Luhong Granules Prevent Ventricular Remodelling after Myocardial Infarction by Reducing the Metabolites TMAO and LPS of the Intestinal Flora

Abstract

Background Ventricular remodelling is a common pathological change at all stages of heart disease. Luhong granules are widely used in patients with chronic ventricular remodelling after myocardial infarction and can alleviate chest tightness, shortness of breath, and other symptoms. However, its effect on ventricular remodelling remains to be studied. Purpose In this study, we investigated the effects of these granules on myocardial fibrosis in a rat model of myocardial infarction in vivo. Methods Male Wistar rats were randomly divided into four groups: the sham operation group, the acute myocardial infarction (AMI) group, the Luhong granule group, and the vancomycin group, with a sample size (n) of 10 rats in each group. The AMI model was established in all rats by ligation of the left anterior descending (LAD) coronary artery (the sham operation group did not undergo ligation). Luhong granules (0.5 ml·kg−1·d−1), vancomycin (0.075 g·ml−1·d−1), and 0.9% saline (5 ml·kg−1·d−1 for the sham operation and AMI groups) were administered orally for 6 weeks. Echocardiography was used to check cardiac structure and function. Myocardial and small intestinal tissue morphology was observed by haematoxylin and eosin (H&E) staining, and heart samples were stained with Masson's trichrome to analyse myocardial fibrosis. 16S rDNA sequencing was performed to detect changes in the gut flora. The level of trimethylamine N-oxide (TMAO) in plasma samples was quantified by stable isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS). Results H&E and Masson's trichrome staining of cardiac tissues showed that Luhong granules could partially reverse ventricular remodelling and improve intestinal barrier function (P < 0.05). Echocardiographic analysis showed that, compared with the AMI group, the left ventricular ejection fraction (LVEF) in the Luhong granule group was increased (P < 0.05). Stool sequencing and microbiological analysis showed changes in Bacteroidales, Alistipes, Phascolarctobacterium, etc., which can produce TMAO. We found that Luhong granules can reduce Bacteroidales, Alistipes, and Phascolarctobacterium at the genus level. The levels of TMAO and lipopolysaccharides (LPS) in plasma samples were reduced in the Luhong granule group (P < 0.05). Conclusions Our results indicate that Luhong granules reduce TMAO and LPS levels in circulating blood by improving intestinal flora and intestinal barrier function to delay ventricular remodelling after myocardial infarction.

Astragaloside IV Ameliorates Isoprenaline-Induced Cardiac Fibrosis in Mice via Modulating Gut Microbiota and Fecal Metabolites

“…In this study, Bacteroidetes abundance was increased in CF model group mice relative to the control group mice, but the abundance of Bacteroidetes was reduced after AS-IV treatment. This result agreed with the alterations of gut microbiota in the treatment of ventricular remodeling with Chinese herbal medicine ( Yang et al., 2019 ). Strikingly, we found that Akkermansia, Defluviitaleaceae_UCG-011, and Rikenella abundances were markedly increased in ISO-induced CF mice treated with AS-IV, which is consistent with the findings of a published study where drug-administered increased the genus Defluviitaleaceae_UCG-011 in hyperlipidemic rats ( Zhang et al., 2021 ), and in contrast to the outcomes of previous studies where drug-administered decreased the genus Rikenella in high-fat diet mice ( He W. S. et al, 2020 ; Liu J. et al, 2021 ).…”

Dietary bioactive ingredients to modulate the gut microbiota-derived metabolite TMAO. New opportunities for functional food development

“…Yang et al (2019) found that oral administration of Luhong granules, a complex mixture of various herb leaves, seeds, roots, flowers, and animal parts, for 6 weeks in acute myocardial infarction-induced Wistar rats could partially reverse ventricular remodeling and improve intestinal barrier function. 152 To note, the serum TMAO and lipopolysaccharides levels in the untreated acute myocardial infarction-induced rats was increased, but the levels of both bacteria-derived products were decreased in the Luhong granules-treated rats. Amplicon sequencing of fecal material of untreated acute myocardial infarction-induced rats showed changes in Desulfovibrionaceae, Escherichia, Akkermansia, Bacteroidales, Alistipes, and Phascolarctobacterium, in which there are potential TMAO producers.…”

LuQi Formula Regulates NLRP3 Inflammasome to Relieve Myocardial-Infarction-Induced Cardiac Remodeling in Mice

“…MI surgery was performed as described previously [ 15 ]. The mice were anesthetized and mechanically ventilated using a rodent ventilator.…”

“…Proteins were isolated from the frozen cardiac tissue, and their concentration was calculated using the bicinchoninic acid (BCA) method (Thermo Fisher Scientific, Waltham, MA, USA; A53225). Immunoblotting was performed as previously described [ 15 ]. In this study, the primary antibodies used recognized NLRP3(1 : 1000, CST, 15101S), Cle-caspase-1 (1 : 1000, Abcam, ab1789515), ASC (1 : 1000, CST, 67824), thioredoxin-interacting protein (TXNIP) (1 : 1000, CST, 14715), caspase-3 (1 : 1000, CST, 9662), BCL-2 apoptosis regulator (Bcl-2) (1 : 1000, CST, 3498), IL-1 β (1 : 1000, Abcam, ab234437), Bax(1 : 1000, Abcam, ab32503), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (1 : 20000, Proteintech, 60004-1-Ig).…”