Despite numerous efforts to overcome neuropathic pain,various pharmacological drugs often fail to meet the needs and have many side effects.Muscovite is an aluminosilicate mineral that has been reported to have an ant...Despite numerous efforts to overcome neuropathic pain,various pharmacological drugs often fail to meet the needs and have many side effects.Muscovite is an aluminosilicate mineral that has been reported to have an anti-inflammatory effect,but the efficacy of muscovite for neuropathic pain has not been investigated.Here,we assessed whether muscovite nanoparticles can reduce the symptoms of pain by controlling the inflammatory process observed in neuropathic pain.The analgesic effects of muscovite nanoparticles were explored using partial sciatic nerve ligation model of neuropathic pain,in which one-third to onehalf of the nerve trifurcation of the sciatic nerve was tightly tied to the dorsal side.Muscovite nanoparticles(4 mg/100μL)was given intramuscularly to evaluate its effects on neuropathic pain(3 days per week for 4 weeks).The results showed that the muscovite nanoparticle injections significantly alleviated partial sciatic nerve ligation-induced mechanical and cold allodynia.In the spinal cord,the muscovite nanoparticle injections exhibited inhibitory effects on astrocyte and microglia activation and reduced the expression of pro-inflammatory cytokines,such as interleukin-1β,tumor necrosis factor-α,interleiukin-6 and monocyte chemoattractant protein-1,which were upregulated in the partial sciatic nerve ligation model.Moreover,the muscovite nanoparticle injections resulted in a decrease in activating transcription factor 3,a neuronal injury marker,in the sciatic nerve.These results suggest that the analgesic effects of muscovite nanoparticle on partial sciatic nerve ligation-induced neuropathic pain may result from inhibiting activation of astrocytes and microglia as well as pro-inflammatory cytokines.We propose that muscovite nanoparticle is a potential anti-nociceptive candidate for neuropathic pain.All experimental protocols in this study were approved by the Institutional Animal Ethics Committee(IACUC)at Dongguk University,South Korea(approval No.2017-022-1)on September 28,2017.展开更多
Objective Atopic dermatitis(AD)is a chronic inflammatory skin disease that may be linked to changes in the gut microbiome.Acupuncture has been proven to be effective in reducing AD symptoms without serious adverse eve...Objective Atopic dermatitis(AD)is a chronic inflammatory skin disease that may be linked to changes in the gut microbiome.Acupuncture has been proven to be effective in reducing AD symptoms without serious adverse events,but its underlying mechanism is not completely understood.The purpose of this study was to investigate whether the potential effect of acupuncture on AD is gut microbiota-dependent.Methods AD-like skin lesions were induced by applying MC903 topically to the cheek of the mouse.Acupuncture was done at the Gok-Ji(LI11)acupoints.AD-like symptoms were assessed by lesion scores,scratching behavior,and histopathological changes;intestinal barrier function was measured by fecal output,serum lipopolysaccharide levels,histopathological changes,and mRNA expression of markers involved in intestinal permeability and inflammation.Gut microbiota was profiled using 16S rRNA gene sequencing from fecal samples.Results Acupuncture effectively improved chronic itch as well as the AD-like skin lesions with epidermal thickening,and also significantly altered gut microbiota structure as revealed byβ-diversity indices and analysis of similarities.These beneficial effects were eliminated by antibiotic depletion of gut microbiota,but were reproduced in gut microbiota-depleted mice that received a fecal microbiota transplant from acupuncture-treated mice.Interestingly,AD mice had intestinal barrier dysfunction as indicated by increased intestinal permeability,atrophy of the mucosal structure(reduced villus height and crypt depth),decreased expression of tight junctions and mucus synthesis genes,and increased expression of inflammatory mediators in the ileum.Acupuncture attenuated these abnormalities,which was gut microbiota-dependent.Conclusion Acupuncture ameliorates AD-like phenotypes in a gut microbiota-dependent manner and some of these positive benefits are explained by modulation of the intestinal barrier,providing new perspective for non-pharmacological strategies for modulating gut microbiota to prevent and treat AD.展开更多
基金supported by grants from the National Research Foundation of Korea funded by the Korean government(NRF-2017R1A2B4009963,to JYO,TYH,JHJ and HJP)from the Korea Institute of Oriental Medicine(grant K18182,to JYP,YR and HJP)。
文摘Despite numerous efforts to overcome neuropathic pain,various pharmacological drugs often fail to meet the needs and have many side effects.Muscovite is an aluminosilicate mineral that has been reported to have an anti-inflammatory effect,but the efficacy of muscovite for neuropathic pain has not been investigated.Here,we assessed whether muscovite nanoparticles can reduce the symptoms of pain by controlling the inflammatory process observed in neuropathic pain.The analgesic effects of muscovite nanoparticles were explored using partial sciatic nerve ligation model of neuropathic pain,in which one-third to onehalf of the nerve trifurcation of the sciatic nerve was tightly tied to the dorsal side.Muscovite nanoparticles(4 mg/100μL)was given intramuscularly to evaluate its effects on neuropathic pain(3 days per week for 4 weeks).The results showed that the muscovite nanoparticle injections significantly alleviated partial sciatic nerve ligation-induced mechanical and cold allodynia.In the spinal cord,the muscovite nanoparticle injections exhibited inhibitory effects on astrocyte and microglia activation and reduced the expression of pro-inflammatory cytokines,such as interleukin-1β,tumor necrosis factor-α,interleiukin-6 and monocyte chemoattractant protein-1,which were upregulated in the partial sciatic nerve ligation model.Moreover,the muscovite nanoparticle injections resulted in a decrease in activating transcription factor 3,a neuronal injury marker,in the sciatic nerve.These results suggest that the analgesic effects of muscovite nanoparticle on partial sciatic nerve ligation-induced neuropathic pain may result from inhibiting activation of astrocytes and microglia as well as pro-inflammatory cytokines.We propose that muscovite nanoparticle is a potential anti-nociceptive candidate for neuropathic pain.All experimental protocols in this study were approved by the Institutional Animal Ethics Committee(IACUC)at Dongguk University,South Korea(approval No.2017-022-1)on September 28,2017.
基金supported by grants from the National Research Foundation of Korea funded by the Korean government(No.2020R1A4A1018598,NRF-2021R1A2C2006818,2022M3A9B6017813 and NRF-2023R1A2C1006836).
文摘Objective Atopic dermatitis(AD)is a chronic inflammatory skin disease that may be linked to changes in the gut microbiome.Acupuncture has been proven to be effective in reducing AD symptoms without serious adverse events,but its underlying mechanism is not completely understood.The purpose of this study was to investigate whether the potential effect of acupuncture on AD is gut microbiota-dependent.Methods AD-like skin lesions were induced by applying MC903 topically to the cheek of the mouse.Acupuncture was done at the Gok-Ji(LI11)acupoints.AD-like symptoms were assessed by lesion scores,scratching behavior,and histopathological changes;intestinal barrier function was measured by fecal output,serum lipopolysaccharide levels,histopathological changes,and mRNA expression of markers involved in intestinal permeability and inflammation.Gut microbiota was profiled using 16S rRNA gene sequencing from fecal samples.Results Acupuncture effectively improved chronic itch as well as the AD-like skin lesions with epidermal thickening,and also significantly altered gut microbiota structure as revealed byβ-diversity indices and analysis of similarities.These beneficial effects were eliminated by antibiotic depletion of gut microbiota,but were reproduced in gut microbiota-depleted mice that received a fecal microbiota transplant from acupuncture-treated mice.Interestingly,AD mice had intestinal barrier dysfunction as indicated by increased intestinal permeability,atrophy of the mucosal structure(reduced villus height and crypt depth),decreased expression of tight junctions and mucus synthesis genes,and increased expression of inflammatory mediators in the ileum.Acupuncture attenuated these abnormalities,which was gut microbiota-dependent.Conclusion Acupuncture ameliorates AD-like phenotypes in a gut microbiota-dependent manner and some of these positive benefits are explained by modulation of the intestinal barrier,providing new perspective for non-pharmacological strategies for modulating gut microbiota to prevent and treat AD.