Abstract
Objective Jian-Pi-Yi-Shen formula (JPYSF) is a traditional Chinese herbal decoction and has been used for treating chronic kidney disease (CKD) in clinics for decades. However, the potential mechanisms have not been fully elucidated. This study was designed to test the efficacy of JPYSF in treating CKD and explore the underlying mechanism. Methods Two CKD rat models were established by 5/6 nephrectomy (5/6 Nx) and feeding with adenine-containing feed, respectively. The intervention dose of JPYSF was 10.89 g/kg/d by gastric irrigation. Renal function was assessed by serum creatinine (Scr) and blood urea nitrogen (BUN). Periodic acid-Schiff (PAS) and Masson's trichrome staining were used to evaluate renal histopathological changes. The levels of nicotinamide adenine dinucleotide (NAD+) were measured by using the enzyme-linked immunosorbent assay kit. The proteins expressions of renal fibrosis, quinolinate phosphoribosyltransferase (QPRT), sirtuin 3 (SIRT3), and mitochondrial dynamics were determined and quantified by Western blot analysis. Results The results show that administration of JPYSF significantly lowered Scr and BUN levels, improved renal tubular atrophy and interstitial fibrosis, and decreased renal extracellular matrix deposition in two CKD rat models. In addition, CKD rats exhibited suppressed QPRT/NAD+/SIRT3 signal, increased mitochondrial fission, and decreased mitochondrial fusion. JPYSF treatment promoted QPRT/NAD+/SIRT3 signal and restored mitochondrial fission/fusion balance. Conclusion In conclusion, administration of JPYSF effectively alleviated CKD progression in two rat models, which may be related with regulation of the QPRT/NAD+/SIRT3/mitochondrial dynamics pathway.
Highlights
Xinhui Liu,1 Siqi Liu,1 Bing Zhang,1 Denggui Luo,1 Shiying Huang,2 Fochang Wang,2 Lin Zheng,2 Jiandong Lu,1 Jianping Chen,2 and Shunmin Li 1
Administration of Jian-Pi-Yi-Shen formula (JPYSF) effectively alleviated chronic kidney disease (CKD) progression in two rat models, which may be related with regulation of the quinolinate phosphoribosyltransferase (QPRT)/Nicotinamide adenine dinucleotide optic atrophy 1 (OPA-1) (NAD)+/sirtuin 3 (SIRT3)/mitochondrial dynamics pathway
JPYSF is composed of eight traditional Chinese herbal medicines, including Astragalus mongholicus Bunge (Fabaceae), Atractylodes macrocephala Koidz. (Asteraceae), Dioscorea oppositifolia L. (Dioscoreaceae), Cistanche deserticola Ma (Orobanchaceae), Wurfbainia vera (Blackw.) Skornick. and A
Summary
JPYSF is composed of eight traditional Chinese herbal medicines, including Astragalus mongholicus Bunge (Fabaceae), Atractylodes macrocephala Koidz. The supernatant was dried by a freeze dryer and stored at −80°C. e chemical profile and quality control of JPYSF extract have been well described by using ultraperformance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOFMS/MS) in our previous study [18]. A total of 71 compounds were identified from JPYSF extract, including saponins, flavonoids, sesquiterpenoids, coumarins, phenylpropanoids, anthranones, anthraquinones, tannins, phenolic acids, and others. Twelve main constituents were chosen as chemical markers to evaluate the quality of JPYSF extract. Is standard guarantees the quality of JPYSF extract used in our study Twelve main constituents were chosen as chemical markers to evaluate the quality of JPYSF extract. e minimum quantities (in μg/g) of these 12 constituents present in JPYSF extract dry powder are 1361.01 for rhein, 519.60 for salvianolic acid A, 251.73 for liquiritin, 98.03 for acteoside, 76.06 for calycosin 7-O-glucoside, 61.64 for rosmarinic acid, 41.39 for formononetin, 25.03 for calycosin, 13.05 for astragaloside IV, 8.95 for atractylenolide I, 3.45 for dioscin, and 0.21 for tanshinone IIA. is standard guarantees the quality of JPYSF extract used in our study
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