最新研究：天然抗氧剂姜黄素可增强自噬改善动脉粥样硬化形成中的炎症机制

为了保持汽车平稳运行，我们定期更换机油、更换火花塞和刹车片等磨损部件，并执行其他基本维护任务。

我们的细胞的工作方式大致与这个例子相似

随着年龄增长，我们的细胞中会积累受损蛋白质和其他有毒碎片。这会导致细胞退化过程加速，并增加罹患慢性疾病的风险。

自噬是一种自然的管家过程，它充当着一种内置的清洁服务，可以识别和消除受损的细胞成分。[1-3]

重要的自噬过程会随着年龄的增长而衰退。[1,3,4]

姜黄素是香料姜黄中的一种化合物，已被证明能促进自噬。[5-11]临床前和临床研究表明，它有助于对抗与退行性衰老有关的几个关键因素。

自噬的重要性

人体有一种自然的方式来检测、清除和回收随着时间推移而积累的细胞损伤。[1-4]这一过程称为自噬，它使细胞能够清除其代谢废物。

自噬的字面意思是“自我吞噬”。在这个过程中，细胞吞噬并分解旧的、磨损的内部组件，为新的替代品腾出空间。

这有助于使细胞继续发挥最佳功能。

衰老和不良饮食会降低自噬率。随着自噬率的降低，代谢废物会在细胞内堆积，影响最佳功能。

细胞和动物研究表明，当自噬功能不足时，生物体会遭受过早衰老、慢性疾病和寿命缩短的困扰。[1,4]在几项动物研究中，当自噬功能增强时，寿命会延长。[12-15]

例如，一项研究显示，激活小鼠的自噬可使 平均寿命延长17.2 %。[15]

刺激自噬的方法

研究表明，抗阻力运动16和间歇性禁食或卡路里限制17可刺激自噬。

代谢异常会导致慢性疾病。mTOR和AMPK酶在调节细胞自噬方面发挥着关键作用。[1,4]

当卡路里摄入量较高时，mTOR被激活并关闭自噬，而抑制过多的mTOR活性可以增加自噬。[18]

AMPK 激活自噬。研究表明，增加细胞AMPK活性可改善代谢健康和寿命。[1]

当AMPK增加且mTOR减少时，自噬最为活跃。[1,4]

随着年龄的增长，自噬过程可能会受损或减弱，从而导致灾难性的后果。大多数与年龄有关的慢性疾病，从心血管疾病到神经退行性疾病和癌症，都与自噬减弱有关。[1,4]

自噬功能下降会导致代谢疾病，进而进一步损害自噬，形成加速衰老的恶性循环。[1]

自噬

溶酶体（橙色）与自噬体（大球体）融合。自噬是一种自然机制，可以破坏不必要或功能失调的细胞成分并回收其物质。

目标成分首先在双膜自噬体内与细胞的其余部分分离。然后与溶酶体融合，溶酶体的内容物会降解目标成分。

姜黄素促进自噬

姜黄素是姜黄根中发现的一种多酚化合物。

在临床研究中，姜黄素长期以来被认为是一种有效的抗炎药。通过减少氧化应激和慢性炎症，它可以支持代谢、心血管和胃肠道健康。[19-21]保持代谢健康可减缓与衰老和慢性病相关的损害进展。[22]

过去十年的临床前研究也已证实姜黄素是自噬的促进剂。[5-7,23-25]

它通过抑制mTOR活性和增强 AMPK活性发挥作用。[5,6,23,24]它还结合并激活细胞中一种称为转录因子 EB 或 TFEB 的关键蛋白质，从而触发对自噬很重要的细胞机制。[25]

在细胞和动物模型中，姜黄素已被证明可以增强自噬，[5-7,26]改善健康，[5-7,23-27]并延长寿命。[28,29]

给果蝇提供姜黄素可使其  平均寿命延长26 %。[28]

降低患慢性疾病的风险

通过促进自噬和对抗氧化应激和炎症，姜黄素可以降低多种与年龄相关的疾病和慢性疾病的风险。

足够水平的自噬有助于降低大多数慢性衰老疾病的风险，这表明姜黄素的潜在益处还延伸到其他疾病。[8,30]

轻度认知障碍、阿尔茨海默病、帕金森病和其他神经退行性疾病都与神经系统中异常蛋白质的积累有关。自噬可能有助于清除这些蛋白质。

在阿尔茨海默病动物模型中，姜黄素摄入可诱导自噬并减少淀粉样斑块的积聚。[5,31]在帕金森病模型中，它已被证明可以减少一种名为α-突触核蛋白的异常蛋白质的积累并改善疾病症状。[6,32]

肥胖和超重会增加患心脏病、中风、癌症和糖尿病等慢性病的风险。肥胖引起的炎症也会加速衰老过程。[33]

对 876 名随机接受姜黄素补充剂的受试者进行的荟萃分析显示，体重和身体质量指数 (BMI)有所下降。[34]

在临床前研究中，姜黄素已被证明对糖尿病23和非糖尿病模型中的心血管疾病有益。[35]激活自噬有助于保护血管健康并保护心脏免受损害。[23,36]

在一项针对高脂饮食的糖尿病小鼠的研究中，补充姜黄素可增加心肌中的AMPK 活性和自噬，从而改善整体心肌功能。[23]

在一项针对年轻肥胖男性的人体研究中，与安慰剂相比，服用 12 周特制的姜黄素-半乳甘露聚糖补充剂可使保护性高密度脂蛋白（“好”）胆固醇增加34% ，同型半胱氨酸（一种与动脉粥样硬化发展有关的氨基酸）减少29 % 。[37]

姜黄素促进自噬，有益健康

• 在细胞自噬过程中，旧的和有缺陷的细胞成分会被移除，为新成分腾出空间。这有助于恢复每个细胞的活力，使其保持平稳运行。

• 自噬通常会随着年龄的增长而下降，导致受损和功能失调的部分不断积累。自噬减少会导致大多数与年龄相关的慢性疾病，包括神经退化、心血管疾病和癌症。

• 在细胞和动物模型中，增强自噬有助于健康衰老并延长寿命。

• 姜黄素是姜黄根中的一种化合物，细胞和动物模型已证明它可以激活自噬，使细胞恢复活力并对抗与年龄相关的疾病。

• 姜黄素可以延长动物的寿命，并在人体研究中显示出改善记忆力、心血管健康等的能力。

1. Aman Y, Schmauck-Medina T, Hansen M, et al. Autophagy in healthy aging and disease. Nat Aging. 2021 Aug;1(8):634-50.
2. Giampieri F, Afrin S, Forbes-Hernandez TY, et al. Autophagy in Human Health and Disease: Novel Therapeutic Opportunities. Antioxid Redox Signal. 2019 Feb 1;30(4):577-634.
3. Saha S, Panigrahi DP, Patil S, et al. Autophagy in health and disease: A comprehensive review. Biomed Pharmacother. 2018 Aug;104:485-95.
4. Klionsky DJ, Petroni G, Amaravadi RK, et al. Autophagy in major human diseases. EMBO J. 2021 Oct 1;40(19):e108863.
5. Forouzanfar F, Read MI, Barreto GE, et al. Neuroprotective effects of curcumin through autophagy modulation. IUBMB Life. 2020 Apr;72(4):652-64.
6. He HJ, Xiong X, Zhou S, et al. Neuroprotective effects of curcumin via autophagy induction in 6-hydroxydopamine Parkinson’s models. Neurochem Int. 2022 May;155:105297.
7. Shakeri A, Cicero AFG, Panahi Y, et al. Curcumin: A naturally occurring autophagy modulator. J Cell Physiol. 2019 May;234(5):5643-54.
8. Zia A, Farkhondeh T, Pourbagher-Shahri AM, et al. The role of curcumin in aging and senescence: Molecular mechanisms. Biomed Pharmacother. 2021 Feb;134:111119.
9. Tang C, Li L, Shi J, et al. Curcumin in age-related diseases. Pharmazie. 2020 Nov 1;75(11):534-9.
10. Sadeghian M, Rahmani S, Jamialahmadi T, et al. The effect of oral curcumin supplementation on health-related quality of life: A systematic review and meta-analysis of randomized controlled trials. J Affect Disord. 2021 Jan 1;278:627-36.
11. Bielak-Zmijewska A, Grabowska W, Ciolko A, et al. The Role of Curcumin in the Modulation of Ageing. Int J Mol Sci. 2019 Mar 12;20(5).
12. Nakamura S, Yoshimori T. Autophagy and Longevity. Mol Cells. 2018 Jan 31;41(1):65-72.
13. Hansen M, Rubinsztein DC, Walker DW. Autophagy as a promoter of longevity: insights from model organisms. Nat Rev Mol Cell Biol. 2018 Sep;19(9):579-93.
14. Fernandez AF, Sebti S, Wei Y, et al. Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes longevity in mice. Nature. 2018 Jun;558(7708):136-40.
15. Pyo JO, Yoo SM, Ahn HH, et al. Overexpression of Atg5 in mice activates autophagy and extends lifespan. Nat Commun. 2013;4:2300.
16. Halling JF, Pilegaard H. Autophagy-Dependent Beneficial Effects of Exercise. Cold Spring Harb Perspect Med. 2017 Aug 1;7(8).
17. Shabkhizan R, Haiaty S, Moslehian MS, et al. The Beneficial and Adverse Effects of Autophagic Response to Caloric Restriction and Fasting. Adv Nutr. 2023 Sep;14(5):1211-25.
18. Fernandes SA, Demetriades C. The Multifaceted Role of Nutrient Sensing and mTORC1 Signaling in Physiology and Aging. Front Aging. 2021;2:707372.
19. Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J. 2013 Jan;15(1):195-218.
20. Panknin TM, Howe CL, Hauer M, et al. Curcumin Supplementation and Human Disease: A Scoping Review of Clinical Trials. Int J Mol Sci. 2023 Feb 24;24(5).
21. Zeng Y, Luo Y, Wang L, et al. Therapeutic Effect of Curcumin on Metabolic Diseases: Evidence from Clinical Studies. Int J Mol Sci. 2023 Feb 7;24(4):3323.
22. Palmer AK, Jensen MD. Metabolic changes in aging humans: current evidence and therapeutic strategies. J Clin Invest. 2022 Aug 15;132(16).
23. Yao Q, Ke ZQ, Guo S, et al. Curcumin protects against diabetic cardiomyopathy by promoting autophagy and alleviating apoptosis. J Mol Cell Cardiol. 2018 Nov;124:26-34.
24. Yi LT, Dong SQ, Wang SS, et al. Curcumin attenuates cognitive impairment by enhancing autophagy in chemotherapy. Neurobiol Dis. 2020 Mar;136:104715.
25. Zhang J, Wang J, Xu J, et al. Curcumin targets the TFEB-lysosome pathway for induction of autophagy. Oncotarget. 2016 Nov 15;7(46):75659-71.
26. Xiao K, Jiang J, Guan C, et al. Curcumin induces autophagy via activating the AMPK signaling pathway in lung adenocarcinoma cells. J Pharmacol Sci. 2013;123(2):102-9.
27. Huang L, Chen C, Zhang X, et al. Neuroprotective Effect of Curcumin Against Cerebral Ischemia-Reperfusion Via Mediating Autophagy and Inflammation. J Mol Neurosci. 2018 Jan;64(1):129-39.
28. Shen LR, Xiao F, Yuan P, et al. Curcumin-supplemented diets increase superoxide dismutase activity and mean lifespan in Drosophila. Age (Dordr). 2013 Aug;35(4):1133-42.
29. Soh JW, Marowsky N, Nichols TJ, et al. Curcumin is an early-acting stage-specific inducer of extended functional longevity in Drosophila. Exp Gerontol. 2013 Feb;48(2):229-39.
30. Bahrami A, Montecucco F, Carbone F, et al. Effects of Curcumin on Aging: Molecular Mechanisms and Experimental Evidence. Biomed Res Int. 2021;2021:8972074.
31. Shabbir U, Rubab M, Tyagi A, et al. Curcumin and Its Derivatives as Theranostic Agents in Alzheimer’s Disease: The Implication of Nanotechnology. International Journal of Molecular Sciences. 2021;22(1):196.
32. Donadio V, Incensi A, Rizzo G, et al. The Effect of Curcumin on Idiopathic Parkinson Disease: A Clinical and Skin Biopsy Study. J Neuropathol Exp Neurol. 2022 Jun 20;81(7):545-52.
33. Ellulu MS, Patimah I, Khaza’ai H, et al. Obesity and inflammation: the linking mechanism and the complications. Arch Med Sci. 2017 Jun;13(4):851-63.
34. Mousavi SM, Milajerdi A, Varkaneh HK, et al. The effects of curcumin supplementation on body weight, body mass index and waist circumference: a systematic review and dose-response meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr. 2020;60(1):171-80.
35. Zhang J, Wang Q, Rao G, et al. Curcumin improves perfusion recovery in experimental peripheral arterial disease by upregulating microRNA-93 expression. Exp Ther Med. 2019 Jan;17(1):798-802.
36. Han J, Pan XY, Xu Y, et al. Curcumin induces autophagy to protect vascular endothelial cell survival from oxidative stress damage. Autophagy. 2012 May 1;8(5):812-25.
37. Campbell MS, Ouyang A, I MK, et al. Influence of enhanced bioavailable curcumin on obesity-associated cardiovascular disease risk factors and arterial function: A double-blinded, randomized, controlled trial. Nutrition. 2019 Jun;62:135-9.
38. Lee YM, Kim Y. Is Curcumin Intake Really Effective for Chronic Inflammatory Metabolic Disease? A Review of Meta-Analyses of Randomized Controlled Trials. Nutrients. 2024 May 31;16(11):1728.
39. Fu H, Wang C, Yang D, et al. Curcumin regulates proliferation, autophagy, and apoptosis in gastric cancer cells by affecting PI3K and P53 signaling. J Cell Physiol. 2018 Jun;233(6):4634-42.
40. Kim JY, Cho TJ, Woo BH, et al. Curcumin-induced autophagy contributes to the decreased survival of oral cancer cells. Arch Oral Biol. 2012 Aug;57(8):1018-25.
41. Zhao G, Han X, Zheng S, et al. Curcumin induces autophagy, inhibits proliferation and invasion by downregulating AKT/mTOR signaling pathway in human melanoma cells. Oncol Rep. 2016 Feb;35(2):1065-74.
42. Zhuang W, Long L, Zheng B, et al. Curcumin promotes differentiation of glioma-initiating cells by inducing autophagy. Cancer Sci. 2012 Apr;103(4):684-90.
43. Karaboga Arslan AK, Uzunhisarcikli E, Yerer MB, et al. The golden spice curcumin in cancer: A perspective on finalized clinical trials during the last 10 years. J Cancer Res Ther. 2022 Jan-Mar;18(1):19-26.