ABSTRACT
The aim of this paper is to explore the key anti-fatigue active components in the saponin-like composition of American ginseng. The anti-fatigue activity of western ginseng samples was evaluated using a zebrafish model; metabolomics techniques were used to identify the main saponins in western ginseng from different origins; the active substances and relevant targets of the anti-fatigue effect of western ginseng were initially screened by constructing a PPI protein interaction network between western ginseng saponins and disease targets, and the key active ingredients were screened using a molecular docking method; finally, the anti-fatigue activity of the key active ingredients was evaluated using a zebrafish, animal experiment was approved by the Ethics Committee of Shandong Academy of Medical Sciences (SYXK20220005). The anti-fatigue activity of the key active ingredients was evaluated using a zebrafish model. The results of the zebrafish activity evaluation showed that there were significant differences in the activities of the western ginseng samples from the two origins, and a total of 10 different saponins were identified as possibly related to the anti-fatigue activity after further metabolomic testing and pattern discrimination. The core anti-fatigue targets were screened with the help of component-disease target PPI, combined with pharmacophore-like parameters and molecular docking techniques, and pseudoginsenoside F11 was found to have good binding activity to five of the targets. Finally, the zebrafish model revealed that pseudoginsenoside F11 exhibited significant anti-fatigue activity. This study used metabolomics and zebrafish model to screen the key active substances of pseudoginsenoside F11 for its anti-fatigue activity, which will provide a reference for further research on the anti-fatigue of pseudoginsenosides.
ABSTRACT
Aim To explore the antidepressant effect and the mechanism of self-made prescription of strengthening spleen and replenishing Qi ( SMP-SS-RQ) . Methods The depression model of chronic un-predictable mild stress ( CUMS ) was established in mice. The animals were randomly divided into control group, model group, SMP-SSRQ low, middle and high dose groups (8, 16, 32 mg·kg-1), with 12 mice for each group. The control group and the model group were given the same volume of saline, and other groups were given corresponding dose of SMP-SSRQ. Animals of each group were administered by gavage twice a day for two weeks. Behavioral indexes of mice were deter-mined by open field experiment, sugar consumption test, forced swimming test and tail suspension test. Quantitative real-time PCR (qPCR) and Western blot were respectively performed to detect mRNA and pro-tein expression levels of Igsf11 , Pdia2 and Sec14 l2 inprefrontal cortex and hippocampus. Results Com-pared with model group, depressed mice' s horizontal mobile score, upright number and the sugar water pref-erence index increased and FST as well as TST de-creased in all SMP-SSRQ groups(P<0.05). The de-pression symptoms in mice were obviously improved by SMP-SSRQ therapy. Low and high doses of SMP-SSRQ significantly reduced mRNA and protein expression lev-el of Igsf11 , Pdia2 and Sec14 l2 in the prefrontal cortex and hippocampus of the depressed mice, presenting significant statistical difference compared with model group ( P<0.05 ) . Conclusions SMP-SSRQ can ef-fectively improve mouse depressive behavior, and its mechanism may be related to the down-regulation of Igsf11 , Pdia2 and Sec14 l2 in mouse prefrontal cortex and hippocampus.
ABSTRACT
<p><b>OBJECTIVE</b>To better assess the role of p38 MAPK, this project was designed to investigate whether intraventricular injection of antisense oligodeoxynucleotide (As-ODN) directed against the p38 MAPK of pyramidal neurons in hippocampus could affect the brain ischemic tolerance induced by limb ischemic preconditioning (LIP).</p><p><b>METHODS</b>The rat 4-vessel occlusion global cerebral ischemic model was used. Forty-eight male Wistar rats with permanently occlusion of the bilateral vertebral arteries were divided into 8 groups (n=6): sham, LIP, brain ischemic insult, LIP + brain ischemic insult, distilled water + LIP + brain ischemic insult, p38 MAPK As-ODN and p38 MAPK As-ODN + LIP + brain ischemic insult (two doses of 5 nmol/5 microl and 10 nmol/5 microl were used) groups. Thionin staining was used for observing histological changes of the hippocampus.</p><p><b>RESULTS</b>No significant delayed neuronal death (DND) was detected in the CA1 hippocampus of the rats that underwent sham and LIP operation. Brain ischemic insult for 8 min induced obvious DND as represented with the increase in histological grade (HG) and decrease in neuronal density (ND) significantly compared with sham and LIP groups. LIP protected the CA1 hippocampal pyramidal neurons against DND induced by global brain ischemic insult, suggesting the occurrence of brain ischemic tolerance. However, pretreatment with p38 MAPK As-ODN effectively blocked the ischemic tolerance induced by LIP in a dose dependent manner.</p><p><b>CONCLUSION</b>It could be concluded that p38 MAPK plays an important role in the brain ischemic tolerance induced by LIP.</p>