Papers by Najihah Mohd. Hashim

Phytomedicine, 2013
Please cite this article in press as: Sidahmed, H.M.A., et al., Pyranocycloartobiloxanthone A, a ... more Please cite this article in press as: Sidahmed, H.M.A., et al., Pyranocycloartobiloxanthone A, a novel gastroprotective compound from Artocarpus obtusus Jarret, against ethanol-induced acute gastric ulcer in vivo. Phytomedicine (2013), http://dx.a b s t r a c t Pyranocycloartobiloxanthone A (PA), a xanthone derived from the Artocarpus obtusus Jarret, belongs to the Moraceae family which is native to the tropical forest of Malaysia. In this study, the efficacy of PA as a gastroprotective compound was examined against ethanol-induced ulcer model in rats. The rats were pretreated with PA and subsequently exposed to acute gastric lesions induced by absolute ethanol. The ulcer index, gastric juice acidity, mucus content, histological analysis, glutathione (GSH) levels, malondialdehyde level (MDA), nitric oxide (NO) and non-protein sulfhydryl group (NP-SH) contents were evaluated in vivo. The activities of PA as anti-Helicobacter pylori, cyclooxygenase-2 (COX-2) inhibitor and free radical scavenger were also investigated in vitro. The results showed that the oral administration of PA protects gastric mucosa from ethanol-induced gastric lesions. PA pretreatment significantly (p < 0.05) restored the depleted GSH, NP-SH and NO levels in the gastric homogenate. Moreover, PA significantly (p < 0.05) reduced the elevated MDA level due to ethanol administration. The gastroprotective effect of PA was associated with an over expression of HSP70 and suppression of Bax proteins in the ulcerated tissue. In addition, PA exhibited a potent FRAP value and significant COX-2 inhibition. It also showed a significant minimum inhibitory concentration (MIC) against H. pylori bacterium. The efficacy of PA was accomplished safely without the presence of any toxicological parameters. The results of the present study indicate that the gastroprotective effect of PA might contribute to the antioxidant and anti-inflammatory properties as well as the anti-apoptotic mechanism and antibacterial action against Helicobacter pylori.
Pharmacognosy Journal, 2014

Journal of Ethnopharmacology, 2002
The ulcer protective potential of methanolic extract of Emblica officinalis Gaertn. (EOE) was ass... more The ulcer protective potential of methanolic extract of Emblica officinalis Gaertn. (EOE) was assessed in different acute gastric ulcer models in rats induced by aspirin, ethanol, cold restraint stress and pyloric ligation and healing effect in chronic gastric ulcers induced by acetic acid in rats. EOE, 10 Á/50 mg/kg administered orally, twice daily for 5 days showed dose-dependent ulcer protective effects in all the above acute ulcer models (36.0 Á/98.3% protection, P B/0.2 to P B/0.001) and significant ulcer healing effect in dose of 20 mg/kg after 5 (control ulcer index: 20.29/2.3 mm 2 /rat, % healing 59.6%, P B/0.001) and 10 (control UI: 11.09/1.7, % healing 65.5%, P B/0.01) days treatment. Further study on gastric mucosal factors showed that it significantly decreased the offensive factors like acid (acid output-control 118.79/12.1 mEq/4 h, EOE% decrease 65.9%, P B/0.01) and pepsin (peptic output-control 738.8 mmol/4 h, EOE% decrease 46.2%, P B/0.001) and increased the defensive factors like mucin secretion (TC:P ratio-control 1.219/0.15, EOE% increase 95.0%, P B/0.01), cellular mucus (TC:P ratio-control 1.169/0.13, EOE% increase 53.4%, P B/0.05) and life span of mucosal cells (DNA content of gastric juice-control 77.39/8.7 mg/m per 100 g body weight, EOE% decrease 42.1%, P B/0.05). EOE showed significant antioxidant effect in stressed animals (control UI 35.89/2.5, antioxidant status: LPO 0.589/0.03 nmol MDA/mg protein, SOD and CAT 227.89/6.3 and 18.49/1.2 U/mg protein respectively; EOE% decrease in UI 88.2%, mucosal LPO 69.0%, SOD 53.1% and increase in mucosal CAT 59.8%, P B/0.001 respectively) and did not have any effect on cell proliferation in terms of DNA mg/mg protein or glandular weight. The results showed that EOE had significant ulcer protective and healing effects and this might be due to its effects both on offensive and defensive mucosal factors. #

Phytomedicine, 2013
Please cite this article in press as: Sidahmed, H.M.A., et al., Pyranocycloartobiloxanthone A, a ... more Please cite this article in press as: Sidahmed, H.M.A., et al., Pyranocycloartobiloxanthone A, a novel gastroprotective compound from Artocarpus obtusus Jarret, against ethanol-induced acute gastric ulcer in vivo. Phytomedicine (2013), http://dx.a b s t r a c t Pyranocycloartobiloxanthone A (PA), a xanthone derived from the Artocarpus obtusus Jarret, belongs to the Moraceae family which is native to the tropical forest of Malaysia. In this study, the efficacy of PA as a gastroprotective compound was examined against ethanol-induced ulcer model in rats. The rats were pretreated with PA and subsequently exposed to acute gastric lesions induced by absolute ethanol. The ulcer index, gastric juice acidity, mucus content, histological analysis, glutathione (GSH) levels, malondialdehyde level (MDA), nitric oxide (NO) and non-protein sulfhydryl group (NP-SH) contents were evaluated in vivo. The activities of PA as anti-Helicobacter pylori, cyclooxygenase-2 (COX-2) inhibitor and free radical scavenger were also investigated in vitro. The results showed that the oral administration of PA protects gastric mucosa from ethanol-induced gastric lesions. PA pretreatment significantly (p < 0.05) restored the depleted GSH, NP-SH and NO levels in the gastric homogenate. Moreover, PA significantly (p < 0.05) reduced the elevated MDA level due to ethanol administration. The gastroprotective effect of PA was associated with an over expression of HSP70 and suppression of Bax proteins in the ulcerated tissue. In addition, PA exhibited a potent FRAP value and significant COX-2 inhibition. It also showed a significant minimum inhibitory concentration (MIC) against H. pylori bacterium. The efficacy of PA was accomplished safely without the presence of any toxicological parameters. The results of the present study indicate that the gastroprotective effect of PA might contribute to the antioxidant and anti-inflammatory properties as well as the anti-apoptotic mechanism and antibacterial action against Helicobacter pylori.

PLOS ONE, 2015
Zingiber zerumbet Smith is a perennial herb, broadly distributed in many tropical areas. In Malay... more Zingiber zerumbet Smith is a perennial herb, broadly distributed in many tropical areas. In Malaysia, it&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s locally known among the Malay people as &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;lempoyang&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and its rhizomes, particularly, is widely used in traditional medicine for the treatment of peptic ulcer disease beyond other gastric disorders. The aim of the current study is to evaluate the gastroprotective effect of zerumbone, the main bioactive compound of Zingiber zerumbet rhizome, against ethanol-induced gastric ulcer model in rats. Rats were pre-treated with zerumbone and subsequently exposed to acute gastric ulcer induced by absolute ethanol administration. Following treatment, gastric juice acidity, ulcer index, mucus content, histological analysis (HE and PAS), immunohistochemical localization for HSP-70, prostaglandin E2 synthesis (PGE2), non-protein sulfhydryl gastric content (NP-SH), reduced glutathione level (GSH), and malondialdehyde level (MDA) were evaluated in ethanol-induced ulcer in vivo. Ferric reducing antioxidant power assay (FRAP) and anti-H. pylori activity were investigated in vitro. The results showed that the intragastric administration of zerumbone protected the gastric mucosa from the aggressive effect of ethanol-induced gastric ulcer, coincided with reduced submucosal edema and leukocyte infiltration. This observed gastroprotective effect of zerumbone was accompanied with a significant (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) effect of the compound to restore the lowered NP-SH and GSH levels, and to reduce the elevated MDA level into the gastric homogenate. Moreover, the compound induced HSP-70 up-regulation into the gastric tissue. Furthermore, zerumbone significantly (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) enhanced mucus production, showed intense PAS stain and maintained PG content near to the normal level. The compound exhibited antisecretory activity and an interesting minimum inhibitory concentration (MIC) against H. pylori strain. The results of the present study revealed that zerumbone promotes ulcer protection, which might be attributed to the maintenance of mucus integrity, antioxidant activity, and HSP-70 induction. Zerumbone also exhibited antibacterial action against H. pylori.
Drug Design, Development and Therapy, 2015
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The leaves and stem barks extracts of four plant species, Melicope confusa, M. clemensiae, M. lun... more The leaves and stem barks extracts of four plant species, Melicope confusa, M. clemensiae, M. lunu-ankenda and M. latifolia were screened for their antimicrobial, antioxidant and cytotoxic activities. Almost all extracts of M. clemensia exhibited moderate growth inhibition when tested against the three pathogenic fungi. However, when tested against pathogenic bacteria, the three leaves extracts showed strong activity against methicillin

Drug design, development and therapy, 2014
Cratoxylum arborescens is an equatorial plant belonging to the family Guttiferae. In the current ... more Cratoxylum arborescens is an equatorial plant belonging to the family Guttiferae. In the current study, α-Mangostin (AM) was isolated and its cell death mechanism was studied. HCS was undertaken to detect the nuclear condensation, mitochondrial membrane potential, cell permeability, and the release of cytochrome c. An investigation for reactive oxygen species formation was conducted using fluorescent analysis. To determine the mechanism of cell death, human apoptosis proteome profiler assay was conducted. In addition, using immunofluorescence and immunoblotting, the levels of Bcl-2-associated X protein (Bax) and B-cell lymphoma (Bcl)-2 proteins were also tested. Caspaces such as 3/7, 8, and 9 were assessed during treatment. Using HCS and Western blot, the contribution of nuclear factor kappa-B (NF-κB) was investigated. AM had showed a selective cytotoxicity toward the cancer cells with no toxicity toward the normal cells even at 30 μg/mL, thereby indicating that AM has the attribute...
Journal of Natural Medicines, 2010
Pharmacognosy Journal, 2014

Molecules, 2013
The oxoaporphine alkaloid lysicamine (1), and three proaporphine alkaloids, litsericinone (2), 8,... more The oxoaporphine alkaloid lysicamine (1), and three proaporphine alkaloids, litsericinone (2), 8,9,11,12-tetrahydromecambrine (3) and hexahydromecambrine A (4) were isolated from the leaves of Phoebe grandis (Nees) Merr. (Lauraceae). Compounds 2 and 3 were first time isolated as new naturally occurring compounds from plants. The NMR data for the compounds 2-4 have never been reported so far. Compounds 1 and 2 showed significant cytotoxic activity against a MCF7 (human estrogen receptor (ER+) positive breast cancer) cell line with IC 50 values of 26 and 60 µg/mL, respectively. Furthermore, in vitro cytotoxic activity against HepG2 (human liver cancer) cell line was evaluated for compounds 1-4 with IC 50 values of 27, 14, 81 and 20 µg/mL, respectively. Lysicamine (1) displayed strong antibacterial activity against Bacillus subtilis (B145), Staphylococcus aureus (S1434) and Staphylococus epidermidis (a clinically isolated strain) with inhibition zones of 15.50 ± 0.57, 13.33 ± 0.57 and 12.00 ± 0.00 mm, respectively.

Molecules, 2012
One of the most promising plants in biological screening test results of thirteen Artocarpus spec... more One of the most promising plants in biological screening test results of thirteen Artocarpus species was Artocarpus obtusus FM Jarrett and detailed phytochemical investigation of powdered dried bark of the plant has led to the isolation and identification of three xanthones; pyranocycloartobiloxanthone A (1), dihydroartoindonesianin C (2) and pyranocycloartobiloxanthone B (3). These compounds were screened for antioxidant, antimicrobial and tyrosinase inhibitory activities. Pyranocycloartobiloxanthone A (1) exhibited a strong free radical scavenger towards DPPH free radicals with IC 50 value of 2 µg/mL with prominent discoloration observed in comparison with standard ascorbic acid, α-tocopherol and quercetin, The compound also exhibited antibacterial activity against methicillin resistant Staphylococcus aureus (ATCC3359) and Bacillus subtilis (clinically isolated) with inhibition zone of 20 and 12 mm, respectively. However the other two xanthones were found to be inactive. For the tyrosinase inhibitory activity, again compound (1) displayed strong activity comparable with the standard kojic acid.

Journal of Ethnopharmacology, 2014
mangostin suppress LPS-induced inflammatory response in RAW264.7 macrophages in vitro and carrage... more mangostin suppress LPS-induced inflammatory response in RAW264.7 macrophages in vitro and carrageenan-induced peritonitis in vivo, Journal of Ethnopharmacology, http://dx.Abstract Ethnopharmacological relevance: The fruit hull of Garcinia mangostana Linn. has been used in traditional medicine for treatment of various inflammatory diseases. Hence, this study aims to investigate the in vitro and in vivo anti-inÀammatory effect of ȕ mangostin (ȕM), a major compound present in Garcinia mangostana. Materials and methods: The in silico analysis of inflammatory mediators such as cyclooxygenase (COX) and nuclear factor-kappa B (NF-kB) were performed via molecular docking. Further evaluation of anti-inflammatory effect was conducted in lipopolysaccharide (LPS) induced RAW264.7 macrophages. Suppression of activated NF-kB was analyzed by high content screening. ȕM triggered inhibition of COX-1 and COX-2 in vitro were studied using biochemical kit. The in vivo model used in this study was carrageenan-induced peritonitis model, where reduction in carrageenan-induced peritonitis is measured by leukocyte migration and vascular permeability. In addition, the evaluation of ȕM's effect on carrageenan induced TNF-Į and IL-1ȕ release on peritoneal fluid was also carried out.

Journal of Ethnopharmacology, 2002
A natural source of medicine, Enicosanthellum pulchrum is a tropical plant which belongs to the f... more A natural source of medicine, Enicosanthellum pulchrum is a tropical plant which belongs to the family Annonaceae. In this study, methanol extract from the leaves and stems of this species was evaluated for its gastroprotective potential against mucosal lesions induced by ethanol in rats. Seven groups of rats were assigned, groups 1 and 2 were given Tween 20 (10% v/v) orally. Group 3 was administered omeprazole 20 mg/kg (10% Tween 20) whilst the remaining groups received the leaf and stem extracts at doses of 150 and 300 mg/kg, respectively. After an additional hour, the rats in groups 2-7 received ethanol (95% v/v; 8 mL/kg) orally while group 1 received Tween 20 (10% v/v) instead. Rats were sacrificed after 1 h and their stomachs subjected to further studies. Macroscopically and histologically, group 2 rats showed extremely severe disruption of the gastric mucosa compared to rats pre-treated with the E. pulchrum extracts based on the ulcer index, where remarkable protection was noticed. Meanwhile, a significant percentage of inhibition was shown with the stem extract at 62% (150 mg/kg) and 65% (300 mg/kg), whilst the percentage with the leaf extract at doses of 150 and 300 mg/kg was 63% and 75%, respectively. An increase in mucus content, nitric oxide, glutathione, prostaglandin E2, superoxide dismutase, protein and catalase, and a decrease in malondialdehyde level compared to group 2 were also obtained. Furthermore, immunohistochemical staining of groups 4-7 exhibited down-regulation of Bax and up-regulation of Hsp70 proteins. The methanol extract from the leaves and the stems showed notable gastroprotective potential against ethanol. Citation: Nordin N, Salama SM, Golbabapour S, Hajrezaie M, Hassandarvish P, et al. (2014) Anti-Ulcerogenic Effect of Methanolic Extracts from Enicosanthellum pulchrum (King) Heusden against Ethanol-Induced Acute Gastric Lesion in Animal Models. PLoS ONE 9(11): e111925.

Journal of Biomedicine and Biotechnology, 2012
An investigation of the chemical constituents in Artocarpus obtusus species led to the isolation ... more An investigation of the chemical constituents in Artocarpus obtusus species led to the isolation of three new xanthones, pyranocycloartobiloxanthone A (1), dihydroartoindonesianin C (2), and pyranocycloartobiloxanthone B (3). The compounds were subjected to antiproliferative assay against human promyelocytic leukemia (HL60), human chronic myeloid leukemia (K562), and human estrogen receptor (ER+) positive breast cancer (MCF7) cell lines. Pyranocycloartobiloxanthone A (1) consistently showed strong cytotoxic activity against the three cell lines compared to the other two with IC 50 values of 0.5, 2.0 and 5.0 μg/mL, respectively. Compound (1) was also observed to exert antiproliferative activity and apoptotic promoter towards HL60 and MCF7 cell lines at respective IC 50 values. The compound (1) was not toxic towards normal cell lines human nontumorigenic breast cell line (MCF10A) and human peripheral blood mononuclear cells (PBMCs) with IC 50 values of more than 30 μg/mL.
Journal of Asian Natural Products Research, 2010
Two new xanthones, pyranocycloartobiloxanthone A (1) and dihydroartoindonesianin C (2), were isol... more Two new xanthones, pyranocycloartobiloxanthone A (1) and dihydroartoindonesianin C (2), were isolated from the stem bark of Artocarpus obtusus Jarrett by chromatographic separation. Their structures were determined by using spectroscopic methods and comparison with known related compounds. Pyranocycloartobiloxanthone A (1) showed strong free radical scavenging activity by using DPPH assay as well as cytotoxicity towards K562, HL-60, and MCF7 cell lines.
BMC Complementary and Alternative Medicine, 2013
Background: Mitrella kentii (M. kentii) (Bl.) Miq, is a tree-climbing liana that belongs to the f... more Background: Mitrella kentii (M. kentii) (Bl.) Miq, is a tree-climbing liana that belongs to the family Annonaceae. The plant is rich with isoquinoline alkaloids, terpenylated dihydrochalcones and benzoic acids and has been reported to possess anti-inflammatory activity. The purpose of this study is to assess the gastroprotective effects of desmosdumotin C (DES), a new isolated bioactive compound from M. kentii, on gastric ulcer models in rats.
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Papers by Najihah Mohd. Hashim