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Purpose: To investigate the antidepressant effect of methanol extract of smokeless tobacco and identify its bioactive compounds. Methods: Adult Wistar rats were randomly assigned to five groups of five rats each: normal control group, standard (reference) control group as well as 100, 200 and 500 mg/kg extract group. The extract, standard drug (imipramine) and normal saline were administered via the intraperitoneal (i.p.) route. The rats were subjected to forced swim test (FST) and tail suspension test (TST) to assess the antidepressant effect of methanol extract of smokeless tobacco. Gas chromatography–mass spectrometry (GC-MS) was used to identify the bioactive compounds of the extract. Results: The oral LD50 of the extract was > 2000 mg/kg. Significant decrease in immobility time was observed after single administration of imipramine (p < 0.05). The extract significantly and dosedependently decreased the immobility time, but increased climbing and swimming times, when compared with normal control group (p < 0.05). The immobility time of stressed rats regardless of sex was significantly and dose-dependently lowered, relative to normal control group (p < 0.05). Four major compounds were identified in the extract: nicotine (45.88 %); 1,5-dimethyl-2-pyrrolidinone (23.00 %), nhexadecanoic acid (11.31 %) and vitamin A aldehyde (9.38 %). Conclusion: These results demonstrate that the methanol extract of smokeless tobacco possesses antidepressant and mood-elevating effects in rats. However, its use should be discouraged since it contains a number of hazardous and carcinogenic components such as N-nitroso compounds and benzo(a)pyrene which are categorized as Class-I carcinogens.

Curry leaves (Murraya koenigii) are a leafy spice used in Indian cookery for its fragrant aroma. Many bioactive functional compounds have been identified, and among them carbazole alkaloids have attracted wide attention due to their multi-dimensional medicinal value. Even though it has been established that the carbazole alkaloid is responsible for the anti-ulcer effect showed by this culinary herb, there is no further evidence to say which phytochemical is responsible for this. In the present study, we investigated the gastro-protective effects and mechanism of girinimbine, a major carbazole alkaloid present in curry leaves. Rats were administered with ethanol to produce gastric ulcers, and the prophylactic effect of girinimbine was evaluated. A macroscopic and histological examination was carried out to examine the lesions. Furthermore, the mucus production, NO production, PGE2 synthesis, mucosal nonprotein sulphydryls, glutathione (GSH) level, lipid peroxidation (MDA) level and COX inhibition were assessed. In addition, in particular, TNF-α and IL-6, two important cytokines, were evaluated. Immunohistochemical and gene expression studies were conducted to determine the HSP70 and iNOS biomarkers. Our results indicated that girinimbine significantly reduced the ulcer index and totally safeguarded the mucosa from lesions. The protective effect of girinimbine was complemented through the restoration of the reduced GSH and NP-SH level. This was associated with a reduction of MDA, which was elevated by the administration of ethanol. Pre-treatment of the ethanol induced ulcer with girinimbine reduced the NO concentration in the plasma and elevated PGE2 together with a decreased level of TNF-α and IL-6. Girinimbine had shown suppressing effects on COX-2 enzymes, but not on COX-1. In addition, significantly upregulated HSP70 and downregulated iNOS were observed in girinimbine treated rat tissue at both the transcriptional and translational level. Our results clearly indicated that girinimbine displayed a significant gastro-protection effect, via the capacity to inhibit inflammatory responses and antioxidant potential.

We investigated the protective and in vivo antioxidant effects of p-coumaric acid on carbon tetrachloride-induced hepatotoxicity in Sprague-Dawley rats. The rats were orally pre-treated with p-coumaric acid (at 50 and 100 mg/kg body weight) for 15 days before the subcutaneous injection of carbon tetrachloride (1.5 mL/kg). Silymarin served as a positive control for hepatoprotection. Blood and tissue samples were obtained and used to assess the effects of p-coumaric acid using quantitative and qualitative histological evaluation, glutathione levels, protein determination, and liver enzymes. p-Coumaric acid treatment did not demonstrate any toxicological abnormalities in mice. p-Coumaric acid and silymarin reduced the extent of carbon tetrachloride-induced liver damage and preserved normal hepatic enzymes (P < 0.05). p-Coumaric acid pre-treatment led to a diminution in increased malondialdehyde and decreased glutathione following carbon tetrachloride administration (P < 0.05). Furthermore, p-coumaric acid restored changes in superoxide dismutase and caspase-3 gene expression as a result of carbon tetrachloride exposure. In conclusion, p-coumaric acid helps restore toxicant-induced liver injury in rats via avoidance of lipid peroxidation, inhibition of cell death and preservation of antioxidant mechanism.

A series of the title curcuminoids with structural variance in the heteroatom of the cycloalkanone and the p-substituents of the phenyl rings were tested for their activities against Leishmania major and Toxoplasma gondii parasites. The majority of them showed high activities against both parasite forms with EC50 values in the sub-micromolar concentration range. Bis(p-pentafluorothio)-substituted 3,5-di[(E)-benzylidene]piperidin-4-one 1b was not just noticeable antiparasitic, but also exhibited a considerable selectivity for L. major promastigotes over normal Vero cells. While derivatives differing only in the p-phenyl substituents being CF3 or SF5 showed similar antiparasitic activities, the cyclic ketone hub was more decisive both for the anti-parasitic activities and the selectivities for the parasites vs. normal cells. QSAR calculations confirmed the observed structure-activity relations and suggested structural variations for a further improvement of the antiparasitic activity. Docking studies based on DFT calculations revealed L. major pteridine reductase 1 as a likely molecular target protein of the title compounds.

Background Clausena excavata Burm.f. (Rutaceae) has been used for the treatment of stomach disorders including peptic ulcer. Purpose In this study, we aimed to investigate dentatin isolated from C. excavata Burm.f., for anti-ulcer activity against ethanol ulcer model in rats. Methods Gastric acid output, ulcer index, serum profile, histological evaluation using Hematoxylin and eosin (HE), periodic acid Schiff base stainings and immunohistochemical localization for heat shock proteins 70 (HSP70) were all investigated. Possible involvement of reduced glutathione (GSH), lipid peroxidation, prostaglandin E2 (PGE2), superoxide dismutase (SOD) enzymes, radical scavenging, and anti-Helicobacter pylori activity were investigated. Results Dentatin showed anti-secretory activity against the pylorus ligature model and protected the gastric mucosa from ethanol ulceration, as revealed by the improved macroscopic and histological appearance. Dentatin significantly increased the gastric homogenate content of PGE2 GSH and SOD. Dentatin inhibited the lipid peroxidation as revealed by the reduced gastric content of malondialdehyde (MDA). Moreover, dentatin up-regulated HSP70 expression. However, dentatin showed insignificant anti-H. pylori activity. Conclusion Dentatin possesses gastro-protective activity, which could be attributed to the anti-secretory, mucus production, anti-oxidant, and HSP70 activities.

Ethnopharmacological relevance Boesenbergia rotunda (L.) Mansf. Kulturpfl., previously known as Boesenbergia pandurata (Family: Zingiberaceae) is a ginger species, locally known as fingerroot. It is an integral part of Southeast Asian traditional medicine in alleviating many gastrointestinal disorders such as flatulence, carminative, stomach ache, dyspepsia, and peptic ulcer. Aim of the study Earlier we have investigated the cytoprotective effect of Boesenbergia rotunda extract. In the present study, we investigated the gastroprotection activity of Boesenbergin A (BA), a chalcone isolated from Boesenbergia rotunda extract in ethanol-induced ulcer model in rats. Besides, the contribution of anti-inflammatory and anti-oxidant ability of BA as probable mechanisms involved in the anti-ulcer activity, also been studied. Materials and methods BA was orally administered in rats before ulcer induction with ethanol. The lesions of the gastric mucosa were evaluated macroscopically and histopathologically. The efficiency of BA in mucus production, NO production, PGE2 synthesis, mucosal nonprotein sulphydryls, glutathione (GSH) level, and lipid peroxidation (MDA) level were studied. The involvement of the anti-inflammatory capacity of BA was analyzed by using the measurement of cytokines such as TNF-α and IL-6. Finally, the expression of biomarkers such as HSP 70 and iNOS was analyzed at the transcriptional and translational levels. Results We confirmed the protective capacity of BA via the reduction of ulcerated and haemorrhagic areas. It has induced the protection through lowering GSH, MDA and increased NP-SH level. The plasma NO levels were significantly less in BA treated rats. Both cytokines TNF-α and IL-6 were decreased together with elevated PGE2. Upregulation of HSP and downregulation of iNOS were determined in immunohistochemical and gene expression studies Conclusions The current results suggest that the prophylactic effect found with BA is due to (i) boosting of gastric mucus production and suppression of inflammatory mediators, via pro-inflammatory cytokines and (ii) modulating the oxidative stress response. The usefulness of Boesenbergia rotunda in folk medicine in treating ulcers partially could be due to the presence of this chalcone.

Therapy that directly targets apoptosis and/or inflammation could be highly effective for the treatment of cancer. Murraya koenigii is an edible herb that has been traditionally used for cancer treatment as well as inflammation. Here, we describe that girinimbine, a carbazole alkaloid isolated from M. koenigii, induced apoptosis and inhibited inflammation in vitro as well as in vivo. Induction of apoptosis in human colon cancer cells (HT-29) by girinimbine revealed decreased cell viability in HT-29, whereas there was no cytotoxic effect on normal colon cells. Changes in mitochondrial membrane potential, nuclear condensation, cell permeability, and cytochrome c translocation in girinimbine-treated HT-29 cells demonstrated involvement of mitochondria in apoptosis. Early-phase apoptosis was shown in both acridine orange/propidium iodide and annexin V results. Girinimbine treatment also resulted in an induction of G0/G1 phase arrest which was further corroborated with the upregulation of two cyclin-dependent kinase proteins, p21 and p27. Girinimbine treatment activated apoptosis through the intrinsic pathway by activation of caspases 3 and 9 as well as cleaved caspases 3 and 9 which ended by triggering the execution pathway. Moreover, apoptosis was confirmed by downregulation of Bcl-2 and upregulation of Bax in girinimbine-treated cells. In addition, the key tumor suppressor protein, p53, was seen to be considerably upregulated upon girinimbine treatment. Induction of apoptosis by girinimbine was also evidenced in vivo in zebrafish embryos, with results demonstrating significant distribution of apoptotic cells in embryos after a 24-hour treatment period. Meanwhile, anti-inflammatory action was evidenced by the significant dose-dependent girinimbine inhibition of nitric oxide production in lipopolysaccharide/interferon-gamma-induced cells along with significant inhibition of nuclear factor-kappa B translocation from the cytoplasm to nucleus in stimulated RAW 264.7 cells. Girinimbine was also shown to have considerable antioxidant activity whereby 20 μg/mL of girinimbine was equivalent to 82.17±1.88 μM of Trolox. In mice with carrageenan-induced peritonitis, oral pretreatment with girinimbine helped limit total leukocyte migration (mainly of neutrophils), and reduced pro-inflammatory cytokine levels (interleukin-1beta and tumor necrosis factor-alpha) in the peritoneal fluid. These findings strongly suggest that girinimbine could act as a chemopreventive and/or chemotherapeutic agent by inducing apoptosis while suppressing inflammation. There is a potential for girinimbine to be further investigated for its applicability in treating early stages of cancer.

β-mangostin (βM) was isolated from Cratoxylum arborescens to investigate anti-breast cancer effect in vitro and in vivo. βM exhibited an inhibitory effect on the growth of LA-7 cells in vitro with apoptosis formation. In the animal model, βM treatment was found to be effective in improving the tissue antioxidant enzymes such as superoxide dismutase and catalase activity (P

α-Mangostin (αMN) is a xanthone present in the pericarp of Garcinia mangostana Linn. which is mentioned in Ayurveda and is a widely used functional food supplement. However, its anti-inflammatory mechanism is not well studied. Hence, we used in silico, in vitro and in vivo models to provide information of the mechanism on how αMN could prevent inflammation. Firstly, molecular docking was used to find out the binding energy of αMN with NFκB and COX proteins. Secondly, LPS induced RAW 264.7 cells were used to measure the production of cytokines, the prevention of translocation of NFκB and the inhibition of COX-1 and -2 enzymes. Finally, carrageenan-induced peritonitis was used in vivo to check cytokine release, leukocyte migration and vascular permeability. The in silico modelling had showed that αMN has the lowest binding energy with COX-2 and NFκB proteins. αMN has been found to inhibit the production of PGE2 and nitric oxide, and iNOS protein expression. TNF-α and IL-6 cytokines were inhibited significantly (p < 0.05) at 8 and 14 μg ml−1 concentration. αMN at higher doses inhibits the translocation of NFκB together with suppressing the COX-2 enzymes, but not COX-1. αMN inhibited the total leukocyte migration, predominantly, neutrophils in vivo. The level of TNFα and IL-1β was significantly (p < 0.05) reduced in the peritoneal fluids as measured by ELISA analysis. Taken together, these results demonstrate that αMN acts well as an anti-inflammatory agent via inhibiting the hallmark mechanisms of inflammation. It can be considered as a potential alternative lead compound. In addition, the current results support the traditional use of this fruit pericarp as a functional food.

Ibrahim MY, Hashim NM, Mohan S, et al. Involvement of NF-κB and HSP70 signaling pathways in the apoptosis of MDA-MB-231 cells induced by a prenylated xanthone compound, α-mangostin, from Cratoxylum arborescens [Corrigendum]. Drug Des Devel Ther. 2015;9:3001–3002 was published subsequent to Ibrahim MY, Hashim NM, Mohan S, et al, Involvement of NF-ΚB and HSP70 signaling pathways in the apoptosis of MDA-MB-231 cells induced by a prenylated xanthone compound, α-mangostin, from Cratoxylum arborescens. Drug Des Devel Ther. 2014;8:2193–2211, and Ibrahim MY, Hashim NM, Mohan S, et al, α-Mangostin from Cratoxylum arborescens demonstrates apoptogenesis in MCF-7 with regulation of NF-κB and Hsp70 protein modulation in vitro, and tumor reduction in vivo. Drug Des Devel Ther. 2014;8:1629–1647.When comparing the papers it becomes apparent that they have an unacceptably high degree of similarity and re-use. Further, there is no clear scientific distinction between the cell lines and the results in both. Accordingly, the Editor-in-Chief and Publisher issued a Notice of Retraction for Ibrahim MY, Hashim NM, Mohan S, et al, Involvement of NF-ΚB and HSP70 signaling pathways in the apoptosis of MDA-MB-231 cells induced by a prenylated xanthone compound, α-mangostin, from Cratoxylum arborescens. Drug Des Devel Ther. 2014;8:2193–2211 and the subsequent Corrigendum.This retraction relates to this Corrigendum&nbsp

Long-term khat (Catha edulis Forsk.) chewing has negative effects on human body. Khat constituents appear to be capable of disturbing the delicate equilibrium between damaging and protective mechanisms of a cell that is essential for optimal activity, thereby producing oxidative damage. Therefore, the current study was designed to understand the role of khat on cell toxicity, oxidative stability, and inflammation. Khat was extracted using 60% methanol and assessed calorimetrically for its phenolic and flavonoid contents. 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, oxygen radical absorbance capacity (ORAC), and ferric reducing/antioxidant power (FRAP) assays were used to assess the antioxidant properties. Lipopolysaccharide and interferon gamma induced murine monocytic macrophages cell line (RAW 264.7) were used to assess khat effects on cellular inflammation, oxidative stability, and viability. Khat possesses high content of polyphenols and flavonoids. The results showed a strong potency of antioxidants in DPPH, ORAC, and FRAP assays. Khat decreases the production of the proinflammatory nitric oxide and induces cytotoxicity and reactive oxygen species inhibition. Heavy khat consumption induced-toxicity and symptoms are probably due the harmful effects of its polyphenolic contents.

Background: Sider (Ziziphus spina-christi (L.) Desf.) Honey has been used for the treatment of gastrointestinal disorders including peptic ulcer. Aim of the study: The mechanism of the antiulcer effect of sider honey was studied placing emphasis on its role to block oxidative damage and apoptosis during ethanol-induced gastric ulceration in rats. The mechanism of the antiulcer effect of sider honey was studied placing emphasis on its role to block oxidative damage and apoptosis during ethanol-induced gastric ulceration in rats. Materials and methods: Experimental animals were orally treated with sidr honey (100, 250 and 500 mg/kg, respectively) or omeprazole and subsequently exposed to 95%ethanol (5 mL/Kg, orally) to induce acute gastroulcerogenesis. Effectiveness of sidr honey was evaluated using ulcer index, pH of gastric juice, mucus content, morphological analyses, glutathione assay and malondialdehyde level. The anti-apoptotic role of sidr honey was studied using immunohistochemical staining of gastric tissues using monoclonal antibodies of Bax pathway. Results: Dose-response studies in ethanol-induced ulcer indicate that sidr honey significantly blocks gastric lesions at lower dose (100 mg/kg). Lipid peroxidation and glutathione depletion were significantly inhibited by sidr honey. Sidr honey modulated the immuno-expression of mitochondrial associated protein (Bax). Conclusion: Thus, sider honey plays a considerable role in gastro protection by acting as a potent antioxidant and antiapoptotic agent. Future study is required to explore its potential clinical usage.

α -Mangostin (AM) is believed to be beneficial for health due to its versatile biological activities such as antioxidant, antiviral and anticancer properties. In this study, the air-dried stem bark of Cratoxylum arborescens was extracted consecutively with hexane, chloroform and methanol. The hexane extract was chromatographed, fractionated and purified to yield AM. The toxic effects of AM have not been completely investigated; therefore, the current study investigates its in vitro cytotoxicity on WRL-68 normal cells and in vivo effects on renal and hepatic histobiochemical parameters, relative organ weight, lipid profile, peroxidation and reduced glutathione of ICR female and male mice. AM was fed orally at single doses of 0 (as normal group), 100, 500 and 1000 mg/kg body weight. The results showed that AM did not show adverse effects on body weight, organ weight, serum biochemistry, histopathology and oxidative stress biomarkers. On the other hand, this natural compound showed low cytotoxic activities against normal liver cells (WRL-68) with IC 50 = 65 μg/ml. To our knowledge, this paper is the first to report the toxicity effects of AM in rodents.

Mohamed Yousif Ibrahim,1 Najihah Mohd Hashim,1 Syam Mohan,2 Mahmood Ameen Abdulla,3 Siddig Ibrahim Abdelwahab,2 Behnam Kamalidehghan,1 Mostafa Ghaderian,1,4 Firouzeh Dehghan,1,5 Landa Zeenelabdin Ali,1 Hamed Karimian,1 Maizatulakmal Yahayu,6 Gwendoline Cheng Lian Ee,7 Abdoreza Soleimani Farjam,8 Hapipah Mohd Ali9 1Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Medical Research Centre, Jazan University, Jazan, Saudi Arabia; 3Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 4Epigenetics Lab, HIR Building, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia; 5Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 6Department of Bioproduct Research and Innovation, Institute of Bioproduct Development (IBD), Universiti Teknologi Malaysia, UTM Johor Bahru, Johor, Malaysia; 7Department of Chemistry, Faculty of Science, Universiti Putra Malaysia (UPM), Serdang, Selangor, Malaysia; 8Institute of Tropical Agriculture, Universiti Putra Malaysia (UPM), Serdang, Selangor, Malaysia; 9Department of Chemistry, University of Malaya, Kuala Lumpur, Malaysia Background: Cratoxylum arborescens has been used traditionally in Malaysia for the treatment of various ailments. Methods: α-Mangostin (AM) was isolated from C. arborescens and its cell death mechanism was investigated. AM-induced cytotoxicity was observed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Acridine orange/propidium iodide staining and annexin V were used to detect cells in early phases of apoptosis. High-content screening was used to observe the nuclear condensation, cell permeability, mitochondrial membrane potential, and cytochrome c release. The role of caspases-3/7, -8, and -9, reactive oxygen species, Bcl-2 and Bax expression, and cell cycle arrest were also investigated. To determine the role of the central apoptosis-related proteins, a protein array followed by immunoblot analysis was conducted. Moreover, the involvement of nuclear factor-kappa B (NF-ΚB) was also analyzed. Results: Apoptosis was confirmed by the apoptotic cells stained with annexin V and increase in chromatin condensation in nucleus. Treatment of cells with AM promoted cell death-transducing signals that reduced MMP by downregulation of Bcl-2 and upregulation of Bax, triggering cytochrome c release from the mitochondria to the cytosol. The released cytochrome c triggered the activation of caspase-9 followed by the executioner caspase-3/7 and then cleaved the PARP protein. Increase of caspase-8 showed the involvement of extrinsic pathway. AM treatment significantly arrested the cells at the S phase (P

Purpose: To investigate the inflammatory and nociceptive alterations due to the use of Nicotiana tabacum or smokeless tobacco (MEST) owing to the fact that it is used by some people to relieve dental pain.Methods: Hepatic biochemical indicators and thiobarbituric acid reactive substances assay were used to assess MEST toxicity and pharmacological doses selection. The effects on inflammation of different pharmacological doses (100, 200 and 500 mg/kg i.p.) of MEST were evaluated using xylene-induced ear edema and cotton pellet granuloma tests. Indomethacin (10 mg/kg, i.p.) was used as positive standard drug, whereas the vehicle 0.5 % CMC treated group was considered as negative control. Acetic acid-induced abdominal contraction test and formalin-induced hind paw licking model were utilized to assess the role of MEST in nociception. Indomethacin (10 mg/kg i.p.) and diclofenac sodium (10 mg/kg i.p.) were used as positives standard drugs. The vehicle used was 0.5% CMC which served as the negative control.Results: MEST (50 %, 200 mg/kg) and indomethacin (47.5 %) both elicited a significant (p < 0.001) anti-edematogenic effect on xylene-induced ear edema. MEST also showed a significant (p < 0.001) inhibitory effect on granuloma formation at all administered doses as compared to the untreated groups which was comparable to standard drug indomethacin. The number of acetic acid induced writhings was observed to be significantly increased (p < 0.001) by MEST at all doses, unlike diclofenac that led to significant reduction (p < 0.001) in the number of writhings, when compared to the untreated group. MEST also showed a significant (p < 0.05) dose-dependent reduction of the hind paw licking caused by formalin when compared to the vehicle control.Conclusion: These results signify that administration of MEST induces inflammatory and nociceptive alterations. However, the extract is not recommended for dental pain due to its other toxic effects that have previously been reported.Keywords: Nicotiana tabacum, Smokeless tobacco, Inflammation, Nociception

Background: Recently, there are clinical reports on the potential of Catha edulis (khat) to induce muscular toxicity. C. edulis (khat) is an evergreen shrub and a well-known controversial plant due to the content of natural stimulant, cathine and cathinone. Objective: The main objective of the study is to evaluate the possible effect of C. edulis leaves extract to induce rhabdomyolysis in vivo. Materials and Methods: Sprague Dawley rats were grouped and treated with khat extract at two different doses (250 and 500 mg/kg), while atorvastatin was used as positive control for 28 days. Body weight was measured throughout the study period. Overnight urine was collected from each rat at the 28th day for myoglobin (Myo) analysis. Terminal blood samples were collected from sacrificed animals for the measurement of serum biomarkers and clinical chemistry. The standard clinical pathology assays aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum creatinine (CR) were monitored. Skeletal muscle, cardiac muscle, and kidney were collected for histopathological examination. Results: Animals received 250 mg/kg khat extract had shown mild-to-no gait disorders, while at higher dose extract (500 mg/kg) had reduced the body weight of rats with marked increase of gait disorders compared to control. CR, AST, and ALT were elevated in high-dose administration and in rats received ethanol. The tested biomarkers such as heart-type fatty acid-binding protein (HFABP) 3, Troponin I Type 1 slow skeletal (TNNI1), and Myo were significantly increased in khat high dose and statin treatment, but not in low-dose extract and alcohol. The increase in HFABP and TNN1 results were well reflected in histopathological findings of skeletal myofiber degeneration and in the hemorrhages and pyknosis of nucleus observed in the cardiac muscle. Conclusion: These results provide evidence that khat chewing contributes to the development of muscle toxicity and probable rhabdomyolysis. The current subject thus warrants detailed studies which could emphasize on the cardiac complications and muscular toxicity mechanisms.

There has been a growing interest in naturally occurring compounds from traditional medicine with anti-cancer potential. Nigella sativa (black seed) is one of the most widely studied plants. This annual herb grows in countries bordering the Mediterranean Sea and India. Thymoquinone (TQ) is an active ingredient isolated from Nigella sativa. The anti-cancer effect of TQ, via the induction of apoptosis resulting from mitochondrial dysfunction, was assessed in an acute lymphocyte leukemic cell line (CEMss) with an IC50 of 1.5 µg/mL. A significant increase in chromatin condensation in the cell nucleus was observed using fluorescence analysis. The apoptosis was then confirmed by Annexin V and an increased number of cellular DNA breaks in treated cells were observed as a DNA ladder. Treatment of CEMss cells with TQ encouraged apoptosis with cell death-transducing signals by a down-regulation of Bcl-2 and up-regulation of Bax. Moreover, the significant generation of cellular ROS, HSP70 and activation of caspases 3 and 8 were also observed in the treated cells. The mitochondrial apoptosis was clearly associated with the S phase cell cycle arrest. In conclusion, the results from the current study indicated that TQ could be a promising agent for the treatment of leukemia.

Sclerocarya birrea (Anacardiaceae) is a popular African wild tree distributed in many African countries where the leaves, stem bark, root, and fruits are used in food and traditional medicine; the fruit is rich in ascorbic acid. The fruit juice contains sesquiterpene hydrocarbon, which are terpenes found in plants that are reported to have bacteriostatic properties. The fruit contains a hard brown seed. The seed encloses a soft white kernel rich in oil and protein. The oil contains oleic, palmitic, myristic, and stearic acids; the kernel protein contains amino acids, with a predominance of glutamic acid and arginine. The extracts from different parts showed high total phenolic compounds and radical-scavenging capacities and antioxidant activities. Sclerocarya birrea is widely studied with regard to its antidiabetic, anti-inflammatory, analgesic, antiparasitic, antimicrobial, and antihypertenisve activities.

In the Indian system of traditional medicine (Ayurveda) it is recommended to consume Ipomoea aquatica to mitigate disorders like jaundice. In this study, the protective effects of ethanol extract of I. aquatica against liver damage were evaluated in thioacetamide (TAA)-induced chronic hepatotoxicity in rats. There was no sign of toxicity in the acute toxicity study, in which Sprague-Dawley (SD) rats were orally fed with I. aquatica (250 and 500 mg/kg) for two months along with administration of TAA (i.p injection 200 mg/kg three times a week for two months). The results showed that the treatment of I. aquatica significantly lowered the TAA-induced serum levels of hepatic enzyme markers (ALP, ALT, AST, protein, albumin, bilirubin and prothrombin time). The hepatic content of activities and expressions SOD and CAT that were reduced by TAA were brought back to control levels by the plant extract supplement. Meanwhile, the rise in MDA level in the TAA receiving groups also were significantly reduced by I. aquatica treatment. Histopathology of hepatic tissues by H&E and Masson trichrome stains displayed that I. aquatica has reduced the incidence of liver lesions, including hepatic cells cloudy swelling, infiltration, hepatic necrosis, and fibrous connective tissue proliferation induced by TAA in rats. Therefore, the results of this study show that the protective effect of I. aquatica in TAA-induced liver damage might be contributed to its modulation on detoxification enzymes and its antioxidant and free radical scavenger effects. Moreover, it confirms a scientific basis for the traditional use of I. aquatica for the treatment of liver disorders.

Interleukin-6 is one of the factors affecting sensitivity to cytotoxic agents. Therefore, the current study was designed to investigate the role of IL-6 and IL6 receptors in the cytotoxic effects of zerumbone in ovarian and cervical cancer cell lines (Caov-3 and HeLa, respectively). Exposure of both cancer cells to zerumbone or cisplatin demonstrated growth inhibition at a dose-dependent manner as determined by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,Sdiphenyltetrazolium bromide) reduction assay. Both laser scanning confocal microscopy and TUNEL assay showed typical apoptotic features in treated cells. The studies conducted seems to suggest that zerumbone induces cell death by stimulating apoptosis better than cisplatin, based on the significantly higher percentage of apoptotic cells in zerumbone's treated cancer cells as compared to cisplatin. In addition, zerumbone and cisplatin arrest cancer cells at G2/M phase as analyzed by flow cytometry. Our results indicated that zerumbone significantly decreased the levels of IL-6 secreted by both cancer cells. In contrast, HeLa and Caov-3 cells were still sensitive to cisplatin and zerumbone, even in the presence of exogenous IL-6. However, membrane-bound IL-6 receptor is still intact after zerumbone treatment as demonstrated using an immune-fluorescence technique. This study concludes that the compound, zerumbone inhibits both cancer cell growth through the induction of apoptosis, arrests cell cycle at G2/M phase and inhibits the secretion levels of IL-6 in both cancer cells. Therefore, zerumbone is a potential candidate as a useful chemotherapeutic agent in treating both cervical and ovarian cancers in future.

Current anti-gastric ulcer agents have side effects, despite the progression and expansion of advances in treatment. This study aimed to investigate the gastroprotective mechanisms of Pithecellobium jiringa ethanol extract against ethanol-induced gastric mucosal ulcers in rats. For this purpose, Sprague Dawley rats were randomly divided into five groups: Group 1 (normal control) rats were orally administered with vehicle (carboxymethyl cellulose), Group 2 (ulcer control) rats were also orally administered with vehicle. Group 3 (positive control) rats were orally administered with 20 mg/kg omeprazole, Groups 4 and 5 (experimental groups) received ethanol extract of Pithecellobium jiringa ethanol extract at a concentration of 250 and 500 mg/kg, respectively. Sixty minutes later, vehicle was given orally to the normal control group, and absolute ethanol was given orally to the ulcer control, positive control and experimental groups to generate gastric mucosal injury. The rats were sacrificed an hour later. The effect of oral administration of plant extract on ethanol-induced gastric mucosal injury was studied grossly and histology. The level of lipid peroxidation, (malondialdehyde—MDA), superoxide dismutase (SOD) and gastric wall mucus were measured from gastric mucosal homogenate. The ulcer control group exhibited severe gastric mucosal injury, and this finding was also confirmed by histology of gastric mucosa which showed severe damage to the gastric mucosa with edema and leucocyte infiltration of the submucosal layer. Pre-treatment with plant extract significantly reduced the formation of ethanol-induced gastric lesions, and gastric wall mucus was significantly preserved. The study also indicated a significant increase in SOD activity in gastric mucosal homogenate, whereas a significant decrease in MDA was observed. Acute toxicity tests did not show any signs of toxicity and mortality up to 5 g/kg. The ulcer protective effect of this plant may possibly be due to its preservation of gastric wall mucus along with increased SOD activity and reduction of oxidative stress (MDA). The extract is non-toxic, even at relatively high concentrations.

The current study described the synthesis and the in vivo acute oral toxicity evaluations in Sprague Dawley rats. The compounds were characterized by elemental analyses, LC-MS, FTIR, (1)H NMR, (13)C NMR and UV-visible spectroscopy. In the acute toxicity study, a single administration of the compounds was performed orally to the rats at the single doses of 2000 mg/kg and they were then monitored for possible side effects, mortality or behavioral changes up to 14 days. The serum level of aspartate (AST), alanine aminotransferases (ALT), alkaline phosphate (ALP), triglyceride, high density lipoprotein (HDL), immunoglobulins (GAM) and the C-reactive proteins did not significantly change. The hematological indices white blood cells (WBC), haematocrit (HCT), red blood cells (RBC), mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC), and mean corpuscular hemoglobin (MCH) were within the normal range. The renal function indices examined were also within the reference range. Generally, the compounds exhibited low toxic effects as required for further in vivo therapeutic studies.

Zinc complexes were reported to have anti-ulcer activity and used as drug for the treatment of gastrointestinal disorders. A novel compound dichlorido-zinc(II)-4-(2-(5-methoxybenzylidene amino)ethyl)piperazin-1-iumphenolate (ZnHMS) was synthesized, characterized and evaluated for its gastroprotective activity against ethanol-induced ulcer in rats. Gross and microscopic lesions, histochemical staining of glycogen storage, biochemical and immunological parameters were taken into consideration. Oral administration of ZnHMS (30 and 60 mg/kg; 14 days) dose-dependently inhibited gastric lesions. It significantly increased the mucus content and total acidity compared to the control group (P < 0.01). Serum levels of aspartate (AST), alanine (ALT) transaminases, pro-inflammatory interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a) and anti-inflammatory interleukin-10 (IL-10) in the rats exposed to ethanol induced ulceration have been altered. ZnHMS considerably enhances (P < 0.05) the protection of gastric epithelia by modulating the acute alterations of AST, ALT, IL-6, IL-10, TNF-a and stomach glycogen. Interestingly, ZnHMS did interfere with the natural release of nitric oxide. In addition, acute toxicity study revealed no abnormal sign to the rats treated with ZnHMS (2000 mg/kg). These findings suggest that the gastroprotective activity of ZnHMS might contribute in adjusting the inflammatory cytokine-mediated oxidative damage to the gastric mucosa.

The compound dichlorido-copper(II)-4-(2-5-bromobenzylideneamino)ethyl) piperazin-1-ium phenolate (CuLBS) was synthesized, characterized and screened for acute toxicity and protective activity against ethanol-induced gastric mucosal injury in rats. Gross microscopic lesions, biochemical and immunological parameters and histochemcial staining of glycogen storage were taken into consideration. Oral administration of CuLBS (30 and 60 mg/Kg) for two weeks dose-dependently flattened gastric mucosa, significantly increased gastric mucus and total acidity, compared with control group (P < 0.01). Serum levels of liver enzymes aspartate (AST) and alanine transaminases (ALT), pro-inflammatory (IL-6 and TNF-α) and anti-inflammatory (IL-10) cytokines in the rats exposed to ethanol induced ulceration have been altered. Administration of CuLBS showed considerable (P < 0.05) protection against ulceration by modulating the acute alterations of cytokines AST, ALT and stomach glycogen. Interestingly, CuLBS did not interfere with the natural release of nitric oxide. CuLBS alone (60 mg/Kg) did not exhibit any ulcerogenic effect as assessed using Adami’s scoring scale. An acute toxicity study showed that rats treated with CuLBS (1,000 and 2,000 mg/Kg) manifested no abnormal signs. These findings therefore, suggested that the gastroprotective activity of CuLBS might contribute in modulating the inflammatory cytokine-mediated oxidative damage to gastric mucosa.

This study was carried out to determine the effect of infusing food grade organic acids on the shelf life of fresh beef kept at refrigeration temperature of 5C. Citric, lactic, acetic and tartaric acids were infused individually in concentrations of 0.5, 0.75 and 1.00% into fresh beef slices. Infusion was carried out under pulled of 29.5 in. Hg. for 20 min. Samples were dropped dried and stored at 5C for 28 days. pH, water activity, total plate count (TPC), thiobarbaturic acid values, Hunter color values and instrumental texture were determined. The pH value of the treated samples dropped from the initial pH of 5.30 (untreated) to 4.20–4.47 and the TPC values were lower than 107 colony-forming units/g on day 16, 20 and 28 in samples treated with 0.5, 0.75 and 1.00% acids, respectively. The instrumental texture of the treated samples was harder upon treatment, which decreased gradually during storage period. The maximum shelf life of treated beef was extended to 12–24 days and citric acid in concentration of 1.00% gave the best effect.

The use of evidence-based complementary and alternative medicine is increasing rapidly.Eleucine indica(EI) is traditionally used in ailments associated with liver and kidneys. The therapeutic benefit of the medicinal plants is often attributed to their antioxidant properties. Therefore, the aim of this study was to screen the hexane, dicholoromethane, ethyl acetate (EA) and methanol extracts (MeTH) of EI for their antioxidant, antibacterial and anti-cancer effects using total phenolic contents (TPCs) and DPPH, disc diffusion method and MTT cytotoxicity assays, respectively. The MeTH was showed to have the highest TPC and scavenging activity (77.7%) on DPPH assay, followed by EA (64.5%), hexane (47.19%) and DCM (40.83%) extracts, whereas the MeTH showed no inhibitory effect on all tested bacteria strains. However, the EA extract exhibited a broad spectrum antibacterial activity against all tested bacteria exceptBacillus subtilis, in which this bacterium was found to be resistant to all EI extracts. Meanwhile, hexane extract was demonstrated to have a remarkable antibacterial activity against methicillin resistantStaphylococcus aureus(MRSA) andPseudomonas aeruginosa, while the dicholoromethane extract did not exhibit significant activity againstP. aeruginosa. None of the extracts showed significant cytotoxic activity towards MCF-7, HT-29 and CEM-SS human cancer cell lines after 72 h incubation time (IC50> 30 μg/ml). These results demonstrate that the extract prepared from the EI possesses antioxidant activityin vitroin addition to antibacterial properties. Further investigations are needed to verify the antioxidant effectsin vitroandin vivo.

BACKGROUND: Plant essential oils are widely used as fragrances and flavours. Therefore, the essential oils from the leaves of Cinnamomum pubescens Kochummen (CP) and the whole plant of Etlingera elatior (EE) were investigated for their antioxidant, antibacterial and phytochemical properties. RESULTS: CP and EE were found to contain appreciable levels of total phenolic contents (50.6 and 33.41 g kg(-1) as gallic acid equivalent) and total flavonoid contents (205.6 and 244.8 g kg(-1) as rutin equivalent), respectively. DPPH free radical scavenging activity of CP is superior to EE (P < 0.05) showing IC(50) of 77.2 and 995.1 µg mL(-1), respectively. Methicillin-resistant Staphylococcus aureus (MRSA), Bacillus subtilis, Pseudomonas aeruginosa and Salmonella choleraesuis were tested against CP and EE. Only MRSA was the most susceptible bacteria to CP. GC/MS studies resulted in the identification of 79 and 73 compounds in CP and EE, respectively. The most abundant components of EE included β-pinene (24.92%) and 1-dodecene (24.31%). While the major compound in CP were 1,6-octadien-3-ol,3,7-dimethyl (11.55%), cinnamaldehyde (56.15%) and 1-phenyl-propane-2,2-diol diethanoate (11.38%). CONCLUSION: This study suggests that the essential oils from Cinnamomum pubescens Kochummen and Etlingera elatior could be potentially used as a new source of natural antioxidant and antibacterial in the food and pharmaceutical industries.

Zerumbone (ZER), a monosesquiterpene found in the subtropical ginger (Zingiber zerumbet Smith), possesses antiproliferative properties to several cancer cells lines, including the cervical, skin and colon cancers. In this study, the antitumourigenic effects of ZER were assessed in rats induced to develop liver cancer with a single intraperitoneal injection of diethylnitrosamine (DEN, 200 mg/kg) and dietary 2-acetylaminofluorene (AAF) (0.02%). The rats also received intraperitoneal ZER injections at 15, 30 or 60 mg/kg body wt. twice a week for 11 weeks, beginning week four post-DEN injection. The hepatocytes of positive control (DEN/AAF) rats were smaller with larger hyperchromatic nuclei than normal, showing cytoplasmic granulation and intracytoplasmic violaceous material, which were characteristics of hepatocarcinogenesis. Histopathological evaluations showed that ZER protects the rat liver from the carcinogenic effects of DEN and AAF. Serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (AP) and alpha-fetoprotein (AFP) were significantly lower (P < 0.05) in ZER-treated than untreated rats with liver cancer. The liver malondialdehyde (MDA) concentrations significantly (P < 0.05) increased in the untreated DEN/AAF rats indicating hepatic lipid peroxidation. There was also significant (P < 0.05) reduction in the hepatic tissue glutathione (GSH) concentrations. The liver sections of untreated DEN/AAF rats also showed abundant proliferating cell nuclear antigen (PCNA), while in ZER-treated rats the expression of this antigen was significantly (P < 0.05) lowered. By the TUNEL assay, there were significantly (P < 0.05) higher numbers of apoptotic cells in DEN/AAF rats treated with ZER than those untreated. Zerumbone treatment had also increased Bax and decreased Bcl-2 protein expression in the livers of DEN/AAF rats, which suggested increased apoptosis. Even after 11 weeks of ZER treatment, there was no evidence of abnormality in the liver of normal rats. This study suggests that ZER reduces oxidative stress, inhibits proliferation, induces mitochondria-regulated apoptosis, thus minimising DEN/AAF-induced carcinogenesis in rat liver. Therefore, ZER has great potential in the treatment of liver cancers.

Background: Catha edulis is an evergreen plant belonging to the Celastraceae family, used by the people of Africa, Yemen, and some part of Saudi Arabia as a recreational plant. They chew it alone or in combination with alcohol for attaining euphoria. Objective: There are contradictory studies in the genotoxic potential of the leaves of this plant. So far, the accomplished studies were conducted with much high doses. Hence, the current study has been designed to check the genotoxicity of khat-leaves extract with subcytotoxic concentration in human peripheral blood lymphocytes. Materials and Methods: We have employed comet assay, micronuclei (MN) analysis, and Ames test to evaluate the objectives. Results: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay has revealed that there is a dose-dependent reduction in cell viability with an IC50value of 76.5 μg/ml at 24-h treatment. The results of the comet assay have showed a nonsignificant difference between control and treatment up to 40 μg/ml extract. There was no dose-dependent increase in the frequency of binucleated cells with MN and reduction of cell proliferation in all the doses. The extract showed no mutagenic effect, in both TA98 and TA100 strains even with S9 activation. Conclusion: Under the experimental conditions employed in the present study, khat has been found to be nongenotoxic at subcytotoxic level. Abbreviations used: DMSO: Dimethyl sulfoxide; GIT: gastrointestinal tract; HPBL: Human peripheral blood lymphocytes; KCL: Potassium chloride; LCQ: Low-content quantification; MMC: Mitomycin C; RPMI: Roswell park memorial institute; SWGDRUG: Scientific working group for seized drugs.

Oil extracted from the kernel of Sclerocarya birrea with different harvesting dates was studied in terms of the oil content, fatty acids, tocopherols, phenolic compounds and antimicrobial activity. A quantitative increase in the oil content was observed to reach 63.0% at the end of the last harvesting date. The percentage of total fatty acids had altered and palmitic acid content was found to be 16.8% at the first date of harvesting and dropping for the rest of the dates to reach 14.6% by the end of the harvesting process. In the same manner, stearic acid was found to be 15.2% at the first date and this dropped dramatically to reach 8.8% by the end of the harvesting, while oleic and linoleic acids increased from 58.9 and 4.3% to 67.3 and 5.9%, respectively. Alpha and gamma tocopherols decreased rapidly, whereas the δ-tocopherol and δ-tocotrienol were 4.8 and 4.9 mg/100 g, respectively at the beginning and had disappeared completely by the last harvesting date. Total phenolic and flavonoid content increased continuously through the different harvesting dates. Sclerocarya birrea kernel oil was effective in inhibiting the growth of three out of four bacterial strains tested. This inhibitory effect was less than that of the control.

The proximate analysis of seeds and physicochemical properties of oils extracted from six Sudanese cucurbit seeds Cucumis mello var. agrestis, Cucumis melo var. flexuosus, Cucumis sativus, Citrullus lanatus var. colocynthoides, Cucumis prophetarum, and Luffa echinata were examined by established methods. For each variety, the proximate analysis showed ranges for moisture, protein, and carbohydrates as 3.70–6.87, 14.50–17.50, and 15.62–28.89% on a dry matter basis, respectively. The oils were extracted by Soxhlet using petroleum ether, with yields that ranged from 10.9 to 27.10% (wt/wt). The obtained extracted oils were subjected to phyiscochemical, fatty acid, and tocopherol analysis. The physicochemical characterization of the oil revealed that the refractive indices and relative densities of the oils fell within the narrow ranges of 1.334–1.442 and 0.874–0.920 g/cm3, respectively. Unsaponifiable matters ranged between 0.8 and 1.2 mg KOH/g, whilst peroxide values (PV) ranged from 2.3 to 4.1 meq/kg. The ranges of the values for free fatty acid (FFA %) were 1.2–4.0%. The predominant fatty acids were 16:0, 18:0, 18:1, and 18:2 with ranges of 8.9–14.2, 6.0–9.4, 14.6–32.1, and 43.6–65.5%, respectively. γ-Tocopherol was the predominant tocopherol in all samples ranging from 0.8 to 43.2% of the total tocopherols, followed by δ-tocopherol and α-tocopherol.

The oil and meal from Monechma ciliatum (black mahlab) and Prunus mahaleb (white mahlab) seeds were characterized for their physicochemical properties. The oil content was found to be 30.95 and 13.15% in white and black mahlab seeds, respectively. The refractive indices of white mahlab oil (WMO) and black mahlab oil (BMO) were 1.475 and 1.470, and specific gravities were 0.8511 and 0.8167 g/cm3, respectively. Saponification values were 184.23 and 180.3 mg KOH/g, peroxide values were 2.54 and 4.43 meq/kg, and unsaponifiable matter was 0.92 and 0.66%, respectively. The major fatty acids were palmitic 4.5%, stearic 16.0%, oleic 47.3%, and linoleic 31.4% in BMO, while in WMO they were palmitic 5.7%, oleic 45.0%, and linoleic acid 47.0%. A moderate amount of tocopherols were found at 45.2 and 28.5 mg/100 g in BMO and WMO, respectively. Protein content was found to be 21% in black and 28% in white mahlab seeds. The total amount of amino acids in black and white mahlab seeds was found to be 783.3 and 1,223.2 mg/g N, respectively. The concentration (on ppm dry-weight basis) of major elements (Ca, K, and Mg) and of minor elements (Al, Pb Ni, Mn, Cu, Cr, Co, and Fe) was also determined in the meals.

The aim of this study is to evaluate the anticancer and antimicrobial activities of zerumbone (ZER) from the rhizomes of Zingiber zerumbut. ZER is a crystalline sesquiterpene from the wild ginger, Z. zerumbet. This bioactive component has its unique structure, with a cross-conjugated ketone in an 11-membered ring, as well as remarkable biological activity. Thus, this compound has been isolated from the fresh rhizomes of Z. zerumbet using steam distillation and evaluated for its antimicrobial and anticancer activities. The antimicrobial effects were examined using disc diffusion method and group of microorganism, namely known as Methicilin resistant Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella choleraesuis, Bacillus subtilis, Candida albicans, Aspergillus ochraceaus and Sacchoromyces cerevisiae. However, MTT assay was performed to determine the anti-cancer properties of zerumbone on human cervical cancer cells (HeLa) compared to cisplatin as positive control. Zerumbone has shown a dose dependent (p

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-inflammatory effect of β mangostin (βM), 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 RAW 264.7 macrophages. Suppression of activated NF-kB was analyzed by high content screening. βM 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 βM׳s effect on carrageenan induced TNF-α and IL-1β release on peritoneal fluid was also carried out. Results Treatment with βM could inhibit the LPS-induced NO production but not the viability of RAW 264.7. Similarly, βM inhibited PGE2 production and the cytokines: TNF-α and IL-6. The COX catalyzed prostaglandin biosynthesis assay had showed selective COX-2 inhibition with a 53.0±6.01% inhibition at 20 µg/ml. Apart from this, βM was capable in repressing translocation of NF-kB into the nucleus. These results were concurrent with molecular docking which revealed COX-2 selectivity and NF-kB inhibition. The in vivo analysis showed that after four hours of peritonitis, βM was unable to reduce vascular permeability, yet could decrease the total leukocyte migration; particularly, neutrophils. Meanwhile, dexamethasone 0.5 mg/kg, successfully reduced vascular permeability. The levels of TNF-α and IL-1β in peritoneal fluid was reduced significantly by βM treatment. Conclusion The current study supports the traditional use of Garcinia mangostana fruit hull for treatment of inflammatory conditions. In addition, it is clear that the anti-inflammatory efficacy of this plant is not limited to the presence of α and γ, but β also with significant activity.

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. Methods DES was isolated from the bark of M. kentii. Experimental rats were orally pretreated with 5, 10 and 20 mg/kg of the isolated compound and were subsequently subjected to absolute ethanol-induced acute gastric ulcer. Gross evaluation, mucus content, gastric acidity and histological gastric lesions were assessed in vivo. The effects of DES on the anti-oxidant system, non-protein sulfhydryl (NP-SH) content, nitric oxide (NO)level, cyclooxygenase-2 (COX-2) enzyme activity, bcl-2-associated X (Bax) protein expression and Helicabacter pylori (H pylori) were also investigated. Results DES pre-treatment at the administered doses significantly attenuated ethanol-induced gastric ulcer; this was observed by decreased gastric ulcer area, reduced or absence of edema and leucocytes infiltration compared to the ulcer control group. It was found that DES maintained glutathione (GSH) level, decreased malondialdehyde (MDA) level, increased NP-SH content and NO level and inhibited COX-2 activity. The compound up regulated heat shock protein-70 (HSP-70) and down regulated Bax protein expression in the ulcerated tissue. DES showed interesting anti-H pylori effects. The efficacy of DES was accomplished safely without any signs of toxicity. Conclusions The current study reveals that DES demonstrated gastroprotective effects which could be attributed to its antioxidant effect, activation of HSP-70 protein, intervention with COX-2 inflammatory pathway and potent anti H pylori effect.

This study describes the protective effects of piperazine derived compounds against aspirin induced gastric injuries and evaluated the role of nitric oxide, inflammatory cytokines and serum level of aspartate aminotransaminases (AST), alanine aminotransaminases (ALT), high density lipoprotein (HDL) and malondialdehyde (MDA). The oral administration of the compounds at doses 30 and 60 mg/kg protected the gastric against the nectrotizing effects of aspirin. The level of nitric oxide (NO) was elevated in the group pretreated with the compounds. The results also showed that pre-treatment with piperazine compounds has led to the decrease in the amount of MDA and increased the activity of AST, ALT and HDL. In conclusion, pre-treatment with piperazine derived compounds; (E)-2-(1-(2-(piperazin-1-yl)ethylimino)ethyl)phenol (2HP), (E)-4-(1-(2-(piperazin-1-yl)ethylimino)ethyl) benzene-1,3-diol (DHP) and their zinc complexes has provided a significant protection to the gastric from damaging effects of aspirin.

Boesenbergia rotunda is a medicinal plant that used traditionally in South East Asia as a healing for various ailments including neurological disorders. Therefore, this research was designed to describe the biological evaluation pertaining to anti-human cholinesterase (hAChE) activities, molecular docking and in silico prediction of Boesenbergin A (BA), a natural chalcone isolated from B. rotunda. The anti-hAChE activity of BA was evaluated using acetylthiocholine as a substrate and 5,5-dithiobis[2-nitrobenzoic acid] (DTNB) as chromogen. Docking study with flexible boesenbergin A was done using Autodock 4.2 software and A Lamarkian Genetic Algorithm search method. ADME/Tox analysis was also performed using ADMET Descriptors software. The inhibitory activities of BA and the standard drugs tacrin and propidium iodide on human acetylcholinesterase are 70.1±5.43, 76.6±5.11 and 28.2±2.47, respectively. Molecular docking investigation showed that BA occupies the active site of hAChE and this strongly suggests that it acts as a competitive inhibitor and ultimately reduces the activity of the enzyme. BA also exhibited good ADMET properties indicating capacity for further studies towards developing this compound into a potent drug candidate for the treatment of Alzheimer’s disease. The present study extends the understanding on the molecular mechanism underlying the diverse biological activities of Boesenbergia rotunda.

Some phytochemicals demonstrate gastroprotective effects by inhibiting gastric acid secretion or through antioxidant action. One of these antioxidant phytochemicals which have been studied is gallic acid. However, its mechanism in the treatment and prevention of gastric ulcer remains unclear. This study evaluated the anti-ulcerogenic mechanism(s) of gallic acid (GA) and its novel synthetic derivative (GD). Adult male Sprague Dawley rats were orally pretreated with GA and GD and 30min later exposed to acute gastric ulcerogenesis induced by 95% ethanol (5ml/kg). Potential gastric chemoprevention of GA and GD were assessed using qualitative and quantitative evaluation of gastric lesions, gastric juice acidity, mucus production, histolopathology, PAS histochemistry, immunostaining of Hsp70 and Bax, nitric oxide, prostaglandin E2, TNF-α and thiobarbituric acid reactive substances (TBARS) assay. Oral administration of GA and GD (25 and 50mg/kg) inhibited significantly (P0.05) ethanol-induced gastric lesions. Treatment with the compounds protected rat's stomach and modulated remarkably the levels of PAS-reactive substances, gastric pH, TBARS, immunological and apoptosis marker. The in vivo antioxidant properties, immunomodulator proteins and inhibition of mitochondrial apoptosis may contribute to the gastroprotective activity of gallic acid (GA) and its novel derivative (GD).

Cratoxylum arborescens(Vahl) Blume is an Asian herbal medicine with versatile ethnobiological properties including treatment of gastric ulcer. This study evaluated the antiulcerogenic mechanism(s) ofα-mangostin (AM) in a rat model of ulcer. AM is a prenylated xanthone derived through biologically guided fractionation ofC. arborescens. Rats were orally pretreated with AM and subsequently exposed to acute gastric lesions induced by ethanol. Following treatment, ulcer index, gastric juice acidity, mucus content, histological and immunohistochemical analyses, glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), and nonprotein sulfhydryl groups (NP-SH) were evaluated. The anti-Helicobacter pylori, cyclooxygenase-2 (COX-2) inhibitory effect, and antioxidant activity of AM were also investigatedin vitro. AM (10 and 30 mg/kg) inhibited significantly (P<0.05) ethanol-induced gastric lesions by 66.04% and 74.39 %, respectively. The compound induces the expression of Hsp70, restores GSH levels, decreases lipid peroxidation, and inhibits COX-2 activity. The minimum inhibitory concentration (MIC) of AM showed an effectivein vitroanti-H. pyloriactivity. The efficacy of the AM was accomplished safely without presenting any toxicological parameters. The results of the present study indicate that the antioxidant properties and the potent anti-H. pylori, in addition to activation of Hsp70 protein, may contribute to the gastroprotective activity ofα-mangostin.

Ethnopharmacological relevance Bauhinia thonningii Schum. (Cesalpiniaceae) is locally known as Tambarib and used to treat various diseases including gastric ulcer. Aim of the study The current study aims to evaluate the gastroprotecive mechanism(s) of methanolic (MEBT) and chloroform (CEBT) extracts of Bauhinia thonningii leaves on ethanol-induced gastric ulceration. Materials and methods Gastric acidity, quantification and histochemistry of mucus, gross and microscopic examination, nitric oxide, lipid peroxidation, 2D gel electrophoresis, mass spectroscopy and biochemical tests were utilized to assess the mechanism(s) underlying the gastroprotective effects of MEBT and CEBT. Effect of these extracts into lipopolysaccharide/interferon-γ stimulated rodent cells were done in vitro. In vitro and in vivo toxicity studies were also conducted. Antioxidant activities of MEBT and CEBT were examined using DPPH, FRAP and ORAC assays. Phytochemical analyses of MEBT and CEBT were conducted using chemical and spectroscopic methods. Results Gross and histological features confirmed the anti-ulcerogenic properties of Bauhinia thonningii. Gastroprotective mechanism of MEBT was observed to be mediated through the modulation of PAS-reactive substances, MDA and proteomics biomarkers (creatine kinase, malate dehydrogenase, ATP synthase, actin and thioredoxin). MEBT and CEBT showed no significant in vitro and in vivo effects on nitric oxide. Methanolic extract (MEBT) showed superior gastroprotective effects, polyphenolic content and antioxidant activities compared to CEBT. The plant extracts showed no in vitro or in vivo toxicity. Conclusion It could be concluded that MEBT possesses anti-ulcer activity, which could be attributed to the inhibition of ethanol-induced oxidative damage and the intervention in proteomic pathways but not the nitric oxide pathway.

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.

Background: Catha edulis (Khat) is an evergreen shrub or small tree, traditionally used by various peoples of the Arabian Peninsula and Africa as an integral component of the socioeconomic traditions. It is believed that the psychostimulant nature and toxic nature of khat is primarily due to the presence of cathinone and cathine respectively. Studies have shown that khat chewing is closely associated with cardiac complications, especially myocardial infarction. Hence in this study, we exposed cathine-rich khat extract in a cardiomyoblast H9c2 (2-1) cell line to check the cell death mechanism. Materials and Methods: Extraction of Catha edulis leaves was done and the presence of cathine was confirmed with LC-MS-MS. The anti-proliferative activity was assayed using MTT and apoptosis detection by acridine orange/propidium iodide assay. The expression of Bcl-2 and Bax protein and caspase-3/7 expression were analyzed. The level of reactive oxygen species generation was also evaluated. Results: The khat extract showed an IC50 value of 86.5 μg/ml at 48 hours treatment. We have observed significant early apoptosis events by intervened acridine orange within the fragmented DNA with bright green fluorescence upon treatment. The Bcl-2 expression in the treatment with IC50 concentration of khat extract for 24, 48 and 72 hours of incubation significantly decreased with increase in bax level. The increased activation of caspase-3/7 was significantly observed upon treatment together with significant increase of ROS was detected at 24 and 48 hours treatment. Conclusion: Collectively, our results provide insight into the mechanisms by which Catha edulis leaves mediate cell death in cardiomyocytes. SUMMARY Catha edulis (Khat) is an evergreen psychotropic shrub or small treeExtraction of khat leaves was done and the presence of cathine was confirmed with liquid chromatography-mass spectrometry-mass spectrometryThe khat extract showed an IC50 value of 86.5 μg/ml at 48 h treatment in H9c2 (2–1) cell lineThe observed cell death was associated with increased expression of Bcl2 and caspase-3Significant increase of reactive oxygen species was also detected in the cell with treatment. Abbreviations used: CNS: central nervous system; AMI: acute myocardial infarction; TLC: thin layer chromatography; ESI: electrospray ionization; FBS: fetal bovine serum; DMSO: dimethylsulfoxide; AO; acridine orange; PI; propidium iodide; HRP: horseradish peroxidase; HBSS: hank's balanced salt solution; DCFH-DA: 2’,7’-dichlorofluorescin diacetate; NAC, 10 mM: NAC: N-acetyl cysteine; ROS: reactive oxygen species.

Heyam Mohamed Ali Sidahmed,1 Najihah Mohd Hashim,1 Syam Mohan,2 Siddig Ibrahim Abdelwahab,2 Manal Mohamed Elhassan Taha,2 Firouzeh Dehghan,3 Maizatulakmal Yahayu,4 Gwendoline Cheng Lian Ee,5 Mun Fai Loke,6 Jamuna Vadivelu6 1Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Medical Research Center, Jazan University, Jazan, Saudi Arabia; 3Department of Exercise Science, Sports Centre, University of Malaya, Kuala Lumpur, 4Department of Bioproduct Research and Innovation, Institute of Bioproduct Development (IBD), Universiti Teknologi Malaysia (UTM), Johor Bahru, 5Department of Chemistry, Faculty of Science, Universiti Putra Malaysia (UPM), Serdang, 6Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Purpose: β-Mangostin (BM) from Cratoxylum arborescens demonstrated various pharmacological activities such as anticancer and anti-inflammatory. In this study, we aimed to investigate its antiulcer activity against ethanol ulcer model in rats. Materials and methods: BM was isolated from C. arborescens. Gastric acid output, ulcer index, gross evaluation, mucus production, histological evaluation using hematoxylin and eosin and periodic acid–Schiff staining and immunohistochemical localization for heat shock protein 70 (HSP70) and Bax proteins were investigated. Possible involvement of reduced glutathione, lipid peroxidation, prostaglandin E2, antioxidant enzymes, superoxide dismutase and catalase enzymes, radical scavenging, nonprotein sulfhydryl compounds, and anti-Helicobacter pylori were investigated. Results: BM showed antisecretory activity against the pylorus ligature model. The pretreatment with BM protect gastric mucosa from ethanol damaging effect as seen by the improved gross and histological appearance. BM significantly reduced the ulcer area formation, the submucosal edema, and the leukocytes infiltration compared to the ulcer control. The compound showed intense periodic acid–Schiff staining to the gastric mucus layer and marked amount of alcian blue binding to free gastric mucus. BM significantly increased the gastric homogenate content of prostaglandin E2 glutathione, superoxide dismutase, catalase, and nonprotein sulfhydryl compounds. The compound inhibited the lipid peroxidation revealed by the reduced gastric content of malondialdehyde. Moreover, BM upregulate HSP70 expression and downregulate Bax expression. Furthermore, the compound showed interesting anti-H.pylori activity. Conclusion: Thus, it could be concluded that BM possesses gastroprotective activity, which could be attributed to the antisecretory, mucus production, antioxidant, HSP70, antiapoptotic, and anti-H.pylori mechanisms. Keywords: gastric ulcer, reactive oxygen species, heat shock protein 70

Ethnopharmacological relevance: Clausena excavataBurm.f. has been used in folk medicines in eastern Thailand for the treatment of cancer. Materials and methods:To investigate the apoptosis mechanism, we isolated dentatin (DTN) from this plant using a bioassay-guided approach. DTN-induced cytotoxicity was observed with the MTT assay. Acridine orange/propidium iodide staining was used to detect cells in early apoptosis and high content screening (HCS) to observe nuclear condensation, cell permeability, mitochondrial membrane potential (MMP) and cytochrome c release. Apoptosis was confirmed witha clonogenic assay, DNA laddering and caspase 3/7 and 9 assays. Reactive oxygen specie s( ROS) formation, Bcl-2 and Bax expression, and cell cycle arrest were also investigated. The involvement of nuclear factor-kappa B (NF-kB) was analysed with the HCS assay. Results: As ignif icant increase in chromatin condensationin the cell nucleus was observed by fluorescence analysis. Apoptosis was confirmed by the reduced number of colonies in the clonogenic assay and the increased number of cellular DNA breaks in treated cells observed as a DNA ladder. Treatment of MCF-7 cells with DTN encouraged apoptosis with cell death-transducing signals that reduced MMP by down-regulation of Bcl-2 and up-regulation of Bax, triggering cytochrome c release from the mitochondria to the cytosol. The released cytochrome c triggered the activation of caspase 9 followedby the executioner caspase 3/7. DTN treatment significantly arrested MCF-7 cells at the G0/G1 phase (po0.05) and ROS was significantly elevated. Moreover, DTN significantly blocked the induced translocation of NF-k Bf rom cytoplasm to nucleus. Conclusion:Together, the results demonstrated that the DTN isolated fromClausena excavatainhibited the proliferation of MCF-7 cells, leading to cell cyclearrest and programmed cell death, which was confirmed to occur through the mitochondrial pathway with involvement of the NF-k Bs ignalling pathway.

In this study four samn samples prepared from cow milk using two processing methods (traditional T1, T2 and factory processed T3, T4) were investigated for their physico-chemical properties, fatty acids composition, oxidative stability and sensory properties. The traditionally processed samples showed a significance difference (p < 0.05) in peroxide value and acid value in comparison to factory processed ones. The peroxide value was 2.5 meq O 2/kg of samn for both T3 and T4 samples, which was higher than the peroxide value of T1 and T2, which was 1.5 and 2.0, respectively. The acid value of T3, T4, T1 and T2 are 2.58, 2.54, 1.122 and 1.121, respectively. The results showed that the FFA% of T3, T4, T1 and T2 are 1.29, 1.27, 0.6 and 0.6, respectively. The major fatty acids of the four samn samples were palmitic, oleic, stearic, myristic and capric acid. T3 and T4 contain high percentage of palmitc acid 37.29 and 39.23%, respectively. Traditionally processed sample T1 contains high amount of oleic acid (26.1%) in comparison with the other three samples. Method of processing affects samn properties, quality and oxidative stability, where traditionally processed samples were significantly preferred (P ≤ 0.05) by the panelists for their color, odor, taste and overall acceptability to the factory processed samples.

Several chalcones were synthesized and their in vitro cytotoxicity against various human cell lines, including human breast adenocarcinoma cell line MCF-7, human lung adenocarcinoma cell line A549, human prostate cancer cell line PC3, human adenocarcinoma cell line HT-29 (colorectal cancer) and human normal liver cell line WRL-68 was evaluated. Most of the compounds being active cytotoxic agents, four of them with minimal IC50 values were chosen and studied in detail with MCF-7 cells. The compounds 1, 5, 23, and 25 were capable in eliciting apoptosis in MCF-7 cells as shown by multiparameter cytotoxicity assay and caspase-3/7, -8, and -9 activities (p < 0.05). The ROS level showed 1.3-fold increase (p < 0.05) at the low concentrations used and thus it was concluded that the compounds increased the ROS level eventually leading to apoptosis in MCF-7 cells through intrinsic as well as extrinsic pathways.