Buyang Huanwu Decoction improves energy metabolism disorders after cerebral ischemia–reperfusion by regulating the SIRT1/AMPK signaling pathway to promote glycolysis and the tricarboxylic acid cycle
Abstract Background Buyang Huanwu Decoction (BYHWD), a traditional Chinese medicine formula for cerebral infarction, exerts neuroprotective effects by enhancing cerebral energy metabolism, yet its precise mechanisms remain elusive. Objective To explore the effects of BYHWD on improving cerebral isch...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
|
| Series: | Chinese Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13020-025-01163-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849388770159230976 |
|---|---|
| author | Zhongji Hu Nujiao Deng Yanling Li Yang Bai Xiao Lan Tingting Xiong Huang Ding Xiaodan Liu Changqing Deng |
| author_facet | Zhongji Hu Nujiao Deng Yanling Li Yang Bai Xiao Lan Tingting Xiong Huang Ding Xiaodan Liu Changqing Deng |
| author_sort | Zhongji Hu |
| collection | DOAJ |
| description | Abstract Background Buyang Huanwu Decoction (BYHWD), a traditional Chinese medicine formula for cerebral infarction, exerts neuroprotective effects by enhancing cerebral energy metabolism, yet its precise mechanisms remain elusive. Objective To explore the effects of BYHWD on improving cerebral ischemia–reperfusion injury (CIRI) with Qi deficiency and blood stasis syndrome from an energy metabolism perspective and verify it through experiments. Methods A rat model of CIRI with Qi deficiency and blood stasis syndrome was established and intervened with BYHWD. The therapeutic effect of BYHWD was evaluated using Longa score, Qi deficiency and blood stasis syndrome score, pathological staining, and colorimetric assays. Untargeted metabolomics was used to identify differential metabolites and regulatory mechanisms, and in vivo and in vitro models were constructed for validation. Results BYHWD ameliorated neurological deficits and Qi deficiency and blood stasis syndrome in rats, reduced brain pathology, and increased energy substances. Untargeted metabolomics analysis suggested BYHWD enhanced cerebral energy metabolism via nicotinate and nicotinamide metabolism and AMPK signaling, involving SIRT1/AMPK regulation and promotion of glycolysis and the tricarboxylic acid (TCA) cycle. Validation experiments showed BYHWD activated the SIRT1/AMPK signaling pathway in brain tissue, promoting glucose uptake and enhancing the expression of proteins related to glycolysis, mitochondrial biogenesis, and the TCA cycle. Similar results were observed in HT22 cells subjected to oxygen–glucose deprivation/reperfusion (OGD/R). Conclusion BYHWD improved cerebral energy metabolic disorders by activating the SIRT1/AMPK signaling pathway, thereby enhancing glycolytic capacity and TCA cycle capacity. This study elucidated the mechanisms of BYHWD and provided a theoretical basis for its rational application. |
| format | Article |
| id | doaj-art-0639df4265244122826545ecb741cc97 |
| institution | Kabale University |
| issn | 1749-8546 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Medicine |
| spelling | doaj-art-0639df4265244122826545ecb741cc972025-08-20T03:42:10ZengBMCChinese Medicine1749-85462025-07-0120112210.1186/s13020-025-01163-5Buyang Huanwu Decoction improves energy metabolism disorders after cerebral ischemia–reperfusion by regulating the SIRT1/AMPK signaling pathway to promote glycolysis and the tricarboxylic acid cycleZhongji Hu0Nujiao Deng1Yanling Li2Yang Bai3Xiao Lan4Tingting Xiong5Huang Ding6Xiaodan Liu7Changqing Deng8Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese MedicineThe First Hospital of Hunan University of Chinese MedicineKey Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese MedicineKey Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese MedicineKey Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese MedicineKey Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese MedicineKey Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese MedicineKey Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese MedicineKey Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese MedicineAbstract Background Buyang Huanwu Decoction (BYHWD), a traditional Chinese medicine formula for cerebral infarction, exerts neuroprotective effects by enhancing cerebral energy metabolism, yet its precise mechanisms remain elusive. Objective To explore the effects of BYHWD on improving cerebral ischemia–reperfusion injury (CIRI) with Qi deficiency and blood stasis syndrome from an energy metabolism perspective and verify it through experiments. Methods A rat model of CIRI with Qi deficiency and blood stasis syndrome was established and intervened with BYHWD. The therapeutic effect of BYHWD was evaluated using Longa score, Qi deficiency and blood stasis syndrome score, pathological staining, and colorimetric assays. Untargeted metabolomics was used to identify differential metabolites and regulatory mechanisms, and in vivo and in vitro models were constructed for validation. Results BYHWD ameliorated neurological deficits and Qi deficiency and blood stasis syndrome in rats, reduced brain pathology, and increased energy substances. Untargeted metabolomics analysis suggested BYHWD enhanced cerebral energy metabolism via nicotinate and nicotinamide metabolism and AMPK signaling, involving SIRT1/AMPK regulation and promotion of glycolysis and the tricarboxylic acid (TCA) cycle. Validation experiments showed BYHWD activated the SIRT1/AMPK signaling pathway in brain tissue, promoting glucose uptake and enhancing the expression of proteins related to glycolysis, mitochondrial biogenesis, and the TCA cycle. Similar results were observed in HT22 cells subjected to oxygen–glucose deprivation/reperfusion (OGD/R). Conclusion BYHWD improved cerebral energy metabolic disorders by activating the SIRT1/AMPK signaling pathway, thereby enhancing glycolytic capacity and TCA cycle capacity. This study elucidated the mechanisms of BYHWD and provided a theoretical basis for its rational application.https://doi.org/10.1186/s13020-025-01163-5Qi deficiency and blood stasis syndromeCerebral ischemia reperfusion injuryBuyang Huanwu DecoctionEnergy metabolismMetabolomicsGlycolysis |
| spellingShingle | Zhongji Hu Nujiao Deng Yanling Li Yang Bai Xiao Lan Tingting Xiong Huang Ding Xiaodan Liu Changqing Deng Buyang Huanwu Decoction improves energy metabolism disorders after cerebral ischemia–reperfusion by regulating the SIRT1/AMPK signaling pathway to promote glycolysis and the tricarboxylic acid cycle Chinese Medicine Qi deficiency and blood stasis syndrome Cerebral ischemia reperfusion injury Buyang Huanwu Decoction Energy metabolism Metabolomics Glycolysis |
| title | Buyang Huanwu Decoction improves energy metabolism disorders after cerebral ischemia–reperfusion by regulating the SIRT1/AMPK signaling pathway to promote glycolysis and the tricarboxylic acid cycle |
| title_full | Buyang Huanwu Decoction improves energy metabolism disorders after cerebral ischemia–reperfusion by regulating the SIRT1/AMPK signaling pathway to promote glycolysis and the tricarboxylic acid cycle |
| title_fullStr | Buyang Huanwu Decoction improves energy metabolism disorders after cerebral ischemia–reperfusion by regulating the SIRT1/AMPK signaling pathway to promote glycolysis and the tricarboxylic acid cycle |
| title_full_unstemmed | Buyang Huanwu Decoction improves energy metabolism disorders after cerebral ischemia–reperfusion by regulating the SIRT1/AMPK signaling pathway to promote glycolysis and the tricarboxylic acid cycle |
| title_short | Buyang Huanwu Decoction improves energy metabolism disorders after cerebral ischemia–reperfusion by regulating the SIRT1/AMPK signaling pathway to promote glycolysis and the tricarboxylic acid cycle |
| title_sort | buyang huanwu decoction improves energy metabolism disorders after cerebral ischemia reperfusion by regulating the sirt1 ampk signaling pathway to promote glycolysis and the tricarboxylic acid cycle |
| topic | Qi deficiency and blood stasis syndrome Cerebral ischemia reperfusion injury Buyang Huanwu Decoction Energy metabolism Metabolomics Glycolysis |
| url | https://doi.org/10.1186/s13020-025-01163-5 |
| work_keys_str_mv | AT zhongjihu buyanghuanwudecoctionimprovesenergymetabolismdisordersaftercerebralischemiareperfusionbyregulatingthesirt1ampksignalingpathwaytopromoteglycolysisandthetricarboxylicacidcycle AT nujiaodeng buyanghuanwudecoctionimprovesenergymetabolismdisordersaftercerebralischemiareperfusionbyregulatingthesirt1ampksignalingpathwaytopromoteglycolysisandthetricarboxylicacidcycle AT yanlingli buyanghuanwudecoctionimprovesenergymetabolismdisordersaftercerebralischemiareperfusionbyregulatingthesirt1ampksignalingpathwaytopromoteglycolysisandthetricarboxylicacidcycle AT yangbai buyanghuanwudecoctionimprovesenergymetabolismdisordersaftercerebralischemiareperfusionbyregulatingthesirt1ampksignalingpathwaytopromoteglycolysisandthetricarboxylicacidcycle AT xiaolan buyanghuanwudecoctionimprovesenergymetabolismdisordersaftercerebralischemiareperfusionbyregulatingthesirt1ampksignalingpathwaytopromoteglycolysisandthetricarboxylicacidcycle AT tingtingxiong buyanghuanwudecoctionimprovesenergymetabolismdisordersaftercerebralischemiareperfusionbyregulatingthesirt1ampksignalingpathwaytopromoteglycolysisandthetricarboxylicacidcycle AT huangding buyanghuanwudecoctionimprovesenergymetabolismdisordersaftercerebralischemiareperfusionbyregulatingthesirt1ampksignalingpathwaytopromoteglycolysisandthetricarboxylicacidcycle AT xiaodanliu buyanghuanwudecoctionimprovesenergymetabolismdisordersaftercerebralischemiareperfusionbyregulatingthesirt1ampksignalingpathwaytopromoteglycolysisandthetricarboxylicacidcycle AT changqingdeng buyanghuanwudecoctionimprovesenergymetabolismdisordersaftercerebralischemiareperfusionbyregulatingthesirt1ampksignalingpathwaytopromoteglycolysisandthetricarboxylicacidcycle |