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1.广西中医药大学,南宁 530200
2.广西中医药大学,广西壮瑶药重点实验室,南宁 530200
Received:13 October 2021,
Published Online:27 December 2021,
Published:20 March 2022
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秦慧真,林思,邓玲玉等.穿心莲内酯药理作用及机制研究进展[J].中国实验方剂学杂志,2022,28(06):272-282.
QIN Hui-zhen,LIN Si,DENG Ling-yu,et al.Pharmacological Effect and Mechanism of Andrographolide: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(06):272-282.
秦慧真,林思,邓玲玉等.穿心莲内酯药理作用及机制研究进展[J].中国实验方剂学杂志,2022,28(06):272-282. DOI: 10.13422/j.cnki.syfjx.20220306.
QIN Hui-zhen,LIN Si,DENG Ling-yu,et al.Pharmacological Effect and Mechanism of Andrographolide: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(06):272-282. DOI: 10.13422/j.cnki.syfjx.20220306.
穿心莲内酯是从传统中药穿心莲中提取出来的二萜内酯类化合物,是穿心莲发挥药理药效作用的重要物质基础。现代药理研究表明,穿心莲内酯具有抗炎、抑菌、抗病毒、抗肿瘤、保肝利胆、保护心血管系统与神经系统等多种药理活性。穿心莲内酯具有显著的抗炎活性,其抗炎作用涉及多个炎症相关靶点,可通过抑制核转录因子-
κ
B(NF-
κ
B)、信号转导和转录激活因子3(STAT3)等信号通路的表达和激活,减少其下游炎症介质合成与释放、调节氧化应激和免疫反应等多种途径来实现对各种炎症性疾病的抗炎作用。同时,穿心莲内酯对多种肿瘤细胞均有抑制作用,可通过抑制肿瘤细胞增殖,阻滞细胞周期,诱导肿瘤细胞凋亡发挥抗肿瘤活性。其抗肿瘤机制涉及Notch、磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)、NF-
κ
B、分泌型糖蛋白/
β
-连环蛋白(Wnt/
β
-catenin)等细胞信号通路,能够通过调控不同的信号通路从而达到抑制肿瘤的效果。此外,穿心莲内酯还可通过调控糖代谢从而改善糖尿病的发展。在查阅穿心莲内酯相关文献时,笔者发现穿心莲内酯往往通过多途径,多靶点调控发挥药理作用,但大部分的研究并未明确其发挥药效的具体靶点,有待后续深入研究。本文就穿心莲内酯近3年药理作用及机制的相关研究进行归纳总结,并就其研究现状存在的不足提出相关建议,以期为其进一步深入研究及开发利用提供一定有益参考。
Andrographolide, a diterpene lactone, is the important material basis for the pharmacological effect of the Chinese medicinal
Andrographis paniculata
(Burm.f.)Nees. Modern pharmacological research has shown that andrographolide has many pharmacological activities such as anti-inflammation, bacteriostat, anti-virus, anti-tumor, protecting liver, promoting the function of gallbladder, and protecting the cardiovascular system and nervous system. It has significant anti-inflammatory activity which involves multiple targets. To be specific, it can inhibit nuclear factor-
κ
B (NF-
κ
B), signal transduction and activator of transcription 3 (STAT3), and other signaling pathways, reduce the synthesis and release of downstream inflammatory mediators, and regulate oxidative stress and immune response to achieve anti-inflammatory effect on various inflammatory diseases. At the same time, it suppresses a variety of tumor cells by inhibiting tumor cell proliferation, blocking cell cycle, and inducing tumor cell apoptosis. Its anti-tumor mechanism involves cellular signaling pathways such as Notch, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), NF-
κ
B, and secreted glycoprotein/
β
-catenin (Wnt/
β
-catenin). In addition, it can also alleviate diabetes by regulating glucose metabolism. According to related research, it often exerts pharmacological effects through multiple pathways and multiple targets, but the specific targets are unclear. Therefore, this article summarizes the relevant studies on the pharmacological effects and mechanisms of andrographolide in the past three years and puts forward the future research directions, which is expected to serve as a reference for the further in-depth research and development and utilization of andrographolide.
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CHEN S , LUO Z , CHEN X . Andrographolide mitigates cartilage damage via miR-27-3p-modulated matrix metalloproteinase13 repression [J]. J Gene Med , 2020 , 22 ( 8 ): e3187 .
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ZHANG L H , CAO N , WANG Y W , et al . Improvement of oxazolone-induced ulcerative colitis in rats using andrographolide [J]. Molecules , 2019 , 25 ( 1 ): 76 .
盘爱花 , 邝小玲 , 陈永敏 , 等 . 穿心莲内酯对脑梗死合并细菌性肺炎大鼠模型肺组织炎症和神经功能的影响 [J]. 中华医院感染学杂志 , 2021 , 31 ( 7 ): 961 - 966 .
亢瑞娜 , 何国莉 , 黄靓妹 , 等 . 穿心莲内酯对克雷伯杆菌肺炎大鼠肺脏病理损伤、免疫功能紊乱及TLR4/NF- κ B信号通路的调节作用 [J]. 中国免疫学杂志 , 2020 , 36 ( 12 ): 1453 - 1456 .
杨敏华 , 姚友杰 , 王娟 , 等 . 穿心莲内酯对脓毒症大鼠急性心肺组织损伤和炎症反应的影响 [J]. 医药导报 , 2021 , 40 ( 4 ): 454 - 460 .
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ZHANG X F , DING M J , CHENG C , et al . Andrographolide attenuates oxidative stress injury in cigarette smoke extract exposed macrophages through inhibiting SIRT1/ERK signaling [J]. Int Immunopharmacol , 2020 , 81 : 106230 .
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金典 , 陈思敏 , 王丽娟 , 等 . 穿心莲内酯对金黄色葡萄球菌氨基酸及糖代谢的影响研究 [J]. 中药药理与临床 , 2019 , 35 ( 1 ): 39 - 42 .
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郝丹 , 岳磊 , 黄金明 . 穿心莲内酯通过调控miR-206/STC2抑制前列腺癌细胞增殖并诱导凋亡的机制 [J]. 中国老年学杂志 , 2019 , 39 ( 19 ): 4802 - 4807 .
FORESTIER-ROMÁN I S , LÓPEZ-RIVAS A , SÁNCHEZ-VÁZQUEZ M M , et al . Andrographolide induces DNA damage in prostate cancer cells [J]. Oncotarget , 2019 , 10 ( 10 ): 1085 - 1101 .
LI J C , HUANG L X , HE Z N , et al . Andrographolide suppresses the growth and metastasis of luminal-like breast cancer by inhibiting the NF- κ B/miR-21-5p/PDCD4 signaling pathway [J]. Front Cell Dev Biol , 2021 , 9 : 643525 .
BEESETTI S L , JAYADEV M , SUBHASHINI G V , et al . Andrographolide as a therapeutic agent against breast and ovarian cancers [J]. Open Life Sci , 2019 , 14 ( 1 ): 462 - 469 .
LI Y X , JIANG B , WANG R Y , et al . Synergistic effects of tanshinone Ⅱ A and andrographolide on the apoptosis of cancer cells via crosstalk between p53 and reactive oxygen species pathways [J]. Pharmacol Rep , 2020 , 72 ( 1 ): 400 - 417 .
PASHA A , KUMBHAKAR D V , DONETI R , et al . Inhibition of inducible nitric oxide synthase (iNOS) by andrographolide and evaluation of Its antiproliferative and proapoptotic effects on cervical cancer [J]. Oxid Med Cell Longev , 2021 , 2021 : 6692628 .
魏东艳 , 魏冬梅 , 滕利 . 穿心莲内酯对人宫颈癌SiHa细胞增殖、凋亡及细胞周期的影响 [J]. 中国妇幼保健 , 2019 , 34 ( 14 ): 3341 - 3344 .
王忠玲 , 唐文哲 , 林芳荣 . 穿心莲内酯抑制宫颈癌Hela细胞生长和迁徙的研究 [J]. 中国药师 , 2019 , 22 ( 4 ): 614 - 618 .
魏东艳 , 魏冬梅 , 滕利 . 穿心莲内酯对宫颈癌U14荷瘤小鼠抗肿瘤作用的影响 [J]. 中成药 , 2020 , 42 ( 2 ): 477 - 480 .
SHARDA N , IKUSE T , HILL E , et al . Impact of andrographolide and melatonin combinatorial drug therapy on metastatic colon cancer cells and organoids [J]. Clin Med Insights-on , 2021 , doi: 10.1177/11795549211012672 http://dx.doi.org/10.1177/11795549211012672 .
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KHAN I , MAHFOOZ S , FAISAL M , et al . Andrographolide induces apoptosis and cell cycle arrest through inhibition of aberrant hedgehog signaling pathway in colon cancer cells [J]. Nutr Cancer , 2020 : 11 - 19 .
KHAN I , MAHFOOZ S A , ANSARI I A . Antiproliferative and apoptotic properties of andrographolide against human colon cancer DLD1 cell line [J]. Endocr Metab Immune , 2020 , 20 ( 6 ): 930 - 942 .
黄桔 , 李晓文 , 蒋艳平 , 等 . 穿心莲内酯对人胶质瘤细胞U87-MG的生长抑制及凋亡诱导作用的研究 [J]. 右江民族医学院学报 , 2020 , 42 ( 6 ): 685 - 689 .
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范羿 , 周宇 , 高伟 , 等 . 穿心莲内酯通过抑制PI3K/Akt通路对人肝癌HEPG2细胞凋亡的影响 [J]. 肿瘤学杂志 , 2020 , 26 ( 6 ): 496 - 500 .
刘红英 , 王协奇 , 袁丽娜 , 等 . 穿心莲内酯对人肝癌细胞MHCC97H增殖的影响及其机制研究 [J]. 广州中医药大学学报 , 2019 , 36 ( 3 ): 395 - 402 .
杨金华 , 刘向前 , 赵天增 . 穿心莲内酯对IL-6诱导的非小细胞肺癌细胞侵袭转移的影响及机制 [J]. 中国老年学杂志 , 2019 , 39 ( 17 ): 4297 - 4301 .
周颖 , 李洪水 , 王宸 , 等 . 穿心莲内酯通过影响SIRT3-p53信号通路诱导鼻咽癌C666-1细胞凋亡的机制研究 [J]. 南开大学学报:自然科学版 , 2020 , 53 ( 1 ): 106 - 112 .
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李晓文 , 周越菡 , 邓健志 , 等 . 穿心莲内酯对急性淋巴细胞白血病细胞的生长抑制及凋亡诱导作用 [J]. 中国病理生理杂志 , 2020 , 36 ( 6 ): 977 - 984 .
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李学勤 , 郝长锁 , 付迎新 . 穿心莲内酯对LPS吸入性肺炎新生大鼠NLRP3、ASC及caspase-1表达的影响 [J]. 重庆医学 , 2020 , 49 ( 13 ): 2071 - 2076,2081 .
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杨毅猛 , 田俊斌 , 马磊 . 穿心莲内酯对高脂血症大鼠心肌缺血再灌注损伤保护作用研究 [J]. 辽宁中医药大学学报 , 2020 , 22 ( 6 ): 29 - 33 .
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丁丁 , 车千红 , 徐樱溪 , 等 . 穿心莲内酯通过抑制TNF- α 活化的NF- κ B信号途径保护和促进成骨分化 [J]. 解剖科学进展 , 2019 , 25 ( 3 ): 316 - 319 .
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