Inhibitory effects of Shenkang injection and its main component emodin on the proliferation of high glucose-induced renal mesangial cells through cell cycle regulation and induction of apoptosis

Increased mesangial cell proliferation is a major pathological feature of early-stage diabetic nephropathy (DN). The present study investigated the effects of the Traditional Chinese Medicine Shenkang injection (SKI) and its main component emodin (EM) on high glucose-cultured mesangial cells. The proliferation rate, cell cycle distribution, apoptosis and morphology of rat renal mesangial cells (RMCs) cultured in the presence of various concentrations of glucose (5.6 or 25 mM), SKI (25, 50 or 100 mg/l) or EM (10, 20 or 40 mu M) were assessed at time-points of 12, 24 or 48 h. High-glucose treatment promoted the proliferation of RMCs, which was significantly inhibited by SKI and EM, while these drugs had no effect on RMCs under normal glucose conditions, as indicated by an MTT assay. Furthermore, flow cytometric analysis revealed that SKI and EM inhibited the cell cycle progression of RMCs and induced apoptosis. Transmission electron microscopy revealed morphological characteristics of apoptosis and western blot analysis demonstrated the upregulation of B-cell lymphoma 2-associated X protein (bax) and activation of caspases in RMCs following treatment with SKI or EM under high-glucose conditions. In conclusion, SKI and its major active component EM were shown to inhibit high-glucose-induced proliferation of RMCs via inducing cell cycle arrest at G(1) phase as well as cellular apoptosis via upregulation of pro-apoptotic mediators bax and caspase activation, and may therefore be suitable for the treatment of DN.