Fisetin Improves Hyperuricemia-Induced Chronic Kidney Disease via Regulating Gut Microbiota-Mediated Tryptophan Metabolism and Aryl Hydrocarbon Receptor Activation

Ren, Qian; Cheng, Lu; Guo, Fan; Tao, Sibei; Fu, Ping

doi:10.1021/acs.jafc.1c03449

Cited by 35 publications

(30 citation statements)

References 47 publications

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“…In addition, studies also found that some chemical drugs also modulate Trp metabolism in gut microbiota, such that Fisetin can modulate the gut microbiota-mediated Trp metabolism [ 57 ]. Rifaximin affected Trp synthesis in the gut microbiota [ 58 ].…”

Section: Trp Metabolism In Gut Microbiotamentioning

confidence: 99%

“…Fructooligosaccharides protect against OVA-induced food allergy in mice by regulating the Th17/Treg cell balance using Trp metabolites [ 46 ]. Fisetin could improve hyperuricemia-induced chronic kidney disease via regulating the gut microbiota-mediated Trp metabolism [ 57 ]. Interestingly, honeybee gut lactobacillus modulates host learning and memory behaviors via regulating the Trp metabolism [ 175 ].…”

Section: Potential Application Of Gut Microbiota-derived Trp Metaboli...mentioning

confidence: 99%

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Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis

Gao

Yang

2022

Cells

130

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Tryptophan is an essential amino acid from dietary proteins. It can be metabolized into different metabolites in both the gut microbiota and tissue cells. Tryptophan metabolites such as indole-3-lactate (ILA), indole-3-acrylate (IAC), indole-3-propionate (IPA), indole-3-aldehyde (IAID), indoleacetic acid (IAA), indole-3-acetaldehyde and Kyn can be produced by intestinal microorganisms through direct Trp transformation and also, partly, the kynurenine (Kyn) pathway. These metabolites play a critical role in maintaining the homeostasis of the gut and systematic immunity and also potentially affect the occurrence and development of diseases such as inflammatory bowel diseases, tumors, obesity and metabolic syndrome, diseases in the nervous system, infectious diseases, vascular inflammation and cardiovascular diseases and hepatic fibrosis. They can not only promote the differentiation and function of anti-inflammatory macrophages, Treg cells, CD4+CD8αα+ regulatory cells, IL-10+ and/or IL-35+B regulatory cells but also IL-22-producing innate lymphoid cells 3 (ILC3), which are involved in maintaining the gut mucosal homeostasis. These findings have important consequences in the immunotherapy against tumor and other immune-associated diseases. We will summarize here the recent advances in understanding the generation and regulation of tryptophan metabolites in the gut microbiota, the role of gut microbiota-derived tryptophan metabolites in different immune cells, the occurrence and development of diseases and immunotherapy against immune-associated diseases.

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Section: Trp Metabolism In Gut Microbiotamentioning

confidence: 99%

Section: Potential Application Of Gut Microbiota-derived Trp Metaboli...mentioning

confidence: 99%

Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis

Gao

Yang

2022

Cells

130

View full text Add to dashboard Cite

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“…Wang et al identified novel poricoic acids from Poria cocos and found that they attenuated renal fibrosis through the modulation of AHR signaling pathway in TGF-β1-induced cultured human kidney proximal tubular epithelial cells and mice with unilateral ureteral obstruction ( Wang M. et al, 2020 ). Fisetin, a bioactive flavonol, was reported to improve hyperuricemia-induced CKD via regulating gut microbiota-mediated tryptophan metabolism and AHR activation ( Ren et al, 2021 ). In our study, JPYSF was found to suppress the activation of AHR signaling in the kidney of CKD rat.…”

Section: Discussionmentioning

confidence: 99%

“…Among uremic toxins, those derived from tryptophan metabolism are particularly of importance because they are associated with cardiovascular toxicity and are the ligands of the aryl hydrocarbon receptor (AHR) ( Brito et al, 2017 ). Emerging evidence implicated that the AHR signaling pathway was activated both in CKD patients and in animal models of CKD ( Dou et al, 2018 ; Ren et al, 2021 ). The AHR is a ligand-activated nuclear transcription factor that belongs to the basic helix-loop-helix protein superfamily.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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“…Additional putative mechanisms of action of fisetin in prostate cancer include microtubule stabilization (10 µM) [58], inhibition of epithelial-to-mesenchymal transition (60 µM) via inhibition of YB-1 [53], TRAILmediated augmentation of apoptosis (50 µM) [59], inhibition of cell cycle (1-50 µM) [60][61][62], induction of autophagic cell death via mTOR suppression [63], and inactivation of the JNK and PI3K/Akt signaling pathways [64]. Fisetin may also favorably modulate gut microbiota [65], which is possibly involved in prostate cancer etiopathogenesis [66].…”

Section: Fisetin Preclinical Studiesmentioning

confidence: 99%

Kaempferol, Myricetin and Fisetin in Prostate and Bladder Cancer: A Systematic Review of the Literature

et al. 2021

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Prostate and bladder cancer represent the two most frequently diagnosed genito-urinary malignancies. Diet has been implicated in both prostate and bladder cancer. Given their prolonged latency and high prevalence rates, both prostate and bladder cancer represent attractive candidates for dietary preventive measures, including the use of nutritional supplements. Flavonols, a class of flavonoids, are commonly found in fruit and vegetables and are known for their protective effect against diabetes and cardiovascular diseases. Furthermore, a higher dietary intake of flavonols was associated with a lower risk of both bladder and prostate cancer in epidemiological studies. In this systematic review, we gathered all available evidence supporting the anti-cancer potential of selected flavonols (kaempferol, fisetin and myricetin) against bladder and prostate cancer. A total of 21, 15 and 7 pre-clinical articles on bladder or prostate cancer reporting on kaempferol, fisetin and myricetin, respectively, were found, while more limited evidence was available from animal models and epidemiological studies or clinical trials. In conclusion, the available evidence supports the potential use of these flavonols in prostate and bladder cancer, with a low expected toxicity, thus providing the rationale for clinical trials that explore dosing, settings for clinical use as well as their use in combination with other pharmacological and non-pharmacological interventions.

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Fisetin Improves Hyperuricemia-Induced Chronic Kidney Disease via Regulating Gut Microbiota-Mediated Tryptophan Metabolism and Aryl Hydrocarbon Receptor Activation

Cited by 35 publications

References 47 publications

Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis

Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis

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

Kaempferol, Myricetin and Fisetin in Prostate and Bladder Cancer: A Systematic Review of the Literature

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