Planta Med
DOI: 10.1055/a-2542-0756
Reviews

Andrographolide and its Derivatives in Cardiovascular Disease: A Comprehensive Review

Shenjie Zhang
1   Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China
,
Xiaokai Xie
1   Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China
,
Juan Zhao
2   Department of Cardiology, Tongzhou Peopleʼs Hospital, Nantong, China
,
Yilong Jiang
1   Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China
,
Chao Huang
3   Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, China
,
Qi Li
1   Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China
,
Boyu Xia
1   Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China
,
Le Yin
2   Department of Cardiology, Tongzhou Peopleʼs Hospital, Nantong, China
,
Xiaomei Yuan
4   Department of Cardiology, Sichuan Provincial Peopleʼs Hospital, University of Electronic Science and Technology of China, Chengdu, China
,
1   Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China
› Author Affiliations

Abstract

Cardiovascular disease is one of the main causes of mortality worldwide. Andrographolide represents an important category of natural phytochemicals that has significant therapeutic potential in various conditions such as acute lung injury, heart disease, and viral infections due to its anti-oxidative, anti-inflammatory, and anti-apoptotic properties. This compound plays a protective role in human pathophysiology. This review provides a comprehensive overview of the effects of andrographolide on cardiovascular disease and examines its essential roles and mechanisms in cardiovascular disease and other vascular dysfunctions. The data collected in this review serve as a comprehensive reference for the role of andrographolide in cardiovascular disease and provide valuable insights for further research and the development of andrographolide as a novel therapeutic approach for cardiovascular disease.



Publication History

Received: 16 October 2024

Accepted after revision: 03 February 2025

Article published online:
07 March 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 
  • References

  • 1 World Health Organization. World Health Statistics 2022 report: monitoring health for the SDGs, sustainable development goals. Accessed May 20, 2022 at: https://www.who.int/data/gho/publications/world-health-statistics
  • 2 Zhai ZJ, Li HW, Liu GW, Qu XH, Tian B, Yan W, Lin Z, Tang TT, Qin A, Dai KR. Andrographolide suppresses RANKL-induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo. Br J Pharmacol 2014; 171: 663-675
  • 3 Gao S, Wang D, Chai H, Xu J, Li T, Niu Y, Chen X, Qiu F, Li Y, Li H, Chen L. Unusual ent-labdane diterpenoid dimers and their selective activation of TRPV channels. J Org Chem 2019; 84: 13595-13603
  • 4 Zhang H, Li S, Si Y, Xu H. Andrographolide and its derivatives: Current achievements and future perspectives. Eur J Med Chem 2021; 224: 113710
  • 5 Zhang CY, Tan BK. Mechanisms of cardiovascular activity of Andrographis paniculata in the anaesthetized rat. J Ethnopharmacol 1997; 56: 97-101
  • 6 Lin KH, Marthandam Asokan S, Kuo WW, Hsieh YL, Lii CK, Viswanadha V, Lin YL, Wang S, Yang C, Huang CY. Andrographolide mitigates cardiac apoptosis to provide cardio-protection in high-fat-diet-induced obese mice. Environ Toxicol 2020; 35: 707-713
  • 7 Wu QQ, Ni J, Zhang N, Liao HH, Tang QZ, Deng W. Andrographolide Protects against aortic banding-induced experimental cardiac hypertrophy by inhibiting MAPKs signaling. Front Pharmacol 2017; 8: 808
  • 8 World Health Organization. World Health News. Cardiovascular diseases (CVDs). 2021 June 11. Accessed June 11, 2021 at: https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds
  • 9 GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 385: 117-171
  • 10 Institute of Medicine (US) Committee on Preventing the Global Epidemic of Cardiovascular Disease. Meeting the Challenges in Developing Countries. In: Fuster V, Kelly BB. eds. Promoting Cardiovascular Health in the Developing World: A Critical Challenge to Achieve Global Health. Washington, D.C.: National Academies Press (US); 2010
  • 11 Moran AE, Forouzanfar MH, Roth GA, Mensah GA, Ezzati M, Murray CJ, Naghavi M. Temporal trends in ischemic heart disease mortality in 21 world regions, 1980 to 2010: The global burden of disease 2010 study. Circulation 2014; 129: 1483-1492
  • 12 Vilahur G, Badimon JJ, Bugiardini R, Badimon L. Perspectives: The burden of cardiovascular risk factors and coronary heart disease in Europe and worldwide. Eur Heart J Suppl 2014; 16: A7-A11
  • 13 Mendis S, Puska P, Norrving B. World Health Organization. Global Atlas on Cardiovascular Disease Prevention and Control. Geneva: World Health Organization; 2011
  • 14 Raffa D, Maggio B, Raimondi MV, Plescia F, Daidone G. Recent discoveries of anticancer flavonoids. Eur J Med Chem 2017; 142: 213-228
  • 15 Scott J. Pathophysiology and biochemistry of cardiovascular disease. Curr Opin Genet Dev 2004; 14: 271-279
  • 16 Chakravarti RN, Chakravarti D. Andrographolide, the active constituent of Andrographis paniculata Nees; a preliminary communication. Ind Med Gaz 1951; 86: 96-97
  • 17 Abu-Ghefreh AA, Canatan H, Ezeamuzie CI. In vitro and in vivo anti-inflammatory effects of andrographolide. Int Immunopharmacol 2009; 9: 313-318
  • 18 Gupta S, Mishra KP, Ganju L. Broad-spectrum antiviral properties of andrographolide. Arch Virol 2017; 162 (03) 611-623
  • 19 Suresh K, Goud NR, Nangia A. Andrographolide: Solving chemical instability and poor solubility by means of cocrystals. Chemistry – A European journal 2013; 19: 3032-3041
  • 20 Bera R, Ahmed SK, Sarkar L, Sen T, Karmakar S. Pharmacokinetic analysis and tissue distribution of andrographolide in rat by a validated LC-MS/MS method. Pharm Biol 2014; 52: 321-329
  • 21 Bothiraja C, Shinde MB, Rajalakshmi S, Pawar AP. Evaluation of molecular pharmaceutical and in-vivo properties of spray-dried isolated andrographolide–PVP. J Pharm Pharmacol 2009; 61: 1465-1472
  • 22 Megantara S, Levita J, Iwo MI, Ibrahim S. Absorption, distribution, and toxicity prediction of andrographolide and its derivatives as anti-HIV drugs. Res J Chem Environ 2018; 22: 82-85
  • 23 Ye L, Wang T, Tang L, Liu W, Yang Z, Zhou J, Zheng Z, Cai Z, Hu M, Liu Z. Poor oral bioavailability of a promising anticancer agent andrographolide is due to extensive metabolism and efflux by P-glycoprotein. J Pharm Sci 2011; 100: 5007-5017
  • 24 Li XP, Zhang CL, Gao P, Gao J, Liu D. Effects of andrographolide on the pharmacokinetics of aminophylline and doxofylline in rats. Drug Res 2013; 63: 258-262
  • 25 Xu J, Ma Y, Xie Y, Chen Y, Liu Y, Yue P, Yang M. Design and evaluation of novel solid self-nanodispersion delivery system for andrographolide. AAPS PharmSciTech 2017; 18: 1572-1584
  • 26 Ma Y, Yang Y, Xie J, Xu J, Yue P, Yang M. Novel nanocrystal-based solid dispersion with high drug loading, enhanced dissolution, and bioavailability of andrographolide. Int J Nanomedicine 2018; 13: 3763-3779
  • 27 Zhang T, Zhu L, Li M, Hu Y, Zhang E, Jiang Q, Han G, Jin Y. Inhalable andrographolide-β-cyclodextrin inclusion complexes for treatment of Staphylococcus aureus pneumonia by regulating immune responses. Mol Pharm 2017; 14: 1718-1725
  • 28 Songvut P, Rangkadilok N, Pholphana N, Suriyo T, Panomvana D, Puranajoti P, Akanimanee J, Satayavivad J. Comparative pharmacokinetics and safety evaluation of high dosage regimens of Andrographis paniculata aqueous extract after single and multiple oral administration in healthy participants. Front Pharmacol 2023; 14: 1-12
  • 29 Tan HK, Muhammad TST, Tan ML. 14-Deoxy-11, 12-didehydroandrographolide induces DDIT3-dependent endoplasmic reticulum stress-mediated autophagy in T-47D breast carcinoma cells. Toxicol Appl Pharmacol 2016; 300: 55-69
  • 30 Cai W, Wen H, Zhou Q, Wu L, Chen Y, Zhou H, Jin M. 14-Deoxy-11, 12-didehydroandrographolide inhibits apoptosis in influenza A(H5N1) virus-infected human lung epithelial cells via the caspase-9-dependent intrinsic apoptotic pathway which contributes to its antiviral activity. Antiviral Res 2020; 181: 104885
  • 31 Liu YT, Chen HW, Lii CK, Jhuang JH, Huang CS, Li ML, Yao HT. A diterpenoid, 14-deoxy-11, 12-didehydroandrographolide, in Andrographis paniculata reduces steatohepatitis and liver injury in mice fed a high-fat and high-cholesterol diet. Nutrients 2020; 12: 523
  • 32 Burgos RA, Loyola M, Hidalgo MA, Labranche TP, Hancke JL. Effect of 14-deoxyandrographolide on calcium-mediated rat uterine smooth muscle contractility. Phytother Res 2003; 17: 1011-1015
  • 33 Roy DN, Mandal S, Sen G, Mukhopadhyay S, Biswas T. 14-Deoxyandrographolide desensitizes hepatocytes to tumor necrosis factor-alpha-induced apoptosis through calcium-dependent tumor necrosis factor receptor superfamily member 1A release via the NO/cGMP pathway. Br J Pharmacol 2010; 16: 1103-1116
  • 34 Mandal S, Nelson VK, Mukhopadhyay S, Bandhopadhyay S, Maganti L, Ghoshal N, Sen G, Biswas T. 14-Deoxyandrographolide targets adenylate cyclase and prevents ethanol-induced liver injury through constitutive NOS dependent reduced redox signaling in rats. Food Chem Toxicol 2013; 59: 236-248
  • 35 Zhang CY, Tan BK. Vasorelaxation of rat thoracic aorta caused by 14-deoxyandrographolide. Clin Exp Pharmacol Physiol 1998; 25: 424-429
  • 36 Zhang J, Sun Y, Zhong LY, Yu NN, Ouyang L, Fang RD, Wang Y, He QY. Structure-based discovery of neoandrographolide as a novel inhibitor of Rab5 to suppress cancer growth. Comput Struct Biotechnol J 2020; 18: 3936-3946
  • 37 Liu Y, Liu Y, Zhang HL, Yu FF, Yin XR, Zhao YF, Ye F, Wu XQ. Amelioratory effect of neoandrographolide on myocardial ischemic-reperfusion injury by its anti-inflammatory and anti-apoptotic activities. Environ Toxicol 2021; 36: 2367-2379
  • 38 Sharma R, Kumar K, Tanvi K. Dealkenylation of neoandrographolide, a phytochemical from Andrographis paniculata, stimulates FXR (Farnesoid X Receptor) and enhances gallstone dissolution. J Biomol Struct Dyn 2023; 41: 3339-3348
  • 39 Xu FF, Fu SJ, Gu SP, Wang ZM, Wang ZZ, He X, Xiao W. Simultaneous determination of andrographolide, dehydroandrographolide, and neoandrographolide in dog plasma by LC-MS/MS and its application to a dog pharmacokinetic study of Andrographis paniculata tablet. J Chromatogr B Analyt Technol Biomed Life Sci 2015; 990: 125-131
  • 40 Duan Y, Huang P, Sun L, Wang P, Cai Y, Shi T, Li Y, Zhou Y, Yu S. Dehydroandrographolide ameliorates doxorubicin-mediated cardiotoxicity by regulating autophagy through the mTOR-TFEB pathway. Chem Biol Interact 2024; 399: 111132
  • 41 Hsieh MJ, Chen JC, Yang WE, Chien SY, Chen MK, Lo YS, Hsi YT, Chuang YC, Lin CC, Yang SF. Dehydroandrographolide inhibits oral cancer cell migration and invasion through NF-κB-, AP-1-, and SP-1-modulated matrix metalloproteinase-2 inhibition. Biochem Pharmacol 2017; 130: 10-20
  • 42 Pu Z, Sui B, Wang X, Wang W, Li L, Xie H. The effects and mechanisms of the anti-COVID-19 traditional Chinese medicine, dehydroandrographolide from Andrographis paniculata (Burm.f.) Wall, on acute lung injury by the inhibition of NLRP3-mediated pyroptosis. *Phytomedicine: international journal of phytotherapy and phytopharmacology 2023; 114: 154753
  • 43 Ambrose JA, Singh M. Pathophysiology of coronary artery disease leading to acute coronary syndromes. F1000Prime Rep 2015; 7: 08
  • 44 Getachew R, Ballinger ML, Burch ML, Reid JJ, Khachigian LM, Wight TN, Little PJ, Osman N. PDGF beta-receptor kinase activity and ERK1/2 mediate glycosaminoglycan elongation on biglycan and increases binding to LDL. Endocrinology 2010; 151: 4356-4367
  • 45 Little PJ, Ballinger ML, Burch ML, Osman N. Biosynthesis of natural and hyperelongated chondroitin sulfate glycosaminoglycans: New insights into an elusive process. Open Biochem J 2008; 2: 135-142
  • 46 Ruparelia N, Chai JT, Fisher EA, Choudhury RP. Inflammatory processes in cardiovascular disease: A route to targeted therapies. Nat Rev Cardiol 2017; 14: 314
  • 47 Alam MA, Subhan N, Rahman MM, Uddin SJ, Reza HM, Sarker SD. Effect of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanisms of action. Adv Nutr 2014; 5: 404-417
  • 48 Lo CW, Yen CC, Chen CY, Chen HW, Lii CK. Benzyl isothiocyanate attenuates activation of the NLRP3 inflammasome in Kupffer cells and improves diet-induced steatohepatitis. Toxicol Appl Pharmacol 2023; 462: 116424
  • 49 Kirii H, Niwa T, Yamada Y, Wada H, Saito K, Iwakura Y, Asano M, Moriwaki H, Seishima M. Lack of interleukin-1beta decreases the severity of atherosclerosis in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 2003; 23: 656-660
  • 50 Kitagawa K, Matsumoto M, Sasaki T, Hashimoto H, Kuwabara K, Ohtsuki T, Hori M. Involvement of ICAM-1 in the progression of atherosclerosis in APOE-knockout mice. Atherosclerosis 2002; 160: 305-310
  • 51 Chen CC, Lii CK, Liu KL, Lin YL, Lo CW, Li CC, Yang YC, Chen HW. Andrographolide attenuates oxidized LDL-induced activation of the NLRP3 inflammasome in bone marrow-derived macrophages and mitigates HFCCD-induced atherosclerosis in mice. Am J Chin Med (Gard City N Y) 2023; 51: 2175-2193
  • 52 Al Batran R, Al-Bayaty F, Al-Obaidi MM. Evaluation of the effect of andrographolide on atherosclerotic rabbits induced by Porphyromonas gingivalis. Biomed Res Int 2014; 2014: 724718
  • 53 Batran R, Al-Bayaty F, Al-Obaidi MM, Ashrafi A. Insights into the anti-atherogenic molecular mechanisms of andrographolide against Porphyromonas gingivalis-induced atherosclerosis in rabbits. Naunyn Schmiedebergs Arch Pharmacol 2014; 387: 1141-1152
  • 54 Wu T, Chen X, Wang Y, Xiao H, Peng Y, Lin L, Xia W, Long M, Tao J, Shuai X. Aortic plaque-targeted andrographolide delivery with oxidation-sensitive micelle effectively treats atherosclerosis via simultaneous ROS capture and anti-inflammation. Nanomedicine 2018; 14: 2215-2226
  • 55 Medina-Leyte DJ, Zepeda-García O, Domínguez-Pérez M, González-Garrido A, Villarreal-Molina T, Jacobo-Albavera L. Endothelial dysfunction, inflammation and coronary artery disease: Potential biomarkers and promising therapeutical approaches. Int J Mol Sci 2021; 22: 3850
  • 56 Shu J, Huang R, Tian Y, Liu Y, Zhu R, Shi G. Andrographolide protects against endothelial dysfunction and inflammatory response in rats with coronary heart disease by regulating PPAR and NF-κB signaling pathways. Ann Palliat Med 2020; 9: 1965-1975
  • 57 Lie JT, Lawrie GM, Morris G. Aortocoronary bypass saphenous vein graft atherosclerosis. Am J Cardiol 1997; 40: 907-914
  • 58 Atkinson JB, Forman MB, Vaughn WK, Robinowitz M, McAllister HA, Virmani R. Morphologic changes in long-term saphenous vein bypass grafts. Chest 1985; 88: 341-348
  • 59 Zhu ZT, Jiang XS, Wang BC, Meng WX, Liu HY, Tian Y. Andrographolide inhibits intimal hyperplasia in a rat model of autogenous vein grafts. Cell Biochem Biophys 2011; 60: 231-239
  • 60 Tham YK, Bernardo BC, Ooi JY, Weeks KL, McMullen JR. Pathophysiology of cardiac hypertrophy and heart failure: Signaling pathways and novel therapeutic targets. Arch Toxicol 2015; 89: 1401-1438
  • 61 Mali AJ, Bothiraja C, Purohit RN, Pawar AP. In vitro and in vivo performance of novel spray dried andrographolide loaded scleroglucan based formulation for dry powder inhaler. Curr Drug Deliv 2017; 14: 968-980
  • 62 Yoopan N, Thisoda P, Rangkadilok N, Sahasitiwat S, Pholphana N, Ruchirawat S, Satayavivad J. Cardiovascular effects of 14-deoxy-11, 12-didehydroandrographolide and Andrographis paniculata extracts. Planta Med 2007; 73: 503-511
  • 63 Tian Q, Liu J, Chen Q, Zhang M. Andrographolide contributes to the attenuation of cardiac hypertrophy by suppressing endoplasmic reticulum stress. Pharm Biol 2023; 61: 61-68
  • 64 Hsieh YL, Shibu MA, Lii CK, Viswanadha VP, Lin YL, Lai CH, Chen YF, Lin KH, Kuo WW, Huang CY. Andrographis paniculata extract attenuates pathological cardiac hypertrophy and apoptosis in high-fat diet fed mice. J Ethnopharmacol 2016; 192: 170-177
  • 65 Hashmi S, Al-Salam S. Acute myocardial infarction and myocardial ischemia-reperfusion injury: A comparison. Int J Clin Exp Pathol 2015; 8: 8786-8796
  • 66 Elasoru SE, Rhana P, de Oliveira Barreto T, Naves de Souza DL, Menezes-Filho JER, Souza DS, Loes Moreira MV, Gomes Campos MT, Adedosu OT, Roman-Campos D, Melo MM, Cruz JS. 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 2021; 906: 174194
  • 67 Liu X, Xu Z. Osteogenesis in calcified aortic valve disease: From histopathological observation towards molecular understanding. Prog Biophys Mol Biol 2016; 122: 156-161
  • 68 Rutkovskiy A, Malashicheva A, Sullivan G, Bogdanova M, Kostareva A, Stensløkken KO, Fiane A, Vaage J. Valve interstitial cells: The key to understanding the pathophysiology of heart valve calcification. J Am Heart Assoc 2017; 6: e006339
  • 69 Xu K, Xie S, Huang Y, Zhou T, Liu M, Zhu P, Wang C, Shi J, Li F, Sellke FW, Dong N. Cell-type transcriptome atlas of human aortic valves reveal cell heterogeneity and endothelial to mesenchymal transition involved in calcific aortic valve disease. Arterioscler Thromb Vasc Biol 2020; 40: 2910-2921
  • 70 Liu Y, Li Z, Wang X, Ni T, Ma M, He Y, Yang R, Luo M. Effects of adjuvant Chinese patent medicine therapy on major adverse cardiovascular events in patients with coronary heart disease angina pectoris: A population-based retrospective cohort study. Acupunct Herb Med 2022; 2: 109-117
  • 71 Huang Y, Xu K, Zhou T, Zhu P, Dong N, Shi J. Comparison of rapidly proliferating, multipotent aortic valve-derived stromal cells and valve interstitial cells in the human aortic valve. Stem Cells Int 2019; 2019: 7671638
  • 72 Bortnick AE, Buzkova P, Otvos JD, Jensen MK, Tsai MY, Budoff MJ, Mackey RH, el Khoudary SR, Favari E, Kim RS, Rodriguez CJ, Thanassoulis G, Kizer JR. High-density lipoprotein and long-term incidence and progression of aortic valve calcification: The Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol 2022; 42: 1272-1282
  • 73 Wang C, Xia Y, Qu LH, Liu YJ, Liu XQ, Xu K. Cardamonin inhibits osteogenic differentiation of human valve interstitial cells and ameliorates aortic valve calcification via interfering in the NF-κB/NLRP3 inflammasome pathway. Food Funct 2021; 12: 11808-11818
  • 74 Huang Y, Liu M, Liu C, Dong N, Chen L. The natural product andrographolide ameliorates calcific aortic valve disease by regulating the proliferation of valve interstitial cells via the MAPK-ERK pathway. Front Pharmacol 2022; 13: 871748
  • 75 Huang Y, Zhou X, Liu M, Zhou T, Shi J, Dong N, Xu K. The natural compound andrographolide inhibits human aortic valve interstitial cell calcification via the NF-kappa B/Akt/ERK pathway. Biomed Pharmacother 2020; 125: 109985
  • 76 Wang C, Huang Y, Liu X, Li L, Xu H, Dong N, Xu K. Andrographolide ameliorates aortic valve calcification by regulation of lipid biosynthesis and glycerolipid metabolism targeting MGLL expression in vitro and in vivo. Cell Calcium 2021; 100: 102495
  • 77 Xie F, Han J, Wang D, Liu P, Liu C, Sun F, Xu K. Disturbing effect of cepharanthine on valve interstitial cells calcification via regulating glycolytic metabolism pathways. Front Pharmacol 2022; 13: 1070922
  • 78 Zhang D, Tang Z, Huang H, Zhou G, Cui C, Weng Y, Liu W, Kim S, Lee S, Perez-Neut M, Ding J, Czyz D, Hu R, Ye Z, He M, Zheng YG, Shuman HA, Dai L, Ren B, Zhao Y. Metabolic regulation of gene expression by histone lactylation. Nature 2019; 574: 575-580
  • 79 Wang C, Wang S, Wang Z, Han J, Jiang N, Qu L, Xu K. Andrographolide regulates H3 histone lactylation by interfering with p 300 to alleviate aortic valve calcification. Br J Pharmacol 2024; 181: 1843-1856
  • 80 Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med 2007; 357: 1121-1135
  • 81 Woo AY, Cheng CHK, Waye MM. Baicalein protects rat cardiomyocytes from hypoxia/reoxygenation damage via prooxidant mechanism. Cardiovasc Res 2005; 65: 244-253
  • 82 Woo AYH, Waye MMY, Tsui SKW, Yeung STW, Cheng CHK. Andrographolide up-regulates cellular-reduced glutathione level and protects cardiomyocytes against hypoxia/reoxygenation injury. Pharmacol Rev 2008; 325: 226-235
  • 83 Xie S, Deng W, Chen J, Wu QQ, Li H, Wang J, Wei L, Liu C, Duan M, Cai Z, Xie Q, Hu T, Zeng X, Tang Q. Andrographolide protects against adverse cardiac remodeling after myocardial infarction through enhancing Nrf2 signaling pathway. Int J Biol Sci 2020; 16: 12-26
  • 84 Gao S, Wang D, Chai H, Xu J, Li T, Niu Y, Chen X, Qiu F, Li Y, Li H, Chen L. Unusual ent-labdane diterpenoid dimers and their selective activation of TRPV channels. J Org Chem 2019; 84: 13595-13603
  • 85 Li Y, Xiang LL, Miao JX, Miao MS, Wang C. Protective effects of andrographolide against cerebral ischemia reperfusion injury in mice. Int J Mol Med 2021; 48: 186
  • 86 Liang E, Liu X, Du Z, Yang R, Zhao Y. Andrographolide ameliorates diabetic cardiomyopathy in mice by blockage of oxidative damage and NF-κB-mediated inflammation. Oxid Med Cell Longev 2018; 2018: 9086747
  • 87 Rajesh M, Bátkai S, Kechrid M, Mukhopadhyay P, Lee WS, Horváth B, Holovac E, Cinar R, Liaudet L, Mackie K, Haskó G, Pacher P. Cannabinoid 1 receptor promotes cardiac dysfunction, oxidative stress, inflammation, and fibrosis in diabetic cardiomyopathy. Diabetes 2012; 61: 716-727
  • 88 Kajstura J, Fiordaliso F, Andreoli AM, Li B, Chimenti S, Medow MS, Limana F, Nadal-Ginard B, Leri A, Anversa P. IGF-1 overexpression inhibits the development of diabetic cardiomyopathy and angiotensin II-mediated oxidative stress. Diabetes 2001; 50: 1414-1424
  • 89 Rajesh M, Mukhopadhyay P, Bátkai S, Patel V, Saito K, Matsumoto S, Kashiwaya Y, Horváth B, Mukhopadhyay B, Becker L, Haskó G, Liaudet L, Wink DA, Veves A, Mechoulam R, Pacher P. Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy. J Am Coll Cardiol 2010; 56: 2115-2125
  • 90 Chugh SS, Havmoeller R, Narayanan K, Singh D, Rienstra M, Benjamin EJ, Gillum RF, Kim YH, McAnulty jr. JH, Zheng ZJ, Forouzanfar MH, Naghavi M, Mensah GA, Ezzati M, Murray CJ. Worldwide epidemiology of atrial fibrillation: A global burden of disease 2010 study. Circulation 2014; 129: 837-847
  • 91 Chung MK, Refaat M, Shen WK, Kutyifa V, Cha YM, Di Biase L, Baranchuk A, Lampert R, Natale A, Fisher J, Lakkireddy DR. ACC Electrophysiology Section Leadership Council. Atrial fibrillation: JACC council perspectives. J Am Coll Cardiol 2020; 75: 1689-1713
  • 92 Dobrev D, Nattel S. New antiarrhythmic drugs for treatment of atrial fibrillation. Lancet 2010; 375: 1212-1223
  • 93 Brunner G, Abboud L, Shaikh KA, Dave AS, Morrisett J, Zoghbi WA, Valderrábano M, Shah DJ. Left atrial scar burden determined by delayed enhancement cardiac magnetic resonance at post radiofrequency ablation: association with atrial fibrillation recurrence. J Cardiovasc Magn Reson 2012; 14: P204
  • 94 Kloosterman M, Chua W, Fabritz L, Al-Khalidi HR, Schotten U, Nielsen JC, Piccini JP, Di Biase L, Häusler KG, Todd D, Mont L, Van Gelder IC, Kirchhof P. AXAFA-AFNET 5 investigators. Sex differences in catheter ablation of atrial fibrillation: Results from AXAFA-AFNET 5. Europace 2020; 22: 1026-1035
  • 95 Ye S, Luo W, Khan ZA, Wu G, Xuan L, Shan P, Lin K, Chen T, Wang J, Hu X, Wang S, Huang W, Liang G. Celastrol attenuates angiotensin II-induced cardiac remodeling by targeting STAT3. Circ Res 2020; 126: 1007-1023
  • 96 Zhang L, Po SS, Wang H, Scherlag BJ, Li H, Sun J, Lu Y, Ma Y, Hou Y. Autonomic remodeling: how atrial fibrillation begets atrial fibrillation in the first 24 hours. J Cardiovasc Pharmacol 2015; 66: 307-315
  • 97 Yu P, Cao J, Sun H, Gong Y, Ying H, Zhou X, Wang Y, Qi C, Yang H, Lv Q, Zhang L, Sheng X. Andrographolide protects against atrial fibrillation by alleviating oxidative stress injury and promoting impaired mitochondrial bioenergetics. J Zhejiang Univ Sci B 2023; 24: 632-649
  • 98 Yin B, Zhang S, Huang Y, Long Y, Chen Y, Zhao S, Zhou A, Cao M, Yin X, Luo D. The antithrombosis effect of dehydroandrographolide succinate: In vitro and in vivo studies. Pharm Biol 2022; 60: 175-184
  • 99 Zhang JY, Sun GB, Wang M, Liao P, Du YY, Yang K, Sun XB. Arsenic trioxide triggered calcium homeostasis imbalance and induced endoplasmic reticulum stress-mediated apoptosis in adult rat ventricular myocytes. Toxicol Res (Camb) 2016; 5: 682-688
  • 100 Alamolhodaei NS, Shirani K, Karimi G. Arsenic cardiotoxicity: An overview. Environ Toxicol Pharmacol 2015; 40: 1005-1014
  • 101 Chen B, Peng X, Pentassuglia L, Lim CC, Sawyer DB. Molecular and cellular mechanisms of anthracycline cardiotoxicity. Cardiovasc Toxicol 2007; 7: 114-121
  • 102 Akimoto H, Bruno NA, Slate DL, Billingham ME, Torti SV, Torti FM. Effect of verapamil on doxorubicin cardiotoxicity: altered muscle gene expression in cultured neonatal rat cardiomyocytes. Cancer Res 1993; 53: 4658-4664
  • 103 Kalyanaraman B, Joseph J, Kalivendi S, Wang S, Konorev E, Kotamraju S. Doxorubicin-induced apoptosis: Implications in cardiotoxicity. Mol Cell Biochem 2002; 234 – 235: 119-124
  • 104 Tokarska-Schlattner M, Zaugg M, Zuppinger C, Wallimann T, Schlattner U. New insights into doxorubicin-induced cardiotoxicity: The critical role of cellular energetics. J Mol Cell Cardiol 2006; 41: 389-405
  • 105 Safaeian L, Shafiee F, Haghighatnazar S. Andrographolide protects against doxorubicin-and arsenic trioxide-induced toxicity in cardiomyocytes. Mol Biol Rep 2023; 50: 389-397
  • 106 Ratiani L, Pachkoria E, Mamageishvili N, Shengelia R, Hovhannisyan A, Panossian A. Efficacy of Kan Jang® in patients with mild COVID-19: A randomized, quadruple-blind, placebo-controlled trial. Pharmaceuticals (Basel) 2023; 16: 1196
  • 107 Kanokkangsadal P, Mingmalairak C, Mukkasombat N, Kuropakornpong P, Worawattananutai P, Khawcharoenporn T, Sakpakdeejaroen I, Davies NM, Itharat A. Andrographis paniculata extract versus placebo in the treatment of COVID-19: A double-blinded randomized control trial. Res Pharm Sci 2023; 18: 592-603