Anti-stress effects of ginseng total saponins on hindlimb-unloaded rats assessed by a metabolomics study.
BACKGROUND
Ginseng, the roots and rhizomes of Panax ginseng C.A. Mey. (Araliaceae), is used as a tonic herb for thousands of years in Asian countries. Saponins are recognized as its major active ingredients and reportedly can ease disorders caused by various adverse stimuli. Nevertheless, it is unclear whether ginseng saponins have beneficial effects on stress caused by microgravity.


OBJECTIVE
This study aimed to assess the anti-stress effects and corresponding mechanisms of ginseng total saponins (GTSs) on simulated microgravity (SM) hindlimb-unloaded rats using a metabolomics method.


METHODS
The stressed rats were induced by hindlimb unloading for 7 continuous days. Levels of plasma corticosterone (CORT) and weights of immune organs including the thymuses, spleens, and adrenal glands were determined. Urinary metabolic profiles of the rats under the simulated microgravity condition with and without GTSs intervention were compared using an ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF-MS) based metabolomics method. Multivariate statistical analysis including Principal Component Analysis (PCA) and Partial Least Squares project to latent structures-Discriminant Analysis (PLS-DA) were performed.


RESULTS
Compared with control (66.22±10.40ng/mL), the plasma CORT level of the SM rats (82.67±13.64ng/mL) were significantly (p<0.05) elevated, and GTSs could restore this elevation to a lower level (77.75±14.35ng/mL). GTSs could also significantly alleviate the atrophy of the thymuses and the spleens, as well as the hypertrophy of the adrenal glands of the SM rats. Urinary metabolic profiling showed comprehensive metabolic variation among the three groups. A series of metabolic pathways including taurine and hypotaurine, purine and pyridine, and amino acid were affected. Eleven potential biomarkers such as taurine, adenine, and valine were identified. GTSs could correct the disturbed metabolic pathways and restore the variation of these potential markers.


CONCLUSIONS
GTSs can exert anti-stress effects by reducing the secretion of plasma CORT, enhancing the immune function, and restoring an array of disturbed metabolic pathways and metabolites. The findings of this study provide crucial evidence of a link between metabolic imbalance and microgravity, and reveal a molecular basis for the anti-stress benefits of GTSs in the management of microgravity-related disorders.
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, P.R. China.
Li
L
Feng
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, P.R. China.
Xin-Min
XM
Liu
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, P.R. China.
Fang-Rui
FR
Cao
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, P.R. China.
Li-Sha
LS
Wang
Sichuan Medical University, Luzhou 646000, P.R. China.
Yi-Xi
YX
Chen
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, P.R. China.
Rui-le
RL
Pan
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, P.R. China.
Yong-Hong
YH
Liao
Sichuan Medical University, Luzhou 646000, P.R. China.
Qiong
Q
Wang
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, P.R. China. Electronic address: qchang@implad.ac.cn.
Qi
Q
Chang
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000596:Amino Acids / Q000652:urine*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D019295:Computational Biology; D003345:Corticosterone / Q000097:blood; D019417:Hindlimb Suspension; D006984:Hypertrophy; D016018:Least-Squares Analysis; D008297:Male; D055432:Metabolomics / Q000379:methods; D015999:Multivariate Analysis; D005894:Panax / Q000737:chemistry*; D010363:Pattern Recognition, Automated; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D025341:Principal Component Analysis; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013312:Stress, Physiological / Q000187:drug effects*; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D016482:Urinalysis; D018474:Weightlessness Simulation
D000596:Amino Acids; D015415:Biomarkers; D010936:Plant Extracts; D012503:Saponins; D003345:Corticosterone
Ginseng total saponins; Hindlimb unloading; LC/MS; Metabolomics; Stress; Urine