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 proliferatoractivated 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. The number of patients with chronic kidney disease (CKD) progressing to end-stage renal disease is increasing worldwide. Not only does CKD lead to end-stage renal disease, it is also associated with a high risk of cardiovascular disease and mortality. In patients with CKD, malnutrition, inflammation, and arteriosclerosis adversely affect each other and exacerbate their poor prognosis 1,2. Therefore, the effective management of these pathological conditions is the key for the treatment of CKD. Rikkunshito (RKT) is a traditional Japanese herbal medicine (Kampo medicine) that has historically been used to treat abnormalities of the digestive/nutrient absorption system. Ghrelin activation by RKT has been

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“…Paces for discovering the mechanism of renal fibrosis have never stopped. Motivated by the goal of developing novel therapies for kidney diseases, researchers have made great efforts to investigate potential solutions (Klinkhammer et al, 2017 ; Liu and Zhuang, 2019 ; Wakui et al, 2020 ). Our study has uncovered a TRIM6-involved regulatory mechanism of renal fibrosis through the mTOCR1 signaling pathway for the first time.…”

Japanese Traditional Herbal Medicine, Rikkunshito, Partially Suppresses Inflammatory Responses in Myocardial Ischemia/Reperfusion Injury

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“…2190043010) were supplied by Tsumura &Co. (Tokyo, Japan) and dissolved in distilled water (DW). RKT is formulated from eight kinds of herbal components [ 26 ]. The detailed components of RKT are shown in Table 1 .…”

Effects of 5/6 nephrectomy and high-protein diet on glomerular and tubular injuries in mice

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