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Water-soluble alkaloids extracted from Aconiti Radix lateralis praeparata protect against chronic heart failure in rats via a calcium signaling pathway
- Source :
- Biomedicine & Pharmacotherapy, Vol 135, Iss, Pp 111184-(2021)
- Publication Year :
- 2021
- Publisher :
- Elsevier, 2021.
-
Abstract
- Ethnopharmacological relevance Many studies have shown the beneficial effects of aconite water-soluble alkaloid extract (AWA) in experimental models of heart disease, which have been ascribed to the presence of aconine, hypaconine, talatisamine, fuziline, neoline, and songorine. This study evaluated the effects of a chemically characterized AWA by chemical content, evaluated its effects in suprarenal abdominal aortic coarctation surgery (AAC)-induced chronic heart failure (CHF) in rats, and revealed the underlying mechanisms of action by proteomics. Methods Rats were distributed into different groups: sham, model, and AWA-treated groups (10, 20, and 40 mg/kg/day). Sham rats received surgery without AAC, whereas model rats an AWA-treated groups underwent AAC surgery. after 8 weeks, the treatment group was fed AWA for 4 weeks, and body weight was assessed weekly. At the end of the treatment, heart function was tested by echocardiography. AAC-induced chronic heart failure, including myocardial fibrosis, cardiomyocyte hypertrophy, and apoptosis, was evaluated in heart tissue and plasma by RT-qPCR, ELISA, hematoxylin and eosin (H&E) staining, Masson's trichrome staining, TUNEL staining, and immunofluorescence staining of α-SMA, Col Ⅰ, and Col Ⅲ. Then, a proteomics approach was used to explore the underlying mechanisms of action of AWA in chronic heart failure. Results AWA administration reduced body weight gain, myocardial fibrosis, cardiomyocyte hypertrophy, and apoptosis, and rats showed improvement in cardiac function compared to model group. The extract significantly ameliorated the AAC-induced altered expression of heart failure markers such as ANP, NT-proBNP, and β-MHC, as well as fibrosis, hypertrophy markers MMP-2 and MMP-9, and other heart failure-related factors including plasma levels of TNF-α and IL-6. Furthermore, the extract reduced the protein expression of α-SMA, Col Ⅰ, and Col Ⅲ in the left ventricular (LV), thus inhibiting the LV remodeling associated with CHF. In addition, proteomics characterization of differentially expressed proteins showed that AWA administration inhibited left ventricular remodeling in CHF rats via a calcium signaling pathway, and reversed the expression of RyR2 and SERCA2a. Conclusions AWA extract exerts beneficial effects in an AAC-induced CHF model in rats, which was associated with an improvement in LV function, hypertrophy, fibrosis, and apoptotic status. These effects may be related to the regulation of calcium signaling by the altered expression of RyR2 and SERCA2a.
- Subjects :
- 0301 basic medicine
Cardiac function curve
Heart disease
Apoptosis
RM1-950
Pharmacology
Ventricular Function, Left
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Muscle hypertrophy
Rats, Sprague-Dawley
Masson's trichrome stain
Ventricular Dysfunction, Left
03 medical and health sciences
Aconite water-alkaloids
0302 clinical medicine
Fibrosis
medicine
Animals
Myocytes, Cardiac
Calcium Signaling
Ventricular remodeling
Heart Failure
Aconitum
Ventricular Remodeling
Plant Extracts
business.industry
Water
Proteomic
Cardiovascular Agents
Ryanodine Receptor Calcium Release Channel
General Medicine
medicine.disease
Chronic heart failure
Calcium signaling pathway
Disease Models, Animal
030104 developmental biology
Solubility
030220 oncology & carcinogenesis
Heart failure
Chronic Disease
Solvents
Hypertrophy, Left Ventricular
Myocardial fibrosis
Therapeutics. Pharmacology
business
Subjects
Details
- Language :
- English
- ISSN :
- 07533322
- Volume :
- 135
- Database :
- OpenAIRE
- Journal :
- Biomedicine & Pharmacotherapy
- Accession number :
- edsair.doi.dedup.....322d340117adb49579a97aace34d48c1