Biochanin A ameliorated oleate‐induced steatosis in HepG2 cells by activating the SIRT3/AMPK/ULK‐1 signaling pathway

Abstract

Biochanin A (Bio‐A), an isoflavone abundant in chickpeas, possesses hypoglycemic, hypolipidemic, and anti‐inflammatory effects. However, whether Bio‐A has antihepatosteatosis effect remains unclear. This study aimed to evaluate the antihepatosteatosis effect of Bio‐A on oleate (OA)‐treated hepatocytes, and explore the underlying mechanism. When incubated with OA for 24 h, HepG2 cells were treated with various concentrations of Bio‐A for 24 h to obtain an optimal antihepatosteatosis dose. HepG2 cells were treated with the AMP‐activated protein kinase (AMPK) inhibitor Compound C, or the sirtuin‐3 (SIRT3) inhibitor 3‐TYP, and incubated with 50 μM Bio‐A. The results indicated that 12.6% of lipid content, particularly 11.0% of triglyceride content, and the expression of adipocyte differentiation‐related protein were significantly decreased in Bio‐A‐treated hepatosteatosis cells, followed by an increase in the expression of Beclin 1, phosphorylation of Unc‐51‐like kinase 1 (ULK‐1), the microtubule‐associated protein 1 light chain 3 (LC3)‐II/LC3‐I ratio, and a decrease in expression of p62. The results indicated that Bio‐A upregulated autophagosome formation and autophagy flux. In addition, Bio‐A increased SIRT3 expression and AMPK phosphorylation in OA‐treated HepG2 cells. Blockade of AMPK and SIRT3 blocked the antihepatosteatosis effect and ULK‐1 activation by Bio‐A. AMPK inhibition did not eliminate the activation of SIRT3 by Bio‐A. AutoDock analysis demonstrated that interaction might exist between Bio‐A and SIRT3. In conclusion, Bio‐A reduced fat accumulation in OA‐treated HepG2 cells by activating SIRT3/AMPK/ULK‐1‐mediated autophagy. The findings provide a theoretical basis for the effect of Bio‐A on hepatic steatosis‐related diseases. Practical applications This study highlights the antihepatosteatosis effects of biochanin A (Bio‐A) on oleate (OA)‐treated hepatocytes. Bio‐A, one of the isoflavones in Cicer arietinum Linn., possesses multiple bioactivities such as antiobesity, anti‐inflammation, and hypoglycemic and hypolipidemic effects. This study provides a new application of Bio‐A to treat hepatic steatosis, and revealed the underlying mechanism of Bio‐A involved in the activation of the SIRT3/AMPK/ULK‐1‐mediated autophagy. The findings provide a theoretical basis for the application of Bio‐A to hepatic steatosis‐related diseases.

Modified Linggui Zhugan Decoction protects against ventricular remodeling through ameliorating mitochondrial damage in post-myocardial infarction rats

“…Therefore, MLZD may protect hearts by targeting SIRT3 to inhibit mitochondrial oxidation, regulate mitochondrial dynamics, and improve mitochondrial structure and function abnormalities. Even though the inhibition of 3-TYP on SIRT3 expression and its adverse effects on cells or animals have been widely reported (39,(110)(111)(112)(113), it is noteworthy that a few studies have shown that 3-TYP can only inhibit the activity of SIRT3 but not affect its expression (114,115). This may be due to the difference in the study subjects, the effects of the combined drugs, the effects of the dose and duration of 3-TYP, or some other factors.…”

Specnuezhenide ameliorates ultraviolet‐induced skin photoaging in mice by regulating the Sirtuin 3/8‐Oxoguanine DNA glycosylase signal

“…A binding model was visualized using PyMOL 2.3.1 and PLIP (https://plip-tool.biotec.tu-dresden.de/plip-web/plip/index). Docking energy was calculated by a consistency scoring function for ligand‐receptor affinity 18 . The complex of specnuezhenide and SIRT3 with the lowest affinity value was obtained.…”

“…Docking energy was calculated by a consistency scoring function for ligand-receptor affinity. 18 The complex of specnuezhenide and SIRT3 with the lowest affinity value was obtained.…”