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Chinese Journal of Experimental Traditional Medical Formulae ; (24): 49-56, 2021.
Article in Chinese | WPRIM | ID: wpr-906111

ABSTRACT

Objective:To investigate the effect of total ginsenoside ginseng root on the learning and memory impairment and anxiety of hindlimb suspension rats by detecting the performance of rats in the water maze, elevated plus maze, and the expression of hypothalamic-pituitary-adrenal (HPA) axis, inflammatory factors and tryptophan pathway related factors through the intervention of ginsenosides in hindlimb suspension rats. Method:The Wistar male rats were divided into normal group, hindlimb suspension model group, Huperzine A group (0.1 mg·kg<sup>-1</sup>), and total ginsenoside ginseng root low and high dose groups (100, 200 mg·kg<sup>-1</sup>), with 8 rats in each group. Except for the normal group, the rats in the other groups maintained a -30° hindlimb suspension state for 24 h. The normal group and the model group received intragastric administration of 10 mL·kg<sup>-1</sup> pure water . After 28 days of continuous administration, the water maze and elevated plus maze behavioral tests were performed. After the tests, blood was taken from the abdominal aorta, and the rat brain cortex was peeled off on ice, quenched with liquid nitrogen, and stored at -80 ℃ for later use. LC-MS/MS was used to detect neurotransmitter levels of dopamine, acetylcholine, glutamate, <italic>γ</italic>-aminobutyric acid and tryptophan pathway metabolites (tryptophan, 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, kynurenine, 3-hydroxykynurenine, and kynurenine) in rat brain cortex. An enzyme-linked immunosorbent assay (ELISA) kit was used to detect the levels of inflammatory factors interleukin-6 (IL-6), interleukin-10 (IL-10, the HPA axis-related hormone corticotropin (ACTH), and the level of corticosterone (CORT). Result:Compared with the normal group, the escape latency in the water maze significantly increased, the number of crossings was significantly reduced, and the number of open-arm entry and the percentage of open-arm entry were significantly reduced in the elevated plus maze in model group (<italic>P</italic><0.05,<italic> P</italic><0.01), the content of dopamine, acetylcholine, glutamic acid, and <italic>γ</italic>-aminobutyric acid in the cortex decreased, kynurenine and kynurenic acid showed an upward trend, 3-hydroxykynurenine, 5-hydroxytryptamine, 5-hydroxyindole acetic acid showed a downward trend, and the levels of IL-6, IL-10, ACTH, and CORT in the serum significantly increased (<italic>P</italic><0.05, <italic>P</italic><0.01). Compared with the model group of rats, total ginsenoside ginseng root low and high dose groups group reduced the avoidance latency in the water maze, and increased the number of crossings and the number of open arms of the elevated plus maze, dopamine, acetylcholine, glutamate, and <italic>γ</italic>-aminobutyl content increased, while kynurenine and kynurenic acid showed a downward trend, 3-hydroxykynurenine, serotonin, and 5-hydroxyindole acetic acid showed an upward trend, and IL-6, IL-10, ACTH, and CORT factor levels were down-regulated(<italic>P</italic><0.05, <italic>P</italic><0.01). Conclusion:Hindlimb suspension for 28 days in simulated microgravity can impair the learning and memory ability of rats and cause anxiety-like behaviors. Total ginsenoside ginseng root can improve their learning and memory impairment and anxiety-like behaviors. The mechanism may be mainly related to inhibiting body inflammation and regulating HPA axis imbalance.

2.
Chinese Medical Journal ; (24): 805-810, 2019.
Article in English | WPRIM | ID: wpr-772206

ABSTRACT

BACKGROUND@#Abnormally activated mechanistic target of rapamycin (mTOR) pathway has been reported in several model animals with inherited metabolic myopathies (IMMs). However, the profiles of mTOR pathway in skeletal muscles from patients are still unknown. This study aimed to analyze the activity of mTOR pathway in IMMs muscles.@*METHODS@#We collected muscle samples from 25 patients with mitochondrial myopathy (MM), lipid storage disease (LSD) or Pompe disease (PD). To evaluate the activity of mTOR pathway in muscle specimens, phosphorylation of S6 ribosomal protein (p-S6) and p70S6 kinase (p-p70S6K) were analyzed by Western blotting and immunohistochemistry.@*RESULTS@#Western blotting results showed that p-p70S6K/p70S6K in muscles from LSD and MM was up-regulated when compared with normal controls (NC) (NC vs. LSD, U = 2.000, P = 0.024; NC vs. MM: U = 6.000, P = 0.043). Likewise, p-S6/S6 was also up-regulated in muscles from all three subgroups of IMMs (NC vs. LSD, U = 0.000, P = 0.006; NC vs. PD, U = 0.000, P = 0.006; NC vs. MM, U = 1.000, P = 0.007). Immunohistochemical study revealed that p-S6 was mainly expressed in fibers with metabolic defect. In MM muscles, most p-S6 positive fibers showed cytochrome C oxidase (COX) deficiency (U = 5.000, P = 0.001). In LSD and PD muscles, p-S6 was mainly overexpressed in fibers with intramuscular vacuoles containing lipid droplets (U = 0.000, P = 0.002) or basophilic materials (U = 0.000, P = 0.002).@*CONCLUSION@#The mTOR pathway might be activated in myofibers with various metabolic defects, which might provide evidence for mTOR inhibition therapy in human IMMs.


Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , Blotting, Western , Glycogen Storage Disease Type II , Genetics , Metabolism , Immunohistochemistry , In Vitro Techniques , Lipid Metabolism, Inborn Errors , Genetics , Metabolism , Mitochondrial Myopathies , Genetics , Metabolism , Muscular Diseases , Genetics , Metabolism , Signal Transduction , Genetics , Physiology , TOR Serine-Threonine Kinases , Metabolism
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