Diabetic peripheral neuropathy(DPN) is a progressive neurodegenerative disease of peripheral nervous system with high energy requirement. The adenosine monophosphate-activated protein kinase(AMPK)/peroxisome prolifera...Diabetic peripheral neuropathy(DPN) is a progressive neurodegenerative disease of peripheral nervous system with high energy requirement. The adenosine monophosphate-activated protein kinase(AMPK)/peroxisome proliferator-activated receptor-γ coactivator 1α(PGC-1α) axis plays a key role in regulating mitochondrial energy metabolism. Increasing preclinical evidences have shown that inhibition of AMPK/PGC-1α pathway leading to mitochondrial dysfunction in neurons or Schwann cells contributes to neuron apoptosis, distal axonopathy and nerve demyelination in DPN. Some Chinese medicine formulae or extracts from herbs may have potential neuroprotective effects on DPN via activating AMPK/PGC-1α pathway and improving mitochondrial function.展开更多
Objective： TO examine the effects of the combination of quercetin （Q）, cinnamaldehyde （C） and hirudin （H）, a Chinese medicine formula on high glucose （HG）-induced apoptosis of cultured dorsal root ganglion （...Objective： TO examine the effects of the combination of quercetin （Q）, cinnamaldehyde （C） and hirudin （H）, a Chinese medicine formula on high glucose （HG）-induced apoptosis of cultured dorsal root ganglion （DRG） neurons. Methods： DRG neurons exposed to HG （45 mmol/L） for 24 h were employed as an in vitro model of diabetic neuropathy. Cell viability, reactive oxygen species （ROS） level and apoptosis were determined. The expression of nuclear factor of Kappa B （NF- κB）, inhibitory kappa B α （IκBα ）, phosphorylated IκBα and Nf-E2 related factor 2 （Nrf2） were examined using reverse transcription-polymerase chain reaction （RT-PCR） and Western blot assay. The expression of hemeoxygenase-1 （HO-1）, interleukin-6 （IL-6）, tumor necrosis factor （TNF-α） and caspase-3 were also examined by RT-PCR and Western blot assay. Results： HG treatment markedly increased DRG neuron apoptosis via increasing intracellular ROS level and activating the NF- κB signaling pathway （P〈0.05）. Co-treatment with Q, C, H and their combination decreased HG-induced caspase-3 activation and apoptosis （P〈0.05 or P〈0.01）. The expressions of NF- κB, IL-6 and TNF-α were down- regulated, and Nrf2/HO-1 expression was up-regulated （P〈0.05 or P〈0.01）. QCH has better effect in scavenging ROS, activating Nrf-2/HO-1, and down-regulating the NF- κB pathway than other treatment group. Conclusions： DRG neurons＇ apoptosis was increased in diabetic conditions, which was reduced by QCH formula treatment. The possible reason could be activating Nrf-2/HO-1 pathway, scavenging ROS, and inhibition of NF- κB activation. The effect of QCH combination was better than each monomer or the combination of the two monomers.展开更多
基金Supported by the National Natural Science Foundation of China(No.81473639)the Fundamental Research Funds for the Central Universities(No.3332018037)
文摘Diabetic peripheral neuropathy(DPN) is a progressive neurodegenerative disease of peripheral nervous system with high energy requirement. The adenosine monophosphate-activated protein kinase(AMPK)/peroxisome proliferator-activated receptor-γ coactivator 1α(PGC-1α) axis plays a key role in regulating mitochondrial energy metabolism. Increasing preclinical evidences have shown that inhibition of AMPK/PGC-1α pathway leading to mitochondrial dysfunction in neurons or Schwann cells contributes to neuron apoptosis, distal axonopathy and nerve demyelination in DPN. Some Chinese medicine formulae or extracts from herbs may have potential neuroprotective effects on DPN via activating AMPK/PGC-1α pathway and improving mitochondrial function.
基金the office of Traditional Chinese Medicine of Peking Union Medical College Hospitalthe Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences, Pecking, China, for supporting this research.
文摘Objective： TO examine the effects of the combination of quercetin （Q）, cinnamaldehyde （C） and hirudin （H）, a Chinese medicine formula on high glucose （HG）-induced apoptosis of cultured dorsal root ganglion （DRG） neurons. Methods： DRG neurons exposed to HG （45 mmol/L） for 24 h were employed as an in vitro model of diabetic neuropathy. Cell viability, reactive oxygen species （ROS） level and apoptosis were determined. The expression of nuclear factor of Kappa B （NF- κB）, inhibitory kappa B α （IκBα ）, phosphorylated IκBα and Nf-E2 related factor 2 （Nrf2） were examined using reverse transcription-polymerase chain reaction （RT-PCR） and Western blot assay. The expression of hemeoxygenase-1 （HO-1）, interleukin-6 （IL-6）, tumor necrosis factor （TNF-α） and caspase-3 were also examined by RT-PCR and Western blot assay. Results： HG treatment markedly increased DRG neuron apoptosis via increasing intracellular ROS level and activating the NF- κB signaling pathway （P〈0.05）. Co-treatment with Q, C, H and their combination decreased HG-induced caspase-3 activation and apoptosis （P〈0.05 or P〈0.01）. The expressions of NF- κB, IL-6 and TNF-α were down- regulated, and Nrf2/HO-1 expression was up-regulated （P〈0.05 or P〈0.01）. QCH has better effect in scavenging ROS, activating Nrf-2/HO-1, and down-regulating the NF- κB pathway than other treatment group. Conclusions： DRG neurons＇ apoptosis was increased in diabetic conditions, which was reduced by QCH formula treatment. The possible reason could be activating Nrf-2/HO-1 pathway, scavenging ROS, and inhibition of NF- κB activation. The effect of QCH combination was better than each monomer or the combination of the two monomers.
