Bazi Bushen capsule improves the deterioration of the intestinal barrier function by inhibiting NLRP3 inflammasome-mediated pyroptosis through microbiota-gut-brain axis

PurposeThe senescence-accelerated prone mouse 8 (SAMP8) is a widely used model for accelerating aging, especially in central aging. Mounting evidence indicates that the microbiota-gut-brain axis may be involved in the pathogenesis and progression of central aging-related diseases. This study aims to...

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Main Authors: Shixiong Zhang, Mengnan Li, Liping Chang, Xinjing Mao, Yuning Jiang, Xiaogang Shen, Kunxu Niu, Xuan Lu, Runtao Zhang, Yahui Song, Kun Ma, Hongrong Li, Cong Wei, Yunlong Hou, Yiling Wu
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-01-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2023.1320202/full
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author Shixiong Zhang
Shixiong Zhang
Mengnan Li
Mengnan Li
Liping Chang
Liping Chang
Xinjing Mao
Xinjing Mao
Yuning Jiang
Yuning Jiang
Xiaogang Shen
Xiaogang Shen
Kunxu Niu
Kunxu Niu
Xuan Lu
Xuan Lu
Runtao Zhang
Runtao Zhang
Yahui Song
Yahui Song
Kun Ma
Kun Ma
Hongrong Li
Hongrong Li
Cong Wei
Cong Wei
Yunlong Hou
Yiling Wu
Yiling Wu
author_facet Shixiong Zhang
Shixiong Zhang
Mengnan Li
Mengnan Li
Liping Chang
Liping Chang
Xinjing Mao
Xinjing Mao
Yuning Jiang
Yuning Jiang
Xiaogang Shen
Xiaogang Shen
Kunxu Niu
Kunxu Niu
Xuan Lu
Xuan Lu
Runtao Zhang
Runtao Zhang
Yahui Song
Yahui Song
Kun Ma
Kun Ma
Hongrong Li
Hongrong Li
Cong Wei
Cong Wei
Yunlong Hou
Yiling Wu
Yiling Wu
author_sort Shixiong Zhang
collection DOAJ
description PurposeThe senescence-accelerated prone mouse 8 (SAMP8) is a widely used model for accelerating aging, especially in central aging. Mounting evidence indicates that the microbiota-gut-brain axis may be involved in the pathogenesis and progression of central aging-related diseases. This study aims to investigate whether Bazi Bushen capsule (BZBS) attenuates the deterioration of the intestinal function in the central aging animal model.MethodsIn our study, the SAMP8 mice were randomly divided into the model group, the BZ-low group (0.5 g/kg/d BZBS), the BZ-high group (1 g/kg/d BZBS) and the RAPA group (2 mg/kg/d rapamycin). Age-matched SAMR1 mice were used as the control group. Next, cognitive function was detected through Nissl staining and two-photon microscopy. The gut microbiota composition of fecal samples was analyzed by 16S rRNA gene sequencing. The Ileum tissue morphology was observed by hematoxylin and eosin staining, and the intestinal barrier function was observed by immunofluorescence. The expression of senescence-associated secretory phenotype (SASP) factors, including P53, TNF-α, NF-κB, IL-4, IL-6, and IL-10 was measured by real-time quantitative PCR. Macrophage infiltration and the proliferation and differentiation of intestinal cells were assessed by immunohistochemistry. We also detected the inflammasome and pyroptosis levels in ileum tissue by western blotting.ResultsBZBS improved the cognitive function and neuronal density of SAMP8 mice. BZBS also restored the intestinal villus structure and barrier function, which were damaged in SAMP8 mice. BZBS reduced the expression of SASP factors and the infiltration of macrophages in the ileum tissues, indicating a lower level of inflammation. BZBS enhanced the proliferation and differentiation of intestinal cells, which are essential for maintaining intestinal homeostasis. BZBS modulated the gut microbiota composition, by which BZBS inhibited the activation of inflammasomes and pyroptosis in the intestine.ConclusionBZBS could restore the dysbiosis of the gut microbiota and prevent the deterioration of intestinal barrier function by inhibiting NLRP3 inflammasome-mediated pyroptosis. These results suggested that BZBS attenuated the cognitive aging of SAMP8 mice, at least partially, by targeting the microbiota-gut-brain axis.
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spelling doaj.art-c19da3949d63421f9ea35b9d7feff0682024-01-08T06:12:33ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2024-01-011410.3389/fmicb.2023.13202021320202Bazi Bushen capsule improves the deterioration of the intestinal barrier function by inhibiting NLRP3 inflammasome-mediated pyroptosis through microbiota-gut-brain axisShixiong Zhang0Shixiong Zhang1Mengnan Li2Mengnan Li3Liping Chang4Liping Chang5Xinjing Mao6Xinjing Mao7Yuning Jiang8Yuning Jiang9Xiaogang Shen10Xiaogang Shen11Kunxu Niu12Kunxu Niu13Xuan Lu14Xuan Lu15Runtao Zhang16Runtao Zhang17Yahui Song18Yahui Song19Kun Ma20Kun Ma21Hongrong Li22Hongrong Li23Cong Wei24Cong Wei25Yunlong Hou26Yiling Wu27Yiling Wu28College of Traditional Chinese Medicine, College of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, ChinaKey Laboratory of State Administration of TCM (Cardio-Cerebral Vessel Collateral Disease), Shijiazhuang, ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, ChinaKey Laboratory of State Administration of TCM (Cardio-Cerebral Vessel Collateral Disease), Shijiazhuang, ChinaCollege of Traditional Chinese Medicine, College of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, ChinaCollege of Traditional Chinese Medicine, College of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, ChinaKey Laboratory of State Administration of TCM (Cardio-Cerebral Vessel Collateral Disease), Shijiazhuang, ChinaHigh-level TCM Key Disciplines of National Administration of Traditional Chinese Medicine—Luobing Theory, Shijiazhuang, ChinaKey Laboratory of State Administration of TCM (Cardio-Cerebral Vessel Collateral Disease), Shijiazhuang, ChinaHigh-level TCM Key Disciplines of National Administration of Traditional Chinese Medicine—Luobing Theory, Shijiazhuang, ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, ChinaHigh-level TCM Key Disciplines of National Administration of Traditional Chinese Medicine—Luobing Theory, Shijiazhuang, ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, ChinaHigh-level TCM Key Disciplines of National Administration of Traditional Chinese Medicine—Luobing Theory, Shijiazhuang, ChinaKey Laboratory of State Administration of TCM (Cardio-Cerebral Vessel Collateral Disease), Shijiazhuang, ChinaHigh-level TCM Key Disciplines of National Administration of Traditional Chinese Medicine—Luobing Theory, Shijiazhuang, ChinaKey Laboratory of State Administration of TCM (Cardio-Cerebral Vessel Collateral Disease), Shijiazhuang, ChinaHigh-level TCM Key Disciplines of National Administration of Traditional Chinese Medicine—Luobing Theory, Shijiazhuang, ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, ChinaKey Laboratory of State Administration of TCM (Cardio-Cerebral Vessel Collateral Disease), Shijiazhuang, ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, ChinaKey Laboratory of State Administration of TCM (Cardio-Cerebral Vessel Collateral Disease), Shijiazhuang, ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, ChinaCollege of Traditional Chinese Medicine, College of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaNational Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, ChinaPurposeThe senescence-accelerated prone mouse 8 (SAMP8) is a widely used model for accelerating aging, especially in central aging. Mounting evidence indicates that the microbiota-gut-brain axis may be involved in the pathogenesis and progression of central aging-related diseases. This study aims to investigate whether Bazi Bushen capsule (BZBS) attenuates the deterioration of the intestinal function in the central aging animal model.MethodsIn our study, the SAMP8 mice were randomly divided into the model group, the BZ-low group (0.5 g/kg/d BZBS), the BZ-high group (1 g/kg/d BZBS) and the RAPA group (2 mg/kg/d rapamycin). Age-matched SAMR1 mice were used as the control group. Next, cognitive function was detected through Nissl staining and two-photon microscopy. The gut microbiota composition of fecal samples was analyzed by 16S rRNA gene sequencing. The Ileum tissue morphology was observed by hematoxylin and eosin staining, and the intestinal barrier function was observed by immunofluorescence. The expression of senescence-associated secretory phenotype (SASP) factors, including P53, TNF-α, NF-κB, IL-4, IL-6, and IL-10 was measured by real-time quantitative PCR. Macrophage infiltration and the proliferation and differentiation of intestinal cells were assessed by immunohistochemistry. We also detected the inflammasome and pyroptosis levels in ileum tissue by western blotting.ResultsBZBS improved the cognitive function and neuronal density of SAMP8 mice. BZBS also restored the intestinal villus structure and barrier function, which were damaged in SAMP8 mice. BZBS reduced the expression of SASP factors and the infiltration of macrophages in the ileum tissues, indicating a lower level of inflammation. BZBS enhanced the proliferation and differentiation of intestinal cells, which are essential for maintaining intestinal homeostasis. BZBS modulated the gut microbiota composition, by which BZBS inhibited the activation of inflammasomes and pyroptosis in the intestine.ConclusionBZBS could restore the dysbiosis of the gut microbiota and prevent the deterioration of intestinal barrier function by inhibiting NLRP3 inflammasome-mediated pyroptosis. These results suggested that BZBS attenuated the cognitive aging of SAMP8 mice, at least partially, by targeting the microbiota-gut-brain axis.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1320202/fullintestinal barrier functionmicrobiota-gut-brain axisinflammasomepyroptosisSAMP8
spellingShingle Shixiong Zhang
Shixiong Zhang
Mengnan Li
Mengnan Li
Liping Chang
Liping Chang
Xinjing Mao
Xinjing Mao
Yuning Jiang
Yuning Jiang
Xiaogang Shen
Xiaogang Shen
Kunxu Niu
Kunxu Niu
Xuan Lu
Xuan Lu
Runtao Zhang
Runtao Zhang
Yahui Song
Yahui Song
Kun Ma
Kun Ma
Hongrong Li
Hongrong Li
Cong Wei
Cong Wei
Yunlong Hou
Yiling Wu
Yiling Wu
Bazi Bushen capsule improves the deterioration of the intestinal barrier function by inhibiting NLRP3 inflammasome-mediated pyroptosis through microbiota-gut-brain axis
Frontiers in Microbiology
intestinal barrier function
microbiota-gut-brain axis
inflammasome
pyroptosis
SAMP8
title Bazi Bushen capsule improves the deterioration of the intestinal barrier function by inhibiting NLRP3 inflammasome-mediated pyroptosis through microbiota-gut-brain axis
title_full Bazi Bushen capsule improves the deterioration of the intestinal barrier function by inhibiting NLRP3 inflammasome-mediated pyroptosis through microbiota-gut-brain axis
title_fullStr Bazi Bushen capsule improves the deterioration of the intestinal barrier function by inhibiting NLRP3 inflammasome-mediated pyroptosis through microbiota-gut-brain axis
title_full_unstemmed Bazi Bushen capsule improves the deterioration of the intestinal barrier function by inhibiting NLRP3 inflammasome-mediated pyroptosis through microbiota-gut-brain axis
title_short Bazi Bushen capsule improves the deterioration of the intestinal barrier function by inhibiting NLRP3 inflammasome-mediated pyroptosis through microbiota-gut-brain axis
title_sort bazi bushen capsule improves the deterioration of the intestinal barrier function by inhibiting nlrp3 inflammasome mediated pyroptosis through microbiota gut brain axis
topic intestinal barrier function
microbiota-gut-brain axis
inflammasome
pyroptosis
SAMP8
url https://www.frontiersin.org/articles/10.3389/fmicb.2023.1320202/full
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