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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Frontiers Media S.A.
2024-01-01
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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. |
first_indexed | 2024-03-08T16:05:49Z |
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institution | Directory Open Access Journal |
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last_indexed | 2024-03-08T16:05:49Z |
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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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