Pak. J. Pharm. Sci., Vol.27, No.4, July 2014, pp.831-835 831 Effect of aqueous extract of Dicranopteris linearis leaves against paracetamol and carbon tetrachloride-induced liver toxicity in rats Noor Aisyah Ismail 1 , Nor Syafawati Shamsahal Din 1 , Siti Syariah Mamat 1 , Zalina Zabidi 1 , Wan Noraziemah Wan Zainulddin 1 , Farah Hidayah Kamisan 1 , Farhana Yahya 1 , Norhafizah Mohtarrudin 2 , Mohd Nasir Mohd Desa 1 and Zainul Amiruddin Zakaria 1,3* 1 Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia 2 Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia 3 Pharmacogenomics Center, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam, Selangor, Malaysia Abstract: The present study aimed to determine the hepatoprotective activity of Dicranopteris linearis L. (family Gleicheniaceae) leaf aqueous extract (DLAE) using two models of liver injury in rats. Rats were divided into ten groups (n=6) and received dH 2 O (negative control), 200 mg/kg silymarin (positive control) or DLAE (50, 250 and 500 mg/kg) orally once daily for 7 consecutive days and on the 8 th day subjected to the hepatotoxic induction either using carbon tetrachloride (CCl 4 ) or paracetamol (PCM). The bloods and livers were collected and subjected to biochemical and microscopical analysis. From the data obtained, only the highest dose of DLAE significantly (p<0.05) reduced the ALP, ALT and AST levels in CCl 4 -and PCM-induced hepatotoxic rats while the other doses caused significant (p<0.05) reduction only in the levels of ALT and AST. The histological results obtained were in line with the biochemical analysis wherein reduction in the CCl 4 - and PCM-induced tissue formation of necrosis, steatosis and inflammation occurred in a dose-dependent manner. In conclusion, the DLAE possesses hepatoprotective activity, which could be attributed to its free radicals scavenging and antioxidant activities, and high flavonoids content. Thus, in-depth studies regarding the hepatoprotective activity of DLAE are warranted. Keywords: Dicranopteris linearis; Gleicheniaceae; in vivo; hepatoprotective activity; aqueous extract; leaves. INTRODUCTION Acute liver failure can results from toxic liver damage by drugs or poisons with oxidation process has been partly associated with the hepatic injury mediated by those agents (Adewusi and Afolayan, 2010). Despite extensive improvement in the field of modern medicine, it offers little benefit, particularly, towards the management of acute liver failure (Wagh et al., 2010; Taub 2003). Furthermore, the incidence of relapse as well as side effects and development of tolerance upon uses of standard drugs on clinical evaluation make their efficacy arguable. This has been the basis for the development of new plant-based drugs, which include plant-based hepatoprotective agents (Mard et al., 2008). One of the plants that have been reported to possess several pharmacological activities and is presently being studied in our laboratory for its hepatoprotective effect is Dicranopteris linearis L. Despite its limited usages within the Malay traditional medicine (Zakaria et al., 2010), this plant, which is called ‘pokok resam’ by the Malay and belongs to the family Gleicheniaceae, has been proven to possess several pharmacological properties (Zakaria et al., 2010; Zakaria et al., 2006; Zakaria et al., 2008; Zakaria et al., 2011a). Of those pharmacological activities, the mechanisms of anti-inflammation, antioxidation and anti- proliferation are known to be interrelated to each other as well as to the hepatoprotective mechanism (Dash et al., 2007; Chattopadhyay 2003). Based on these facts, the potential of D. linearis leaf aqueous extract (DLAE) to exert hepatoprotective activity was investigated in the present study using various rat models. MATERIALS AND METHODS Plant material and preparation of the aqueous extract (DLAE) The leaves of D. linearis were collected between July and August, 2010 from its natural habitat around Serdang, Selangor, Malaysia. A new voucher specimen, IR 0128/11, was deposited at the Herbarium of the Institute of Bioscience (IBS), Universiti Putra Malaysia. The preparation of DLAE was performed as previously described (Zakaria et al., 2008; Zakaria et al., 2011a). Eighty gram (80 g) of dried powdered leaves was soaked for 72 h in distilled water (dH 2 O) in the ratio of 1:20 (w/v) at room temperature. After 72 h, the aqueous supernatant was collected and the residue was soaked again for another two times. The supernatant was pooled together and freeze-dried to yield approximately 15.7 g of dried DLAE (percentage yielded was ≈19.5%). *Corresponding author: e-mail: dr_zaz@yahoo.com