中药有效成分减轻对乙酰氨基酚肝损伤研究进展

阮豪南, 王露露, 孙航, 何晓凤, 刘芳芳, 张晶

中国药学杂志 ›› 2019, Vol. 54 ›› Issue (2) : 81-85.

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中国药学杂志
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中国药学杂志 ›› 2019, Vol. 54 ›› Issue (2) : 81-85. DOI: 10.11669/cpj.2019.02.001
综述

中药有效成分减轻对乙酰氨基酚肝损伤研究进展

  • 阮豪南1, 王露露2, 孙航1, 何晓凤1, 刘芳芳2*, 张晶1,3*
作者信息 +

Research Advance of Effective Components of Traditional Chinese Medicine on Alleviating Acetaminophen-Induced Liver Injury

  • RUAN Hao-nan1, WANG Lu-lu2, SUN Hang1, HE Xiao-feng1, LIU Fang-fang2*, ZHANG Jing1,3*
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文章历史 +

摘要

对乙酰氨基酚(APAP)是普遍使用的镇痛解热消炎药物之一,其由于盲目大量用药、联合用药或长期用药会引起药物性肝损伤,甚至急性肝衰竭。APAP所诱导肝毒性的机制研究主要集中在其毒性代谢产物的生成、线粒体功能障碍、炎症反应、氧化应激、损伤相关的分子模式(damage associated molecular patterns,DAMPs)的释放、细胞自噬、内质网应激以及微循环功能障碍等方面。笔者归纳了APAP所致药物性肝损伤的毒性机制,并整理了中药有效成分对APAP致肝损伤保护作用的研究进展,其中包括多酚类、黄酮类、皂苷、有机酸、萜类化合物、苯丙素类化合物、糖类、生物碱以及其他化合物,旨在为开发防治APAP致肝损伤的药物提供参考。

Abstract

Acetaminophen (APAP) is one of the commonly used analgesic antipyretic anti-inflammatory drugs, which cause drug-induced liver damage and even acute liver failure due to take large amounts of drugs blindly, combination drugs-using or long-term medication. The mechanisms of APAP-induced hepatotoxicity mainly focus on the generation of toxic metabolites, mitochondrial dysfunction, inflammatory response, oxidative stress, the release of damage associated molecular patterns (DAMPs), autophagy, endoplasmic reticulum stress, and microcirculatory dysfunction. This article summarizes the toxic mechanism of drug-induced liver injury induced by APAP, and summarizes the research progress of active ingredients of traditional Chinese medicine on the protective effect of APAP-induced liver injury, including polyphenols, flavonoids, saponins, organic acids, terpenoids, phenylpropanoids compounds, sugars, alkaloids and other compounds, to provide a reference for the development of drugs to prevent and treat APAP-induced liver injury.

关键词

中药 / 对乙酰氨基酚 / 肝损伤 / 保护作用 / 多酚类 / 黄酮类

Key words

traditional Chinese medicine / acetaminophen / liver injury / protective effect / polyphenols / flavonoids

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阮豪南, 王露露, 孙航, 何晓凤, 刘芳芳, 张晶. 中药有效成分减轻对乙酰氨基酚肝损伤研究进展[J]. 中国药学杂志, 2019, 54(2): 81-85 https://doi.org/10.11669/cpj.2019.02.001
RUAN Hao-nan, WANG Lu-lu, SUN Hang, HE Xiao-feng, LIU Fang-fang, ZHANG Jing. Research Advance of Effective Components of Traditional Chinese Medicine on Alleviating Acetaminophen-Induced Liver Injury[J]. Chinese Pharmaceutical Journal, 2019, 54(2): 81-85 https://doi.org/10.11669/cpj.2019.02.001
中图分类号： R965   

参考文献

[1] LEISE M D, POTERUCHA J J, TALWALKAR J A. Drug-induced liver injury[J]. Mayo Clin Proc, 2014, 89(1): 95-106.
[2] LANCASTER E M, HIATT J R, ZARRINPAR A. Acetaminophen hepatotoxicity: an updated review[J]. Arch Toxicol, 2015, 89(2):193-199.
[3] MICHAUT A, MOREAU C, ROBIN M A, et al. Acetaminophen-induced liver injury in obesity and nonalcoholic fatty liver disease[J]. Liver Int, 2014, 34(7): 1-9.
[4] YANG X J. The role of FGF21 in acetaminophen-induced acute liver failure in mice [D]. Changchun:Jilin University, 2014.
[5] BUNCHORNTAVAKUL C, REDDY K R. Acetaminophen-related hepatotoxicity[J]. Clin Liver Dis, 2013, 17(4):587-607.
[6] WANG X, SUN R, WEI H, et al. High-mobility group box 1 (HMGB1)-toll-like receptor (TLR)4-interleukin (IL)-23-IL-17A axis in drug-induced damage-associated lethal hepatitis: interaction of γδ T cells with macrophages[J]. Hepatology, 2013, 57(1):373-384.
[7] LEE K K, IMAIZUMI N, CHAMBERLAND S R, et al. Targeting mitochondria with methylene blue protects mice against acetaminophen-induced liver injury[J]. Hepatology, 2015, 61(1):326-336.
[8] SAITO C, LEMASTERS J H. c-Jun N-terminal kinase modulates oxidant stress and peroxynitrite formation independent of inducible nitric oxide synthase in acetaminophen hepatotoxicity[J]. Toxicol Appl Pharmacol, 2010, 246(2):8-17.
[9] YANG R. Inflammation plays a dual role in acetaminophen hepatotoxicity[J]. Trans Med J, 2016, 5(3):129-133.
[10] WU K, GUO C, WU X, et al. Ameliorative effectiveness of allicin on acetaminophen-induced acute liver damage in mice[J]. J Funct Foods, 2015, 18:665-672.
[11] ZHANG L, ZHAN J, WU B, et al. The role of TNF-α in acetaminophen-induced drug-induced liver injury in rats[J]. J Gastroevcterol Hepatol, 2014, 23(10): 1181-1183.
[12] DU K, ANUP R, HARTMUT J. Oxidative stress during acetaminophen hepatotoxicity: sources, pathophysiological role and therapeutic potential[J]. Redox Biol, 2016, 10:148-156.
[13] KNOCKAERT L, DESCATOIRE V, VADROT N, et al. Mitochondrial CYP2E1 is sufficient to mediate oxidative stress and cytotoxicity induced by ethanol and acetaminophen[J]. Toxicol In Vitro, 2011, 25(2):475-484.
[14] TANG D, KANG R, COYNE C B, et al. PAMPs and DAMPs: signal 0s that spur autophagy and immunity[J]. Immunol Rev, 2012, 249(1):158-175.
[15] KURAMOCHI M, IZAWA T, PERVIN M, et al. The kinetics of damage-associated molecular patterns (DAMPs) and toll-like receptors during thioacetamide-induced acute liver injury in rats[J]. Exp Toxicol Pathol, 2016, 68(8):471-477.
[16] MOORE M N. Autophagy as a second level protective process in conferring resistance to environmentally-induced oxidative stress[J]. Autophagy, 2008, 4(2):254-256.
[17] CHAO X,WANG H,JAESCHKE H,et al. Role and mechanisms of autophagy in acetaminophen-induced liver injury[J]. Liver Int, 2018, 3(5):201-209.
[18] NI H M, MCGILL M R, CHAO X, et al. Removal of acetaminophen protein adducts by autophagy protects against acetaminophen-induced liver injury in mice[J]. J Hepatol, 2016, 65(2):354-362.
[19] DARA L, JI C, KAPLOWITZ N. The contribution of endoplasmic reticulum stress to liver diseases[J]. Hepatology, 2011, 53(5):1752-1763.
[20] NAGY G, SZARKA A, LOTZ G, et al. BGP-15 inhibits caspase-independent programmed cell death in acetaminophen-induced liver injury[J]. Toxicol Appl Pharmacol, 2010, 243(1):96-103.
[21] UZI D, BARDA L, SCAIEWICZ V, et al. CHOP is a critical regulator of acetaminophen-induced hepatotoxicity[J]. J Hepatol, 2013, 59(3):495-503.
[22] ITO Y, BETHEA N W, ABRIL E R, et al. Early hepatic microvascular injury in response to acetaminophen toxicity[J]. Microcirculation, 2015, 10(5):391-400.
[23] MIYAKAWA K, JOSHI N, SULLIVAN B P, et al. Platelets and protease-activated receptor-4 contribute to acetaminophen-induced liver injury in mice[J]. Blood, 2015, 126(15):1835-1843.
[24] KOPEC A K, JOSHI N, CLINE-FEDEWA H, et al. Fibrin(ogen) drives repair after acetaminophen-induced liver injury via leukocyte α M β 2, integrin-dependent upregulation of Mmp12[J]. J Hepatol, 2017, 66(4):240-249.
[25] NGUYEN N U, STAMPER B D. Polyphenols reported to shift APAP-induced changes in MAPK signaling and toxicity outcomes[J]. Chem Biol Interact, 2017, 183(277): 129-136.
[26] HASANEIN P, SHARIFI M. Effects of rosmarinic acid on acetaminophen-induced hepatotoxicity in male Wistar rats[J]. Pharm Biol, 2017, 55(1):1809-1816.
[27] WU H, PANG H, CHEN Y, et al. Anti-inflammatory effect of a polyphenol-enriched fraction from acalyphawilkesiana on lipopolysaccharide-stimulated RAW 264.7 macrophages and acetaminophen-induced liver injury in mice[J]. Oxid Med Cell Longev, 2018, 68(3):21-38.
[28] TSAI M S, WANG Y H, LAI Y Y, et al. Kaempferol protects against propacetamol-induced acute liver injury through CYP2E1 inactivation, UGT1A1 activation, and attenuation of oxidative stress, inflammation and apoptosis in mice[J]. Toxicol Lett, 2018, 290:97-109.
[29] QI Z L, WANG W, LI W, et al. Protective effects of ginseng anthocyanins on acetaminophen-induced liver injury in mice[J]. Chin Tradit Herb Drug(中草药), 2017, 48(13): 2704-2710.
[30] XIE W, JIANG Z, JIAN W, et al. Protective effect of hyperoside against acetaminophen (APAP) induced liver injury through enhancement of APAP clearance[J]. Chem Biol Interact, 2016, 246(3):11-19.
[31] FU T, WANG S, LIU J, et al. Protective effects of α-mangostin against acetaminophen-induced acute liver injury in mice[J]. Eur J Pharmacol, 2018, 827(53):33-48.
[32] LV H, XIAO Q, ZHOU J, et al. Licochalcone A upregulates Nrf2 antioxidant pathway and thereby alleviates acetaminophen-induced hepatotoxicity[J]. Front Pharmacol, 2018, 9:147.
[33] XU X Y, HU J N, LIU Z, et al. Saponins (ginsenosides) from the leaves of panax quinquefolius ameliorated acetaminophen-induced hepatotoxicity in mice[J]. J Agric Food Chem, 2017, 65(18):3684-3692.
[34] HU J N, XU X Y, LI W, et al. Ginsenoside Rk1 ameliorates acetaminophen-induced hepatotoxicity in mice through inhibition of inflammation, oxidative stress, nitrative stress and apoptosis[J]. J Ginseng Res, 2017, 3(7):1-12.
[35] NING C Q, GAO X G, WANG C Y, et al. Ginsenoside Rg1 protects against acetaminophen-induced liver injury via activating Nrf2 signaling pathway in vivo and in vitro[J]. Regul Toxicol Pharmacol, 2018, 98: 58-68.
[36] LENG J, WANG Z, FU C L, et al. NF-κB and AMPK/PI3K/Akt signaling pathways are involved in the protective effects of Platycodon grandiflorum saponins against acetaminophen-induced acute hepatotoxicity in mice[J]. Phytother Res, 2018, 31(11):1-12.
[37] HEIDARI R, JAMSHIDZADEH A, NIKNAHAD H, et al. Effect of taurine on chronic and acute liver injury: focus on blood and brain ammonia[J]. Toxicol Rep, 2016, 3:870-879.
[38] JIANG W P, HUANG S S, MATSUDA Y, et al. Protective effects of tormentic acid, a major component of suspension cultures of eriobotrya japonica cells, on acetaminophen-induced hepatotoxicity in mice[J]. Molecules, 2017, 22(5):830-844.
[39] CHA H, LEE S, LEE J H, et al. Protective effects of p-coumaric acid against acetaminophen-induced hepatotoxicity in mice[J]. Food Chem Toxicol, 2018, 121: 131-139.
[40] UCHIDA N S, SILVAFILHO S E, AGUIAR R P, et al. Protective effect of Cymbopogon citratus essential oil in experimental model of acetaminophen-induced liver injury[J]. Am J Chin Med, 2017,45(3):1-18.
[41] ZHANG J, ZHANG S, BI J, et al. Astaxanthin pretreatment attenuates acetaminophen-induced liver injury in mice[J]. Int Immunopharmacol, 2017, 45:26-33.
[42] YOSHIOKA H, AOYAGI Y, FUKUISHI N, et al. Suppressive effect of kamebakaurin on acetaminophen-induced hepatotoxicity by inhibiting lipid peroxidation and inflammatory response in mice[J]. Pharmacol Rep, 2017, 69(5):903-918.
[43] JIANG Y, FAN X, WANG Y, et al. Hepato-protective effects of six schisandra lignans on acetaminophen-induced liver injury are partially associated with the inhibition of CYP-mediated bioactivation[J]. Chem Biol Interact, 2015, 231(10):83-89.
[44] JIANG Y M, WANG Y, TAN H S, et al. Schisandrol B protects against acetaminophen-induced acute hepatotoxicity in mice via activation of the NRF2/ARE signaling pathway[J]. Acta Pharmacol Sin(中国药理学报), 2016, 37(3):382-389.
[45] YAN M Z, YE L H, YIN S T, et al. Glycycoumarin protects mice against acetaminophen-induced liver injury predominantly via activating sustained autophagy[J]. Br J Pharmacol, 2018, 175(19): 3747-3757.
[46] LIN G S, LUO D D, LIU J J, et al. Hepatoprotective effect of polysaccharides isolated from against acetaminophen-induced liver injury in mice via regulation of the Nrf2-Keap1 signaling pathway[J]. Oxid Med Cell Longev, 2018, 69(6): 24-39.
[47] ZHAO W H, ZENGC, JIA Q Q, et al. Effects of the Kunlun snow chrysanthemum polysaccharides on acetaminophen-induced oxidative stress, inflammation and apoptosis using animal model[J]. Pak J Pharm Sci, 2018, 31(3): 985-990.
[48] WU K, FAN J L, HUANG X Y, et al. Hepatoprotective effects exerted by Poria Cocos polysaccharides against acetaminophen-induced liver injury in mice[J]. Int J Biol Macromol, 2018, 114: 137-142.
[49] LI J, PANY, KAN M J, et al. Hepatoprotective effects of berberine on liver fibrosis via activation of AMP-activated protein kinase[J]. Life Sci, 2014, 98(1): 24-30.
[50] ZHAO Z, WEI Q Y, HUA W W, et al. Hepatoprotective effects of berberine on acetaminophen-induced hepatotoxicity in mice[J]. Biomed Pharmacother, 2018, 103: 1319-1326.
[51] PARK G, KIM K M, CHOI S, et al. Aconitum carmichaelii protects against acetaminophen-induced hepatotoxicity via B-cell lymphoma-2 protein-mediated inhibition of mitochondrial dysfunction[J]. Environ Toxicol Pharmacol, 2016, 42:218-225.
[52] BIAN X B, WANG S J, LIU J P, et al. Hepatoprotective effect of chiisanoside against acetaminophen-induced acute liver injury in mice[J]. Nat Prod Res, 2018, 14(6):1478-1486.
[53] WANGKHEIRAKPAM S D, JOSHI D D, LEISHANGTHEM G D, et al. Hepatoprotective effect of Auricularia delicata (Agaricomycetes) from India in rats: biochemical and histopathological studies and antimicrobial activity[J]. Int J Med Mushrooms, 2018, 20(3): 213-225.
[54] GUO S, ZHANG S, LIU L, et al. Pinelliae rhizoma praeparatum involved in the regulation of bile acids metabolism in hepatic injury[J]. Biol Pharm Bull, 2018, 41(6): 869-876.
[55] IBRAHIM R M, EL-AGAMY D S, ABDALLAH H M, et al. Protective activity of tovophyllin A, a xanthone isolated from Garcinia mangostana pericarps, against acetaminophen-induced liver damage: role of Nrf2 activation[J]. Food Funct, 2018, 9(6): 3291-3300.
[56] ZHANG J, SONG Q, HAN X, et al. Multi-targeted protection of acetaminophen-induced hepatotoxicity in mice by tannic acid[J]. Int Immunopharmacol, 2017, 47:95-105.

基金

吉林省科技发展计划项目资助(20160204004YY);长春市科技计划项目资助(18SS017)
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