Keishibukuryogan Reduces Renal Injury in the Early Stage of Renal Failure in the Remnant Kidney Model

Takako Nakagawa,Yutaka Shimada,Hiroshi Oka,Hirozo Goto,Shinya Sakai,Naotoshi Shibahara,Izumi Tashiro,Makoto Fujimoto,Michiko Jo

doi:10.1093/ecam/nep089

Abstract

The effects of keishibukuryogan on the early stage of progressive renal failure were examined in rats subjected to 5/6 nephrectomy. Keishibukuryogan, one of the traditional herbal formulations, was given orally at a dose of 1% (w/w) and 3% (w/w) in chow. Administration of keishibukuryogan was started at 1 week after 5/6 nephrectomy and was continued for 4 weeks. At the end of the experiment, Azan staining did not reveal any severe histological changes in the kidneys of the nephrectomized rats. On the other hand, significant increases in mRNA expressions of transforming growth factor-β 1 and fibronectin related to tissue fibrosis, as examined by Reverse Transcriptase-Polymerase Chain Reaction, were observed in nephrectomized rats, and they were significantly suppressed by 3% keishibukuryogan treatment. Against gene expressions related to macrophage infiltration, 3% keishibukuryogan treatment significantly suppressed osteopontin mRNA levels, and monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1 mRNA levels showed a tendency to decrease, but without statistical significance. It was also observed that 3% keishibukuryogan attenuated serum urea nitrogen and urinary protein excretion levels. From these results, it was suggested that keishibukuryogan exerts beneficial effects that result in slowing the progression of chronic renal failure.

Highlights

Chronic renal failure (CRF) is one of the serious health problems that are linked to increasing incidence and prevalence as well as a reduction in the quality of life and a rise in the cost of its care
Significant increases in mRNA expressions of transforming growth factor-β1 and fibronectin related to tissue fibrosis, as examined by Reverse Transcriptase-Polymerase Chain Reaction, were observed in nephrectomized rats, and they were significantly suppressed by 3% keishibukuryogan treatment
Among the renal structural changes, tubulointerstitial fibrosis is known to be a common histological appearance in patients with CRF, and it is thought to be correlated with the decline of renal function and prognosis [13, 14]

Summary

Introduction

Chronic renal failure (CRF) is one of the serious health problems that are linked to increasing incidence and prevalence as well as a reduction in the quality of life and a rise in the cost of its care. Current therapy with agents that block the renin-angiotensin system and exert protein restriction are commonly employed management strategies of renal failure [1]. The number of patients with renal failure, especially patients undergoing hemodialysis and facing end-stage renal failure, is increasing worldwide. Searches for new effective therapeutic approaches are needed for CRF, including the use of alternative medicines such as traditional herbal medicine. Traditional Chinese/Japanese medicine has a long history and has contributed to the prevention and treatment of various diseases. Keishibukuryogan was first mentioned in “Kinki-Yohryaku” (Jin-Gui-Yao-Lue), a classic text of Chinese medical science written in the 3rd century AD

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