关键词
新型冠状病毒肺炎的病原体是严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)。SARS-CoV-2传播迅速,致死率高,迫切需要寻找安全、有效的治疗药物。天然化合物中的生物活性成分在近二十年来的病毒防控事件中发挥了一定的作用,这为COVID-19的预防和治疗提供了思路。姜黄素是姜黄的主要活性成分,具有降血脂、抗凝、抗氧化、利胆以及抗癌等作
姜黄素对猪瘟病毒、马立克病毒、人巨细胞病毒、人类免疫缺陷病毒以及呼吸道流感病毒等均有作
SARS-CoV-2通过刺突蛋白(S蛋白)与人体细胞表面的ACE2蛋白结合进入细
RNA依赖性RNA聚合酶(RdRp)和主要蛋白酶(MPro;也称为3c样蛋白酶)是SARS-CoV-2复制的关键
ACE是血管紧张素II(AngII)生成的关键酶,表达于细胞表

图1 姜黄素调节ACE相关通路
AngII刺激血管紧张素AT1受体激活相应的信号通路是SARS-CoV-2感染引发病理后果的基
血管紧张素AT1受体与AngII的结合也触发了整合素和金属蛋白酶17(ADAM17)的激活,ADAM17可激活EGFR及其通路,引起sIL-6R和肿瘤坏死因子-α(TNF-α)释放。姜黄素被证明可以通过miR145抑制ADAM17的活性,从而抑制EGFR介导的信号传导改善COVID-1
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SARS-CoV-2被机体免疫细胞上的受体识别后,通过一系列信号转导,释放大量细胞因子,从而激活更多的免疫细胞来参与病毒的清除,以至于越来越多的免疫细胞和细胞因子聚集引发细胞因子风暴。一旦形成细胞因子风暴,免疫系统不一定能杀死病毒,但是肯定会杀死大量正常肺细胞,严重破坏肺的换气功能,患者会呼吸衰竭,直至缺氧死
Liu Z
SARS-CoV-2感染II型肺泡(ATII)导致肺泡ATII细胞的死亡和供血不足,使再生气体交换障碍。大量细胞死亡和炎症导致弥漫性肺泡损伤。反复感染、细胞死亡和进行性的组织损伤促进ARDS的发展。姜黄素在炎症性肺损伤模型中证实对肺泡ATII细胞具有保护作
骨髓来源的抑制细胞水平与COVID-19的严重程度有
综上,姜黄素具有改善SARS-CoV-2对靶细胞和组织的损伤作用。
临床和临床前研究显示姜黄素几乎没有任何明显的毒性作用。Burgos-Mor′on提出,姜黄素副作用包括DNA损伤,诱导活性氧产生,抑制药物代谢
姜黄素可以干预SARS-CoV-2进入宿主细胞,控制病毒复制和通过分子级联反应调节COVID-19的病理生理反应。尽管没有直接的证据(体外和体内实验)证明姜黄素对SARS-CoV-2有效,但先前的实验证据表明其在呼吸系统疾病(包括流感和其他冠状病毒感染)、炎症性疾病和凝血病均有效,因此,其可以作为治疗COVID-19的候选药物之一。姜黄素保护和预防器官组织损伤的能力以及改善免疫细胞的功能将为COVID-19患者的健康带来益处。概括姜黄素抗SARS-CoV-2感染的潜在作用靶标,可为其临床研究提供重要的理论依据。本课题组长期从事姜黄素抗酒精性肝损伤的研究,已发现其肝保护的相关作用机制,并与厦门大学附属第一医院检验科合作建立xMAP液态芯片多重快速检测新冠病毒(2019-nCoV)和儿童呼吸道感染冠状病毒NL63、-HKU1、-OC43、-229E、HMPV、HBoV的检测法,因此姜黄素抗新型冠状病毒肺炎潜在机制的研究也将成为本课题组接下来研究的方向。
参考文献
刘红艳,王海燕,叶 松等.姜黄素药理作用及其机制研究进展[J].中国现代医学杂志,2012,22(6):48-51. [百度学术]
范世珍,王文杰,于波海.姜黄素抗病毒作用研究进展[J].现代中西医结合杂志,2020,29(24):2734-2736. [百度学术]
高 雅,李晓晗,孙睿聪,等.姜黄素对猪瘟病毒复制的抑制作用[J].畜牧与兽医,2021,53(6):116-121. [百度学术]
冯 春,杨 帆,乔丹丹等.姜黄素抑制马立克氏病病毒在CEF细胞中的复制[J].中国动物传染病学报,2020,28(2):72-79. [百度学术]
贾阳杰,吕亚丽,刘丽宏.姜黄素对人巨细胞病毒感染人胚肺成纤维细胞后细胞凋亡的影响[J].中国医药导报,2018,15(34):4-9,22. [百度学术]
张锋镝,卢洪洲.姜黄素抗人类免疫缺陷病毒等作用研究进展[J].中国感染与化疗杂志,2015,15(5):487-490. [百度学术]
WEN CC,KUO YH,JAN JT,et al.Specific plant terpenoids and lignoidspossess potent antiviral activities against severe acute respiratory syndromecoronavirus[J].Journalof MedicinalChemistry,2007,50(17):4087-4097. [百度学术]
LU R,ZHAO X,LI J,et al.Genomiccharacterisation and epidemiology of 2019 novel coronavirus:implications for virusorigins and receptor binding[J].Lancet,395(10224):565-574. [百度学术]
CHEN L,HU C,HOOD M,et al.A novelcombination of vitamin C, curcumin and glycyrrhizic acid potentially regulatesimmune and inflammatory response associated with coronavirus infections: aperspective from system biology analysis[J].Nutrients,12(4):1193. [百度学术]
HOFFMANNM, KLEINEWEBERH,SCHROEDERS,et al. SARS-CoV-2 cell entry dependson ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor[J].Cell,2020,181(2):271-280. [百度学术]
MAURYAVK, KUMARS,PRASADAK,et al.Structure-baseddrug designing for potential antiviral activity of selected natural products fromAyurveda against SARS-CoV-2 spike glycoprotein and its cellular receptor[J]. VirusDisease,2020,31(2):179-193. [百度学术]
AHLAMES,MARIANAK, LISEV,et al.Curcumin inhibits the TGF-β1-dependent differentiation of lungfibroblasts via PPARγ-driven upregulation of cathepsins B and L[J].ScientificReports,2019,9(1):491-506. [百度学术]
HUANGPK,LINSR,CHANGCH,et al.Naturalphenolic compounds potentiate hypoglycemia via inhibition of Dipeptidyl peptidaseIV[J].Scientific Reports,2019,9(1):1-11. [百度学术]
SUNJ,CHENY,FANX,et al.Advances in the possible treatment of COVID-19:A review[J].European journal of pharmacology,2020, 883:173372. [百度学术]
江明金,温金华,潘德城,等.新型冠状病毒刺突蛋白及其受体的结构与功能[J].中国药理学通报,2020,36(11):1497-1501. [百度学术]
KANDEELM,AL-NAZAWIM.Virtual screening and repurposing of FDA approveddrugs against COVID-19 main protease[J].Life Science,2020,251:117627. [百度学术]
ENMOZHISK, RAJAK, SEBASTINEI,et al.Andrographolide as a potential inhibitor of SARS-CoV-2 main protease: an in silico approach[J]. J BiomolStructDynam,2020,1-7. [百度学术]
DU T,FANG L,LU J,et al.Multi-site inhibitors for enteric.coronavirus: antiviral cationic carbon dots based on curcumin[J].ACS Applied NanoMaterials,2018,1(10):5451-5459. [百度学术]
SHANG J, WAN Y, LUO C.et al. Cell entrymechanisms of SARS-CoV-2[J].Proceeding ofNationalAcademy ofSciences,2020,117 (21):11727-11734. [百度学术]
ENMOZHISK, RAJAK, SEBASTINEI,et al. Andrographolide as a potentialinhibitor of SARS-CoV-2 main protease: an in silico approach[J]. Journal of Biomolecular Structure Dynamics,2021,39(9):3092-3098 [百度学术]
孙 萌,高永红.姜黄素对老年高血压大鼠肾脏血管紧张素转化酶/血管紧张素转化酶2平衡的调节作用[J].中国临床医师杂志,2015,9 (11):2169-2173. [百度学术]
HIRANOT, MURAKAMIM.COVID-19: a new virus, but a familiar receptor andcytokine release syndrome[J].Immunity,2020,52 (5):731-733. [百度学术]
VISHVAKARMA,NK.Novel antitumor mechanisms of curcumin:implication ofaltered tumor metabolism,reconstituted tumor microenvironment and augmentedmyelopoiesis[J].PhytochemistryReviews,2014,13(9): 717-724. [百度学术]
MATTSONMP,MAUDSLEYS.Live longer sans the AT1A receptor[J]. Cell Metabol,2009,9(5):403-405. [百度学术]
KUNNUMAKKARAAB,BORDOLOID, PADMAVATHIG,et al.Curcumin,the golden nutraceutical: multitargeting formultiple chronic diseases[J].BritishJournalPharmacology,2017,174(11):1325-1348. [百度学术]
YUCC,TSAILL,WANGML,et al.MiR145 targets the SOX9/ADAM17 Axis to inhibittumor-initiating cells and IL-6–mediated paracrine effects in head and neck cancer[J].Cancer Research,2013,73(11):3425-3440. [百度学术]
GEORGEPM, WELLSAU,JENKINSRG,et al.Pulmonary fibrosis and COVID-19:thepotential role for antifibrotictherapy[J].The Lancet,Respiratory medicine,2020,8(8):807-815. [百度学术]
KOTHARR,LUTHRIADL.Curcumin:biological, pharmaceutical, nutraceutical,and analytical aspects[J].Molecules,2019,24(16):29-30. [百度学术]
刘 通,林 玮,张燕丽.冠状病毒肺炎的细胞因子风暴与治疗研究进展[J].中南医学科学杂志,2021,49(3):351-356 [百度学术]
LIU Z,YING Y.The inhibitory effect of curcumin on virus-induced cytokine stormand its potential use in the associated severe pneumonia[J].Frontiers in Celland Developmental Biology,2020,8(1):1-14. [百度学术]
施婵妹,黄琨伦,闵婧琦,等.姜黄素对肺部疾病的作用研究进展[J]. 医学研究杂志,2019,48(2):15-18. [百度学术]
TITTOM,ANKITT,SAUMYAB,et al.Curcumin prophylaxis refurbishes alveolar epithelial barrier integrity and alveolar fluid clearanceunderhypoxia[J].Respiratory Physiology Neurobiology,2020,274:103336. [百度学术]
KE S,ZHANG Y,LAN Z,et al.Curcumin protects murine lungmesenchymal stem cells from H2O2 by modulating the Akt/Nrf 2/HO-1 pathway[J].Journal ofInternation Medical Research,2020,48(4):1-11. [百度学术]
AGRATIC,SACCHIA, BORDONIV,et al.Expansion of myeloid-derivedsuppressor cells in patients with severe coronavirus disease(COVID-19)[J].Cell Death&Differentiation,2020,27(11):3196-3207. [百度学术]
李京洋,姚毅章,赵国廷,等.姜黄素对变异链球菌产酸、耐酸能力的影响[J].口腔医学,2020,40(8):707-710. [百度学术]
BOSCH-BARRERAJ, MARTIN-CASTILLOB, BUXO, et al. Silibinin and SARS-CoV-2: dual targeting of host cytokine storm and virusreplication machinery for clinical management of COVID-19 patients[J].Journal of Clinical Medicine,2020,9(6):1770-1782. [百度学术]
KURIENBT,DILLONSP,DORRIY,et al.Curcumin does not bind or intercalate into DNA and a note on the gray side of curcumin[J].InternationalJournal of Cancer,2011,128(1):242-245. [百度学术]
DOU Y,LUO J,WU X,et al.Curcumin attenuates collagen-induced inflammatory responsethrough the “gut-brain axis”[J].Journal of Neuroinflammation,2018,15(1):1-15. [百度学术]
KUNNUMAKKARAAB,HARSHAC, BANIKK,et al.Is curcumin bioavailability a problem in humans:lessons from clinical trials[J].Expert Opinion on Drug Metabolism &Toxicology,2019,15(9):705-733. [百度学术]