Modified Huangqi Chifeng Decoction Attenuates Proteinuria by Reducing Podocyte Injury in a Rat Model of Immunoglobulin a Nephropathy

Abstract

Modified Huangqi Chifeng decoction (MHCD) has been used to reduce proteinuria in immunoglobulin A nephropathy (IgAN) for many years. Previously, we have demonstrated its protective role in glomerular mesangial cells. Podocyte injury, another key factor associated with proteinuria in IgAN, has also attracted increasing attention. However, whether MHCD can reduce proteinuria by protecting podocytes remains unclear. The present study aimed to investigate the protective effects of MHCD against podocyte injury in a rat model of IgAN. To establish the IgAN model, rats were administered bovine serum albumin, carbon tetrachloride, and lipopolysaccharide. MHCD in three doses or telmisartan was administered once daily for 8 weeks (n = 10 rats/group). Rats with IgAN developed proteinuria at week 6, which worsened over time until drug intervention. After drug intervention, MHCD reduced proteinuria and had no effect on liver and kidney function. Furthermore, MHCD alleviated renal pathological lesions, hyperplasia of mesangial cells, mesangial matrix expansion, and podocyte foot process fusion. Western blot analysis revealed that MHCD increased the expression of the podocyte-associated proteins nephrin and podocalyxin. Additionally, we stained podocyte nuclei with an antibody for Wilms’ tumor protein one and found that MHCD increased the podocyte number in rats with IgAN. In conclusion, these results demonstrate that MHCD attenuates proteinuria by reducing podocyte injury.

Protective effects of budesonide on LPS‑induced podocyte injury by modulating macrophage M1/M2 polarization: Evidence from in vitro and in silico studies

“…As aforementioned, podocyte injury is a key factor associated with proteinuria in IgAN ( 5 ), in which inflammation-induced podocyte injury serves an important role ( 42 ). To establish an in vitro podocyte injury model, the specific LPS concentration able to induce podocyte injury was determined with a CCK-8 assay before sampling and testing.…”

“…IgAN patients will develop proteinuria, which will continue to worsen. Podocyte injury under inflammatory stress is a key factor associated with proteinuria in IgAN patients ( 5 ). Based on a microarray dataset GSE83233, the TNF-α pathway was identified as an important signal when Bud exerts its anti-inflammatory effects.…”

“…The mainstay of therapy is therefore optimized supportive care, i.e., measures that lower blood pressure, reduce proteinuria and help to decrease nonspecific insults to the kidneys ( 4 ). Glomerular podocyte injury is a key factor associated with proteinuria in IgAN ( 5 ). Clinical research shows that Bud is effective in the treatment of patients with IgAN at high risk of progression in terms of reducing proteinuria and preserving renal function over 24 months of therapy ( 6 ).…”

“…5 cells/ml) were cultured with normal medium, 0.1 µg/ml LPS, 10 µM curcumin, 5 µM Bud, 10 µM Bud, or 20 µM Bud and (Nor)MS, (LPS)MS, (Cur)MS, (Bud5)MS, (Bud10)MS, or (Bud20)MS for 22 h at 37˚C. Podocytes were then seeded into 96-well plates.…”

Efficacy and safety of Shenkang injection in the treatment of chronic renal failure

“…Shenkang injection contains dahuang ( Radix et Rhizoma Rhei ), danshen ( Radix Salviae Miltiorrhiae ), honghua ( Flos Carthami ), and huangqi ( Radix Astragali ). Modern studies have found that dahuang ( Radix et Rhizoma Rhei ) can improve kidney function and improve pathological kidney damage, [ 23 ] reduce the LPS-induced inflammatory macrophage response, [ 24 ] reduce renal fibrosis and delay renal failure [ 25 ] ; huangqi ( Radix Astragali ) can protect glomerular mesangial cells and reduce proteinuria, [ 26 ] promote water and sodium excretion, and protect the kidney [ 27 ] ; danshen ( Radix Salviae Miltiorrhiae ) has anti-inflammatory, anticoagulant, and antioxidant properties [ 28 ] and anti-anemia effect, [ 29 ] can effectively improve the microcirculation in CRF patients.…”