Stereoselective separation, configuration determination, and quantification of flavanone glycosides in Citrus using chiral HPLC-UV in combination with CD spectra.

Flavanone glucosides, such as naringin and neohesperidin, are present in specific Citrus species and manifest a chiral center at the C-2 position of their flavanone moiety. This study successfully achieved the simultaneous stereoselective separation of the C-2 diastereomers of naringin, neohesperidin and hesperidin, as well as the partial separation of narirutin using a chiral high performance liquid chromatography with ultraviolet detection method with cellulose tris(3,5-dichlorophenylcarbamate) as the stationary phase under normal-phase mode. The mobile phase comprised n-hexane and ethanol (containing 0.25% formic acid) at a proportion of 65 : 35 (v/v) with a flow rate of 0.6 mL min-1. Each single epimer of chiral flavanone glycosides was prepared using chiral semi-preparative chromatography, and the absolute configuration was then characterized by combining the experimental electronic circular dichroism detection and time-dependent density functional theory calculations. The epimer composition of each chiral flavonoid glycoside in Fructus aurantii (Zhiqiao) and Fructus aurantii immaturus (Zhishi) was determined revealing variations among herbs collected from different production regions. Additionally, the epimer composition was found to be related to the harvesting time of the herbs. Considering the safety and efficacy, the existence of epimers of different stereo-configurations should be given more attention in the quality evaluation of natural drugs.

Protective effects of Emblica officinalis polysaccharide against lead induced liver injury in mice model.

Heavy metal contamination especially lead (Pb) causes a serious threat to global public health. In the current study, we explored the protective and regulating effects of Emblica officinalis polysaccharide (EOP) in the liver against Pb-induced toxicity. According to our findings, EOP decreased the Pb-induced pathological lesions of liver and overall weight index in mice (p < 0.05). Following treatment with EOP, the levels of biological biomarkers for liver hepatic function (i.e., ALT and AST) were significantly decreased (p < 0.01) in a dose-dependent manner, consisted with histopathological changes. The key proteins involved in hepatic oxidative stress and apoptosis, including Nrf2, HO-1, Bcl-2, and Bax were quantified, which indicated EOP as an effective approach in protecting against the liver injury. Moreover, EOP treatment ameliorated the negative changes of liver metabolic profile (i.e., metabolites concentrations and metabolic patterns). In conclusion, EOP could protect the liver against oxidative stress and apoptosis induced by Pb poisoning, associated with the efficacy of ameliorating the negative changes in liver metabolic profile. Hence, the current findings recommend EOP as an efficient way for alleviating liver injury in lead poisoning.

Chiral Separation, Configuration Confirmation and Bioactivity Determination of the Stereoisomers of Hesperidin and Narirutin in Citrus reticulata Blanco.

Hesperidin and narirutin are a class of flavanone glycosides, which are the main active constituents in Citrus reticulata Blanco. In the present study, a chiral HPLC-UV method with amylose tris(3,5-dimethylphenylcarbamate) as a stationary phase under a normal-phase mode was used to achieve the stereoselective separation of the C-2 diastereomers of hesperidin and narirutin simultaneously. The single epimer was then successfully prepared by applying semi-preparative chromatography, whose absolute configuration (R/S) was characterized by combining the experimental electronic circular dichroism (ECD) detection with time-dependent density functional theory (TDDFT) calculations. The epimer composition of these two chiral flavanone glycosides in Citrus reticulata Blanco was then determined, which was found to be slightly different in the herbs from different production regions. The anti-inflammatory activity of each prepared single epimer was further evaluated, and some differences between one pair of epimers of hesperidin and narirutin were observed, which suggested that the presence of different epimers should be considered in the quality evaluation and control of natural medicine.

Pyruvate dehydrogenase kinase regulates macrophage polarization in metabolic and inflammatory diseases.

Macrophages are highly heterogeneous and plastic, and have two main polarized phenotypes that are determined by their microenvironment, namely pro- and anti-inflammatory macrophages. Activation of pro-inflammatory macrophages is closely associated with metabolic reprogramming, especially that of aerobic glycolysis. Mitochondrial pyruvate dehydrogenase kinase (PDK) negatively regulates pyruvate dehydrogenase complex activity through reversible phosphorylation and further links glycolysis to the tricarboxylic acid cycle and ATP production. PDK is commonly associated with the metabolism and polarization of macrophages in metabolic and inflammatory diseases. This review examines the relationship between PDK and macrophage metabolism and discusses the mechanisms by which PDK regulates macrophage polarization, migration, and inflammatory cytokine secretion in metabolic and inflammatory diseases. Elucidating the relationships between the metabolism and polarization of macrophages under physiological and pathological conditions, as well as the regulatory pathways involved, may provide valuable insights into the etiology and treatment of macrophage-mediated inflammatory diseases.