The Study of Chinese Medicinal Herbal Formula Shen San Fang in the Treatment of Experimental IgA Nephropathy

Abstract

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, yet there is no effective or specific therapy. Shen San Fang (S3F) is a traditional Chinese herbal medicinal formula that has been used in China for many years to treat patients with hematuria. The aim of this study is to test the therapeutic value of S3F in an experimental model of IgAN. IgAN was induced in Lewis rats by continuous oral immunization with bovine gamma-globulin (BGG) in the drinking water for 8 weeks, followed by intravenous injection of 1 mg BGG daily for 3 successive days. The rats were randomly divided into four groups (five rats/group): control, control receiving S3F, induction of IgAN, and IgAN receiving S3E S3F decoction was fed to rats beginning week 4 from the first day of oral sensitization with BGG. The S3F treatment was continued until the rats were sacrificed or for a 4-week period. Hematuria, renal immunohistochemistry for IgA and transforming growth factor-beta 1 (TGF-beta1), renal histopathology, and renal content of TGF-beta1 were measured. Rats developing IgAN had marked hematuria, profound mesangial proliferation and mesangial expansion, intense and diffuse glomerular IgA deposition, increased glomerular TGF-beta1 expression, and raised renal TGF-beta1 levels. S3F treatment resulted in a significant reduction of hematuria, decreased mesangial IgA deposition, weaker immunostaining of TGF-beta1 in glomerulus, and a lower renal TGF-beta1 concentration. Our animal data suggests a therapeutic value for the Chinese medicinal formula S3F in experimental IgAN. This beneficial effect was due to reduced glomerular IgA deposition and TGF-beta1 expression. Our preliminary findings hold promise for future human therapy.

Additive effect of PPAR-γ agonist and ARB in treatment of experimental IgA nephropathy

“…In preliminary experiments, hematuria and glomerular IgA deposition were only observed at week 6 after oral immunization and thereafter [10]. The rats were then randomly divided into six groups (five rats/group): control, IgAN without nephrectomy (IgAN/2K) receiving vehicle, IgAN with unilateral nephrectomy (IgAN/1K) receiving vehicle, and IgAN/1K receiving rosiglitazone (Ros) at 10 mg/kg/day, losartan (Los) at 10 mg/kg/day, or Ros plus Los at 10 mg each/kg/day.…”

“…IgA nephropathy was induced in 4-week-old Lewis rats by continuous oral immunization with BGG in the drinking water for 8 weeks, followed by intravenous injection of 1 mg BGG daily for 3 successive days as described previously [10]. In preliminary experiments, hematuria and glomerular IgA deposition were only observed at week 6 after oral immunization and thereafter [10].…”

“…In this report, we explored the clinical implication of these in vitro findings in an accelerated model of murine IgAN induced by oral immunization with bovine gamma-globulin (BGG). The reason for performing unilateral nephrectomy (Unx) stems from the known mild histopathology with this model even after prolonged observation [10]. Unilateral nephrectomy will hasten the development of typical glomerular abnormalities [11].…”

Rapamycin Slows IgA Nephropathy Progression in the Rat

“…IgAN was induced by continuous oral immunization with bovine γ-globulin (BGG) 0.1% (Sigma, St. Louis, Mo., USA) with 6 m M HCl in tap water for 8 weeks, followed by tail intravenous injection of 1 mg BGG daily for 3 successive days [22,23,24,25]. For the control group, saline replaced the BGG.…”

Does Arkadia contribute to TGF-β1-induced IgA expression through up-regulation of Smad signaling in IgA nephropathy?

“…TGF-b 1 is a multifunctional cytokine that affects a variety of biological processes, including extracellular matrix accumulation, inflammation, wound repair, differentiation and immune response [3]. Extensive clinical and experimental evidence shows that the expression of TGF-b 1 is increased in human IgAN and experimental mesangial proliferative glomerulonephritis compared with control groups [4][5][6][7][8], and TGF-b 1 antagonist prevents the development of glomerular sclerosis in an experimental mesangial proliferative glomerulonephritis [9]. However, these studies only demonstrated that TGF-b 1 mediated the progression of IgAN through inducing extracellular matrix accumulation, but the effect of TGF-b 1 on IgA has not been investigated in the mechanism of IgAN.…”