Phenolic acids from Prunella vulgaris alleviate cardiac remodeling following myocardial infarction partially by suppressing NLRP3 activation

Author:

Wei Jinna12,Leng Ling123ORCID,Sui Yunchan1,Song Shaofei1,Owusu Felix Boahen1,Li Xue13,Cao Yu1,Li Peijie1,Wang Hongda1,Li Ruiqiao13,Yang Wenzhi123,Gao Xiumei2,Wang Qilong12345

Affiliation:

1. Institute of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine Tianjin China

2. Key Lab of Pharmacological Traditional Chinese Medicine Formulae Ministry of Education Tianjin China

3. State Key Laboratory of Component‐Based Chinese Medicine Ministry of Education Tianjin China

4. Haihe Laboratory of Modern Chinese Medicine Tianjin China

5. Endocrinology Department Fourth Teaching Hospital of Tianjin University of Traditional Chinese Medicine Tianjin China

Abstract

AbstractAcute myocardial infarction (MI) is one of the leading causes of mortality around the world. Prunella vulgaris (Xia‐Ku‐Cao in Chinese) is used in traditional Chinese medicine practice for the treatment of cardiovascular diseases. However, its active ingredients and mechanisms of action on cardiac remodeling following MI remain unknown. In this study, we investigated the cardioprotective effect of P. vulgaris on MI rat models. MI rats were treated with aqueous extract of P. vulgaris or phenolic acids from P. vulgaris, including caffeic acid, ursolic acid or rosmarinic acid, 1 day after surgery and continued for the following 28 days. Then the cardioprotective effect, such as cardiac function, inflammatory status, and fibrosis areas were evaluated. RNA‐sequencing (RNA‐seq) analysis, real‐time polymerase chain reaction (PCR), western blotting, and ELISA were used to explore the underlying mechanism. In addition, ultra‐high performance liquid chromatography/mass spectrometer analysis was used to identify the chemicals from P. vulgaris. THP‐1NLRP3‐GFP cells were used to confirm the inhibitory effect of P. vulgaris and phenolic acids on the expression and activity of NLRP3. We found that P. vulgaris significantly improved cardiac function and reduced infarct size. Meanwhile, P. vulgaris protected cardiomyocyte against apoptosis, evidenced by increasing the expression of anti‐apoptosis protein Bcl‐2 in the heart and decreasing lactate dehydrogenase (LDH) levels in serum. Results from RNA‐seq revealed that the therapeutic effect of P. vulgaris might relate to NLRP3‐mediated inflammatory response. Results from real‐time PCR and western blotting confirmed that P. vulgaris suppressed NLRP3 expression in MI heart. We also found that P. vulgaris suppressed NLRP3 expression and the secretion of HMGB1, IL‐1β, and IL‐18 in THP‐1NLRP3‐GFP cells. Further studies indicated that the active components of P. vulgaris were three phenolic acids, those were caffeic acid, ursolic acid, and rosmarinic acid. These phenolic acids inhibited LPS‐induced NLRP3 expression and activity in THP‐1 cells, and improved cardiac function, suppressed inflammatory aggregation and fibrosis in MI rat models. In conclusion, our study demonstrated that P. vulgaris and phenolic acids from P. vulgaris, including caffeic acid, ursolic acid, and rosmarinic acid, could improve cardiac function and protect cardiomyocytes from ischemia injury during MI. The mechanism was partially related to inhibiting NLRP3 activation.

Funder

National Key Research and Development Program of China

Publisher

Wiley

Subject

Pharmacology

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