Preventive treatment with ginsenoside Rb1 ameliorates monocrotaline-induced pulmonary arterial hypertension in rats and involves store-operated calcium entry inhibition

Autor: Jing-Yi Guo, Rui-Xing Wang, Zhi-Juan Wu, Rui-Lan He, Long-Xin Gui, Run-Tian Zhang, Mo-Jun Lin, Hai-Xia Jiao, Xiao-Ru Liu
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Ginsenosides
Pharmaceutical Science
Panax
RM1-950
Pulmonary arterial pressure
Pharmacology
Pulmonary Artery
pulmonary vascular remodelling
030226 pharmacology & pharmacy
01 natural sciences
Rats
Sprague-Dawley
03 medical and health sciences
Ginseng
0302 clinical medicine
right ventricle hypertrophy
Drug Discovery
medicine
Animals
Pulmonary arterial smooth muscle cells
Calcium entry
Active ingredient
Pulmonary Arterial Hypertension
Monocrotaline
business.industry
General Medicine
Store-operated calcium entry
eye diseases
0104 chemical sciences
Rats
pulmonary arterial pressure
010404 medicinal & biomolecular chemistry
Disease Models
Animal
Complementary and alternative medicine
Vasoconstriction
Ginsenoside Rb1
Molecular Medicine
Calcium
Therapeutics. Pharmacology
medicine.symptom
business
Ex vivo
Research Article
Zdroj: Pharmaceutical Biology
article-version (VoR) Version of Record
Pharmaceutical Biology, Vol 58, Iss 1, Pp 1055-1063 (2020)
ISSN: 1744-5116
1388-0209
Popis: Context Ginsenoside Rb1, the main active ingredient of ginseng, exhibits ex vivo depression of store-operated calcium entry (SOCE) and related vasoconstriction in pulmonary arteries derived from pulmonary hypertension (PH) rats. However, the in vivo effects of ginsenoside Rb1 on PH remain unclear. Objective This study explored the possibility of using ginsenoside Rb1 as an in vivo preventive medication for type I PH, i.e., pulmonary arterial hypertension (PAH), and potential mechanisms involving SOCE. Materials and methods Male Sprague-Dawley rats (170–180 g) were randomly divided into Control, MCT, and MCT + Rb1 groups (n = 20). Control rats received only saline injection. Rats in the MCT + Rb1 and MCT groups were intraperitoneally administered single doses of 50 mg/kg monocrotaline (MCT) combined with 30 mg/kg/day ginsenoside Rb1 or equivalent volumes of saline for 21 consecutive days. Subsequently, comprehensive parameters related to SOCE, vascular tone, histological changes and hemodynamics were measured. Results Ginsenoside Rb1 reduced MCT-induced STIM1, TRPC1, and TRPC4 expression by 35.00, 31.96, and 32.24%, respectively, at the protein level. SOCE-related calcium entry and pulmonary artery contraction decreased by 162.6 nM and 71.72%. The mean pulmonary artery pressure, right ventricle systolic pressure, and right ventricular mass index decreased by 19.5 mmHg, 21.6 mmHg, and 39.50%. The wall thickness/radius ratios decreased by 14.67 and 17.65%, and the lumen area/total area ratios increased by 18.55 and 15.60% in intrapulmonary vessels with 51–100 and 101–150 μm o.d. Conclusion Ginsenoside Rb1, a promising candidate for PH prevention, inhibited SOCE and related pulmonary vasoconstriction, and relieved MCT-induced PAH in rats.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje