Danggui Shaoyao San: comprehensive modulation of the microbiota-gut-brain axis for attenuating Alzheimer’s disease-related pathology
Background: Alzheimer’s disease (AD), an age-associated neurodegenerative disorder, currently lacks effective clinical therapeutics. Traditional Chinese Medicine (TCM) holds promising potential in AD treatment, exemplified by Danggui Shaoyao San (DSS), a TCM formulation. The precise therapeutic mech...
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1338804/full |
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| author | Jiawei He Jiawei He Yijie Jin Yijie Jin Chunxiang He Chunxiang He Ze Li Ze Li Wenjing Yu Wenjing Yu Jinyong Zhou Jinyong Zhou Rongsiqing Luo Rongsiqing Luo Qi Chen Qi Chen Yixiao Wu Yixiao Wu Shiwei Wang Shiwei Wang Zhenyan Song Zhenyan Song Shaowu Cheng Shaowu Cheng Shaowu Cheng |
| author_facet | Jiawei He Jiawei He Yijie Jin Yijie Jin Chunxiang He Chunxiang He Ze Li Ze Li Wenjing Yu Wenjing Yu Jinyong Zhou Jinyong Zhou Rongsiqing Luo Rongsiqing Luo Qi Chen Qi Chen Yixiao Wu Yixiao Wu Shiwei Wang Shiwei Wang Zhenyan Song Zhenyan Song Shaowu Cheng Shaowu Cheng Shaowu Cheng |
| author_sort | Jiawei He |
| collection | DOAJ |
| description | Background: Alzheimer’s disease (AD), an age-associated neurodegenerative disorder, currently lacks effective clinical therapeutics. Traditional Chinese Medicine (TCM) holds promising potential in AD treatment, exemplified by Danggui Shaoyao San (DSS), a TCM formulation. The precise therapeutic mechanisms of DSS in AD remain to be fully elucidated. This study aims to uncover the therapeutic efficacy and underlying mechanisms of DSS in AD, employing an integrative approach encompassing gut microbiota and metabolomic analyses.Methods: Thirty Sprague-Dawley (SD) rats were allocated into three groups: Blank Control (Con), AD Model (M), and Danggui Shaoyao San (DSS). AD models were established via bilateral intracerebroventricular injections of streptozotocin (STZ). DSS was orally administered at 24 g·kg−1·d−1 (weight of raw herbal materials) for 14 days. Cognitive functions were evaluated using the Morris Water Maze (MWM) test. Pathological alterations were assessed through hematoxylin and eosin (HE) staining. Bloodstream metabolites were characterized, gut microbiota profiled through 16S rDNA sequencing, and cortical metabolomics analyzed. Hippocampal proinflammatory cytokines (IL-1β, IL-6, TNF-α) were quantified using RT-qPCR, and oxidative stress markers (SOD, CAT, GSH-PX, MDA) in brain tissues were measured with biochemical assays.Results: DSS identified a total of 1,625 bloodstream metabolites, predominantly Benzene derivatives, Carboxylic acids, and Fatty Acyls. DSS significantly improved learning and spatial memory in AD rats and ameliorated cerebral tissue pathology. The formulation enriched the probiotic Ligilactobacillus, modulating metabolites like Ophthalmic acid (OA), Phosphocreatine (PCr), Azacridone A, Inosine, and NAD. DSS regulated Purine and Nicotinate-nicotinamide metabolism, restoring balance in the Candidatus Saccharibacteria-OA interplay and stabilizing gut microbiota-metabolite homeostasis. Additionally, DSS reduced hippocampal IL-1β, IL-6, TNF-α expression, attenuating the inflammatory state. It elevated antioxidative enzymes (SOD, CAT, GSH-PX) while reducing MDA levels, indicating diminished oxidative stress in AD rat brains.Conclusion: DSS addresses AD pathology through multifaceted mechanisms, encompassing gut microbiome regulation, specific metabolite modulation, and the mitigation of inflammation and oxidative stress within the brain. This holistic intervention through the Microbial-Gut-Brain Axis (MGBA) underscores DSS’s potential as an integrative therapeutic agent in combatting AD. |
| first_indexed | 2024-03-08T14:37:31Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-08T14:37:31Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-aa20228bfbfd4a038cd067ad38e49c3b2024-01-12T04:31:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-01-011410.3389/fphar.2023.13388041338804Danggui Shaoyao San: comprehensive modulation of the microbiota-gut-brain axis for attenuating Alzheimer’s disease-related pathologyJiawei He0Jiawei He1Yijie Jin2Yijie Jin3Chunxiang He4Chunxiang He5Ze Li6Ze Li7Wenjing Yu8Wenjing Yu9Jinyong Zhou10Jinyong Zhou11Rongsiqing Luo12Rongsiqing Luo13Qi Chen14Qi Chen15Yixiao Wu16Yixiao Wu17Shiwei Wang18Shiwei Wang19Zhenyan Song20Zhenyan Song21Shaowu Cheng22Shaowu Cheng23Shaowu Cheng24School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaLaboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaLaboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaLaboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaLaboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaLaboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaLaboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaLaboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaLaboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaLaboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaLaboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaLaboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaLaboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaOffice of Science and Technology, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaBackground: Alzheimer’s disease (AD), an age-associated neurodegenerative disorder, currently lacks effective clinical therapeutics. Traditional Chinese Medicine (TCM) holds promising potential in AD treatment, exemplified by Danggui Shaoyao San (DSS), a TCM formulation. The precise therapeutic mechanisms of DSS in AD remain to be fully elucidated. This study aims to uncover the therapeutic efficacy and underlying mechanisms of DSS in AD, employing an integrative approach encompassing gut microbiota and metabolomic analyses.Methods: Thirty Sprague-Dawley (SD) rats were allocated into three groups: Blank Control (Con), AD Model (M), and Danggui Shaoyao San (DSS). AD models were established via bilateral intracerebroventricular injections of streptozotocin (STZ). DSS was orally administered at 24 g·kg−1·d−1 (weight of raw herbal materials) for 14 days. Cognitive functions were evaluated using the Morris Water Maze (MWM) test. Pathological alterations were assessed through hematoxylin and eosin (HE) staining. Bloodstream metabolites were characterized, gut microbiota profiled through 16S rDNA sequencing, and cortical metabolomics analyzed. Hippocampal proinflammatory cytokines (IL-1β, IL-6, TNF-α) were quantified using RT-qPCR, and oxidative stress markers (SOD, CAT, GSH-PX, MDA) in brain tissues were measured with biochemical assays.Results: DSS identified a total of 1,625 bloodstream metabolites, predominantly Benzene derivatives, Carboxylic acids, and Fatty Acyls. DSS significantly improved learning and spatial memory in AD rats and ameliorated cerebral tissue pathology. The formulation enriched the probiotic Ligilactobacillus, modulating metabolites like Ophthalmic acid (OA), Phosphocreatine (PCr), Azacridone A, Inosine, and NAD. DSS regulated Purine and Nicotinate-nicotinamide metabolism, restoring balance in the Candidatus Saccharibacteria-OA interplay and stabilizing gut microbiota-metabolite homeostasis. Additionally, DSS reduced hippocampal IL-1β, IL-6, TNF-α expression, attenuating the inflammatory state. It elevated antioxidative enzymes (SOD, CAT, GSH-PX) while reducing MDA levels, indicating diminished oxidative stress in AD rat brains.Conclusion: DSS addresses AD pathology through multifaceted mechanisms, encompassing gut microbiome regulation, specific metabolite modulation, and the mitigation of inflammation and oxidative stress within the brain. This holistic intervention through the Microbial-Gut-Brain Axis (MGBA) underscores DSS’s potential as an integrative therapeutic agent in combatting AD.https://www.frontiersin.org/articles/10.3389/fphar.2023.1338804/fullDanggui Shaoyao SanAlzheimer’s disease16S rDNAmetabonomicsnicotinate and nicotinamide metabolismmicrobial-gut-brain axis |
| spellingShingle | Jiawei He Jiawei He Yijie Jin Yijie Jin Chunxiang He Chunxiang He Ze Li Ze Li Wenjing Yu Wenjing Yu Jinyong Zhou Jinyong Zhou Rongsiqing Luo Rongsiqing Luo Qi Chen Qi Chen Yixiao Wu Yixiao Wu Shiwei Wang Shiwei Wang Zhenyan Song Zhenyan Song Shaowu Cheng Shaowu Cheng Shaowu Cheng Danggui Shaoyao San: comprehensive modulation of the microbiota-gut-brain axis for attenuating Alzheimer’s disease-related pathology Frontiers in Pharmacology Danggui Shaoyao San Alzheimer’s disease 16S rDNA metabonomics nicotinate and nicotinamide metabolism microbial-gut-brain axis |
| title | Danggui Shaoyao San: comprehensive modulation of the microbiota-gut-brain axis for attenuating Alzheimer’s disease-related pathology |
| title_full | Danggui Shaoyao San: comprehensive modulation of the microbiota-gut-brain axis for attenuating Alzheimer’s disease-related pathology |
| title_fullStr | Danggui Shaoyao San: comprehensive modulation of the microbiota-gut-brain axis for attenuating Alzheimer’s disease-related pathology |
| title_full_unstemmed | Danggui Shaoyao San: comprehensive modulation of the microbiota-gut-brain axis for attenuating Alzheimer’s disease-related pathology |
| title_short | Danggui Shaoyao San: comprehensive modulation of the microbiota-gut-brain axis for attenuating Alzheimer’s disease-related pathology |
| title_sort | danggui shaoyao san comprehensive modulation of the microbiota gut brain axis for attenuating alzheimer s disease related pathology |
| topic | Danggui Shaoyao San Alzheimer’s disease 16S rDNA metabonomics nicotinate and nicotinamide metabolism microbial-gut-brain axis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1338804/full |
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