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Astragaloside IV in Hypoxic Pulmonary Hypertension: an In Vivo and In Vitro Experiments
XinTian1, Xiaofeng Zhang2, Yi Feng3
1Department of Cardiology, Shaanxi Provincial Hospital of Chinese Medicine, No. 4 Xihuamen Street, Xian 710003, China.
Abstract:
The objective of study was to find the actions of astragaloside IV (ASIV) on PAH due to monocrotaline (MCT) in rats. Intraperitoneal injection of 60 mg/ kg MCT was injected to rats, come after by ASIV treatment with doses of 10 mg/kg daily once or 30 mg/kg of dose for twenty one days once daily. RVSP, serum inflammatory cytokines, RVH, and the other pathological parameters of the pulmonary arteries were evaluated. ASIV attenuated the increased pulmonary artery pressure and its structure in rat modification due to MCT. Additionally, ASIV avoided the rise in tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels in the blood serum, and their expression of gene in the pleural parts, which was caused by MCT. ASIV promoted apoptotic resistance of HPASMCs and weakened the hypoxia-induced proliferation. ASIV shows over expression of caspase-3, caspase-9, p21, p27, and Bax, while ASIV downregulated Bcl-2, phospho-ERK, HIF-1α, and protein appearance in HPASMCs. These findings of the in vitro and the in vivo experiment indicate that astragaloside IV exerts protective effects against pulmonary arterial pressure, and may have action to be improved into pharmacological drug for pulmonary arterial pressure treatment.
Insights
Astragaloside IV (ASIV) effectively treats pulmonary arterial hypertension (PAH) in rats induced by monocrotaline (MCT). ASIV reduces pulmonary artery pressure and inflammation, offering potential as a PAH therapeutic drug.
Area of Science:
- Pharmacology
- Cardiovascular Research
- Toxicology
Background:
- Pulmonary arterial hypertension (PAH) is a severe condition characterized by high blood pressure in the pulmonary arteries.
- Monocrotaline (MCT) is a toxin commonly used to induce PAH in animal models for research purposes.
- Astragaloside IV (ASIV) is a natural compound with potential therapeutic properties.
Purpose of the Study:
- To investigate the protective effects of astragaloside IV (ASIV) against monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in a rat model.
- To evaluate the impact of ASIV on hemodynamic parameters, cardiac structure, and inflammatory markers in rats with MCT-induced PAH.
Main Methods:
- Rats were injected with MCT (60 mg/kg) to induce PAH.
- ASIV was administered daily at doses of 10 mg/kg or 30 mg/kg for 21 days.
- Evaluated parameters included right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH), serum inflammatory cytokines (TNF-α, IL-1β), and gene/protein expression in pulmonary artery cells (HPASMCs).
Main Results:
- ASIV significantly attenuated the increase in pulmonary artery pressure and structural changes caused by MCT.
- ASIV reduced elevated serum levels and gene expression of TNF-α and IL-1β induced by MCT.
- In vitro, ASIV promoted apoptotic resistance, inhibited hypoxia-induced proliferation of HPASMCs, and modulated key proteins involved in apoptosis and cell signaling (e.g., caspase-3, Bax, Bcl-2, HIF-1α).
Conclusions:
- Astragaloside IV demonstrates significant protective effects against MCT-induced PAH in rats.
- ASIV mitigates pulmonary hypertension, inflammation, and vascular remodeling.
- These findings suggest ASIV holds promise as a potential pharmacological agent for treating pulmonary arterial hypertension.
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