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- W2953587999 abstract "Targeting gut microbiota dysbiosis and uremic toxins accumulation is important for the amelioration of renal dysfunction in chronic renal failure (CRF). Total flavone of abelmoschus manihot (TFA), a natural extract, has been applied extensively for treatment of the CRF patients in China. However, its therapeutic mechanisms remained elusive. Therefore, in this study, using an adenine-induced renal failure (RF) rat model, we examined the effects of TFA on the gut-kidney axis in vivo, compared with lubiprostone (LUB), then to clarify the potential mechanisms. Rats were randomly divided into 4 groups, the Sham-operated group, the Vehicle-given group, the TFA-treated group and the LUB-treated group. TFA, LUB and saline were daily administrated for 4 weeks after induction of RF by adenine gavage with unilateral ureteral obstruction (UUO). Renal injurious and dysfunctional indicators, tubulointerstitial fibrosis (TIF), fecal microbiota, gut-derived uremic toxins, colon histological characteristics and tight junction proteins expressions, as well as the key protein expression levels of TLR4/NF-κB/NLRP3 inflammasome pathways in the colon and the kidneys were examined, respectively. In the RF model rats, in addition to renal lesions and uremic toxins accumulation, the abundance of Lactobacillus in the gut was decreased, while that of C. perfringens in the gut was increased; There appeared the ulcers in the colon, accompanied with the low-expression of ZO-1 and claudin-1; Besides, TLR4/NF-κB/NLRP3 inflammasome pathways in the colon and the kidneys were activated, respectively. After the treatment of TFA or LUB, renal dysfunction and TIF in the RF model rats were significantly improved. Furthermore, the disordered Lactobacillus, Enterococcus, E. coli and C. perfringens in the gut, the damaged intestinal environment and the accumulative indoxyl sulfate and p-cresyl sulfate in serum were all ameliorated. More notably, TFA synchronously inhibited TLR4/NF-κB/NLRP3 inflammasome pathways activity in the colon and the kidneys, whereas, LUB only suppressed TLR4/NF-κB/NLRP3 inflammasome pathway activity in the colon. TFA, as a natural regulator in vivo, regulates the gut-kidney axis and ameliorates renal dysfunction in the RF model rats by modulating gut microbiota, reducing uremic toxins and inhibiting TLR4/NF-κB/NLRP3 inflammasome pathways activity in the colon and the kidneys, which is different from LUB. These findings may provide the first evidence for the gut-kidney axis, as the unusual target of TFA treatment in CRF." @default.
- W2953587999 created "2019-07-12" @default.
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- W2953587999 date "2019-07-01" @default.
- W2953587999 modified "2023-09-26" @default.
- W2953587999 title "SUN-004 THE REGULATION OF THE GUT-KIDNEY AXIS IN VIVO BY TOTAL FLAVONE OF ABELMOSCHUS MANIHOT, A NATURAL EXTRACT, CONTRIBUTES TO THE AMELIORATION OF ADENINE-INDUCED RENAL FAILURE" @default.
- W2953587999 doi "https://doi.org/10.1016/j.ekir.2019.05.396" @default.
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