Previous studies showed that acetyl-11-keto-beta-boswellic acid(AKBA),the active ingredient in the natural Chinese medicine Boswellia,can stimulate sciatic nerve injury repair via promoting Schwann cell proliferation....Previous studies showed that acetyl-11-keto-beta-boswellic acid(AKBA),the active ingredient in the natural Chinese medicine Boswellia,can stimulate sciatic nerve injury repair via promoting Schwann cell proliferation.However,the underlying molecular mechanism remains poorly understood.In this study,we performed genomic sequencing in a rat model of sciatic nerve crush injury after gastric AKBA administration for 30 days.We found that the phagosome pathway was related to AKBA treatment,and brain-derived neurotrophic factor expression in the neurotrophic factor signaling pathway was also highly up-regulated.We further investigated gene and protein expression changes in the phagosome pathway and neurotrophic factor signaling pathway.Myeloperoxidase expression in the phagosome pathway was markedly decreased,and brain-derived neurotrophic factor,nerve growth factor,and nerve growth factor receptor expression levels in the neurotrophic factor signaling pathway were greatly increased.Additionally,expression levels of the inflammatory factors CD68,interleukin-1β,pro-interleukin-1β,and tumor necrosis factor-αwere also decreased.Myelin basic protein-andβ3-tubulin-positive expression as well as the axon diameter-to-total nerve diameter ratio in the injured sciatic nerve were also increased.These findings suggest that,at the molecular level,AKBA can increase neurotrophic factor expression through inhibiting myeloperoxidase expression and reducing inflammatory reactions,which could promote myelin sheath and axon regeneration in the injured sciatic nerve.展开更多
Glioblastoma is the most common and aggressive primary tumor in the central nervous system,accounting for 12%-15%of all brain tumors.3-O-Acetyl-11-keto-β-boswellic acid(AKBA),one of the most active ingredients of gum...Glioblastoma is the most common and aggressive primary tumor in the central nervous system,accounting for 12%-15%of all brain tumors.3-O-Acetyl-11-keto-β-boswellic acid(AKBA),one of the most active ingredients of gum resin from Boswellia carteri Birdw.,was reported to inhibit the growth of glioblastoma cells and subcutaneous glioblastoma.However,whether AKBA has antitumor effects on orthotopic glioblastoma and the underlying mechanisms are still unclear.An orthotopic mouse model was used to evaluate the anti-glioblastoma effects of AKBA.The effects of AKBA on tumor growth were evaluated using MRI.The effects on the alteration of metabolic landscape were detected by MALDIMSI.The underlying mechanisms of autophagy reducing by AKBA treatment were determined by immunoblotting and immunofluorescence,respectively.Transmission electron microscope was used to check morphology of cells treated by AKBA.Our results showed that AKBA(100 mg/kg)significantly inhibited the growth of orthotopic U87-MG gliomas.Results from MALDI-MSI showed that AKBA improved the metabolic profile of mice with glioblastoma,while immunoblot assays revealed that AKBA suppressed the expression of ATG5,p62,LC3 B,p-ERK/ERK,and P53,and increased the ratio of p-mTOR/mTOR.Taken together,these results suggested that the antitumor effects of AKBA were related to the normalization of aberrant metabolism in the glioblastoma and the inhibition of autophagy.AKBA could be a promising chemotherapy drug for glioblastoma.展开更多
基金supported by the National Natural Science Foundation of China, No.31972725(to WHY)
文摘Previous studies showed that acetyl-11-keto-beta-boswellic acid(AKBA),the active ingredient in the natural Chinese medicine Boswellia,can stimulate sciatic nerve injury repair via promoting Schwann cell proliferation.However,the underlying molecular mechanism remains poorly understood.In this study,we performed genomic sequencing in a rat model of sciatic nerve crush injury after gastric AKBA administration for 30 days.We found that the phagosome pathway was related to AKBA treatment,and brain-derived neurotrophic factor expression in the neurotrophic factor signaling pathway was also highly up-regulated.We further investigated gene and protein expression changes in the phagosome pathway and neurotrophic factor signaling pathway.Myeloperoxidase expression in the phagosome pathway was markedly decreased,and brain-derived neurotrophic factor,nerve growth factor,and nerve growth factor receptor expression levels in the neurotrophic factor signaling pathway were greatly increased.Additionally,expression levels of the inflammatory factors CD68,interleukin-1β,pro-interleukin-1β,and tumor necrosis factor-αwere also decreased.Myelin basic protein-andβ3-tubulin-positive expression as well as the axon diameter-to-total nerve diameter ratio in the injured sciatic nerve were also increased.These findings suggest that,at the molecular level,AKBA can increase neurotrophic factor expression through inhibiting myeloperoxidase expression and reducing inflammatory reactions,which could promote myelin sheath and axon regeneration in the injured sciatic nerve.
基金supported by National Natural Science Foundation of China(No.81573454 for Jinhua Wang and No.81703536 for Wan Li)supported by Beijing Natural Science Foundation(7172142,China)+1 种基金supported by CAMS Innovation Fund for Medical Sciences(2016-I2M-3-007,China)Science and Technology Major Projects for“Major New Drugs Innovation and Development”(2018ZX09711001-005-025,China).
文摘Glioblastoma is the most common and aggressive primary tumor in the central nervous system,accounting for 12%-15%of all brain tumors.3-O-Acetyl-11-keto-β-boswellic acid(AKBA),one of the most active ingredients of gum resin from Boswellia carteri Birdw.,was reported to inhibit the growth of glioblastoma cells and subcutaneous glioblastoma.However,whether AKBA has antitumor effects on orthotopic glioblastoma and the underlying mechanisms are still unclear.An orthotopic mouse model was used to evaluate the anti-glioblastoma effects of AKBA.The effects of AKBA on tumor growth were evaluated using MRI.The effects on the alteration of metabolic landscape were detected by MALDIMSI.The underlying mechanisms of autophagy reducing by AKBA treatment were determined by immunoblotting and immunofluorescence,respectively.Transmission electron microscope was used to check morphology of cells treated by AKBA.Our results showed that AKBA(100 mg/kg)significantly inhibited the growth of orthotopic U87-MG gliomas.Results from MALDI-MSI showed that AKBA improved the metabolic profile of mice with glioblastoma,while immunoblot assays revealed that AKBA suppressed the expression of ATG5,p62,LC3 B,p-ERK/ERK,and P53,and increased the ratio of p-mTOR/mTOR.Taken together,these results suggested that the antitumor effects of AKBA were related to the normalization of aberrant metabolism in the glioblastoma and the inhibition of autophagy.AKBA could be a promising chemotherapy drug for glioblastoma.
