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Volume 42 Issue 5
May  2024
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ZHANG Linchen, ZHANG Xiaoqin, ZHANG Junping. Research progress on the pharmacological effects of maslinic acid[J]. Journal of Pharmaceutical Practice and Service, 2024, 42(5): 185-189. doi: 10.12206/j.issn.2097-2024.202307052
Citation: ZHANG Linchen, ZHANG Xiaoqin, ZHANG Junping. Research progress on the pharmacological effects of maslinic acid[J]. Journal of Pharmaceutical Practice and Service, 2024, 42(5): 185-189. doi: 10.12206/j.issn.2097-2024.202307052

Research progress on the pharmacological effects of maslinic acid

doi: 10.12206/j.issn.2097-2024.202307052
  • Received Date: 2023-07-25
  • Rev Recd Date: 2023-12-02
  • Available Online: 2024-05-22
  • Publish Date: 2024-05-25
  • Maslinic acid is a pentacyclic triterpenoid that is widely found in natural plants such as olives and hawthorns. Maslinic acid has anti-tumor, anti-inflammation, anti-oxidation, antibacterial, cardiovascular protection, neuroprotection, and other pharmacological effects. In this paper, the research progress of pharmacological activities and the mechanism of action of maslinic acid were reviewed, which provides the basis for the development and utilization of maslinic acid in the future.
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    [2] SU X, WANG H X, ZHAO N, et al. Trends in innovative drug development in China[J]. Nat Rev Drug Discov, 2022, 21(10):709-710. doi:  10.1038/d41573-022-00077-3
    [3] WEI Q, ZHANG B Y, LI P, et al. Maslinic acid inhibits colon tumorigenesis by the AMPK–mTOR signaling pathway[J]. J Agric Food Chem, 2019, 67(15):4259-4272. doi:  10.1021/acs.jafc.9b00170
    [4] REYES-ZURITA F J, RUFINO-PALOMARES E E, GARCÍA-SALGUERO L, et al. Maslinic acid, a natural triterpene, induces a death receptor-mediated apoptotic mechanism in caco-2 p53-deficient colon adenocarcinoma cells[J]. PLoS One, 2016, 11(1):e0146178. doi:  10.1371/journal.pone.0146178
    [5] RUFINO-PALOMARES E E, REYES-ZURITA F J, GARCÍA-SALGUERO L, et al. Maslinic acid, a triterpenic anti-tumoural agent, interferes with cytoskeleton protein expression in HT29 human colon-cancer cells[J]. J Proteom, 2013, 83:15-25. doi:  10.1016/j.jprot.2013.02.031
    [6] HSIA T C, LIU W H, QIU W W, et al. Maslinic acid induces mitochondrial apoptosis and suppresses HIF-1α expression in A549 lung cancer cells under normoxic and hypoxic conditions[J]. Molecules, 2014, 19(12):19892-19906. doi:  10.3390/molecules191219892
    [7] 白雪, 李慧, 张月, 等. MicroRNA在山楂酸诱导A549细胞凋亡中的作用研究[J]. 实用药物与临床, 2017, 20(5):502-505.
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    [17] 周芳亮, 胡梅, 胡晶, 等. 山楂酸通过PI3K/Akt/mTOR通路诱导鼻咽癌CNE2细胞自噬研究[J]. 中草药, 2020, 51(9):2481-2485.
    [18] 罗康宁, 刘昌化. 山楂酸通过调控DNA损伤修复逆转结人结肠癌HT-29细胞5-氟尿嘧啶耐药[J]. 中药材, 2021, 44(10):2430-2434.
    [19] WANG K, ZHU X E, YIN Y X. Maslinic acid enhances docetaxel response in human docetaxel-resistant triple negative breast carcinoma MDA-MB-231 cells via regulating MELK-FoxM1-ABCB1 signaling cascade[J]. Front Pharmacol, 2020, 11:835. doi:  10.3389/fphar.2020.00835
    [20] YU Y, WANG J H, XIA N X, et al. Maslinic acid potentiates the antitumor activities of gemcitabinein vitro and in vivo by inhibiting NF-κB-mediated survival signaling pathways in human gallbladder cancer cells[J]. Oncol Rep, 2015, 33(4):1683-1690. doi:  10.3892/or.2015.3755
    [21] SÁNCHEZ-QUESADA C, LÓPEZ-BIEDMA A, GAFORIO J J. Maslinic Acid enhances signals for the recruitment of macrophages and their differentiation to m1 state[J]. Evid Based Complement Alternat Med, 2015, 2015:654721.
    [22] 陈磊. 山楂酸对LPS诱导的RAW264.7细胞的抗炎作用及其机制研究[D]. 太谷: 山西农业大学, 2019.
    [23] KYOKO S, SATOSHI F, TOMOKO I, et al. The anti-arthritis effect of olive-derived maslinic acid in mice is due to its promotion of tissue formation and its anti-inflammatory effects[J]. Mol Nutr Food Res, 2019, 63(3):e1800543. doi:  10.1002/mnfr.201800543
    [24] CHEN Y L, YAN D Y, WU C Y, et al. Maslinic acid prevents IL-1β-induced inflammatory response in osteoarthritis via PI3K/AKT/NF-κB pathways[J]. J Cell Physiol, 2021, 236(3):1939-1949. doi:  10.1002/jcp.29977
    [25] WANG Z H, MONG M C, YANG Y C, et al. Asiatic acid and maslinic acid attenuated kainic acid-induced seizure through decreasing hippocampal inflammatory and oxidative stress[J]. Epilepsy Res, 2018, 139:28-34. doi:  10.1016/j.eplepsyres.2017.11.003
    [26] 相佳瑶. 天然萜类成分山楂酸的抗癫痫作用和机制研究[D]. 昆明: 昆明理工大学, 2021.
    [27] BAE H J, KIM J, KIM J, et al. The effect of maslinic acid on cognitive dysfunction induced by cholinergic blockade in mice[J]. Br J Pharmacol, 2020, 177(14):3197-3209. doi:  10.1111/bph.15042
    [28] QIAN Y S, HUANG M H, GUAN T, et al. Maslinic acid promotes synaptogenesis and axon growth via Akt/GSK-3β activation in cerebral ischemia model[J]. Eur J Pharmacol, 2015, 764:298-305. doi:  10.1016/j.ejphar.2015.07.028
    [29] LIU Y L, KONG C Y, SONG P, et al. Maslinic acid protects against pressure overload-induced cardiac hypertrophy in mice[J]. J Pharmacol Sci, 2018, 138(2):116-122. doi:  10.1016/j.jphs.2018.08.014
    [30] FANG M, DENG J, ZHOU Q P, et al. Maslinic acid protects against pressure-overload-induced cardiac hypertrophy by blocking METTL3-mediated m6A methylation[J]. Aging, 2022, 14(6):2548-2557. doi:  10.18632/aging.203860
    [31] LI Q, XU M P, LI Z Q, et al. Maslinic acid attenuates ischemia/reperfusion injury-induced myocardial inflammation and apoptosis by regulating HMGB1-TLR4 axis[J]. Front Cardiovasc Med, 2021, 8:768947. doi:  10.3389/fcvm.2021.768947
    [32] WANG N, MA Z F, CHEN C, et al. Effects of maslinic acid on cardiac function in ischemia–reperfusion injury rats[J]. J Investig Med, 2022, 70(1):20-28. doi:  10.1136/jim-2021-001927
    [33] LI L, LIN L, LEI S Q, et al. Maslinic acid inhibits myocardial ischemia–reperfusion injury-induced apoptosis and necroptosis via promoting autophagic flux[J]. DNA Cell Biol, 2022, 41(5):487-497. doi:  10.1089/dna.2021.0918
    [34] SHAIK A H, SHAIK S R, SHAIK A S, et al. Analysis of maslinic acid and Gallic acid compounds as xanthine oxidase inhibitors in isoprenaline administered myocardial necrotic rats[J]. Saudi J Biol Sci, 2021, 28(4):2575-2580. doi:  10.1016/j.sjbs.2021.01.062
    [35] WANG L, FAN Y F, LI B R, et al. Maslinic acid suppresses high glucose-induced inflammation by epigenetically inhibiting TXNIP expression[J]. Curr Med Sci, 2022, 42(6):1213-1219. doi:  10.1007/s11596-022-2657-6
    [36] PHANG S W, OOI B K, AHEMAD N, et al. Maslinic acid suppresses macrophage foam cells formation: regulation of monocyte recruitment and macrophage lipids homeostasis[J]. Vasc Pharmacol, 2020, 128-129:106675. doi:  10.1016/j.vph.2020.106675
    [37] LIOU C J, DAI Y W, WANG C L, et al. Maslinic acid protects against obesity-induced nonalcoholic fatty liver disease in mice through regulation of the Sirt1/AMPK signaling pathway[J]. FASEB J, 2019, 33(11):11791-11803. doi:  10.1096/fj.201900413RRR
    [38] LI T Q, WANG H, DONG S Y, et al. Protective effects of maslinic acid on high fat diet-induced liver injury in mice[J]. Life Sci, 2022, 301:120634. doi:  10.1016/j.lfs.2022.120634
    [39] 魏蕾, 卫倩倩, 李思维, 等. 山楂酸对急性酒精肝损伤小鼠部分生化指标的影响[J]. 临床医学研究与实践, 2020, 5(33):4-6.
    [40] 王颖, 蔡永青, 黄明春, 等. 山楂酸对四氯化碳致小鼠急性肝损伤的保护作用及机制研究[J]. 中国临床药理学与治疗学, 2016, 21(8):854-858.
    [41] WANG Y Y, DIAO B Z, ZHONG L H, et al. Maslinic acid protects against lipopolysaccharide/d-galactosamine-induced acute liver injury in mice[J]. Microb Pathog, 2018, 119:49-53. doi:  10.1016/j.micpath.2018.04.002
    [42] LIU J, WANG X, CHEN Y P, et al. Maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase[J]. Chin J Nat Med, 2014, 12(4):259-265.
    [43] ALSABAANI N A, OSMAN O M, DALLAK M A, et al. Maslinic acid protects against streptozotocin-induced diabetic retinopathy by activating Nrf2 and suppressing NF-κB[J]. J Ophthalmol, 2022, 2022:1-14.
    [44] MKHWANAZI B N, SERUMULA M R, MYBURG R B, et al. Antioxidant effects of maslinic acid in livers, hearts and kidneys of streptozotocin-induced diabetic rats: effects on kidney function[J]. Ren Fail, 2014, 36(3):419-431. doi:  10.3109/0886022X.2013.867799
    [45] SUN W J, CHOI H S, KIM C S, et al. Maslinic acid attenuates ischemia/reperfusion-induced acute kidney injury by suppressing inflammation and apoptosis through inhibiting NF-κB and MAPK signaling pathway[J]. Front Pharmacol, 2022, 13:807452. doi:  10.3389/fphar.2022.807452
    [46] GAO H J, WU H. Maslinic acid activates renal AMPK/SIRT1 signaling pathway and protects against diabetic nephropathy in mice[J]. BMC Endocr Disord, 2022, 22(1):25. doi:  10.1186/s12902-022-00935-6
    [47] SUN W J, BYON C H, KIM D H, et al. Renoprotective effects of maslinic acid on experimental renal fibrosis in unilateral ureteral obstruction model via targeting MyD88[J]. Front Pharmacol, 2021, 12:708575. doi:  10.3389/fphar.2021.708575
    [48] 郑开丰. 山楂酸对H2O2诱导BRL-3A细胞氧化损伤的保护作用及其机制的初步研究[D]. 太谷: 山西农业大学, 2020.
    [49] BLANCO-CABRA N, VEGA-GRANADOS K, MOYA-ANDÉRICO L, et al. Novel oleanolic and maslinic acid derivatives as a promising treatment against bacterial biofilm in nosocomial infections: an in vitro and in vivo study[J]. ACS Infect Dis, 2019, 5(9):1581-1589. doi:  10.1021/acsinfecdis.9b00125
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    [51] 刘海涛. 山楂酸对糖皮质激素诱发骨质疏松大鼠的干预作用研究[J]. 中国临床药理学杂志, 2015, 31(14):1443-1445.
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Research progress on the pharmacological effects of maslinic acid

doi: 10.12206/j.issn.2097-2024.202307052

Abstract: Maslinic acid is a pentacyclic triterpenoid that is widely found in natural plants such as olives and hawthorns. Maslinic acid has anti-tumor, anti-inflammation, anti-oxidation, antibacterial, cardiovascular protection, neuroprotection, and other pharmacological effects. In this paper, the research progress of pharmacological activities and the mechanism of action of maslinic acid were reviewed, which provides the basis for the development and utilization of maslinic acid in the future.

ZHANG Linchen, ZHANG Xiaoqin, ZHANG Junping. Research progress on the pharmacological effects of maslinic acid[J]. Journal of Pharmaceutical Practice and Service, 2024, 42(5): 185-189. doi: 10.12206/j.issn.2097-2024.202307052
Citation: ZHANG Linchen, ZHANG Xiaoqin, ZHANG Junping. Research progress on the pharmacological effects of maslinic acid[J]. Journal of Pharmaceutical Practice and Service, 2024, 42(5): 185-189. doi: 10.12206/j.issn.2097-2024.202307052
  • 山楂酸(MA)属于五环三萜类化合物(图1),又名马斯里酸、2α-羟基齐墩果酸,主要存在于油橄榄、山楂等天然植物中,在桔梗、藿香等传统草药中的含量也很丰富。MA多从油橄榄中提取,也可以齐墩果酸为原料半合成制备,目前已经形成成熟的合成路线,实现MA商业化供应[1]。MA具有抗癌、抗炎、心脏保护和肝保护等多种药理作用,临床应用前景广阔。本文综述了MA药理作用和机制的最新研究进展,以期为MA未来的开发利用提供参考依据。

    • 癌症是全球第二大死亡疾病,抗癌药物的研发因临床需求增加而不断发展。2010—2020年,我国首次获得新药临床研究审批(IND)批准的创新药在抗肿瘤领域占62%,但大多数尚处于Ⅰ期临床阶段[2]。大量研究表明,MA可抑制多种肿瘤细胞增殖、侵袭,并诱导细胞凋亡,其机制涉及多条细胞内信号通路,总结见表1

      癌细胞类型 作用机制 参考文献
      结肠癌 激活腺苷酸活化蛋白激酶(AMPK),负反馈调节雷帕霉素靶蛋白(mTOR)信号通路 [3]
      触发Caco-2细胞外源性凋亡途径,诱导HT-29细胞线粒体凋亡 [4]
      调节细胞骨架,抑制肿瘤细胞增殖 [5]
      肺癌 诱导线粒体凋亡,抑制缺氧诱导因子-1α(HIF-1α)表达 [6]
      调控微小RNA(miRNA),诱导肿瘤细胞凋亡 [7]
      胰腺癌 下调热休克蛋白HSPA8,诱导癌细胞自噬 [8]
      下调热休克蛋白HSP7C,诱导癌细胞凋亡 [9]
      宫颈癌 诱导DNA损伤,调节参与DNA损伤和修复的蛋白表达 [10]
      抑制白细胞介素-6(IL-6) [11]
      胃癌 上调AMPK/mTOR信号通路,促进癌细胞自噬 [12]
      抑制Janus激酶(JAK)/信号转导与转录激活因子3(STAT3)通路,诱导癌细胞凋亡 [13]
      乳腺癌 通过丝裂原活化蛋白激酶(MAPK)信号通路影响细胞周期,改变线粒体膜电位和活性氧(ROS)水平,导致癌细胞凋亡 [14]
      胶质瘤 抑制癌细胞增殖、侵袭和迁移,通过MAPK信号通路诱导癌细胞凋亡 [15]
      神经母细胞瘤 靶向MAPK/细胞外调节蛋白激酶(ERK)信号通路,并激活胱天蛋白酶(caspase),促进癌细胞凋亡 [16]
      鼻咽癌 抑制磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(AKT)、mTOR磷酸化水平,诱导癌细胞自噬 [17]

      除此之外,MA与一些抗癌药物联用还能有效缓解肿瘤耐药性,增强药效。MA可抑制HT-29人结肠癌细胞DNA损伤修复能力,逆转肿瘤细胞对5-氟尿嘧啶的耐药性[18]。MA与多西他赛联用,可以降低三阴性乳腺癌细胞对多西他赛的耐药性[19]。MA通过抑制核因子κB(NF-κB)信号通路,可增强吉西他滨对胆囊癌细胞的抗癌作用[20]。虽然MA对多种肿瘤细胞的增殖具有抑制作用,能够调控癌细胞多条信号级联传导,但目前体内研究不充分,其确切的作用靶点尚不清楚。

    • MA在不同炎症模型中显示出强效的保护作用,主要与抑制NF-κB和STAT3信号通路相关。在炎症反应中巨噬细胞起着重要作用。研究发现,MA可以作用于巨噬细胞发挥抗炎作用。MA不仅可以增强巨噬细胞募集并促进其向M1极化,还抑制RAW264.7小鼠腹腔巨噬细胞STAT3、JAK1磷酸化,缓解脂多糖(LPS)诱导的炎症反应[21,22]。MA也可以使Toll样受体失活,通过糖皮质激素受体下调白三烯来促进组织形成并抑制滑膜炎症,预防胶原诱导的关节炎[23]。此外,MA还能够阻断PI3K/AKT/NF-κB信号通路,从而减轻炎症介质,减少细胞外基质降解,保护骨关节[24]。不仅如此,MA亦可以通过影响NF-κB/环氧化酶-2(COX-2)的表达、抑制蛋白激酶C(PKC)和磷脂酶A2(PLA2)的活性,调节花生四烯酸代谢,抑制炎症反应。

    • MA对癫痫、阿尔兹海默症等中枢神经系统疾病具有治疗潜力。癫痫的发病机制与海马组织发生氧化和炎症反应相关。MA可减少癫痫小鼠模型中海马组织炎症因子的释放,降低谷氨酸水平,缓解癫痫发作[25]。此外,MA的抗癫痫活性还与抑制钠电流有关[26]。阿尔兹海默病是中枢神经系统进行性疾病,目前尚无逆转神经元丢失和疾病进程的治疗药物。有研究表明,MA可作为乙酰胆碱酯酶或丁酰胆碱酯酶抑制剂,靶向治疗阿尔兹海默症,还可以激活海马中脑源性神经营养因子(BDNF)信号通路,增强认知功能,逆转东莨菪碱诱导的记忆障碍[27]。MA还对多种神经损伤模型具有保护作用,包括皮质神经元氧糖剥夺损伤模型、LPS诱导的星形胶质细胞炎症损伤模型等。在缺血性脑损伤模型中,MA还能改善神经胶质功能,促进突触发生和轴突再生[28]

    • MA可缓解心肌肥厚、心肌炎和心肌梗死等心脏疾病。MA能够通过调节甲基转移酶-3(METTL3)介导的N6-甲基腺嘌呤(m6A)甲基化并抑制AKT/ERK信号通路,有效缓解心肌肥厚[29,30]。在心肌缺血再灌注损伤模型中,MA抑制高迁移率族蛋白B1(HMGB1)/Toll样受体4(TLR4)/NF-κB信号通路,抑制炎症反应和细胞凋亡[31];激活沉默信息调节因子(SIRT1)/AMPK信号通路,减少心室组织氧化损伤[32];促进自噬通量,减少心肌细胞的凋亡和坏死[33]。MA对心肌梗死的保护作用主要与其降脂、抗氧化特性有关,通过抑制黄嘌呤氧化酶(XOD)改善心肌坏死[34]

      高血糖诱导的炎症和内皮损伤是动脉粥样硬化等心血管疾病的发病机制之一。MA能够抑制高糖诱导的人脐静脉内皮细胞(HUVECs)中ROS和促炎因子的生成,改善血管内皮炎症和损伤[35]。除此之外,MA还能够抑制巨噬细胞向泡沫细胞转化,减少单核细胞与内皮细胞的黏附,下调清道夫受体,促进血管胆固醇清除[36]

    • MA对非酒精性脂肪肝和急性肝损伤具有保护作用。MA可降低高脂饮食引起的小鼠肝脏的脂质积累,调节SIRT1/AMPK信号通路,改善肝脏脂肪变性[37]。MA还能够通过抗炎、抑制肝细胞凋亡等方式,减轻非酒精性脂肪肝的肝脏病变[38]。MA可显著降低肝脏中丙二醛(MDA)含量,增加过氧化氢酶(CAT)和谷胱甘肽还原酶(GR)含量,保护急性酒精性肝病患者[39]。在四氯化碳(CCl4)诱导的小鼠急性肝损伤模型中,MA能够激活核因子E2相关因子2(Nrf2)/Kelch样ECH相关蛋白1(Keap1)信号通路,抑制NF-κB p65表达,促进氧自由基清除,减少炎症反应[40]。除此之外,MA还能够通过调节NF-κB和Nrf2信号通路,预防LPS/D-氨基半乳糖(D-galactosamine, D-GalN)诱导的小鼠急性肝损伤[41]

    • MA具有抗糖尿病作用,不仅可以降低血糖,还能缓解糖尿病诱发的视网膜病变、肾衰竭等并发症。MA能够特异性激活AKT,抑制糖原磷酸化酶活性,促进胰岛素合成,调节糖原代谢[42]。在糖尿病患者中,视网膜病变是一种最常见的微血管并发症。在大鼠1型糖尿病模型中,MA可通过激活Nrf2增强抗氧化能力,改善视网膜病变[43]。此外,MA还能增加尿液中钠输出量,有效改善糖尿病患者肾功能[44]

    • MA具有肾保护作用,对肾损伤、糖尿病肾病和肾纤维化均有治疗效果。在小鼠缺血再灌注急性肾损伤模型中,MA可抑制ERK、c-Jun氨基末端激酶(JNK)和p38磷酸化,缓解肾损伤[45]。同时,体外研究还发现,MA可以抑制MAPK信号通路,减少过氧化氢(H2O2)诱导NRK-52E大鼠近端肾小管上皮细胞的凋亡[45]。在链脲佐菌素(STZ)诱导的小鼠糖尿病模型中,20 mg/kg MA可激活AMPK/SIRT1信号通路,显著减轻糖尿病小鼠肾脏的氧化应激和炎症损伤,保护肾脏结构和功能[46]。在单侧输尿管结扎诱导的肾纤维化模型中,MA可显著降低α-平滑肌肌动蛋白(α-SMA)、波形蛋白(vimenti)等纤维化标志物的表达,靶向TGF-β/Smad信号通路,并特异性抑制衔接蛋白MyD88,改善肾间质纤维化[47]

    • 除了上述药理作用外,MA在抗氧化应激、抗病毒和治疗骨质疏松等方面的研究也有很多。

      MA的抗氧化作用主要作用于酶类抗氧化系统。在H2O2诱导BRL-3A大鼠肝细胞氧化损伤模型中,MA可激活p38 MAPK/Nrf2/血红素氧合酶1(HO-1)信号通路,降低ROS、MDA水平,提高超氧化物歧化酶(SOD)和CAT活力,抑制细胞氧化应激[48]

      MA及其衍生物对多种病原体具有杀伤作用。研究发现,MA酰胺衍生物可以穿透并破坏金黄色葡萄球菌细胞膜,还可以降低细菌导管内抗生素膜形成能力[49]。此外,结构中含有氨基酸残基和共轭二肽的MA衍生物能够抑制1型人类免疫缺陷病毒活性,被氯化异恶咗修饰的MA衍生物对新型冠状病毒(SARS-CoV-2)显示出良好的抗病毒活性[50]

      除此之外,MA还可以治疗骨质疏松,改善骨骼肌质量。在泼尼松致大鼠骨质疏松模型中,MA可使骨中钙盐和羟脯氨酸(Hyp)含量上升,增加骨密度,缓解骨质疏松[51]。MA还可以激活mTOR复合物1(mTORC1)和G蛋白偶联胆汁酸受体5(TGR5),促进骨骼肌肥大[52]。此外,MA还能够诱导胰岛素样生长因子1(Igf1)表达,下调Atrogin-1、Murf1和Tgfb基因,防止去神经支配导致的腓肠肌质量和骨骼肌力量的降低,有效缓解肌肉萎缩[53]

    • 作为天然小分子活性化合物,MA可以抗肿瘤、抗炎、抗氧化和调节血糖,对中枢神经系统、心脏、肝脏和肾脏均具有保护作用,未来可以应用于癌症和多种器官相关疾病的预防与治疗。目前,MA抗癌作用的研究多集中于抑制肿瘤细胞增殖、促进肿瘤细胞凋亡和自噬,但对原癌基因和抑癌基因、机体免疫功能和肿瘤微环境等的调控作用却鲜有报道,后续还需进行深入研究。另一方面,MA的抗肿瘤作用提示其可能存在细胞毒性,但在MA保护中枢神经系统、心血管、肝脏等研究中,均未涉及对MA毒副作用的研究。MA广泛的药理作用,提示其可能具有多个作用靶点。可以采用化学探针或高选择性配体等方法筛选MA作用靶点,并配合基因敲除或基因沉默等技术比较MA对不同靶点的选择性和活性强度,为MA药理作用的进一步研究和应用提供更加充分的依据。

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