Lignin-derived low-molecular-weight oxidized lignophenol stimulates AMP-activated protein kinase and suppresses renal inflammation and interstitial fibrosis in high fat diet-fed mice.

Excess weight and obesity increase the risk of developing major risk factors for chronic kidney disease. Lignin comprises 20%-30% of the global plant biomass; however, it is not well utilized because of its resistance to chemical and biological degradation. We investigated whether low-molecular-weight oxidized lignophenol (LOLP), a lignin derivative, could alter inflammation and fibrosis in the kidneys of a high-fat diet (HFD)-fed mice. Male mice were divided into three treatment groups: HFD; HFD +0.3% LOLP; and HFD +0.6% LOLP. The control mice (Cont) were fed a low-fat diet. Macrophage kinetics, the degree of fibrosis, the extent of phosphorylation of AMP-activated protein kinase (AMPK), and mRNA expression of proinflammatory mediators in the kidneys were examined. The number of macrophages, the percentage of fibrotic area, and the mRNA expression of proinflammatory markers, TNF-α and Ccl2, and a marker of fibrosis, TGF-ß, were significantly higher in the kidneys of mice in the HFD group than those in the Cont group. Conversely, treatment with 0.6% LOLP for 8 weeks significantly suppressed the degree of macrophage infiltration, interstitial fibrotic area, and the increased mRNA expression of proinflammatory and fibrosis markers induced by HFD. In conclusion, LOLP suppressed macrophage infiltration and the increase in fibrotic area, and upregulated AMPK phosphorylation in the kidneys of HFD-fed mice; thus, it may ameliorate HFD-induced kidney injury.

Effect of lignin-derived lignophenols on hepatic lipid metabolism in rats fed a high-fat diet.

The effect of lignin-derived lignophenols on lipid metabolism in the livers of rats fed a high-fat diet was investigated. Rats fed a diet providing 45% of energy from fat were divided into 2 groups, namely 0% and 0.5% lignophenols-containing diets. The controls were fed a diet providing 10% of energy from fat. Plasma blood parameters, protein expression of acetyl-CoA carboxylase (ACC) and sterol regulatory element-binding protein (SREBP)-1, and SREBP-1c mRNA expression in the livers were examined. The plasma triglyceride levels in the rats fed lignophenols-containing diets were decreased. SREBP-1c mRNA expression in the rats fed lignophenols-containing diets was significantly reduced compared with the rats fed high-fat diets, and phosphorylated ACC protein in the rats fed lignophenols-containing diets was significantly increased. Our results suggested that lignophenols suppress the expression of SREBP-1c mRNA and the phosphorylation of ACC in the liver, and may lead to a decrease in plasma triglyceride levels.

Effect of lignin-derived lignophenols on vascular oxidative stress and inflammation in streptozotocin-induced diabetic rats.

Lignophenols (LP) are the derivatives of native lignin, which is an abundant organic polymer in the plant kingdom. This study investigated whether LP can attenuate vascular oxidative stress and inflammation in streptozotocin (STZ)-induced diabetic rats. The diabetic rats induced by a single intravenous injection of STZ were randomly divided into two groups fed either 0 or 1.0% LP-containing diet. After 5 weeks of treatment, the superoxide (O(2)(-)) production, mRNA expression levels of nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidase subunits, monocyte chemoattractant protein-1 (MCP-1) and its receptor C-C chemokine receptor 2 (CCR2), and protein expression level of inducible nitric oxide synthase (iNOS) were examined in the aorta of vehicle-injected control and diabetic rats treated with or without LP. The increased O(2)(-) production and mRNA expression levels of NAD(P)H oxidase subunits Nox4 and p47phox were found to be significantly reduced in the aorta of diabetic rats treated with LP. The mRNA expression of MCP-1 and CCR2, and the protein expression of iNOS were found to be increased in the aorta of untreated diabetic rats, whereas these levels were significantly lower in the LP-treated group. These findings suggest that LP could attenuate vascular oxidative stress and/or inflammation via inhibition of NAD(P)H oxidase. This may lead to an improvement in the vascular impairment of diabetes.

Lignophenols decrease oleate-induced apolipoprotein-B secretion in HepG2 cells.

Lignin is one of the components in the plant cell wall, after cellulose, making up 20-30% of the global plant biomass. Lignophenols (LPs) are derivatives of lignin with high phenolic function and antioxidant properties. However, their medicinal property is not well characterised. Apolipoprotein-B (apo-B) is an essential component in very low-density lipoprotein, and high levels of serum apolipoprotein-B (apo-B) are a major factor for coronary heart disease. In this study, we examined the effect of lignophenols on apo-B secretion in HepG2 cells. HepG2 cells were treated with varying concentrations of LPs and 0.8 mm sodium oleate. LPs decreased oleate-induced apo-B secretion in a dose-dependent manner. LPs also decreased oleate-induced microsomal triglyceride transfer protein (MTTP) mRNA expression and cellular total cholesterol, suggesting that lipid bioavailability and lipidation of lipoprotein are likely involved in the decreased secretion of apo-B. Furthermore, LPs decreased oleate-induced mature sterol regulatory element binding protein 2 (SREBP-2), a transcription factor that activates cholesterol biosynthesis. This is the first study to show that LPs can decrease oleate-induced apo-B secretion in HepG2 cells. The modulations of MTTP mRNA expression, cellular total cholesterol metabolism and mature SREBP-2 expression may be important factors in the regulation of apo-B secretion by LPs.

Lignin-derived lignophenols attenuate oxidative and inflammatory damage to the kidney in streptozotocin-induced diabetic rats.

This study investigated the effects of lignin-derived lignophenols (LPs) on the oxidative stress and infiltration of macrophages in the kidney of streptozotocin (STZ)-induced diabetic rats. The diabetic rats were divided into four groups with 0%, 0.11%, 0.33% and 1.0% LP diets. The vehicle-injected controls were given a commercial diet. At 5 weeks, superoxide (O(2)(-)) production, macrophage kinetics, the degree of fibrosis in glomeruli and mRNA expression for monocyte chemoattractant protein-1 (MCP-1) were examined. The NADPH-stimulated O(2)(-) levels in the kidney of the diabetic rats treated with 1.0% LP were significantly lower than those in untreated diabetic rats. The number of macrophages, levels of MCP-1 mRNA expression and degree of glomerular fibrosis increased in untreated LP and these levels were significantly lower in 1.0%LP-treated rats. The results suggested that LPs suppress the excess oxidative stress, the infiltration and activation of macrophages and the glomerular expansion in STZ-induced diabetic kidneys.