Jian-Pi-Yi-Shen Formula Improves Adenine-Induced Chronic Kidney Disease via Regulating Tryptophan Metabolism and Aryl Hydrocarbon Receptor Signaling
Liu X, Deng R, Chen Y, Huang S, Lu J, Zheng L, Xiong G, Li S · Frontiers in Pharmacology · 2022 July 05
DOI 10.3389/fphar.2022.922707
Objective
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.
Conclusions
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.
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Insights
The Jian Pi Yi Shen formula in traditional Chinese medicine demonstrates a protective effect on kidneys by modulating tryptophan metabolism and Aryl hydrocarbon receptor activation.
A chronic kidney disease (CKD) rat model was induced by feeding a diet containing 0.75% adenine over a four-week period. Concurrently, the Jian-Pi-Yi-Shen formula was administered every day starting from the third week and continued for four additional weeks. Multiple factors were evaluated including renal injury, fibrotic markers expression, and serum creatinine and blood urea nitrogen levels. The levels of 10 tryptophan metabolites in the rat serum and Aryl hydrocarbon receptor signaling were detected and analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry and Western blot analysis, respectively.
The Jian-Pi-Yi-Shen formula demonstrated significant effects of reducing both serum creatinine and blood urea nitrogen levels and improving renal pathological injuries in the CKD rat model. It was found that the formula also regulated tryptophan metabolism and decreased the levels of tryptophan metabolites in the serum. Furthermore, the formula suppressed the overactivated Aryl hydrocarbon receptor signaling in the kidney. These observations imply that the actions of the Jian-Pi-Yi-Shen formula could effectively protect against CKD.
