Mahmood Ameen Abdulla

Publications

1 Gastroprotective Activity of Swietenia Mahagoni Seed Extract on Ethanol-Induced Gastric Mucosal Injury in Rats

Authors: Salma Saleh Alrdahe, Mahmood Ameen Abdulla, Shaharudin Abul Razak, Farkaad Abdul Kadir, Pouya Hassandarvish

Abstract:

Swietenia mahagoni have been used in traditional medicine for treatment of different diseases. Present study was performed to evaluate anti-ulcerogenic activity of ethanol seed extract against ethanol induced gastric mucosal injury in rats. Six groups of rats were orally pre-treated respectively with carboxymethyl cellulose, omeprazole 20 mg/kg, 50, 100, 200 and 400 mg/kg plant extract one hour before oral administration of absolute ethanol to generate gastric mucosal injury. After additional hour, rats were sacrificed and ulcer areas of gastric walls were determined. Grossly, carboxymethyl cellulose group exhibited severe mucosal injury, whereas pre-treatment with plant extract exhibited significant protection of gastric mucosa. Histology, carboxymethyl cellulose group exhibited severe damage of gastric mucosa; edema and leucocytes infiltration of sub mucosa compared to plant extract which showed gastric protection. Acute toxicity study did not manifest any toxicological signs in rats. Conclusions, results suggest that S. mahagoni promotes ulcer protection as ascertained grossly and histologically.

Keywords: Histology, cytoprotection, gastric ulcer, Swieteniamahagoni seed

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Abstracts

8 Mechanisms of Atiulcerogenic Activity of Costus speciosus Rhizome Extract in Ethanol-Induced Gastric Mucosal Injury in Rats

Authors: Mahmood Ameen Abdulla, Somayeh Fani

Abstract:

Costus speciosus is an important Malaysian medicinal plant commonly used traditionally in the treatment of many aliments. The present investigation is designed to elucidate preventive effects of ethanolic extracts of C. speciosus rhizome against absolute ethanol-induced gastric mucosal injury in Sprague-Dawley rats. Five groups of rats were orally pre-treated with vehicle, carboxymethylcellulose (CMC) as normal control group (Group 1), ethanol as ulcer control group (Group 2), omeprazole 20 mg/kg (reference group) (Group 3), and 250 and 500 mg/kg of C. speciosus extract (experimental groups) (Group 4 and 5), respectively. An hour later, CMC was given orally to Group 1 rats and absolute ethanol was given orally to Group 2-5 rats to generate gastric mucosal injury. After an additional hour, the rats were sacrificed. Grossly, ulcer control group exhibited severe of gastric mucosal hemorrhagic injury and increased in ulcer area, whereas groups pre-treated with omeprazole or plant’s rhizomes exhibited the significant reduction of gastric mucosal injury. Significant increase in the pH and mucous of gastric content was observed in rats re-treated with C. speciosus rhizome. Histology, ulcer control rats, demonstrated remarkable disruption of gastric mucosa, increased in edema and inflammatory cells infiltration of submucosal layer compared to rats pre-treated with rhizomes extract. Periodic acid Schiff staining for glycoprotein, rats pre-fed with C. speciosus C. displayed remarkably intense uptake of magenta color by glandular gastric mucosa compared with ulcer control rats. Immunostaining of gastric epithelium, rats pre-treatment with rhizome extract provide evidence of up-regulation of HSP70 and down-regulation of Bax proteins compared to ulcer control animals. Gastric tissue homogenate, C. speciosus significantly increased the activity of superoxide dismutase (SOD), and catalase (CAT), increased the level of non-protein sulfhydryl (NP-SH) and decreased the level of lipid peroxidation after ethanol administration. Acute toxicity test did not show any signs of toxicity. The mechanisms implicated the gasrtoprotective property of C. speciosus depend upon the antisecretory activity, increased in gastric mucus glycoprotein, up-regulation of HSP70 protein and down-regulation of Bax proteins, reduction in the lipid peroxidation and increase in the level of NP-SH and antioxidant enzymes activity in gastic homogenate.

Keywords: Histology, antioxidant, omeprazole, gastric ulcer, Costus speciosus

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7 New Quinazoline Derivative Induce Cytotoxic Effect against Mcf-7 Human Breast Cancer Cell

Authors: Hapipah Mohd Ali, Mahmood Ameen Abdulla, Nazia Abdul Majid, Maryam Zahedi Fard

Abstract:

New quinazoline schiff base 3-(5-bromo-2-hydroxy-3-methoxybenzylideneamino)-2-(5-bromo-2-hydroxy-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one was investigated for anticancer activity against MCF-7 human breast cancer cell line with involved mechanism of apoptosis. The compound demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41 ± 0.34, after 72 hours of treatment. Morphological apoptotic features in treated MCF-7 cells were observed by AO/PI staining. Furthermore, treated MCF-7 cells subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome c release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity test demonstrated the nontoxic nature of the compound in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potent candidate for further in vivo and clinical breast cancer studies.

Keywords: apoptosis, MCF-7 human breast cancer cell line, antiproliferative effect, caspases

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6 New Quinazoline Derivative Exhibit Cytotoxic Effect agaisnt MCF-7 Human Breast Cancer Cell

Authors: Hapipah Mohd Ali, Mahmood Ameen Abdulla, Nazia Abdul Majid, Maryam Zahedifard, Fadhil Lafta Faraj

Abstract:

The new quinazoline Schiff bases have been synthesized through condensation reaction of 2-aminobenzhydrazide with 5-bromosalicylaldehyde and 3-methoxy-5-bromosalicylaldehyde. The compound was investigated for anticancer activity against MCF-7 human breast cancer cell line. It demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41±0.34, after 72 hours of treatment. Most apoptosis morphological features in treated MCF-7 cells were observed by AO/PI staining. The results of cell cycle analysis indicate that compounds did not induce S and M phase arrest in cell after 24 hours of treatment. Furthermore, MCF-7 cells treated with compound subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome C release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity results demonstrated the nontoxic nature of the compounds in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potential candidate for further in vivo and clinical breast cancer studies.

Keywords: apoptosis, Cell Cycle, acute toxicity, MCF-7, Quinazoline Schiff base, caspase

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5 Chemopreventive Efficacy Of Cdcl2(C14H21N3O2) in Rat Colon Carcinogenesis Model Using Aberrant Crypt Foci (ACF) as Endpoint Marker

Authors: Mahmood Ameen Abdulla, Maryam Hajrezaie, Maryam Zahedifard, Nazia AbdulMajid

Abstract:

Colon cancer is one of the most prevalent cancers in the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. New schiff based compounds are reported to exhibit a wide spectrum of biological activities of therapeutic importance. To evaluate inhibitory properties of CdCl2(C14H21N3O2) complex on colonic aberrant crypt foci, five groups of 7-week-old male rats were used. Control group was fed with 10% Tween 20 once a day, cancer control group was intra-peritoneally injected with 15 mg/kg Azoxymethan, drug control group was injected with 15 mg/kg azoxymethan and 5-Flourouracil, experimental groups were fed with 2.5 and 5 mg/kg CdCl2(C14H21N3O2) compound each once a day. Administration of compound were found to be effectively chemoprotective. Andrographolide suppressed total colonic ACF formation up to 72% to 74%, respectively, when compared with control group. The results also showed a significant increase in glutathione peroxidase, superoxide dismutase, catalase activities and a decrease in malondialdehyde level. Immunohistochemical staining demonstrated down-regulation of PCNA protein. According to the Western blot comparison analysis, COX-2 and Bcl2 is up-regulated whilst the Bax is down-regulated. according to these data, this compound plays promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, aberrant crypt foci (ACF), Schiff based compound, immunohistochemical staining

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4 Synthesis and Cytotoxic Activity of New Quinazolinone-Based Compounds against Human Breast Cancer Cell Line MCF-7

Authors: Hapipah Mohd Ali, Mahmood Ameen Abdulla, Nazia Abdul Majid, Maryam Hajrezaie, Maryam Zahedifard, Fadhil Lafta Faraj

Abstract:

In the current study, we prepared two new quinazoline schiff bases through condensation reaction of 2-aminobenzhydrazide with 5-bromosalicylaldehyde and 3-methoxy-5-bromosalicylaldehyde. The chemical structures of both newly synthesized compounds (1 and 2) were confirmed by FT-IR and X-ray crystallography studies. The cytotoxic effect of compounds was investigated against MCF-7 human breast cancer cells. MTT results showed that (1) and (2) decreased the viability of MCF-7 cells in a time-dependent manner, exhibiting an IC50 value of 3.23 ± 0.28 µg/mL and 3.41 ± 0.34 µg/mL, respectively, after a 72-hours treatment period. In contrast, they did not show significant anti-proliferative effect towards MCF-10A normal breast cells and WRL-68 normal liver cells. We found a perturbation in mitochondrial membrane potential and increased cytochrome c release from the mitochondria to the cytosol, suggesting an activation of apoptosis by compounds, which was confirmed by activation of the initiator caspase-9 and the executioner caspases-3/7. (1) was also able to trigger extrinsic pathway via activation of caspase-8 and inhibition of NF-κB translocation. The acute toxicity test showed no toxicity effect of the compounds in rats. Our results showed that the selected synthesized compounds are highly potent to induce apoptosis in MCF-7 cells via either intrinsic or extrinsic mitochondrial pathway.

Keywords: apoptosis, Quinazoline Schiff base, MCF-7 human breast cancer cell line, caspase, NF-κB translocation

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3 Chemopreventive Efficacy of Andrographolide in Rat Colon Carcinogenesis Model Using Aberrant Crypt Foci (ACF) as Endpoint Marker

Authors: Mahmood Ameen Abdulla, Pouya Hassandarvish, Nazia Abdul Majid, Maryam Hajrezaie, Hapipa Mohd Ali, Maryam Zahedi Fard

Abstract:

Background: Colon cancer is one of the most prevalent cancers in the world and is the third leading cause of death among cancers in both males and females. The incidence of colon cancer is ranked fourth among all cancers but varies in different parts of the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. Andrographolide is the major labdane diterpenoidal constituent of the plant Andrographis paniculata (family Acanthaceae), used extensively in the traditional medicine. Extracts of the plant and their constituents are reported to exhibit a wide spectrum of biological activities of therapeutic importance. Laboratory animal model studies have provided evidence that Andrographolide play a role in inhibiting the risk of certain cancers. Objective: Our aim was to evaluate the chemopreventive efficacy of the Andrographolide in the AOM induced rat model. Methods: To evaluate inhibitory properties of andrographolide on colonic aberrant crypt foci (ACF), five groups of 7-week-old male rats were used. Group 1 (control group) were fed with 10% Tween 20 once a day, Group 2 (cancer control) rats were intra-peritoneally injected with 15 mg/kg Azoxymethan, Gropu 3 (drug control) rats were injected with 15 mg/kg azoxymethan and 5-Flourouracil, Group 4 and 5 (experimental groups) were fed with 10 and 20 mg/kg andrographolide each once a day. After 1 week, the treatment group rats received subcutaneous injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Control rats were continued on Tween 20 feeding once a day and experimental groups 10 and 20 mg/kg andrographolide feeding once a day for 8 weeks. All rats were sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated grossly and histopathologically for ACF. Results: Administration of 10 mg/kg and 20 mg/kg andrographolide were found to be effectively chemoprotective, as evidenced microscopily and biochemically. Andrographolide suppressed total colonic ACF formation up to 40% to 60%, respectively, when compared with control group. Pre-treatment with andrographolide, significantly reduced the impact of AOM toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT) activities. Grossly, colorectal specimens revealed that andrographolide treatments decreased the mean score of number of crypts in AOM-treated rats. Importantly, rats fed andrographolide showed 75% inhibition of foci containing four or more aberrant crypts. The results also showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histologically all treatment groups showed a significant decrease of dysplasia as compared to control group. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. Conclusion: The current study demonstrated that Andrographolide reduce the number of ACF. According to these data, Andrographolide might be a promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: Colon Cancer, andrographolide, chemopreventive, aberrant crypt foci (ACF)

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2 Hexane Extract of Thymus serpyllum L.: GC-MS Profile, Antioxidant Potential and Anticancer Impact on HepG2 (Liver Carcinoma) Cell Line

Authors: Hapipah Mohd Ali, Mahmood Ameen Abdulla, Elham Rouhollahi, Salma Baig, Bakrudeen Ali Ahmad, Ainnul Hamidah Syahadah Azizan

Abstract:

Free radical damage induced by reactive oxygen species (ROS) contributes to etiology of many chronic diseases, cancer being one of them. Recent studies have been successful in ROS targeted therapies via antioxidants using mouse models in cancer therapeutics. The present study was designed to scrutinize anticancer activity, antioxidant activity of 5 different extracts of Thymus serpyllum in MDA-MB-231, MCF-7, HepG2, HCT-116, PC3, and A549. Identification of the phytochemicals present in the most active extract of Thymus serpyllum was conducted using gas chromatography coupled with mass spectrophotometry and antioxidant activity was measured by using DPPH radical scavenging and FRAP assay. Anticancer impact of the extract in terms of IC50 was evaluated using MTT cell viability assay. Results revealed that the hexane extract showed the best anticancer activity in HepG2 (Liver Carcinoma Cell Line) with an IC50 value of 23 ± 0.14 µg/ml followed by 25 µg/ml in HCT-116 (Colon Cancer Cell Line), 30 µm/ml in MCF-7 (Breast Cancer Cell Line), 35 µg/ml in MDA-MB-231 (Breast Cancer Cell Line), 57 µg/ml in PC3 (Prostate Cancer Cell Line) and 60 µg/ml in A549 (Lung Carcinoma Cell Line). GC-MS profile of the hexane extract showed the presence of 31 compounds with carvacrol, thymol and thymoquione being the major compounds. Phenolics such as Vitamin E, terpinen-4-ol, borneol and phytol were also identified. Hence, here we present the first report on cytotoxicity of hexane extract of Thymus serpyllum extract in HepG2 cell line with a robust anticancer activity with an IC50 of 23 ± 0.14 µg/ml.

Keywords: Anticancer Activity, antioxidant activity, Thymus serpyllum L, hexane extract, GC-MS profile, HepG2 cell line

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1 Evaluation of Wound Healing Activity of Curcuma purpurascens BI. Rhizomes in Rats

Authors: Mahmood Ameen Abdulla, Soheil Zorofchian Moghadamtousi, Elham Rouhollahi, Salma Baig, Zahurin Mohamed

Abstract:

This study was designed to assess cutaneous wound healing potential of hexane extract of Curcuma purpurascens rhizomes (HECP). Twenty-four rats were divided into 4 groups: 1. Negative, 2. Low dose, 3. High dose and 4. Treatment, with 6 rats in each group. Full-thickness incisions with a diameter of 2 cm were made on the back of each rat. Rats were topically treated two times a day for 15 days. Group 1-4 were treated with sterile distilled water, 5% and 10% of extract and intrasite gel, respectively. Masson's trichrome and hematoxylin staining techniques are employed for histological analysis revealed strong wound healing potential closer to that of conventional drug intrasite gel. HECP significantly decreased wound area and an increase in hydroxyproline, cellular proliferation, the number of blood vessels and the level of collagen synthesis was observed. Thus, it could be concluded that HECP possesses strong wound healing potential.

Keywords: Histopathology, Wound Healing, Curcuma purpurascens, hematoxylin staining

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