ABSTRACT
Both the total amount and annual growth rate of Alzheimer's disease (AD) patients in China are much higher than in other regions in the world. This trend of rapid growth will be difficult to change in the next few decades, hence the prevention and treatment situation of AD patients in China is more severe. Maintaining the balance between the production and removal pathways of Aß is an important guarantee for the body to maintain its normal physiological state. The dysfunction of Aß clearance is an important factor of Aß accumulation in brain tissue of AD patients causing neurotoxicity of synaptic damage and neuronal death. Based on the literature review, it introduced the important role of microglias in clearing Aß deposits in the process of Alzheimer's disease. And most of these phagocytic cells were the specific phenotype of disease-related microglia (DAM-I/DAM-II) that induced microglial differentiation after activation. IL-10KO promoted the transformation of microglial phenotype DAM-II, and enhanced its phagocytosis for Aß oligomers. There is a hypothesis that IL-10R/STAT3 negatively regulates microglial phagocytosis. It was learnt that blocking the IL-10R/STAT3 pathway promoted microglial activation and enhanced phagocytosis. The comprehensive review on the involvement of IL-10R/STAT3 pathway in the process of AD would open up new ideas and discover new targets for the development of new therapeutic drugs.
Subject(s)
Alzheimer Disease/immunology , Amyloid beta-Peptides/metabolism , Microglia/pathology , Receptors, Interleukin-10/metabolism , STAT3 Transcription Factor/metabolism , Alzheimer Disease/pathology , Amyloid beta-Peptides/immunology , Animals , Brain/immunology , Brain/pathology , Disease Models, Animal , Humans , Microglia/immunology , Phagocytosis/immunology , Signal Transduction/immunologyABSTRACT
D-Amino acid oxidase (DAAO) specifically catalyzes the oxidative deamination of neutral and polar D-amino acids and finally yields byproducts of hydrogen peroxide. Our previous work demonstrated that the spinal astroglial DAAO/hydrogen peroxide (H2 O2 ) pathway was involved in the process of pain and morphine antinociceptive tolerance. This study aimed to report mouse strain specificity of DAAO inhibitors on antinociception and explore its possible mechanism. DAAO inhibitors benzoic acid, CBIO, and SUN significantly inhibited formalin-induced tonic pain in Balb/c and Swiss mice, but had no antinociceptive effect in C57 mice. In contrast, morphine and gabapentin inhibited formalin-induced tonic pain by the same degrees among Swiss, Balb/c and C57 mice. Therefore, mouse strain difference in antinociceptive effects was DAAO inhibitors specific. In addition, intrathecal injection of D-serine greatly increased spinal H2 O2 levels by 80.0% and 56.9% in Swiss and Balb/c mice respectively, but reduced spinal H2 O2 levels by 29.0% in C57 mice. However, there was no remarkable difference in spinal DAAO activities among Swiss, Balb/c and C57 mice. The spinal expression of glutathione (GSH) and glutathione peroxidase (GPx) activity in C57 mice were significantly higher than Swiss and Balb/c mice. Furthermore, the specific GPx inhibitor D-penicillamine distinctly restored SUN antinociception in C57 mice. Our results reported that DAAO inhibitors produced antinociception in a strain-dependent manner in mice and the strain specificity might be associated with the difference in spinal GSH and GPx activity.
Subject(s)
Analgesics/administration & dosage , Biological Variation, Population , D-Amino-Acid Oxidase/antagonists & inhibitors , Nociception/drug effects , Analgesics/pharmacokinetics , Animals , D-Amino-Acid Oxidase/metabolism , Glutathione/analysis , Glutathione/metabolism , Glutathione Peroxidase/analysis , Glutathione Peroxidase/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Spinal Cord/drug effects , Spinal Cord/metabolismABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Immunomodulation has become a crucial modality for cancer treatment. Chinese Herbal Medicines (CHMs) are expected as adjuvant therapy for immunomodulation against cancer, but face the key challenge of poor scientific evidence. Changes of natural killer (NK) cells on numbers and/or cytotoxicity are a novel respect to evaluate the immunomodulation of CHMs. AIM OF THE STUDY: The purpose of this review is to investigate the immunomodulation of Chinese Herbal Medicines (CHMs) on NK cell populations for cancer therapy. MATERIALS AND METHODS: A systematic review was conducted and outside mainstream electronic databases were screened for potential reference articles. This review tried to report and critically analyzed all the correlative studies, especially these clinical trials (3 CHM extracts and 11 CHM formulas). RESULTS: Evidence-based functions of CHMs against cancer could be summarized as: (1) enhancement of NK cells activity or relative percentage; (2) prevention of tumor growth and metastasis; (3) relief on side-effects or complications of therapeutic strategies (i.e. chemotherapy, radiotherapy and resection). Briefly, most of cellular studies and two thirds animal studies were based on the extract or components of single herbs, whilst most of clinical trials were keen on formula or prescription of CHMs. The main components of CHMs were demonstrated active on promoting the cytotoxicity of NK cells, including Angelica sinensis, Ganoderma lucidum, Panax ginseng, Radix Astragali, Lentinus edodes, etc. CONCLUSIONS: This comprehensive review demonstrated NK cells activity was positively associated with quality of life but not survival benefit of cancer patients. Thus exploring the roles of NK cells in adjuvant therapy against cancer is confirmed to be beneficial to explore the underlying relationship between immunomodulation and quality of life.
