Apigenin Alleviates Renal Fibroblast Activation through AMPK and ERK Signaling Pathways In Vitro

Abstract

Aims: The purpose of this study was to investigate the influences of apigenin on proliferation, differentiation and function of renal fibroblast after TGF-β1 stimulation and to uncover the underlying mechanisms. Background: Renal fibrosis is a common pathway leading to the progression of chronic kidney disease. Activated fibroblasts contribute remarkably to the development of renal fibrosis. Although apigenin has been demonstrated to play a protective role from fibrotic diseases, its pharmacological effect on renal fibroblast activation remains largely unknown. Objective: Here, we examined the functional role of apigenin in the activation of renal fibroblasts response to transforming growth factor (TGF)-β1 and its potential mechanisms. Method: Cultured renal fibroblasts (NRK-49F) were exposed to apigenin (1, 5, 10 and 20 µM) followed by the stimulation of TGF-β1 (2 ng/mL) for 24 h. The markers of fibroblast activation were determined. In order to confirm the anti-fibrosis effect of apigenin, the expression of fibrosis-associated genes in renal fibroblasts was assessed. Result: As a consequence, apigenin alleviated fibroblast proliferation and fibroblast-myofibroblast differentiation induced by TGF-β1. Notably, apigenin significantly inhibited the fibrosis-associated genes expression in renal fibroblasts. Moreover, apigenin treatment significantly increased phosphorylation of AMP-activated protein kinase (AMPK). Apigenin treatment also obviously reduced TGF-β1 induced phosphorylation of ERK1/2 but not Smad2/3, p38 and JNK MAPK in renal fibroblasts. Conclusion: In a summary, these results indicate that apigenin inhibits renal fibroblast proliferation, differentiation and function by AMPK activation and reduced of ERK1/2 phosphorylation, suggesting it could be an attractive therapeutic potential for the treatment of renal fibrosis.

Apigenin role as cell-signaling pathways modulator: implications in cancer prevention and treatment

“…Apigenin has been stated to modulate the MAPK/ERK signaling. It has shown to suppress the proliferative ability of MAPK/ERK through modulation of the expression of AkT, ERK, DR4/DR5 and NF-kB [70,71]. Apigenin administration promoted TRAIL-mediated apoptosis in human lung cancer cells [35].…”

Molecular Mechanistic Pathways Targeted by Natural Antioxidants in the Prevention and Treatment of Chronic Kidney Disease

“…Previous studies have shown the renoprotective effect of apigenin through the attenuation of renal fibrosis via activation of AMPK leading to the inactivation of the TGF-β1/Smad2/3 signaling pathway [ 182 , 183 ]. Uremia associated with the build-up of toxic compounds secondary to renal dysfunction is a major contributor to endothelial dysfunction and cardiovascular disease.…”

Transcriptomics reveals apigenin alleviates airway inflammation and epithelial cell apoptosis in allergic asthma via MAPK pathway

“…Through network pharmacology and liquid‐phase mass spectrometry techniques, API has been identified as one of the pharmacological substances that might contribute to the anti‐asthma effect of Loki Zupa decoction (Mohammadtursun et al, 2020; Wei et al, 2016; Wuniqiemu et al, 2021). API, previously reported to have good antioxidant and anti‐inflammatory activities, is a potent inhibitor of MAP kinase (Li et al, 2020; Salehi et al, 2019). Considerable literature demonstrates that API acts on the three major mitogen‐activated protein kinase (ERK, JNK, and p38) pathways, the NF‐κB pathway and the PI3K/Akt pathway, among other different anti‐inflammatory pathways, and can prevent IκB degradation, p65 subunit phosphorylation and nuclear translocation of NF‐κB, activate B cells, and inhibit COX‐2 activity (He et al, 2021; Li et al, 2020) In addition, API has been shown to enhance the expression of the cellular antioxidants SOD, CAT, and GSH‐Px, inhibit ROS and MDA production, and suppress lipid metabolism and oxidative stress abnormalities through Nrf2 and PPARγ (Feng et al, 2017; Wu et al, 2021; Zhang et al, 2020).…”