Ram Dayal, Ruhi, Bimlesh Kumar, Indu Melkani, Ankita Sood, Narendra Kumar Pandey, Sukhanpreet kaur, Gagandeep Kaur, Saurabh Singh, Dileep Singh Baghel, Kardam Joshi, Dhara Patel, Anupriya
bimlesh1Pharm@gmail.com , email@example.com
Ram Dayal1, Ruhi1, Bimlesh Kumar1*, Indu Melkani1, Ankita Sood1, Narendra Kumar Pandey1, Sukhanpreet kaur1, Gagandeep Kaur1, Saurabh Singh1, Dileep Singh Baghel1, Kardam Joshi2, Dhara Patel2, Anupriya1
1School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India.
2Topicals Research and Development, Amneal Pharmaceuticals, Piscataway, New Jersey, USA.
Volume - 15,
Issue - 7,
Year - 2022
Hibiscus rosasinensis and Butea monosperma have been traditionally claimed to be protective against liver injury. However, the hepatoprotective effect against iron overload is not yet validated scientifically. The present study was undertaken to evaluate the possible ameliorating effect of aqueous extract of Hibiscus rosasinensis (AQEHR) and Butea monosperma (AQEBM) against ferric nitrilotriacetate (Fe-NTA) induced hepatotoxicity in rats. After extraction, total phenolics and flavonoids content of AQEHR and AQEBM were estimated. Further, antioxidant effect followed by hepatoprotective efficacy of AQEHR and AQEBM were evaluated against chronic iron overload by administering Fe-NTA for 8 successive days to rats in increasing order of doses from 6-15mg Fe/kg. Treatments with both the extracts were started 3 days before the administration of iron and together with iron administration for 8 days. Level of liver function tests, triglycerides, protein, and lipid were recorded. Oxidative biomarkers and histopathology were performed to find out the level of protection by extracts. AQEBM contains a high amount of total phenolic and flavonoids contents and exhibited potent antioxidant effects in all assays. Supplementation of both the extract showed hepatoprotective effect by amelioration of biochemical changes and oxidative biomarkers. AQEBM possesses a higher amount of phenolic components and exhibited better therapeutic potential than AQEHR.
Cite this article:
Ram Dayal, Ruhi, Bimlesh Kumar, Indu Melkani, Ankita Sood, Narendra Kumar Pandey, Sukhanpreet kaur, Gagandeep Kaur, Saurabh Singh, Dileep Singh Baghel, Kardam Joshi, Dhara Patel, Anupriya. Hepatoprotective Potential of Aqueous Extract of Hibiscus rosasinensis and Butea monosperma against Fe-NTA induced Hepatotoxicity in Rats. Research Journal of Pharmacy and Technology. 2022; 15(7):3213-0. doi: 10.52711/0974-360X.2022.00539
Ram Dayal, Ruhi, Bimlesh Kumar, Indu Melkani, Ankita Sood, Narendra Kumar Pandey, Sukhanpreet kaur, Gagandeep Kaur, Saurabh Singh, Dileep Singh Baghel, Kardam Joshi, Dhara Patel, Anupriya. Hepatoprotective Potential of Aqueous Extract of Hibiscus rosasinensis and Butea monosperma against Fe-NTA induced Hepatotoxicity in Rats. Research Journal of Pharmacy and Technology. 2022; 15(7):3213-0. doi: 10.52711/0974-360X.2022.00539 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2022-15-7-61
1. Ingawale DK, Mandlik SK, Naik SR 2014. Models of hepatotoxicity and the underlying cellular, biochemical and immunological mechanism (s): a critical discussion. Environmental Toxicology and Pharmacology 37(1):118-133.
2. Zachariah SM, Aleykutty N, Viswanad V, Halima O 2012. An Overview on Hepatoprotective Activity of Natural Products. Research Journal of Pharmacy and Technology 5(3):317.
3. Rowland I, Gibson G, Heinken A, Scott K, Swann J, Thiele I, Tuohy K 2018. Gut microbiota functions: metabolism of nutrients and other food components. European Journal of Nutrition 57(1):1-24.
4. Patel J, Reddy V, Kumar G 2015. Evaluation of hepatoprotective activity of ethanolic extract of Diospyros melanoxylon (Roxb) leaves against CCl4 induced hepatotoxicity in albino rats. Research Journal of Pharmacy and Technology 8(5):571-574.
5. Patel A, Kushwah P, Pillai S, Raghuvanshi A, Deshmukh N 2017. Formulation and evaluation of Herbal Hand wash containing Ethanolic extract of Glycyrrhiza glabra root extract. Res J Pharm Technol 10(1):55-57.
6. Abboud G, Kaplowitz N 2007. Drug-induced liver injury. Drug Safety 30(4):277-294.
7. Kaplowitz N 2004. Drug-induced liver injury. Clinical Infectious Diseases 38(Supplement_2):S44-S48.
8. Acocella G 1978. Clinical pharmacokinetics of rifampicin. Clinical Pharmacokinetics 3(2):108-127.
9. Aithal GP, Day CP 2007. Nonsteroidal anti-inflammatory drug–induced hepatotoxicity. Clinics in Liver Disease 11(3):563-575.
10. Masini A, Ceccarelli D, Giovannini F, Montosi G, Garuti C, Pietrangelo A 2000. Iron-induced oxidant stress leads to irreversible mitochondrial dysfunctions and fibrosis in the liver of chronic iron-dosed gerbils. The effect of silybin. Journal of Bioenergetics and Biomembranes 32(2):175-182.
11. Nimbalkar V, Pansare P, Nishane B 2015. Screening Methods for Hepatoprotective Agents in Experimental Animal's. Research Journal of Pharmacy and Technology 8(12):1725.
12. Kaur G, Jabbar Z, Athar M, Alam MS 2006. Punica granatum (pomegranate) flower extract possesses potent antioxidant activity and abrogates Fe-NTA induced hepatotoxicity in mice. Food and Chemical Toxicology 44(7):984-993.
13. Deiana M, Aruoma OI, Rosa A, Crobu V, Casu V, Piga R, Dessi MA 2001. The effect of ferric-nitrilotriacetic acid on the profile of polyunsaturated fatty acids in the kidney and liver of rats. Toxicology Letters 123(2-3):125-133.
14. Poornima K, Chella Perumal P, Gopalakrishnan VK 2014. Protective effect of ethanolic extract of Tabernaemontana divaricata (L.) R. Br. against DEN and Fe NTA induced liver necrosis in Wistar Albino rats. BioMed Research International 2014.
15. Sakurai K, Cederbaum AI 1998. Oxidative stress and cytotoxicity induced by ferric-nitrilotriacetate in HepG2 cells that express cytochrome P450 2E1. Molecular Pharmacology 54(6):1024-1035.
16. Iqbal M, Sharma S, Rezazadeh H, Hasan N, Abdulla M, Athar M 1996. Glutathione metabolizing enzymes and oxidative stress in ferric nitrilotriacetate mediated hepatic injury. Redox Report 2(6):385-391.
17. Agarwal MK, Iqbal M, Athar M 2005. Vitamin E inhibits hepatic oxidative stress, toxicity and hyperproliferation in rats treated with the renal carcinogen ferric nitrilotriacetate. Redox Report 10(2):62-70.
18. Prabha S, Rao M, Kumar MR 2017. Evaluation of in vitro Antioxidant, Antibacterial and Anticancer activities of leaf extracts of Cleome rutidosperma. Research Journal of Pharmacy and Technology 10(8):2492-2496.
19. Lone IA, Kaur G, Athar M, Alam MS 2007. Protective effect of Rumex patientia (English Spinach) roots on ferric nitrilotriacetate (Fe-NTA) induced hepatic oxidative stress and tumor promotion response. Food and Chemical Toxicology 45(10):1821-1829.
20. Thomson AM, Rogers JT, Leedman PJ 1999. Iron-regulatory proteins, iron-responsive elements and ferritin mRNA translation. The International Journal of Biochemistry and Cell Biology 31(10):1139-1152.
21. Verma P, Srivastava S, Rao CV 2018. Hepatoprotective effect of Ethanolic Extract of Holarrhena antidysenterica against Paracetamol Induced Toxicity in Wistar Rats. Research Journal of Pharmacy and Technology 11(4):1633-1639.
22. Venkatalakshmi P, Ragadevi M 2012. Protective effect of tinospora cordifolia linn., on paracetamol and alcohol induced hepatotoxicity in albino rats. Research Journal of Pharmacy and Technology 5(2):281.
23. Shimizu N, Tomoda M, Suzuki I, Takada K 1993. Plant mucilages. XLIII. A representative mucilage with biological activity from the leaves of Hibiscus rosa-sinensis. Biological and Pharmaceutical Bulletin 16(8):735-739.
24. Reddy C, Murthy D, Patil S 1997. Antispermatogenic and androgenic activities of various extracts of Hibiscus rosa sinesis in albino mice. Indian Journal of Experimental Biology 35(11):1170-1174.
25. Serrame E, Lim-Sylianco C 1995. Anti-tumor promoting activity of decoctions and expressed juices from Philippine Medicinal plants. Philippine Journal of Science 124(3):275-281.
26. Kasture V, Chopde C, Deshmukh V 2000. Anticonvulsive activity of Albizzia lebbeck, Hibiscus rosa sinesis and Butea monosperma in experimental animals. Journal of Ethnopharmacology 71(1-2):65-75.
27. Sharma U 1994. Cure of heart diseases with ayurvedic drugs. Sachitra Ayurved 47:95-96.
28. Jadhav V, Thorat R, Kadam V, Sathe N 2009. Traditional medicinal uses of Hibiscus rosa-sinensis. J Pharm Res 2(8):1220-1222.
29. Obi FO, Usenu IA, Osayande JO 1998. Prevention of carbon tetrachloride-induced hepatotoxicity in the rat by H. rosasinensis anthocyanin extract administered in ethanol. Toxicology 131(2-3):93-98.
30. Somani R, Kasture S, Singhai AK 2006. Antidiabetic potential of Butea monosperma in rats. Fitoterapia 77(2):86-90.
31. Shahavi V, Desai S 2008. Anti-inflammatory activity of Butea monosperma flowers. Fitoterapia 79(2):82-85.
32. Bhatwadekar A, Chintawar S, Logade N, Somani R, Kasture VS, Kasture S 1999. Antistress activity of Butea monosperma flowers. Indian Journal of Pharmacology 31(2):153-155.
33. Wagner H, Geyer B, Fiebig M, Kiso Y, Hikino H 1986. Isoputrin and butrin, the antihepatotoxic principles of Butea monosperma flowers1. Planta Medica 52(02):77-79.
34. Burlia D, Khadeb A 2007. Phcog Rev.: Plant Review A Comprehensive review on Butea monosperma (Lam.) Kuntze. Pharmacognosy Reviews 1(2).
35. Harborne J 1998, Phytochemical Methods: A guide to modern techniques of plant analysis. Champman and Hall, London.
36. Herborne J 1973. Phytochemical methods. A guide to modern Techniques of Plant Analysis: 5-11.
37. Wall ME, Eddy CR, McClennan ML, Klumpp ME 1952. Detection and estimation of steroidal sapogenins in plant tissue. Analytical Chemistry 24(8):1337-1341.
38. Roopashree T, Dang R, Rani S, Narendra C 2008. Antibacterial activity of antipsoriatic herbs: Cassia tora, Momordica charantia and Calendula officinalis. International Journal of Applied Research in Natural Products 1(3):20-28.
39. Kapoor L, Singh A, Kapoor S 1969. Survey of Indian plants for saponins, alkaloids and flavonoids. I.
40. Sofowara A 1993. Medicinal plants and Traditional medicines in africa. chichester john, willeyandsons. New York:97-145.
41. De S, Dey Y, Ghosh A 2010. Phytochemical investigation and chromatographic evaluation of the different extracts of tuber of Amorphaphallus paeoniifolius (Araceae). Int J Pharm Biol Res 1(5):150-157.
42. Naskar S, Islam A, Mazumder U, Saha P, Haldar P, Gupta M 2010. In vitro and in vivo antioxidant potential of hydromethanolic extract of Phoenix dactylifera fruits. Journal of Scientific Research 2(1):144-157.
43. Prior RL, Cao G, Martin A, Sofic E, McEwen J, O'Brien C, Lischner N, Ehlenfeldt M, Kalt W, Krewer G 1998. Antioxidant capacity as influenced by total phenolic and anthocyanin content, maturity, and variety of Vaccinium species. Journal of Agricultural and Food Chemistry 46(7):2686-2693.
44. Pithayanukul P, Nithitanakool S, Bavovada R 2009. Hepatoprotective potential of extracts from seeds of Areca catechu and nutgalls of Quercus Infectoria. Molecules 14(12):4987-5000.
45. Mon M, Maw S, Oo Z 2011. Quantitative determination of free radical scavenging activity and anti-tumor activity of some Myanmar herbal plants. World Acad Sci Eng Technol 75:524-530.
46. Czochra M, Widensk A 2002. Spectrophotometric determination of H2O2 activity. Anal Chem Acta 452:177-184.
47. Ebrahimzadeh M, Nabavi S, Nabavi S 2009. Essential oil Composition and Antioxidant Activity of Pterocaryaﬁvaxinifolia. Pak J Biol Sci 12(13):957-963.
48. Nabavi SF, Ebrahimzadeh MA, Nabavi SM, Eslami B 2010. Antioxidant activity of flower, stem and leaf extracts of Ferula gummosa Boiss. Grasasy Aceites 61(3):244-250.
49. Sudha G, Priya MS, Shree RI, Vadivukkarasi S 2011. In vitro free radical scavenging activity of raw pepino fruit (Solanum muricatum aiton). Int J Curr Pharm Res 3(2):137-140.
50. Awai M, Narasaki M, Yamanoi Y, Seno S 1979. Induction of diabetes in animals by parenteral administration of ferric nitrilotriacetate. A model of experimental hemochromatosis. The American Journal of Pathology 95(3):663.
51. El-Maraghy SA, Rizk SM, El-Sawalhi MM 2009. Hepatoprotective potential of crocin and curcumin against iron overload-induced biochemical alterations in rat. Afr J Biochem Res 3(5):215-221.
52. Bradley D, Maynard J, Emery G, Webster H 1972. Transaminase activities in serum of long-term hemodialysis patients. Clinical Chemistry 18(11):1442-1442.
53. Rej R, Fasce CF, Vanderlinde RE 1973. Increased aspartate aminotransferase activity of serum after in vitro supplementation with pyridoxal phosphate. Clinical Chemistry 19(1):92-98.
54. MacComb R, Bowers G 1972. Alkaline phosphatase activity in serum. Clin Chem 18(97):12.
55. Pearlman FC, Lee RT 1974. Detection and measurement of total bilirubin in serum, with use of surfactants as solubilizing agents. Clinical Chemistry 20(4):447-453.
56. Allain CC, Poon LS, Chan CS, Richmond W, Fu PC 1974. Enzymatic determination of total serum cholesterol. Clinical Chemistry 20(4):470-475.
57. Basu S, Das M, Datta G 2013. Protective activity of ethanolic extract of Amorphophallus campanulatus against ethanol induced hepatotoxicity in rats. Int J Pharm Pharm Sci 5:412-417.
58. Luck H 1963. Spectrophotometric method for the estimation of catalase. Methods of Enzymatic Analysis.
59. Draper H, Hadley M. 1990.  Malondialdehyde determination as index of lipid Peroxidation. Methods in Enzymology, ed.: Elsevier. p 421-431.
60. Ohkawa H, Ohishi N, Yagi K 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry 95(2):351-358.
61. Ellman GL 1959. Tissue sulfhydryl groups. Archives of Biochemistry and Biophysics 82(1):70-77.
62. Saha MR, Alam MA, Akter R, Jahangir R 2008. In vitro free radical scavenging activity of Ixora coccinea L. Bangladesh Journal of Pharmacology 3(2):90-96.
63. Lobo VC, Phatak A, Chandra N 2010. Antioxidant and free radical scavenging activity of Hygrophila schulli (Buch.-Ham.) Almeida and Almeida. seeds. Adv Biores 1(2):72-78.
64. Uzunhisarcikli M, Kalender Y 2011. Protective effects of vitamins C and E against hepatotoxicity induced by methyl parathion in rats. Ecotoxicology and Environmental Safety 74(7):2112-2118.
65. Anusha M, Venkateswarlu M, Prabhakaran V, Taj SS, Kumari BP, Ranganayakulu D 2011. Hepatoprotective activity of aqueous extract of Portulaca oleracea in combination with lycopene in rats. Indian Journal of Pharmacology 43(5):563.
66. Hogg N. Seminars in reproductive endocrinology, 1998, pp 241-248.
67. Farber JL 1994. Mechanisms of cell injury by activated oxygen species. Environmental Health Perspectives 102(suppl 10):17-24.
68. Toyokuni S 1996. Iron-induced carcinogenesis: the role of redox regulation. Free Radical Biology and Medicine 20(4):553-566.
69. Matos HR, Capelozzi VL, Gomes OF, Di Mascio P, Medeiros MH 2001. Lycopene inhibits DNA damage and liver necrosis in rats treated with ferric nitrilotriacetate. Archives of Biochemistry and Biophysics 396(2):171-177.
70. Iqbal M, Athar M 1998. Attenuation of iron-nitrilotriacetate (Fe-NTA)-mediated renal oxidative stress, toxicity and hyperproliferative response by the prophylactic treatment of rats with garlic oil. Food and Chemical Toxicology 36(6):485-495.
71. Iqbal M, Giri U, Athar M 1995. Ferric nitrilotriacetate (Fe-NTA) is a potent hepatic tumor promoter and acts through the generation of oxidative stress. Biochemical and Biophysical Research Communications 212(2):557-563.
72. Iqbal M, Giri U, Giri DK, Alam M, Athar M 1999. Age-dependent renal accumulation of 4-hydroxy-2-nonenal (HNE)-modified proteins following parenteral administration of ferric nitrilotriacetate commensurate with its differential toxicity: implications for the involvement of HNE–protein adducts in oxidative stress and carcinogenesis. Archives of Biochemistry and Biophysics 365(1):101-112.
73. Deiana M, Rosa A, Casu V, Piga R, Dessı̀ MA, Aruoma OI 2004. L-ergothioneine modulates oxidative damage in the kidney and liver of rats in vivo: studies upon the profile of polyunsaturated fatty acids. Clinical Nutrition 23(2):183-193.
74. Athar M, Iqbal M 1998. Ferric nitrilotriacetate promotes N-diethylnitrosamine-induced renal tumorigenesis in the rat: implications for the involvement of oxidative stress. Carcinogenesis 19(6):1133-1139.
75. Ye Sf, Hou Zq, Zhang Qq 2007. Protective effects of Phellinus linteus extract against Iron overload‐mediated oxidative stress in cultured rat hepatocytes. Phytotherapy Research 21(10):948-953.