Andrographis paniculata Ethanolic Extract Improved Doxorubicin-induced Cardiac Inflammation, Alterations in Liver Function Parameters and Anemia

Oluebube Magnificient Eziefule, Wawaimuli Arozal, Septelia Inawati Wanandi, Melva Louisa, Puspita Eka Wuyung, Syarifah Dewi, Nafrialdi Nafrialdi, Yulia Ratna Dewi, Deya Adiby Nabillah

Abstract


Background: Doxorubicin (DOX), an efficacious chemotherapy drug is compromised by cardiotoxicity, myelosuppression, and hepatotoxicity. Due to the limited success of current treatments for DOX toxicity, there is a pressing need to explore alternative medical interventions, particularly from plant sources. This study was conducted to investigate the potential protective effect of ethanolic extract of Andrographis paniculata leaves (EEAP) against DOX-induced cardiac inflammation, liver toxicity, and anemia.

Materials and methods: Sprague-Dawley rats were intraperitoneally injected with DOX at a total dose of 16 mg/kgBW. EEAP was administered orally for 4 weeks at doses of 125, 250, and 500 mg/kgBW/day according to the assigned treatment groups. The mRNA expression levels of interleukin-1β (IL-1β) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) in the heart tissue, along with the concentrations of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and calcium level were examined. Additionally, the hematological parameters (including hematocrit, hemoglobin and red blood cells (RBCs)), aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and malondialdehyde (MDA) levels in blood were also analyzed.

Results: EEAP dose-dependently decreased the mRNA expressions of IL-1β (p<0.05), tended to decrease mRNA expression of NLRP3 and the concentrations of NFκB and calcium in heart tissue compared with the DOX-only group. Additionally, EEAP dose-dependently decreased ALP values (p<0.0001) and tended to improve hematological parameters, as well as AST and MDA levels in serum.

Conclusion: This extract may prevent DOX-induced cardiac inflammation, anemia, and hepatotoxicity. However, further studies are needed to confirm these findings, including the efficacy profile of the extract in cancer rats treated with DOX.

Keywords: doxorubicin, Andrographis paniculata, inflammation, anemia, hepatotoxicity, herbal medicine


Full Text:

PDF

References


Pugazhendhi A, Edison TNJI, Velmurugan BK, Jacob JA, Karuppusamy I. Toxicity of doxorubicin (Dox) to different experimental organ systems. Life Sci. 2018; 200: 26-30, CrossRef.

Carvalho C, Santos R, Cardoso S, Correia S, Oliveira P, Santos M, et al. Doxorubicin: The good, the bad and the ugly effect. Curr Med Chem. 2009; 16(25): 3267-85, CrossRef.

Chen T, Shen HM, Deng ZY, Yang ZZ, Zhao RL, Wang L, et al. A herbal formula, SYKT, reverses doxorubicin induced myelosuppression and cardiotoxicity by inhibiting ROS mediated apoptosis. Mol Med Rep. 2017; 15(4): 2057-66, CrossRef.

Goyal SN, Patil CR, Mishra N, Mohanraj R, Ojha S. Cardioprotective potential of medicinal plants in attenuating doxorubicin-induced cardiotoxicity. In: Cardioprotective Natural Products. Promises and Hopes. Singapore: World Scientific Publishing; 2017. p.149-91, CrossRef.

Alsnoussi YA, Aziza S, Hussein A, Bakry S. Biochemical and hematological alterations associated with doxorubicin induced toxicity in rats. AlAzhar Bull Sci. 2021; 32(1): 11-6, CrossRef.

Ikewuchi JC, Ikewuchi CC, Ifeanacho MO, Jaja VS, Okezue EC, Jamabo CN, et al. Attenuation of doxorubicin-induced cardiotoxicity in wistar rats by aqueous leaf-extracts of Chromolaena odorata and Tridax procumbens. J Ethnopharmacol. 2021; 274: 114004, CrossRef.

Songbo M, Lang H, Xinyong C, Bin X, Ping Z, Liang S. Oxidative stress injury in doxorubicin-induced cardiotoxicity. Toxicol Lett. 2019; 307: 41-8, CrossRef.

Reis-Mendes A, Padrão AI, Duarte JA, Gonçalves-Monteiro S, Duarte-Araújo M, Remião F, et al. Role of inflammation and redox status on doxorubicin-induced cardiotoxicity in infant and adult cd-1 male mice. Biomolecules. 2021; 11(11): 1725, CrossRef.

Androne AS, Katz SD, Lund L, LaManca J, Hudaihed A, Hryniewicz K, et al. Hemodilution is common in patients with advanced heart failure. Circulation. 2003; 107(2): 226-9, CrossRef.

Billett HH. Hemoglobin and hematocrit. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd ed. Boston: Butterworths; 1990. p.149-91, CrossRef.

Damodar G, Smitha T, Gopinath S, Vijayakumar S, Rao Y. An evaluation of hepatotoxicity in breast cancer patients receiving injection doxorubicin. Ann Med Health Sci Res. 2014; 4(1): 74-9, CrossRef.

Wali AF, Rashid S, Rashid SM, Ansari MA, Khan MR, Haq N, et al. Naringenin regulates doxorubicin-induced liver dysfunction: Impact on oxidative stress and inflammation. Plants. 2020; 9(4): 1-17, CrossRef.

Epstein RS, Weerasinghe RK, Parrish AS, Krenitsky JA, Sanborn RE, Salimi T. Real-world burden of chemotherapy-induced myelosuppression in patients with small cell lung cancer: A retrospective analysis of electronic medical data from community cancer care providers. J Med Econ. 2022; 25(1): 108-18, CrossRef.

Langer SW. Dexrazoxane for the treatment of chemotherapy-related side effects. Cancer Manag Res. 2014; 6: 357-63, CrossRef.

Pinal-Fernandez I, Casal-Dominguez M, Mammen AL. Statins: Pros and cons. Med Clin. 2018; 150(10): 398-402, CrossRef.

Sangweni NF, van Vuuren D, Mabasa L, Gabuza K, Huisamen B, Naidoo S, et al. Prevention of anthracycline-induced cardiotoxicity: The good and bad of current and alternative therapies. Front Cardiovasc Med. 2022; 9: 907266, CrossRef.

Karimi A, Majlesi M, Rafieian-Kopaei M. Herbal versus synthetic drugs; Beliefs and facts. J Nephropharmacol. 2015; 4(1): 27-30, article.

Kodi GM, Mustafa HA, Idris AAA. The effects of Moringa oleifera leaves on complete blood count, renal and liver functions as potential therapy for malnutrition. Mol Cell Biomed Sci. 2022; 6(2): 55-62, CrossRef.

Wang H, Yu X, Xun Z, Wu Y. Aqueous extract of Andrographis paniculata ameliorates cardiotoxicity induced by doxorubicin in vivo. Int J Pharmacol. 2022; 18(3): 466-74, CrossRef.

Hossain MS, Urbi Z, Sule A, Rahman KMH. Andrographis paniculata (Burm. f.) Wall. Ex nees: A review of ethnobotany, phytochemistry, and pharmacology. ScientificWorldJournal. 2014; 2014: 274905, CrossRef.

Mussard E, Cesaro A, Lespessailles E, Berteina BLS. Andrographolide, a natural antioxidant: An update. Antioxidants. 2019; 8(12): 571, CrossRef.

Chakravarti RN, Chakravarti D. Andrographolide, the active constituent of Andrographis paniculata Nees; A preliminary communication. Ind Med Gaz. 1951; 86(3): 96-7, article.

Eziefule OM, Arozal W, Wanandi SI, Dewi S, Nafrialdi N, Saraswati M, et al. Andrographis paniculata: A potential supplementary therapy for cardiovascular diseases - A systematic review of its effects and molecular actions. J Pharm Pharmacogn Res. 2024; 12(3): 487-513, CrossRef.

Patintingan CG, Louisa M, Juniantito V, Arozal W, Hanifah S, Wanandi SI, et al. Moringa oleifera leaves extract ameliorates doxorubicin-induced cardiotoxicity via its mitochondrial biogenesis modulatory activity in rats. J Exp Pharmacol. 2023; 15: 307-19, CrossRef.

Arozal W, Wanandi SI, Louisa M, Wuyung PE, Noviana D, Eziefule OM, et al. Evaluating the acute toxicity and in vivo protective effect of standardized Andrographis paniculata extract against doxorubicin-induced cardiotoxicity in sprague-dawley rats. Trop J Nat Prod Res. 2024; 8(5): 7134-41, CrossRef.

Wills ED. The effect of inorganic iron on the thiobarbituric acid method for the determination of lipid peroxides. Biochim Biophys Acta. 1964; 84: 475-7, CrossRef.

Tuo H, Li W, Zhao W, Zhao J, Li D, Jin L. Shikonin alleviates doxorubicin-induced cardiotoxicity via Mst1/Nrf2 pathway in mice. Sci Rep. 2024; 14(1): 1-13, CrossRef.

Zhang L, Jiang YH, Fan C, Zhang Q, Jiang YH, Li Y, et al. MCC950 attenuates doxorubicin-induced myocardial injury in vivo and in vitro by inhibiting NLRP3-mediated pyroptosis. Biomed Pharmacother. 2021; 143: 112133, CrossRef.

Sheeja K, Kuttan G. Ameliorating effects of Andrographis paniculata extract against cyclophosphamide-induced toxicity in mice. Asian Pac J Cancer Prev. 2006; 7(4): 609-14, article.

Kalirajan J, Rajalakshmi MG. Hepatoprotective activity of Andrographis paniculata on paracetamol induced liver damage in Rats. J Pharm Res. 2012; 5(6): 2983-6, article.

Eisner DA, Caldwell JL, Kistamás K, Trafford AW. Calcium and excitation-contraction coupling in the heart. Circ Res. 2017; 121(2): 181-95, CrossRef.

Katz AM, Lorell BH. Regulation of cardiac contraction and relaxation. Circulation. 2000; 102 (20 Suppl 4): IV69-74, CrossRef.

Agustini FD, Arozal W, Louisa M, Siswanto S, Soetikno V, Nafrialdi N, et al. Cardioprotection mechanism of mangiferin on doxorubicin-induced rats: Focus on intracellular calcium regulation. Pharm Biol. 2016; 54(7): 1289-97, CrossRef.

Wu BB, Leung KT, Poon EN. Mitochondrial-targeted therapy for doxorubicin-induced cardiotoxicity. Int J Mol Sci. 2022; 23(3): 1912, CrossRef.

Gajbhiye N, Makasana J, Geetha KA, Saha A, Raju S. Simultaneous quantification of major bio-active diterpenoid lactones and flavonoids in Andrographis paniculata (Burm. F.) nees: LC-ESI-MS/MS method validation and uncertainty determination. ChemistrySelect. 2023; 8(38): e202301855, CrossRef.

Loureiro Damasceno JP, Silva da Rosa H, Silva de Araújo L, Jacometti Cardoso Furtado NA. Andrographis paniculata formulations: Impact on diterpene lactone oral bioavailability. Eur J Drug Metab Pharmacokinet. 2022; 47(1): 19-30, CrossRef.

Kumari L, Choudhari Y, Patel P, Gupta GD, Singh D, Rosenholm JM, et al. Advancement in solubilization approaches: A step towards bioavailability enhancement of poorly soluble drugs. Life. 2023; 13(5): 1099, CrossRef.

Xu Q, Higgins T, Cembrowski GS. Limiting the testing of AST: A diagnostically nonspecific enzyme. Am J Clin Pathol. 2015; 144(3): 423-6, CrossRef.

Sharma U, Pal D, Prasad R. Alkaline Phosphatase: An Overview. 2014; 29(3):269-78, CrossRef.

Prasanna PL, Renu K, Valsala Gopalakrishnan A. New molecular and biochemical insights of doxorubicin-induced hepatotoxicity. Life Sci. 2020; 250: 117599, CrossRef.

Gurel C, Kuscu GC, Buhur A, Dagdeviren M, Oltulu F, Karabay Yavasoglu NU, Yavasoglu A. Fluvastatin attenuates doxorubicin-induced testicular toxicity in rats by reducing oxidative stress and regulating the blood – testis barrier via mTOR signaling pathway. Hum Exp Toxicol. 2019; 38(12):1329-43, CrossRef.




DOI: https://doi.org/10.21705/mcbs.v8i2.444

Copyright (c) 2024 Cell and BioPharmaceutical Institute

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Indexed by:

               

                      


Cell and BioPharmaceutical Institute