Protective effect of Huang Gan formula in 5/6 nephrectomized rats by depressing the Wnt/β-catenin signaling pathway

Abstract

Huang Gan formula (HGF) is a new traditional Chinese herbal medicine created according to the basic theory of traditional Chinese medicine. The aim of this study is to evaluate the effects of HGF on chronic kidney disease and determine the mechanisms of action. The extract of HGF was prepared, and qualitative and quantitative determination of phytochemical was performed with quadrupole time-of-flight mass spectrometer and high-performance liquid chromatography. Sprague-Dawley rats (n=72) were submitted to 5/6 nephrectomy (Nx), and then respectively treated with uremic clearance granule, losartan, HGF low dose, HGF middle dose, and HGF high dose once per day for 12 weeks. The sham group of operated rats (n=22) was treated with normal saline or HGF middle dose as a background control group. Blood and urine biochemical parameters, renal tissue morphology, and mRNA and proteins of Wnt/β-catenin signaling pathways were investigated. The results showed that the quality of the extraction process could be controlled, and a total of eight major compounds were identified and quantified. HGF could decrease the level of serum creatinine, blood urea nitrogen, and urine protein and increase the renal index and creatinine clearance rate in a dose-dependent manner. HGF also remarkably reduced the glomerulosclerosis and tubulointerstitial fibrosis by blocking the Wnt/β-catenin signaling pathway through inhibiting the Wnt1, β-catenin, transcription factor 4, and fibronectin 1 expressions, simultaneously measured through mRNA and protein levels in the remnant kidney. These results suggest that extraction of HGF could improve remnant renal function and possibly ameliorate glomerulosclerosis and tubulointerstitial fibrosis by depressing the Wnt/β-catenin signaling pathway.

Cyclin G2 Suppresses Glomerulosclerosis by Regulating Canonical Wnt Signalling

“…High-glucose conditions and oxidative stress promote the activation of canonical Wnt signalling in the kidneys in diabetic animal models [ 12 ]. Investigators have demonstrated that the Huang Gan formula improved remnant renal function and alleviated glomerulosclerosis and tubulointerstitial fibrosis potentially by suppressing the canonical Wnt signalling pathway [ 28 ]. These results indicated that the canonical Wnt signalling pathway plays a vital role in DN.…”

Global miRNA expression is temporally correlated with acute kidney injury in mice

“…Furthermore, 10 KEGG pathways were revealed to be significantly regulated by miRNAs in renal pathology, which was consistent with previous studies reporting that miRNAs are vital regulators of signal transduction in renal pathologies ( Badal & Danesh, 2015 ; Trionfini, Benigni & Remuzzi, 2015 ). Dysregulated p53 and Wnt signaling pathways were associated with the increased level of serum creatinine aroused by renal pathology ( Ghosh et al, 2015 ; Mo et al, 2015 ). Our results revealed a potential role of miR-18a in regulating the p53 signaling pathway and abnormal expression of miR-210 in AKI might influence the Wnt and apoptosis signaling pathways.…”

Huang Gan Formula Eliminates the Oxidative Stress Effects of Advanced Oxidation Protein Products on the Divergent Regulation of the Expression of AGEs Receptors via the JAK2/STAT3 Pathway

“…All compounds were supplied by Kangmei Pharmaceutical Co., Ltd (Guangdong, China) and were identified by Professor Hongwei Zhang of the School of Traditional Chinese Medicine at Southern Medical University. HGF was prepared according to our previous study [ 14 ].…”

“…HGF compound was chemically characterized by HPLC–Q-TOF-MS spectrometry. Eight major compounds were found and measured by comparison with reference standards [ 14 ]. We previously showed that HGF significantly decreased oxidative stress, improved renal function, and delayed renal fibrosis in rat models of CKD caused by adenine or 5/6 nephrectomy [ 14 ].…”

“…Eight major compounds were found and measured by comparison with reference standards [ 14 ]. We previously showed that HGF significantly decreased oxidative stress, improved renal function, and delayed renal fibrosis in rat models of CKD caused by adenine or 5/6 nephrectomy [ 14 ]. However, the precise mechanisms by which HGF regulates RAGE expression have not been fully clarified.…”