ABSTRACT
Background: Demyelination has been observed in neurological disorders, motivating researchers to search for components for enhancing remyelination. Previously we found that Rb1, a major ginsenoside in Korean Red Ginseng (KRG), enhances myelin formation. However, it has not been studied whether Rb1 or KRG function in remyelination after demyelination in vivo. Methods: Mice were fed 0.2% cuprizone-containing chow for 5 weeks and returned to normal chow with daily oral injection of vehicle, KRG, or Rb1 for 3 weeks. Brain sections were stained with luxol fast blue (LFB) staining or immunohistochemistry. Primary oligodendrocyte or astrocyte cultures were subject to normal or stress condition with KRG or Rb1 treatment to measure gene expressions of myelin, endoplasmic reticulum (ER) stress, antioxidants and leukemia inhibitory factor (LIF). Results: Compared to the vehicle, KRG or Rb1 increased myelin levels at week 6.5 but not 8, when measured by the LFB+ or GST-pi+ area within the corpus callosum. The levels of oligodendrocyte precursor cells, astrocytes, and microglia were high at week 5, and reduced afterwards but not changed by KRG or Rb1. In primary oligodendrocyte cultures, KRG or Rb1 increased expression of myelin genes, ER stress markers, and antioxidants. Interestingly, under cuprizone treatment, elevated ER stress markers were counteracted by KRG or Rb1. Under rotenone treatment, reduced myelin gene expressions were recovered by Rb1. In primary astrocyte cultures, KRG or Rb1 decreased LIF expression. Conclusion: KRG and Rb1 may improve myelin regeneration during the remyelination phase in vivo, potentially by directly promoting myelin gene expression.
ABSTRACT
Dendropanax trifidus (DT) is a medicinal herb native to East Asia, which has been used extensively for its therapeutic properties in traditional medicine. In this study, we examined the effects of DT sap on the regulation of body weight and muscle metabolism in mice. Obese model db/db mice were administered daily with DT sap or vehicle control over a 6-week period. The effects of DT sap on muscle metabolism were studied in C2C12 muscle cells, where glycolytic and mitochondrial respiration rates were monitored. As AMP-activated protein kinase (AMPK) is a master regulator of metabolism and plays an important function as an energy sensor in muscle tissue, signaling pathways related with AMPK were also examined. We found that DT sap inhibited body weight increase in db/db, db/+, and +/+ mice over a 6-week period, while DT sap-treated muscle cells showed increased muscle metabolism and also increased phosphorylation of AMPK and Acetyl-CoA Carboxylase (ACC). Finally, we found that DT sap, which is enriched in estrogen in our previous study, significantly activates estrogen alpha receptor in a concentration-dependent manner, which can drive the activation of AMPK signaling and may be related to the muscle metabolism and weight changes observed here.
