1H NMR-based dynamic metabolomics delineates the therapeutic effects of Baoyuan decoction on isoproterenol-induced cardiac hypertrophy.

Cardiac hypertrophy (CH) is a major risk factor for many serious heart diseases. Sustained CH is catastrophic, resulting in cardiac dysfunction that eventually leads to heart failure (HF). Baoyuan decoction (BYD) is a famous traditional Chinese medicine (TCM) formula for supplementing and reinforcing Qi, clinically used for the treatment of cardiovascular diseases (CVDs). However, the therapeutic effects of BYD on CH remain unidentified. We herein investigated the effect of BYD on isoproterenol (ISO)-induced CH in rats and the underlying mechanisms by comprehensive pharmacodynamics and 1H NMR-based dynamic metabolomics analysis of the plasma and urine samples. Results showed that BYD treatment markedly attenuated ISO-induced CH as evidenced by decreasing the left ventricular wall thickness, pathological cardiomyocyte hypertrophy, myocardial collagen fiber deposition and apoptosis, and plasma natriuretic peptide levels. Multivariate trajectory analysis revealed that the BYD treatment could restore the CH-disturbed plasma and urinary metabolite profiles towards the normal metabolic status featuring with a time-dependent tendency. Moreover, the key metabolic alterations in CH rats at different BYD-treated time stages involved energy metabolism, oxidative stress responses, amino acid metabolism, and gut microbiota metabolism. Of particularly, the significant roles of BYD for treating CH lie in the improvement of cardiac energy generation and antioxidant capacity. Our investigation provides a holistic view of BYD for therapeutic intervention of CH through monitoring of the dynamic metabolic changes and the results indicate that BYD may be applied as a potential agent for treating CH.

Plasma and urine metabolite profiling reveals the protective effect of Clinacanthus nutans in an ovalbumin-induced anaphylaxis model: 1H-NMR metabolomics approach.

The present study sought to identify the key biomarkers and pathways involved in the induction of allergic sensitization to ovalbumin and to elucidate the potential anti-anaphylaxis property of Clinacanthus nutans (Burm. f.) Lindau water leaf extract, a Southeast Asia herb in an in vivo ovalbumin-induced active systemic anaphylaxis model evaluated by 1H-NMR metabolomics. The results revealed that carbohydrate metabolism (glucose, myo-inositol, galactarate) and lipid metabolism (glycerol, choline, sn-glycero-3-phosphocholine) are the key requisites for the induction of anaphylaxis reaction. Sensitized rats treated with 2000 mg/kg bw C. nutans extract before ovalbumin challenge showed a positive correlation with the normal group and was negatively related to the induced group. Further 1H-NMR analysis in complement with Kyoto Encyclopedia of Genes and Genomes (KEGG) reveals the protective effect of C. nutans extract against ovalbumin-induced anaphylaxis through the down-regulation of lipid metabolism (choline, sn-glycero-3-phosphocholine), carbohydrate and signal transduction system (glucose, myo-inositol, galactarate) and up-regulation of citrate cycle intermediates (citrate, 2-oxoglutarate, succinate), propanoate metabolism (1,2-propanediol), amino acid metabolism (betaine, N,N-dimethylglycine, methylguanidine, valine) and nucleotide metabolism (malonate, allantoin). In summary, this study reports for the first time, C. nutans water extract is a potential anti-anaphylactic agent and 1H-NMR metabolomics is a great alternative analytical tool to explicate the mechanism of action of anaphylaxis.

Mitochondrial Bioenergetics by 13C-NMR Isotopomer Analysis.

Metabolic reprogramming has been associated to a plethora of diseases, and there has been increased demand for methodologies able to determine the metabolic alterations that characterize the pathological states and help developing metabolically centered therapies. In this chapter, methodologies for monitoring TCA cycle turnover and its interaction with pyruvate cycling and anaplerotic reactions will be presented. These methodologies are based in the application of stable 13C isotope "tracers"/substrates and 13C-NMR isotopomer analysis of metabolic intermediates. These methodologies can be applied at several organizational levels, ranging from isolated organelles and organs to whole organisms/humans. For the sake of simplicity, only very simple and well-defined models will be presented, including isolated heart mitochondria and isolated perfused hearts and livers.

A nested phosphorus and proton coil array for brain magnetic resonance imaging and spectroscopy.

A dual-nuclei radiofrequency coil array was constructed for phosphorus and proton magnetic resonance imaging and spectroscopy of the human brain at 7T. An eight-channel transceive degenerate birdcage phosphorus module was implemented to provide whole-brain coverage and significant sensitivity improvement over a standard dual-tuned loop coil. A nested eight-channel proton module provided adequate sensitivity for anatomical localization without substantially sacrificing performance on the phosphorus module. The developed array enabled phosphorus spectroscopy, a saturation transfer technique to calculate the global creatine kinase forward reaction rate, and single-metabolite whole-brain imaging with 1.4cm nominal isotropic resolution in 15min (2.3cm actual resolution), while additionally enabling 1mm isotropic proton imaging. This study demonstrates that a multi-channel array can be utilized for phosphorus and proton applications with improved coverage and/or sensitivity over traditional single-channel coils. The efficient multi-channel coil array, time-efficient pulse sequences, and the enhanced signal strength available at ultra-high fields can be combined to allow volumetric assessment of the brain and could provide new insights into the underlying energy metabolism impairment in several neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, as well as mental disorders such as schizophrenia.

Optimized (31)P MRS in the human brain at 7 T with a dedicated RF coil setup.

The design and construction of a dedicated RF coil setup for human brain imaging ((1)H) and spectroscopy ((31)P) at ultra-high magnetic field strength (7 T) is presented. The setup is optimized for signal handling at the resonance frequencies for (1)H (297.2 MHz) and (31)P (120.3 MHz). It consists of an eight-channel (1)H transmit-receive head coil with multi-transmit capabilities, and an insertable, actively detunable (31)P birdcage (transmit-receive and transmit only), which can be combined with a seven-channel receive-only (31)P array. The setup enables anatomical imaging and (31)P studies without removal of the coil or the patient. By separating transmit and receive channels and by optimized addition of array signals with whitened singular value decomposition we can obtain a sevenfold increase in SNR of (31)P signals in the occipital lobe of the human brain compared with the birdcage alone. These signals can be further enhanced by 30 ± 9% using the nuclear Overhauser effect by B1-shimmed low-power irradiation of water protons. Together, these features enable acquisition of (31)P MRSI at high spatial resolutions (3.0 cm(3) voxel) in the occipital lobe of the human brain in clinically acceptable scan times (~15 min).

The use of magnetic resonance spectroscopy as a tool for the measurement of bi-hemispheric transcranial electric stimulation effects on primary motor cortex metabolism.

Transcranial direct current stimulation (tDCS) is a neuromodulation technique that has been increasingly used over the past decade in the treatment of neurological and psychiatric disorders such as stroke and depression. Yet, the mechanisms underlying its ability to modulate brain excitability to improve clinical symptoms remains poorly understood. To help improve this understanding, proton magnetic resonance spectroscopy ((1)H-MRS) can be used as it allows the in vivo quantification of brain metabolites such as γ-aminobutyric acid (GABA) and glutamate in a region-specific manner. In fact, a recent study demonstrated that (1)H-MRS is indeed a powerful means to better understand the effects of tDCS on neurotransmitter concentration. This article aims to describe the complete protocol for combining tDCS (NeuroConn MR compatible stimulator) with (1)H-MRS at 3 T using a MEGA-PRESS sequence. We will describe the impact of a protocol that has shown great promise for the treatment of motor dysfunctions after stroke, which consists of bilateral stimulation of primary motor cortices. Methodological factors to consider and possible modifications to the protocol are also discussed.