虾青素的抗炎机制及其对多种疾病防治作用的研究进展

张建青, 牛钦, 陈莹, 欧阳杰, 思永玉

【作者机构】 昆明医科大学第二附属医院麻醉科
【分 类 号】 R977
【基    金】 云南省科技厅基础研究计划项目(202401AT070024) 昆明医科大学硕士研究生创新基金项目(2025S097)。
全文 参考文献 出版信息
虾青素的抗炎机制及其对多种疾病防治作用的研究进展

虾青素的抗炎机制及其对多种疾病防治作用的研究进展

张建青 牛 钦 陈 莹 欧阳杰 思永玉

昆明医科大学第二附属医院麻醉科,云南昆明 650106

[摘要] 虾青素作为一种天然红色脂溶性类胡萝卜素,广泛存在于微藻、酵母、虾蟹、三文鱼等生物中,具有显著的抗氧化、抗炎、抗增殖和抗凋亡特性。本文系统综述虾青素的抗炎作用机制及其在神经系统、胃肠道、糖尿病及其并发症、心血管、肝脏、肾脏、皮肤、眼科等疾病防治中的研究进展,简要阐述其通过PI3K/Akt、Nrf-2/HO-1、NF-κB、ERK1/2、p38 MAPK等信号通路介导的抗炎相关防治效应,为其深入研究、实际应用及临床转化提供参考。

[关键词] 虾青素;抗炎机制;信号通路;炎症相关疾病;临床应用

虾青素是叶黄素家族天然类胡萝卜素,化学名称为3,3’-二羟基-4,4’-二酮基-β,β’-胡萝卜素(C40H52O4,相对分子质量596.86),其分子结构中的不对称碳原子与长链共轭双键,是其强抗氧化及抗炎活性的结构基础[1]。天然虾青素主要来源于雨生红球藻(含量达细胞干重2%~4%)、红发夫酵母等,也存在于鲑鱼、磷虾等水生动物中,全反式结构使其生物活性高、安全性佳;合成虾青素多为顺反异构体混合物,生物利用度低且长期大量摄入可能有潜在健康影响[2-3]。其抗氧化能力是维生素E的550倍、维生素C的1 000倍,可高效清除活性氧(reactive oxygen species,ROS)、抑制脂质过氧化,同时兼具抗凋亡、免疫调节等功能[4]。随着剂型优化技术发展,其生物利用度与靶向性显著提升,在炎症相关疾病防治中的潜力备受关注。

1 虾青素在各种疾病中的抗炎作用

1.1 神经保护作用

虾青素可穿透血-脑屏障,靶向调控脑内炎症,发挥神经保护作用。在阿尔茨海默病中,其可降低神经炎症介质如神经胶质细胞原纤维酸性蛋白和肿瘤坏死因子-α水平,减轻脂质过氧化,改善认知功能[5-6]。二十二碳六烯酸酰化修饰的虾青素-二十二碳六烯酸在抑制神经炎症、减少β-淀粉样蛋白及磷酸化tau蛋白沉积方面的疗效优于游离虾青素,提示分子(及剂型)修饰是提升其生物活性的重要方向[7]。此外,氧化应激平衡调控是虾青素抗炎的核心关联通路,该通路与其他抗氧化剂的联合应用,为优化阿尔茨海默病病理进程干预方案提供新思路[8]。

对帕金森病,虾青素-二十二碳六烯酸通过线粒体通路及JNK、p38 MAPK信号通路抑制多巴胺能神经元凋亡,改善小鼠行为缺陷[9];游离虾青素可调控miR-7/SNCA轴抑制内质网应激,阻断帕金森病进展[10];MAPK信号通路抑制是其应对百草枯诱导帕金森病模型的关键机制[11]。乳铁蛋白修饰脂质体可提升虾青素脑穿透性与细胞摄取效率,通过抑制胶质细胞活化、强化抗氧化及抗炎效应,为帕金森病靶向治疗提供新策略[12]。

针对缺血性脑损伤,其通过激活Nrf-2/HO-1信号通路、调节NF-κB平衡,下调促炎性细胞因子表达,抑制氧化应激与神经元凋亡,保护血-脑屏障完整性,且其抗炎作用呈现一定剂量相关性,中等剂量下对脑组织炎症损伤的抑制效果更显著[13-16]。

综上所述,虾青素在神经退行性疾病及脑损伤中的抗炎作用具有通路多样性,分子及剂型改良与剂量优化是提升其临床应用潜力的核心抓手,但其组织特异性调控机制仍需进一步明确。

1.2 胃肠道保护作用

虾青素可针对性干预胃肠道疾病炎症进程,核心通过调控NF-κB及下游通路实现抗炎护膜效应。对非甾体抗炎药诱导的胃溃疡、新生儿坏死性小肠结肠炎及葡聚糖硫酸钠诱导的结肠炎,虾青素分别通过下调NF-κB/Caspase-3表达、抑制TLR4/NF-κB信号通路、阻断NF-κB/AP-1/MAPK信号通路发挥作用,且对结肠炎的改善呈剂量依赖性,纳米载体修饰后可通过靶向线粒体进一步提升疗效[17-20]。调节肠道菌群及短链脂肪酸水平、维持胃肠道稳态则拓展其抗炎作用的多维机制[21]。虾青素对胃肠道炎症的干预兼具针对性与广谱性,剂型改良可突破其生物利用度瓶颈,但其在慢性胃肠道疾病中的长期干预效果及与临床常规药物的协同作用,仍需更多临床数据支撑。

1.3 糖尿病及其并发症的保护作用

虾青素通过抗炎-抗氧化交互调控,改善糖尿病及并发症损伤。可调节NOX4、Nrf2等信号通路,修复糖尿病心肌病和肾病的炎症与氧化应激损伤[22];针对糖尿病视网膜病变,激活Nrf2/Keap1信号通路并调控ROS-PI3K/Akt-NF-κB级联,抑制炎症与凋亡,同时可改善糖尿病相关牙周破坏、认知障碍及妊娠糖尿病症状[23-27]。对糖尿病肾病,虾青素不仅能减轻线粒体氧化应激,还可抑制非酶糖基化终末产物诱导的细胞紊乱[28]。体现其多维度抗炎护肾效能。虾青素的抗炎-抗氧化协同效应是其改善糖尿病并发症的核心优势,但其在不同并发症中的最优剂量、疗程差异尚未明确,联合抗氧化剂的抗炎干预方案值得进一步探索。

1.4 镇痛效果

虾青素具有多途径、多靶点抗炎镇痛活性,可覆盖炎性疼痛、神经性疼痛等多种类型。炎性疼痛中,其通过抑制COX-2、p38 MAPK信号通路及调控Nrf2/HO-1信号通路发挥作用,与塞来昔布联用可产生协同效应[29-32]。神经性疼痛及慢性盆腔疼痛中,NF-κB、ERK1/2信号通路抑制与肠道菌群调节是关键机制[33-36]。此外,虾青素可通过抑制NLRP3炎症小体缓解纤维肌痛相关疼痛及抑郁症状,还能调控ERK、Akt信号通路减轻脊髓损伤后疼痛[37-39]。虾青素的镇痛作用与抗炎机制深度绑定,且适用疼痛类型广泛,为慢性疼痛的非甾体类药物替代干预提供新方向,但其在临床疼痛管理中的定位仍需大样本量研究验证。

1.5 心血管的保护作用

虾青素在动脉粥样硬化、心肌损伤等心血管疾病中展现显著抗炎保护作用,核心依赖TLR4/NF-κB、氧化应激相关通路调控。其可减轻异丙肾上腺素诱导的心肌损伤,缓解慢性间歇性低压缺氧所致右心室肥厚,并通过抑制自噬、铁死亡及炎症反应,改善多柔比星、PM2.5诱导的心肌损伤[40-43]。在动脉粥样硬化模型中,虾青素通过circTPP2/miR-3073b-5p/ABCA1信号通路调节脂质代谢与炎症状态,保护心血管功能[44-45]。线粒体功能保护与炎症相关蛋白表达调控则进一步强化其效能,现有研究凸显虾青素在心血管炎症干预中的广谱性,但其在不同心血管疾病中的通路特异性差异,为精准干预方案的制订提供研究方向,剂量优化与联合用药是未来探索重点[46-47]。

1.6 肝脏的保护作用

针对药物性肝损伤,虾青素可下调肿瘤坏死因子-α等炎症因子,激活Nrf2/HO-1信号通路,缓解5-氟尿嘧啶、对乙酰氨基酚诱导的肝脏毒性[48-49]。对真菌毒素诱导损伤,可抑制白细胞介素-6、白细胞介素-1β释放,调节内质网应激与线粒体平衡[50]。对代谢性肝病,可通过调控AMPK/Nrf2轴、抑制miR-21等,减轻非酒精性脂肪肝及高脂饮食诱导的肝脏脂肪变性[51-52]。在酒精性肝损伤中,虾青素可通过修复线粒体中的氧化还原平衡与钙稳态,激活Nrf2/ARE信号通路减少脂质过氧化产物生成,发挥抗炎保护作用,纳米载体制剂能强化肝组织靶向抗炎与抗氧化效果[53-55]。此外,虾青素可通过调节p38 MAPK及PI3K/Akt信号通路,抑制高糖诱导的肝细胞炎症与凋亡,在自身免疫性肝炎中还能通过调控CD8+T淋巴细胞功能及炎症因子分泌,减轻肝组织免疫炎症损伤[56-57]。综上所述,虾青素对肝损伤的干预覆盖多类型诱因,通路调控具有针对性,剂型改良是提升其临床应用潜力的重要方向。

1.7 肾脏的保护作用

虾青素凭借显著的抗炎活性,对多种诱因引发的肾损伤发挥保护作用,其机制涉及多条信号通路的调控及炎症反应的多环节抑制。缺血再灌注性肾损伤中,可降低肾组织炎症水平,减少凋亡与组织损伤[58]。对造影剂诱导的急性肾损伤,通过SIRT1/p53信号通路及抑制ROS/NLRP3轴,减轻炎症与氧化应激[59-60]。对顺铂、锂中毒性肾损伤,分别调控MALAT-1/miR-146a/NF-κB信号通路及NF-κB/p65活性,改善肾功能,同时可缓解高糖饮食、阿特拉津及烧伤诱导的肾损伤,其多靶点抗炎特性为复杂诱因所致肾损伤的干预提供新思路,但不同肾损伤类型的最优干预剂量与疗程仍需进一步验证[61-65]。

1.8 皮肤保护作用

急性皮肤创伤中,虾青素抑制炎症细胞浸润及肿瘤坏死因子-α、白细胞介素-6表达,促进M2型巨噬细胞极化,加速创面愈合[66]。对紫外线B诱导的皮肤损伤,可清除ROS、抑制角质形成细胞凋亡,离子液体脂质体修饰后,通过调控TGF-β1/smad信号通路增强抗炎效能[67-68]。此外,可促进Nrf2核转位,缓解高糖诱导的成纤维细胞衰老,同时改善皮肤屏障功能,发挥抗衰作用[69-70]。综上所述,虾青素对皮肤的保护作用兼具抗炎、抗氧化与修复特性,适配急性损伤、光老化等多种场景,局部靶向剂型的开发是其拓展皮肤护理与治疗应用的关键。

1.9 眼保护作用

虾青素对干眼症具有显著抗炎护眼效果,可抑制高迁移率组蛋白B1、肿瘤坏死因子-α、白细胞介素-1β表达,调控PI3K/Akt信号通路以减轻眼表上皮炎症[71]。同时激活Keap1/Nrf2/HO-1信号通路,协同抑制炎症与氧化应激,保护角膜上皮细胞活力,还可通过强化SLC7A11/GPX4信号通路抑制角膜上皮细胞铁死亡[72];高亲和力脂质体剂型可提升角膜亲和力,进一步强化抗炎效果[73]。目前虾青素眼部应用研究集中于干眼症,其在结膜炎、角膜炎等其他眼部炎症疾病中的潜力仍需进一步探索。

1.10 虾青素抗炎活性的临床证据

多项随机对照试验研究证实虾青素的抗炎效能,如2型糖尿病患者每日补充10 mg虾青素,可下调炎症相关miRNA及白细胞介素-6、肿瘤坏死因子-α表达,改善代谢指标[74]。社区获得性肺炎患者每日12 mg虾青素联合抗生素治疗,可显著降低促炎性细胞因子水平,改善疾病严重程度评分[75]。心力衰竭患者每日20 mg虾青素干预8周,可抑制氧化应激与全身炎症,实现对心血管系统的保护作用[76]。针对职业消防员的研究显示,每日补充12 mg虾青素连续4周,能减轻增量最大运动测试中的炎症应答,抑制灭火作业时白细胞介素-1β、皮质醇及尿酸水平的升高,进而改善心血管健康,为高应激职业群体的炎症管理提供新思路[77]。在口腔领域,含虾青素牙科凝胶可缩短义齿适应时间,降低口腔炎风险[78];口腔黏膜下纤维化患者每日服用10 mg虾青素(分两次),可改善张口度及烧灼感[79]。在皮肤健康方面,每日4 mg虾青素补充4周可改善皮肤表面成分,实现年轻化效果[80]。Ng等[81]研究证实,现有临床数据支持每日3~6 mg虾青素补充对皮肤健康的益处,尤其适用于光老化皮肤的改善。此外,每日8 mg虾青素可缓解多囊卵巢综合征炎症状态[82]。

临床研究初步验证虾青素在多系统炎症干预中的安全性与有效性,但现有数据仍存在样本量小、场景局限等问题,难以形成统一临床应用指南。

2 局限性

尽管虾青素的抗炎作用在基础实验中得到充分验证,但其临床研究及转化仍存在以下局限性:①临床研究数量少、样本量小,多聚焦于健康群体或轻症患者,缺乏重症疾病大样本量长期随访数据,难以充分验证临床有效性与安全性;②研究设计异质性大,剂量、疗程、给药途径不一致,无法横向比较以确定最优方案;③作用机制尚未完全阐明,组织特异性调控、与其他物质协同效应及代谢产物活性仍不明确;④自身理化性质局限(水溶性差、稳定性低),改良剂型的临床研究及转化处于初级阶段;⑤文献检索存在遗漏,非英文及未公开发表的相关研究未纳入,影响结论全面性。

3 小结与展望

虾青素凭借多靶点、多通路协同抗炎特性,核心通过调控NF-κB、MAPK、Nrf2/HO-1等关键信号通路,在多系统炎症相关疾病中展现广泛保护潜力,天然虾青素及其分子修饰、改良剂型的生物利用度与效能更具优势。现有研究为临床转化奠定基础,但仍需突破临床研究规模、机制解析及产业化技术等瓶颈。

未来可聚焦于以下3个方面的研究:①开展大样本量、多中心长期临床试验,明确摄取方式、量-效关系及联合抗炎方案;②借助组学技术解析抗炎分子网络,挖掘虾青素对各类炎症相关疾病的特异性靶点;③优化提取与剂型技术,开发低成本靶向制剂,探索协同作用以拓展应用场景。虾青素凭借天然安全性与广谱抗炎活性,有望成为炎症相关疾病防治的新型候选物质和天然先导化合物,具有重要研究价值与广阔的应用前景。

利益冲突声明:所有作者均声明不存在利益冲突。

[参考文献]

[1] Ambati R R,Phang S M,Ravi S,et al. Astaxanthin:sources,extraction,stability,biological activities and its commercial applications-a review [J]. Mar Drugs,2014,12(1):128-152.

[2] Higuera-Ciapara I,Félix-Valenzuela L,Goycoolea F M.Astaxanthin:a review of its chemistry and applications [J].Crit Rev Food Sci Nutr,2006,46(2):185-196.

[3] Guerin M,Huntley M E,Olaizola M. Haematococcus astaxanthin:applications for human health and nutrition [J].Trends Biotechnol,2003,21(5):210-216.

[4] Pashkow F J,Watumull D G,Campbell C L. Astaxanthin:a novel potential treatment for oxidative stress and inflammation in cardiovascular disease [J]. Am J Cardiol,2008,101(10A):58D-68D.

[5] Chang M X,Xiong F. Astaxanthin and its effects in inflammatory responses and inflammation-associated diseases:recent advances and future directions [J]. Molecules,2020,25(22):5342.

[6] Medzhitov R. Inflammation 2010:new adventures of an old flame [J]. Cell,2010,140(6):771-776.

[7] Wang X,Song Y,Cong P,et al. Docosahexaenoic acid-acylated astaxanthin monoester ameliorates amyloid-β pathology and neuronal damage by restoring autophagy in Alzheimer’s disease models [J]. Mol Nutr Food Res,2024,68(2):e2300414.

[8] Balendra V,Singh S K. Therapeutic potential of astaxanthin and superoxide dismutase in Alzheimer’s disease [J].Open Biol,2021,11(6):210013.

[9] Wang C,Shi H,Xu J,et al. Docosahexaenoic acid-acylated astaxanthin ester exhibits superior performance over non-esterified astaxanthin in preventing behavioral deficits coupled with apoptosis in MPTP-induced mice with Parkinson’s disease [J]. Food Funct,2020,11(9):8038-8050.

[10] Shen D F,Qi H P,Ma C,et al. Astaxanthin suppresses endoplasmic reticulum stress and protects against neuron damage in Parkinson’s disease by regulating miR-7/SNCA axis [J]. Neurosci Res,2021,165:51-60.

[11] Wang L,Lu K,Lou X,et al. Astaxanthin ameliorates dopaminergic neuron damage in paraquat-induced SH-SY5Y cells and mouse models of Parkinson’s disease [J].Brain Res Bull,2023,202:110762.

[12] Nguyen T D,Khanal S,Lee E,et al. Astaxanthin-loaded brain-permeable liposomes for Parkinson’s disease treatment via antioxidant and anti-inflammatory responses [J]. J Nanobiotechnol,2025,23(1):78.

[13] Yang B,Zou M,Zhao L,et al. Astaxanthin attenuates acute cerebral infarction via Nrf-2/HO-1 pathway in rats [J].Curr Res Transl Med,2021,69(2):103271.

[14] Taheri F,Sattari E,Hormozi M,et al. Dose-dependent effects of astaxanthin on ischemia/reperfusion induced brain injury in MCAO model rat [J]. Neurochem Res,2022,47(6):1736-1750.

[15] Park J H,Lee T K,Kim D W,et al. Astaxanthin confers a significant attenuation of hippocampal neuronal loss induced by severe ischemia-reperfusion injury in gerbils by reducing oxidative stress [J]. Mar Drugs,2022,20(4):267.

[16] Xue Y,Qu Z,Fu J,et al. The protective effect of astaxanthin on learning and memory deficits and oxidative stress in a mouse model of repeated cerebral ischemia/reperfusion [J]. Brain Res Bull,2017,131:221-228.

[17] Aly M H,Said A K,Farghaly A M,et al. Protective effect of astaxanthin on indomethacin-induced gastric ulcerations in mice [J]. Naunyn Schmiedebergs Arch Pharmacol,2024,397(12):9897-9907.

[18] Zhang X,Luo Y,Gu R,et al. Astaxanthin alleviates inflammatory response in neonatal necrotizing enterocolitis rats by regulating NOD2/TLR4 pathway [J]. Gastroent Res Pract,2023,2023:6078308.

[19] Sakai S,Nishida A,Ohno M,et al. Astaxanthin,a xanthophyll carotenoid,prevents development of dextran sulphate sodium-induced murine colitis [J]. J Clin Biochem Nutr,2019,64(1):66-72.

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

[21] Yasuda R,Kamada K,Murakami T,et al. Astaxanthin attenuated the stress-induced intestinal motility disorder via altering the gut microbiota [J]. Int J Vitam Nutr Res,2023,93(5):427-437.

[22] El-Nasr N M E A,Hussien Y A,El-Baset M A,et al.Astaxanthin mitigates diabetic cardiomyopathy and nephropathy in HF/HFr/STZ diabetic rats via modulating NOX4,fractalkine,Nrf2,and AP-1 pathways [J]. Sci Rep,2025,15(1):20199.

[23] Fang J,Bai W,Yang L. Astaxanthin inhibits oxidative stress and apoptosis in diabetic retinopathy [J]. Acta Histochemica,2023,125(6):152069.

[24] Janani R,Anitha R E,Divya P,et al. Astaxanthin ameliorates hyperglycemia induced inflammation via PI3K/Akt-NF-κB signaling in ARPE-19 cells and diabetic rat retina [J]. Eur J Pharmacol,2022,926:174979.

[25] Bhattarai G,So H,Kieu T T T,et al. Astaxanthin inhibits diabetes-triggered periodontal destruction,ameliorates oxidative complications in STZ-injected mice, and recovers Nrf2-dependent antioxidant system [J]. Nutrients,2021,13(10):3575.

[26] Chen Y,Tang J,Zhang Y,et al. Astaxanthin alleviates gestational diabetes mellitus in mice through suppression of oxidative stress [J]. Naunyn Schmiedebergs Arch Pharmacol,2020,393(12):2517-2527.

[27] Saleh S A,Hanna G S,El-Naby S H,et al. Astaxanthin attenuates DNA fragmentation and cognitive decline in type 2 diabetic rats [J]. Sci Rep,2025,15(1):20122.

[28] Naito Y,Uchiyama K,Handa O,et al. Therapeutic potential of astaxanthin in diabetic kidney disease [J]. Adv Exp Med Biol,2021,1261:239-248.

[29] Cai L,Cai Y,Yu R,et al. Synergistic analgesic effects of astaxanthin combined with celecoxib on a mouse bone cancer pain model:from behavioral validation to target prediction [J]. Int Immunopharmacol,2025,166:115564.

[30] Chida R,Takeda M. Astaxanthin alleviates inflammatory mechanical hyperalgesia by reducing hyperexcitability of trigeminal nociceptive secondary neurons:potential as an NSAID alternative [J]. Molecules,2025,30(18):3664.

[31] Zhao L,Tao X,Wan C,et al. Astaxanthin alleviates inflammatory pain by regulating the p38 mitogen-activated protein kinase and nuclear factor-erythroid factor 2-related factor/heme oxygenase-1 pathways in mice [J]. Food Funct,2021,12(24):12381-12394.

[32] Kuedo Z,Sangsuriyawong A,Klaypradit W,et al. Effects of astaxanthin from litopenaeus vannamei on carrageenaninduced edema and pain behavior in mice [J]. Molecules,2016,21(3):382.

[33] Zhao L,Tao X,Song T. Astaxanthin alleviates neuropathic pain by inhibiting the MAPKs and NF-κB pathways [J]. Eur J Pharmacol,2021,912:174575.

[34] Li J,Dong D,Sun Y,et al. Astaxanthin alleviates spinal nerve ligation-induced neuropathic pain by modulating propionic acid levels [J]. Phytomedicine,2025,139:156448.

[35] Jiang J,Xiao F,Yang L,et al. Protective effect of astaxanthin on chronic prostatitis/chronic pelvic pain syndrome in rat through modulating NF-κB signaling pathway [J]. Transl Androl Urol,2024,13(9):1971-1983.

[36] Liu Y,Xie W,Xi P,et al. Astaxanthin alleviates chronic prostatitis/chronic pelvic pain syndrome by increasing colonization of Akkermansia muciniphila in the intestine [J]. Phytomedicine,2024,123:155249.

[37] Zhao L,Tao X,Wang K,et al. Astaxanthin alleviates fibromyalgia pain and depression via NLRP3 inflammasome inhibition [J]. Biomed Pharmacother,2024,176:116856.

[38] Fakhri S,Dargahi L,Abbaszadeh F,et al. Effects of astaxanthin on sensory-motor function in a compression model of spinal cord injury:involvement of ERK and Akt signalling pathway [J]. Eur J Pain,2019,23(4):750-764.

[39] Fakhri S,Dargahi L,Abbaszadeh F,et al. Astaxanthin attenuates neuroinflammation contributed to the neuropathic pain and motor dysfunction following compression spinal cord injury [J]. Brain Res Bull,2018,143:217-224.

[40] Zaafan M A, Abdelhamid A M. The cardioprotective effect of astaxanthin against isoprenaline-induced myocardial injury in rats:involvement of TLR4/NF-κB signaling pathway [J]. Eur Rev Med Pharmacol Sci,2021,25(11):4099-4105.

[41] Pena E,El Alam S,Gonzalez C,et al. Astaxanthin supplementation effects in right ventricle of rats exposed to chronic intermittent hypobaric hypoxia [J]. Antioxidants,2024,13(10):1269.

[42] Yin B,Ren J,Liu X,et al. Astaxanthin mitigates doxorubicin-induced cardiotoxicity via inhibiting ferroptosis and autophagy:a study based on bioinformatic analysis and in vivo/vitro experiments [J]. Front Pharmacol,2025,16:1524448.

[43] Ren J,Yin B,Guo Z,et al. Astaxanthin alleviates PM2.5-induced cardiomyocyte injury via inhibiting ferroptosis [J].Cell Mol Biol Lett,2023,28(1):95.

[44] Khodir S A,Sweed E,Gadallah M,et al. Astaxanthin attenuates cardiovascular dysfunction associated with deoxycorticosterone acetate-salt-induced hypertension in rats [J]. Clin Exp Hypertens,2022,44(4):382-395.

[45] Zhang Z,Qiu Y,Li W,et al. Astaxanthin alleviates foam cell formation and promotes cholesterol efflux in Ox-LDL-induced RAW264.7 cells via circTPP2/miR-3073b-5p/ABCA1 pathway [J]. Molecules,2023,28(4):1701.

[46] Krestinin R R,Kobyakova M I,Baburina Y L,et al. Astaxanthin reduces H2O2-and doxorubicin-induced cardiotoxicity in H9c2 cardiomyocyte cells [J]. Biochemistry,2024,89(10):1823-1833.

[47] Baburina Y,Krestinin R,Fedorov D,et al. The improvement of functional state of brain mitochondria with astaxanthin in rats after heart failure [J]. Int J Mol Sci,2023,24(1):31.

[48] Öztürk Y,Öztürk M,Dörtbudak M B,et al. Astaxanthin mitigates 5-fluorouracil-induced hepatotoxicity and oxidative stress in male rats [J]. Nutrients,2025,17(7):1230.

[49] Cai X,Hua S,Deng J,et al. Astaxanthin activated the Nrf2/HO-1 pathway to enhance autophagy and inhibit ferroptosis,ameliorating acetaminophen-induced liver injury [J]. ACS Appl Mater Interfaces,2022,14(38):42887-42903.

[50] Zou Y,Zhang S,Yang J,et al. Protective effects of astaxanthin on ochratoxin a-induced liver injury:effects of endoplasmic reticulum stress and mitochondrial fissionfusion balance [J]. Toxins,2024,16(2):68.

[51] Li Y,Liu J,Ye B,et al. Astaxanthin alleviates nonalcoholic fatty liver disease by regulating the intestinal flora and targeting the AMPK/Nrf2 signal axis [J]. J Agr Food Chem,2022,70(34):10620-10634.

[52] Shatoor A S,Al Humayed S,Almohiy H M. Astaxanthin attenuates hepatic steatosis in high-fat diet-fed rats by suppressing microRNA-21 via transactivation of nuclear factor erythroid 2-related factor 2 [J]. J Physiol Biochem,2022,78(1):151-168.

[53] Wang P,Zheng X,Du R,et al. Astaxanthin protects against alcoholic liver injury via regulating mitochondrial redox balance and calcium homeostasis [J]. J Agric Food Chem,2023,71(49):19531-19550.

[54] Lv Y,Hao S,Wang Y,et al. Hepatocytes and mitochondria dual-targeted astaxanthin WPI-SCP nanoparticles for the alleviation of alcoholic liver injury [J]. Int J Biol Macromol,2025,285:137992.

[55] Che T,Song Y,Su W,et al. Hepatic parenchymal cell and mitochondrial-targeted astaxanthin nanocarriers for relief of high fat diet-induced nonalcoholic fatty liver disease [J]. Food Funct,2023,14(6):2908-2920.

[56] Liao Z,He X,Chen A,et al. Astaxanthin attenuates glucose-induced liver injury in largemouth bass:role of p38MAPK and PI3K/Akt signaling pathways [J]. Cell Biosci,2024,14(1):122.

[57] He Y,Ding M,Zhang J,et al. Astaxanthin alleviates autoimmune hepatitis by modulating CD8+ T cells:insights from mass cytometry and single-cell RNA sequencing analyses [J]. Adv Sci(Weinh),2024,11(30):e2403148.

[58] Qiu X,Fu K,Zhao X,et al. Protective effects of astaxanthin against ischemia/reperfusion induced renal injury in mice [J]. J Transl Med,2015,13(1):28.

[59] Gao D,Wang H,Xu Y,et al. Protective effect of astaxanthin against contrast-induced acute kidney injury via SIRT1-p53 pathway in rats [J]. Int Urol Nephrol,2019,51(2):351-358.

[60] Song L,Yao S,Zheng D,et al. Astaxanthin attenuates contrast-induced acute kidney injury in rats via ROS/NLRP3 inflammasome [J]. Int Urol Nephrol,2022,54(6):1355-1364.

[61] Shalaby A M,Keshk W A,Shalaby R H,et al. The possible role of astaxanthin in cisplatin-induced nephrotoxicity in rats:interplay between non-coding RNA,redox state,inflammation,and ferroptosis:a histological,immunohistochemical,and biochemical study [J]. J Mol Histol,2026,57(1):56.

[62] Erbaş E,Üstündağ H,Öztürk E,et al. Astaxanthin treatment reduces kidney damage and facilitates antioxidant recovery in lithium-intoxicated rats [J]. Toxicon,2024,241:107664.

[63] Soliman M M,Alotaibi K S,Albattal S B,et al. Ameliorative impacts of astaxanthin against atrazine-induced renal toxicity through the modulation of ionic homeostasis and Nrf2 signaling pathways in mice [J]. Toxicol Res,2024,13(3):tfae71.

[64] Guo S,Guo L,Fang Q,et al. Astaxanthin protects against early acute kidney injury in severely burned rats by inactivating the TLR4/MyD88/NF-κB axis and upregulating heme oxygenase-1 [J]. Sci Rep,2021,11(1):6679.

[65] Joubert M B V,Ingaramo P I,Collins P,et al. Astaxanthin improves lipotoxicity,lipid peroxidation and oxidative stress in kidney of sucrose-rich diet-fed rats [J]. J Nutr Biochem,2025,135:109779.

[66] Gao H,Zheng H. Astaxanthin expedites the healing of acute skin wounds in rats by facilitating M2 macrophage polarization and enhancing collagen secretion [J]. Disc Med,2024,36(185):1180.

[67] Chung B Y,Park S H,Yun S Y,et al. Astaxanthin protects ultraviolet b-induced oxidative stress and apoptosis in human keratinocytes via intrinsic apoptotic pathway [J]. Ann Dermatol,2022,34(2):125-131.

[68] Lu B,Ruan B,Zhang J,et al. Potential antioxidant and anti-inflammatory effects of astaxanthin ionic liquid liposomes [J]. ACS Appl Bio Mater,2025,8(4):3052-3060.

[69] Tang L J,Fan L H,Wang J R,et al. Effect and mechanism of astaxanthin on the aging of high glucose-treated human skin fibroblasts [J]. Zhonghua Shao Shang Yu Chuang Mian Xiu Fu Za Zhi,2025,41(11):1101-1110.

[70] Liu S,Manabe Y,Sugawara T. Oral administration of astaxanthin mitigates chronological skin aging in mice [J].Biosci Biotechnol Biochem,2025,89(4):612-621.

[71] Li H,Li J,Hou C,et al. The effect of astaxanthin on inflammation in hyperosmolarity of experimental dry eye model in vitro and in vivo [J]. Exp Eye Res,2020,197:108113.

[72] Liu Z,Li Y,Bao J,et al. Astaxanthin ameliorates benzalkonium chloride-induced dry eye disease through suppressing inflammation and oxidative stress via Keap1-Nrf2/HO-1 signaling pathways [J]. Animal Model Exp Med,2025,8(6):1056-1079.

[73] Shimokawa T,Fukuta T,Inagi T,et al. Protective effect of high-affinity liposomes encapsulating astaxanthin against corneal disorder in the in vivo rat dry eye disease model [J]. J Clin Biochem Nutr,2020,66(3):224-232.

[74] Sharifi-Rigi A,Zal F,Aarabi M H,et al. Astaxanthin modulates inflammation in type 2 diabetes via regulation of micrornas,lysophosphatidylcholine,and α-hydroxybutyrate [J]. Int J Endocrinol,2025,2025:5878361.

[75] Youssef F M,Ateyya H,Hanna Samy A E,et al. The antiinflammatory and antioxidant effects of astaxanthin as an adjunctive therapy in community-acquired pneumonia:a randomized controlled trial [J]. Front Pharmacol,2025,16:1621308.

[76] Mohammadi S G,Feizi A,Bagherniya M,et al. The effect of astaxanthin supplementation on inflammatory markers,oxidative stress indices,lipid profile,uric acid level,blood pressure,endothelial function,quality of life,and disease symptoms in heart failure subjects [J]. Trials,2024,25(1):518.

[77] Gonzalez D E,Dickerson B L,Johnson S E,et al. Impact of astaxanthin supplementation on markers of cardiometabolic health and tactical performance among firefighters [J]. J Int Soc Sports Nutr,2024,21(1):2427751.

[78] Kosyreva T F,Samoylova M B,Voeykova O V,et al. The effect of astaxanthin on the adaptation of the oral mucosa to a removable denture [J]. Stomatologiya,2022,101(1):17.

[79] Perumal E,Patil S,Karobari M I. Efficacy and safety of astaxanthin in the management of oral submucous fibrosis:a preliminary randomized controlled trial [J]. Cureus,2024,16(2):e54667.

[80] Chalyk N E,Klochkov V A,Bandaletova T Y,et al. Continuous astaxanthin intake reduces oxidative stress and reverses age-related morphological changes of residual skin surface components in middle-aged volunteers [J].Nutr Res,2017,48:40-48.

[81] Ng Q X,De Deyn M L Z Q,Loke W,et al. Effects of astaxanthin supplementation on skin health:a systematic review of clinical studies [J]. J Diet Suppl,2021,18(2):169-182.

[82] Jabarpour M,Amidi F,Aleyasin A,et al. Randomized clinical trial of astaxanthin supplement on serum inflammatory markers and ER stress-apoptosis gene expression in PBMCs of women with PCOS [J]. J Cell Mol Med,2024,28(14):e18464.

Research progress on anti-inflammatory mechanism of astaxanthin and its preventive and therapeutic effects on various diseases

ZHANG Jianqing NIU Qin CHEN Ying OUYANG Jie SI Yongyu

Department of Anesthesiology, the Second Affiliated Hospital of Kunming Medical University, Yunnan Province,Kunming 650106, China

[Abstract] Astaxanthin as a natural red fat-soluble carotenoid, is widely found in microalgae, yeast, shrimp and crabs,salmon, and other organisms, and possesses notable antioxidant, anti-inflammatory, anti-proliferative, and antiapoptotic properties. This article systematically reviews anti-inflammatory action mechanisms of astaxanthin and its research progress in the prevention and treatment of nervous system, gastrointestinal tract, diabetes and its complications,cardiovascular, liver, kidney, skin, ophthalmology and other diseases, briefly describes its anti-inflammatory related preventive and therapeutic effects mediated through signaling pathways such as PI3K/Akt, Nrf-2/HO-1, NF-κB, ERK1/2,and p38 MAPK, providing a reference for further research, practical application, and clinical translation.

[Key words] Astaxanthin; Anti-inflammatory mechanisms; Signaling pathways; Inflammation related diseases; Clinical application

[中图分类号] R977

[文献标识码] A

[文章编号] 1673-7210(2026)08(c)-0187-07

DOI:10.20047/j.issn1673-7210.26012333

[基金项目] 云南省科技厅基础研究计划项目(202401AT070024);昆明医科大学硕士研究生创新基金项目(2025S097)。

[通信作者] 思永玉(1972.1-),男,博士,主任医师;研究方向:围手术期心血管并发症的防治。

(收稿日期:2026-01-31)

(修回日期:2026-03-03)

X