Alleviation of carbon tetrachloride-induced hepatocellular damage and oxidative stress with a leaf extract of Glyphae brevis (Tiliaceae)
-
Lucky Legbosi Nwidu
,
Yibala I. Oboma
Abstract
Background
Glyphae brevis leaf is reported in ethnomedicine as a treatment for hepatitis and jaundice; however, no studies have hitherto investigated the mechanistic basis of these claims.
Methods
A hepato-protective role of G. brevis hydromethanolic (GBH) leaf extract was established against carbon tetrachloride (CCl4)-induced hepatotoxicity. Twenty-four hours after a CCl4 challenge, rats were sacrificed and serum hematological indices, lipid profile, and biochemical parameters were determined. The antioxidant enzymes parameters (glutathione, catalase, and superoxide dismutase) and lipid peroxidation product (thiobarbituric reactive substances) levels in liver homogenates were evaluated. Changes in the liver cyto-architecture of different treatment groups were also investigated.
Results
The GBH extract produced no significant impact on weight and hematological indices. Intoxication with CCl4 significantly (p<0.001–0.05) increased total cholesterol (TC) and low-density lipoproteins (LDL) compared with control rats. Pretreatment with GBH leaf extract significantly reduced triglycerides, TC, and LDL to approaching control levels (p<0.001–0.05). The GBH leaf extract significantly alleviated CCl4-induced elevation of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and the CCl4-induced depression of total protein, and albumin. Liver antioxidant parameters were significantly increased in plant extract-treated rats, and this antagonized the pro-oxidant effect of CCl4. Histopathological studies also supported a hepato-protective effect of GBH. Collectively, the GBH leaf extract alleviated the CCl4-induced hepatotoxicity through improvement of innate antioxidant enzyme levels and lipid metabolism and stabilized the hepatocyte cyto-architecture of intoxicated rats.
Conclusions
This study establishes the ethnomedicinal role of G. brevis leaf in hepatitis and the mechanistic basis of hepato-protection against CCl4-induced hepatotoxicity.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Sofowora A, Ogunbodede E, Onayade A. The role and place of medicinal plants in the strategies for disease prevention. Afr J Tradit Complement Altern Med 2013;10:210–29.10.4314/ajtcam.v10i5.2Search in Google Scholar
2. Hussain L, Ikram J, Rehman K, Tariq M, Ibrahim M, Akash MH. Hepatoprotective effects of Malva sylvestris L. against paracetamol-induced hepatotoxicity. Turk J Biol 2014;38:396–402.10.3906/biy-1312-32Search in Google Scholar
3. Lee IC, Kim SH, Baek HS, Moon C, Kim SH, Kim YB, et al. Protective effects of diallyl disulfide on carbon tetrachloride-induced hepatotoxicity through activation of Nrf2. Environ Toxicol 2015;30:538–48.10.1002/tox.21930Search in Google Scholar
4. Pareek A, Godavarthi A, Issarani R, Nagori BP. Antioxidant and hepatoprotective activity of Fagonia schweinfurthii (Hadidi) Hadidi extract in carbon tetrachloride induced hepatotoxicity in HepG2 cell line and rats. J Ethnopharmacol 2013;150:973–81.10.1016/j.jep.2013.09.048Search in Google Scholar
5. Brai BC, Adisa RA, Odetola AA. Hepatoprotective properties of aqueous leaf extract of Persea americana, Mill (Lauraceae) ‘avocado’ against CCl4-induced damage in rats. Afr J Tradit Complement Altern Med 2014;11:237–44.10.4314/ajtcam.v11i2.2Search in Google Scholar
6. Sangi S, El-feky SA, Ali SS, Ahmedani EI, Tashtoush MH. Hepatoprotective effects of oleuropein, thymoquinone and fruit of Phoenix dactylifera on CCl4 induced hepatotoxicity in rats. World J Pharm Pharma Sci 2014;3:3475–86.Search in Google Scholar
7. Aloh GS, Obeagu EI, Odo CE, Kanu SN, Udezuluigbo CN, Ugwu GU. Hepatoprotective potentials of methanol extracts of Gossweilerodendron balsamifarum and lipid profile of albino rats. Eur J Pharma Med Res 2015;2:124–39.Search in Google Scholar
8. Sur TK, Hazra A, Hazra AK, Bhattacharyya D. Antioxidant and hepatoprotective properties of Indian Sunderban mangrove Bruguiera gymnorrhiza L. leaves. J Basic Clin Pharm 2016;7:75–9.10.4103/0976-0105.183262Search in Google Scholar
9. El-Sayed MA, Elkomy A, Samer S, ElBanna AH. Hepatoprotective effect of Pimpinella anisum and Foeniculum vulgare against carbon tetrachloride induced fibrosis in rats. World J Pharm Pharm Sci 2015;4:78–88.Search in Google Scholar
10. Awogbindin IO, Tade OJ, Metibemu SD, Olorunsogo OO, Farombi EO. Assessment of flavonoid content, free radical scavenging and hepatoprotective activities of Ocimum gratissimum and Spondias mombin in rats treated with dimethylnitrosamine. Arch Basic Appl Med 2014;2:45–54.Search in Google Scholar
11. Burkill H. The useful plants of West Africa, Vol. 1. Kew, UK: Royal Botanic Gardens, 1985.Search in Google Scholar
12. Mahmoodzadeh Y, Mazani M, Rezagholizadeh L. Hepatoprotective effect of methanolic Tanacetum parthenium extract on CCl4-induced liver damage in rats. Toxicol Rep 2017;4:455–62.10.1016/j.toxrep.2017.08.003Search in Google Scholar
13. Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: carbontetrachlorideasatoxicologicalmodel. Crit Rev Toxicol 2003;33:105–36.10.1080/713611034Search in Google Scholar
14. Boll M, Weber LW, Becker E, Stampfl A. Mechanism of carbon tetrachloride-induced hepatotoxicity. Hepatocellular damage by reactive carbon tetrachloride metabolites. Z Naturforsch 2001;56:649–59.10.1515/znc-2001-7-826Search in Google Scholar
15. Noumi E, Yomi A. Medicinal plants used for intestinal diseases in Mbalmayo Region, Central Province, Cameroon. Fitoterapia 2001;72:246–54.10.1016/S0367-326X(00)00288-4Search in Google Scholar
16. Ogbonnia S, Van Staden J, Jager AK, Coker HA. Anticonvulsant effect of Glyphae brevis (Spreng) Moraches leaf extracts in mice and preliminary phytochemical tests. Nig Q J Hosp Med 2003;13:62–4.10.4314/nqjhm.v13i3-4.12662Search in Google Scholar
17. Dickson RA, Ekuadzi E, Annan K, Komlaga G. Antibacterial, anti-inflammatory, and antioxidant effects of the leaves and stem bark of Glyphaea brevis (Spreng) Monachino (Tiliaceae): a comparative study. Pharmacognosy Res 2011;3:166–72.10.4103/0974-8490.85001Search in Google Scholar
18. Vasilea B. Plantas Medicinales de Guinea, Conakry, Republic of Guinea. Moscow, USSR: Moscow University, 1969.Search in Google Scholar
19. Dakam W, Oben JE, Ngogang JY. Antioxidant activity and extractability of phenolic compounds from medicinal plants: a study of Glyphaea brevis Spreng. (Monach). Pharmacol Online 2008;3:708–18.Search in Google Scholar
20. Ojelabi BA, Areola JO, Babalola OO. Roles of Glyphaea brevis (Spreng) extract in cadmium induced hepatocellular damage and oxidative stress in rabbit. E3 J Biotech Pharm Res 2012;3:123–8.Search in Google Scholar
21. Mbosso ET, Ngouela J, Nguedia JC, Beng VP, Rohmer M, Tsamo E. In vitro antimicrobial activity of extracts and compounds of some selected medicinal plants from Cameroon. J Ethnopharmacol 2010;128:476–81.10.1016/j.jep.2010.01.017Search in Google Scholar
22. Trease GE, Evans WC. A textbook of pharmacognosy. London: Baillière Tindall, 2001:600.Search in Google Scholar
23. Lorke D. A new approach to practical acute toxicity testing. Arch Toxicol 1983;54:275–89.10.1007/BF01234480Search in Google Scholar
24. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82:70–7.10.1016/0003-9861(59)90090-6Search in Google Scholar
25. Aebi HE. Catalase. In: Bergmeryer H, Verlag C, Weinheim A, editors. Methods of enzymatic analysis, 3rd ed. Weinheim, Germany: Verlag Chemie, 1983:273–7.Search in Google Scholar
26. Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biol 1984;21:130–2.Search in Google Scholar
27. Draper HH, Hadley H. Malondiadehyde determination as index of lipid peroxidation. Methods Enzymol 1990;186:421–31.10.1016/0076-6879(90)86135-ISearch in Google Scholar
28. Bancroft JD, Gamble M. Theory and practice of histological techniques, 5th ed. London: Churchill Livingstone, 2002: 63–76.Search in Google Scholar
29. Meyer SA, Kulkarni AP. Hepatotoxicity. In: Hodgson E, Smart RC, editors. Introduction to biochemical toxicology, 3rd ed. New York: John Wiley and Sons, 2001:487–90.Search in Google Scholar
30. Ahsan R, Islam KM, Bulbul IJ, Musaddik MA, Haque E. Hepatoprotective activity of methanol extract of some medicinal plants against carbon tetrachloride-induced hepatotoxicity in rats. Eur J Sci Res 2009;37:302–10.Search in Google Scholar
31. McCay PB, Lai EK, Poyer JL, DuBose CM, Janzen EG. Oxygen- and carbon-centred free radical formation during carbon tetrachloride metabolism. J Biol Chem 1984;259:2135–43.10.1016/S0021-9258(17)43327-8Search in Google Scholar
32. Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S. The current state of serum biomarkers of hepatotoxicity. Toxicology 2008;245:194–205.10.1016/j.tox.2007.11.021Search in Google Scholar PubMed
33. Yang L, Wang C, Ye J, Li H. Hepatoprotective effects of polyprenols from Ginkgo biloba L. leaves on CCl4-induced hepatotoxicity in rats. Fitoterapia 2011;82:834–40.10.1016/j.fitote.2011.04.009Search in Google Scholar PubMed
34. Park WH, Lee SK, Kim CH. A Korean herbal medicine, Panax notoginseng, prevents liver fibrosis and hepatic microvascular dysfunction in rats. Life Sci 2005;76:1675–90.10.1016/j.lfs.2004.07.030Search in Google Scholar PubMed
35. Rajesh MG, Latha MS. Protective effect of Glycyrrhiza glabra Linn. on carbon tetrachloride-induced peroxidative damage. Ind J Pharmacol 2004;36:284–87.Search in Google Scholar
36. Arıcı OF, Cetin N. Protective role of ghrelin against carbon tetrachloride (CCl4)-induced coagulation disturbances in rats. Regul Pept 2011;166:139–42.10.1016/j.regpep.2010.10.009Search in Google Scholar PubMed
37. Singh A, Bhat TK, Sharma OP. Clinical biochemistry of hepatotoxicity. J Clin Toxicol 2011;S4:001. DOI: 10.4172/2161-0495.S4-001.10.4172/2161-0495.S4-001Search in Google Scholar
38. Drotman RB, Lawhorn GT. Serum enzymes as indicators of chemically induced liver damage. Drug Chem Toxicol 1978;1:163–71.10.3109/01480547809034433Search in Google Scholar
39. Ranawat L, Bhatt J, Patel J. Hepatoprotective activity of ethanolic extracts of bark of Zanthoxylum armatum DC in CCl4 induced hepatic damage in rats. J Ethnopharmacol 2010;127:777–80.10.1016/j.jep.2009.10.019Search in Google Scholar
40. Saba AB, Oyagbemi AA, Azeez OI. Amelioration of carbon tetrachloride-induced hepatotoxicity and haemotoxicity by aqueous leaf extract of Cnidoscolus aconitifolius in rats. Niger J Physiol Sci 2010;25:139–47.Search in Google Scholar
41. Thabrew MI, Joice PD, Rajatissa W. A comparative study of the efficacy of Pavetta indica and Osbeckia octandra in the treatment of liver dysfunction. Planta Med 1987;53:239–41.10.1055/s-2006-962691Search in Google Scholar
42. Sun F, Hamagawa E, Tsutsui C, Ono Y, Ogiri Y, Kojo S. Evaluation of oxidative stress during apoptosis and necrosis caused by carbon tetrachloride in rat liver. Biochim Biophys Acta 2001;1535:186–91.10.1016/S0925-4439(00)00098-3Search in Google Scholar
43. Khan AA, Alzohairy MA. Hepatoprotective effects of camel milk against CCl4-induced hepatotoxicity in rats. Asian J Biochem 2011;6:171–80.10.3923/ajb.2011.171.180Search in Google Scholar
44. Ghosh S, Derle A, Ahire M, More P, Jagtap S, Phadatare SD, et al. Phytochemical analysis and free radical scavenging activity of medicinal plants Gnidia glauca and Dioscorea bulbifera. PLoS One 2013;8:e82529.10.1371/journal.pone.0082529Search in Google Scholar PubMed PubMed Central
45. Adeosun AM, Oni SO, Ighodaro OM, Durosinlorun OH, Oyedele OM. Phytochemical, minerals and free radical scavenging profiles of Phoenix dactilyfera L. seed extract. J Taibah Univ Med Sci 2016;11:1–6.10.1016/j.jtumed.2015.11.006Search in Google Scholar
46. Oni SO, Adeosun AM, Ladokun OA, Ighodaro OM, Oyedele OM. Nutritional and phytochemical profile of Niger cultivated date palm (Phoenix dactilyfera L). J Food Nutr Sci 2015;3:114–8.10.11648/j.jfns.20150303.16Search in Google Scholar
47. Sundararajan R, Haja NA, Venkatesan K, Mukherjee K, Saha BP, Bandyopadhyay A, et al. Cystisus scoparius link – a natural antioxidant. BMC Complement Altern Med 2006;6:8.10.1186/1472-6882-6-8Search in Google Scholar PubMed PubMed Central
©2018 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review
- Pharmacotherapy of ulcerative colitis – current status and emerging trends
- Reproduction
- Bisphenol A decreases the spontaneous contractions of rat uterus in vitro through a nitrergic mechanism
- Cardiovascular Function
- An aqueous extract of the Anogeissus leiocarpus bark (AEAL) induces the endothelium-dependent relaxation of porcine coronary artery rings involving predominantly nitric oxide
- Oxidative Stress
- Alleviation of carbon tetrachloride-induced hepatocellular damage and oxidative stress with a leaf extract of Glyphae brevis (Tiliaceae)
- Protective effect of chloroform extract of Stereospermum chelonoides bark against amyloid beta42 induced cell death in SH-SY5Y cells and against inflammation in Swiss albino mice
- Metabolism
- Iodine in excess in the alterations of carbohydrate and lipid metabolic pattern as well as histomorphometric changes in associated organs
- Immune Response
- Screening of the immunomodulatory and antibacterial activity of Termitomyces letestui (Pat.) Heim (Lyophyllaceae), an edible mushroom from Cameroon
- Inflammation
- High-fat diet modifies cytokine gene expression and exacerbates the effects of acute pancreatitis in the liver of rats
- The acute anti-inflammatory action of xylopic acid isolated from Xylopia aethiopica
- Infection
- Prevalence and antibiotic utilization pattern of uropathogens causing community-acquired urinary tract infection in Kerala, India
- Phytotherapy
- Assessment of azadirachtin-A, a neem tetranortritarpinoid, on rat spermatozoa during in vitro capacitation
- Phenolic-rich extracts of Eurycoma longifolia and Cylicodiscus gabunensis inhibit enzymes responsible for the development of erectile dysfunction and are antioxidants
- Evaluation of anti-obesity and lipid-lowering properties of Vaccinium myrtillus leaves powder extract in a hamster model
Articles in the same Issue
- Frontmatter
- Review
- Pharmacotherapy of ulcerative colitis – current status and emerging trends
- Reproduction
- Bisphenol A decreases the spontaneous contractions of rat uterus in vitro through a nitrergic mechanism
- Cardiovascular Function
- An aqueous extract of the Anogeissus leiocarpus bark (AEAL) induces the endothelium-dependent relaxation of porcine coronary artery rings involving predominantly nitric oxide
- Oxidative Stress
- Alleviation of carbon tetrachloride-induced hepatocellular damage and oxidative stress with a leaf extract of Glyphae brevis (Tiliaceae)
- Protective effect of chloroform extract of Stereospermum chelonoides bark against amyloid beta42 induced cell death in SH-SY5Y cells and against inflammation in Swiss albino mice
- Metabolism
- Iodine in excess in the alterations of carbohydrate and lipid metabolic pattern as well as histomorphometric changes in associated organs
- Immune Response
- Screening of the immunomodulatory and antibacterial activity of Termitomyces letestui (Pat.) Heim (Lyophyllaceae), an edible mushroom from Cameroon
- Inflammation
- High-fat diet modifies cytokine gene expression and exacerbates the effects of acute pancreatitis in the liver of rats
- The acute anti-inflammatory action of xylopic acid isolated from Xylopia aethiopica
- Infection
- Prevalence and antibiotic utilization pattern of uropathogens causing community-acquired urinary tract infection in Kerala, India
- Phytotherapy
- Assessment of azadirachtin-A, a neem tetranortritarpinoid, on rat spermatozoa during in vitro capacitation
- Phenolic-rich extracts of Eurycoma longifolia and Cylicodiscus gabunensis inhibit enzymes responsible for the development of erectile dysfunction and are antioxidants
- Evaluation of anti-obesity and lipid-lowering properties of Vaccinium myrtillus leaves powder extract in a hamster model
