Rhodiola crenulata protects against Alzheimer's disease in rats: A brain lipidomics study by Fourier‐transform ion cyclotron resonance mass spectrometry coupled with high‐performance reversed‐phase liquid chromatography and hydrophilic interaction liquid chromatography

Abstract

Rationale Alzheimer's disease (AD) is a chronic, severe, progressive neurodegenerative disorder associated with cognitive and memory impairment that ultimately causes death. Most approved drugs can only alleviate some of the symptoms of AD, but no interventions have been found that reverse the underlying disease mechanisms. Rhodiola crenulata extract (RCE) has been reported to alleviate AD symptoms in rats. However, its underlying mechanism of action is still unclear. Methods A brain lipidomics study was conducted to investigate the protective effects of RCE against AD in rats to identify potential biomarkers of AD using Fourier‐transform ion cyclotron resonance mass spectrometry (FT‐ICR MS) coupled with high‐performance reversed‐phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC). Differences in lipid metabolism profiles were evaluated using multivariate statistical analysis. Finally, the possible mechanism of action of RCE on AD was investigated by analysing metabolic pathways. Results The RPLCHILIC/FT‐ICR MS results showed 20 lipid components with significant differences between the control and model groups. After administration of RCE, the levels of 10 lipids in AD rats tended to shift toward reference levels. The pathway analysis revealed that the protective effect of RCE against AD might be related to regulation of glycerophospholipid metabolism. Conclusions This study provides a novel perspective on the potential intervention mechanism of RCE in the treatment of AD.

Bibliometric and visualized mapping: two decades of lipidomics, with special focus on pregancy and women

“…Both postpartum depression and dementia are prevalent mental disorders, ω −3 PUFA can protect against both diseases (De Vriese et al, 2003; Lim et al, 2006). In dementia, the medical treatment (Sun et al, 2021) may be related to the lipidomics profile. To our knowledge, postpartum depression has no such study.…”

Phospholipidomics in Clinical Trials for Brain Disorders: Advancing our Understanding and Therapeutic Potentials

“…- The biological sample can introduce the matrix effect and could interrupt the GC-MS quantification [ 104 , 106 , 107 ] Gas chromatography–combustion–isotope ratio mass spectrometry (GC-C-IRMS) - An analytical technique used to determine the isotopic composition of carbon and, other elements (such as nitrogen, hydrogen, sulfur, and oxygen) in lipid molecules - Technique to trace the origin of a lipid in a biological system - Investigate the dietary source of lipids in humans and animals - Suitable for quantification of labeled lipids with isotopes such as 13C and 2H - Provides results with high sensitivity and specificity - Method offering detailed analysis of lipid profiles in patient samples - Relatively complex and expensive analytical method compared to GC-MS and GC-FID - Only used for limited element analysis, such as carbon isotope analysis. - Isotope fractionation could happen during the sample’s preparation [ 108 – 111 ] Reversed-phase liquid chromatography (RP-LC) Highly retained hydrophilic lipids, separation based on carbon chain length and degree of FA unsaturation - Reliable, efficient, and selective separation - Suitable for complex lipid separation - Highly sensitive and could provide accurate results at low concentrations - Could be connected with a wide range of detectors including UV-Vis, fluorescence, and mass spectrometry for quantitative and qualitative analysis - RP-LC offers excellent peak shape and high resolution, enabling the separation of complex mixtures with accuracy - Not well-suited for the separation of highly polar compounds - Does not work properly for the separation of high-molecular-weight compounds, such as large peptides or protein - Expensive to purchase and needs skilled manpower to operate and maintain - RP-LC columns can degrade over time, leading to the loss of column efficiency and reproducibility - Some process of RP-LC uses non-volatile or semi-volatile mobile phases, which could leave residue in the mass spectrometer [ 112 – 114 ] Hydrophilic interaction liquid chromatography (HILIC) - Suitable for analyzing polar compounds like sugars, amino acids, and glycerophospholipids - Uses a mobile phase that is typically highly aqueous - The stationary phase in HILIC is often made of materials like amino, amide, or zwitterionic phases - Interface method between RP-LC and NP-LC - Highly effective for the separation of polar and hydrophilic compounds - Suitable for separation of LysoPLs isomers - Often provides improved peak shapes for polar compounds compared to RP-LC - Can reduce matrix effects - Not the ideal choice for less polar or hydrophobic analytes - HILIC method development could be more challenging compared to RP-LC - The retention time of peaks is highly dependent on pH and temperature, hard to transfer the methods by keeping ...…”

“…- Isotope fractionation could happen during the sample’s preparation [ 108 – 111 ] Reversed-phase liquid chromatography (RP-LC) Highly retained hydrophilic lipids, separation based on carbon chain length and degree of FA unsaturation - Reliable, efficient, and selective separation - Suitable for complex lipid separation - Highly sensitive and could provide accurate results at low concentrations - Could be connected with a wide range of detectors including UV-Vis, fluorescence, and mass spectrometry for quantitative and qualitative analysis - RP-LC offers excellent peak shape and high resolution, enabling the separation of complex mixtures with accuracy - Not well-suited for the separation of highly polar compounds - Does not work properly for the separation of high-molecular-weight compounds, such as large peptides or protein - Expensive to purchase and needs skilled manpower to operate and maintain - RP-LC columns can degrade over time, leading to the loss of column efficiency and reproducibility - Some process of RP-LC uses non-volatile or semi-volatile mobile phases, which could leave residue in the mass spectrometer [ 112 – 114 ] Hydrophilic interaction liquid chromatography (HILIC) - Suitable for analyzing polar compounds like sugars, amino acids, and glycerophospholipids - Uses a mobile phase that is typically highly aqueous - The stationary phase in HILIC is often made of materials like amino, amide, or zwitterionic phases - Interface method between RP-LC and NP-LC - Highly effective for the separation of polar and hydrophilic compounds - Suitable for separation of LysoPLs isomers - Often provides improved peak shapes for polar compounds compared to RP-LC - Can reduce matrix effects - Not the ideal choice for less polar or hydrophobic analytes - HILIC method development could be more challenging compared to RP-LC - The retention time of peaks is highly dependent on pH and temperature, hard to transfer the methods by keeping the same accuracy - Can introduce matrix effect - Water is the main mobile phase for this equipment, which might not be suitable for all sample types [ 115 – 118 ] Normal phase liquid chromatography (NP-LC) - Uses a polar stationary phase and a nonpolar mobile phase - It is the opposite of reversed-phase liquid chromatography (RP-LC) - The stationary phase is polar and the mobile phase is non-polar - NP-LC is highly effective for the separation of polar compounds, that may not be well-retained on reversed-phase columns - NP-LC can be used for sample cleanup and fractionation - Could be used for the separation of natural products - Not suitable for the separation of non-polar compounds - Not provide accurate results for complex samples, containing a wide range of compounds with varying polarities - Extensive sample preparation is required - Like other HPLC methods, it i...…”