Gardeniae Fructus Attenuates Thioacetamide-Induced Liver Fibrosis in Mice via Both AMPK/SIRT1/NF-κB Pathway and Nrf2 Signaling

Abstract

Liver fibrosis, which means a sort of the excessive accumulation of extracellular matrices (ECMs) components through the liver tissue, is considered as tissue repair or wound-healing status. This pathological stage potentially leads to cirrhosis, if not controlled, it progressively results in hepatocellular carcinoma. Herein, we investigated the pharmacological properties and underlying mechanisms of Gardeniae Fructus (GF) against thioacetamide (TAA)-induced liver fibrosis of mice model. GF not only attenuated hepatic tissue oxidation but also improved hepatic inflammation. We further confirmed that GF led to ameliorating liver fibrosis by ECMs degradations. Regarding the possible underlying mechanism of GF, we observed GF regulated epigenetic regulator, Sirtuin 1 (SIRT1), in TAA-injected liver tissue. These alterations were well supported by SIRT1 related signaling pathways through regulations of its downstream proteins including, AMP-activated protein kinase (AMPK), p47phox, NADPH oxidase 2, nuclear factor erythroid 2–related factor 2 (Nrf2), and heme oxygenase-1, respectively. To validate the possible mechanism of GF, we used HepG2 cells with hydrogen peroxide treated oxidative stress and chronic exposure conditions via deteriorations of cellular SIRT1. Moreover, GF remarkably attenuated ECMs accumulations in transforming growth factor–β1-induced LX-2 cells relying on the SIRT1 existence. Taken together, GF attenuated liver fibrosis through AMPK/SIRT1 pathway as well as Nrf2 signaling cascades. Therefore, GF could be a clinical remedy for liver fibrosis patients in the future.

The Azadirachta indica (Neem) Seed Oil Reduced Chronic Redox-Homeostasis Imbalance in a Mice Experimental Model on Ochratoxine A-Induced Hepatotoxicity

“…SIRT1 is correlated with mitochondrial function, energy metabolism, autophagy, apoptosis, and oxidative stress processes and plays a significant role in liver diseases. SIRT1 overexpression leads to increased levels of PPARα and its coactivator PPARγ by a mechanism including acetylation of the peroxisome proliferator-activated receptor-γ coactivator-1α, PGC-1α, which can regulate a function of the multi-functional transcriptional coactivator [ 62 ]. In the present study, we analyzed the gene and protein expressions of SIRT1 and PGC-1α in the liver.…”

Arsenic exposure induced renal fibrosis via regulation of mitochondrial dynamics and the NLRP3‐TGF‐β1/SMAD signaling pathway

“…For instance, TNF and IL-17 can play a role in tissue inflammation and fibrosis caused by NLRP3 inflammatory activation, [60][61][62][63] PI3K-Akt signaling pathway is involved in tissue NLRP3 inflammation and fibrosis, 64,65 PPARγ is also a major regulator of tissue inflammation and fibrosis like TGF-β, 66,67 Th1, and Th2 cell differentiation has also taken parting in tissue fibrosis, 68,69 and AMPK signaling pathway is associated with tissue NLRP3 inflammation and fibrosis. [70][71][72] In summary, the present study revealed that arsenic exposure induced mitochondrial damage, inflammation, and fibrosis in the kidney of SD rats and HK2 cells. Arsenic exposure contributes to renal fibrosis via regulating mitochondrial dynamics and the NLRP3-TGF-β1/SMAD signaling axis, ultimately leading to CKD.…”

Metabolomics reveals that chronic restraint stress alleviates carbon tetrachloride-induced hepatic fibrosis through the INSR/PI3K/AKT/AMPK pathway

“…It was found that 28 patients with advanced brosis/cirrhosis had lower AMPK activity compared to healthy individuals [35] . Some research were demonstrated that activation of AMPK inhibited the expression of TGF-β, tissue inhibitor of metalloproteinase I, collagen and α-SMA, all of which are important factors in promoting liver brosis in mice with carbon tetrachloride-induced HF [36][37][38] . This is consistent with the results of our study.…”