Justicidin B Inhibits PDGF-BB-Induced Proliferation and ECM Accumulation in Mesangial Cells via Nrf2/HO-1 and Akt/mTOR Signaling Pathway

Abstract

Mesangial proliferative glomerulonephritis (MsPGN) is characterized by mesangial cell proliferation, inflammation, and extracellular matrix deposition in the mesangial area, which develops into glomerulosclerosis and contributes to end-stage renal disease. Justicidin B is a bioactive compound isolated from Justicia procumbens L., a traditional herbal remedy that reduces proteinuria in nephritis. However, the mechanism of Justicidin B’s therapeutic effect on MsPGN remains unclear. This study was aimed to explore the positive effect of Justicidin B on MsPGN. The results showed that Justicidin B attenuated the proliferation induced by platelet-derived growth factor-BB (PDGF-BB) in MCs and blocked cell cycle progression. Likewise, inflammatory factors, including monocyte chemotactic protein 1 (MCP-1) and tumor necrosis factor alpha (TNF-α), in MCs were decreased after treatment with Justicidin B. In addition, Justicidin B exhibited antioxidant activity in PDGF-BB-induced MCs, shown by the decreased production of malondialdehyde and T-AOC, and increased the expression of superoxide dismutase. Besides, Justicidin B suppressed extracellular matrix (ECM) deposition by reducing the protein levels of collagen IV and fibronectin. Furthermore, we found that Justicidin B significantly inhibited activation of the Akt/mammalian target of rapamycin (mTOR) signaling pathway in MCs induced by PDGF-BB, but enhanced the levels of proteins in the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. Taken together, Justicidin B prevented PDGF-BB-induced proliferation, inflammation, oxidative stress, and ECM accumulation via regulating the activation of the Nrf2/HO-1 pathway and the Akt/mTOR signaling pathway.