js4399金沙线集团

虾青素是自然界中最有效的抗衰老剂，具有显著的抗氧化、抗炎和抗凋亡特性[1]，本文将梳理虾青素的生理活性、机制研究以及应用进展，以期为虾青素在炎症性疾病包括口腔疾病中的应用提供循证依据。

虾青素是一种六元环结构，两端各有一个异戊二烯单元，中间有四个异戊二烯单元通过共轭双键连接，具有三种异构体，也可被一种或两种脂肪酸酯化。虾青素目前可以从直接水产品、藻类，酵母、细菌、真菌、石化产品中提取，或者通过生物、化学等手段合成获得。

1 虾青素的生理活性

1.1抗氧化活性

呼吸（氧化反应）、环境污染、放射暴露等因素不断地在人体体内产生自由基，已有大量研究表明虾青素可以在人体各个系统通过 NOX4/DUOX1途径[2]，NRF2 途径[3]，PI3K/Akt/NF-κB 途径[4]，ERK1/2途径[5]以及改变巨噬细胞M1、M2表型[6]的方式等清除氧化自由基（ROS），进而减少效应器官实质细胞的线粒体功能障碍和细胞凋亡，提高细胞增殖能力，促进组织愈合。

虾青素对氧化自由基的调控是双向的，在正常组织中常常清除ROS，在肿瘤细胞中却可增加局部ROS，进而通过诱导肿瘤细胞的凋亡[7]，促进肿瘤细胞铁死亡[8]，抑制其增殖[9]的方式抑制肿瘤发生。

1.2 抗炎作用

炎症的发生往往是由于机体全身或局部环境无法完全清除病原体导致的。虾青素可以发挥积极的抗炎作用。一方面，虾青素可以直接作用于病原体，比如通过破坏细菌粘附性和侵袭性[10]、或者改变菌群结构[11]，降低屏障组织的炎症水平。另一方面，虾青素可以阻断炎症的级联反应。如消除炎性因子[12]以及阻断经典炎症反应通路PI3K/AKT[13]、Nrf2[14]、NF- κB[15]、p38MAPK[16]和JAK-2/STAT-3[17]。同时，虾青素还可以增强组织的修复愈合能力。如促进巨噬细胞的M2极化，增强基质细胞的增殖和迁移，促进新血管生成[18]，从而加速机体的恢复。

1.3 抗衰老作用

许多研究显示，虾青素可能通过阻断年龄相关的氧化应激、细胞凋亡和突变率增加，从而达到延缓衰老的作用。在低等生物中，虾青素已被证明可以延长酿酒酵母[19]、秀丽隐杆线虫[20]的寿命。对于高等动物，虾青素已有证据可以改善衰老相关炎症的疾病结局，包括 神经退行性疾病[21]、骨质疏松症[22]等。

2虾青素相关材料的研究进展

虽然虾青素具备良好的药用潜力，但是存在水溶性不佳、易氧化性、光热不稳定等问题。为了更好地应用，目前虾青素常常被包装进递送系统、或者与其他材料进行复合来改善药理特性。

2.1虾青素的药物改良

对虾青素本身的改良包括异构和纳米化。通常虾青素的反式异构体比顺式构型稳定[23]，而Z异构体可以提高虾青素的光稳定性和药效[24]。对虾青素进行无载体纳米化，可以增加虾青素的光稳定性和抗氧化能力[25]。

2.2虾青素的全身应用

将虾青素封装或嵌入口服递送系统内，可以克服消化道 pH值和水解酶的影响，降低其疏水行为，增加其药物利用度、稳定性或者屏障穿透能力。封装虾青素用的外层材料多由蛋白质和多糖等生物基和可食用的包合物组成[26]，根据不同的添加材料、目的与技术原理，虾青素口服递送系统展现出各自的优势。

2.3虾青素的局部应用

2.3.1局部递送系统 在局部，虾青素也可以通过

包埋、聚合、底物修饰等多种方式，增加局部的药物靶向缓释，跨膜转运和药物稳定性，延长药效。

2.3.2虾青素复合敷料 除了口服递送系统、局部

递送系统，虾青素还可与多种膜类材料以及3D材料复合，改变材料的结构并延迟其体外降解速度，更稳定地递送药物，可以在局部获得更理想的长效恒速释放，有利于伤口愈合或者缺损修复。

3虾青素在口腔医学中的应用研究

虾青素对口腔领域的多种疾病都有一定的作用。不少文献聚焦在对牙周炎的治疗。Lektemur Alpan[51]和H. Balci Yuce[52]等人发现虾青素灌胃可以减少实验性牙周炎大鼠的牙槽骨缺损。X. Dang等人将虾青素与静电纺丝制备的壳聚糖/聚乙烯醇/氧化石墨烯复合制成纳米纤维膜，在体外实验[53]和体内实验[50]中均显示出明显的抑制炎症和促进牙周组织再生作用。对于伴糖尿病的牙周炎，G. Bhattarai等人发现虾青素可以抑制糖尿病模式小鼠牙周组织中破骨细胞的形成，阻断了高血糖引发的人源牙

周膜细胞的氧化应激和生长抑制[54]。在口腔黏膜病中，Miyachi M等人发现虾青素可以改善口腔扁平苔藓细胞模型的炎性表达[55]。在口腔鳞癌领域，DuYuheng 等人认为虾青素可能部分通过促进肿瘤细胞铁死亡的通路与电离辐射产生协同治疗口腔鳞状细胞癌的作用[8]。

4总结与展望

各种研究表明，虾青素具有明显的抗氧化、抗炎和抗衰老特性，对多种疾病具有潜在的治疗作用。然而，一方面，虾青素相关的药物研究仍不够深入、相关机制尚不明确，同时也缺少大量长期的临床研究进一步明确其临床价值。另一方面，虾青素获得途径多样，但如何选择生物利用度更高的来源，开发更符合临床用途的靶向、缓释和负载材料，明确不同材料、药物与虾青素的相互作用，遴选具有协同作用的材料与药物，也需要进一步的研究。

参考资料

[ 1 ] Brendler T

， Williamson E M. Astaxanthin: How much is too  much? A safety review [J]. Phytother Res, 2019, 33(12): 3090-3111.

[ 2 ] Tang H, Zhang Y, Wang Q, et al. Astaxanthin attenuated ciga‐rette smoke extract-induced apoptosis via decreasing oxidative  DNA damage in airway epithelium[J]. Biomed Pharmacother,2023, 167: 115471.

[ 3 ] Nan B, Zhao Z, Jiang K, et al. Astaxanthine attenuates cisplatin  ototoxicity in vitro and protects against cisplatin-induced hear‐ing loss in vivo [J]. Acta Pharm Sin B, 2022, 12(1): 167-181.

[ 4 ] Janani R, Anitha RE, Divya P, et al. Astaxanthin ameliorates hy‐perglycemia induced inflammation via PI3K/Akt-NF-κB signal‐ing in ARPE-19 cells and diabetic rat retina[J]. Eur J Pharmacol,2022, 926: 174979.

[ 5 ] Xiong Z, Li Z, Sima X, et al. Astaxanthin reduces TBPHinduced neurobehavioral deficits in mice by the ROS-ERK1/2-FOS pathway[J]. Ecotoxicol Environ Saf, 2024, 281: 116674.

[ 6 ] Li H, Yuan Y, Zhang L, et al. Reprogramming Macrophage Po‐larization, Depleting ROS by Astaxanthin and ThioketalContaining Polymers Delivering Rapamycin for Osteoarthritis  Treatment[J]. Adv Sci (Weinh), 2024, 11(9): e2305363.

[ 7 ] Saini RK, Keum YS, Daglia M, et al. Dietary carotenoids in can‐cer chemoprevention and chemotherapy: A review of emerging  evidence[J]. Pharmacol Res, 2020. 157: 104830.

[ 8 ] Du Y, Shuai Y, Liu Z, et al. Astaxanthin Synergizes with Ioniz‐ing Radiation (IR) in Oral Squamous Cell Carcinoma (OSCC)[J]. Mol Biotechnol, 2024, 66(5): 1220-1228.

[ 9 ] Tanaka T, Makita H, Ohnishi M, et al. Chemoprevention of rat  oral carcinogenesis by naturally occurring xanthophylls, astaxan‐thin and canthaxanthin[J]. Cancer Res, 1995, 55(18): 4059-4064.

[10] Costanzo M, Cesi V, Prete E, et al. Krill oil reduces intestinal in‐flammation by improving epithelial integrity and impairing  adherent-invasive Escherichia coli pathogenicity[J]. Dig Liver  Dis, 2016, 48(1): 34-42.

[11] Zhang X, Zhao X, Hua Z, et al. ROS-triggered self-disintegrating and pH-responsive astaxanthin nanoparticles for regulating the  intestinal barrier and colitis[J]. Biomaterials, 2023, 292: 121937.

[12] Sun RL, Shang JC, Han RH, et al. Protective effect of astaxan‐thin on ANCA-associated vasculitis[J]. Int Immunopharmacol,2024, 132: 111928.

[13] Aras-Tosun D, Önder C, Akdoğan N, et al. Astaxanthin Enhances Gingival Wound Healing following High Glucose-Induced Oxi‐dative Stress[J]. Biomed Res Int, 2022, 2022: 4043105.

[14] Li MY, Sun L, Niu XT, et al. Astaxanthin protects  lipopolysaccharide-induced inflammatory response in Channa  argus through inhibiting NF-κB and MAPKs signaling pathways[J]. Fish Shellfish Immunol, 2019, 86: 280-286.

[15] Woo J, Lim JW, Kim H, Astaxanthin inhibits integrin α5 expres‐sion by suppressing activation of JAK1/STAT3 in Helico‐bacter pyloristimulated gastric epithelial cells[J]. Mol Med Rep,2023, 27(6): 127.

[16] Kang Y, Xu L, Dong J, et al. Programmed microalgae-gel pro‐motes chronic wound healing in diabetes[J]. Nat Commun, 2024,15(1): 1042.

[17] Liu A, He M, Liu C, et al. Prevention of Hypercholesterolemia  with "Liposomes in Microspheres" Composite Carriers: A Prom‐ising Approach for Intestinal-Targeted Oral Delivery of Astaxan‐thin[J]. J Agric Food Chem, 2024, 72(12): 6118-6132.

[18] Zhang C, Xu Y, Wu S, et al. Fabrication of astaxanthin-enriched  colon-targeted alginate microspheres and its beneficial effect on  dextran sulfate sodium-induced ulcerative colitis in mice[J].Int J  Biol Macromol, 2022, 205: 396-409.

[19] Gulzar S, Balange AK, Nagarajarao RC, et al. Microcapsules of  Shrimp Oil Using Kidney Bean Protein Isolate and κ -Carra‐geenan as Wall Materials with the Aid of Ultrasonication or  High-Pressure Microfluidization: Characteristics and OxidativeStability[J]. Foods, 2022, 11(10): 1431.

[20] Huang J, Zhang S, Liu D, et al. Preparation and characterization of  astaxanthin-loaded microcapsules stabilized by lecithin-chitosanalginate interfaces with layer-by-layer assembly method[J]. Int J  Biol Macromol, 2024, 268(Pt 1): 131909.

[21] Zhang X, Su W, Chen Y, et al. Bi-functional astaxanthin macromo‐lecular nanocarriers to alleviate dextran sodium sulfate-induced in‐flammatory bowel disease[J]. Int J Biol Macromol, 2024, 256(Pt 2): 128494.

[22] Binatti E, Zoccatelli G, Zanoni F, et al. Phagocytosis of  Astaxanthin-Loaded Microparticles Modulates TGFβ Produc‐tion and Intracellular ROS Levels in J774A. 1 Macrophages[J].Mar Drugs, 2021, 19(3): 163.

[23] Luo F, Wang S, Zhang X, et al. Extraction of Astaxanthin from  Haematococcus pluvialis and Preparation of Astaxanthin Lipo‐somes[J]. Molecules, 2024, 29(14): 3320.

[24] Wang S, Chen K, Liu G. Monoglyceride oleogels for lipophilic  bioactive delivery - Influence of self-assembled structures on  stability and in vitro bioaccessibility of astaxanthin[J]. Food  Chem, 2022, 375: 131880.

[25] Zhang K, Xiang Y, Zhong L, et al. Enhancing the emulsion prop‐erties and bioavailability of loaded astaxanthin by selecting the  reaction sequence of ternary conjugate emulsifiers in nanoemul‐sions[J]. Food Chem, 2024, 449: 139310.

[26] Ge Y, Jiang X, Peng W, et al. Preparation, characterization, and  stability of chitosan-tremella polysaccharide layer-by-layer en‐capsulated astaxanthin nanoemulsion delivery system[J]. Int J  Biol Macromol, 2024, 282(Pt 1): 136741.

[27] Jitpasutham S, Sinsomsak W, Chuesiang P, et al. Green active  coating from chitosan incorporated with spontaneous cinnamon  oil nanoemulsion: Effects on dried shrimp quality and shelf life[J]. Int J Biol Macromol, 2024, 262(Pt 2): 129711.

[28] Zhao Y, Wang Z, Liu S, et al. Lyoprotectant Formulation and  Optimization of the J-Aggregates Astaxanthin/BSA/Chitosan  Nanosuspension[J]. Biomolecules, 2023. 13(3): 496.

[29] Phothong N, Boontip T, Chouwatat P, et al. Preparation and  characterization of astaxanthin-loaded biodegradable polyhy‐droxybutyrate (PHB) microbeads for personal care and cosmetic  applications[J]. Int J Biol Macromol, 2024, 257(Pt 2): 128709.

[30] Heo Y, Shin SW, Kim DS, et al. Bioactive PCL microspheres  with enhanced biocompatibility and collagen production for  functional hyaluronic acid dermal fillers[J]. Biomater Sci, 2022,10(4): 947-959.

[31] Yang S, Wu Y, Cheng X, et al. Harnessing astaxanthin-loaded  diselenium cross-linked apotransferrin nanoparticles for the  treatment of secretory otitis media[J]. J Control Release, 2024,365: 398-411.

[32] Chang W, Lv X, Zhu J, et al. Multifunctional Nanotherapeutics  with Long-Acting Release against Macular Degeneration by Mini‐mally Invasive Administration[J]. ACS Nano, 2024 Jul 17. doi:10.1021/acsami.2c19570.

[33] Nurdianti L, Rusdiana T, Sopyan I, et al. Characteristic Com‐parison of an Intraoral Thin Film Containing Astaxanthin Nano‐emulsion Using Sodium Alginate and Gelatin Polymers[J]. Turk J Pharm Sci, 2021, 18(3): 289-295.

[34] Gu J, Chen Y, Tong L, et al. Astaxanthin-loaded polymer-lipid  hybrid nanoparticles (ATX-LPN): assessment of potential oto‐protective effects[J]. J Nanobiotechnology, 2020, 18(1): 53.

[35] Ma X, Zhang B, Ma N, et al. Unveiling the Mechanism of Alleviat‐ing Ischemia Reperfusion Injury via a Layered Double HydroxideBased Nanozyme[J]. ACS Appl Mater Interfaces, 2023 Mar 13.doi: 10.1021/acsami.2c19570.

[36] Monavari M, Homaeigohar S, Medhekar R, et al. A 3D-Printed  Wound-Healing Material Composed of Alginate DialdehydeGelatin Incorporating Astaxanthin and Borate Bioactive Glass  Microparticles[J]. ACS Appl Mater Interfaces. 2023 May 8. doi:10.1021/acsami.2c23252

[37] Veeruraj A, Liu L, Zheng J, et al. Evaluation of astaxanthin in‐corporated collagen film developed from the outer skin waste of  squid Doryteuthis singhalensis for wound healing and tissue re‐generative applications[J]. Mater Sci Eng C Mater Biol Appl,2019, 95: 29-42.

[38] Chae SY, Park R, Hong SW. Surface-mediated high antioxidant  and anti-inflammatory effects of astaxanthin-loaded ultrathin  graphene oxide film that inhibits the overproduction of intracel‐lular reactive oxygen species[J]. Biomater Res, 2022, 26(1): 30.

[39] Łupina K, Kowalczyk D, Kazimierczak W. Gum Arabic/Gelatin  and Water-Soluble Soy Polysaccharides/Gelatin Blend Films as  Carriers of Astaxanthin-A Comparative Study of the Kinetics of  Release and Antioxidant Properties[J]. Polymers (Basel), 2021,13(7): 1062

[40] Li P, Xu T, Dang X, et al. Improving astaxanthin-loaded chito‐san/polyvinyl alcohol/graphene oxide nanofiber membranes and  their application in periodontitis[J]. Int J Biol Macromol, 2024,258(Pt 2): 128980.

[41] Lektemur Alpan A, Çalışır M. The Effect of Two Different  Doses of Astaxanthin on Alveolar Bone Loss in an Experimental  Model of Periodontitis in Diabetic Rats[J]. J Vet Dent, 2022, 39(3): 224-233.

[42] Bhattarai G, So HS, Kieu TTT, et al. Astaxanthin Inhibits  Diabetes-Triggered Periodontal Destruction, Ameliorates Oxida‐tive Complications in STZ-Injected Mice, and Recovers Nrf2-Dependent Antioxidant System[J]. Nutrients, 2021, 13(10): 3575.

[43] Miyachi M, Matsuno T, Asano K, et al. Anti-inflammatory ef‐fects of astaxanthin in the human gingival keratinocyte line  NDUSD-1[J]. J Clin Biochem Nutr, 2015, 56(3): 171-178.

来源：本文摘自《口腔材料器械》杂志2025年第34卷第5期，仅作科普用途，内容版权归原作者所有，如侵权请联系删除。