Enhanced protective effects of naringenin on elastase-induced mouse abdominal aortic aneurysm through nanoliposome delivery

doi:10.5246/jcps.2024.03.016

Abstract

Abstract:

Abdominal aortic aneurysm (AAA) is a severe inflammatory vascular illness characterized by the increased matrix metalloproteinases (MMPs), degradation of extracellular matrix (ECM), and inflammatory responses. Recent evidence indicates that naringenin (NGN), a bioactive flavanone, can inhibit AAA. However, the poor water solubility and oral absorption of NGN limit its efficacy. In this study, we developed a nanoliposome formulation of NGN (NGN-NL) to enhance the preventive effect of NGN on AAA induced by pancreatic elastase in mice. We investigated the NGN-NL prescription and found that a 9:1 ratio of phospholipids to NGN was the optimized formulation. Additionally, we observed that NGN, when prepared into liposomes, demonstrated a stronger ability to counteract LPS-induced macrophage M1 polarization compared to the physical mixture of NGN with the prescription materials of liposomes. Moreover, at an equal dose, NGN-NL exhibited a better inhibitory effect on macrophage M1 polarization than NGN alone. Furthermore, the liposome carrier itself displayed some extent of anti-M1 polarization properties, synergistically enhancing NGN’s ability to inhibit macrophage M1 polarization. In vivo experiments revealed that intraperitoneal administration of NGN-NL at an NGN dose of 25 mg/kg on alternate days demonstrated a similar effect to a double dose of NGN crude drug (50 mg/kg) in preventing AAA. This was evidenced by an overall improvement in abdominal aorta diameter dilation, preservation of aortic structural integrity, mitigation of elastin degradation, reduction in macrophage infiltration, and downregulation of MMP-2 and MCP-1 in the abdominal aortas. However, an equal dose of NGN crude drug (25 mg/kg) could not efficiently inhibit the occurrence and development of AAA compared with NGN-NL. In conclusion, NGN-NL significantly improved NGN’s efficacy in inhibiting mouse AAA, demonstrating its potential application in clinical AAA treatment in the future.

Key words: Nanoliposome, Naringenin, Abdominal aortic aneurysm, Inflammation

Supporting:

Du Chen, Maomao Yu, Qingyi Zhang, Rui Hu, Xiqiao Zhou, Bei Tai, Youqun Lu, Rong Qi. Enhanced protective effects of naringenin on elastase-induced mouse abdominal aortic aneurysm through nanoliposome delivery[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(3): 201-215.

Figures/Tables 6

References 40

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