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- Title
Andrographolide Attenuates Oxidized LDL-Induced Activation of the NLRP3 Inflammasome in Bone Marrow-Derived Macrophages and Mitigates HFCCD-Induced Atherosclerosis in Mice.
- Authors
Chen, Chih-Chieh; Lii, Chong-Kuei; Liu, Kai-Li; Lin, Yi-Ling; Lo, Chia-Wen; Li, Chien-Chun; Yang, Ya-Chen; Chen, Haw-Wen
- Abstract
Andrographolide (AND) is a bioactive component of the herb Andrographis paniculata and a well-known anti-inflammatory agent. Atherosclerosis is a chronic inflammatory disease of the vasculature, and oxidized LDL (oxLDL) is thought to contribute heavily to atherosclerosis-associated inflammation. The aim of this study was to investigate whether AND mitigates oxLDL-mediated foam cell formation and diet-induced atherosclerosis (in mice fed a high-fat, high-cholesterol, high-cholic acid [HFCCD] diet) and the underlying mechanisms involved. AND attenuated LPS/oxLDL-mediated foam cell formation, IL-1 β mRNA and protein (p37) expression, NLR family pyrin domain containing 3 (NLRP3) mRNA and protein expression, caspase-1 (p20) protein expression, and IL-1 β release in BMDMs. Treatment with oxLDL significantly induced protein and mRNA expression of CD36, lectin-like oxLDL receptor-1 (LOX-1), and scavenger receptor type A (SR-A), whereas pretreatment with AND significantly inhibited protein and mRNA expression of SR-A only. Treatment with oxLDL significantly induced ROS generation and Dil-oxLDL uptake; however, pretreatment with AND alleviated oxLDL-induced ROS generation and Dil-oxLDL uptake. HFCCD feeding significantly increased aortic lipid accumulation, ICAM-1 expression, and IL-1 β mRNA expression, as well as blood levels of glutamic pyruvic transaminase (GPT), total cholesterol, and LDL-C. AND co-administration mitigated aortic lipid accumulation, the protein expression of ICAM-1, mRNA expression of IL-1 β and ICAM-1, and blood levels of GPT. These results suggest that the working mechanisms by which AND mitigates atherosclerosis involve the inhibition of foam cell formation and NLRP3 inflammasome-dependent vascular inflammation as evidenced by decreased SR-A expression and IL-1 β release, respectively.
- Subjects
BIOLOGICAL models; INTERLEUKINS; ANTI-inflammatory agents; DIETARY cholesterol; ANIMAL experimentation; INFLAMMATION; MACROPHAGES; LOW density lipoproteins; SIGNAL peptides; CELL receptors; LDL cholesterol; ATHEROSCLEROSIS; HYDROCARBONS; GENE expression; BILE acids; MESSENGER RNA; RESEARCH funding; BONE marrow; REACTIVE oxygen species; DIETARY fats; MICE; CASPASES; ALANINE aminotransferase; CHOLESTEROL; PHARMACODYNAMICS
- Publication
American Journal of Chinese Medicine, 2023, Vol 51, Issue 8, p2175
- ISSN
0192-415X
- Publication type
Article
- DOI
10.1142/S0192415X23500933