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.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

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 DOI: https://doi.org/10.4103/2231-0762.175416

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 DOI: https://doi.org/10.1016/j.mjafi.2014.09.011

Jing Q, Wang M. Dengue epidemiology. Glob Health J. 2019;3(2):37-45. https://doi.org/10.1016/j.glohj.2019.06.002 DOI: 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 DOI: https://doi.org/10.1371/journal.pntd.0007785

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 DOI: https://doi.org/10.1155/2013/756832

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 DOI: https://doi.org/10.1371/journal.pntd.0002055

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 DOI: https://doi.org/10.1186/s13104-019-4379-9

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 DOI: https://doi.org/10.1590/S1413-86702007000400007

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 DOI: https://doi.org/10.12998/wjcc.v3.i2.125

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 DOI: https://doi.org/10.3390/nu10070855

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 DOI: https://doi.org/10.1007/s00705-013-1849-6

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 DOI: https://doi.org/10.1016/j.bcp.2007.08.016

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 DOI: 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 DOI: https://doi.org/10.1038/labinvest.2009.83

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 DOI: https://doi.org/10.1371/journal.pntd.0005483

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 DOI: https://doi.org/10.1186/s12967-018-1538-z

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 DOI: https://doi.org/10.1002/hep.510310136

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 DOI: https://doi.org/10.1128/JVI.79.17.11403-11411.2005

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 DOI: https://doi.org/10.1590/S0074-02762006000800014

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 DOI: https://doi.org/10.1007/s004280000329

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 DOI: https://doi.org/10.1371/journal.ppat.0030183

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 DOI: 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 DOI: https://doi.org/10.1371/journal.pone.0062482

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 DOI: https://doi.org/10.1016/j.antiviral.2018.12.002

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 DOI: https://doi.org/10.1371/journal.ppat.1004566

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 DOI: https://doi.org/10.1080/09537100802155284

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 DOI: https://doi.org/10.1016/j.virol.2010.12.013

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 DOI: https://doi.org/10.1186/s13104-017-2409-z

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 DOI: https://doi.org/10.1155/2020/8761435

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 DOI: https://doi.org/10.1152/ajpgi.00474.2002

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 DOI: https://doi.org/10.1124/mol.107.039818

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 DOI: https://doi.org/10.1371/journal.pntd.0001676

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 DOI: https://doi.org/10.1186/s12879-017-2601-8

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 DOI: https://doi.org/10.3346/jkms.2001.16.5.585

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 DOI: https://doi.org/10.1371/journal.pone.0203220

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 DOI: https://doi.org/10.1016/j.virol.2005.04.042

Downloads

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 2024 Nov. 21];11(A):111-6. Available from: https://oamjms.eu/index.php/mjms/article/view/8993