Vasculoprotective Potential of Baicalein in Angiotensin II-Infused Abdominal Aortic Aneurysms through Inhibiting Inflammation and Oxidative Stress

Erna Sulistyowati; Shang-En Huang; Tsung-Lin Cheng; Yu-Ying Chao; Chia-Yang Li; Ching-Wen Chang; Meng-Xuan Lin; Ming-Chung Lin; Jwu-Lai Yeh

doi:10.3390/ijms242116004

Vasculoprotective Potential of Baicalein in Angiotensin II-Infused Abdominal Aortic Aneurysms through Inhibiting Inflammation and Oxidative Stress

Int J Mol Sci. 2023 Nov 6;24(21):16004. doi: 10.3390/ijms242116004.

Authors

Erna Sulistyowati¹, Shang-En Huang^{2

3}, Tsung-Lin Cheng^{4

5

6}, Yu-Ying Chao⁷, Chia-Yang Li³, Ching-Wen Chang^{2

3}, Meng-Xuan Lin^{2

3}, Ming-Chung Lin^{8

9}, Jwu-Lai Yeh^{2

3

10

11}

Affiliations

¹ Faculty of Medicine, University of Islam Malang, Malang City 65145, Indonesia.
² Department of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
³ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁴ Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁵ Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁶ College of Professional Studies, National Pingtung University of Science and Technology, Pingtung 912, Taiwan.
⁷ Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁸ Department of Anesthesiology, Chi Mei Medical Center, Tainan 710, Taiwan.
⁹ Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan 717, Taiwan.
¹⁰ Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
¹¹ Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804, Taiwan.

Abstract

Aortic wall inflammation, abnormal oxidative stress and progressive degradation of extracellular matrix proteins are the main characteristics of abdominal aortic aneurysms (AAAs). The nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome dysregulation plays a crucial role in aortic damage and disease progression. The first aim of this study was to examine the effect of baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one) on AAA formation in apolipoprotein E-deficient (ApoE^-/-) mice. The second aim was to define whether baicalein attenuates aberrant vascular smooth muscle cell (VSMC) proliferation and inflammation in VSMC culture. For male ApoE^-/- mice, a clinically relevant AAA model was randomly divided into four groups: saline infusion, baicalein intraperitoneal injection, Angiotensin II (Ang II) infusion and Ang II + baicalein. Twenty-seven days of treatment with baicalein markedly decreased Ang II-infused AAA incidence and aortic diameter, reduced collagen-fiber formation, preserved elastic structure and density and prevented smooth muscle cell contractile protein degradation. Baicalein inhibited rat VSMC proliferation and migration following the stimulation of VSMC cultures with Ang II while blocking the Ang II-inducible cell cycle progression from G₀/G₁ to the S phase in the synchronized cells. Cal-520 AM staining showed that baicalein decreased cellular calcium in Ang II-induced VSMCs; furthermore, a Western blot assay indicated that baicalein inhibited the expression of PCNA and significantly lowered levels of phospho-Akt and phospho-ERK, along with an increase in baicalein concentration in Ang II-induced VSMCs. Immunofluorescence staining showed that baicalein pretreatment reduced NF-κB nuclear translocation in Ang II-induced VSMCs and furthered the protein expressions of NLRP3 while ASC and caspase-1 were suppressed in a dose-dependent manner. Baicalein pretreatment upregulated Nrf2/HO-1 signaling in Ang II-induced VSMCs. Thus, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining showed that its reactive oxygen species (ROS) production decreased, along with the baicalein pretreatment. Our overall results indicate that baicalein could have therapeutic potential in preventing aneurysm development.

Keywords: abdominal aortic aneurysm; baicalein; inflammation; oxidative stress; vasculoprotective.

MeSH terms

Angiotensin II* / metabolism
Animals
Aortic Aneurysm, Abdominal* / chemically induced
Aortic Aneurysm, Abdominal* / drug therapy
Apolipoproteins E / metabolism
Disease Models, Animal
Inflammation / complications
Inflammation / drug therapy
Male
Mice
Mice, Inbred C57BL
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Oxidative Stress
Rats

Substances

Angiotensin II
baicalein
NLR Family, Pyrin Domain-Containing 3 Protein
Apolipoproteins E

Abstract

MeSH terms

Substances

Grants and funding