Jian-Pi-Yi-Shen Formula Improves Adenine-Induced Chronic Kidney Disease via Regulating Tryptophan Metabolism and Aryl Hydrocarbon Receptor Signaling

Abstract

Traditional Chinese medicine (TCM) is an important complementary and alternative branch of chronic kidney disease (CKD) therapy. Jian-Pi-Yi-Shen formula (JPYSF) is a TCM formula used for treating CKD with good efficacy. However, the underlying mechanisms of JPYSF in treating CKD remain to be elucidated. The purpose of the present study was to investigate the renoprotective effect and potential mechanism of JPYSF in treating CKD. CKD rat model was induced by feeding a diet containing 0.75% w/w adenine for 4 weeks. JPYSF was given by gavage every day, starting from the 3rd week of the adenine-containing diet and continuing for 4 weeks at the dose of 10.89 g/kg. Renal injury was evaluated by serum creatinine (Scr), blood urea nitrogen (BUN), histopathology, and fibrotic markers expression. Serum levels of tryptophan metabolites were detected by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Aryl hydrocarbon receptor (AHR) signaling was tested by Western blot analysis. The results found that JPYSF treatment significantly lowered Scr and BUN levels, improved renal pathological injury, and down-regulated fibrotic markers expression in CKD rats. Furthermore, JPYSF significantly reduced the levels of 10 tryptophan metabolites in the serum of CKD rats and restored the level of tryptophan. Additionally, the kidney expression of AHR signaling was enhanced in CKD rats and was further suppressed in JPYSF treated rats. These results suggested that JPYSF protected against adenine-induced CKD via modulating tryptophan metabolism and AHR activation.

Potential Effects of Traditional Chinese Medicine in Anti-Aging and Aging-Related Diseases: Current Evidence and Perspectives

“…Salvia miltiorrhiza Bunge , Rheum palmatum L., Glycyrrhiza uralensis Fisch Modulate QPRT/NAD+/SIRT3/Mitochondrial Dynamics Pathway and regulate Tryptophan Metabolism and Aryl Hydrocarbon Receptor Signaling. [ 102 , 103 ] Type 2 diabetes Qijian mixture Astragalus membranaceus, Ramulus euonymi, Coptis chinensis and Pueraria lobata, Acte through TP53, AKT1 and PPARA proteins [ 104 ] Chronic obstructive pulmonary disease Bufei Yishen formula Ginseng Radix et Rhizoma, Astragali Radix, Corni Fructus, Lycii Fructus, Schisandra Chinensis Fructus, Fritillariae Thunbergii Bulbus, Perillae Fructus, Citri Reticulatae Pericarpium, Epimedii Folium, Paeoniae Rubra Radix, Pheretima, Ardisiae Japonicae Herba Restore Th17/Treg balance via reciprocally modulating the activities of STAT3 and STAT5 [ 105 ] …”

Moshen granule ameliorates membranous nephropathy by regulating NF-ƙB/Nrf2 pathways via aryl hydrocarbon receptor signalling

“…These findings indicate that AHR signaling is extensive activated in various pathological types of patients with CKD. Several recent publications demonstrated that Chinese traditional patent medicines, such as Jian-Pi-Yi-Shen formula, Dahuang Fuzi decoction and Bupi Yishen formula ameliorated CKD partly by inhibiting AHR signaling [ [43] , [44] , [45] ].…”

Jian-Pi-Yi-Shen formula alleviates renal fibrosis by restoring NAD+ biosynthesis in vivo and in vitro

“…Renal fibrosis is a common terminal outcome of CKD, leading to progressive loss of renal function and eventually kidney failure. Studies have shown that JPYSF protected kidney from fibrotic injury [12,13,51]. Some active ingredients in JPYSF have been reported to exert anti-fibrotic effects through acting on cellular signal pathways, such as inhibiting the TGF-β1 pathway, activating Sirt1-mediated autophagy, and inhibiting the Wnt3a/β-catenin pathway [52][53][54][55][56].…”

“…Jian-Pi-Yi-Shen formula (JPYSF), a Chinese herbal prescription with a decades-long history, has demonstrated significant efficacy in the treatment of CKD. Our previous studies have shown that JPYSF possesses the ability to alleviate renal fibrosis and retard CKD progression in rat models induced by 5/6 nephrectomy or adenine [11][12][13]. However, the renoprotective mechanism of JPYSF warrants further investigation.…”