The Hepatoprotective Effect of Curcuma longa Extract on Dengue Virus Serotype-2 infected BALB/c Mice

Authors

  • Ni Wayan Anantika Riani Department of Internal Medicine, Udayana University, Sanglah General Hospital, Bali, Indonesia https://orcid.org/0000-0002-6208-0742
  • I Made Susila Utama Tropical and Infectious Disease Division, Department of Internal Medicine, Udayana University, Sanglah General Hospital, Bali, Indonesia
  • Ida Bagus Oka Winaya Laboratory of Pathology, Faculty of Veterinary Medicine, Udayana University, Bali, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2023.8993

Keywords:

Alanine transaminase, Curcuma longa, Dengue, Liver, Pathology

Abstract

BACKGROUND: Dengue infection has a wide clinical spectrum ranging from asymptomatic infection to severe form with organ damage. Liver is among the common organ affected. Curcuma longa is a widely used herb that exhibits a hepatoprotective effect.

AIM: This study aimed to investigate effect of C. longa on liver necroinflammatory activity and alanine aminotransferase (ALT) levels in dengue virus serotype-2 (DENV-2) infected BALB/c mice.

MATERIALS AND METHODS: BALB/c mice were assigned into Group 1 (healthy mice), Group 2 (without C. longa administration), and Group 3 (C. longa administered). DENV-2 was inoculated intraperitoneally in Groups 2 and 3. C. longa extract was given at dose of 0.147 mg/mL intraorally in the 1st  to 7th day. Liver histopathology and ALT level were assessed on the 7th day. Necroinflammatory activity was assessed with a Knodell histology activity index (HAI) score.

RESULTS: The median Knodell HAI score in Group 1, Group 2, and Group 3 were 1.0 (0–5), 7.0 (4–10), and 3.5 (0–8), respectively. The mean difference of Knodell HAI score between Group 2 and Group 3 is 4.1 (95% CI 1.75–6.45, p = 0.002). The mean ALT in Groups 1, 2, and 3 were 58.22 ± 18.31 IU/L, 58.26 ± 18.31 IU/L, and 57.00 ± 10.71 IU/L, respectively. One-way analysis of variance test showed no significant differences in ALT level levels among the three groups (F = 0.26, p = 0.974).

CONCLUSION:  This  study  showed  the  hepatoprotective  effect  of  C.  longa  that  might  decrease  the  liver necroinflammatory activity in dengue infection.

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References

Hasan S, Jamdar SF, Alalowi M, Al Beaiji SM. Dengue virus: A global human threat: Review of literature. J Int Soc Prev Community Dent. 2016;6(1):1-6. https://doi.org/10.4103/2231-0762.175416 PMid:27011925

Mustafa MS, Rasotgi V, Jain S, Gupta V. Discovery of fifth serotype of dengue virus (DENV-5): A new public health dilemma in dengue control. Med J Armed Forces India. 2015;71(1):67-70. https://doi.org/10.1016/j.mjafi.2014.09.011 PMid:25609867

Jing Q, Wang M. Dengue epidemiology. Glob Health J. 2019;3(2):37-45. https://doi.org/10.1016/j.glohj.2019.06.002

Utama IM, Lukman N, Sukmawati DD, Alisjahbana B, Alam A, Murniati D, et al. Dengue viral infection in Indonesia: Epidemiology, diagnostic challenges, and mutations from an observational cohort study. PLoS Negl Trop Dis. 2019;13(10):e0007785. https://doi.org/0.1371/journal.pntd.0007785 PMid:31634352

Harrington J, Kroeger A, Runge-Ranzinger S, O’Dempsey T. Detecting and responding to a dengue outbreak: Evaluation of existing strategies in country outbreak response planning. J Trop Med. 2013;2013:756832. https://doi.org/10.1155/2013/756832 PMid:24222774

Shepard DS, Undurraga EA, Halasa YA. Economic and disease burden of dengue in Southeast Asia. PLoS Negl Trop Dis. 2013;7(2):e2055. https://doi.org/10.1371/journal.pntd.0002055 PMid:23437406

Harapan H, Michie A, Mudatsir M, Sasmono RT, Imrie A. Epidemiology of dengue hemorrhagic fever in Indonesia: Analysis of five decades data from the national disease surveillance. BMC Res Notes. 2019;12(1):350. https://doi.org/10.1186/s13104-019-4379-9 PMid:31221186

De Souza L, Nogueira R, Soares L, Ribas B, Alves F, Vieira F, et al. The impact of dengue on liver function as evaluated by aminotransferase levels. Braz J Infect Dis. 2007;11(4):407-10. https://doi.org/10.1590/s1413-86702007000400007 PMid:17873994

Samanta J, Sharma V. Dengue and its effects on liver. World J Clin Cases. 2015;3(2):125-31. https://doi.org/10.12998/wjcc.v3.i2.125 PMid:25685758

Farzaei MH, Zobeiri M, Parvizi F, El-Senduny FF, Marmouzi I, Coy-Barrera E, et al. Curcumin in liver diseases: A systematic review of the cellular mechanisms of oxidative stress and clinical perspective. Nutrients. 2018;10(7):855. https://doi.org/10.3390/nu10070855 PMid:29966389

Padilla-S L, Rodríguez A, Gonzales MM, Gallego-G JC, Castaño-O JC. Inhibitory effects of curcumin on dengue virus Type 2-infected cells in vitro. Arch Virol. 2014;159(3):573-9. https://doi.org/10.1007/s00705-013-1849-6 PMid:24081825

Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “Curecumin”: From kitchen to clinic. Biochem Pharmacol. 2008;75(4):787-809. https://doi.org/10.1016/j.bcp.2007.08.016 PMid:17900536

Ichsyani M, RidhanyaA, Risanti M, Desti H, Ceria R, Putri DH, et al. Antiviral effects of Curcuma longa L. against dengue virus in vitro and in vivo. IOP Conf Ser Earth Environ Sci. 2017;101(1):012005. https://doi.org/10.1088/1755-1315/101/1/012005

Paes MV, Lenzi HL, Nogueira AC, Nuovo GJ, Pinhão ÂT,

Mota EM, et al. Hepatic damage associated with dengue-2 virus replication in liver cells of BALB/c mice. Lab Invest.

;89(10):1140-51. https://doi.org/10.1038/labinvest.2009.83 PMid:19721415

Megawati D, Masyeni S, Yohan B, Lestarini A, Hayati RF, Meutiawati F, et al. Dengue in Bali: Clinical characteristics and genetic diversity of circulating dengue viruses. PLoS Negl Trop Dis. 2017;11(5)e0005483. htpps://doi.org/10.1371/journal.pntd.0005483 PMid:28531223

Shen FF, Wang Y, Wang YF, Zheng RD, Xian JC, Shi JP, et al. Prediction of hepatic necroinflammatory activity in patients with chronic hepatitis B by a simple noninvasive model. J Transl Med. 2018;16(1):166. https://doi.org/10.1186/s12967-018-1538-z PMid:29914513

Brunt EM. Grading and staging the histopathological lesions of chronic hepatitis: The knodell histology activity index and beyond. Hepatology. 2000;31(1):241-6. https://doi.org/10.1002/hep.510310136 PMid:10613753

Alcon-LePoder S, Drouet MT, Roux P, Frenkiel MP, Arborio M, Durand-Schneider AM, et al. The secreted form of dengue virus nonstructural protein NS1 Is endocytosed by hepatocytes and accumulates in late endosomes: Implications for viral infectivity. J Virol. 2005;79(17):11403-11. https://doi.org/10.1128/jvi.79.17.11403-11411.2005 PMid:16103191

Barth OM, Barreto DF, Paes MV, Takiya CM, Pinhão AT, Schatzmayr HG. Morphological studies in a model for dengue-2 virus infection in mice. Mem Inst Oswaldo Cruz. 2006;101(8):905-15. https://doi.org/10.1590/S0074-02762006000800014 PMid:17293987

Huerre MR, Lan N, Marianneau P, Hue N, Khun H, Hung NT, et al. Liver histopathology and biological correlates in five cases of fatal dengue fever in vietnamese children. Virchows Arch. 2001;438(2):107-15. https://doi.org/10.1007/s004280000329 PMid:11253111

Avirutnan P, Zhang L, Punyadee N, Manuyakorn A, Puttikhunt C, Kasinrerk W, et al. Secreted NS1 of dengue virus attaches to the surface of cells via interactions with heparan sulfate and chondroitin sulfate E. PLoS Pathog. 2007;3(11):e183. https://doi.org/10.1371/journal.ppat.0030183 PMid:18052531

Ageep K. Degree of liver injury in Dengue virus infection. J Gen Mol Virol. 2012;4(1):1-5. https://doi.org/10.5897/JGMV11.023

Chen TY, Chen DY, Wen HW, Ou JL, Chiou SS, Chen JM, et al. Inhibition of enveloped viruses Infectivity by Curcumin. PLoS One. 2013;8(5):e62482. https://doi.org/10.1371/journal.pone.0062482 PMid:23658730

Balasubramanian A, Pilankatta R, Teramoto T, Sajith A, Nwulia E, Kulkarni A, et al. Inhibition of dengue virus by curcuminoids. Antiviral Res. 2019;162:71-8. https://doi.org/10.1016/j.antiviral.2018.12.002 PMid:30529358

Olagnier D, Peri S, Steel C, Van Montfoort N, Chiang C, Beljanski V, et al. Cellular oxidative stress response controls the antiviral and apoptotic programs in dengue virus-infected dendritic cells. PLoS Pathog. 2014;10(12):e1004566. https://doi.org/10.1371/journal.ppat.1004566 PMid:25521078

Soundravally R, Sankar P, Bobby Z, Hoti SL. Oxidative stress in severe dengue viral infection : Association of thrombocytopenia with lipid peroxidation. Platelets. 2008;19(6):447-54. https://doi.org/10.1080/09537100802155284 PMid:18925513

Chen TH, Tang P, Yang CF, Kao LH, Lo YP, Chuang CK, et al. Antioxidant defense is one of the mechanisms by which mosquito cells survive dengue 2 viral infection. Virology. 2011;410(2):410-7. https://doi.org/10.1016/j.virol.2010.12.013 PMid:21216424

Lee GH, Lee HY, Choi MK, Chung HW, Kim SW, Chae HJ.

Protective effect of Curcuma longa L. Extract on CCl 4induced acute hepatic stress. BMC Res Notes. 2017;10(1):77. https://doi.org/10.1186/s13104-017-2409-z PMid:28143589

An S, Jang E, Lee JH. Preclinical evidence of Curcuma longa and its noncurcuminoid constituents against hepatobiliary diseases: A review. Evid Based Complement Alternat Med. 2020;2020:8761435. https://doi.org/10.1155/2020/8761435 PMid:32802138

Xu J, Fu Y, Chen A. Activation of peroxisome proliferator- activated receptor-gamma contributes to the inhibitory effects of curcumin on rat hepatic stellate cell growth. Am J Physiol Gastrointest Liver Physiol. 2003;285(1):G20-30. https://doi.org/10.1152/ajpgi.00474.2002 PMid:12660143

Fu Y, Zheng S, Lin J, Ryerse J, Chen A. Curcumin protects the rat liver from CCl4-Caused injury and fibrogenesis by attenuating oxidative stress and suppressing inflammation. Mol Pharmacol. 2008;73(2):399-409. https://doi.org/10.1124/mol.107.039818.genesis PMid:18006644

Lee LK, Gan VC, Lee VJ, Tan AS, Leo YS, Lye DC. Clinical relevance and discriminatory value of elevated liver aminotransferase levels for dengue severity. PLoS Negl Trop Dis. 2012;6(6):e1676. https://doi.org/10.1371/journal.pntd.0001676 PMid:22679523

Sani SS, Han WH, Bujang MA, Ding HJ, Ng KL, Shariffuddin MA. Evaluation of creatine kinase and liver enzymes in identification of severe dengue. BMC Infect Dis. 2017;17(1):505. https://doi.org/10.1186/s12879-017-2601-8 PMid:28732476

Lee YS, Yoon SK, Chung ES, Bae SH, Choi JY, Han JY, et al. The relationship of histologic activity to serum ALT, HCV genotype and HCV RNA titers in chronic hepatitis C. J Korean Med Sci. 2001;16(5):585-91. https://doi.org/10.3346/jkms.2001.16.5.585 PMid:11641527

Xing YF, Zhou DQ, He JS, Wei CS, Zhong WC, Han ZY, et al. Clinical and histopathological features of chronic hepatitis B virus infected patients with high HBV-DNA viral load and normal alanine aminotransferase level: A multicentre-based study in China. PLoS One. 2018;13(9):e0203220. https://doi.org/10.1371/journal.pone.0203220 PMid:30180183

Paes MV, Pinhão AT, Barreto DF, Costa SM, Oliveira MP, Nogueira AC, et al. Liver injury and viremia in mice infected with dengue-2 virus. Virology. 2005;338(2):236-46. https://doi.org/10.1016/j.virol.2005.04.042 PMid:15961136

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Published

2023-01-02

How to Cite

1.
Riani NWA, Utama IMS, Winaya IBO. The Hepatoprotective Effect of Curcuma longa Extract on Dengue Virus Serotype-2 infected BALB/c Mice. Open Access Maced J Med Sci [Internet]. 2023 Jan. 2 [cited 2026 Oct. 19];11(A):111-6. Available from: https://oamjms.eu/index.php/mjms/article/view/8993