Preliminary study of the mechanism underlying how Jianshen Granules ameliorate renal failure in 5/6 nephrectomy model rats

Abstract

Background Chronic renal failure (CRF) is a worldwide public health concern, and at present, there are limited treatment options available. Jianshen Granules, a traditional Chinese herbal medicine, have been used clinically in the treatment of renal diseases for a large number of years in the Air Force Medical Center of the Chinese People's Liberation Army (PLA), and have shown great efficacy. In the present study, both the effectiveness and the mechanism of action of Jianshen Granules to treat CRF were investigated. Methods A rat model of CRF was established by 5/6 nephrectomy. Rats were administered distilled water, Uremic Clearance Granules (UCGs), or Jianshen Granules. During the administration period, the physiological state of the rats was observed, and the biochemical parameters of interest were measured. The pathology of the kidney tissues were assessed using hematoxylin and eosin, and Masson’s staining. In addition, the expression level of transforming growth factorβ1 (TGFβ1) was detected. Human kidney cells (HKC cells) were used to investigate the effects of Jianshen Granules on apoptosis induced by hydrogen peroxide (H2O2), whereas cell viability was assessed by Cell Counting Kit8 (CCK8) assay. The level of apoptosis, the mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) and Ca2 + levels were measured using flow cytometry. Results The results revealed that Jianshen Granules could reduce the levels of serum creatinine, blood urea nitrogen, alanine aminotransferase and aspartate aminotransferase, and the volume of urine in CRF rats. Renal histopathological examinations revealed that Jianshen Granules had an ameliorative effect on renal injury. In addition, Jianshen Granules led to a marked decrease in TGFβ1 levels in CRF rats. Following treatment with Jianshen Granules, cell viability and the level of the MMP increased, whereas the levels of ROS and Ca2+ were reduced significantly. The increased level of TGFβ1 was detected in the H2O2treated group, although this increase was attenuated by treatment with Jianshen Granules. Conclusion Taken together, the results of the present study have shown that Jianshen Granules are able to ameliorate renal failure in CRF rats, and to inhibit apoptosis of HKC cells induced by H2O2 via downregulation of TGFβ1.