AbMole小課堂|槲皮素（Quercetin）：從腫瘤凋亡到端粒修復(fù)Quercetin（槲皮素，AbMole，M3902）是一種廣泛存在于自然界中的黃酮類化合物，其分子結(jié)構(gòu)由兩個苯環(huán)（A環(huán)和B環(huán)）通過C3位含氧雜環(huán)（吡喃環(huán)）連接而成，Quercetin因其多種生物活性而受到廣泛關(guān)注，尤其是在抗氧化、抗炎、抗腫瘤等方面的研究中表現(xiàn)出顯著的潛力。一、Quercetin（槲皮素）的抗氧化活性Quercetin（Meletin，AbMole，M3902）的抗氧化活性是其最重要的生物特性之一。研究表明，Quercetin能夠通過清除多種自由基（如DPPH、超氧陰離子、羥自由基等）來抑制氧化應(yīng)激ADDINEN.CITE<EndNote><Cite><Author>Azeem</Author><Year>2023</Year><RecNum>131</RecNum><DisplayText><styleface="superscript">[1]</style></DisplayText><record><rec-number>131</rec-number><foreign-keys><keyapp="EN"db-id="wextdpxe9sewdueavvl5zv97re9rpwdd59dx"timestamp="1750224661">131</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Azeem,M.</author><author>Hanif,M.</author><author>Mahmood,K.</author><author>Ameer,N.</author><author>Chughtai,F.R.S.</author><author>Abid,U.</author></authors></contributors><auth-address>DepartmentofPharmaceutics,FacultyofPharmacy,Baha-Uddin-ZakariyaUniversity,Multan,Pakistan. HamdardInstituteofPharmaceuticalSciences,HamdardUniversity,IslamabadCampus,Islamabad,Pakistan.GRID:grid.411955.d.ISNI:0000000406073729 InstituteofChemicalSciences,Baha-Uddin-ZakariyaUniversity,Multan,Pakistan.</auth-address><titles><title>Aninsightintoanticancer,antioxidant,antimicrobial,antidiabeticandanti-inflammatoryeffectsofquercetin:areview</title><secondary-title>PolymBull(Berl)</secondary-title></titles><periodical><full-title>PolymBull(Berl)</full-title></periodical><pages>241-262</pages><volume>80</volume><number>1</number><edition>20220130</edition><keywords><keyword>Anti-inflammatory</keyword><keyword>Anticancer</keyword><keyword>Antidiabetic</keyword><keyword>Antimicrobial</keyword><keyword>Antioxidant</keyword><keyword>Quercetin</keyword></keywords><dates><year>2023</year></dates><isbn>0170-0839(Print) 0170-0839</isbn><accession-num>35125574</accession-num><urls></urls><custom1>ConflictofinterestTheauthorshaveindicatedthattheyhavenootherconflictsofinterestwithregardtothecontentofthisarticle.</custom1><custom2>PMC8800825</custom2><electronic-resource-num>10.1007/s00289-022-04091-8</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[1]。此外，Quercetin還可以通過上調(diào)抗氧化酶的表達(dá)（如超氧化物歧化酶、過氧化氫酶等）來增強(qiáng)細(xì)胞的抗氧化防御能力ADDINEN.CITE<EndNote><Cite><Author>Azeem</Author><Year>2023</Year><RecNum>131</RecNum><DisplayText><styleface="superscript">[1]</style></DisplayText><record><rec-number>131</rec-number><foreign-keys><keyapp="EN"db-id="wextdpxe9sewdueavvl5zv97re9rpwdd59dx"timestamp="1750224661">131</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Azeem,M.</author><author>Hanif,M.</author><author>Mahmood,K.</author><author>Ameer,N.</author><author>Chughtai,F.R.S.</author><author>Abid,U.</author></authors></contributors><auth-address>DepartmentofPharmaceutics,FacultyofPharmacy,Baha-Uddin-ZakariyaUniversity,Multan,Pakistan. HamdardInstituteofPharmaceuticalSciences,HamdardUniversity,IslamabadCampus,Islamabad,Pakistan.GRID:grid.411955.d.ISNI:0000000406073729 InstituteofChemicalSciences,Baha-Uddin-ZakariyaUniversity,Multan,Pakistan.</auth-address><titles><title>Aninsightintoanticancer,antioxidant,antimicrobial,antidiabeticandanti-inflammatoryeffectsofquercetin:areview</title><secondary-title>PolymBull(Berl)</secondary-title></titles><periodical><full-title>PolymBull(Berl)</full-title></periodical><pages>241-262</pages><volume>80</volume><number>1</number><edition>20220130</edition><keywords><keyword>Anti-inflammatory</keyword><keyword>Anticancer</keyword><keyword>Antidiabetic</keyword><keyword>Antimicrobial</keyword><keyword>Antioxidant</keyword><keyword>Quercetin</keyword></keywords><dates><year>2023</year></dates><isbn>0170-0839(Print) 0170-0839</isbn><accession-num>35125574</accession-num><urls></urls><custom1>ConflictofinterestTheauthorshaveindicatedthattheyhavenootherconflictsofinterestwithregardtothecontentofthisarticle.</custom1><custom2>PMC8800825</custom2><electronic-resource-num>10.1007/s00289-022-04091-8</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[1]。二、Quercetin（槲皮素）的抗腫瘤活性Quercetin（Sophoretin，AbMole，M3902）能夠抑制多種腫瘤細(xì)胞的體外增殖。例如Quercetin可有效抑制結(jié)腸癌細(xì)胞系HCT-15和RKO的細(xì)胞活性ADDINEN.CITE<EndNote><Cite><Author>Reyes-Farias</Author><Year>2019</Year><RecNum>133</RecNum><DisplayText><styleface="superscript">[2]</style></DisplayText><record><rec-number>133</rec-number><foreign-keys><keyapp="EN"db-id="wextdpxe9sewdueavvl5zv97re9rpwdd59dx"timestamp="1750225409">133</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Reyes-Farias,M.</author><author>Carrasco-Pozo,C.</author></authors></contributors><auth-address>DepartmentofEndocrinologyandNutrition,GermansTriasiPujolResearchInstitute,08916Barcelona,Spain2DiscoveryBiology,GriffithInstituteforDrugDiscovery,GriffithUniversity,Nathan,QLD4111,Australia.</auth-address><titles><title>TheAnti-CancerEffectofQuercetin:MolecularImplicationsinCancerMetabolism</title><secondary-title>IntJMolSci</secondary-title></titles><periodical><full-title>IntJMolSci</full-title></periodical><volume>20</volume><number>13</number><edition>20190628</edition><keywords><keyword>Animals</keyword><keyword>AntineoplasticAgents/*pharmacology/therapeuticuse</keyword><keyword>Apoptosis/drugeffects</keyword><keyword>EnergyMetabolism/*drugeffects</keyword><keyword>Humans</keyword><keyword>Neoplasms/drugtherapy/*metabolism</keyword><keyword>Quercetin/*pharmacology/therapeuticuse</keyword><keyword>SignalTransduction/drugeffects</keyword><keyword>PI3K/Aktpathway</keyword><keyword>cancer</keyword><keyword>glycolysis</keyword><keyword>mitochondrialfunction</keyword><keyword>quercetin</keyword></keywords><dates><year>2019</year><pub-dates><date>Jun28</date></pub-dates></dates><isbn>1422-0067</isbn><accession-num>31261749</accession-num><urls></urls><custom1>Theauthorsdeclarenoconflictofinterest.</custom1><custom2>PMC6651418</custom2><electronic-resource-num>10.3390/ijms20133177</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[2]。此外，Quercetin在一定濃度范圍內(nèi)對B淋巴瘤細(xì)胞系（如BC3、BCBL1和BC1）表現(xiàn)出抑制作用，且對正常B淋巴細(xì)胞無毒性ADDINEN.CITE<EndNote><Cite><Author>Reyes-Farias</Author><Year>2019</Year><RecNum>134</RecNum><DisplayText><styleface="superscript">[2]</style></DisplayText><record><rec-number>134</rec-number><foreign-keys><keyapp="EN"db-id="wextdpxe9sewdueavvl5zv97re9rpwdd59dx"timestamp="1750225457">134</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Reyes-Farias,M.</author><author>Carrasco-Pozo,C.</author></authors></contributors><auth-address>DepartmentofEndocrinologyandNutrition,GermansTriasiPujolResearchInstitute,08916Barcelona,Spain2DiscoveryBiology,GriffithInstituteforDrugDiscovery,GriffithUniversity,Nathan,QLD4111,Australia.</auth-address><titles><title>TheAnti-CancerEffectofQuercetin:MolecularImplicationsinCancerMetabolism</title><secondary-title>IntJMolSci</secondary-title></titles><periodical><full-title>IntJMolSci</full-title></periodical><volume>20</volume><number>13</number><edition>20190628</edition><keywords><keyword>Animals</keyword><keyword>AntineoplasticAgents/*pharmacology/therapeuticuse</keyword><keyword>Apoptosis/drugeffects</keyword><keyword>EnergyMetabolism/*drugeffects</keyword><keyword>Humans</keyword><keyword>Neoplasms/drugtherapy/*metabolism</keyword><keyword>Quercetin/*pharmacology/therapeuticuse</keyword><keyword>SignalTransduction/drugeffects</keyword><keyword>PI3K/Aktpathway</keyword><keyword>cancer</keyword><keyword>glycolysis</keyword><keyword>mitochondrialfunction</keyword><keyword>quercetin</keyword></keywords><dates><year>2019</year><pub-dates><date>Jun28</date></pub-dates></dates><isbn>1422-0067</isbn><accession-num>31261749</accession-num><urls></urls><custom1>Theauthorsdeclarenoconflictofinterest.</custom1><custom2>PMC6651418</custom2><electronic-resource-num>10.3390/ijms20133177</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[2]。在乳腺癌細(xì)胞系SK-Br3和MDA-MB-453中，Quercetin（槲皮素）以劑量依賴的方式抑制細(xì)胞增殖ADDINEN.CITE<EndNote><Cite><Author>Reyes-Farias</Author><Year>2019</Year><RecNum>134</RecNum><DisplayText><styleface="superscript">[2]</style></DisplayText><record><rec-number>134</rec-number><foreign-keys><keyapp="EN"db-id="wextdpxe9sewdueavvl5zv97re9rpwdd59dx"timestamp="1750225457">134</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Reyes-Farias,M.</author><author>Carrasco-Pozo,C.</author></authors></contributors><auth-address>DepartmentofEndocrinologyandNutrition,GermansTriasiPujolResearchInstitute,08916Barcelona,Spain2DiscoveryBiology,GriffithInstituteforDrugDiscovery,GriffithUniversity,Nathan,QLD4111,Australia.</auth-address><titles><title>TheAnti-CancerEffectofQuercetin:MolecularImplicationsinCancerMetabolism</title><secondary-title>IntJMolSci</secondary-title></titles><periodical><full-title>IntJMolSci</full-title></periodical><volume>20</volume><number>13</number><edition>20190628</edition><keywords><keyword>Animals</keyword><keyword>AntineoplasticAgents/*pharmacology/therapeuticuse</keyword><keyword>Apoptosis/drugeffects</keyword><keyword>EnergyMetabolism/*drugeffects</keyword><keyword>Humans</keyword><keyword>Neoplasms/drugtherapy/*metabolism</keyword><keyword>Quercetin/*pharmacology/therapeuticuse</keyword><keyword>SignalTransduction/drugeffects</keyword><keyword>PI3K/Aktpathway</keyword><keyword>cancer</keyword><keyword>glycolysis</keyword><keyword>mitochondrialfunction</keyword><keyword>quercetin</keyword></keywords><dates><year>2019</year><pub-dates><date>Jun28</date></pub-dates></dates><isbn>1422-0067</isbn><accession-num>31261749</accession-num><urls></urls><custom1>Theauthorsdeclarenoconflictofinterest.</custom1><custom2>PMC6651418</custom2><electronic-resource-num>10.3390/ijms20133177</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[2]。Quercetin主要通過調(diào)節(jié)細(xì)胞周期相關(guān)蛋白來抑制細(xì)胞增殖。例如，Quercetin通過下調(diào)細(xì)胞周期蛋白和細(xì)胞周期依賴性激酶1（CDK1）的表達(dá)，抑制G2/M期的細(xì)胞周期進(jìn)程ADDINEN.CITEADDINEN.CITE.DATA[3,4]。Quercetin（槲皮素）能夠誘導(dǎo)多種腫瘤細(xì)胞的凋亡。例如，在SKOV-3卵巢癌細(xì)胞和MCF-7乳腺癌細(xì)胞中，Quercetin以時間和劑量依賴的方式增加凋亡標(biāo)志物survivin的水平。此外，負(fù)載Quercetin的膠束能誘導(dǎo)乳腺癌細(xì)胞的凋亡ADDINEN.CITE<EndNote><Cite><Author>Karthick</Author><Year>2019</Year><RecNum>137</RecNum><DisplayText><styleface="superscript">[5]</style></DisplayText><record><rec-number>137</rec-number><foreign-keys><keyapp="EN"db-id="wextdpxe9sewdueavvl5zv97re9rpwdd59dx"timestamp="1750226650">137</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Karthick,V.</author><author>Panda,Sucheta</author><author>Kumar,V.Ganesh</author><author>Kumar,Dinesh</author><author>Shrestha,LokKumar</author><author>Ariga,Katsuhiko</author><author>Vasanth,K.</author><author>Chinnathambi,Shanmugavel</author><author>Dhas,T.Stalin</author><author>Suganya,K.S.Uma</author></authors></contributors><titles><title>QuercetinloadedPLGAmicrospheresinduceapoptosisinbreastcancercells</title><secondary-title>AppliedSurfaceScience</secondary-title></titles><periodical><full-title>AppliedSurfaceScience</full-title></periodical><pages>211-217</pages><volume>487</volume><keywords><keyword>Apoptosis</keyword><keyword>Annexin-V</keyword><keyword>Electronmicroscopy</keyword><keyword>Nuclearmagneticresonance</keyword><keyword>Cancer</keyword></keywords><dates><year>2019</year><pub-dates><date>2019/09/01/</date></pub-dates></dates><isbn>0169-4332</isbn><urls><related-urls><url>/science/article/pii/S0169433219313546</url></related-urls></urls><electronic-resource-num>/10.1016/j.apsusc.2019.05.047</electronic-resource-num></record></Cite></EndNote>[5]。三、Quercetin（槲皮素）用于衰老研究衰老作為復(fù)雜的生物學(xué)過程，其核心機(jī)制包括細(xì)胞衰老（cellularsenescence）、端?？s短、DNA損傷累積、線粒體功能異常、表觀遺傳改變等。Quercetin（槲皮素，AbMole，M3902）可通過多靶點(diǎn)調(diào)控衰老進(jìn)程。Quercetin通過激活SIRT1信號通路，減少氧化應(yīng)激對細(xì)胞的損傷，從而間接調(diào)控hTERT（端粒酶逆轉(zhuǎn)錄酶）的表達(dá)。SIRT1是一種去乙?；?，能夠通過去乙?；饔谜{(diào)節(jié)多種蛋白質(zhì)的活性，包括hTERT。研究表明，Quercetin通過激活SIRT1，減少氧化應(yīng)激，從而維持端粒長度，延緩細(xì)胞衰老。Quercetin還可以誘導(dǎo)受損線粒體的選擇性降解，維持線粒體功能穩(wěn)態(tài)ADDINEN.CITEADDINEN.CITE.DATA[6]，并減少衰老過程中的線粒體ROS生成ADDINEN.CITEADDINEN.CITE.DATA[7]。也有大量文獻(xiàn)證實Quercetin可以通過SIRT1調(diào)控多條信號通路，進(jìn)而抑制帕金森、阿爾茲海默癥，亨廷頓癥等衰老相關(guān)疾病ADDINEN.CITEADDINEN.CITE.DATA[8]。圖1.Quercetin通過調(diào)控SIRT1影響多條信號通路和衰老相關(guān)疾病ADDINEN.CITEADDINEN.CITE.DATA[8]四、Quercetin（槲皮素）的抗炎活性Quercetin（槲皮素，AbMole，M3902）在抗炎方面表現(xiàn)出顯著的潛力。其抗炎機(jī)制主要通過抑制促炎介質(zhì)（如白細(xì)胞介素-6、腫瘤壞死因子-α等）的產(chǎn)生和炎癥相關(guān)酶（如環(huán)氧合酶-2）的活性來實現(xiàn)。例如，Quercetin還可以通過調(diào)節(jié)細(xì)胞信號通路（如NF-κB通路）來抑制炎癥反應(yīng)ADDINEN.CITEADDINEN.CITE.DATA[9]。此外，Quercetin還能抑制MAPK通路，并抑制JNK、p38和ERK1/2的磷酸化，阻斷炎癥信號從細(xì)胞膜到細(xì)胞核的傳遞。五、范例詳解NatCommun.2023Nov27;14(1):7783.中國科學(xué)院深圳先進(jìn)技術(shù)研究院、上海交通大學(xué)的實驗人員在上述文章中探究了局部釋放氫氣（H?）能否重塑衰老微環(huán)境（senescencemicroenvironment,SME），從而改善老年動物個體模型中受損骨骼的修復(fù)能力。研究團(tuán)隊發(fā)現(xiàn)，局部供應(yīng)氫氣可以通過抗炎和抗衰老效應(yīng)來重塑成熟骨骼中各種衰老細(xì)胞的微環(huán)境。實驗人員還開發(fā)了一種能夠釋放高劑量氫氣的支架（CSN@PHA-MBG），并在老年小鼠模型中成功實現(xiàn)了對骨缺損的有效修復(fù)。在實驗中，科研人員使用了AbMole的三個產(chǎn)品，Ruxolitinib（AbMole，M1787）：作為一種衰老形態(tài)劑（senomorphicagent），與氫氣處理的細(xì)胞進(jìn)行對比，以評估其對細(xì)胞衰老的影響；Quercetin（AbMole，M3902）和Dasatinib（AbMole，M1701）：作為衰老溶解劑（SenolyticAgents），用于清除衰老細(xì)胞。圖2.TheeffectofH2onsenescentosteocytesharvestedfromagingbonefrom24-month-oldmiceafter3daysoftreatment.參考文獻(xiàn)ADDINEN.REFLIST[1]M.Azeem,M.Hanif,K.Mahmood,N.Ameer,F.R.S.Chughtai,U.Abid,Aninsightintoanticancer,antioxidant,antimicrobial,antidiabeticandanti-inflammatoryeffectsofquercetin:areview,PolymBull(Berl)80(1)(2023)241-262.[2]M.Reyes-Farias,C.Carrasco-Pozo,TheAnti-CancerEffectofQuercetin:MolecularImplicationsinCancerMetabolism,IntJMolSci20(13)(2019).[3]M.Ogrodnik,Y.Zhu,L.G.