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Formononetin alleviates no reflow after myocardial ischemia-reperfusion via modulation of gut microbiota to inhibit inflammation

Yanyan ZhangKey Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, China; National Key Laboratory Cultivation Base of Chinese Medicinal Powder & Innovative Medicinal Jointly Established by Province and Ministry, Changsha 410208, ChinaJiaxin DengKey Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, ChinaTing ChenKey Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, China; National Key Laboratory Cultivation Base of Chinese Medicinal Powder & Innovative Medicinal Jointly Established by Province and Ministry, Changsha 410208, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China. Electronic address: [email protected]Ting ChenKey Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, China; National Key Laboratory Cultivation Base of Chinese Medicinal Powder & Innovative Medicinal Jointly Established by Province and Ministry, Changsha 410208, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China. Electronic address: [email protected]Siqi LiuKey Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, ChinaTang YanKey Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, ChinaJi Rui ZhaoThe First Hospital of Hunan University of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, ChinaZhen GuoHunan Provincial Key Laboratory of the Fundamental and Clinical Research on Functional Nucleic Acid, Changsha Medical University, Changsha 410219, China; Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha 410219, China; Hunan Provincial Key Laboratory of the TCM Agricultural Biogenomics, Changsha Medical University, Changsha 410219, ChinaWei ZhangKey Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, China. Electronic address: [email protected]Ting ChenKey Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, China; National Key Laboratory Cultivation Base of Chinese Medicinal Powder & Innovative Medicinal Jointly Established by Province and Ministry, Changsha 410208, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China. Electronic address: [email protected]
2024en
ABI

Аннотация

Gut microflora plays an important role in relieving myocardial no-reflow (NR), formononetin (FMN) has potential effects on NR, however, the relationship between this effect and gut microflora remains unclear. This study aimed to evaluate the role of FMN in alleviating NR by regulating gut microflora. We used a myocardial NR rat model to confirm the effect and mechanism of action of FMN in alleviating NR. The rats were randomly divided into sham operation group (Sham), NR group, FMN group and sodium nitroprusside (SNP) group. Thioflavin S staining, Hematoxylin Eosin (HE), myocardial enzyme activity, ultrasonic cardiogram and RT-PCR detection showed that FMN could effectively reduce inflammatory cell infiltration, NR and ischemic area, improve cardiac structure and function and reduce TNF-α and NF-κB gene expression in NR rats. The results of 16S rRNA high-throughput sequencing showed that FMN could increase the abundance of anti-inflammatory bacteria such as Ligilactobacillus, Coprococcus, Blautia and Muribaculaceae and decrease the abundance of pro-inflammatory bacteria such as Treponema in Spirochaetota and Campylobacterota. The correlation between the differential bacteria in the gut microflora(anti-inflammatory bacteria and pro-inflammatory bacteria) and TNF-α and NF-κB, showed that they had a strong correlation. Therefore, the anti-NR mechanism of FMN may be related to increasing the abundance of anti-inflammatory bacteria and reducing the abundance of pro-inflammatory bacteria to inhibit inflammation. This study provides innovative mechanistic insights into the relationship between gut microbiota and myocardial protection, suggesting potential strategy for future treatment of NR.

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