Publications by authors named "Fezah Othman"

9 Publications

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Antinociceptive Activity of Methanolic Extract of Leaves: Possible Mechanisms of Action Involved.

Pain Res Manag 2018 4;2018:9536406. Epub 2018 Mar 4.

Department of Veterinary Pre-Clinical Sciences, Faculty of Veterinary Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.

Methanolic extract of Lindau leaves (MECN) has been proven to possess antinociceptive activity that works via the opioid and NO-dependent/cGMP-independent pathways. In the present study, we aimed to further determine the possible mechanisms of antinociception of MECN using various nociceptive assays. The antinociceptive activity of MECN was (i) tested against capsaicin-, glutamate-, phorbol 12-myristate 13-acetate-, bradykinin-induced nociception model; (ii) prechallenged against selective antagonist of opioid receptor subtypes (-funaltrexamine, naltrindole, and nor-binaltorphimine); (iii) prechallenged against antagonist of nonopioid systems, namely, -noradrenergic (yohimbine), -adrenergic (pindolol), adenosinergic (caffeine), dopaminergic (haloperidol), and cholinergic (atropine) receptors; (iv) prechallenged with inhibitors of various potassium channels (glibenclamide, apamin, charybdotoxin, and tetraethylammonium chloride). The results demonstrated that the orally administered MECN (100, 250, and 500 mg/kg) significantly ( < 0.05) reversed the nociceptive effect of all models in a dose-dependent manner. Moreover, the antinociceptive activity of 500 mg/kg MECN was significantly ( < 0.05) inhibited by (i) antagonists of μ-, -, and -opioid receptors; (ii) antagonists of -noradrenergic, β-adrenergic, adenosinergic, dopaminergic, and cholinergic receptors; and (iii) blockers of different K channels (voltage-activated-, Ca-activated, and ATP-sensitive-K channels, resp.). In conclusion, MECN-induced antinociception involves modulation of protein kinase C-, bradykinin-, TRVP1 receptors-, and glutamatergic-signaling pathways; opioidergic, -noradrenergic, adrenergic, adenosinergic, dopaminergic, and cholinergic receptors; and nonopioidergic receptors as well as the opening of various K channels. The antinociceptive activity could be associated with the presence of several flavonoid-based bioactive compounds and their synergistic action with nonvolatile bioactive compounds.
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September 2018

Anticarcinogenic activity of Muntingia calabura leaves methanol extract against the azoxymethane-induced colon cancer in rats involved modulation of the colonic antioxidant system partly by flavonoids.

Pharm Biol 2017 Dec;55(1):2102-2109

c Halal Product Research Institute , Universiti Putra Malaysia , Serdang , Selangor , Malaysia.

Context: Leaves of Muntingia calabura (Elaeocarpaceae) are widely used in traditional medical practice; scientific findings show various pharmacological activities. However, its anticancer effect has not been investigated thoroughly yet.

Objective: The objective of this study is to study the chemoprevention effects of MEMC against azoxymethane (AOM)-induced colon cancer and to examine the involvement of endogenous antioxidants Materials and methods: Male Sprague-Dawley rats, divided into five groups (n = 7), were injected intraperitoneally once weekly for 2 weeks with 15 mg/kg AOM, except for the normal group (received saline). The animals were then administered orally for 8 weeks with 8% Tween-80 (vehicle; normal group), 8% Tween-80 (vehicle; cancer group) or, 50, 250 or 500 mg/kg MEMC. After treatments, colon samples were collected from each rat for the histopathological analysis, quantification of aberrant crypt foci formed and determination of colon antioxidant levels. MEMC was also subjected to HPLC analysis.

Results: The extract exerted significant (p < 0.05): (i) anti-carcinogenesis activity, indicated by a decrease in the total aberrant crypt formation; (ii) antioxidant activity by increasing the colon tissue antioxidant markers [i.e., superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH)] and reducing the oxidant marker (i.e., malonaldehyde (MDA) levels in comparison with the cancer group. HPLC analysis demonstrated the presence of rutin.

Discussion And Conclusions: Muntingia calabura leaves exert anticancer effect against AOM-induced colon cancer possibly via the action of flavonoids on the colon tissue antioxidant activity.
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December 2017

Methanol extract of Dicranopteris linearis L. leaves impedes acetaminophen-induced liver intoxication partly by enhancing the endogenous antioxidant system.

BMC Complement Altern Med 2017 May 18;17(1):271. Epub 2017 May 18.

Halal Product Research Institute, Universiti Putra Malaysia, 43400, UPM Serdang, Selangor, Malaysia.

Background: The present study investigated the potential of methanolic extract of Dicranopteris linearis (MEDL) leaves to attenuate liver intoxication induced by acetaminophen (APAP) in rats.

Methods: A group of mice (n = 5) treated orally with a single dose (5000 mg/kg) of MEDL was first subjected to the acute toxicity study using the OECD 420 model. In the hepatoprotective study, six groups of rats (n = 6) were used and each received as follows: Group 1 (normal control; pretreated with 10% DMSO (extract's vehicle) followed by treatment with 10% DMSO (hepatotoxin's vehicle) (10% DMSO +10% DMSO)), Group 2 (hepatotoxic control; 10% DMSO +3 g/kg APAP (hepatotoxin)), Group 3 (positive control; 200 mg/kg silymarin +3 g/kg APAP), Group 4 (50 mg/kg MEDL +3 g/kg APAP), Group 5 (250 mg/kg MEDL +3 g/kg APAP) or Group 6 (500 mg/kg MEDL +3 g/kg APAP). The test solutions pre-treatment were made orally once daily for 7 consecutive days, and 1 h after the last test solutions administration (on Day 7th), the rats were treated with vehicle or APAP. Blood were collected from those treated rats for biochemical analyses, which were then euthanized to collect their liver for endogenous antioxidant enzymes determination and histopathological examination. The extract was also subjected to in vitro anti-inflammatory investigation and, HPLC and GCMS analyses.

Results: Pre-treatment of rats (Group 2) with 10% DMSO failed to attenuate the toxic effect of APAP on the liver as seen under the microscopic examination. This observation was supported by the significant (p < 0.05) increased in the level of serum liver enzymes of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), and significant (p < 0.05) decreased in the activity of endogenous antioxidant enzymes of catalase (CAT) and superoxide dismutase (SOD) in comparison to Group 1. Pre-treatment with MEDL, at all doses, significantly (p < 0.05) reduced the level of ALT and AST while the levels of CAT and SOD was significantly (p < 0.05) restored to their normal value. Histopathological studies showed remarkable improvement in the liver cells architecture with increase in dose of the extract. MEDL also demonstrated a low to none inhibitory activity against the respective LOX- and NO-mediated inflammatory activity. The HPLC and GCMS analyses of MEDL demonstrated the presence of several non-volatile (such as rutin, gallic acid etc.) and volatile (such as methyl palmitate, shikimic acid etc.) bioactive compounds.

Conclusion: MEDL exerts hepatoprotective activity against APAP-induced intoxication possibly via its ability to partly activate the endogenous antioxidant system and presence of various volatile and non-volatile bioactive compounds that might act synergistically to enhance the hepatoprotective effect.
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May 2017

Chemopreventive activity of methanol extract of Melastoma malabathricum leaves in DMBA-induced mouse skin carcinogenesis.

Afr J Tradit Complement Altern Med 2014 4;11(4):66-70. Epub 2014 Jun 4.

Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia ; Halal Product Research Institute, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.

Background: Melastoma malabathricum L. Smith (family Melastomaceae) is a shrub that has been used by the Malay practitioners of traditional medicine to treat various types of ailments. The present study aimed to determine the chemopreventive activity of methanol extract of M. malabathricum leaves (MEMM) using the standard 7,12-dimethylbenz(α)anthracene (DMBA)/croton oil-induced mouse skin carcinogenesis model.

Materials And Methods: In the initiation phase, the mice received a single dose of 100µl/100 µg DMBA (group I-V) or 100µl acetone (group VI) topically on the dorsal shaved skin area followed by the promotion phase involving treatment with the respective test solutions (100 µl of acetone, 10 mg/kg curcumin or MEMM (30, 100 and 300mg/kg)) for 30 min followed by the topical application of tumour promoter (100µl croton oil). Tumors were examined weekly and the experiment lasted for 15 weeks.

Results: MEMM and curcumin significantly (p<0.05) reduced the tumour burden, tumour incidence and tumour volume, which were further supported by the histopathological findings.

Conclusion: MEMM demonstrated chemoprevention possibly via its antioxidant and anti-inflammatory activities, and the action of flavonoids like quercitrin.
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June 2015

Anti-inflammatory and anti-hyperalgesic activities of Acanthopanax trifoliatus (L) Merr leaves.

Pharmacognosy Res 2013 Apr;5(2):129-33

Department of Biomedical Science, Faculty of Medicine and Health Sciences, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia.

Context: Acanthopanax trifoliatus is a ginseng-like plant, which has been widely used to treat various diseases including inflammatory-related diseases.

Aims: The present study has been designed to investigate the anti-inflammatory and anti-hyperalgesic effects of various fractions of Acanthopanax trifoliatus leaves ethanolic extract in rats.

Materials And Methods: Anti-inflammatory activity was studied by using carrageenan-induced edema on rat paw whilst anti-hyperalgesic was assessed by using carrageenan-evoked thermal hyperalgesia on plantar test.

Statistical Analysis Used: Data were analyzed using Student t-test to compare with control. Multiple comparisons for difference between control and extract-treated groups were evaluated by Tukey HSD (Honestly Significant Difference) test. P values less than 0.05 (P < 0.05) is considered significant.

Results: Among three different fractions i.e., hexane, dichloromethane, and methanol tested, methanolic fraction displayed the most potent fraction amongst those three. It gave significant anti-inflammatory effect at highest dose, 500 mg/kg, with 77.24% of inhibition. Whilst for anti-hyperalgesic activity, methanolic fraction showed the highest efficacy at 375 mg/kg. Administration of methanolic fraction of Acanthopanax trifoliatus inhibited paw edema in a dose- dependent manner. The inhibition for both activities might be due to possible composition of polar compounds, which are flavonoids and phenolics content.

Conclusions: Methanol fraction of Acanthopanax trifoliatus leaves has potential effect as anti-inflammatory and anti-hyperalgesia in acute inflammation model.
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April 2013

Chemopreventive effect of Ardisia crispa hexane fraction on the peri-initiation phase of mouse skin tumorigenesis.

Med Princ Pract 2013 7;22(4):357-61. Epub 2013 Feb 7.

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University Putra Malaysia, Selangor, Malaysia.

Objective: To investigate the chemopreventive effect of the hexane extract of Ardisia crispa during the peri-initiation phase of mouse skin tumorigenesis.

Materials And Methods: This study was conducted for 12 weeks on two-stage 7,12-dimethylbenz(α)-anthracene (DMBA)-induced tumor initiation followed by croton-oil-induced tumor promotion in mice. A. crispa root hexane extract (ACRH) was applied at various doses (30, 100, 300 mg/kg) 7 days prior to and after DMBA treatment. Throughout the study, morphological observations, i.e., tumor incidence, tumor volume and tumor burden were measured for each of the treated groups. At the end of the experiment, the mice were sacrificed and their skin tissues were examined histopathologically.

Results: The highest dose of ACRH (300 mg/kg) significantly delayed tumor formation (week 9, p < 0.05) and exhibited the lowest tumor volume (0.71 ± 0.00 mm(3), p < 0.05), tumor burden (2.00 ± 0.00, p < 0.05), and tumor incidence (16.67%, p < 0.05) compared to other doses of ACRH. A 100-mg/kg dose produced tumor latency at week 7, tumor volume of 2.44 ± 0.88 mm(3) (p < 0.05), tumor burden of 1.60 ± 0.60 (p < 0.05), and tumor incidence of 50%; 30 mg/kg produced tumor latency at week 8, tumor volume of 2.04 ± 0.45 mm(3) (p < 0.05), tumor burden of 2.17 ± 0.54, tumor incidence of 60% and carcinogen control (tumor latency at week 7; tumor volume, 3.56 mm(3); tumor incidence of 66.67%).

Conclusion: The highest dose of A. crispa hexane extract delayed tumor development, thus showing a chemopreventive effect on mouse skin tumorigenesis.
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September 2014

Anti-tumor effect of Ardisia crispa hexane fraction on 7, 12-dimethylbenz[α]anthracene-induced mouse skin papillomagenesis.

J Cancer Res Ther 2012 Jul-Sep;8(3):404-10

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.

Context: Ardisia crispa Thunb. A. DC (Myrsinaceae) or locally known as hen's eyes has been used in local folk medicine as a remedy in various illnesses. Previously, it has been reported to inhibit various inflammatory diseases. However, research done on this plant is still limited.

Aims: In the present study, the hexane fraction of the A. crispa root (ACRH) was evaluated on the peri-initiation and promotion phases of skin carcinogenesis.

Materials And Methods: This two-stage skin carcinogenesis was induced by a single topical application of 7,12-dimethylbenz(α)anthracene (DMBA) and promoted by repeated treatment with croton oil for 10 weeks in Imprinting Control Region (ICR) mice. Morphological observation would be conducted to measure tumor incidence, tumor burden, and tumor volume. Histological evaluation on the skin tissue would also be done.

Results: The carcinogen control group exhibited 66.67% of tumor incidence. Although, in the ACRH-treated groups, at 30 mg/kg, the mice showed only 10% of tumor incidence with a significant reduction (P < 0.05) in the values of tumor burden and tumor volume of 2.00 and 0.52 mm(3), respectively. Furthermore, the result was significantly lower than that of the carcinogen and curcumin control. At 100 mg/kg, ACRH showed a comparable result to carcinogen control. On the contrary, at 300 mg/kg, ACRH exhibited 100% tumor incidence and showed a significant elevated (P < 0.05) value of tumor burden (3.80) and tumor volume (14.67 ± 2.48 mm(3)).

Conclusions: The present study thus demonstrates that the anti-tumor effect of the chemopreventive potential of ACRH is at a lower dosage (30 mg/kg bwt) in both the initiating and promotion period, yet it exhibits a promoting effect at a higher dosage (300 mg/kg bwt).
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June 2013

Antiulcer activity of the chloroform extract of Bauhinia purpurea leaf.

Pharm Biol 2012 Dec 11;50(12):1498-507. Epub 2012 Sep 11.

Faculty of Pharmacy, Universiti Teknologi MARA , Puncak Alam Campus, Bandar Puncak Alam, Selangor, Malaysia.

Context: Bauhinia purpurea L. (Fabaceae) is a native plant species of many Asian countries, including Malaysia and India. In India, the root, stem, bark, and leaf of B. purpurea are used to treat various ailments, including ulcers and stomach cancer.

Objective: In an attempt to establish its pharmacological potential, we studied the antiulcer activity of lipid-soluble extract of B. purpurea obtained via extraction of air-dried leaves using chloroform.

Materials And Methods: The rats were administered the chloroform extract (dose range of 100-1000 mg/kg) orally after 24 h fasting. They were subjected to the absolute ethanol- and indomethacin-induced gastric ulcer, and pyloric ligation assays after 30 min. The acute toxicity study was conducted using a single oral dose of 5000 mg/kg extract and the rats were observed for the period of 14 days. omeprazole (30 mg/kg) was used as the standard control.

Results: At 5000 mg/kg, the extract produced no sign of toxicity in rats. The extract exhibited significant (p < 0.05) dose-dependent antiulcer activity for the ethanol-induced model. The extract also significantly (p < 0.05) increased the gastric wall mucus production and pH of gastric content, while significantly (p < 0.05) reducing the total volume and total acidity of the gastric content in the pylorus ligation assay.

Discussion And Conclusion: The extract possesses antiulcer, antisecretory and cytoprotective activities, which could be attributed to its flavonoid and tannin content. These findings provide new information regarding the potential of lipid-soluble compounds of B. purpurea for the prevention and treatment of gastric ulcers.
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December 2012

Antiproliferative and Proapoptotic Effects of Labisia pumila Ethanol Extract and Its Active Fraction in Human Melanoma HM3KO Cells.

Evid Based Complement Alternat Med 2012 8;2012:123470. Epub 2012 Mar 8.

School of Biosciences and Biotechnology, Faculty of Science and Technology, National University of Malaysia, 43600 Bangi, Malaysia.

The present study was to determine the anticancer potential of Labisia pumila in in vitro models. Results from the study revealed that ethanol extract of L. pumila was more cytotoxic against HM3KO cells while having reduced effects on nonmalignant cells as compared to aqueous and hexane extracts. Thus, ethanol extract was selected to be further separated by using the bioassay-guided fractionation method to give an active fraction, SF2Lp. Results obtained from the flow cytometry analysis showed that SF2Lp was able to arrest the HM3KO cell cycle at the G1 phase, while morphological findings from AO-EB nuclear staining assays along with the Apoptotic Index confirmed the induction of apoptosis by SF2Lp in HM3KO cells. Results from the mechanistic study further revealed that SF2Lp treatment was able to concurrently increase the expression level of p53 and pro-apoptotic protein Bax and also reduce the expression level of anti-apoptotic protein BCl-2 in HM3KO cells, directly contributing to the increase in Bax/Bcl-2 ratio. These findings, therefore, suggested that L. pumila was able to inhibit HM3KO cell growth possibly by arresting the cell cycle at G1 phase and inducing apoptosis in HM3KO cells via the up- and down-regulation of Bax/Bcl-2 protein, mediated through a p53-dependent pathway.
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August 2012