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Hanita Omar,1,2 Noraziah Nordin,3 Pouya Hassandarvish,4 Maryam Hajrezaie,5 Ainnul Hamidah Syahadah Azizan,1 Mehran Fadaeinasab,6 Nazia Abdul Majid,7 Mahmood Ameen Abdulla,5 Najihah Mohd Hashim,3 Hapipah Mohd Ali1 1Department of Chemistry, Faculty of Science, 2Centre for Foundation Studies in Science, 3Department of Pharmacy, 4Department of Microbiology, 5Department of Biomedical Sciences, Faculty of Medicine, 6Center for Natural Products and Drug Research (CENAR), 7Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia Abstract: Actinodaphne sesquipedalis 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 A. sesquipedalis 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 A. sesquipedalis 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 A. sesquipedalis extract, which showed its prominent gastroprotective potential in rats’ stomach against ethanol-induced ulcer. Keywords: Actinodaphne sesquipedalis, methanol extracts, gastric ulcer, ethanol, mechanism

Ibrahim Abdel Aziz Ibrahim,1 Mahmood Ameen Abdulla,2 Maryam Hajrezaie,2 Ammar Bader,3 Naiyer Shahzad,1 Saeed S Al-Ghamdi,1 Ahmad S Gushash,4 Mohadeseh Hasanpourghadi5 1Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 2Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Pharmacognosy, Faculty of Pharmacy, Umm Al-Qura University, Makkah, 4College of Arts and Science in Baljurashi, Albaha University, Baljurashi, Saudi Arabia; 5Cell Biology and Drug Discovery Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Abstract: 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. Keywords: Monolluma quadrangula, gastroprotective, Hsp70, superoxide dismutase, catalase, malondialdehyde, gastric ulcer

Hamed Karimian,1 Soheil Zorofchian Moghadamtousi,2 Mehran Fadaeinasab,3 Shahram Golbabapour,2 Mahboubeh Razavi,1 Maryam Hajrezaie,2 Aditya Arya,1 Mahmood Ameen Abdulla,4 Syam Mohan,5 Hapipah Mohd Ali,2 Mohamad Ibrahim Noordin1 1Department of Pharmacy, Faculty of Medicine, 2Institute of Biological Sciences, Faculty of Science, 3Department of Chemistry, 4Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia, 5Medical Research Centre, Jazan University, Jazan, Saudi Arabia Abstract: Ferulago angulata is a medicinal plant that is traditionally known for its ­anti-inflammatory and antiulcer properties. The present study was aimed to evaluate its anticancer activity and the possible mechanism of action using MCF-7 as an in vitro model. F. angulata leaf extracts were prepared using solvents in the order of increasing polarity. As determined by MTT assay, F. angulata leaves hexane extract (FALHE) revealed the strongest cytotoxicity against MCF-7 cells with the half maximal inhibitory concentration (IC50) value of 5.3±0.82 µg/mL. The acute toxicity study of FALHE provided evidence of the safety of the plant extract. Microscopic and flow cytometric analysis using annexin-V probe showed an induction of apoptosis in MCF-7 by FALHE. Treatment of MCF-7 cells with FALHE encouraged the intrinsic pathway of apoptosis, with cell death transducing signals that reduced the mitochondrial membrane potential with cytochrome c release from mitochondria to cytosol. The released cytochrome c triggered the activation of caspase-9. Meanwhile, the overexpression of caspase-8 suggested the involvement of an extrinsic pathway in the induced apoptosis at the late stage of treatment. Moreover, flow cytometric analysis showed that FALHE treatment significantly arrested MCF-7 cells in the G1 phase, which was associated with upregulation of p21 and p27 assessed by quantitative polymerase chain reaction. Immunofluorescence and the quantitative polymerase chain reaction analysis of MCF-7 cells after treatment with FALHE revealed an upregulation of Bax and a downregulation of Bcl-2 proteins. These findings proposed that FALHE suppressed the proliferation of MCF-7 cells via cell cycle arrest and the induction of apoptosis through intrinsic pathway. Keywords: Ferulago angulata, apoptosis, cancer, MCF-7, cell cycle, p21/p27

[This corrects the article DOI: 10.1155/2012/404012.].

[This corrects the article DOI: 10.1155/2013/974185.].

This corrects the article DOI: 10.1038/srep09097.

Cibotium barometz 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 C. barometz 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 C. barometz 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 C. barometz extract associated with the ulcerated control group. Histology of rats pretreated with C. barometz 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., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

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., Competing Interests: The authors have declared that no competing interests exist.

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.

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., (Copyright © 2015. Published by Elsevier Ltd.)

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.

The development of metal-based agents has had a tremendous role in the present progress in cancer chemotherapy. One well-known example of metal-based agents is Schiff based metal complexes, which hold great promise for cancer therapy. Based on the potential of Schiff based complexes for the induction of apoptosis, this study aimed to examine the cytotoxic and apoptotic activity of a CdCl2(C14H21N3O2) complex on HT-29 cells. The complex exerted a potent suppressive effect on HT-29 cells with an IC50 value of 2.57 ± 0.39 after 72 h of treatment. The collapse of the mitochondrial membrane potential and the elevated release of cytochrome c from the mitochondria to the cytosol indicate the involvement of the intrinsic pathway in the induction of apoptosis. The role of the mitochondria-dependent apoptotic pathway was further proved by the significant activation of the initiator caspase-9 and the executioner caspases-3 and -7. In addition, the activation of caspase-8, which is associated with the suppression of NF-κB translocation to the nucleus, also revealed the involvement of the extrinsic pathway in the induced apoptosis. The results suggest that the CdCl2(C14H21N3O2) complex is able to induce the apoptosis of colon cancer cells and is a potential candidate for future cancer studies.

Background: Curcuma purpurascens BI. (Zingiberaceae) commonly known as 'Koneng Tinggang' and 'Temu Tis' is a Javanese medicinal plant which has been used for numerous ailments and diseases in rural Javanese communities. In the present study, the apoptogenic activity of dichloromethane extract of Curcuma purpurascens BI. rhizome (DECPR) was investigated against HT-29 human colon cancer cells., Methods: Acute toxicity study of DECPR was performed in Sprague-Dawley rats. Compounds of DECPR were analyzed by the gas chromatography-mass spectrometry-time of flight (GC-MS-TOF) analysis. Cytotoxic effect of DECPR on HT-29 cells was analyzed by MTT and lactate dehydrogenase (LDH) assays. Effects of DECPR on reactive oxygen species (ROS) formation and mitochondrial-initiated events were investigated using a high content screening system. The activities of the caspases were also measured using a fluorometric assay. The quantitative PCR analysis was carried out to examine the gene expression of Bax, Bcl-2 and Bcl-xl proteins., Results: The in vivo acute toxicity study of DECPR on rats showed the safety of this extract at the highest dose of 5 g/kg. The GC-MS-TOF analysis of DECPR detected turmerone as the major compound in dichloromethane extract. IC50 value of DECPR towards HT-29 cells after 24 h treatment was found to be 7.79 ± 0.54 μg/mL. In addition, DECPR induced LDH release and ROS generation in HT-29 cells through a mechanism involving nuclear fragmentation and cytoskeletal rearrangement. The mitochondrial-initiated events, including collapse in mitochondrial membrane potential and cytochrome c leakage was also triggered by DECPR treatment. Initiator caspase-9 and executioner caspase-3 was dose-dependently activated by DECPR. The quantitative PCR analysis on the mRNA expression of Bcl-2 family of proteins showed a significant up-regulation of Bax associated with down-regulation in Bcl-2 and Bcl-xl mRNA expression., Conclusions: The findings presented in the current study showed that DECP suppressed the proliferation of HT-29 colon cancer cells and triggered the induction of apoptosis through mitochondrial-dependent pathway.

The anti-carcinogenic effect of the new quinazolinone compound, named MMD, was tested on MCF-7 human breast cancer cell line. The synthesis of quinazolinone-based compounds attracted strong attention over the past few decades as an alternative mean to produce analogues of natural products. Quinazolinone compounds sharing the main principal core structures are currently introduced in the clinical trials and pharmaceutical markets as anti-cancer agents. Thus, it is of high clinical interest to identify a new drug that could be used to control the growth and expansion of cancer cells. Quinazolinone is a metabolite derivative resulting from the conjugation of 2-aminobenzoyhydrazide and 5-methoxy-2- hydroxybenzaldehyde based on condensation reactions. In the present study, we analysed the influence of MMD on breast cancer adenoma cell morphology, cell cycle arrest, DNA fragmentation, cytochrome c release and caspases activity. MCF-7 is a type of cell line representing the breast cancer adenoma cells that can be expanded and differentiated in culture. Using different in vitro strategies and specific antibodies, we demonstrate a novel role for MMD in the inhibition of cell proliferation and initiation of the programmed cell death. MMD was found to increase cytochrome c release from the mitochondria to the cytosol and this effect was enhanced over time with effective IC50 value of 5.85 ± 0.71 μg/mL detected in a 72-hours treatment. Additionally, MMD induced cell cycle arrest at G0/G1 phase and caused DNA fragmentation with obvious activation of caspase-9 and caspases-3/7. Our results demonstrate a novel role of MMD as an anti-proliferative agent and imply the involvement of mitochondrial intrinsic pathway in the observed apoptosis.

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.

Background: Curcuma purpurascens BI. is a medicinal plant from the Zingiberaceae family, which is widely used as a spice and as folk medicine. The aim of the present study is to investigate the gastroprotective activity of C. purpurascens rhizome hexane extract (CPRHE) against ethanol- induced gastric ulcers in rats., Methods: Acute toxicity test was carried out on 36 rats (18 males and 18 females) with low dose of CPRHE (1 g/kg), high dose of CPRHE (2 g/kg) and vehicle (5% Tween 20). To determine the gastroprotective effect of CPRHE, gastric juice acidity, gross and histological gastric lesions, mucus content and ulcer index were evaluated in ethanol-induced ulcer in rats. In addition, superoxide dismutase activity, nitric oxide level and immunohistochemical evaluation of Bax and HSP70 proteins were examined., Results: The CPRHE acute toxicity test on rats did not reveal any signs of mortality and toxicity up to 2 g/kg. The oral administration of CPRHE at doses of 200 mg/kg and 400 mg/kg and omeprazole (positive control) at a dose of 20 mg/kg to rats remarkably attenuated gastric lesions induced by ethanol. Pre-treatment of rats with CPRHE significantly replenished the depletion of mucus content caused by ethanol administration and decreased the acidity of gastric walls. Further examination of gastric mucosal homogenate revealed significant elevation of superoxide dismutase and nitric oxide activities and reduction in malondialdehyde level in CPRHE-treated group, compared to the lesion control group. Histological assessment of gastric walls obtained from rats pre-treated with CPRHE demonstrated a noteworthy decrease in hemorrhagic mucosal lesions. Immunohistochemical staining showed down-regulation of Bax protein and up-regulation of Hsp70 protein., Conclusion: Taken together, these findings confirmed the gastroprotective effect of Curcuma purpurascens rhizome against gastric damage.

Background: The study was carried out to determine the cytotoxic, antioxidant and gastro-protective effect of ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylid ene)amino] benzoate (ETHAB) in rats., Methodology/principal Findings: The cytotoxic effect of ETHAB was assessed using a MTT cleavage assay on a WRL68 cell line, while its antioxidant activity was evaluated in vitro. In the anti-ulcer study, rats were divided into six groups. Group 1 and group 2 received 10% Tween 20 (vehicle). Group 3 received 20 mg/kg Omeprazole. Groups 4, 5 and 6 received ETHAB at doses of 5, 10, and 20 mg/kg, respectively. After an hour, group 1 received the vehicle. Groups 2-6 received absolute ethanol to induce gastric mucosal lesions. In the WRL68 cell line, an IC50 of more than 100 µg/mL was observed. ETHAB results showed antioxidant activity in the DPPH, FRAP, nitric oxide and metal chelating assays. There was no acute toxicity even at the highest dosage (1000 mg/kg). Microscopy showed that rats pretreated with ETHAB revealed protection of gastric mucosa as ascertained by significant increases in superoxide dismutase (SOD), pH level, mucus secretion, reduced gastric lesions, malondialdehyde (MDA) level and remarkable flattened gastric mucosa. Histologically, pretreatment with ETHAB resulted in comparatively better gastric protection, due to reduction of submucosal edema with leucocyte infiltration. PAS staining showed increased intensity in uptake of Alcian blue. In terms of immunohistochemistry, ETHAB showed down-expression of Bax proteins and over-expression of Hsp70 proteins., Conclusion/significance: The gastroprotective effect of ETHAB may be attributed to antioxidant activity, increased gastric wall mucus, pH level of gastric contents, SOD activity, decrease in MDA level, ulcer area, flattening of gastric mucosa, reduction of edema and leucocyte infiltration of the submucosal layer, increased PAS staining, up-regulation of Hsp70 protein and suppressed expression of Bax.

Background: Based on the potential of Schiff base compounds to act as sources for the development of cancer chemotherapeutic agents, this in vivo study was performed to investigate the inhibitory properties of the synthetic Schiff base compound Cu(BrHAP)2 on colonic aberrant crypt foci (ACF)., Methodology: This study involved five groups of male rats. The negative control group was injected with normal saline once a week for 2 weeks and fed 10% Tween 20 for 10 weeks, the cancer control group was subcutaneously injected with 15 mg/kg azoxymethane once per week for two consecutive weeks, the positive control group was injected with 15 mg/kg azoxymethane once per week for two consecutive weeks and 35 mg/kg 5-fluorouracil (injected intra-peritoneally) for 4 weeks, and the experimental groups were first injected with 15 mg/kg azoxymethane once per week for two consecutive weeks and then fed 2.5 or 5 mg/kg of the Schiff base compound once a day for 10 weeks. Application of the Schiff base compound suppressed total colonic ACF formation by up to 72% to 74% (P<0.05) when compared with the cancer control group. Analysis of colorectal specimens revealed that treatments with the Schiff base compound decreased the mean crypt scores in azoxymethane-treated rats. Significant elevations of superoxide dismutase, glutathione peroxidase and catalase activities and a reduction in the level of malondialdehyde were also observed. Histologically, all treatment groups exhibited significant decreases in dysplasia compared to the cancer control group (P<0.05). Immunohistochemical staining demonstrated down-regulation of the PCNA protein. Comparative western blot analysis revealed that COX-2 and Bcl2 were up-regulated and Bax was down-regulated compared with the AOM control group., Conclusion: The current study demonstrated that the Cu(BrHAP)2 compound has promising chemoprotective activities that are evidenced by significant decreases in the numbers of ACFs in azoxymethane-induced colon cancer.

Metal-based drugs with extensive clinical applications hold great promise for the development of cancer chemotherapeutic agents. In the last few decades, Schiff bases and their complexes have become well known for their extensive biological potential. In the present study, we examined the antiproliferative effect of a copper (II) complex on HT-29 colon cancer cells. The Cu(BrHAP)2 Schiff base compound demonstrated a potent antiproliferative effect in HT-29 cells, with an IC50 value of 2.87  μg/ml after 72 h of treatment. HT-29 cells treated with Cu (II) complexes underwent apoptosis death, as exhibited by a progressive elevation in the proportion of the G1 cell population. At a concentration of 6.25  μg/ml, the Cu(BrHAP)2 compound caused significant elevation in ROS production following perturbation of mitochondrial membrane potential and cytochrome c release, as assessed by the measurement of fluorescence intensity in stained cells. Furthermore, the activation of caspases 3/7 and 9 was part of the Cu (II) complex-induced apoptosis, which confirmed the involvement of mitochondrial-mediated apoptosis. Meanwhile, there was no significant activation of caspase-8. Taken together, these results imply that the Cu(BrHAP)2 compound is a potential candidate for further in vivo and clinical colon cancer studies to develop novel chemotherapeutic agents derived from metal-based agents.

Background: The study was carried out to assess the gastroprotective effect of the zinc (II) complex against ethanol-induced acute hemorrhagic lesions in rats., Methodology/principal Finding: The animals received their respective pre-treatments dissolved in tween 20 (5% v/v), orally. Ethanol (95% v/v) was orally administrated to induce superficial hemorrhagic mucosal lesions. Omeprazole (5.790×10(-5) M/kg) was used as a reference medicine. The pre-treatment with the zinc (II) complex (2.181×10(-5) and 4.362×10(-5) M/kg) protected the gastric mucosa similar to the reference control. They significantly increased the activity levels of nitric oxide, catalase, superoxide dismutase, glutathione and prostaglandin E2, and decreased the level of malondialdehyde. The histology assessments confirmed the protection through remarkable reduction of mucosal lesions and increased the production of gastric mucosa. Immunohistochemistry and western blot analysis indicated that the complex might induced Hsp70 up-regulation and Bax down-regulation. The complex moderately increased the gastroprotectiveness in fine fettle. The acute toxicity approved the non-toxic characteristic of the complex (<87.241×10(-5) M/kg)., Conclusion/significance: The gastroprotective effect of the zinc (II) complex was mainly through its antioxidant activity, enzymatic stimulation of prostaglandins E2, and up-regulation of Hsp70. The gastric wall mucus was also a remarkable protective mechanism.

DNA methylation, histone modifications, and chromatin configuration are crucially important in the regulation of gene expression. Among these epigenetic mechanisms, silencing the expression of certain genes depending on developmental stage and tissue specificity is a key repressive system in genome programming. Polycomb (Pc) proteins play roles in gene silencing through different mechanisms. These proteins act in complexes and govern the histone methylation profiles of a large number of genes that regulate various cellular pathways. This review focuses on two main Pc complexes, Pc repressive complexes 1 and 2, and their phylogenetic relationship, structures, and function. The dynamic roles of these complexes in silencing will be discussed herein, with a focus on the recruitment of Pc complexes to target genes and the key factors involved in their recruitment.

The investigation was to evaluate gastroprotective effects of ethanolic extract of M. pruriens leaves on ethanol-induced gastric mucosal injuries in rats. Forty-eight rats were divided into 8 groups: negative control, extract control, ulcer control, reference control, and four experimental groups. As a pretreatment, the negative control and the ulcer control groups were orally administered carboxymethylcellulose (CMC). The reference control was administered omeprazole orally (20 mg/kg). The ethanolic extract of M. pruriens leaves was given orally to the extract control group (500 mg/kg) and the experimental groups (62.5, 125, 250, and 500 mg/kg). After 1 h, CMC was given orally to the negative and the extract control groups. The other groups received absolute ethanol. The rats were sacrificed after 1 h. The ulcer control group exhibited significant mucosal injuries with decreased gastric wall mucus and severe damage to the gastric mucosa. The extract caused upregulation of Hsp70 protein, downregulation of Bax protein, and intense periodic acid schiff uptake of glandular portion of stomach. Gastric mucosal homogenate showed significant antioxidant properties with increase in synthesis of PGE2, while MDA was significantly decreased. The ethanolic extract of M. pruriens leaves was nontoxic (<5 g/kg) and could enhance defensive mechanisms against hemorrhagic mucosal lesions.

Zingiber officinale is a traditional medicine against various disorders including liver diseases.The aim of this study was to assess the hepatoprotective activity of the ethanolic extract of rhizomes of Z. officinale (ERZO) against thioacetamide-induced hepatotoxicity in rats. Five groups of male Sprague Dawley have been used. In group 1 rats received intraperitoneal (i.p.) injection of normal saline while groups 2-5 received thioacetamide (TAA, 200 mg/kg; i.p.) for induction of liver cirrhosis, thrice weekly for eight weeks. Group 3 received 50 mg/kg of silymarin. The rats in groups 4 and 5 received 250 and 500 mg/kg of ERZO (dissolved in 10% Tween), respectively. Hepatic damage was assessed grossly and microscopically for all of the groups. Results confirmed the induction of liver cirrhosis in group 2 whilst administration of silymarin or ERZO significantly reduced the impact of thioacetamide toxicity. These groups decreased fibrosis of the liver tissues. Immunohistochemistry assessment against proliferating cell nuclear antigen did not show remarkable proliferation in the ERZO-treated rats when compared with group 2. Moreover, factions of the ERZO extract were tested on Hep-G2 cells and showed antiproliferative activity (IC50 38-60 μ g/mL). This study showed hepatoprotective effect of ERZO.

Background: Synthetic steroids, such as 9α-bromobeclomethasonedipropionate, have shown gastroprotective activity. For example, the potent glucocorticoid steroid, beclomethasone dipropionate, has been used for treatment of bowel ulcerations. The purpose of the present study was to evaluate the effect of a synthetic steroid, (20S)-22-acetoxymethyl-6β-methoxy-3α,5-dihydro-3'H-cyclopropa[3α,5]-5α-pregnane (AMDCP), on ethanol-induced gastric mucosa injuries in rats., Methodology/principal Finding: Rats were divided into 8 groups. The negative control and ethanol control groups were administered Tween 20 (10%v/v) orally. The reference control group, 20 mg/kg omeprazole (10% Tween 20, 5 mL/kg), was administrated orally. The experimental groups received 1, 5, 10, 15 or 20 mg/kg of the AMDCP compound (10% Tween 20, 5 mL/kg). After 60 min, Tween 20 and absolute ethanol was given orally (5 mL/kg) to the negative control group and to the rest of the groups, and the rats were sacrificed an hour later. The acidity of gastric content, gastric wall mucus and areas of mucosal lesions were assessed. In addition, histology and immunohistochemistry of the gastric wall were assessed. Prostaglandin E2 (PGE2) and malondialdehyde (MDA) content were also measured. The ethanol control group exhibited severe mucosal lesion compared with the experimental groups with fewer mucosal lesions along with a reduction of edema and leukocyte infiltration. Immunohistochemical staining of Hsp70 and Bax proteins showed over-expression and under-expression, respectively, in the experimental groups. The experimental groups also exhibited high levels of PGE2 as well as a reduced amount of MDA. AMDCP decreased the acidity and lipid peroxidation and increased the levels of antioxidant enzymes., Conclusion/significance: The current investigation evaluated the gastroprotective effects of AMDCP on ethanol-induced gastric mucosal lesions in rats. This study also suggests that AMDCP might be useful as a gastroprotective agent.

Background: Copper is an essential element in various metabolisms. The investigation was carried out to evaluate acute gastroprotective effects of the Copper (II) complex against ethanol-induced superficial hemorrhagic mucosal lesions in rats., Methodology/principal Findings: Rats were divided into 7 groups. Groups 1 and 2 were orally administered with Tween 20 (10% v/v). Group 3 was orally administered with 20 mg/kg omeprazole (10% Tween 20). Groups 4-7 received 10, 20, 40, and 80 mg/kg of the complex (10% Tween 20), respectively. Tween 20 (10% v/v) was given orally to group 1 and absolute ethanol was given orally to groups 2-7, respectively. Rats were sacrificed after 1 h. Group 2 exhibited severe superficial hemorrhagic mucosal lesions. Gastric wall mucus was significantly preserved by the pre-treatment complex. The results showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE(2)) activities and a decrease in malondialdehyde (MDA) level. Histology showed marked reduction of hemorrhagic mucosal lesions in groups 4-7. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. PAS staining of groups 4-7 showed intense stain uptake of gastric mucosa. The acute toxicity revealed the non-toxic nature of the compound., Conclusions/significance: The gastroprotective effect of the Copper (II) complex may possibly be due to preservation of gastric wall mucus; increase in PGE(2) synthesis; GSH, SOD, and NO up-regulation of Hsp70 protein; decrease in MDA level; and down-regulation of Bax protein.

Polygonum chinense is a Malaysian ethnic plant with various healing effects. This study was to determine preventive effect of aqueous leaf extract of P. chinense against ethanol-induced gastric mucosal injury in rats. Sprague Dawley rats were divided into seven groups. The normal and ulcer control groups were orally administered with distilled water. The reference group was orally administered with 20 mg/kg omeprazole. The experimental groups received the extracts 62.5, 125, 250, and 500 mg/kg, accordingly. After sixty minutes, distilled water and absolute ethanol were given (5 mL/kg) to the normal control and the others, respectively. In addition to histology, immunohistochemical and periodic acid schiff (PAS) stains, levels of lipid peroxidation, malondialdehyde (MDA), antioxidant enzymes, and superoxide dismutase (SOD) were measured. The ulcer group exhibited severe mucosal damages. The experimental groups significantly reduced gastric lesions and MDA levels and increased SOD level. Immunohistochemistry of the experimental groups showed upregulation and downregulation of Hsp70 and Bax proteins, respectively. PAS staining in these groups exhibited intense staining as compared to the ulcer group. Acute toxicity study revealed the nontoxic nature of the extract. Our data provide first evidence that P. chinense extract could significantly prevent gastric ulcer.