Effects of Rikkunshito treatment on renal fibrosis/inflammation and body weight reduction in a unilateral ureteral obstruction model in mice.

Abstract

Chronic kidney disease (CKD) progresses to end-stage renal failure via renal tubulointerstitial fibrosis. Malnutrition, inflammation, and arteriosclerosis interact to exacerbate the poor prognosis of CKD, and their effective management is thus essential. The traditional Japanese medicine Rikkunshito (RKT) exerts appetite-stimulating effects via ghrelin, which attenuates inflammation and fibrosis. We evaluated the therapeutic effect of RKT in unilateral ureter obstruction (UUO)-induced renal fibrosis/inflammation and body weight loss in mice. UUO and sham-operated mice were fed a standard diet or diet containing 3.0% RKT. Renal fibrosis was investigated by histopathology and macrophage infiltration was determined by immunohistochemistry. Expression levels of genes associated with fibrosis, inflammation, ghrelin, and mitochondrial function were determined by quantitative reverse transcription-polymerase chain reaction and western blot analyses. RKT treatment partially prevented UUO-induced weight loss but failed to attenuate renal fibrosis and inflammation. Renal expression of sirtuin 1, a ghrelin-downstream signalling molecule, and gene expression of peroxisome proliferator-activated receptor-γ coactivator 1α and Bcl-2/adenovirus E1B interacting protein 3 were unaffected by RKT. These results indicate that RKT inhibits weight loss but does not improve renal fibrosis or inflammation in a rapidly progressive renal fibrosis mouse model. RKT may have a protective effect on weight loss associated with CKD.

• Authors: Hiromichi Wakui, Takahiro Yamaji, Kengo Azushima, Kazushi Uneda, Kotaro Haruhara, Akiko Nakamura, Kohji Ohki, Sho Kinguchi, Ryu Kobayashi, Shingo Urate, Toru Suzuki, Daisuke Kamimura, Shintaro Minegishi, Tomoaki Ishigami, Tomohiko Kanaoka, Kohei Matsuo, Tomoyuki Miyazaki, Tetsuya Fujikawa, Akio Yamashita, Kouichi Tamura
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 1782 (02 05 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 32024850 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drugs, Chinese Herbal
• liu-jun-zi-tang
• Sirtuin 1

Topics

• Animals
• Body Weight (drug effects)
• Disease Models, Animal
• Drugs, Chinese Herbal (pharmacology, therapeutic use)
• Fibrosis (drug therapy, etiology, metabolism, pathology)
• Inflammation (drug therapy, etiology)
• Kidney (drug effects, metabolism, pathology)
• Male
• Mice
• Renal Insufficiency, Chronic (drug therapy, etiology, metabolism, pathology)
• Signal Transduction (drug effects)
• Sirtuin 1 (metabolism)
• Ureteral Obstruction (complications, metabolism, pathology)