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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2025, Vol. 30 ›› Issue (2): 209-215.doi: 10.12092/j.issn.1009-2501.2025.02.007

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Radix angelica sinensis and astragalus mongholicus extract mediating the Jagged1/Notch1 pathway to inhibit fibroblast transdifferentiation and resist radiation induced myocardial fibrosis

LI Wen1,3, JIANG Hugang1,3, WANG Xinqiang2,3, LI Yingdong1,2,3, LIU Kai1,2,3, ZHAO Xinke1,2,3   

  1. 1 College of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China; 2 Department of Cardiology, Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou 730000, Gansu, China; 3 Gansu Provincial Key Laboratory of Chinese Medicine Prevention and Treatment of Chronic Diseases, Lanzhou 730000, Gansu, China
  • Received:2023-12-20 Revised:2024-03-26 Online:2025-02-26 Published:2025-02-05

Abstract:

AIM: To study the mechanism of action of radix angelica sinensis and astragalus mongholicus extract (RAS-AM) in inhibiting fibroblast transdifferentiation (CMT) and preventing radiation-induced myocardial fibrosis (RIMF) via the Jagged1/Notch1 pathway. METHODS: Sixty male Wistar rats were randomly divided into blank group, model group, benazepril hydrochloride group, low dose RAS-AM group, medium dose RAS-AM group, and high dose RAS-AM group, with 10 rats in each group. Except for the blank group, all other groups were induced with high-energy radiation at a dose of 38 Gy to establish RIMF models. The blank group and the model group received sterile distilled water by gavage, and the other groups received medication for 4 weeks of intervention: benazepril hydrochloride group (1.0 mg·kg-1·d-1), low dose RAS-AM group (150 mg·kg-1·d-1), medium dose RAS-AM group (300 mg·kg-1·d-1), and high dose RAS-AM group (600 mg·kg-1·d-1). The general condition of rats, the ultrastructure of myocardial tissue were observed using electron microscopy, changes in myocardial tissue fibers using Masson staining, and  CMT related protein Vimentin and α-SMA expression using immunohistochemical staining techniques. ELISA was used to detect serum inflammatory factors IL-6 and TNF-α in rats. The levels of cTnI and ST2, and the expression of Jagged1 and Notch1 were detected by Western blot. RESULTS: Compared with the blank group, the model group rats exhibited symptoms such as mental fatiguem anorexiam and loose stools; The arrangement of some myofibrils in the myocardium is disordered, with dissolution and breakage of myofibrilsm abnormal Z-line structure in some partsm disordered mitochondrial arrangement, rupture of mitochondrial membranem, and rupture or disappearance of mitochondrial ridge structure in some parts. A large amount of collagen fibers proliferate and deposit in the myocardium, and the fibrotic area significantly increases (P<0.01); The expression of myocardial tissue Vimentin α-SMA protein increased (P<0.05), while the expression of Jagged1 and Notch1 proteins decreased (P<0.05); serum IL-6 and TNF-α, the expression of inflammatory factors such as cTnI and ST2 increased (P<0.05). compared with the model group, the RAS-AM and benazepril hydrochloride groups showed varying degrees of improvement in general conditions; the pathological changes of myocardial ultrastructure have been improved, and myocardial fibrosis has been alleviated; The area of collagen fibers significantly decreased (P<0.01); Myocardial tissue Vimentin α-SMA protein expression decreased (P<0.05), while Jagged1 and Notch1 expression increased (P<0.05); Serum IL-6 and TNF-α, The expression of inflammatory factors such as cTnI and ST2 decreased (P<0.05). CONCLUSION: RAS-AM may alleviate RIMF by intervening in the Jagged1/Notch1 pathway to inhibit CMT. The specific mechanism still needs further investigation. 

Key words: radix angelica sinensis and astragalus mongholicus extract, Jagged1/Notch1 pathway, fibroblast transdifferentiation, radiation induced myocardial fibrosis

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