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Journal of Zhejiang University SCIENCE B 2023 Vol.24 No.7 P.632-649


Andrographolide protects against atrial fibrillation by alleviating oxidative stress injury and promoting impaired mitochondrial bioenergetics

Author(s):  Pengcheng YU, Jiaru CAO, Huaxin SUN, Yingchao GONG, Hangying YING, Xinyu ZHOU, Yuxing WANG, Chenyang QI, Hang YANG, Qingbo LV, Ling ZHANG, Xia SHENG

Affiliation(s):  Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China; more

Corresponding email(s):   3101008@zju.edu.cn, ydzhangling@126.com

Key Words:  Traditional Chinese medicine, Atrial fibrillation, Andrographolide, Oxidative stress, Network pharmacology

Pengcheng YU, Jiaru CAO, Huaxin SUN, Yingchao GONG, Hangying YING, Xinyu ZHOU, Yuxing WANG, Chenyang QI, Hang YANG, Qingbo LV, Ling ZHANG, Xia SHENG. Andrographolide protects against atrial fibrillation by alleviating oxidative stress injury and promoting impaired mitochondrial bioenergetics[J]. Journal of Zhejiang University Science B, 2023, 24(7): 632-649.

@article{title="Andrographolide protects against atrial fibrillation by alleviating oxidative stress injury and promoting impaired mitochondrial bioenergetics",
author="Pengcheng YU, Jiaru CAO, Huaxin SUN, Yingchao GONG, Hangying YING, Xinyu ZHOU, Yuxing WANG, Chenyang QI, Hang YANG, Qingbo LV, Ling ZHANG, Xia SHENG",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Andrographolide protects against atrial fibrillation by alleviating oxidative stress injury and promoting impaired mitochondrial bioenergetics
%A Pengcheng YU
%A Jiaru CAO
%A Huaxin SUN
%A Yingchao GONG
%A Hangying YING
%A Xinyu ZHOU
%A Yuxing WANG
%A Chenyang QI
%A Hang YANG
%A Qingbo LV
%J Journal of Zhejiang University SCIENCE B
%V 24
%N 7
%P 632-649
%@ 1673-1581
%D 2023
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2300086

T1 - Andrographolide protects against atrial fibrillation by alleviating oxidative stress injury and promoting impaired mitochondrial bioenergetics
A1 - Pengcheng YU
A1 - Jiaru CAO
A1 - Huaxin SUN
A1 - Yingchao GONG
A1 - Hangying YING
A1 - Xinyu ZHOU
A1 - Yuxing WANG
A1 - Chenyang QI
A1 - Hang YANG
A1 - Qingbo LV
A1 - Ling ZHANG
A1 - Xia SHENG
J0 - Journal of Zhejiang University Science B
VL - 24
IS - 7
SP - 632
EP - 649
%@ 1673-1581
Y1 - 2023
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2300086

atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.


余鹏程1, 曹佳如2, 孙华鑫2, 龚颖超1, 应航鹰1, 周新宇1, 王宇星1, 祁晨阳3, 杨杭2, 吕青波1, 张玲2, 盛夏1
1浙江大学医学院附属邵逸夫医院, 浙江省心血管干预与再生重点实验室, 中国杭州市, 310016
2新疆医科大学第一附属医院, 新疆心电生理与心脏重塑重点实验室, 中国乌鲁木齐市, 830011
3浙江中医药大学第一临床医学院心内科, 中国杭州市, 310006


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]AminA, HoumsseA, IsholaA, et al., 2016. The current approach of atrial fibrillation management. Avicenna J Med, 6(1):8-16.

[2]BrunnerG, AbboudL, ShaikhKA, et al., 2012. Left atrial scar burden determined by delayed enhancement cardiac magnetic resonance at post radiofrequency ablation: association with atrial fibrillation recurrence. J Cardiovasc Magn Reson, 14(S1):P204.

[3]ChenW, SuHM, FengLN, et al., 2016. Andrographolide suppresses preadipocytes proliferation through glutathione antioxidant systems abrogation. Life Sci, 156:21-29.

[4]ChughSS, HavmoellerR, NarayananK, et al., 2014. Worldwide epidemiology of atrial fibrillation: a global burden of disease 2010 study. Circulation, 129(8):837-847.

[5]ChungMK, RefaatM, ShenWK, et al., 2020. Atrial fibrillation: JACC council perspectives. J Am Coll Cardiol, 75(14):1689-1713.

[6]DobrevD, NattelS, 2010. New antiarrhythmic drugs for treatment of atrial fibrillation. Lancet, 375(9721):1212-1223.

[7]DongY, LiaoJQ, YaoKW, et al., 2017. Application of traditional Chinese medicine in treatment of atrial fibrillation. Evid Based Complement Alternat Med, 2017:1381732.

[8]ElasoruSE, RhanaP, de Oliveira BarretoT, et al., 2021. Andrographolide protects against isoproterenol-induced myocardial infarction in rats through inhibition of L-type Ca2+ and increase of cardiac transient outward K+ currents. Eur J Pharmacol, 906:174194.

[9]GuoW, HuangJH, WangN, et al., 2019. Integrating network pharmacology and pharmacological evaluation for deciphering the action mechanism of herbal formula Zuojin pill in suppressing hepatocellular carcinoma. Front Pharmacol, 10:1185.

[10]HopkinsAL, 2008. Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol, 4(11):682-690.

[11]HuangYM, ZhouXM, LiuM, et al., 2020. The natural compound andrographolide inhibits human aortic valve interstitial cell calcification via the NF-kappa B/Akt/ERK pathway. Biomed Pharmacother, 125:109985.

[12]HuangYM, LiuM, LiuCG, et al., 2022. The natural product andrographolide ameliorates calcific aortic valve disease by regulating the proliferation of valve interstitial cells via the MAPK-ERK pathway. Front Pharmacol, 13:871748.

[13]HullTD, BodduR, GuoLL, et al., 2016. Heme oxygenase-1 regulates mitochondrial quality control in the heart. JCI Insight, 1(2):e85817.

[14]KloostermanM, ChuaW, FabritzL, et al., 2020. Sex differences in catheter ablation of atrial fibrillation: results from AXAFA-AFNET 5. EP Europace, 22(7):1026-1035.

[15]KumarA, ButlerBM, KumarS, et al., 2015. Integration of structural dynamics and molecular evolution via protein interaction networks: a new era in genomic medicine. Curr Opin Struct Biol, 35:135-142.

[16]LeiYR, TangY, HuangL, et al., 2021. Systematic review and meta-analysis on efficacy of traditional Chinese medicine for atrial fibrillation through cluster analysis. Ann Palliat Med, 10(8):8982-8990.

[17]LiXL, QiuQ, LiMY, et al., 2021. Chemical composition and pharmacological mechanism of ephedra-glycyrrhiza drug pair against coronavirus disease 2019 (COVID-19). Aging, 13(4):4811-4830.

[18]LinKH, Marthandam AsokanS, KuoWW, et al., 2020. Andrographolide mitigates cardiac apoptosis to provide cardio-protection in high-fat-diet-induced obese mice. Environ Toxicol, 35(6):707-713.

[19]MaYM, ZhangXZ, SuZZ, et al., 2015. Insight into the molecular mechanism of a herbal injection by integrating network pharmacology and in vitro. J Ethnopharmacol, 173:91-99.

[20]MaitiK, MukherjeeK, MuruganV, et al., 2010. Enhancing bioavailability and hepatoprotective activity of andrographolide from Andrographis paniculata, a well-known medicinal food, through its herbosome. J Sci Food Agric, 90(1):43-51.

[21]MittalSPK, KholeS, JagadishN, et al., 2016. Andrographolide protects liver cells from H2O2 induced cell death by upregulation of Nrf-2/HO-1 mediated via adenosine A2a receptor signalling. Biochim Biophys Acta, 1860(11 Pt A):2377-2390. https://

[22]PauklinP, ZilmerM, EhaJ, et al., 2022. Markers of inflammation, oxidative stress, and fibrosis in patients with atrial fibrillation. Oxid Med Cell Longev, 2022:4556671.

[23]RuanXF, JuCW, ShenY, et al., 2018. Suxiao Jiuxin pill promotes exosome secretion from mouse cardiac mesenchymal stem cells in vitro. Acta Pharmacol Sin, 39(4):569-578.

[24]ShiJ, YuTX, SongK, et al., 2021. Dexmedetomidine ameliorates endotoxin-induced acute lung injury in vivo and in vitro by preserving mitochondrial dynamic equilibrium through the HIF-1a/HO-1 signaling pathway. Redox Biol, 41:101954.

[25]SuHM, MoJL, NiJD, et al., 2020. Andrographolide exerts antihyperglycemic effect through strengthening intestinal barrier function and increasing microbial composition of Akkermansia muciniphila. Oxid Med Cell Longev, 2020:6538930.

[26]TanYQ, JinM, HeXH, et al., 2022. Huoxue Qingre decoction used for treatment of coronary heart disease network analysis and metabolomic evaluation. Front Pharmacol, 13:1025540.

[27]WangM, XiongH, LuL, et al., 2022. Serum lipopolysaccharide is associated with the recurrence of atrial fibrillation after radiofrequency ablation by increasing systemic inflammation and atrial fibrosis. Oxid Med Cell Longev, 2022:2405972.

[28]WangZS, TangZ, ZhuWQ, et al., 2017. Efficacy and safety of traditional Chinese medicine on thromboembolic events in patients with atrial fibrillation: a systematic review and meta-analysis. Complement Ther Med, 32:1-10.

[29]WuQQ, NiJ, ZhangN, et al., 2017. Andrographolide protects against aortic banding-induced experimental cardiac hypertrophy by inhibiting MAPKs signaling. Front Pharmacol, 8:808.

[30]XieSY, DengW, ChenJJ, et al., 2020. Andrographolide protects against adverse cardiac remodeling after myocardial infarction through enhancing Nrf2 signaling pathway. Int J Biol Sci, 16(1):12-26.

[31]YeSJ, LuoW, KhanZA, et al., 2020. Celastrol attenuates angiotensin ii-induced cardiac remodeling by targeting STAT3. Circ Res, 126(8):1007-1023.

[32]ZengML, JiangWZ, TianYJ, et al., 2017. Andrographolide inhibits arrhythmias and is cardioprotective in rabbits. Oncotarget, 8(37):61226-61238.

[33]ZhanSK, LiangJY, LinHT, et al., 2023. SATB1/SLC7A11/HO-1 axis ameliorates ferroptosis in neuron cells after ischemic stroke by Danhong injection. Mol Neurobiol, 60(1):413-427.

[34]ZhangL, PoSS, WangH, et al., 2015. Autonomic remodeling: how atrial fibrillation begets atrial fibrillation in the first 24 hours. J Cardiovasc Pharmacol, 66(3):307-315.

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