Effects of Farnesiferol B on Ischemia-Reperfusion-Induced Renal Damage, Inflammation, and NF-κB Signaling

Abstract

Background: G-protein-coupled bile acid receptor (TGR5), a membrane bile acid receptor, regulates macrophage reactivity, and attenuates inflammation in different disease models. However, the regulatory effects of TGR5 in ischemia/reperfusion (I/R)-induced kidney injury and inflammation have not yet been extensively studied. Therefore, we hypothesize that Farnesiferol B, a natural TGR5 agonist, could alleviate renal I/R injury by reducing inflammation and macrophage migration through activating TGR5. Methods: Mice were treated with Farnesiferol B before I/R or sham procedures. Renal function, pathological analysis, and inflammatory mediators were examined. In vitro, the regulatory effects of Farnesiferol B on the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in macrophages were investigated. Results: After I/R, Farnesiferol B-treated mice displayed better renal function and less tubular damage. Farnesiferol B reduced renal oxidative stress and inflammation significantly. In vitro, Farnesiferol B treatment alleviated lipopolysaccharide (LPS)-induced macrophage migration and activation, as well as LPS-induced NF-κB activation through TGR5. Conclusions: Farnesiferol B could protect kidney function from I/R-induced damage by attenuating inflammation though activating TGR5 in macrophages. Farnesiferol B might be a potent TGR5 ligand for the treatment of I/R-induced renal inflammation.

Renal-Protective Effects and Potential Mechanisms of Traditional Chinese Medicine after Ischemia-Reperfusion Injury

“…Additionally, cordycepin, the extract from Cordyceps sinensis , could decrease secretion of proinflammatory factors and alleviate inflammatory reaction [ 10 ], including IL-1 β , IL-6, and TNF- α , at the protein and mRNA levels. The same effect was observed after treatment with Yisheng injection, Fufang Shenhua Tablet, glycyrrhizin, honokiol, cryptotanshinone, notoginsenoside R1, brazilin, total glucosides of paeony, hydroxysafflor yellow A, arctigenin, farnesiferol B, and anemoside B4 [ 2 – 4 , 6 , 8 , 12 , 13 , 15 – 17 , 19 , 20 , 23 ]. Moreover, the infiltration of neutrophils and macrophages was observed in some studies.…”

“…[ 1 ]. During the renal I/R process, excess reactive oxygen species (ROS) are likely to cause oxidative stress, which subsequently triggers lipid peroxidation [ 2 ] and cell death due to apoptosis, autophagy, pyroptosis, and ferroptosis caused by DNA and protein damage in ischemic tissue [ 3 ]. In addition, inflammation plays an important role in renal I/R injury, along with leukocyte infiltration and tissue damage in the kidney, followed by excessive production of proinflammatory cytokines [ 4 ].…”

“…Increase in blood urea nitrogen (BUN) and creatinine (Cr) [ 3 ] and a higher urinary total protein level are reported to occur after renal I/R injury [ 6 ]. Histopathology of renal I/R injury shows luminal narrowing, intraluminal necrotic cellular debris, tubular basal membrane rupture, tubular vacuolization, interstitial congestion, apparent cell swelling and nuclear infiltration in the H&E staining of renal tissues [ 7 ], and higher Kim-1 expression, thus causing a higher renal tubular injury score [ 2 ].…”

Kidney Inflammation, Injury and Regeneration

“…The findings of Mocker and co-workers demonstrate that renal chemerin expression, a chemoattractant adipokine, is associated with processes of inflammation and fibrosis during renal damage [2]. The protection of kidney function by attenuating induced renal inflammation was shown with the use of Farnesiferol B, an agonist of a receptor that is expressed by renal tubular epithelial cells [1]. The xanthin oxidase inhibitor febuxostat is shown to exert anti-inflammatory action and protect against diabetic nephropathy development [3].…”

“…This Special Issue covers research articles that investigated the molecular mechanisms of inflammation [1][2][3] and injury [4,5] during different renal pathologies and renal regeneration [6], diagnostics using new biomarkers [7][8][9], and the effects of different stimuli like medication or bacterial components on isolated renal cells or in vivo models [10][11][12], all of which were summarized in a very simplified manner. Furthermore, this Special Issue contains important reviews that dealt with the current knowledge of cell death and regeneration [13,14], inflammation [15][16][17][18], and the molecular mechanisms of kidney diseases [19][20][21][22].…”