title: Ginsenosides attenuate methylglyoxal-induced impairment of insulin signaling and subsequent apoptosis in primary astrocytes.
abstract: Diabetes mellitus (DM), which is characterized by chronic hyperglycemia, is known to increase the risk of neurodegeneration. In type 2 diabetes, hyperglycemia could cause insulin resistance and neurodegeneration in various cells including neurons and astrocytes. Hyperglycemia is also known to result in the formation of advanced glycation end-products (AGE) Methylglyoxal (MG) is one of the most reactive AGE precursors in which its abnormal accumulation is usually found in diabetic patients and induces neuronal cell death in central nervous system. Ginseng is a herb that has been widely used to treat various diseases in traditional Chinese medicine. Ginsenosides, the pharmacologically active component isolated from ginseng, have been shown to have cryoprotective effects in different neural cells. In the present study we investigated the effects of MG in disturbing insulin signaling and leading to further cellular apoptosis in rat primary astrocytes. Furthermore, the protective effects of different subtypes of ginsenosides were studied. From the results, impairment of insulin signaling was found in astrocytes under MG treatment. Moreover, cleavage of caspase and Poly ADP ribose polymerase (PARP) was observed in line with insulin signaling disruption, showing the neurotoxic effects of MG towards astrocytes. The effects of ginsenosides in MG treated astrocytes were also investigated. After treatment, ginsenosides Rd and R-Rh2 were shown to ameliorate the cell viability of MG-treated astrocytes. In addition, Rd and R-Rh2 could improve insulin signaling and inhibit apoptosis, indicating that Rd, R-Rh2 and related compounds may have therapeutic potential in treating diabetes-induced neurodegeneration.
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong; Department of Biology, Hong Kong Baptist University, Hong Kong.
authors.forename: John M T
authors.initials: JM
authors.lastname: Chu
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong.
authors.forename: Dicky K M
authors.initials: DK
authors.lastname: Lee
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong.
authors.forename: Daniella P K
authors.initials: DP
authors.lastname: Wong
authors.affiliation: Department of Biology, Hong Kong Baptist University, Hong Kong.
authors.forename: Ricky N S
authors.initials: RN
authors.lastname: Wong
authors.affiliation: Department of Biology, Hong Kong Baptist University, Hong Kong.
authors.forename: Ken K L
authors.initials: KK
authors.lastname: Yung
authors.affiliation: School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong.
authors.forename: Christopher H K
authors.initials: CH
authors.lastname: Cheng
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong. Electronic address: kkmyue@hkbu.edu.hk.
authors.forename: Kevin K M
authors.initials: KK
authors.lastname: Yue
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D036145:Ginsenosides / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011765:Pyruvaldehyde / Q000633:toxicity*; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D036145:Ginsenosides; D005904:Glial Fibrillary Acidic Protein; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D018696:Neuroprotective Agents; D011765:Pyruvaldehyde; D011065:Poly(ADP-ribose) Polymerases; D011972:Receptor, Insulin; C049863:ginsenoside Rd
keywords: Astrocytes; Diabetes; Ginsenosides; Insulin signaling; Methylglyoxal