Serum lipidomics study reveals protective effects of Rhodiola crenulata extract on Alzheimer's disease rats.

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder. Rhodiola crenulata extract (RCE) has shown its protective effects on AD, however, the underlying mechanism is still unclear. In this work, serum lipidomics was conducted to reveal the action mechanism of RCE on AD by HPLC coupled with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). The animal model of AD was reproduced by intrahippocampal injection of Aß1-42 in rats. The novel object recognition test and passive avoidance test were performed to evaluate the protective effects of RCE on AD rats. The differences of lipid metabolism profiles in rats were evaluated by multivariate statistical analysis. Then, the potential lipid biomarkers were identified and the possible mechanism of RCE on AD was elucidated by metabolic pathways analysis. As a result, twenty-eight lipids with significant differences between the control group and the model group were screened out. With the treatment of RCE, 19 lipids in AD rats showed a trend of callback to the normal levels. The results of pathway analysis indicated that the protective effects of RCE on AD might be closely related to the regulation of linoleic acid metabolism, α-linoleic acid metabolism, sphingolipid metabolism and ether lipid metabolism. In conclusion, this study provides a new perspective on the potential intervention mechanism of RCE for AD treatment.

A simplified strategy for molecular formula determination of chemical constituents in traditional Chinese medicines based on accurate mass, A + 1 and A + 2 isotopic peaks using Fourier transform ion cyclotron resonance mass spectrometry.

RATIONALE: Recently, isotopic fine structures derived from Fourier transform ion cyclotron resonance mass spectrometry have been used to determine the molecular formula for unknown compounds in many complex systems. However, a simplified strategy for molecular formula determination of chemical constituents in traditional Chinese medicines (TCMs) based on accurate mass, A + 1 and A + 2 isotopic peaks is necessary. METHODS: Salviae miltiorrhizae was selected as a representative species. First, the chemical constituents were chromatographically separated and their accurate masses were obtained. The A + 1 and A + 2 isotopic peaks of all chemical constituents were then also acquired. Finally, the chemical formulae of the chemical constituents were determined. RESULTS: In the sample of Salviae miltiorrhizae, the formulae of 38 CHO-containing chemical constituents were quickly determined, and all chemical constituents were identified using their tandem mass spectrometric data. Moreover, the method was validated by comparison of the A + 1 and A + 2 isotopic peaks, their fragmentation patterns and the retention times of six selected standard substances. CONCLUSIONS: The results demonstrate that the described strategy performs well for molecular formula determination of chemical constituents in TCMs. This also indicates that this method will be meaningful for the structural identification of chemical constituents of TCMs.

Brain metabolomics study for the protective effects of Rhodiola crenulata extract on Alzheimer's disease by HPLC coupled with Fourier transform-ion cyclotron resonance mass spectrometry.

In order to investigate the protective effects of Rhodiola crenulata extract on Alzheimer's disease, a brain metabolomics study in rats was conducted by high performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry. Rat model was constructed by bilateral hippocampal injection of amyloid-ß peptide and immunohistochemistry was performed to evaluate the pharmacological effect of Rhodiola crenulata extract. Multivariate statistical analysis was used to discover potential biomarkers in rat brain and related metabolic pathways analysis was conducted to elucidate the action mechanism of Rhodiola crenulata extract. As a result, a total of 19 metabolites contributing to Alzheimer's disease progress were identified and nine of them were restored to the normal levels after drug administration. Pathway analysis revealed that the protective effects of Rhodiola crenulata extract are related to the regulation of glutathione metabolism and arachidonic acid metabolism in rat brain. In conclusion, this work demonstrates that the developed metabolomics method is useful to investigate the protective effects of Rhodiola crenulata extract against Alzheimer's disease. These outcomes may further provide reliable evidence to illuminate the intervention mechanism of other traditional Chinese medicines on Alzheimer's disease.

Neuroprotective effects of a Rhodiola crenulata extract on amyloid-ß peptides (Aß1-42) -induced cognitive deficits in rat models of Alzheimer's disease.

BACKGROUND: Rhodiola crenulata has been wildly used as a healthy food, antidepressant and antifatigue for many years in China. Recent studies suggested that Rhodiola crenulata extract (RCE) has cognitive protective effects in the treatment of Alzheimer's disease (AD). PURPOSE: To assess the protective effects of RCE on cognitive deficits and clarify its therapeutic mechanisms in Aß1-42 -induced rat models of AD. STUDY DESIGN: RCE was prepared by freeze-drying technology. Their protective effects on Aß1-42-induced rat models of AD and the preliminary therapeutic mechanisms were studied. METHODS: The Y maze test and Morris water maze (MWM) test were conducted to evaluate the learning and memory abilities of the rats. Subsequently, biochemical assays, hematoxylin-eosin staining, immunohistochemistry and Western blotting were performed to elucidate the mechanisms. RESULTS: RCE significantly increased the spontaneous alternation (F (6, 111) = 8.165, p < 0.001), prolonged the swimming time (F (6, 111) = 20.143, p < 0.001) and decreased the escape latency in rat models of AD. In addition, RCE significantly increased the acetylcholine (Ach) level and the choline acetyl transferase (ChAT) activity (F (6, 34) = 6.033, p < 0.001; F (6, 34) = 6.958, p < 0.001, respectively), repaired the damage of hippocampus neurons and prevented Aß formation in the hippocampus in Aß1-42 injected rats. Moreover, RCE increased the superoxide dismutase (SOD) activity and decreased the malondialdehyde (MDA) level in cortex of Aß1-42 injected rats (F (6, 34) = 5.097, p < 0.01; F (6, 34) = 2.907, p < 0.05, respectively), significantly reduced the expressions of p-tau (ser396) and induced the expressions of p-GSK3ß (ser9) in hippocampus (F (6, 34) = 15.297, p < 0.001; F (6, 34) = 9.652, p < 0.001, respectively). CONCLUSION: Our findings demonstrated that RCE significantly alleviated the learning and memory deficits in the Aß1-42-induced rat models of AD. The mechanisms involved its protection effects against cholinergic system deficiency, oxidative stress damage and GSK3ß activation. RCE may be a potential therapeutic medicine with multi-targets to prevent the progression of cognitive deterioration in AD.