Objective:Parkinson’s disease(PD)is the second largest neurodegenerative disease following Alzheimer’s disease(AD),which associated with aging.There are many similarities in pathology and pathogenesis,even in the TC...Objective:Parkinson’s disease(PD)is the second largest neurodegenerative disease following Alzheimer’s disease(AD),which associated with aging.There are many similarities in pathology and pathogenesis,even in the TCM theory understanding,so we can learn from each other in the process of drug discovery.The clinical results showed that Bushen-Yizhi formula(BSYZ)could effectively improve the neurological function score of senile dementia patients and had a better anti-dementia effect.Further pharmacological studies showed that BSYZ had neuroprotective effects,such as anti-inflammatory,anti-oxidation,anti-apoptosis and neurotrophic effects.In this study,the therapeutic effect of BSYZ on PD was evaluated in vivo and in vivo,and its molecular mechanism was discussed in order to expand the scope of application of BSYZ and to provide strategies for drug discovery of related neurodegenerative diseases.Methods:C57 BL/6 mice were injected intraperitoneally with MPTP to construct a PD mouse model.BSYZ(1.46,2.92,5.84 mg·kg-1)was administered for two weeks,and the positive control group was given a NSAID,piroxicam(12.5 mg·kg-1).After 1 week of pretreatment,MPTP was used to construct a PD mouse model.The mice were subjected to Rotation test on days 1,3 and 5,6th day.and the movement coordination and exercise ability of the drug on PD mice were observed on theThe number of TH-positive cells,Iba1 and CD68-labeled microglial cells in SNpc region were observed by immunofluorescence to observe the proliferation and activation of microglial cells and GFAP-labeled astrocytes.Western blotting was used to detect the nuclear transfer of NLRP3,Caspase-1,ASC,pro-IL-1β,IL-1βand NF-κB in the midbrain.Results:1.BSYZ could significantly improve the expression of MPTP model mice in the experiment of fatigue and Y-maze,increase the number of neurons in SNpc region and the positive expression of TH protein.2.BSYZ significantly inhibited the number of Iba1/CD68-positive microglial cells in MPTP-model mice and decreased the number of GFAP-positive astrocytes.3.BSYZ significantly inhibited the expression of NLRP3-associated protein in BV2 microglial cells induced by LPS+ATP and inhibited the nuclear transfer of NF-κB.Conclusion:BSYZ can effectively relieve the motor dysfunction of PD model mice,improve the damage of dopaminergic neurons,inhibit the proliferation and activation of microglial cells and astrocytes,and have good anti-MPTPinduced neuroinflammation and neuroinflammation mediated by nuclear transfer of NF-κB.The results show that BSYZ has a good prospect of anti-Parkinson’s disease and provides valuable drug discovery strategies for the related neurodegenerative diseases.展开更多
Western diet(rich in highly refined sugar and fat)can induce a range of metabolic dysfunctions in animals and humans,including neuroinflammation and cognitive function decline.Neuroinflammation and cognitive impairmen...Western diet(rich in highly refined sugar and fat)can induce a range of metabolic dysfunctions in animals and humans,including neuroinflammation and cognitive function decline.Neuroinflammation and cognitive impairment,two critical pathological characteristics of Alzheimer’s disease,have been closely associated with microbial alteration via the gut-brain axis.Thus,the present study aimed to investigate the influence of 2-O-β-D-glucopyranosyl-L-ascorbic acid(AA-2βG)isolated from the fruits of Lycium barbarum on preventing the high-fructose diet(HFrD)induced neuroinflammation in mice.It was found that AA-2βG prevented HFr D-induced cognitive deficits.AA-2βG also predominantly enhanced the gut barrier integrity,decreased lipopolysaccharide entry into the circulation,which subsequently countered the activation of glial cells and neuroinflammatory response.These beneficial effects were transmissible by horizontal fecal microbiome transplantation,transferring from AA-2βG fed mice to HFr D fed mice.Additionally,AA-2βG exerted neuroprotective effects involving the enrichment of Lactobacillus and Akkermansia,potentially beneficial intestinal bacteria.The present study provided the evidence that AA-2βG could improve indices of cognition and neuroinflammmation via modulating gut dybiosis and preventing leaky gut.As a potential functional food ingredient,AA-2βG may be applied to attenuate neuroinflammation associated with Western-style diets.展开更多
文摘Objective:Parkinson’s disease(PD)is the second largest neurodegenerative disease following Alzheimer’s disease(AD),which associated with aging.There are many similarities in pathology and pathogenesis,even in the TCM theory understanding,so we can learn from each other in the process of drug discovery.The clinical results showed that Bushen-Yizhi formula(BSYZ)could effectively improve the neurological function score of senile dementia patients and had a better anti-dementia effect.Further pharmacological studies showed that BSYZ had neuroprotective effects,such as anti-inflammatory,anti-oxidation,anti-apoptosis and neurotrophic effects.In this study,the therapeutic effect of BSYZ on PD was evaluated in vivo and in vivo,and its molecular mechanism was discussed in order to expand the scope of application of BSYZ and to provide strategies for drug discovery of related neurodegenerative diseases.Methods:C57 BL/6 mice were injected intraperitoneally with MPTP to construct a PD mouse model.BSYZ(1.46,2.92,5.84 mg·kg-1)was administered for two weeks,and the positive control group was given a NSAID,piroxicam(12.5 mg·kg-1).After 1 week of pretreatment,MPTP was used to construct a PD mouse model.The mice were subjected to Rotation test on days 1,3 and 5,6th day.and the movement coordination and exercise ability of the drug on PD mice were observed on theThe number of TH-positive cells,Iba1 and CD68-labeled microglial cells in SNpc region were observed by immunofluorescence to observe the proliferation and activation of microglial cells and GFAP-labeled astrocytes.Western blotting was used to detect the nuclear transfer of NLRP3,Caspase-1,ASC,pro-IL-1β,IL-1βand NF-κB in the midbrain.Results:1.BSYZ could significantly improve the expression of MPTP model mice in the experiment of fatigue and Y-maze,increase the number of neurons in SNpc region and the positive expression of TH protein.2.BSYZ significantly inhibited the number of Iba1/CD68-positive microglial cells in MPTP-model mice and decreased the number of GFAP-positive astrocytes.3.BSYZ significantly inhibited the expression of NLRP3-associated protein in BV2 microglial cells induced by LPS+ATP and inhibited the nuclear transfer of NF-κB.Conclusion:BSYZ can effectively relieve the motor dysfunction of PD model mice,improve the damage of dopaminergic neurons,inhibit the proliferation and activation of microglial cells and astrocytes,and have good anti-MPTPinduced neuroinflammation and neuroinflammation mediated by nuclear transfer of NF-κB.The results show that BSYZ has a good prospect of anti-Parkinson’s disease and provides valuable drug discovery strategies for the related neurodegenerative diseases.
基金the financial support from the Key Research and Development Program of Ningxia Hui Autonomous Region of China(2021BEF02008)the National Natural Science Foundation of China(32272330)the Priority Academic Program Development of Jiangsu Higher Education Institutions。
文摘Western diet(rich in highly refined sugar and fat)can induce a range of metabolic dysfunctions in animals and humans,including neuroinflammation and cognitive function decline.Neuroinflammation and cognitive impairment,two critical pathological characteristics of Alzheimer’s disease,have been closely associated with microbial alteration via the gut-brain axis.Thus,the present study aimed to investigate the influence of 2-O-β-D-glucopyranosyl-L-ascorbic acid(AA-2βG)isolated from the fruits of Lycium barbarum on preventing the high-fructose diet(HFrD)induced neuroinflammation in mice.It was found that AA-2βG prevented HFr D-induced cognitive deficits.AA-2βG also predominantly enhanced the gut barrier integrity,decreased lipopolysaccharide entry into the circulation,which subsequently countered the activation of glial cells and neuroinflammatory response.These beneficial effects were transmissible by horizontal fecal microbiome transplantation,transferring from AA-2βG fed mice to HFr D fed mice.Additionally,AA-2βG exerted neuroprotective effects involving the enrichment of Lactobacillus and Akkermansia,potentially beneficial intestinal bacteria.The present study provided the evidence that AA-2βG could improve indices of cognition and neuroinflammmation via modulating gut dybiosis and preventing leaky gut.As a potential functional food ingredient,AA-2βG may be applied to attenuate neuroinflammation associated with Western-style diets.
