Publications by authors named "Mahmood Ameen Abdulla"

98 Publications

acute toxicity evaluation and molecular mechanism study of antiproliferative activity of a novel indole Schiff base -diiminato manganese complex in hormone-dependent and triple negative breast cancer cells.

PeerJ 2019 7;7:e7686. Epub 2019 Oct 7.

Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Breast cancer is the most frequently diagnosed cancer among women worldwide. Recently, increasing attention has been paid to the anticancer effects of transition metal complexes of indole Schiff bases. β-diiminato Manganese complex has shown promising cell cycle arrest and apoptosis induction against MCF-7 and MDA-MB-231 breast cancer cells. In this study, time- and dose- dependent inhibitory activity were evaluated using MTT assay after 48 h and 72 h exposure time. In addition, median effect analysis was conducted according to Chou-Talalay method to investigate whether Mn complex has synergistic effect in combination with chemotherapeutic drugs on inhibiting breast cancer cell growth. The molecular mechanisms underlying its potent antiproliferative effect was determined through bioluminescent caspase-3/7, -8 and -9 activity assays and quantitative expression analysis of cell cycle- and apoptosis-related genes. Furthermore, safety evaluation of Mn complex was assessed through the acute oral toxicity test in model. The MTT assay results revealed that it potently reduced the viability of MCF-7 (IC of 0.63 ± 0.07 µg/mL for 48 h and 0.39 ± 0.08 µg/mL for 72 h) and MDA-MB-231 (1.17 ± 0.06 µg/mL for 48 h, 1.03 ± 0.15 µg/mL for 72 h) cells in dose- and time-dependent manner. Combination treatment also enhanced the cytotoxic effects of doxorubicin but not tamoxifen on inhibiting breast cancer cell growth. The involvement of intrinsic and extrinsic pathway in apoptosis induction was exhibited through the increased activity of caspase-9 and caspase-8, respectively, leading to enhanced downstream executioner caspase-3/7 activity in treated MCF-7 and MDA-MB-231 cells. In addition, gene expression analysis revealed that Mn complex exerts its antiproliferative effect via up-and down-regulation of p21 and cyclin D1, respectively, along with increased expression of Bax/Bcl-2 ratio, TNF-α, initiator caspase-8 and -10 and effector caspase-3 in MCF-7 and MDA-MB-231 cells. However, the results did not show increased caspase-8 activity in treated MCF-7 cells. Furthermore, acute oral toxicity test revealed no signs of toxicity and mortality in treated animal models compared to the control group. Collectively, the promising inhibitory effect and molecular and mechanistic evidence of antiproliferative activity of Mn complex and its safety characterization have demonstrated that it may have therapeutic value in breast cancer treatment worthy of further investigation and development.
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http://dx.doi.org/10.7717/peerj.7686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786247PMC
October 2019

Corrigendum to "A Comparison of Wound Healing Rate Following Treatment with Aftamed and Chlorine Dioxide Gels in Streptozotocin-Induced Diabetic Rats".

Evid Based Complement Alternat Med 2019 10;2019:4265081. Epub 2019 Jan 10.

Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

[This corrects the article DOI: 10.1155/2012/468764.].
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http://dx.doi.org/10.1155/2019/4265081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348817PMC
January 2019

Corrigendum to "Gastroprotective Activity of Aqueous Leaf Extract on Ethanol-Induced Hemorrhagic Mucosal Lesions in Rats".

Evid Based Complement Alternat Med 2018 2;2018:8961462. Epub 2018 Dec 2.

Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

[This corrects the article DOI: 10.1155/2012/404012.].
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http://dx.doi.org/10.1155/2018/8961462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320006PMC
December 2018

Corrigendum to "Peripheral Nerve Regeneration Following Crush Injury to Rat Peroneal Nerve by Aqueous Extract of Medicinal Mushroom (Bull.: Fr) Pers. (Aphyllophoromycetideae)".

Evid Based Complement Alternat Med 2018 16;2018:9820769. Epub 2018 Dec 16.

Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia.

[This corrects the article DOI: 10.1093/ecam/neq062.].
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http://dx.doi.org/10.1155/2018/9820769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311275PMC
December 2018

Hepatoprotectivity of Panduratin A against liver damage: In vivo demonstration with a rat model of cirrhosis induced by thioacetamide.

APMIS 2018 Sep 29;126(9):710-721. Epub 2018 Jul 29.

Biophysics Department, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey.

This experiment evaluated Panduratin A (PA), a chalcone isolated from Boesenbergia rotunda rhizomes, for its hepatoprotectivity. Rats were subjected to liver damage induced by intra-peritoneal injection of thioacetamide (TAA). PA was tested first for its acute toxicity and then administered by oral gavage at doses 5, 10, and 50 mg/kg to rats. At the end of the 8 week, livers from all rats were excised and evaluated ex vivo. Measurements included alkaline phosphatase (AP), alanine transaminase (ALT), aspartate transaminase (AST) and gamma-glutamyl transferase (GGT), serum platelet-derived growth factor (PDGF) and transforming growth factor (TGF-β1), and hepatic metalloproteinase enzyme (MMP-2) and its inhibitor extracellular matrix protein (TIMP-1). Oxidative stress was measured by liver malondialdehyde (MDA) and nitrotyrosine levels, urinary 8-hydroxy 2- deoxyguanosine (8-OH-dG), and hepatic antioxidant enzyme activities. The immunohistochemistry of TGF-β was additionally performed. PA revealed safe dose of 250 mg/kg on experimental rats and positive effect on the liver. The results suggested reduced hepatic stellate cells (HSCs) activity as verified from the attenuation of serum PDGF and TGF-β1, hepatic MMP-2 and TIMP-1, and oxidative stress. The extensive data altogether conclude that PA treatment could protect the liver from the progression of cirrhosis through a possible mechanism inhibiting HSCs activity.
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http://dx.doi.org/10.1111/apm.12878DOI Listing
September 2018

Synthesis of Novel Derivatives of Quinazoline Schiff base Compound Promotes Epithelial Wound Healing.

Curr Pharm Des 2018 ;24(13):1395-1404

Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

Quinazoline is an aromatic bicyclic compound exhibiting several pharmaceutical and biological activities. This study was conducted to investigate the potential wound healing properties of Synthetic Quinazoline Compound (SQC) on experimental rats. The toxicity of SQC was determined by MTT cell proliferation assay. The healing effect of SQC was assessed by in vitro wound healing scratch assay on the skin fibroblast cells (BJ-5ta) and in vivo wound healing experiment of low and high dose of SQC on adult Sprague-Dawley rats compared with negative (gum acacia) and positive control (Intrasite-gel). Hematoxylin and Eosin (H&E), Masson's Trichrome (MT) staining and immunohistochemistry analysis were performed to evaluate the histopathological alterations and proteins expression of Bax and Hsp70 on the wound tissue after 10 days. In addition, levels of antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase), and malondialdehyde (MDA) were measured in wound tissue homogenates. The SQC significantly enhanced BJ-5ta cell proliferation and accelerated the percentage of wound closure, with less scarring, increased fibroblast and collagen fibers and less inflammatory cells compared with the negative control. The compound also increases endogenous enzymes and decline lipid peroxidation in wound homogenate.
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http://dx.doi.org/10.2174/1381612824666180130124308DOI Listing
November 2019

Persistent infection due to a small-colony variant of Burkholderia pseudomallei leads to PD-1 upregulation on circulating immune cells and mononuclear infiltration in viscera of experimental BALB/c mice.

PLoS Negl Trop Dis 2017 Aug 18;11(8):e0005702. Epub 2017 Aug 18.

Center of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia.

Background: Melioidosis is a neglected tropical disease endemic across South East Asia and Northern Australia. The etiological agent, Burkholderia pseudomallei (B.pseudomallei), is a Gram-negative, rod-shaped, motile bacterium residing in the soil and muddy water across endemic regions of the tropical world. The bacterium is known to cause persistent infections by remaining latent within host cells for prolonged duration. Reactivation of the recrudescent disease often occurs in elders whose immunity wanes. Moreover, recurrence rates in melioidosis patients can be up to ~13% despite appropriate antibiotic therapy, suggestive of bacterial persistence and inefficacy of antibiotic regimens. The mechanisms behind bacterial persistence in the host remain unclear, and hence understanding host immunity during persistent B. pseudomallei infections may help designing potential immunotherapy.

Methodology/principal Findings: A persistent infection was generated using a small-colony variant (SCV) and a wild-type (WT) B. pseudomallei in BALB/c mice via intranasal administration. Infected mice that survived for >60 days were sacrificed. Lungs, livers, spleens, and peripheral blood mononuclear cells were harvested for experimental investigations. Histopathological changes of organs were observed in the infected mice, suggestive of successful establishment of persistent infections. Moreover, natural killer (NK) cell frequency was increased in SCV- and WT-infected mice. We observed programmed death-1 (PD-1) upregulation on B cells of SCV- and WT-infected mice. Interestingly, PD-1 upregulation was only observed on NK cells and monocytes of SCV-infected mice. In contrast, cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) downregulation was seen on NK cells of WT-infected mice, and on monocytes of SCV- and WT-infected mice.

Conclusions/significance: The SCV and the WT of B. pseudomallei distinctly upregulated PD-1 expression on B cells, NK cells, and monocytes to dampen host immunity, which likely facilitates bacterial persistence. PD-1/PD-L1 pathway appears to play an important role in the persistence of B. pseudomallei in the host.
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http://dx.doi.org/10.1371/journal.pntd.0005702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562302PMC
August 2017

Beta-mangostin demonstrates apoptogenesis in murine leukaemia (WEHI-3) cells in vitro and in vivo.

BMC Complement Altern Med 2017 Jul 17;17(1):366. Epub 2017 Jul 17.

Medical Research Centre, Jazan University, Jazan, 11420, Saudi Arabia.

Background: Beta-mangostin (BM) is a xanthone-type of natural compound isolated from Cratoxylum arborescens. This study aimed to examine the apoptosis mechanisms induced by BM in a murine monomyelocytic cell line (WEHI-3) in vitro and in vivo.

Methods: A WEHI-3 cell line was used to evaluate the cytotoxicity of BM by MTT. AO/PI and Hoechst 33342 dyes, Annexin V, multiparametric cytotoxicity 3 by high content screening (HCS); cell cycle tests were used to estimate the features of apoptosis and BM effects. Caspase 3 and 9 activities, ROS, western blot for Bcl2, and Bax were detected to study the mechanism of apoptosis. BALB/c mice injected with WEHI-3 cells were used to assess the apoptotic effect of BM in vivo.

Results: BM suppressed the growth of WEHI-3 cells at an ICvalue of 14 ± 3 μg/mL in 24 h. The ROS production was increased inside the cells in the treated doses. Both caspases (9 and 3) were activated in treating WEHI-3 cells at 24, 48 and 72 h. Different signs of apoptosis were detected, such as cell membrane blebbing, DNA segmentation and changes in the asymmetry of the cell membrane. Another action by which BM could inhibit WEHI-3 cells is to restrain the cell cycle at the G1/G0 phase. In the in vivo study, BM reduced the destructive effects of leukaemia on the spleen and liver by inducing apoptosis in leukaemic cells.

Conclusion: BM exerts anti-leukaemic properties in vitro and in vivo.
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http://dx.doi.org/10.1186/s12906-017-1867-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513316PMC
July 2017

Methanol leaf extract of (Lauraceae) enhances gastric defense against ethanol-induced ulcer in rats.

Drug Des Devel Ther 2017 4;11:1353-1365. Epub 2017 May 4.

Department of Chemistry, Faculty of Science.

Hook. F. Var. Glabra (Kochummen), also known as "Medang payung" by the Malay people, belongs to the Lauraceae family. In this study, methanol leaf extract of was investigated for their acute toxicity and gastroprotective effects to reduce ulcers in rat stomachs induced by ethanol. The rats were assigned to one of five groups: normal group (group 1), ulcer group (group 2), control positive drug group (group 3) and two experimental groups treated with 150 mg/kg (group 4) and 300 mg/kg (group 5) of leaf extract. The rats were sacrificed an hour after pretreatment with extracts, and their stomach homogenates and tissues were collected for further evaluation. Macroscopic and histological analyses showed that gastric ulcers in rats pretreated with the extract were significantly reduced to an extent that it allowed leukocytes penetration of the gastric walls compared with the ulcer group. In addition, an ulcer inhibition rate of >70% was detected in rats treated with both doses of extract, showing a notable protection of gastric layer. Severe destruction of gastric mucosa was prevented with a high production of mucus and pH gastric contents in both omeprazole-treated and extract-treated groups. Meanwhile, an increase in glycoprotein uptake was observed in pretreated rats through accumulation of magenta color in Periodic Acid Schiff staining assay. Analysis of gastric homogenate from pretreated rats showed a reduction of malondialdehyde and elevation of nitric oxide, glutathione, prostaglandin E2, superoxide dismutase and protein concentration levels in comparison with group 2. Suppression of apoptosis in gastric tissues by upregulation of Hsp70 protein and downregulation of Bax protein was also observed in rats pretreated with extract. Consistent results of a reduction of gastric ulcer and the protection of gastric wall were obtained for rats pretreated with extract, which showed its prominent gastroprotective potential in rats' stomach against ethanol-induced ulcer.
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http://dx.doi.org/10.2147/DDDT.S120564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5422334PMC
February 2018

The antiulcer effect of leaves in rats with experimentally induced acute gastric ulcer.

Drug Des Devel Ther 2017 30;11:995-1009. Epub 2017 Mar 30.

Department of Biomedical Science, Faculty of Medicine.

is a pharmaceutical plant customarily used in traditional medicine in Malaysia for the treatment of different diseases, such as gastric ulcer. The gastroprotective effect of leaves against ethanol-induced gastric hemorrhagic abrasions in Sprague Dawley rats has been evaluated in terms of medicinal properties. Seven groups of rats (normal control and ulcerated control groups, omeprazole 20 mg/kg, 62.5, 125, 250, and 500 mg/kg of correspondingly) were used in antiulcer experiment and pretreated with 10% Tween 20. After 1 hour, the normal group was orally administered 10% Tween 20, whereas absolute alcohol was fed orally to ulcerated control, omeprazole, and experimental groups. Gastric's homogenate were assessed for endogenous enzymes activities. Stomachs were examined macroscopically and histologically. Grossly, the data demonstrated a significant decrease in the ulcer area of rats pretreated with plant extract in a dose-dependent manner with respect to the ulcerated group. Homogenates of the gastric tissue exhibited significantly increased endogenous enzymes activities in rats pretreated with extract associated with the ulcerated control group. Histology of rats pretreated with extract group using hematoxylin and eosin staining exhibited a moderate-to-mild disruption of the surface epithelium with reduction in submucosal edema and leucocyte infiltration in a dose-dependent manner. In addition, it showed heat shock protein70 protein up-expression and BCL2-associated X protein downexpression. These outcomes might be attributed to the gastroprotective and antioxidative effects of the plant.
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http://dx.doi.org/10.2147/DDDT.S107018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384742PMC
May 2017

Synthesis and Characterization of a New Benzoindole Derivative with Apoptotic Activity Against Colon Cancer Cells.

Curr Pharm Des 2017 ;23(41):6358-6365

Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.

Background: Colorectal cancer is the third most common form of cancer in both men and women around the world. The chemistry and biological study of heterocyclic compounds have been an interesting area for a long time in pharmaceutical and medicinal chemistry.

Methods: A new synthetic compound, 2-(1,1-dimethyl-1H-benzo[e]indol-2-yl)-3-((2-hydroxyphenyl)amino) acrylaldehyde, abbreviated as DBID, was prepared through the reaction of 2-(diformylmethylidene)-1,1- dimethylbenzo[e]indole with 2-aminophenol. The chemical structure of the synthesized compound was characterized by 1H NMR, 13C NMR and APT-NMR spectroscopy and confirmed by elemental analysis (CHN). The compound was screened for the antiproliferation effect against colorectal cancer cell line, HCT 116 and its possible mechanism of action was elucidated. To determine the IC50 value, the MTT assay was used and its apoptosisinducing effect was investigated.

Results: DBID inhibited the proliferation of HCT 116 cells with an IC50 of 9.32 µg/ml and significantly increased the levels of caspase -8, -9 and -3/7 in the treated cells compared to untreated cells. Apoptosis features in HCT 116 cell was detected in treated cells by using the AO/PI staining that confirmed that the cells had undergone remarkable morphological changes in apoptotic bodies. Furthermore, this changes in expression of caspase -8, -9 and -3 were confirmed by gene and protein quantification using RT-PCR and western blot analysis, respectively.

Conclusion: The current study showed that the DBID compound has demonstrated chemotherapeutic activity which was evidenced by significant increases in the expression and activation of caspase and exploit the apoptotic signaling pathways to trigger cancer cell death.
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http://dx.doi.org/10.2174/1381612823666170321093345DOI Listing
July 2019

Mozaff. activates intrinsic pathway of apoptosis in breast cancer cells associated with S phase cell cycle arrest via involvement of p21/p27 in vitro and in vivo.

Drug Des Devel Ther 2017 1;11:337-350. Epub 2017 Feb 1.

Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur; Malaysian Institute of Pharmaceuticals and Nutraceuticals (IPharm), Pulau Pinang, Malaysia.

Background: The aim of this study was to evaluate the anticancer potential of . Several in vitro and in vivo biological assays were applied to explore the direct effect of an extract and bioactive compound of this plant against breast cancer cells and its possible mechanism of action.

Materials And Methods: methanol extract (KME) was prepared, and MTT assay was used to evaluate the cytotoxicity. To identify the cytotoxic compound, a bioassay-guided investigation was performed on methanol extract. 8-Hydroxy-ar-turmerone was isolated as a bioactive compound. In vivo study was performed in the breast cancer rat model. LA7 cell line was used to induce the breast tumor. Histopathological and expression changes of PCNA, Bcl-2, Bax, p27 and p21 and caspase-3 were examined. The induction of apoptosis was tested using Annexin V-fluorescein isothiocyanate (FITC) assay. To confirm the intrinsic pathway of apoptosis, caspase-7 and caspase-9 assays were utilized. In addition, cell cycle arrest was evaluated.

Results: Our results demonstrated that has an obvious effect on the arrest of proliferation of cancer cells. It induced apoptosis, transduced the cell death signals, decreased the threshold of mitochondrial membrane potential (MMP), upregulated Bax and downregulated Bcl-2.

Conclusion: This study demonstrated that exhibits antitumor activity against breast cancer cells via cell death and cell cycle arrest.
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http://dx.doi.org/10.2147/DDDT.S121518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293364PMC
May 2017

The gastro protective effects of Cibotium barometz hair on ethanol-induced gastric ulcer in Sprague-Dawley rats.

BMC Vet Res 2017 Jan 19;13(1):27. Epub 2017 Jan 19.

Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.

Background: Cibotium barometz is a medical herb used traditionally in the Malaysian peninsula for several ailments, including gastric ulcer. The aim of this study was assessment the anti-ulcer effects of C. barometz hair on ethanol-induced stomach hemorrhagic abrasions in animals. Seven groups of Sprague Dawley (SD) rats were administered 10% Tween 20 in the normal control and ulcer control groups, and omeprazole 20 mg/kg and 62.5, 125, 250, and 500 mg/kg of C. barometz hair extract in the experimental groups. After 60 min, the normal control group of rats was orally administered 10% Tween 20, while absolute ethanol was orally administered to the groups of ulcer control, omeprazole and experimental groups. Stomachs of the rats were examined macroscopically and histologically. Homogenates of stomachs were used to evaluate endogenous antioxidant enzyme activities.

Results: Rats pre-fed with plant extract presented a significant decrease in the sore area, increased pH of gastric contents and preserved stomach wall mucus compared to the ulcer group. Histologically, rats pre-fed with C. barometz hair extract showed mild to moderate disruptions of the surface epithelium while animals pre-fed with absolute ethanol showed severe disruptions of the stomach epithelium with edema and leucocyte penetration of the submucosal layer. A Periodic acid Schiff (PAS) staining revealed that each rat pre-treated with the plant extract displayed an intense uptake of stomach epithelial glycoprotein magenta color compared to the ulcer control group. Immunohistochemical analysis revealed that rats pre-fed with the plant extract showed an up-regulation of the heat shock protein 70 (HSP70) and down-regulation of Bax proteins compared to ulcer control rats. Homogenates of the stomach tissue demonstrated significant increases in the endogenous antioxidant enzymatic activity and decreased lipid peroxidation (MDA) in rats pre-treated with C. barometz hair extract compared with the ulcer control rats. In acute toxicity, the liver and kidney revealed no hepatotoxic or nephrotoxic effects histologically.

Conclusions: The gastric cytoprotective action of C. barometz hair extract might be attributed to antioxidants, an increase in gastric pH, stomach mucus preservation, increased endogenous antioxidant enzymes, decreased lipid peroxidation, up-regulation of HSP70 and down-regulation of Bax proteins.
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http://dx.doi.org/10.1186/s12917-017-0949-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5244617PMC
January 2017

Anticancer activity of a monobenzyltin complex C1 against MDA-MB-231 cells through induction of Apoptosis and inhibition of breast cancer stem cells.

Sci Rep 2016 12 15;6:38992. Epub 2016 Dec 15.

Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

In the present study, we examined the cytotoxic effects of Schiff base complex, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, and C1 on MDA-MB-231 cells and derived breast cancer stem cells from MDA-MB-231 cells. The acute toxicity experiment with compound C1 revealed no cytotoxic effects on rats. Fluorescent microscopic studies using Acridine Orange/Propidium Iodide (AO/PI) staining and flow cytometric analysis using an Annexin V probe confirmed the occurrence of apoptosis in C1-treated MDA-MB-231 cells. Compound C1 triggered intracellular reactive oxygen species (ROS) production and lactate dehydrogenase (LDH) releases in treated MDA-MB-231 cells. The Cellomics High Content Screening (HCS) analysis showed the induction of intrinsic pathways in treated MDA-MB-231 cells, and a luminescence assay revealed significant increases in caspase 9 and 3/7 activity. Furthermore, flow cytometric analysis showed that compound C1 induced G0/G1 arrest in treated MDA-MB-231 cells. Real time PCR and western blot analysis revealed the upregulation of the Bax protein and the downregulation of the Bcl-2 and HSP70 proteins. Additionally, this study revealed the suppressive effect of compound C1 against breast CSCs and its ability to inhibit the Wnt/β-catenin signaling pathways. Our results demonstrate the chemotherapeutic properties of compound C1 against breast cancer cells and derived breast cancer stem cells, suggesting that the anticancer capabilities of this compound should be clinically assessed.
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http://dx.doi.org/10.1038/srep38992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5157033PMC
December 2016

The Gastroprotective Effect of Vitex pubescens Leaf Extract against Ethanol-Provoked Gastric Mucosal Damage in Sprague-Dawley Rats.

PLoS One 2016;11(9):e0157431. Epub 2016 Sep 30.

Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.

Vitex pubescens is a Malaysian therapeutic plant employed in traditional drug to remedy a variety of disorders. The purpose of this research is to assess the gastroprotective efficiency of V. pubescens leaves against ethanol-induced gastric hemorrhagic laceration in rats. Animals were randomly allocated into seven groups and pre-treated, separately, with 10% Tween 20 (normal and ulcer control groups), 20 mg/kg omeprazole (reference group), and 62.5, 125, 250, and 500 mg/kg of V. pubescens extract (experimental groups). All animals were sacrificed after another hour. Histological evaluation of the ulcer control group revealed significant injury to the gastric mucosa with edema and leucocyte infiltration of the submucosal layer. PAS staining, showed remarkably intense magenta color, remarkable increase of HSP70 and decrease of Bax proteins in rats pre-treated with plant extracts compared to the ulcer control group. Gastric homogenates revealed a remarkable increase in endogenous antioxidant enzyme activities (CAT, SOD, GSH) and a decrease in the lipid peroxidation level (MDA) in animals pre-treated with V. pubescens extract compared with the ulcer control group. The gastroprotective activity of this plant might be related to increased antioxidant enzymes and decrease lipid peroxidation upsurge of HSP70 and reduced expression of Bax proteins.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157431PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045201PMC
September 2016

The gastroprotective effects of hydroalcoholic extract of Monolluma quadrangula against ethanol-induced gastric mucosal injuries in Sprague Dawley rats.

Drug Des Devel Ther 2016 30;10:93-105. Epub 2015 Dec 30.

Cell Biology and Drug Discovery Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Monolluma quadrangula (Forssk.) Plowes is used in Saudi traditional medicines to treat gastric ulcers. The hydroalcoholic extract of M. quadrangula (MHAE) was used in an in vivo model to investigate its gastroprotective effects against ethanol-induced acute gastric lesions in rats. Five groups of Sprague Dawley rats were used. The first group was treated with 10% Tween 20 as a control. The other four groups included rats treated with absolute ethanol (5 mL/kg) to induce an ulcer, rats treated with 20 mg/kg omeprazole as a reference drug, and rats treated with 150 or 300 mg/kg MHAE. One hour later, the rats were administered absolute ethanol (5 mL/kg) orally. Animals fed with MHAE exhibited a significantly increased pH, gastric wall mucus, and flattening of the gastric mucosa, as well as a decreased area of gastric mucosal damage. Histology confirmed the results; extensive destruction of the gastric mucosa was observed in the ulcer control group, and the lesions penetrated deep into the gastric mucosa with leukocyte infiltration of the submucosal layer and edema. However, gastric protection was observed in the rats pre-fed with plant extracts. Periodic acid-Schiff staining of the gastric wall revealed a remarkably intensive uptake of magenta color in the experimental rats pretreated with MHAE compared to the ulcer control group. Immunohistochemistry staining revealed an upregulation of the Hsp70 protein and a downregulation of the Bax protein in rats pretreated with MHAE compared with the control rats. Gastric homogenate showed significantly increased catalase and superoxide dismutase, and the level of malondialdehyde (MDA) was reduced in the rats pretreated with MHAE compared to the control group. In conclusion, MHAE exhibited a gastroprotective effect against ethanol-induced gastric mucosal injury in rats. The mechanism of this gastroprotection included an increase in pH and gastric wall mucus, an increase in endogenous enzymes, and a decrease in the level of MDA. Furthermore, protection was given through the upregulation of Hsp70 and the downregulation of Bax proteins.
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http://dx.doi.org/10.2147/DDDT.S91247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699547PMC
October 2016

Evaluation of chemopreventive potential of Strobilanthes crispus against colon cancer formation in vitro and in vivo.

BMC Complement Altern Med 2015 Nov 25;15(1):419. Epub 2015 Nov 25.

Department of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.

Background: With cancer being one of the major causes of death around the world, studies are ongoing to find new chemotherapeutic leads. There are common mechanisms for colorectal cancer (CRC) formation. Several are connected with oxidative stress-induced cell apoptosis and others are related to imbalanced homeostasis or intake of drugs/toxins. Plants that have been used for decades in folk and traditional medicine have been accepted as one of the commonest sources of discovered natural agents of cancer chemotherapy and chemoprevention. The aim was to study the antioxidant and chemopreventive effects of Strobilanthes crispus on colorectal cancer formation.

Methods: Five groups of rats were injected subcutaneously with AOM, 15 mg/kg body weight, each once weekly for 2 weeks. The cancer group was continued on 10 % Tween-20 feeding for 8 weeks. The standard drug group was continued on 35 mg/kg 5-fluorouracil intraperitoneal injection twice a week for 8 weeks, and the experimental groups were continued on 250 and 500 mg/kg S. crispus extract oral feeding for 8 weeks, respectively. The normal group was injected subcutaneously with normal saline once a week for 2 weeks, followed by oral administration of 10 % Tween-20 for 8 weeks. All the rats were sacrificed after 10 weeks. The colons were evaluated grossly and histopathologically for aberrant crypt foci (ACF). Gene expression was performed for Bax, Bcl2, Defa24, Slc24a3, and APC genes by real-time PCR. S. crispus and its fractions were evaluated for their chemopreventive effects against human colorectal adenocarcinoma cell line HT29 and cytotoxicity for normal human colon epithelial cell line CCD 841, and the active fraction was assessed for its components.

Results: We observed significant decrease in total colonic ACF formation, malonaldehyde (MDA) and lactate dehydrogenase (LDH), increase in superoxide dismutase (SOD), up-regulation of APC, Bax and Slc24a3, and down-regulation of Defa24 and Bcl-2 in rats treated with Strobilanthes crispus.

Conclusion: Our results support the in vivo protection of S. crispus against CRC formation (azoxymethane-induced aberrant crypt foci) and suggest that the mechanism is highly specific to protect from oxidative insults and the following apoptotic cascade.
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http://dx.doi.org/10.1186/s12906-015-0926-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658747PMC
November 2015

Lentinus squarrosulus (Mont.) mycelium enhanced antioxidant status in rat model.

Drug Des Devel Ther 2015 6;9:5957-64. Epub 2015 Nov 6.

Mushroom Research Centre, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.

Aim: Lentinus squarrosulus is an edible wild mushroom commonly found in Asia. This species has several interesting features such as rapid mycelial growth, and hence has the potential to be used as food, functional food, and nutraceuticals. Our previous study shows that L. squarrosulus contains potent antioxidant compounds in vitro. This study aims to investigate the in vivo bioavailability of L. squarrosulus mycelium extract and its antioxidant effect on biomarkers of antioxidant defense and oxidative stress.

Methods: Water extract of mycelial biomass of L. squarrosulus was analyzed for in vivo antioxidant effects, including cupric-reducing antioxidant capacity (CUPRAC), glutathione peroxidase (GPx), xanthine oxidase (XO), advanced oxidation protein products (AOPPs), and lipid hydroperoxides (LHPs) at 0 and 28 days. GPx and XO were also analyzed in liver homogenates. Normal Sprague Dawley rats were treated with 250 and 500 mg/kg of extract for 28 days.

Results: The serum CUPRAC level increased after treatment with both concentrations, indicating that there was sufficient bioavailability of the extract which contributed to the total antioxidant capacity. GPx activity in both serum and liver was increased and this correlated with LHP level after treatment with 250 mg/kg of extract, but XO activity was significantly decreased after treatment with 500 mg/kg of the extract. Lack of difference between AOPP levels implied that there were no significant changes in oxidative damage of protein after treatment.

Conclusion: This study clearly showed that L. squarrosulus mycelium antioxidant extract contains absorbable antioxidants that enter the circulating plasma and cause a significant acute increase in plasma antioxidant capacity. Thus, the water extract of L. squarrosulus mycelium, which can be obtained abundantly by liquid fermentation, may serve as an antioxidant ingredient in functional foods and nutraceuticals.
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http://dx.doi.org/10.2147/DDDT.S90746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4642808PMC
September 2016

Curcuma purpurascens BI. rhizome accelerates rat excisional wound healing: involvement of Hsp70/Bax proteins, antioxidant defense, and angiogenesis activity.

Drug Des Devel Ther 2015 27;9:5805-13. Epub 2015 Oct 27.

Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Purpose: Curcuma purpurascens BI. is a member of Zingiberaceae family. The purpose of this study is to investigate the wound healing properties of hexane extract of C. purpurascens rhizome (HECP) against excisional wound healing in rats.

Materials And Methods: Twenty four rats were randomly divided into 4 groups: A) negative control (blank placebo, acacia gum), B) low dose of HECP, C) high dose of HECP, and D) positive control, with 6 rats in each group. Full-thickness incisions (approximately 2.00 cm) were made on the neck area of each rat. Groups 1-4 were treated two-times a day for 20 days with blank placebo, HECP (100 mg/kg), HECP (200 mg/kg), and intrasite gel as a positive control, respectively. After 20 days, hematoxylin and eosin and Masson's trichrome stainings were employed to investigate the histopathological alterations. Protein expressions of Bax and Hsp70 were examined in the wound tissues using immunohistochemistry analysis. In addition, levels of enzymatic antioxidants and malondialdehyde representing lipid peroxidation were measured in wound tissue homogenates.

Results: Macroscopic evaluation of wounds showed conspicuous elevation in wound contraction after topical administration of HECP at both doses. Moreover, histopathological analysis revealed noteworthy reduction in the scar width correlated with the enhanced collagen content and fibroblast cells, accompanied by a reduction of inflammatory cells in the granulation tissues. At the molecular level, HECP facilitates wound-healing process by downregulating Bax and upregulating Hsp70 protein at the wound site. The formation of new blood vessel was observed in Masson's trichrome staining of wounds treated with HECP (100 and 200 mg/kg). In addition, HECP administration caused a significant surge in enzymatic antioxidant activities and a decline in lipid peroxidation.

Conclusion: These findings suggested that HECP accelerated wound-healing process in rats via antioxidant activity, angiogenesis effect and anti-inflammatory responses involving Hsp70/Bax.
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http://dx.doi.org/10.2147/DDDT.S88196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629958PMC
September 2016

Chemopreventive effects of Strobilanthes crispus leaf extract on azoxymethane-induced aberrant crypt foci in rat colon.

Sci Rep 2015 Aug 26;5:13312. Epub 2015 Aug 26.

Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.

In this work, microscopic and histological studies suggest that Strobilanthes crispus ethanol extract reduce azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. S. crispus is considered a traditional medicine and used as an antioxidant. Its leaf contains a large amount of phenolic compounds to which its radical scavenging role is attributed and enhance its ability to eradicate oxidative stress reactions. The study was designed to determine the chemopreventive effect of S. crispus ethanol extract in vivo and in vitro by elucidating the effect of the extract on intermediate biomarkers which can be used as effective predictors of colon cancer. S. crispus was analyzed for DPPH free radical scavenging, nitric oxide (NO) and ferric acid reduction. The results indicated that S. crispus oral administration significantly inhibited colorectal carcinogenesis induced by AOM as revealed by the reduction in the number of ACF. S. crispus down-regulated the expression of PCNA, Bcl2 and β-catenin. Additionally, it exerted a pronounced inhibitory effect on MDA and NO levels and stimulatory effect on CAT and GPx activities. These results demonstrate that S. crispus is a chemopreventive agent for colorectal cancer through the suppression of early and intermediate carcinogenic phases that may be related to its flavonoid content.
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http://dx.doi.org/10.1038/srep13312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4642519PMC
August 2015

The chemopreventive potential of Curcuma purpurascens rhizome in reducing azoxymethane-induced aberrant crypt foci in rats.

Drug Des Devel Ther 2015 27;9:3911-22. Epub 2015 Jul 27.

Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Curcuma purpurascens BI. rhizome, a member of the Zingiberaceae family, is a popular spice in Indonesia that is traditionally used in assorted remedies. Dichloromethane extract of C. purpurascens BI. rhizome (DECPR) has previously been shown to have an apoptosis-inducing effect on colon cancer cells. In the present study, we examined the potential of DECPR to prevent colon cancer development in rats treated with azoxymethane (AOM) (15 mg/kg) by determining the percentage inhibition in incidence of aberrant crypt foci (ACF). Starting from the day immediately after AOM treatment, three groups of rats were orally administered once a day for 2 months either 10% Tween 20 (5 mL/kg, cancer control), DECPR (250 mg/kg, low dose), or DECPR (500 mg/kg, high dose). Meanwhile, the control group was intraperitoneally injected with 5-fluorouracil (35 mg/kg) for 5 consecutive days. After euthanizing the rats, the number of ACF was enumerated in colon tissues. Bax, Bcl-2, and proliferating cell nuclear antigen (PCNA) protein expressions were examined using immunohistochemical and Western blot analyses. Antioxidant enzymatic activity was measured in colon tissue homogenates and associated with malondialdehyde level. The percentage inhibition of ACF was 56.04% and 68.68% in the low- and high-dose DECPR-treated groups, respectively. The ACF inhibition in the treatment control group was 74.17%. Results revealed that DECPR exposure at both doses significantly decreased AOM-induced ACF formation, which was accompanied by reduced expression of PCNA. Upregulation of Bax and downregulation of Bcl-2 suggested the involvement of apoptosis in the chemopreventive effect of DECPR. In addition, the oxidative stress resulting from AOM treatment was significantly attenuated after administration of DECPR, which was shown by the elevated antioxidant enzymatic activity and reduced malondialdehyde level. Taken together, the present data clearly indicate that DECPR significantly inhibits ACF formation in AOM-treated rats and may offer protection against colon cancer development.
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http://dx.doi.org/10.2147/DDDT.S84560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524378PMC
April 2016

Chemoprevention of Colonic Aberrant Crypt Foci by Novel Schiff Based Dichlorido(4-Methoxy-2-{[2-(Piperazin-4-Ium-1-Yl)Ethyl]Iminomethyl}Phenolate)Cd Complex in Azoxymethane-Induced Colorectal Cancer in Rats.

Sci Rep 2015 Jul 23;5:12379. Epub 2015 Jul 23.

Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

Schiff-based complexes as a source of cancer chemotherapeutic compounds have been subjected to the variety of anticancer studies. The in-vitro analysis confirmed the CdCl2(C14H21N3O2) complex possess cytotoxicity and apoptosis induction properties in colon cancer cells, so lead to investigate the inhibitory efficiency of the compound on colonic aberrant crypt foci (ACF). Five groups of adult male rats were used in this study: Vehicle, cancer control, positive control groups and the groups treated with 25 and 50 mg/kg of complex for 10 weeks. The rats in vehicle group were injected subcutaneously with 15 mg/kg of sterile normal saline once a week for 2 weeks and orally administered with 5% Tween-20 (5 ml/kg) for 10 weeks, other groups were injected subcutaneously with 15 mg/kg azoxymethane once a week for 2 weeks. The rats in positive groups were injected intra-peritoneally with 35 mg/kg 5-Flourouracil four times in a month. Administration of the complex suppressed total colonic ACF formation up to 73.4% (P < 0.05). The results also showed that treatment with the complex significantly reduced the level of malondialdehyde while increasing superoxide dismutase and catalase activities. Furthermore, the down-regulation of PCNA and Bcl2 and the up-regulation of Bax was confirmed by immunohistochemical staining.
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http://dx.doi.org/10.1038/srep12379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511874PMC
July 2015

Synthesis, characterization and apoptotic activity of quinazolinone Schiff base derivatives toward MCF-7 cells via intrinsic and extrinsic apoptosis pathways.

Sci Rep 2015 Jun 25;5:11544. Epub 2015 Jun 25.

Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

The current study investigated the cytotoxic effect of 3-(5-chloro-2-hydroxybenzylideneamino)-2-(5-chloro-2-hydroxyphenyl)-2,3-dihydroquinazolin-41(H)-one (A) and 3-(5-nitro-2-hydroxybenzylideneamino)-2-(5-nitro-2-hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (B) on MCF-7, MDA-MB-231, MCF-10A and WRL-68 cells. The mechanism involved in apoptosis was assessed to evaluate the possible pathways induced by compound A and B. MTT assay results using A and B showed significant inhibition of MCF-7 cell viability, with IC50 values of 3. 27 ± 0.171 and 4.36 ± 0.219 μg/mL, respectively, after a 72 hour treatment period. Compound A and B did not demonstrate significant cytotoxic effects towards MDA-MB-231, WRL-68 and MCF-10A cells. Acute toxicity tests also revealed an absence of toxic effects on mice. Fluorescent microscopic studies confirmed distinct morphological changes (membrane blebbing and chromosome condensation) corresponding to typical apoptotic features in treated MCF-7 cells. Using Cellomics High Content Screening (HCS), we found that compound A and B could trigger the release of cytochrome c from mitochondria to the cytosol. The release of cytochrome c activated the expression of caspases-9 and then stimulated downstream executioner caspase-3/7. In addition, caspase-8 showed remarkable activity, followed by inhibition of NF-κB activation in A-and B-treated MCF-7 cells. The results indicated that A and B could induce apoptosis via a mechanism that involves either extrinsic or intrinsic pathways.
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http://dx.doi.org/10.1038/srep11544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479988PMC
June 2015

Wound-healing potential of the fruit extract of Phaleria macrocarpa.

Bosn J Basic Med Sci 2015 05 12;15(2):25-30. Epub 2015 May 12.

‎1-Department of Biomedical Science, Faculty of Medicine, University of Malaya,Kuala ‎Lumpur, Malaysia.‎ ‎2-Department of Microbiology and Immunology, Faculty of Medicine, University of Diyala, Iraq. ‎.

The wound-healing potential of Phaleria macrocarpa was evaluated by monitoring the levels of inflammatory mediators, collagen, and antioxidant enzymes. Experimentally, two-centimeter-wide full-thickness-deep skin excision wounds were created on the posterior neck area of the rats. The wounds were topically treated with gum acacia as a vehicle in the control group, intrasite gel in the reference group, and 100 and 200 mg/mL P. macrocarpa ‎fruit extract in the treatment group. Granulation tissues were excised on the 15th day and were further processed for histological and biochemical analyzes. Wound healing was evaluated by measuring the contractions and protein contents of the wounds. Cellular redistribution and collagen deposition were assessed morphologically using Masson's trichrome stain. Superoxide dismutase (SOD) and catalase (CAT) activities, along with malondialdehyde (MDA) level were determined in skin tissue homogenates of the dermal wounds. Serum levels of transforming growth factor beta 1 (TGF-β1) and tumor necrosis factor alpha (TNF-α) were evaluated in all the animals. A significant decrease in wound area was caused by a significant increase in TGF-β1 level in the treated groups. Decrease in TNF-α level and increase in the collagen formation were also observed in the treated groups. Topical treatment with P. macrocarpa fruit extract increased the SOD and CAT activities in the healing wounds, thereby significantly increasing MDA level. The topical treatment with P. macrocarpa fruit extract showed significant healing effect on excision wounds and demonstrated an important role in the inflammation process by increasing antioxidant enzyme activities, thereby accelerating the wound healing process and reducing tissue injury.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469932PMC
http://dx.doi.org/10.17305/bjbms.2015.39DOI Listing
May 2015

Chemopreventive Activity of Ferulago angulate against Breast Tumor in Rats and the Apoptotic Effect of Polycerasoidin in MCF7 Cells: A Bioassay-Guided Approach.

PLoS One 2015 21;10(5):e0127434. Epub 2015 May 21.

Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Ferulago angulata leaf hexane extract (FALHE) was found to be a potent inducer of MCF7 cell apoptosis. The aims of the present study were to investigate the in vivo chemopreventive effect of FALHE in rats, to identify the contributing anticancer compound in FALHE and to determine its potential mechanism of action against MCF7 cells. Thirty rats harboring LA7-induced breast tumors were divided into five groups: tumor control, low-dose FALHE, high-dose FALHE, treatment control (tamoxifen) and normal control. Breast tissues were then subjected to histopathological and immunohistochemical analyses. A bioassay-guided investigation on FALHE was performed to identify the cytotoxic compound and its mechanism of action through flow cytometry, real-time qPCR and western blotting analyses. An in vivo study showed that FALHE suppressed the expression of the tumor markers PCNA and Ki67. The tumor size was reduced from 2031 ± 281 mm3 to 432 ± 201 mm3 after FALHE treatment. FALHE administration induced apoptosis in breast tumor cells, and this was confirmed by high expression levels of Bax, p53 and caspase 3. Cell cycle arrest was suggested by the expression of p21 and p27. The in vitro experimental results resulted in the isolation of polycerasoidin as a bioactive ingredient of FALHE with an IC50 value of 3.16 ± 0.31 μg/ml against MCF7 cells. Polycerasoidin induced mitochondrial-dependent apoptosis in breast cancer cells via caspase activation and changes in the mRNA and protein expression of Bax and Bcl-2. In addition, flow cytometric analysis demonstrated that the treated MCF7 cells were arrested at the G1 phase, and this was associated with the up-regulation of p21 and p27 at both the mRNA and protein levels. The results of the present study reinforce further investigations scrutinizing the promising potential of the F. angulata chemical constituents as breast cancer chemopreventive agents.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0127434PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440818PMC
March 2016

Annona muricata leaves accelerate wound healing in rats via involvement of Hsp70 and antioxidant defence.

Int J Surg 2015 Jun 18;18:110-7. Epub 2015 Apr 18.

Biomolecular Research Group, Biochemistry Program, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address:

Introduction: Annona muricata, a member of the Annonaceae family, is commonly known as soursop and graviola. The leaves of this tropical fruit tree are widely used in folk medicine against skin diseases and abscesses, however there is no scientific evidence justifying the use of A. muricata leaves. The aim of the present study is to evaluate the wound healing potential of ethyl acetate extract of A. muricata leaves (EEAM) towards excisional wound models in rats.

Methods: Sprague Dawley rats (24) were randomly divided into four groups, viz. (A) vehicle control, (B) low dose of EEAM (5% w/w), (C) high dose of EEAM (10% w/w) and (D) positive control with excisional wound created on the neck area. Wounds were topically dressed twice a day for 15 days. On the 15th day, animals were sacrificed and then processed for immunohistochemical and histological evaluations, including Hematoxylin & Eosin and Masson Trichrome stainings. The activity of antioxidants, namely catalase, glutathione peroxidase and superoxide dismutase, and malondialdehyde (MDA) was measured in wound tissue homogenate.

Results: Macroscopic and microscopic analysis of wounds demonstrated a significant wound healing activity shown by EEAM at two doses. Treatment of wounds with ointment containing EEAM caused significant surge in antioxidants activities and decrease in the MDA level of wound tissues compared with vehicle control. The immunohistochemical evaluation revealed conspicuous up-regulation of Hsp70 in treated wounds with EEAM, suggesting the anti-inflammatory effect of EEAM.

Conclusion: EEAM exhibited a promising wound healing potential towards excisional wound models in rats.
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http://dx.doi.org/10.1016/j.ijsu.2015.03.026DOI Listing
June 2015

The chemopotential effect of Annona muricata leaves against azoxymethane-induced colonic aberrant crypt foci in rats and the apoptotic effect of Acetogenin Annomuricin E in HT-29 cells: a bioassay-guided approach.

PLoS One 2015 10;10(4):e0122288. Epub 2015 Apr 10.

Biomolecular Research Group, Biochemistry Program, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.

Annona muricata has been used in folk medicine for the treatment of cancer and tumors. This study evaluated the chemopreventive properties of an ethyl acetate extract of A. muricata leaves (EEAML) on azoxymethane-induced colonic aberrant crypt foci (ACF) in rats. Moreover, the cytotoxic compound of EEAML (Annomuricin E) was isolated, and its apoptosis-inducing effect was investigated against HT-29 colon cancer cell line using a bioassay-guided approach. This experiment was performed on five groups of rats: negative control, cancer control, EEAML (250 mg/kg), EEAML (500 mg/kg) and positive control (5-fluorouracil). Methylene blue staining of colorectal specimens showed that application of EEAML at both doses significantly reduced the colonic ACF formation compared with the cancer control group. Immunohistochemistry analysis showed the down-regulation of PCNA and Bcl-2 proteins and the up-regulation of Bax protein after administration of EEAML compared with the cancer control group. In addition, an increase in the levels of enzymatic antioxidants and a decrease in the malondialdehyde level of the colon tissue homogenates were observed, suggesting the suppression of lipid peroxidation. Annomuricin E inhibited the growth of HT-29 cells with an IC50 value of 1.62 ± 0.24 μg/ml after 48 h. The cytotoxic effect of annomuricin E was further substantiated by G1 cell cycle arrest and early apoptosis induction in HT-29 cells. Annomuricin E triggered mitochondria-initiated events, including the dissipation of the mitochondrial membrane potential and the leakage of cytochrome c from the mitochondria. Prior to these events, annomuricin E activated caspase 3/7 and caspase 9. Upstream, annomuricin E induced a time-dependent upregulation of Bax and downregulation of Bcl-2 at the mRNA and protein levels. In conclusion, these findings substantiate the usage of A. muricata leaves in ethnomedicine against cancer and highlight annomuricin E as one of the contributing compounds in the anticancer activity of A. muricata leaves.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122288PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393181PMC
March 2016

Biochanin a gastroprotective effects in ethanol-induced gastric mucosal ulceration in rats.

PLoS One 2015 26;10(3):e0121529. Epub 2015 Mar 26.

Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Background: Biochanin A notable bioactive compound which is found in so many traditional medicinal plant. In vivo study was conducted to assess the protective effect of biochanin A on the gastric wall of Spraguedawley rats` stomachs.

Methodology: The experimental set included different animal groups. Specifically, four groups with gastric mucosal lesions were receiving either a) Ulcer control group treated with absolute ethanol (5 ml/kg), b) 20 mg/kg of omeprazole as reference group, c) 25 of biochanin A, d) 50 mg/kg of biochanin A. Histopathological sectioning followed by immunohistochemistry staining were undertaken to evaluate the influence of the different treatments on gastric wall mucosal layer. The gastric secretions were collected in the form of homogenate and exposed to superoxide dismutase (SOD) and nitric oxide enzyme (NO) and the level of malondialdehyde (MDA) and protein content were measured. Ulceration and patchy haemorrhage were clearly observed by light microscopy. The morphology of the gastric wall as confirmed by immunohistochemistry and fluorescent microscopic observations, exhibited sever deformity with notable thickness, oedematous and complete loss of the mucosal coverage however the biochanin-pretreated animals, similar to the omeprazole-pretreated animals, showed less damage compared to the ulcer control group. Moreover, up-regulation of Hsp70 protein and down-regulation of Bax protein were detected in the biochanin A pre-treated groups and the gastric glandular mucosa was positively stained with Periodic Acid Schiff (PAS) staining and the Leucocytes infiltration was commonly seen. Biochanin A displayed a great increase in SOD and NO levels and decreased the release of MDA.

Conclusions: This gastroprotective effect of biochanin A could be attributed to the enhancement of cellular metabolic cycles perceived as an increase in the SOD, NO activity, and decrease in the level of MDA, and also decrease in level of Bax expression and increase the Hsp70 expression level.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0121529PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374864PMC
February 2016