Soyasaponin I alleviates hypertensive intracerebral hemorrhage by inhibiting the renin-angiotensin-aldosterone system.

BACKGROUND: Hypertensive intracerebral hemorrhage (HICH) is a life-threatening disease and lacks effective treatments. Previous studies have confirmed that metabolic profiles altered after ischemic stroke, but how brain metabolism changes after HICH was unclear. This study aimed to explore the metabolic profiles after HICH and the therapeutic effects of soyasaponin I on HICH. METHODS: HICH model was established first. Hematoxylin and eosin staining was used to estimate the pathological changes after HICH. Western blot and Evans blue extravasation assay were applied to determine the integrity of the blood-brain barrier (BBB). Enzyme-linked immunosorbent assay was used to detect the activation of the renin-angiotensin-aldosterone system (RAAS). Next, liquid chromatography-mass spectrometry-untargeted metabolomics was utilized to analyze the metabolic profiles of brain tissues after HICH. Finally, soyasaponin I was administered to HICH rats, and the severity of HICH and activation of the RAAS were further assessed. RESULTS: We successfully constructed HICH model. HICH significantly impaired BBB integrity and activated RAAS. HICH increased PE(14:0/24:1(15Z)), arachidonoyl serinol, PS(18:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, and 19Z)), PS(20:1(11Z)/20:5(5Z, 8Z, 11Z, 14Z, and 17Z)), glucose 1-phosphate, etc., in the brain, whereas decreased creatine, tripamide, D-N-(carboxyacetyl)alanine, N-acetylaspartate, N-acetylaspartylglutamic acid, and so on in the hemorrhagic hemisphere. Cerebral soyasaponin I was found to be downregulated after HICH and supplementation of soyasaponin I inactivated the RAAS and alleviated HICH. CONCLUSION: The metabolic profiles of the brains changed after HICH. Soyasaponin I alleviated HICH via inhibiting the RAAS and may serve as an effective drug for the treatment of HICH in the future.

A pilot study: Gut microbiota, metabolism and inflammation in hypertensive intracerebral haemorrhage.

AIMS: In recent years, the incidence rate of hypertensive intracerebral haemorrhage (HICH) has been increasing, accompanied by high mortality and morbidity, which has brought a heavy burden to the social economy. However, the pathogenesis of HICH is still unclear. This study intends to explore the mechanism of gut microbiota metabolism and inflammation in the process of HICH to provide a theoretical basis for the diagnosis and treatment of HICH. METHODS AND RESULTS: HE staining showed that the brain tissues of model group had obvious oedema injury, which indicated that the HICH model was successfully constructed. ELISA analysis showed that IL-1ß and TNF-α levels in blood and brain tissues were significantly increased, and IL-10 level was significantly decreased in blood. IHC analysis showed that microglia and macrophages were activated in the model group. 16S rRNA sequence showed that the diversity of gut microbiota in HICH patients decreased. Also, the microbiota belonging to Firmicutes, Proteobacteria and Verrucomicrobia changed significantly. LC-MS/MS analysis showed that the metabolic phenotype of HICH patients changed. Also, the 3,7-dimethyluric acid- and 7-methylxanthine-related metabolic pathways of caffeine metabolism pathways were downregulated in patients with HICH. Bacteroides was negatively correlated with the IL-1ß and TNF-α levels. Blautia was negatively correlated with the IL-1ß and TNF-α levels, and positively correlated with the IL-10 level. Akkermansia was negatively correlated with the 3,7-dimethyluric acid and 7-methylxanthine. CONCLUSION: Our study suggested that HICH was accompanied by the increased inflammation marker levels in peripheral blood and brain, decreased gut microbiota diversity, altered gut metabolic phenotype and downregulation of caffeine metabolism pathway. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study reported that HICH accompanied by the increased inflammation, decreased gut microbiota diversity and altered gut metabolic phenotype. Due to the number of patients, this work was a pilot study.