The effect of combination therapy of allicin and fenofibrate on high fat diet-induced vascular endothelium dysfunction and liver damage in rats

<p>Abstract</p> <p>Background</p> <p>It is designed to investigate the effects of combination therapy of allicin and fenofibrate on the endothelial and liver functions in rats with hyperlipidemia.</p> <p>Methods</p> <p>The healthy male Wistar rats fed high fat diet were treated with fenofibrate (80 mg/kg per day) alone, allicin (60 mg/kg per day) alone and a lower dasage of combined therapy (allicin 20 mg/kg per day and fenofibrate 30 mg/kg per day) respectively for 8 weeks. The serum levels of cholesterol, triglyceride, nitrogen oxidative, alanine transferase (ALT) and aspartate transferase (AST) were determined. Acetylcholine-induced endothelium-dependent vascular relaxation (EDVR) of aorta rings was tested, and the morphologic changes of liver tissue were observed.</p> <p>Results</p> <p>Compared with high fat diet control, fenofibrate alone or the combined therapy increased remarkably the levels of high density lipoprotein respectively (P < 0.05). Both single and combined therapy of fenofibrate and allicin significantly enhanced the levels of NO (P < 0.01 or P < 0.05), but the combined therapy had greatest high EDVR responses (P < 0.01). Furthermore, the reduced levels of ALT and AST were significantly obvious in the combined therapy groups (P < 0.01 or P < 0.05). In addition, the lower dosage of combined therapy significantly ameliorated severe fatty degeneration of liver cells occurred in the high fat diet fed rat although the single fenofibrate treatment showed spotty necrosis of liver cells and bile duct expansion.</p> <p>Conclusion</p> <p>Combination therapy with allicin and fenofibrate can effectively enhance the protective effects on endothelial function and reduce the hepatic damage in rats with hyperlipidemia.</p

Systematic Profiling of the Multicomponents and Authentication of Erzhi Pill by UHPLC/Q-Orbitrap-MS Oriented Rapid Polarity-Switching Data-Dependent Acquisition and Selective Monitoring of the Chemical Markers Deduced from Fingerprint Analysis

The analytical platform UHPLC/Q-Orbitrap-MS offers a solution to quality investigation of TCM with high definiteness. Using Erzhi Pill (EZP) as a case, we developed UHPLC/Q-Orbitrap-MS based approaches to achieve systematic multicomponent identification and rapid authentication. Comprehensive multicomponent characterization of EZP was performed by negative/positive switching data-dependent high-energy collision-induced dissociation-MS2 (HCD-MS2) after 25 min chromatographic separation. By reference compounds comparison, elemental composition analysis, fragmentation pathways interpretation, and retrieval of an in-house library, 366 compounds were separated and detected from EZP, and 96 thereof were structurally characterized. The fingerprints of two component drugs (Ligustri Lucidi Fructus, LLF; Ecliptae Herba, EH) for EZP were analyzed under the same LC-MS condition by full scan in negative mode. In combination with currently available pharmacological reports, eight compounds were deduced as the &#8216;identity markers&#8217; of EZP. Selective ion monitoring (SIM) of eight marker compounds was conducted to authenticate six batches of EZP samples. Both LLF and EH could be detected from all EZP samples by analyzing the SIM spectra, which could indicate their authenticity. Conclusively, UHPLC/Q-Orbitrap-MS by rapid polarity switching could greatly expand the potency of untargeted profiling with high efficiency, and SIM of multiple chemical markers rendered a practical approach enabling the authentication of TCM formulae

Simultaneous Profiling and Holistic Comparison of the Metabolomes among the Flower Buds of Panax ginseng, Panax quinquefolius, and Panax notoginseng by UHPLC/IM-QTOF-HDMSE-Based Metabolomics Analysis

The flower buds of three Panax species (PGF: flower bud of P. ginseng; PQF: flower bud of P. quinquefolius; PNF: flower bud of P. notoginseng), widely consumed as healthcare products, are easily confused particularly in the extracts or traditional Chinese medicine (TCM) formulae. We are aimed to develop an untargeted metabolomics approach, by ultra-high performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS) to unveil the chemical markers diagnostic for the differentiation of PGF, PQF, and PNF. Key parameters affecting chromatographic separation and MS detection were optimized in sequence. Forty-two batches of flower bud samples were analyzed in negative high-definition MSE (HDMSE; enabling three-dimensional separations). Efficient metabolomics data processing was performed by Progenesis QI (Waters, Milford, MA, USA), while pattern-recognition chemometrics was applied for species classification and potential markers discovery. Reference compounds comparison, analysis of both HDMSE and targeted MS/MS data, and retrieval of an in-house ginsenoside library, were simultaneously utilized for the identification of discovered potential markers. Satisfactory conditions for metabolite profiling were achieved on a BEH Shield RP18 column and Vion&trade; IMS-QTOF instrument (Waters; by setting the capillary voltage of 1.0 kV and the cone of voltage 20 V) within 37 min. A total of 32 components were identified as the potential markers, of which Rb3, Ra1, isomer of m-Rc/m-Rb2/m-Rb3, isomer of Ra1/Ra2, Rb1, and isomer of Ra3, were the most important for differentiating among PGF, PQF, and PNF. Conclusively, UHPLC/IM-QTOF-MS-based metabolomics is a powerful tool for the authentication of TCM at the metabolome level

Data-Dependent Acquisition and Database-Driven Efficient Peak Annotation for the Comprehensive Profiling and Characterization of the Multicomponents from Compound Xueshuantong Capsule by UHPLC/IM-QTOF-MS

The state of the art ion mobility quadrupole time of flight (IM-QTOF) mass spectrometer coupled with ultra-high performance liquid chromatography (UHPLC) can offer four-dimensional information supporting the comprehensive multicomponent characterization of traditional Chinese medicine (TCM). Compound Xueshuantong Capsule (CXC) is a four-component Chinese patent medicine prescribed to treat ophthalmic disease and angina. However, research systematically elucidating its chemical composition is not available. An approach was established by integrating reversed-phase UHPLC separation, IM-QTOF-MS operating in both the negative and positive electrospray ionization modes, and a &ldquo;Component Knockout&rdquo; strategy. An in-house ginsenoside library and the incorporated TCM library of UNIFITM drove automated peak annotation. With the aid of 85 reference compounds, we could separate and characterize 230 components from CXC, including 155 ginsenosides, six astragalosides, 16 phenolic acids, 16 tanshinones, 13 flavonoids, six iridoids, ten phenylpropanoid, and eight others. Major components of CXC were from the monarch drug, Notoginseng Radix et Rhizoma. This study first clarifies the chemical complexity of CXC and the results obtained can assist to unveil the bioactive components and improve its quality control

Additional file 1 of The potential DNA methylation markers of cardiovascular disease in patients with type 2 diabetes

Supplementary Material