Hepatoprotective Activity of Flueggea virosa Against d-Galactosamine Induced Liver Damage in Rats

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Authors

  • G. Dayanand Reddy
     Department of Pharmacology, Siddha Central Research Institute, Chennai - 600106, Tamil Nadu ,IN
  • R. Ganesan
     Department of Biochemistry, Siddha Central Research Institute, Chennai - 600106, Tamil Nadu ,IN
  • J. Kowsalya
     Department of Pharmacology, Siddha Central Research Institute, Chennai - 600106, Tamil Nadu ,IN
  • Shahana Ahamed
     Department of Pharmacology, Siddha Central Research Institute, Chennai - 600106, Tamil Nadu ,IN
  • A. Arshad Ali
     Department of Pharmacology, Siddha Central Research Institute, Chennai - 600106, Tamil Nadu ,IN
  • Sunil Kumar Podh
     Department of Pharmacology, Siddha Central Research Institute, Chennai - 600106, Tamil Nadu ,IN

DOI:

https://doi.org/10.18311/ti/2024/v31i1/35452

Keywords:

Antioxidant, d-Galactosamine, Flueggea virosa, Hepatotoxicity

Abstract

Flueggea virosa belonging to the family Phyllanthaceae, commonly known as White berry bush was traditionally used for the treatment of rheumatism, sterility, and rashes, and an infusion of the root is taken to relieve malaria. The study was intended to evaluate the hepatoprotective effect of hydroethanolic extract of the roots of Flueggea virosa (200, 400, and 600 mg/kg) against d-Galactosamine-induced liver damage in rats. Silymarin (100 mg/kg) was used as a reference drug. Blood samples were collected after 24 h for haematological and biochemical investigation before the rats were euthanized, and liver samples were taken for histopathology. Oral administration of the HEFV at a dose of 200 mg/kg displayed a significant hepatorenal protective effect against d-Galactosamine by lowering liver biomarkers (SGPT, SGOT, and ALP), kidney biomarker levels (urea and creatinine) and hematological parameters when compared with the disease control group. These findings were strongly supported by the histopathological results of liver sections with fewer pathological changes in comparison with the group treated by the standard drug silymarin and verified the protective effect of the plant extract. The LCMS report of the extract revealed the presence of hepatoprotective ingredients like Tocopherol, Fraxetin, Glaucine, Kaempferol, Methicillin, Capsaicin, and Austinol in the hydroethanolic extract of Flueggea virosa root. The results show that the selected dose of Flueggea virosa (200 and 400 mg/kg) showed dose-dependent hepatoprotective effects on d-Galactosamine-induced hepatotoxicity in rats. The protection of Flueggea virosa against d-Galactosamine-induced liver damage and restoration of biochemical values could result from the content of tocopherols and tetrahydroxy flavones.

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Published

2024-02-28

How to Cite

Reddy, G. D., Ganesan, R., Kowsalya, J., Ahamed, S., Ali, A. A., & Podh, S. K. (2024). Hepatoprotective Activity of <i>Flueggea virosa</i> Against d-Galactosamine Induced Liver Damage in Rats. Toxicology International, 31(1), 141–152. https://doi.org/10.18311/ti/2024/v31i1/35452

Issue

Volume 31, Issue 1, January-March 2024

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Articles

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Copyright (c) 2024 G. Dayanand Reddy, R. Ganesan, J. Kowsalya, Shahana Ahamed, A. Arshad Ali, Sunil Kumar Podh

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

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Europe PMC
Received 2023-10-27
Accepted 2024-02-02
Published 2024-02-28

 

References

Telles S, Pathak S, Singh N, Balkrishna A. Research on traditional medicine: What has been done, the difficulties, and possible solutions. evidence-based complementary and alternative medicine. Hindawi. 2014. 2014:PMID:25013445. https://doi.org/10.1155/2014/495635 DOI: https://doi.org/10.1155/2014/495635

Pan S-Y, Litscher G, Si-Hua, Shu-Feng, Zhi Ling Yu, Hou-Qi Chen, Shuo-Feng Zhang, Min-Ke Tang, Jian Ning Sun, Kam Ming Ko, Historical perspective of traditional indigenous medical practises. The current renaissance and conservation of herbal resources. Evidence based Complementary and Alternative Medicine. 2014. PMC4020364. https://doi. org/10.1155/2014/525340 DOI: https://doi.org/10.1155/2014/525340

Fokunang C, Ndikum V, Tabi O, Jiofack R, Ngameni B, Guedje N, Tembe-Fokunang E, Tomkins P, Barkwan S, Kechia F, Asongalem E, Ngoupayou J, Torimiro N, Gonsu K, Sielinou V, Ngadjui B, Angwafor F, Nkongmeneck A, Abena O, Ngogang J, Asonganyi T, Colizzi V, Lohoue J, Kamsu-Kom. Traditional medicine: past, present and future research and development prospects and integration in the national health system of cameroon. Afr J Tradit Complement Altern Med. 2011; 8(3):284–95. PMCID: PMC3252219. https://doi.org/10.4314/ajtcam.v8i3.65276 DOI: https://doi.org/10.4314/ajtcam.v8i3.65276

Yuan H, Ma Q, Ye L, Piao G. The traditional medicine and modern medicine from natural products. Molecules. 2016; 21(5):559. PMCID: PMC6273146. https://doi.org/10.3390/ molecules21050559 DOI: https://doi.org/10.3390/molecules21050559

Chen S, Pang X, Song J, Shi L, Yao H, Han J, Leon C. A renaissance in herbal medicine identification: from morphology to DNA. Biotechnol Adv. 2014; 32(7):1237– 44. PMID: 25087935. https://doi.org/10.1016/j. biotechadv.2014.07.004 DOI: https://doi.org/10.1016/j.biotechadv.2014.07.004

Kaplowitz N. Herb-induced liver injury: A global concern. Chin J Integr Med. 2018; 24(9):643–4. PMID: 29744785. https://doi.org/10.1007/s11655-018-3004-4 DOI: https://doi.org/10.1007/s11655-018-3004-4

Das J. Liver disease pathophysiology. The Pharmaceutical Journal. Available from: https://pharmaceutical-journal. com/article/ld/liver-disease-pathophysiology.

Byass P. The global burden of liver disease: A challenge for methods and for public health. BMC Med. 2014; 12:159. PMCID: PMC4168048. https://doi. org/10.1186%2Fs12916-014-0159-5

Wang XF, Liu FF, Zhu Z, Fang QQ, Qu SJ, Zhu W, Yang L, Zuo JP, Tan CH. Flueggenoids A – E, new dinorditerpenoids from Flueggea virosa. Fitoterapia. 2019; 133:96–101. https:// doi.org/10.1016/j.fitote.2018.12.025 DOI: https://doi.org/10.1016/j.fitote.2018.12.025

Singh R, Narain S, Rawat A, Kaur J, kumar S, Fatima N. Taxonomy, phytochemistry, pharmacology and traditional uses of Flueggea virosa (Roxb. ex Willd.) Royle: A Review. Int J of Life Sciences. 2018; 6(2):579-85.

Noreen H, Semmar N, Farman M, McCullagh JSO. Measurement of total phenolic content and antioxidant activity of aerial parts of medicinal plant Coronopus didymus. Asian Pacific Journal of Tropical Medicine. 2017; 10(8):792–801. https://doi.org/10.1016/j.apjtm.2017.07.024 DOI: https://doi.org/10.1016/j.apjtm.2017.07.024

Zhao L jia, Liu W, Xiong S hui, Tang J, Lou Z huan, Xie M xia, Xia B hou, Lin L mei, Liao D fang. Determination of total flavonoids contents and antioxidant activity of Ginkgo biloba leaf by near-infrared reflectance method. International Journal of Analytical Chemistry. Hindawi. 2018; 2018:8195784. https://doi. org/10.1155%2F2018%2F8195784

Kosalec I, Pepeljnjak S, Bakmaz M, Vladimir-Knezević S. Flavonoid analysis and antimicrobial activity of commercially available propolis products. Acta Pharm. 2005; 55(4):423–30. PMID: 16375832

Aldayel TS, Grace MH, Lila MA, Yahya MA, Omar UM, Alshammary G. LC-MS characterization of bioactive metabolites from two Yemeni Aloe spp. with antioxidant and antidiabetic properties. Arabian Journal of Chemistry. 2020; 13(4):5040–9. https://doi.org/10.1016/j.arabjc.2020.02.003 DOI: https://doi.org/10.1016/j.arabjc.2020.02.003

Sanna D, Delogu G, Mulas M, Schirra M, Fadda A. Determination of free radical scavenging activity of plant extracts through DPPH assay: An EPR and UV–Vis study. Food Anal Methods. 2012; 5:759–66. https://doi. org/10.1007/s12161-011-9306-1 DOI: https://doi.org/10.1007/s12161-011-9306-1

Sumanont Y, Murakami Y, Tohda M, Vajragupta O, Matsumoto K, Watanabe H. Evaluation of the nitric oxide radical scavenging activity of manganese complexes of curcumin and its derivative. Biol Pharm Bull. 2004; 27(2):170–3. PMID: 14758027. https://doi.org/10.1248/ bpb.27.170 DOI: https://doi.org/10.1248/bpb.27.170

Saha S, Verma RJ. Antioxidant activity of polyphenolic extract of Terminalia chebula Retzius fruits. Journal of Taibah University for Science. 2016; 10(6):805–12. https:// doi.org/10.1016/j.jtusci.2014.09.003 DOI: https://doi.org/10.1016/j.jtusci.2014.09.003

GUIDELINES: Committee for the purpose of control and supervision of experiments on animals. Available from: https://cpcsea.nic.in/Content/55_1_GUIDELINES.aspx

The ARRIVE guidelines 2.0. ARRIVE Guidelines. Available from: https://arriveguidelines.org/arrive-guidelines

Burkill HM. The useful plants of west tropical Africa. Royal Botanic Gardens, Kew: 969; 2004.

Bernardi C, Monetal D, Brughera M, Di Salvo M, Lamparelli D, Mazué G, Iatropoulos MJ. Haematology and clinical chemistry in rats: Comparison of different blood collection sites. Comp Haematol Int. 1996; 6(3):160–6. https://doi. org/10.1007/BF00368460 DOI: https://doi.org/10.1007/BF00368460

Zainan NH, Thiruvenkadam S, Danquah MK, Harun R. Biochemical analysis and potential applications of aqueous and solid products generated from subcritical water extraction of microalgae Chlorella pyrenoidosa biomass. J Appl Phycol. 2020; 32:111– 26. https://doi.org/10.1007/ s10811-019-01960-0 DOI: https://doi.org/10.1007/s10811-019-01960-0

Huang XJ, Choi YK, Im HS, Yarimaga O, Yoon E, Kim HS. Aspartate Aminotransferase (AST/GOT) and Alanine Aminotransferase (ALT/GPT) detection techniques. Sensors (Basel). 2006; 6(7):756–82. PMCID: PMC3894536. https://doi.org/10.3390/s6070756 DOI: https://doi.org/10.3390/s6070756

Ahmed Amar SA, Eryilmaz R, Demir H, Aykan S, Demir C. Determination of oxidative stress levels and some antioxidant enzyme activities in prostate cancer. Aging Male. 2019; 22(3):198–206. PMID: 30322333. https://doi. org/10.1080/13685538.2018.1488955 DOI: https://doi.org/10.1080/13685538.2018.1488955

Ramachandran R, Kakar S. Histological patterns in druginduced liver disease. Journal of Clinical Pathology. BMJ Publishing Group; 2009; 62(6):481–92. PMID: 19474352. https://doi.org/10.1136/jcp.2008.058248 DOI: https://doi.org/10.1136/jcp.2008.058248

Fki I, Sayadi S, Mahmoudi A, Daoued I, Marrekchi R, Ghorbel H. Comparative study on beneficial effects of hydroxytyrosol- and oleuropein-rich olive leaf extracts on high-fat diet-induced lipid metabolism disturbance and liver injury in rats. Biomed Res Int. 2020; 2020:1315202. PMCID: PMC6970490. https://doi.org/10.1155/2020/1315202 DOI: https://doi.org/10.1155/2020/1315202

Rizk A. Protective effect of apelin preconditioning in a for peer review rat model of hepatic ischemia reperfusion injury; Possible interaction between apelin/APJ system, Ang II/AT1R system and eNOS; 2018. https://doi. org/10.1177/2050640619826847

Hothorn LA. The two-step approach- A significant ANOVA F-test before Dunnett’s comparisons against a control- is not recommended. Communications in Statistics - Theory and Methods. Taylor and Francis. 2016; 45(11):3332–43. https://doi.org/10.1080/03610926.2014.902225 DOI: https://doi.org/10.1080/03610926.2014.902225

Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol. 2014; 24(10):R453–62. PMCID: PMC4055301. https://doi.org/10.1016/j.cub.2014.03.034 DOI: https://doi.org/10.1016/j.cub.2014.03.034

Maddrey WC. Drug-induced hepatotoxicity. J Clin Gastroenterol. 2005; 39(4):S83-89. PMID: 15758665. https://doi.org/10.1097/01.mcg.0000155548.91524.6e DOI: https://doi.org/10.1097/01.mcg.0000155548.91524.6e

Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M. Free radicals, metals and antioxidants in oxidative stressinduced cancer. Chem Biol Interact. 2006; 160(1):1–40. PMID: 16430879. https://doi.org/10.1016/j.cbi.2005.12.009 DOI: https://doi.org/10.1016/j.cbi.2005.12.009

Ahmed Z, Ahmed U, Walayat S, Ren J, Martin DK, Moole H, Koppe S, Yong S, Dhillon S. Liver function tests in identifying patients with liver disease. Clin Exp Gastroenterol. 2018; 11:301–7. PMCID: PMC6112813. https://doi.org/10.2147/CEG.S160537 DOI: https://doi.org/10.2147/CEG.S160537

Hsueh CJ, Wang JH, Dai L, Liu CC. Determination of alanine aminotransferase with an electrochemical nano Ir-C biosensor for the screening of liver diseases. Biosensors. 2011; 1(3):107–17. https://doi.org/10.3390/bios1030107 DOI: https://doi.org/10.3390/bios1030107

Ghasemzadeh A, Ghasemzadeh N. Flavonoids and phenolic acids: Role and biochemical activity in plants and human. Journal of Medicinal Plants Research. 2011; 5. https://doi. org/10.5897/JMPR11.1404 DOI: https://doi.org/10.5897/JMPR11.1404

Marks PW. Hematologic manifestations of liver disease. Seminars in Hematology. 2013; 50(3):216–21. https://doi. org/10.1053/j.seminhematol.2013.06.003 DOI: https://doi.org/10.1053/j.seminhematol.2013.06.003

Hematopoietic System - an overview. Wanda M. Haschek. Matthew A. Wallig, in Fundamentals of Toxicologic Pathology. 2nd edition; 2010. Available from: https://www. sciencedirect.com/topics/immunology-and-microbiology/ hematopoietic- system

Etim N. Haematological parameters and factors affecting their values. Agricultural Science. 2014; 2:37–47. https:// doi.org/10.12735/as.v2i1p37 DOI: https://doi.org/10.12735/as.v2i1p37

Alkylating Agents. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Available from: http://www. ncbi.nlm.nih.gov/books/NBK547849/ PMID: 31643188. http://www.ncbi.nlm.nih.gov/books/nbk547852/

Nakeeb A, Toouli J. Bilirubin Metabolism - an overview. Surgery of the Liver, Biliary Tract and Pancreas. 4th edition; 2007. Available from: https://www.sciencedirect.com/ topics/medicine-and-dentistry/bilirubin-metabolism.

Rawal R, Kharangarh PR, Dawra S, Tomar M, Gupta V, Pundir CS. A comprehensive review of bilirubin determination methods with special emphasis on biosensors. Process Biochemistry. 2020; 89:165–74. https:// doi.org/10.1016/j.procbio.2019.10.034 DOI: https://doi.org/10.1016/j.procbio.2019.10.034

Francoz C, Durand F, Kahn JA, Genyk YS, Nadim MK. Hepatorenal syndrome. american society of nephrology. Clinical Journal of the American Society of Nephrology. 2019; 14(5). https://doi.org/10.2215/CJN.12451018 DOI: https://doi.org/10.2215/CJN.12451018

Mohanty A, Garcia-Tsao G. Hyponatremia and hepatorenal syndrome. Gastroenterol Hepatol (N Y). 2015; 11(4):220-9. PMID: 27099594; PMCID: PMC4836593.

Mirończuk-Chodakowska I, Witkowska AM, Zujko ME. Endogenous non-enzymatic antioxidants in the human body. Advances in Medical Sciences. 2018; 63(1):68–78. https://doi.org/10.1016/j.advms.2017.05.005 DOI: https://doi.org/10.1016/j.advms.2017.05.005

Kemelo MK, Wojnarová L, Kutinová Canová N, Farghali H. D-galactosamine/lipopolysaccharide-induced hepatotoxicity downregulates sirtuin 1 in rat liver: role of sirtuin 1 modulation in hepatoprotection. Physiol Res. 2014; 63(5):615–23. PMID: 24908092. https://doi.org/10.33549/physiolres.932761 DOI: https://doi.org/10.33549/physiolres.932761

Kucera O, Lotkova H, Roman K, Renata H, Vladimmira M, Zuzana C. The model of D- galactosamine-induced injury of rat hepatocytes in primary culture. Acta medica (Hradec Kralove). Acta Medica (Hradec Kralove); 2006; 49(1). https://doi.org/10.14712/18059694.2017.111 DOI: https://doi.org/10.14712/18059694.2017.111

As A, Abbiyesuku F, Oparinde P, ‘Niran-Atiba T, Akindele R. Plasma Malondialdehyde (MDA): An indication of liver damage in women with pre-eclamsia. Ethiopian Journal of Health Sciences. 2016; 26:479.PMID:28446854. https://doi. org/10.4314/ejhs.v26i5.10 DOI: https://doi.org/10.4314/ejhs.v26i5.10

Yasin NAE, El-Naggar ME, Ahmed ZSO, Galal MK, Rashad MM, Youssef AM, Elleithy EMM. Exposure to Polystyrene nanoparticles induces liver damage in rat via induction of oxidative stress and hepatocyte apoptosis. Environmental Toxicology and Pharmacology. 2022; 94:103911. https:// doi.org/10.1016/j.etap.2022.103911 DOI: https://doi.org/10.1016/j.etap.2022.103911

Forman HJ, Zhang H, Rinna A. Glutathione: Overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. 2009; 30(1–2):1–12. PMCID: PMC2696075. https://doi.org/10.1016/j.mam.2008.08.006 DOI: https://doi.org/10.1016/j.mam.2008.08.006

Ursini F, Maiorino M. Lipid peroxidation and ferroptosis: The role of GSH and GPx4. Free Radic Biol Med. 2020; 152:175-85. PMID: 32165281. https://doi.org/10.1016/j. freeradbiomed.2020.02.027 DOI: https://doi.org/10.1016/j.freeradbiomed.2020.02.027

Huang ZZ, Chen C, Zeng Z, Yang H, Oh J, Chen L, Lu SC. Mechanism and significance of increased glutathione level in human hepatocellular carcinoma and liver regeneration. FASEB J. 2001; 15(1):19-21. PMID: 11099488. https://doi. org/10.1096/fj.00-0445fje DOI: https://doi.org/10.1096/fj.00-0445fje