J. Pharm. Pharmacogn. Res., vol. 12, no. 3, pp. 487-513, May-Jun 2024.

DOI: https://doi.org/10.56499/jppres23.1841_12.3.487

Review

Andrographis paniculata: A potential supplementary therapy for cardiovascular diseases - A systematic review of its effects and molecular actions

[Andrographis paniculata: Una terapia suplementaria potencial para las enfermedades cardiovasculares - Una revisión sistemática de sus efectos y acciones moleculares]

Oluebube Magnificient Eziefule¹, Wawaimuli Arozal^2*, Septelia Inawati Wanandi³, Syarifah Dewi³, Nafrialdi², Meilania Saraswati⁴, Melva Louisa²

¹Master’s Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Kampus UI Salemba, Central Jakarta 10430, Indonesia.

²Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, JI. Salemba, Raya No. 6, Jakarta 10430 Indonesia.

³Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, JI. Salemba, Raya No. 6, Jakarta 10430 Indonesia.

⁴Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, JI. Salemba, Raya No. 6, Jakarta 10430 Indonesia.

*E-mail: wawaimuli.arozal@ui.ac.id

Abstract

Context: Cardiovascular diseases claim the lives of an estimated 17.9 million people worldwide (report by the World Health Organization), yet the drug pipeline compared to some other life-threatening diseases, including cancer and neurological disorders, is low.

Aims: To investigate the potential of Andrographis paniculata as a supplementary therapy for cardiovascular diseases based on recent in vivo animal studies.

Methods: This study adopted a systematic review approach to analyze preclinical evidence from in vivo animal studies. Three databases (PubMed, Scopus, and Embase) were searched using the keywords “Andrographis paniculata”, “cardiovascular disease”, “CVD”, “heart disease”, “cardioprotective”, “cardio^*”, “inflammation”, “oxidative stress”, “obesity”, “lipopolysaccharide”, “hypertension”, “arrhythmia” and “aortic disease”. The search period was from April 20^th, 2023, to April 26^th, 2023, and included studies published from 2013 to 2023. Only in vivo animal studies were appraised. In contrast, clinical studies, in vitro studies, in silico studies, and review papers were excluded. SYRCLE’s risk of bias tool was used to assess the risk of bias.

Results: Sixteen eligible in vivo animal studies showed that Andrographis paniculata extracts and isolated bioactive compounds have strong anti-inflammatory and antioxidant effects on cardiovascular diseases. These effects lead to lowering the risk of coronary artery disease and myocardial infarction, easing the effects of bad cardiac remodeling, stopping cardiac hypertrophy, and improving diabetic cardiomyopathy. Although SYRCLE's tool detected some bias, the studies were included since they met the inclusion criteria and had no conflicts of interest.

Conclusions: Andrographis paniculata may have the potential to be used as a supplementary therapy for cardiovascular diseases, but more animal studies and clinical trials should be done to establish these findings.

Keywords: Andrographis paniculata; animal models; cardiovascular diseases; herbal medicine; inflammation; oxidative stress.

Resumen

Contexto: Se calcula que las enfermedades cardiovasculares se cobran la vida de 17,9 millones de personas en todo el mundo (informe de la Organización Mundial de la Salud) y, sin embargo, el número de fármacos disponibles es bajo en comparación con otras enfermedades potencialmente mortales, como el cáncer y los trastornos neurológicos.

Objetivos: Investigar el potencial de Andrographis paniculata como terapia complementaria para enfermedades cardiovasculares basándonos en estudios recientes in vivo en animales.

Métodos: Este estudio adoptó un enfoque de revisión sistemática para analizar la evidencia preclínica de estudios in vivo en animales. Se realizaron búsquedas en tres bases de datos (PubMed, Scopus y Embase) utilizando las palabras clave "Andrographis paniculata", "cardiovascular disease", "CVD", "heart disease", "cardioprotective", "cardio*", "inflammation", "oxidative stress", "obesity", "lipopolysaccharide", "hypertension", "arrhythmia" y "aortic disease". El periodo de búsqueda fue del 20 de abril de 2023 al 26 de abril de 2023, e incluyó estudios publicados entre 2013 y 2023. Sólo se valoraron estudios in vivo en animales. Por el contrario, se excluyeron los estudios clínicos, los estudios in vitro, los estudios in silico y los artículos de revisión. Se utilizó la herramienta de riesgo de sesgo de SYRCLE para evaluar el riesgo de sesgo.

Resultados: Dieciséis estudios in vivo con animales demostraron que los extractos de Andrographis paniculata y los compuestos bioactivos aislados tienen potentes efectos antiinflamatorios y antioxidantes sobre las enfermedades cardiovasculares. Estos efectos conducen a la reducción del riesgo de enfermedad coronaria e infarto de miocardio, el alivio de los efectos de la mala remodelación cardiaca, la detención de la hipertrofia cardiaca y la mejora de la cardiomiopatía diabética. Aunque la herramienta SYRCLE detectó cierto sesgo, los estudios se incluyeron ya que cumplían los criterios de inclusión y no presentaban conflictos de intereses.

Conclusiones: Andrographis paniculata puede tener potencial para ser utilizada como terapia complementaria en enfermedades cardiovasculares, pero deben realizarse más estudios en animales y ensayos clínicos para establecer estos hallazgos.

Palabras Clave: Andrographis paniculata; modelos animales; enfermedades cardiovasculares; fitoterapia; inflamación; estrés oxidativo.

 

https://jppres.com/jppres/pdf/vol12/jppres23.1841_12.3.487.pdf

Citation Format: Eziefule OM, Arozal W, Wanandi SI, Dewi S, Nafrialdi, Saraswati M, Louisa M (2024) Andrographis paniculata: A potential supplementary therapy for cardiovascular diseases - A systematic review of its effects and molecular actions. J Pharm Pharmacogn Res 12(3): 487–513. https://doi.org/10.56499/jppres23.1841_12.3.487

References

Ahmad E, Lim S, Lamptey R, Webb DR, Davies MJ (2022) Type 2 diabetes. Lancet 400(10365): 1803–1820. https://doi.org/10.1016/S0140-6736(22)01655-5

Akhtar MT, Sarib MSBM, Ismail IS, Abas F, Ismail A, Lajis NH, Shaari K (2016) Anti-diabetic activity and metabolic changes induced by Andrographis paniculata plant extract in obese diabetic rats. Molecules 21(8): 1026. https://doi.org/10.3390/molecules21081026

Al Batran R, Al-Bayaty F (2014) Insights into the antiatherogenic molecular mechanisms of andrographolide against Porphyromonas gingivalis -induced atherosclerosis in rabbits. Naunyn-Schmiedeberg's Arch Pharmacol 387(12): 1141–1152. https://doi.org/10.1007/s00210-014-1041-x

Al Batran R, Al-Bayaty F, Jamil Al-Obaidi MM, Hussain SF, Mulok TZ (2014) Evaluation of the effect of andrographolide on atherosclerotic rabbits induced by Porphyromonas gingivalis. BioMed Res Int 2014: 724718. https://doi.org/10.1155/2014/724718

Al-Madhagi HA (2023) FDA-approved drugs in 2022: A brief outline. Saudi Pharm J 31(3): 401–409. https://doi.org/10.1016/j.jsps.2023.01.007

Assmann G, Cullen P, Jossa F, Lewis B, Mancini M (1999) Coronary heart disease: Reducing the risk - The scientific background to primary and secondary prevention of coronary heart disease. A worldwide view. Arterioscler Thromb Vasc Biol 19(8): 1819–1824. https://doi.org/10.1161/01.atv.19.8.1819

Bhargava S, de la Puente-Secades S, Schurgers L, Jankowski J (2022) Lipids and lipoproteins in cardiovascular diseases: A classification. Trends Endocrinol Metab 33(6): 409–423. https://doi.org/10.1016/j.tem.2022.02.001

Boudina S, Abel ED (2010) Diabetic cardiomyopathy, causes and effects. Rev Endocr Metab Disord 11(1): 31–39. https://doi.org/0.1007/s11154-010-9131-7

Bryant NJ, Govers R, James DE (2002) Regulated transport of the glucose transporter GLUT4. Nat Rev Mol Cell Biol 3(4): 267–277. https://doi.org/10.1038/nrm782

Chen CC, Lii CK, Lin YH, Shie PH, Yang YC, Huang CS, Chen HW (2020) Andrographis paniculata improves insulin resistance in high-fat diet-induced obese mice and TNFα-treated 3T3-L1 adipocytes. Am J Chin Med 48(5): 1073–1090. https://doi.org/10.1142/S0192415X20500524

Chturvedi GN, Tomar GS, Tiwari SK, Singh KP (1983) Clinical studies of kalmegh (Andrographis paniculata Nees) in effective hepatitis. Anc Sci Life 2(4): 208–215. https://pubmed.ncbi.nlm.nih.gov/22556984/

DiMeglio LA, Evans-Molina C, Oram RA (2018) Type 1 diabetes. Lancet 391(10138): 2449–2462. https://doi.org/10.1016/S0140-6736(18)31320-5

Ding L, Li J, Song B, Xiao X, Huang W, Zhang B, Tang X, Qi M., Yang Q, Yang Q, Yang L, Wang Z (2014) Andrographolide prevents high-fat diet-induced obesity in C57BL/6 mice by suppressing the sterol regulatory element-binding protein pathway. J Pharmacol Exp Ther 351(2): 474–483. https://doi.org/10.1124/jpet.114.217968

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 (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. https://doi.org/10.1016/j.ejphar.2021.174194

Fabricant DS, Farnsworth NR (2001) The value of plants used in traditional medicine for drug discovery. Environ Health Perspect 109: 69–75. https://doi.org/10.1289/ehp.01109s169

Feng B, Zhang Q, Wang X, Sun X, Mu X, Dong H (2017) Effect of andrographolide on gene expression profile and intracellular calcium in primary rat myocardium microvascular endothelial cells. J Cardiovasc Pharmacol 70(6): 369–381. https://doi.org/10.1097/FJC.0000000000000528

Frantz S, Hundertmark MJ, Schulz-Menger J, Bengel FM, Bauersachs J (2022) Left ventricular remodelling post-myocardial infarction: pathophysiology, imaging, and novel therapies. Eur Heart J 43(27): 2549–2561. https://doi.org/10.1093/eurheartj/ehac223

Galle J, Quaschning T, Seibold S, Wanner C (2003) Endothelial dysfunction and inflammation: What is the link? Kidney Int 63(Suppl. 84): S45–S49. https://doi.org/10.1046/j.1523-1755.63.s84.12.x

Garza MA (2015) Cardiac remodeling and physical training post myocardial infarction. World J Cardiol 7(2): 52–64. https://doi.org/10.4330/wjc.v7.i2.52

Gervois P, Torra IP, Fruchart JC, Staels B (2000) Regulation of lipid and lipoprotein metabolism by PPAR activators. Clin Chem Lab Med 38(1): 3–11. https://doi.org/10.1515/cclm.2000.002

Godo S, Shimokawa H (2017) Endothelial functions. Arterioscler Thromb Vasc Biol 37(9): 108–114. https://doi.org/10.1161/ATVBAHA.117.309813

Hajar R (2017) Risk factors for coronary artery disease: Historical perspectives. Heart Views 18(3): 109–114. https://doi.org/10.4103/HEARTVIEWS.HEARTVIEWS_106_17

Heinzel FR, Hohendanner F, Jin G, Sedej S, Edelmann F (2015) Myocardial hypertrophy and its role in heart failure with preserved ejection fraction left ventricular hypertrophy – Clinical presentation. J Appl Physiol 119(10): 1233–1242. https://doi.org/10.1152/japplphysiol.00374.2015

Hooijmans CR, Rovers MM, De Vries RBM, Leenaars M, Ritskes-Hoitinga M, Langendam MW (2014) SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol 14(1): 43. https://doi.org/10.1186/1471-2288-14-43

Horton JD, Goldstein JL, Brown1 MS (2002) SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 109: 1125–1131. https://doi.org/10.1172/JCI200215593

Horton JD, Shah NA, Warrington JA, Anderson NN, Park SW, Brown MS, Goldstein JL (2003) Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proc Natl Acad Sci U S A 100(21): 12027–12032. https://doi.org/10.1073/pnas.1534923100

Hsieh YL, Shibu MA, Lii CK, Viswanadha VP, Lin YL, Lai CH, Chen YF, Lin KH, Kuo WW, Huang CY (2016) Andrographis paniculata extract attenuates pathological cardiac hypertrophy and apoptosis in high-fat diet fed mice. J Ethnopharmacol 192: 170–177. https://doi.org/10.1016/j.jep.2016.07.018

Ikeda U, Matsui K, Murakami Y, Shimada K (2002) Monocyte chemoattractant protein-1 and coronary artery disease. Clin Cardiol 25(4): 143–147. https://doi.org/10.1002/clc.4960250403

Jayakumar T, Hsieh CY, Lee JJ, Sheu JR (2013) Experimental and clinical pharmacology of Andrographis paniculata and its major bioactive phytoconstituent andrographolide. Evid Based Complement Alternat Med 2013: 846740. https://doi.org/10.1155/2013/846740

Karimi A, Majlesi M, Rafieian-Kopaei M (2015) Herbal versus synthetic drugs; beliefs and facts. J Nephropharmacol 4(1): 27–30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297475/

Lattoo SK, Shabnam K, Dhar AK, Choudhary D, Gupta KK, Sharma P (2006) Current science association genetics and mechanism of induced male sterility in Andrographis paniculata (Burm. f.) Nees and its significance. Curr Sci Assoc 91(4): 515–319.

Lee HL, Jang JW, Lee SW, Yoo SH, Kwon JH, Nam SW, Bae SH, Choi JY, Han NI, Yoon SK (2019) Inflammatory cytokines and change of Th1/Th2 balance as prognostic indicators for hepatocellular carcinoma in patients treated with transarterial chemoembolization. Sci Rep 9(1): 3260. https://doi.org/10.1038/s41598-019-40078-8

Liang E, Liu X, Du Z, Yang R, Zhao Y (2018) Andrographolide ameliorates diabetic cardiomyopathy in mice by blockage of oxidative damage and NF-κB-mediated inflammation. Oxid Med Cell Longev 2018: 9086747. https://doi.org/10.1155/2018/9086747

Lin KH, Marthandam Asokan S, Kuo WW, Hsieh YL, Lii CK., Viswanadha V, Lin YL, Wang S, Yang C, Huang CY (2020) Andrographolide mitigates cardiac apoptosis to provide cardio-protection in high-fat-diet-induced obese mice. Environ Toxicol 35(6): 707–713. https://doi.org/10.1002/tox.22906

Louisa M, Patintingan CGH, Wardhani BWK (2022) Moringa oleifera Lam. in cardiometabolic disorders: A systematic review of recent studies and possible mechanism of actions. Front Pharmacol 13: 792794. https://doi.org/10.3389/fphar.2022.792794

Matsuzawa Y, Lerman A (2014) Endothelial dysfunction and coronary artery disease: Assessment, prognosis, and treatment. Coron Artery Dis 25(8): 713–724. https://doi.org/10.1097/MCA.0000000000000178

Mullard A (2020) 2019 FDA drug approvals. Nat Rev Drug Discov 19(2): 79–84. https://doi.org/10.1038/d41573-020-00001-7

Nhs.uk (2022) Cardiovascular disease. https://www.nhs.uk/conditions/cardiovascular-disease/ [Consulted 13^th July, 2023].

Ni WQ, Liu XL, Zhuo ZP, Yuan XL Song JP, Chi HS, Xu J (2015) Serum lipids and associated factors of dyslipidemia in the adult population in Shenzhen. Lipids Health Dis 14: 71. https://doi.org/10.1186/s12944-015-0073-7

Okhuarobo A, Ehizogie Falodun J, Erharuyi O, Imieje V, Falodun A, Langer P (2014) Harnessing the medicinal properties of Andrographis paniculata for diseases and beyond: A review of its phytochemistry and pharmacology. Asian Pac J Trop Dis 4(3): 213–222. https://doi.org/10.1016/S2222-1808(14)60509-0

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Penny W, Moher D (2021) The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. PLoS Med 18(3): 1–15. https://doi.org/10.1371/JOURNAL.PMED.1003583

Palasubramaniam J, Wang X, Peter K (2019) Myocardial infarction - From atherosclerosis to thrombosis: uncovering new diagnostic and therapeutic approaches. Arterioscler Thromb Vasc Biol 39(8): e176–e185. https://doi.org/10.1161/ATVBAHA.119.312578

Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, Squadrito F, Altavilla D, Bitto A (2017) Oxidative stress: Harms and benefits for human health. Oxid Med Cell Longev 2017: 8416763. https://doi.org/10.1155/2017/8416763

Rajendran P, Nandakumar N, Rengarajan T, Palaniswami R, Gnanadhas EN, Lakshminarasaiah U, Gopas J Nishigaki I (2014). Antioxidants and human diseases. Clin Chim Acta 436: 332–347. https://doi.org/10.1016/j.cca.2014.06.004

Salim MFH, Nugraha IMADP, Adilla F, Yanti LPD (2021) Chromatography profiles of terpenoid compounds in the extract of sambiloto (Andrographis paniculata) herb from various solvents. Walisongo J Chem 4(2): 74–80. https://doi.org/10.21580/wjc.v4i2.7783

Samaniego V, Moguel-Ancheita R (2021) Myocardial infarction as a consequence of atherosclerosis. Cardiovasc Metab Sci 32(S3): s247–252. https://doi.org/10.35366/100806

Shaito A, Thuan DTB, Phu HT, Nguyen THD, Hasan H, Halabi S, Abdelhady S, Nasrallah GK, Eid AH, Pintus G (2020) Herbal medicine for cardiovascular diseases: Efficacy, mechanisms, and safety. Front Pharmacol 11: 422. https://doi.org/10.3389/fphar.2020.00422

Shaw DM, Merien F, Braakhuis A, Dulson D (2018) T-cells and their cytokine production: The anti-inflammatory and immunosuppressive effects of strenuous exercise. Cytokine 104: 136–142. https://doi.org/10.1016/j.cyto.2017.10.001

Sheeja K, Shihab PK, Kuttan G (2006). Antioxidant and anti-inflammatory activities of the plant Andrographis paniculata Nees. Immunopharmacol Immunotoxicol 28(1): 129–140. https://doi.org/10.1080/08923970600626007

Shu J, Huang R, Tian Y, Liu Y, Zhu R, Shi G (2020) 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 9(4): 1965–1975. https://doi.org/10.21037/apm-20-960

Stern CS, Lebowitz J (2010) Latest drug developments in the field of cardiovascular disease. Int J Angiol 19(3): e100–e105. https://doi.org/10.1055/s-0031-1278379

Swinney DC (2011) Molecular Mechanism of Action (MMoA) in drug discovery. In Annual Reports in Medicinal Chemistry, volume 46. Elsevier Inc., pp. 301–317. https://doi.org/10.1016/B978-0-12-386009-5.00009-6

Sya’ban PA, Jonathan AP, Respati TS, Siti IR, Fauzia, I, Asep B, Masteria YP, Carmen F, Giuseppina C (2023) Evaluations of andrographolide-rich fractions of Andrographis paniculata with enhanced potential antioxidant, anticancer, antihypertensive, and anti-inflammatory activities. Plants 12(6): 1220. https://doi.org/10.3390/plants12061220

Tang Z, Yu Y, Ng K, Sow D, Hu J, Mei J (2021) Disease network delineates the disease progression profile of cardiovascular diseases. J Biomed Inform 115: 103686. https://doi.org/10.1016/j.jbi.2021.103686

Theofilis P, Sagris M, Oikonomou E, Antonopoulos AS, Siasos G, Tsioufis C, Tousoulis D (2021) Inflammatory mechanisms contributing to endothelial dysfunction. Biomedicines 9(7): 781. https://doi.org/10.3390/biomedicines9070781

Thygesen K, Alpert JS, White HD (2007) Universal definition of myocardial infarction. Circulation 116(22): 2634–2653. https://doi.org/10.1161/CIRCULATIONAHA.107.187397

Tian Q, Liu J, Chen Q, Zhang (2023) Andrographolide contributes to the attenuation of cardiac hypertrophy by suppressing endoplasmic reticulum stress. Pharm Biol 61(1): 61–68. https://doi.org/10.1080/13880209.2022.2157021

Wang C, Huang Y, Liu X, Li L, Xu H, Dong N, Xu K (2021) Andrographolide ameliorates aortic valve calcification by regulation of lipid biosynthesis and glycerolipid metabolism targeting MGLL expression in vitro and in vivo. Cell Calcium 100: 102495. https://doi.org/10.1016/j.ceca.2021.102495

Wang H, Yu X, Xun Z, Wu Y (2022) Aqueous extract of Andrographis paniculata ameliorates cardiotoxicity induced by doxorubicin in vivo. Int J Pharmacol 18(3): 466–474. https://doi.org/10.3923/ijp.2022.466.474

Wang T, Wang J, Hu X, Huang X, Chen G-X (2020) Current understanding of glucose transporter 4 expression and functional mechanisms. World J Biol Chem 11(3): 76–98. https://doi.org/10.4331/wjbc.v11.i3.76

WHO (2023) World Health Organization 2023 data.who.int, Indonesia [Country overview]. (Accessed on 4 December 2023)

WHO (n.d.) Cardiovascular disease. https://www.who.int/health-topics/cardiovascular-diseases#tab=tab_1 [Consulted 13^th July, 2023].

Wong SK, Chin KY, Ima-Nirwana S (2021) A review on the molecular basis underlying the protective effects of Andrographis paniculata and andrographolide against myocardial injury. Drug Des Devel Ther 15: 4615–4632. https://doi.org/10.2147/DDDT.S331027

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 (2020) Andrographolide protects against adverse cardiac remodeling after myocardial infarction through enhancing Nrf2 signaling pathway. Int J Biol Sci 16(1): 12–26. https://doi.org/10.7150/ijbs.37269

Yoon JW, Jun HS (2005) Autoimmune destruction of pancreatic β cells. Am J Ther 12(6): 580–591. https://doi.org/10.1097/01.mjt.0000178767.67857.63

Yoon M (2009) The role of PPARα in lipid metabolism and obesity: Focusing on the effects of estrogen on PPARα actions. Pharmacol Res 60(3): 151–159. https://doi.org/10.1016/j.phrs.2009.02.004

Yusuf S, Hawken S, Ôunpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L; INTERHEART Study Investigators (2004) Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 364: 937–952. https://doi.org/10.1016/s0140-6736(04)17018-9

Zhang C, Gui L, Xu Y, Wu T, Liu D (2013) Preventive effects of andrographolide on the development of diabetes in autoimmune diabetic NOD mice by inducing immune tolerance. Int Immunopharmacol 16(4): 451–456. https://doi.org/10.1016/j.intimp.2013.05.002

Zhang J, Zhu D, Wang Y, Ju Y (2015) Andrographolide attenuates LPS-induced cardiac malfunctions through inhibition of IκB phosphorylation and apoptosis in mice. Cell Physiol Biochem 37(4): 1619–1628. https://doi.org/10.1159/000438528

Zhao H, Wu L, Yan G, Chen Y, Zhou M, Wu Y, Li Y (2021) Inflammation and tumor progression: signaling pathways and targeted intervention. Sig Transduct Target Ther 6: 263. https://doi.org/10.1038/s41392-021-00658-5

Zhu J (2017) GATA3 Regulates the development and functions of innate lymphoid cell subsets at multiple stages. Front Immunol 8: 1571. https://doi.org/10.3389/fimmu.2017.01571

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