Antioxidant and Protective Effect of Ajuga chamaecistus ssp. tomentella on CCl4 -Induced Liver Toxicity in Rat
Abstract
Ajuga chamaecistus ssp. tomentella (known as “komafitoos”) has been used in traditional Persian medicine for treating various illnesses including liver ailments. This study aims to evaluate the antioxidant and hepatoprotective effect of A. chamaecistus ssp. tomentella. Chloroform, ethyl acetate (EAF), and the remaining hydroalcoholic fractions were separated from the total extract of the aerial parts of the plant and their antioxidant activity was evaluated using radical scavenging assay method (2,2-diphenyl-1-picrylhydrazyl, DPPH). The EAF was assessed against carbon tetrachloride (CCl4)-induced toxicity in rats. Rats were parted into 7 groups each containing 6 animals: sham (normal saline), CCl4 (single dose of 1 mL/kg b.w., i.p.), treatment groups 3, 4, 5 (treated 7 days with 25, 50 or 100 mg/kg EAF, respectively, p.o.) and 6 (treated 7 days with 100 mg/kg silymarin, p.o.) following a single dose of 1 mL/kg CCl4, i.p.). Group 7 received 100 mg/kg ethyl acetate fraction for 7 days. Animals were sacrificed 24 h after the last dose and total protein content and biochemical parameters were assayed in the serum. Glutathione, malondialdehyde, and superoxide dismutase levels were measured in the liver homogenates. Histological changes in the liver tissue were examined using a light microscope. EAF showed the best antioxidant activity according to the DPPH free radical scavenging assay (IC50=60.5 µg/mL) in comparison to the other fractions. It significantly alleviated serum transaminase levels, alkaline phosphatase, alanine transaminase, aspartate aminotransferase, and lactate dehydrogenase, especially with 25 and 50 mg/kg doses. Treatment with EAF increased superoxide dismutase activity and glutathione content; while decreasing the malondialdehyde level similar to the Silymarin group. Histological examination further confirmed our biochemical findings. A. chamaecistus ssp. tomentella showed acceptable hepatoprotective activity, as described by traditional Persian medicine.
Basu S. Carbon tetrachloride-induced lipid peroxidation: eicosanoid formation and their regulation by antioxidant nutrients. Toxicology 2003;189:113-127.
Madrigal-Santillan E, Madrigal-Bujaidar E, Alvarez-Gonzalez I, Sumaya-Martinez MT, Gutierrez-Salinas J, et al. Review of natural products with hepatoprotective effects. World J Gastroenterol 2014;20:14787-14804.
Eidi A, Moghadam JZ, Mortazavi P, Rezazadeh S, Olamafar S. Hepatoprotective effects of Juglans regia extract against CCl4-induced oxidative damage in rats. Pharm Biol 2013;51:558-565.
DeFeudis FV, Papadopoulos V, Drieu K. Ginkgo biloba extracts and cancer: a research area in its infancy. Fundam Clin Pharmacol 2003;17:405-417.
Banskota AH, Tezuka Y, Adnyana IK, Xiong Q, Hase K, et al. Hepatoprotective effect of Combretum quadrangulare and its constituents. Biol Pharm Bull 2000;23:456-460.
Mozaffarian V. A dictionary of Iranian Plant Names. Tehran: Farhangmoaser 2007.
Tonkaboni M, In: Rahimi R, Shams-ardekani M, Farjadmand F. Tohfeh-al-Momenin. Tehran, Iran: Shahid Beheshti University of Medical Sciences 2007.
Hsieh WT, Liu YT, Lin WC. Anti-inflammatory properties of Ajuga bracteosa in vivo and in vitro study and their effects on mouse model of liver fibrosis. J Ethnopharmacol 2011;135:116-125.
Gautam R, Jachak SM, Saklani A. Anti-inflammatory effect of Ajuga bracteosa Wall Ex Benth. mediated through cyclooxygenase (COX) inhibition. J Ethnopharmacol 2011;133:928-930.
El-Hilaly J, Tahraoui A, Israili ZH, Lyoussi B. Acute hypoglycemic, hypocholesterolemic and hypotriglyceridemic effects of continuous intravenous infusion of a lyophilised aqueous extract of Ajuga iva L. Schreber whole plant in streptozotocin-induced diabetic rats. Pak J Pharm Sci 2007;20:261-268.
El Hilaly J, Lyoussi B. Hypoglycaemic effect of the lyophilised aqueous extract of Ajuga iva in normal and streptozotocin diabetic rats. J Ethnopharmacol 2002;80:109-113.
Ono Y, Fukaya Y, Imai S, Yamakuni T. Beneficial effects of Ajuga decumbens on osteoporosis and arthritis. Biol Pharm Bull 2008;31:1199-1204.
Kuria KA, Chepkwony H, Govaerts C, Roets E, Busson R, et al. The antiplasmodial activity of isolates from Ajuga remota. J Nat Prod 2002;65:789-793.
Castro A, Coll J, Tandron YA, Pant AK, Mathela CS. Phytoecdysteroids from Ajuga macrosperma var. breviflora roots. J Nat Prod 2008;71:1294-1296.
Vanyolos A, Simon A, Toth G, Polgar L, Kele Z, et al. C-29 ecdysteroids from Ajuga reptans var. reptans. J Nat Prod 2009;72:929-932.
Castro A, Coll J, Pant AK, Pakrash O. Neo-clerodane diterpenoids from Ajuga macrosperma var. breviflora. Nat Prod Commun 2015;10:857-860.
Castro A, Coll J, Arfan M. Neo-clerodane diterpenoids from Ajuga bracteosa. J Nat Prod 2011;74:1036-1041.
Manguro LO, Ogur JA, Okora DM, Wagai SO, Lemmen P. Further flavonol and iridoid glycosides from Ajuga remota aerial parts. J Asian Nat Prod Res 2007;9:617-629.
Akbay P, Calis I, Heilmann J, Sticher O. New stigmastane sterols from Ajuga salicifolia. J Nat Prod 2003;66:461-465.
Akbay P, Calis I, Heilmann J, Sticher O. Ionone, iridoid and phenylethanoid glycosides from Ajuga salicifolia. Z Naturforsch C 2003;58:177-180.
Ardekani MRS, Khanavi M, Taheri P, Samadi N, Safaripour E, et al. The essential oil composition of Ajuga chamaecistus Ging. subsp. Tomentella Rech. f. J Essent Oil-Bear Plants 2010;13:45-51.
Brand-Williams W, Cuvelier M-E, Berset C. Use of a free radical method to evaluate antioxidant activity. LWT-Food Sci Technol 1995;28:25-30.
Kahkeshani N, Farahanikia B, Mahdaviani P, Abdolghaffari A, Hassanzadeh G, et al. Antioxidant and burn healing potential of Galium odoratum extracts. Res Pharm Sci 2013;8:197-203.
Sepand MR, Razavi-Azarkhiavi K, Omidi A, Zirak MR, Sabzevari S, et al. Effect of acetyl-L-carnitine on antioxidant status, lipid peroxidation, and oxidative damage of arsenic in rat. Biol Trace Element Res 2016;171:107-115.
Minaie B. Basic principles and methods of histology and stereology. Tehran University Press. Tehran 2001; pp 15-25.
Ramazanov NS. Phytoecdysteroids and other biologically active compounds from plants of the Genus Ajuga. Chem Nat Compd 2005;41:361-369.
Cai YJ, Dai JQ, Fang JG, Ma LP, Hou LF, et al. Antioxidative and free radical scavenging effects of ecdysteroids from Serratula strangulata. Can J Physiol Pharmacol 2002;80:1187-1194.
Hu J, Luo CX, Chu WH, Shan YA, Qian ZM, et al. 20-Hydroxyecdysone protects against oxidative stress-induced neuronal injury by scavenging free radicals and modulating NF-kappaB and JNK pathways. PLoS One 2012;7:e50764.
Surai PF. Silymarin as a natural antioxidant: an overview of the current evidence and perspectives. Antioxidants 2015;4:204-247.
Lim HK, Kim HS, Choi HS, Choi J, Kim SH, et al. Effects of bergenin, the major constituent of Mallotus japonicus against D-galactosamine-induced hepatotoxicity in rats. Pharmacology 2001;63:71-75.
Tsikas D. Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: Analytical and biological challenges. Anal Biochem 2017;524:13-30.
Zhao H, Ruan H, Li H. Progress in the research of GSH in cells. Chin Sci Bull 2011;56:3057-3063.
Halliwell B. Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? The Lancet 1994;344:721-724.
Bouderbala S, Lamri-Senhadji M, Prost J, Lacaille-Dubois MA, Bouchenak M. Changes in antioxidant defense status in hypercholesterolemic rats treated with Ajuga iva. Phytomedicine 2008;15:453-461.
Taleb-Senouci D, Ghomari H, Krouf D, Bouderbala S, Prost J, et al. Antioxidant effect of Ajuga iva aqueous extract in streptozotocin-induced diabetic rats. Phytomedicine 2009;16:623-631.
Bouderbala S, Prost J, Lacaille-Dubois MA, Bouchenak M. Iridoid extracts from Ajuga iva increase the antioxidant enzyme activities in red blood cells of rats fed a cholesterol-rich diet. Nutr Res 2010;30:358-365.
Rahiminiya A, Herizchi Ghadim H , Sadati Lamardi SN. Medicinal importance of ajuga species in iran: ethnobotanical and traditional applications, phytochemical, and pharmacological studies. Jundishapur J Nat Pharm Prod 2022;17:e119209.
| Issue | Vol 10, No 2, 2025 (In Press) | |
| Section | Research Article(s) | |
| Keywords | ||
| Ajuga chamaecistus ssp Tomentella Antioxidant CCl4 Hepatoprotective effect | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
