma-globulin. However, in this dose, acteoside did not significantly suppress the antibody formation. It can be concluded from these results that acetoside may exert its antinephritic action by suppressing the accumulation of leukocytes in the glomeruli.

Topics: Animals; Cyclosporine; gamma-Globulins; Glomerulonephritis; Glucosides; Immunohistochemistry; Immunosuppressive Agents; Kidney Glomerulus; Leukocyte Count; Leukocytes; Male; Phenols; Plants, Medicinal; Proteinuria; Rats; Rats, Sprague-Dawley