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Biomass valorisation is conventionally associated with the production of green biofuels. However, this could extend beyond the conventional perception of biomass application into other domains such as medical sciences. Acid condensate (AC) obtained from pyrolysis promises a good potential for biomedical applications, notably for its antimicrobial, antioxidant, and anti-inflammatory properties. In this study, concentrated AC extract (CACE) obtained from microwave-assisted pyrolysis of palm kernel shells was fractionated, and the resulting fractions were pooled according to similar thin layer chromatography profiles into combined fractions (CFACs). CFACs were evaluated for total phenolic content, antioxidant level, cytotoxicity, and wound healing activities toward human skin fibroblast cells (HSF 1184). CFAC-3 showed the highest total phenolic content (624.98 ± 8.70 µg GAE/mg of sample) and antioxidant activities (DPPH IC50 of 29.47 ± 0.74 µg/mL, ABTS of 1247.13 ± 27.89 μg TE/mg sample, FRAP of 24.26 ± 0.71 mmol Fe(II)/mg sample, HFRS of 257.74 ± 1.74 µg/mL) compared to CACE (DPPH IC50 of 81.76 ± 2.81 µg/mL, ABTS of 816.95 ± 30.49 μg TE/mg sample, FRAP of 9.22 ± 0.66 mmol Fe(II)/mg sample, HFRS of 689.30 ± 36.00 µg/mL), no cytotoxic properties at ≤50 µg/mL, and significantly faster wound closure (at 1.25 µg/mL) compared to the control 12 h after treatment. The phosphorylation of the phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) were upregulated, thus indicating that wound healing of CFAC-3 followed through this signalling pathway. To conclude, phenolic-rich CFAC-3 obtained from the pyrolysis of palm kernel shells demonstrated potential biomedical application as an alternative wound healing agent with high antioxidant and wound-healing activity. To the best of our knowledge, this was the first study to report on the wound healing activity of AC and its wound healing mechanism.

Seven Bacillus spp. isolated from the marine water and the rhizosphere of the medicinal plant Coscinium fenestratum were studied to produce plant growth promotion (PGP) traits invitro. Among the seven isolates, MMRH22 and RHPR20 produced copious amounts of PGP traits. Based on the 16S rRNA sequence, the two potent bacterial isolates, RHPR20 and MMRH22, were identified as Bacillus mojavensis and Bacillus cereus, respectively. A compatibility test between the isolates RHPR20 and MMRH22 revealed they are compatible and can be used as a consortium. Both isolates were evaluated for the plant growth promotion and the biofortification of sorghum under greenhouse conditions. Treatments included the application of MMRH22, RHPR20, their consortium (RHPR20 + MMRH22), and an uninoculated control. Inoculation with bacterial cultures resulted in a significant increase in the plant height, the number of leaves, the leaf area, the root, shoot, and leaf weight, and the yield of sorghum at 30 and 60 days after sowing (DAS). The scanning electron micrograph of the sorghum plant roots revealed extensive colonization in the plants treated with the bacterial cultures compared to the uninoculated control. The sorghum grains obtained after final harvest were analyzed for their nutrient content by ICP–OES. The biofortification in sorghum grains was varied and was found to enhance the iron content up to 97%. This study revealed that treatments with microbial consortia enhance plant growth, yield, and iron content, which could combat nutrient deficiencies in plants and humans.

This study reports on the microwave-assisted heating optimisation of acid condensate (AC) from palm kernel shell (PKS), using the central composite design (CCD) approach focusing on its total phenolic content (TPC) as response and its antimicrobial activity. Thermogravimetric-derivative thermogravimetric (TG-DTG) analysis clearly depicted the devolatilisation of lignocellulosic content of PKS. The highest TPC in concentrated AC extract (CACE), 451.51 ± 2.37 µg GAE/mg (R2 0.9870), was obtained at microwave power of 580 W, nitrogen flow rate of 2.4 L/min and final temperature of 480 oC. Nitrogen flow rate had the highest effect on TPC with an F value of 63.65. Relative to ascorbic acid, CACE showed a higher Trolox equivalent antioxidant capacity (TEAC) but almost similar 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capabilities which can be attributed to the presence of 1,2-benzendiol, i.e. catechol (27.82%) and 1,3-dimethoxy-2-hydroxybenzene, i.e. syringol (22.76%). CACE also displayed good potential for antimicrobial application with high growth inhibition of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus faecalis, Aspergillus niger and Fusarium oxysporum. In conclusion, PKS has a great potential to be used as raw material to produce AC (acid condensate) using microwave-assisted heating process.

Gaharu oleoresin is a mixture of wood resin and essential oil substances that naturally accumulates in the gaharu plants species. The aim of this study was to determine the appropriate solvent types and the contents of oleoresin and oil as well as the chemical compounds present in the gaharu extracts. Gaharu oleoresin can be extracted from gaharu powder using polar solvents and the essential oil can be separated using non-polar solvents. The extraction was done by Soxhlet method using methanol and ethanol for oleoresin extraction, and n-hexane and toluene for oil extraction from which the most appropriate solvents, extraction yields and the extracts quality were determined. The percentage of oleoresin extraction yield was found highest in methanol (6.97 %) followed by ethanol (6.85 % w/w). Meanwhile, the gaharu oil was found higher in toluene extract (1.06 %) compared to n-hexane (0.38 % w/w). The GC-MS results showed the extracts from ethanol and n-hexane solvents are the best quality due to the present of key compounds of 4-phenyl-2-butanone, β-guaiene, agarospirol, α–bisabolene, alloaromadendrene oxide, γ-Gurjunen and aromadenderene oxide. Different chemical component in gaharu oil determines the characteristic or quality of the gaharu. Meanwhile, the sesquiterpene compounds in gaharu produce its specialty aroma characteristics. Therefore, ethanol and n-hexane solvents are suitable to be used for oleoresin and oil extraction beside less expensive and more environmental-friendly.

Indonesia is the world’s second largest producer of coconut. This at the same time resulted in huge generation of coconut shell waste that need to be properly managed to prevent environmental contamination such as water, air and soil pollution. Current techniques of physical and thermal processing are time and energy consuming. This study reports on the conversion of coconut shell biomass into biochar using microwave-assisted pyrolysis (MAP). The MAP processes were carried out at different microwave power (550-650W) and residence time (15-25 minutes). Two of the highest biochar yields were obtained at 550W with the residence times of 15 minutes (91.31 wt%, termed as S1) and 20 minutes (83.88 wt%, termed as S2), respectively. Both values were higher than biochar yield obtained using conventional pyrolysis process i.e. 30.10 wt%. Both S1 and S2 showed considerable capacity to remove 0.6875 mg.g-1 and 0.5165 mg.g-1 methylene blue which had the initial concentration of 25 mg.L-1. The adsorption efficiencies of S1 and S2 biochars were 55.00% and 41.32%, respectively. Results obtained from the FTIR, FESEM and BET analysis also supported the methylene blue removal properties of both S1 and S2, respectively. As a conclusion, coconut shell showed potential as a useful raw material to produce biochar that can be used for methylene blue removal from solution. Nevertheless, more investigation need to be carried out prior to commercialization venture of the coconut-shell based biochar.

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

The agro-industrial sector in Malaysia generates a significant amount of biomass solid wastes, particularly from palm oil mills which produce enormous amount of biomass that includes empty fruit bunches (EFB), palm kernel shells (PKS), oil palm fibers (OPF), and palm oil mill effluents (POME). Oil palm fronds (leaves stem) are available from the plantation during trimming process, and oil palm trunks are available when the plantation are removing old palm trees for new oil palm cultivation. At present, the fibers and shells are utilized (in weight ratio) in boilers for steam generation in most palm oil mills, whereas empty fruit bunches are being utilized as organic fertilizer and mulching purposes. Thus, there are huge challenges as well as opportunities on the development to utilize these abundant biomass resources. The oil palm biomass appears to be the most promising and potential renewable feedstock for the recovery of various fuels and chemicals.

Xanthones are phytochemical compounds found in a number of fruits and vegetables. Characteristically, they are noted to be made of diverse properties based on their biological, biochemical, and pharmacological actions. Accordingly, the apoptosis mechanisms induced by beta-mangostin, a xanthone compound isolated from Cratoxylum arborescens in the human promyelocytic leukemia cell line (HL60) in vitro, were examined in this study. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was done to estimate the cytotoxicity effect of β-mangostin on the HL60 cell line. Acridine orange/propidium iodide and Hoechst 33342 dyes and Annexin V tests were conducted to detect the apoptosis features. Caspase-3 and caspase-9 activities; reactive oxygen species; real-time polymerase chain reaction for Bcl-2, Bax, caspase-3, and caspase-9 Hsp70 genes; and western blot for p53, cytochrome c, and pro- and cleavage-caspase-3 and caspase-9 were assessed to examine the apoptosis mechanism. Cell-cycle analysis conducted revealed that β-mangostin inhibited the growth of HL60 at 58 µM in 24 h. The administration of β-mangostin with HL60 caused cell morphological changes related to apoptosis which increased the number of early and late apoptotic cells. The β-mangostin-catalyzed apoptosis action through caspase-3, caspase-7, and caspase-9 activation overproduced reactive oxygen species which downregulated the expression of antiapoptotic genes Bcl-2 and HSP70. Conversely, the expression of the apoptotic genes Bax, caspase-3, and caspase-9 were upregulated. Meanwhile, at the protein level, β-mangostin activated the formation of cleaved caspase-3 and caspase-9 and also upregulated the p53. β-mangostin arrested the cell cycle at the G

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

Xanthones are phytochemical compounds found in a number of fruits and vegetables. Characteristically, they are noted to be made of diverse properties based on their biological, biochemical, and pharmacological actions. Accordingly, the apoptosis mechanisms induced by beta-mangostin, a xanthone compound isolated from Cratoxylum arborescens in the human promyelocytic leukemia cell line (HL60) in vitro, were examined in this study. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was done to estimate the cytotoxicity effect of β-mangostin on the HL60 cell line. Acridine orange/propidium iodide and Hoechst 33342 dyes and Annexin V tests were conducted to detect the apoptosis features. Caspase-3 and caspase-9 activities; reactive oxygen species; real-time polymerase chain reaction for Bcl-2, Bax, caspase-3, and caspase-9 Hsp70 genes; and western blot for p53, cytochrome c, and pro- and cleavage-caspase-3 and caspase-9 were assessed to examine the apoptosis mechanism. Cell-cycle analysis conducted revealed that β-mangostin inhibited the growth of HL60 at 58 µM in 24 h. The administration of β-mangostin with HL60 caused cell morphological changes related to apoptosis which increased the number of early and late apoptotic cells. The β-mangostin-catalyzed apoptosis action through caspase-3, caspase-7, and caspase-9 activation overproduced reactive oxygen species which downregulated the expression of antiapoptotic genes Bcl-2 and HSP70. Conversely, the expression of the apoptotic genes Bax, caspase-3, and caspase-9 were upregulated. Meanwhile, at the protein level, β-mangostin activated the formation of cleaved caspase-3 and caspase-9 and also upregulated the p53. β-mangostin arrested the cell cycle at the G 0 /G 1 phase. Overall, the results for β-mangostin showed an antiproliferative effect in HL60 via stopping the cell cycle at the G 0 /G 1 phase and prompted the intrinsic apoptosis pathway.

Natural medicinal products possess diverse chemical structures and have been an essential source for drug discovery. Therefore, in this study, α-mangostin (AM) is a plant-derived compound was investigated for the apoptotic effect on human cervical cancer cells (HeLa). The cytotoxic effects of AM on the viability of HeLa and human normal ovarian cell line (SV40) were evaluated by using MTT assay. Results showed that AM inhibited HeLa cells viability at concentration- and time-dependent manner with IC50 value of 24.53 ± 1.48 µM at 24 h. The apoptogenic effects of AM on HeLa were assessed using fluorescence microscopy analysis. The effect of AM on cell proliferation was also studied through clonogenic assay. ROS production evaluation, flow cytometry (cell cycle) analysis, caspases 3/7, 8, and 9 assessment and multiple cytotoxicity assays were conducted to determine the mechanism of cell apoptosis. This was associated with G2/M phase cell cycle arrest and elevation in ROS production. AM induced mitochondrial apoptosis which was confirmed based on the significant increase in the levels of caspases 3/7 and 9 in a dose-dependent manner. Furthermore, the MMP disruption and increased cell permeability, concurrent with cytochrome c release from the mitochondria to the cytosol provided evidence that AM can induce apoptosis via mitochondrial-dependent pathway. AM exerted a remarkable antitumor effect and induced characteristic apoptogenic morphological changes on HeLa cells, which indicates the occurrence of cell death. This study reveals that AM could be a potential antitumor compound on cervical cancer in vitro and can be considered for further cervical cancer preclinical and in vivo testing.

Improper management of lignocellulosic biomass generated from agricultural activities would lead to serious environmental problems. Pyrolysis offers a simple yet efficient alternative technique where Pyroligneous acid (PA) is a major by-product obtained during slow pyrolysis of lignocellulosic biomass. In this study, the potential anti-termites and anti-fungal properties for PA obtained from the pyrolysis of pineapple waste biomass were investigated. PA from pineapple waste biomass showed insignificant inhibition properties against both Pycnoporus sanguineus and Coriolus versicolor, but were successful in inhibiting the growth of both Aspergillus niger and Botryodiplodia theobromae for 7 days when applied at 70% (v/v) and 100% (v/v) concentrations. PA also exhibited good anti-termites properties based on the 100% mortality of Coptotermes curvignathus after one week incubation. GC-MS analysis revealed the presence of phenolic compounds and phenol with ortho substituents such as 2,6-dimethoxyphenol and 2-methoxy-4-methylphenol. Both compounds have been reported to play an important role in termiticidal activity from previous studies. This study indicates that PA from pineapple waste can act as antifungal and antitermite agents but not as anti-wood decaying fungi. This result can be used as a good preliminary indication for future application of PA from pineapple waste biomass as wood preservative.

Phytochemical and biological studies were carried out the stem bark of Cratoxylum arborescens collected from Sarawak, Malaysia. Chromatographic separation of the plant extracts led to the isolation of three xanthones, ii-mangostin (1), i¢-mangostin (2) and fuscaxanthone C (3) together with the commom stigmasterol. The structural elucidation of the compound was determined by detail spectroscopic analysis and comparison with literature reports. ii-Mangostin exhibited strong inhibition on the growth of bacteria, B. subtilis, B. cereus, S. typhimurium and S. aureus with inhibition zone of 16, 20, 17 and 20 mm, respectively. Both I±-mangostin and i¢-mangostin showed the most significant cytotoxic activity against MCF7 cells with IC50 values of 12.48 µg/ml and 28.42 µg/ml, respectively. However, when tested for antioxidant activity by using DPPH, the extracts and the xanthones failed to give good results. (Keywords: ii-Mangostin; i¢-Mangostin; Fuscaxanthone C; Cratoxylum arborescens; Antimicrobial; Cytotoxicity; Antioxidant )

One of the most promising plants in biological screening test results of thirteen Artocarpus species was Artocarpus obtusus FM Jarrett and detailed phytochemical investigation of powdered dried bark of the plant has led to the isolation and identification of three xanthones; pyranocycloartobiloxanthone A (1), dihydroartoindonesianin C (2) and pyranocycloartobiloxanthone B (3). These compounds were screened for antioxidant, antimicrobial and tyrosinase inhibitory activities. Pyranocycloartobiloxanthone A (1) exhibited a strong free radical scavenger towards DPPH free radicals with IC50 value of 2 µg/mL with prominent discoloration observed in comparison with standard ascorbic acid, α-tocopherol and quercetin, The compound also exhibited antibacterial activity against methicillin resistant Staphylococcus aureus (ATCC3359) and Bacillus subtilis (clinically isolated) with inhibition zone of 20 and 12 mm, respectively. However the other two xanthones were found to be inactive. For the tyrosinase inhibitory activity, again compound (1) displayed strong activity comparable with the standard kojic acid.

One of the most promising plants in biological screening test results of thirteen Artocarpus species was Artocarpus obtusus FM Jarrett and detailed phytochemical investigation of powdered dried bark of the plant has led to the isolation and identification of three xanthones; pyranocycloartobiloxanthone A (1), dihydroartoindonesianin C (2) and pyranocycloartobiloxanthone B (3). These compounds were screened for antioxidant, antimicrobial and tyrosinase inhibitory activities. Pyranocycloartobiloxanthone A (1) exhibited a strong free radical scavenger towards DPPH free radicals with IC50 value of 2 µg/mL with prominent discoloration observed in comparison with standard ascorbic acid, α-tocopherol and quercetin, The compound also exhibited antibacterial activity against methicillin resistant Staphylococcus aureus (ATCC3359) and Bacillus subtilis (clinically isolated) with inhibition zone of 20 and 12 mm, respectively. However the other two xanthones were found to be inactive. For the tyrosinase inhibitory activity, again compound (1) displayed strong activity comparable with the standard kojic acid.

Xanthones are phytochemical compounds found in a number of fruits and vegetables. Characteristically, they are noted to be made of diverse properties based on their biological, biochemical, and pharmacological actions. Accordingly, the apoptosis mechanisms induced by beta-mangostin, a xanthone compound isolated from Cratoxylum arborescens in the human promyelocytic leukemia cell line (HL60) in vitro, were examined in this study. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was done to estimate the cytotoxicity effect of β-mangostin on the HL60 cell line. Acridine orange/propidium iodide and Hoechst 33342 dyes and Annexin V tests were conducted to detect the apoptosis features. Caspase-3 and caspase-9 activities; reactive oxygen species; real-time polymerase chain reaction for Bcl-2, Bax, caspase-3, and caspase-9 Hsp70 genes; and western blot for p53, cytochrome c, and pro- and cleavage-caspase-3 and caspase-9 were assessed to examine the apoptosis mechanism. Cell-cycle analysis conducted revealed that β-mangostin inhibited the growth of HL60 at 58 µM in 24 h. The administration of β-mangostin with HL60 caused cell morphological changes related to apoptosis which increased the number of early and late apoptotic cells. The β-mangostin-catalyzed apoptosis action through caspase-3, caspase-7, and caspase-9 activation overproduced reactive oxygen species which downregulated the expression of antiapoptotic genes Bcl-2 and HSP70. Conversely, the expression of the apoptotic genes Bax, caspase-3, and caspase-9 were upregulated. Meanwhile, at the protein level, β-mangostin activated the formation of cleaved caspase-3 and caspase-9 and also upregulated the p53. β-mangostin arrested the cell cycle at the G0/G1 phase. Overall, the results for β-mangostin showed an antiproliferative effect in HL60 via stopping the cell cycle at the G0/G1 phase and prompted the intrinsic apoptosis pathway.

Mohamed Yousif Ibrahim,1 Najihah Mohd Hashim,1 Syam Mohan,2 Mahmood Ameen Abdulla,3 Behnam Kamalidehghan,1 Mostafa Ghaderian,1,4 Firouzeh Dehghan,1,5 Landa Zeenelabdin Ali,1 Ismail Adam Arbab,6 Maizatulakmal Yahayu,7 Gwendoline Ee Cheng Lian,8 Fatemeh Ahmadipour,1 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, 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; 6School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Selangor, Malaysia; 7Department of Bioproduct Research and Innovation, Institute of Bioproduct Development (IBD), Universiti Teknologi Malaysia, Johor, Malaysia; 8Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Selangor, Malaysia; 9Department of Chemistry, University of Malaya, Kuala Lumpur, Malaysia Abstract: Cratoxylum arborescens is an equatorial plant belonging to the family Guttiferae. In the current study, α-Mangostin (AM) was isolated and its cell death mechanism was studied. HCS was undertaken to detect the nuclear condensation, mitochondrial membrane potential, cell permeability, and the release of cytochrome c. An investigation for reactive oxygen species formation was conducted using fluorescent analysis. To determine the mechanism of cell death, human apoptosis proteome profiler assay was conducted. In addition, using immunofluorescence and immunoblotting, the levels of Bcl-2-associated X protein (Bax) and B-cell lymphoma (Bcl)-2 proteins were also tested. Caspaces such as 3/7, 8, and 9 were assessed during treatment. Using HCS and Western blot, the contribution of nuclear factor kappa-B (NF-κB) was investigated. AM had showed a selective cytotoxicity toward the cancer cells with no toxicity toward the normal cells even at 30 µg/mL, thereby indicating that AM has the attributes to induce cell death in tumor cells. The treatment of MCF-7 cells with AM prompted apoptosis with cell death-transducing signals. This regulated the mitochondrial membrane potential by down-regulation of Bcl-2 and up-regulation of Bax, thereby causing the release of cytochrome c from the mitochondria into the cytosol. The liberation of cytochrome c activated caspace-9, which, in turn, activated the downstream executioner caspace-3/7 with the cleaved poly (ADP-ribose) polymerase protein, thereby leading to apoptotic alterations. Increase of caspace 8 had showed the involvement of an extrinsic pathway. This type of apoptosis was suggested to occur through both extrinsic and intrinsic pathways and prevention of translocation of NF-κB from the cytoplasm to the nucleus. Our results revealed AM prompt apoptosis of MCF-7 cells through NF-κB, Bax/Bcl-2 and heat shock protein 70 modulation with the contribution of caspaces. Moreover, ingestion of AM at (30 and 60 mg/kg) significantly reduced tumor size in an animal model of breast cancer. Our results suggest that AM is a potentially useful agent for the treatment of breast cancer. Keywords: α-Mangostin, apoptosis, mitochondria, protein array, caspace 3/7, NF-κB

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.

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.

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

An investigation of the chemical constituents inArtocarpus obtususspecies led to the isolation of three new xanthones, pyranocycloartobiloxanthone A (1), dihydroartoindonesianin C (2), and pyranocycloartobiloxanthone B (3). The compounds were subjected to antiproliferative assay against human promyelocytic leukemia (HL60), human chronic myeloid leukemia (K562), and human estrogen receptor (ER+) positive breast cancer (MCF7) cell lines. Pyranocycloartobiloxanthone A (1) consistently showed strong cytotoxic activity against the three cell lines compared to the other two with IC50values of 0.5, 2.0 and 5.0 μg/mL, respectively. Compound (1) was also observed to exert antiproliferative activity and apoptotic promoter towards HL60 and MCF7 cell lines at respective IC50values. The compound (1) was not toxic towards normal cell lines human nontumorigenic breast cell line (MCF10A) and human peripheral blood mononuclear cells (PBMCs) with IC50values of more than 30 μg/mL.

Extraction and chromatographic separation of the extracts of dried stem barks of Glycosmis macrantha lead to isolation of two new acridone alkaloids, macranthanine (1) and 7-hydroxynoracronycine (2), and a known acridone, atalaphyllidine (3). The structures of these alkaloids were determined by detailed spectral analysis and also by comparison with reported data.