纳米脂质体促进柚皮素对弹性蛋白酶诱导的小鼠腹主动脉瘤的抑制作用

doi:10.5246/jcps.2024.03.016

中国药学(英文版) ›› 2024, Vol. 33 ›› Issue (3): 201-215.DOI: 10.5246/jcps.2024.03.016

纳米脂质体促进柚皮素对弹性蛋白酶诱导的小鼠腹主动脉瘤的抑制作用

陈都¹^,²^,³^,^#, 鱼毛毛²^,³^,^#, 张庆义²^,³, 胡睿¹^,²^,³^,⁴, 周析巧²^,³, 邰北²^,³, 陆有群²^,³, 祁荣²^,³^,¹^,^*()

^1. 石河子大学药学院新疆植物药资源利用教育部重点实验室, 新疆石河子 832003
^2. 北京大学医学部基础医学院药理学系, 北京 100191
^3. 北京大学血管稳态与重构全国重点实验室; 卫健委血管医学重点实验室; 北京大学分子药物与新型给药系统北京市重点实验室; 天然药物及仿生药物全国重点实验室, 北京 100191
^4. 克拉玛依市中心医院, 新疆克拉玛依 834000

收稿日期:2023-12-13 修回日期:2024-01-16 接受日期:2024-02-24 出版日期:2024-03-31 发布日期:2024-03-31
通讯作者: 祁荣

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

Du Chen¹^,²^,³^,^#, Maomao Yu²^,³^,^#, Qingyi Zhang²^,³, Rui Hu¹^,²^,³^,⁴, Xiqiao Zhou²^,³, Bei Tai²^,³, Youqun Lu²^,³, Rong Qi²^,³^,¹^,^*()

¹ Shihezi University College of Pharmacy; Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Shihezi 832003, Xinjiang, China
² Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
³ State Key Laboratory of Vascular Homeostasis and Remodeling. NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China
⁴ Karamay Central Hospital, Karamay 834000, Xinjiang, China

Received:2023-12-13 Revised:2024-01-16 Accepted:2024-02-24 Online:2024-03-31 Published:2024-03-31
Contact: Rong Qi
About author:
^# Du Chen and Maomao Yu contributed equally to this work.
Supported by:
National Key Research and Development Program (Grant No. 2019YFE0113500).

摘要/Abstract

摘要：

腹主动脉瘤(AAA)是一种严重的炎症性血管疾病, 其特征是基质金属蛋白酶(MMPs)升高、细胞外基质(ECM)降解和血管炎症反应。近年来的研究表明, 柚皮素(NGN)作为一种生物活性黄酮, 有抑制AAA的作用, 但是较低的水溶性及口服吸收特性限制了NGN抑制AAA的有效性。本研究开发了一种NGN纳米脂质体处方(NGN-NL), 以增强NGN对弹性蛋白酶诱导的小鼠AAA的抑制作用。首先, 我们优化了NGN-NL的处方, 发现磷脂和NGN的比例为9:1时为最佳处方。此外, 我们观察到, 与脂质体处方中的药物及辅料的物理混合物相比, NGN制备成脂质体后具有更强的抑制LPS诱导的巨噬细胞M1极化的作用。在同等剂量下, NGN-NL可比游离NGN展现出更强的抑制巨噬细胞M1极化的作用。此外, 脂质体载体本身也呈现一定程度的抑制M1极化的特性, 可协同增强NGN抑制巨噬细胞M1极化的效果。体内研究表明, 以含有25 mg/kg NGN剂量的NGN-NL对小鼠隔日进行腹腔注射, 与游离NGN在使用两倍剂量(50 mg/kg)下产生的AAA抑制效率相近。具体表现为: 改善腹主动脉直径扩张、保持主动脉结构完整性、减缓弹性蛋白降解、减少巨噬细胞浸润和下调腹主动脉MMP-2和MCP-1的表达。但与NGN-NL相比, 同等剂量(25 mg/kg)的游离NGN并不能有效抑制AAA的发生和发展。综上所述, NGN-NL显著提高了NGN对小鼠AAA的抑制作用, 展现出在其未来在AAA临床治疗中的应用潜力。

关键词: 纳米脂质体, 柚皮素, 腹主动脉瘤, 炎症

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:

陈都, 鱼毛毛, 张庆义, 胡睿, 周析巧, 邰北, 陆有群, 祁荣. 纳米脂质体促进柚皮素对弹性蛋白酶诱导的小鼠腹主动脉瘤的抑制作用[J]. 中国药学(英文版), 2024, 33(3): 201-215.

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.

图/表 6

Figure 1. Optimization process (A) of NGN-NL and effects of NGN-NL and NGN-Mix on M1 polarization of RAW264.7 cells (B–C) (n = 3). ***P < 0.001 compared with Control group, ##P < 0.01 compared with LPS group, ###P < 0.001 compared with LPS group and nsP ≥ 0.05 compared with LPS group.

Figure 2. NGN-NL had better inhibitory effect on macrophage M1 polarization than NGN on RAW264.7 cells (A–B). NL means nanoliposome carrier without loading NGN, NGN-NL means NGN loading in nanoliposome carrier, and NGN means NGN crude drug. The equal dose of 50 μM NGN was used to treat the LPS-induced RAW264.7 cells in NGN and NGN-NL groups, and the equal quantity and volume of nanoliposome carrier was used in NL and NGN-NL groups (n = 3). ***P < 0.001 compared with Control group, #P < 0.05 compared with LPS group and ##P < 0.01 compared with LPS group.

Figure 3. Inhibitory effects of NGN-NL and NGN on the elastase-induced AAA in mice. NGN and NGN-NL suppressed mouse AAA in terms of morphology (A), morbidity (B), and relative maximal abdominal aortic diameter (C). ***P < 0.001, **P < 0.01,*P < 0.05, nsP ≥ 0.05. n = 5–6.

Figure 4. NGN-NL and NGN improved the pathological changes of AAA. Effects of NGN and NGN-NL on the integrity of the aortic wall structure by H&E staining (A) and effects of the NGN and NGN-NL on MMP-2 expression in the aortic wall of AAA mice induced by pancreatic elastase (B). n = 5–6.

Figure 5. The NGN-NL and NGN attenuate elastase-induced destruction of elastic fibers in the mouse abdominal aorta walls. Effects of NGN-NL and NGN on the destruction of elastic fibers in the pancreatic elastase-induced AAA by aldehyde fuchsin staining (A) and semi-quantitation of elastin degradation scores (B). *P < 0.05, nsP ≥ 0.05. n = 5–6.

Figure 6. The NGN-NL and NGN reduced inflammation in the aortic vessel wall. NGN-NL and NGN attenuated macrophage infiltration by MAC-2 (A) and high expression of MCP-1 (B) in the aortic vessels induced by pancreatic elastase. n = 5–6.

参考文献 40

[1]	Davis, F.M.; Rateri, D.L.; Daugherty, A. Mechanisms of aortic aneurysm formation: translating preclinical studies into clinical therapies. Heart. 2014, 100, 1498–1505.
[2]	Eckstein, H.H.; Böckler, D.; Flessenkämper, I.; Schmitz-Rixen, T.; Debus, S.; Lang, W. Ultrasonographic screening for the detection of abdominal aortic aneurysms. Dtsch Arztebl. Int. 2009, 106, 657–663.
[3]	Ahmed, R.; Ghoorah, K.; Kunadian, V. Abdominal aortic aneurysms and risk factors for adverse events. Cardiol. Rev. 2016, 24, 88–93.
[4]	Adam, D.J.; Mohan, I.V.; Stuart, W.P.; Bain, M.; Bradbury, A.W. Community and hospital outcome from ruptured abdominal aortic aneurysm within the catchment area of a regional vascular surgical service. J. Vasc. Surg. 1999, 30, 922–928.
[5]	Kitagawa, A.; Mastracci, T.M.; von Allmen, R.; Powell, J.T. The role of diameter versus volume as the best prognostic measurement of abdominal aortic aneurysms. J. Vasc. Surg. 2013, 58, 258–265.
[6]	Rughani, G.; Robertson, L.; Clarke, M. Medical treatment for small abdominal aortic aneurysms. Cochrane Database Syst. Rev. 2012, CD009536.
[7]	Baxter, B.T.; Terrin, M.C.; Dalman, R.L. Medical management of small abdominal aortic aneurysms. Circulation. 2008, 117, 1883–1889.
[8]	Santilli, S.M.; Littooy, F.N.; Cambria, R.A.; Rapp, J.H.; Tretinyak, A.S.; d’Audiffret, A.C.; Kuskowski, M.A.; Roethle, S.T.; Tomczak, C.M.; Krupski, W.C. Expansion rates and outcomes for the 3.0-cm to the 3.9-cm infrarenal abdominal aortic aneurysm. J. Vasc. Surg. 2002, 35, 666–671.
[9]	Vega de Céniga, M.; Gómez, R.; Estallo, L.; Rodríguez, L.; Baquer, M.; Barba, A. Growth rate and associated factors in small abdominal aortic aneurysms. Eur. J. Vasc. Endovasc. Surg. 2006, 31, 231–236.
[10]	Brown, L.C.; Thompson, S.G.; Greenhalgh, R.M.; Powell, J.T.; Small Aneurysm Trial Participants, U.K. Fit patients with small abdominal aortic aneurysms (AAAs) do not benefit from early intervention. J. Vasc. Surg. 2008, 48, 1375–1381.
[11]	Raffort, J.; Lareyre, F.; Clément, M.; Hassen-Khodja, R.; Chinetti, G.; Mallat, Z. Monocytes and macrophages in abdominal aortic aneurysm. Nat. Rev. Cardiol. 2017, 14, 457–471.
[12]	Cheng, Z.; Zhou, Y.Z.; Wu, Y.; Wu, Q.Y.; Liao, X.B.; Fu, X.M.; Zhou, X.M. Diverse roles of macrophage polarization in aortic aneurysm: destruction and repair. J. Transl. Med. 2018, 16, 354.
[13]	Bi, Y.; Zhong, H.; Xu, K.; Ni, Y.; Qi, X.; Zhang, Z.; Li, W. Performance of a modified rabbit model of abdominal aortic aneurysm induced by topical application of porcine elastase: 5-month follow-up study. Eur. J. Vasc. Endovasc. Surg. 2013, 45, 145–152.
[14]	Bhamidipati, C.M.; Mehta, G.S.; Lu, G.Y.; Moehle, C.W.; Barbery, C.; DiMusto, P.D.; Laser, A.; Kron, I.L.; Upchurch, G.R. Jr, Ailawadi, G. Development of a novel murine model of aortic aneurysms using peri-adventitial elastase. Surgery. 2012, 152, 238–246.
[15]	Hämäläinen, M.; Nieminen, R.; Vuorela, P.; Heinonen, M.; Moilanen, E. Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Inflamm. 2007, 2007, 45673.
[16]	Ali Esmaeili, M.; Alilou, M. Naringenin attenuates CCl₄-induced hepatic inflammation by the activation of an Nrf2-mediated pathway in rats. Clin. Exp. Pharmacol. Physiol. 2014, 41, 416–422.
[17]	Mulvihill, E.E.; Assini, J.M.; Sutherland, B.G.; DiMattia, A.S.; Khami, M.; Koppes, J.B.; Sawyez, C.G.; Whitman, S.C.; Huff, M.W. Naringenin decreases progression of atherosclerosis by improving dyslipidemia in high-fat-fed low-density lipoprotein receptor-null mice. Arterioscler. Thromb. Vasc. Biol. 2010, 30, 742–748.
[18]	Kapoor, S. Tumor growth attenuating effects of naringenin. Pathol. Oncol. Res. 2014, 20, 483.
[19]	Jeon, S.M.; Kim, H.K.; Kim, H.J.; Do, G.M.; Jeong, T.S.; Park, Y.B.; Choi, M.S. Hypocholesterolemic and antioxidative effects of naringenin and its two metabolites in high-cholesterol fed rats. Transl. Res. 2007, 149, 15–21.
[20]	Assini, J.M.; Mulvihill, E.E.; Sutherland, B.G.; Telford, D.E.; Sawyez, C.G.; Felder, S.L.; Chhoker, S.; Edwards, J.Y.; Gros, R.; Huff, M.W. Naringenin prevents cholesterol-induced systemic inflammation, metabolic dysregulation, and atherosclerosis in Ldlr(-)/(-) mice. J. Lipid Res. 2013, 54, 711–724.
[21]	Zhang, X.; Wang, A.Y.; Yang, X.T.; Wang, Y.X.; Wang, Q.Y.; Hu, R.; Anwaier, G.; Di, C.; Qi, R.; Huang, Y.B. HPMC improves protective effects of naringenin and isonicotinamide co-crystals against abdominal aortic aneurysm. Cardiovasc. Drugs Ther. 2022, 36, 1109–1119.
[22]	Wang, Q.Y.; Ou, Y.J.; Hu, G.M.; Wen, C.; Yue, S.S.; Chen, C.; Xu, L.; Xie, J.W.; Dai, H.; Xiao, H.; Zhang, Y.Y.; Qi, R. Naringenin attenuates non-alcoholic fatty liver disease by down-regulating the NLRP3/NF-κB pathway in mice. Br. J. Pharmacol. 2019, 177, 1806–1821.
[23]	Jia, Y.T.; Zhang, L.; Liu, Z.Y.; Mao, C.F.; Ma, Z.H.; Li, W.Q.; Yu, F.; Wang, Y.B.; Huang, Y.Q.; Zhang, W.Z.; Zheng, J.G.; Wang, X.; Xu, Q.B.; Zhang, J.; Feng, W.; Yun, C.H.; Liu, C.J.; Sun, J.P.; Fu, Y.; Cui, Q.H.; Kong, W. Targeting macrophage TFEB-14-3-3 epsilon Interface by naringenin inhibits abdominal aortic aneurysm. Cell Discov. 2022, 8, 21.
[24]	Khan, A.W.; Kotta, S.; Ansari, S.H.; Sharma, R.K.; Ali, J. Enhanced dissolution and bioavailability of grapefruit flavonoid Naringenin by solid dispersion utilizing fourth generation carrier. Drug Dev. Ind. Pharm. 2015, 41, 772–779.
[25]	Kerdudo, A.; Dingas, A.; Fernandez, X.; Faure, C. Encapsulation of rutin and naringenin in multilamellar vesicles for optimum antioxidant activity. Food Chem. 2014, 159, 12–19.
[26]	Xu, X.R.; Yu, H.T.; Hang, L.; Shao, Y.; Ding, S.H.; Yang, X.W. Preparation of naringenin/β-cyclodextrin complex and its more potent alleviative effect on choroidal neovascularization in rats. Biomed Res. Int. 2014, 2014, 623509.
[27]	Hermenean, A.; Ardelean, A.; Stan, M.; Hadaruga, N.; Mihali, C.V.; Costache, M.; Dinischiotu, A. Antioxidant and hepatoprotective effects of naringenin and its β-cyclodextrin formulation in mice intoxicated with carbon tetrachloride: a comparative study. J. Med. Food. 2014, 17, 670–677.
[28]	Maiti, K.; Mukherjee, K.; Gantait, A.; Saha, B.P.; Mukherjee, P.K. Enhanced therapeutic potential of naringenin-phospholipid complex in rats. J. Pharm. Pharmacol. 2006, 58, 1227–1233.
[29]	Khan, A.W.; Kotta, S.; Ansari, S.H.; Sharma, R.K.; Ali, J. Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design, characterization, in vitro and in vivo evaluation. Drug Deliv. 2015, 22, 552–561.
[30]	Krishnakumar, N.; Sulfikkarali, N.K.; Manoharan, S.; Nirmal, R.M. Screening of chemopreventive effect of naringenin-loaded nanoparticles in DMBA-induced hamster buccal pouch carcinogenesis by FT-IR spectroscopy. Mol. Cell Biochem. 2013, 382, 27–36.
[31]	Jeong, H.E.; Choi, J.; Oh, I.S.; Son, H.; Jang, S.H.; Jung, S.Y.; Shin, J.Y. Temporal trends of pharmacologic treatments for tuberculosis and multidrug resistant tuberculosis following dissemination of treatment guidelines in South Korea. J. Microbiol. Immunol. Infect. 2022, 55, 917–925.
[32]	Torchilin, V.P. Recent advances with liposomes as pharmaceutical carriers. Nat. Rev. Drug Discov. 2005, 4, 145–160.
[33]	Allen, T.M.; Cullis, P.R. Liposomal drug delivery systems: from concept to clinical applications. Adv. Drug Deliv. Rev. 2013, 65, 36–48.
[34]	Li, M.Y.; Du, C.Y.; Guo, N.; Teng, Y.O.; Meng, X.; Sun, H.; Li, S.S.; Yu, P.; Galons, H. Composition design and medical application of liposomes. Eur. J. Med. Chem. 2019, 164, 640–653.
[35]	Antimisiaris, S.G.; Marazioti, A.; Kannavou, M.; Natsaridis, E.; Gkartziou, F.; Kogkos, G.; Mourtas, S. Overcoming barriers by local drug delivery with liposomes. Adv. Drug Deliv. Rev. 2021, 174, 53–86.
[36]	Chen, C.; Jie, X.; Ou, Y.J.; Cao, Y.N.; Xu, L.; Wang, Y.X.; Qi, R. Nanoliposome improves inhibitory effects of naringenin on nonalcoholic fatty liver disease in mice. Nanomedicine. 2017, 12, 1791–1800.
[37]	Xie, C.P.; Ye, F.M.; Zhang, N.; Huang, Y.X.; Pan, Y.; Xie, X.J. CCL7 contributes to angiotensin II-induced abdominal aortic aneurysm by promoting macrophage infiltration and pro-inflammatory phenotype. J. Cell Mol. Med. 2021, 25, 7280–7293.
[38]	Ma, K.Y.; Liu, W.Q.; Liu, Q.; Hu, P.F.; Bai, L.Y.; Yu, M.; Yang, Y. Naringenin facilitates M2 macrophage polarization after myocardial ischemia-reperfusion by promoting nuclear translocation of transcription factor EB and inhibiting the NLRP3 inflammasome pathway. Environ. Toxicol. 2023, 38, 1405–1419.
[39]	Chen, Z.; Wu, H.; Fan, W.Y.; Zhang, J.S.; Yao, Y.; Su, W.W.; Wang, Y.G.; Li, P.B. Naringenin suppresses BEAS-2B-derived extracellular vesicular cargoes disorder caused by cigarette smoke extract thereby inhibiting M1 macrophage polarization. Front. Immunol. 2022, 13, 930476.
[40]	Toita, R.; Fujita, S.; Kang, J.H. Macrophage uptake behavior and anti-inflammatory response of bovine brain- or soybean-derived phosphatidylserine liposomes. J. Oleo Sci. 2018, 67, 1131–1135.

纳米脂质体促进柚皮素对弹性蛋白酶诱导的小鼠腹主动脉瘤的抑制作用

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

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