5-demethylnobiletin and tangeretin

Rheumatoid arthritis (RA) is an autoimmune disease characterized by long duration and repeated relapse. This study explored the preventive effect of tangeretin (TAN) and 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone (5-HPMF) on RA, and the underlying molecular mechanism based on a rat model stimulated by bovine type II collagen (BIIC). After the intervention of TAN or 5-HPMF (TAN/5-HPMF) for 5 weeks, the RA lesions and autophagy levels of the synovial tissue were significantly reduced, and the ROS content and HO-1 expression level were down-regulated simultaneously. The relative expression levels of p-AKT and p-mTOR were down-regulated after TAN/5-HPMF feeding. Meanwhile, the relative expression level of p62 increased by more than two-fold for TAN/5-HPMF treated rats at 200 mg/kg BW comparing with those in BIIC group. Results of immunofluorescence staining and Western blotting further confirmed that TAN/5-HPMF treatment reduced BIIC-induced conversion from LC3I to LC3II. Observations under transmission electron microscope also demonstrated that the autophagy level was reduced upon TAN/5-HPMF intervention. Collectively, these results revealed that TAN and 5-HPMF prevented the pathological process of BIIC-stimulated arthritis through inhibiting the autophagy of synovial cells, achieved via the ROS-AKT/mTOR signal axis. Thus, our findings confirmed the protective potential of TAN and 5-HPMF for RA disease.

Topics: Animals; Apoptosis; Arthritis, Rheumatoid; Autophagy; Cattle; Cell Proliferation; Collagen Type II; Female; Flavones; Humans; Protective Agents; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Signal Transduction; Synovial Membrane; TOR Serine-Threonine Kinases

This study aimed to reveal the interaction and inhibitory mechanisms of tangeretin (TAN), nobiletin (NBT), and their acidic hydroxylated forms, 5-demethyltangeretin (5-DT) and 5-demethylnobiletin (5-DN) on porcine pancreatic lipase (PPL) using spectroscopic techniques and molecular dynamics (MD) simulation. PPL inhibition assay showed that the inhibitory activity of NBT (IC

Topics: Animals; Citrus; Flavones; Fruit; Kinetics; Lipase; Molecular Docking Simulation; Molecular Dynamics Simulation; Pancreas; Plant Extracts; Swine

In order to establish an efficient method for separation of polymethoxyflavones (PMFs) and explore the anti-inflammatory mechanism of PMF monomers, a citrus variety rich in PMFs, Ougan (

Topics: Animals; Cell Line; Cell Survival; Citrus; Flavones; Lipopolysaccharides; Mice; Microglia; Molecular Structure; Nitric Oxide

Aging and oxidative-related events are closely associated with the oxidative damages induced by excess reactive oxygen species (ROS). The phytochemicals nobiletin (NBT) and tangeretin (TAN) and their 5-demethylated derivatives 5-demethylnobiletin (5-DN) and 5-demethyltangeretin (5-DT) are the representative polymethoxyflavone (PMF) compounds found in aged citrus peels. Although the health benefits from PMFs due to their antioxidant activities have been well documented, a systematic assessment regarding the antioxidation process of PMFs is still lacking attention. Herein, we investigated the effects of the four PMFs subjected to oxidative stress including hydrogen peroxide, carbon tetrachloride, and cadmium sulfate using an emerging model organism Saccharomyces cerevisiae. As expected, all four of the PMFs exhibited improved cellular tolerance with decreasing lipid peroxidation and ROS. Furthermore, by using the mutant strains deficient in catalase, superoxide dismutase, or glutathione synthase, NBT, 5-DN, and TAN appear to contribute to the increased tolerance by activating cytosolic catalase under CCl

Topics: Antioxidants; Citrus; Flavones; Glutathione; Hydrogen Peroxide; Oxidative Stress; Plant Extracts; Reactive Oxygen Species; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Superoxide Dismutase

Quality marker (Q-markers) has been proposed as a novel concept for quality evaluation and standard elaboration of traditional Chinese medicine (TCM). Xin-Su-Ning capsule (XSNC) has been extensively used for the treatment of arrhythmia with the satisfactory therapeutic effects in clinics. However, it is lack of reliable and effective Q-markers of this prescription.. To identify potential Q-markers of XSNC against arrhythmia.. An integrative pharmacology-based investigation was performed.. Ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap) was performed to identify the preliminary chemical profile of XSNC in a rapid and high-throughput manner. Then, in silico Absorption-Distribution-Metabolism-Excretion (ADME) models were utilized to screen candidate active chemical compounds characterized by drug-likeness features. In addition, drug target-disease gene interaction network was constructed, and network features were calculated to identify key candidate targets and the potential Q-markers of XSNC against arrhythmia.. A total of 41 chemical compounds with good drug-likeness and more chances to be absorbed into body were identified as the candidate bioactive chemical compounds which might offer contributions to the therapeutic effects of XSNC against arrhythmia in vivo. Following the prediction of 921 XSNC putative targets and the construction of XSNC putative target-known therapeutic target of arrhythmia interaction network, 315 hub nodes with high connectivity were selected. Functionally, the hub nodes were involved into modulation of cardiac sympatho-vagal balance, regulation of energy production and metabolism, as well as angiogenesis and vascular circulation during the development and progression of arrhythmia. Moreover, 63 major hubs with network topological importance were chosen as XSNC candidate targets against arrhythmia. Furthermore, berberine, palmatine, scopoletin, liquiritigenin, naringenin, formononetin, nobiletin, tangeretin, 5-demethylnobiletin, kushenol E and kurarinone hitting the corresponding XSNC candidate targets were screened out to be the potential Q-markers of XSNC against arrhythmia.. Our integrative pharmacology-based approach combining UHPLC-LTQ-Orbitrap, in silico ADME prediction and network target analysis may be efficient to identify potential Q-markers of TCM prescriptions. Our data showed that berberine, palmatine, scopoletin, liquiritigenin, naringenin, formononetin, nobiletin, tangeretin, 5-demethylnobiletin, kushenol E and kurarinone might function as candidate markers for qualitative evaluation of XSNC.

Topics: Alkaloids; Arrhythmias, Cardiac; Biological Availability; Capsules; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Flavanones; Flavones; Flavonoids; Humans; Medicine, Chinese Traditional; Quality Control; Spectrometry, Mass, Electrospray Ionization

An HPLC method was developed for the simultaneous determination of 11 constituents, 5-hydroxymethyl furfural (5-HMF), vicenin-2, hesperidin, hesperetin, isosinensetin, sinensetin, tetramethyl-O-isoscutellarein (TEOS), nobiletin, 3, 5, 6, 7, 8, 3', 4'-heptamethoxy- flavone (HEPTA), tangeretin, 5-demethylnobiletin in Citrus reticulate 'Chachi'. The separation was conducted on a Hanbon Benatach C18 column (250 mm x 4.6 mm, 5 µm) with acetonitrile and 0.2% formic acid as mobile phases with gradient elution. The flow rate was 1.0 mL/min. The detection wavelength was 280 nm. The column temperature was 25 °C. The results showed that the correlation coefficients (r) between concentration and chromatographic peak area of the 11 constituents were over 0.998 in the selected linear ranges. The limits of detection (LODs, S/N = 3) and limits of quantification (LOQs, S/N = 10) of the 11 constituents were in the range of 0.0125-1.25 mg/L and 0.0502-4.99 mg/L, respectively. The average recoveries (n = 3) of the 11 constituents were in the range of 96.4%-102.4% and the RSDs were 0.25%-4.01%. The developed method has been successfully applied for the analysis of eight samples from different cultivation regions in Guangdong Province. This method is simple, accurate and effective for the simultaneous determination of the 11 components, and suitable for the quality control of Citrus reticulate 'Chachi'.

Topics: Apigenin; Chromatography, High Pressure Liquid; Citrus; Flavones; Flavonoids; Furaldehyde; Glucosides; Hesperidin