Insulin resistance (IR) is the common basis of diabetes and cardiovascular diseases, and its development is closely associated with lipid metabolism disorder. Flavonoids have definite chemical defense effects, including anti-inflammatory effects, anti-cancer effects, and anti-mutation effects. However, the function and mechanism of apigenin (AP, a kind of flavonoids) on IR are still unclear. In our study, intracellular fat accumulation model cells and high-fat diet (HFD) fed model mice were established using palmitate (PA) and HFD. Mechanistically, we first demonstrated that AP could notably downregulate sterol regulatory element-binding protein 1c (SREBP-1c), sterol regulatory element-binding protein 2 (SREBP-2), fatty acid synthase (FAS), stearyl-CoA desaturase 1 (SCD-1), and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCOR) in PA-induced hyperlipidemic cells and mice. Functionally, we verified that AP could markedly reduce lipid accumulation in PA-induced hyperlipidemic cells and decrease the body weight, visceral fat weight, IR, and lipid accumulation in HFD-induced hyperlipidemic mice. Besides, we disclosed that PA could significantly downregulate ERS-related proteins and inhibit ERS. Furthermore, we proved that AP could reduce blood lipids by inhibiting ERS in PA-induced hyperlipidemic cells. Meanwhile, ERS alleviator (4-PBA), like AP, could significantly reduce blood lipids and alleviate IR in HFD fed model mice. Therefore, we concluded that AP could substantially improve the disorder of lipid metabolism, and its mechanism might be related to the decrease of SREBP-1c, SREBP-2, and downstream genes, the inhibition of ERS, and the reduction of blood lipids and IR. Significance Statement Apigenin,a non-toxic and naturally-sourced flavonoid, exerts anti-hyperlipidemia properties in mice and hepatocyte. Our study highlights a new mechanism of Apigenin that this hypolipidemic effects is associated with the mitigation of endoplasmic reticulum stress and insulin resistance in diet-induced obesity. This study might provide tranlational insight for the prevention and treatment of AP in hyperlipidemia related diseases.

Stylo has a great potential for Al³⁺ resistance in acidic soils through secretion of citrate from the roots. To get insight into the molecular mechanisms responsible, transcriptomic changes were investigated in the roots after treatment with T01 (−Al³⁺, pH6.0), T02 (−Al³⁺, pH4.3) and T03 (50 µM AlCl₃, pH4.3). In total, 83,197 unigenes generated from 130,933 contigs were obtained. Of them, 282, 148 and 816 differentially expressed unigenes (DEGs) were revealed in T01_vs_T02, T02_vs_T03 and T01_vs_T03 comparison, respectively (FDR < 0.001, log₂FC > 2). DEGs by Al³⁺ were related to G-proteins, diacyglycerol and inositol metabolism, calcium-signaling, transcription regulation, protein modification and transporters for detoxification of Al³⁺. Additionally, Al³⁺ facilitates citrate synthesis via modifying gene expression of pathways responsible for citrate metabolism. Overall, Al³⁺ resistance in stylo involves multiple strategies and enhancement of citrate anabolism. The Al³⁺ signal transmits through heterotrimeric G-proteins, phospholipase C, inositol triphosphate, diacylglycerol, Ca²⁺ and protein kinases, thereby activating transcription and anion channels in plasma membrane, and resulting in citrate secretion from stylo roots.

Aluminum (Al) toxicity is a major environmental stress that inhibits plant growth and development. There has been impressive progress in recent years that has greatly increased our understanding of the nature of Al toxicity and its mechanisms of tolerance. This review describes the transcription factors (TFs) and plant hormones involved in the adaptation to Al stress. In particular, it discusses strategies to confer plant resistance to Al stress, such as transgenic breeding, as well as small molecules and plant growth-promoting rhizobacteria (PGPRs) to alleviate Al toxicity. This paper provides a theoretical basis for the enhancement of plant production in acidic soils.

Xiao MA, Ruihong WANG, Shitian YU, Guicong Lu, Yongxiong YU*, Caode JIANG*. J. Microbiol. Biotechnol. -0001;0:. https://doi.org/10.4014/jmb.2006.06030

Epicatechin (EC) has significant antiinflammation, antioxidation, and anticancer activities. It also provides a new alternative treatment for mastitis, which can result in great economic losses in the dairy industry if left untreated. The purpose of this study was to investigate the anti-inflammatory effects of EC on mastitis and the underlying mechanism using in vivo and in vitro systems. The use of ELISA and immunohistochemistry assays showed that EC treatment at 1.5, 7.5, 15, and 30 mg/mL decreased protein expression of inflammatory mediators, including cyclooxygenase-2 and inducible nitric oxide synthase; inflammatory cytokines, which were composed of IL-1β, TNF-α, and IL-6 in lipopolysaccharide (LPS)-stimulated bovine mammary epithelial cell line (MAC-T); and mouse mammary gland, together with reduced filtration of T lymphocytes in the mouse mammary gland. Furthermore, EC treatment reduced LPS-induced phosphorylation levels of p65 and inhibitor of NF-κB, and blocked nuclear translocation of p65 as revealed by western blot and immunofluorescence test in MAC-T cells and the mouse mammary gland. Epicatechin also attenuated LPS-induced phosphorylation levels of mitogen-activated protein kinase members (i.e., p38, c-Jun N-terminal kinase 1/2 and extracellular regulated protein kinases 1/2). Using RNA-seq and tandem mass tag analyses, upregulation of TMEM35A and TMPO proteins was disclosed in MAC-T cells cotreated with LPS and EC. Although clustered regularly interspaced short palindromic repeats/Cas9-based knockdown of TMEM35A and TMPO attenuated abundance of phosphorylated (p)-p65, p-p38, TNF-α, and iNOS, overexpression of TMEM35A reversed EC-mediated effects in TMPO knockdown cells. Moreover, interaction between TMEM35A and TMPO was detected using the co-immunoprecipitation method. In conclusion, our data demonstrated that EC inhibited LPS-induced inflammatory response in MAC-T cells and the mouse mammary gland. Importantly, TMEM35A mediated the transmembrane transport of EC, and the interaction between TMEM35A and TMPO inhibited MAPK and NF-κB pathways.