Anti-malarial Activity of Isoquinoline Alkaloids from the Stem Bark of Actinodaphne macrophylla

Seven isoquinoline alkaloids isolated from the bark of Actinodaphne macrophylla in this study demonstrated in vitro antiplasmodial activities against Plasmodium falciparum 3D7 with IC50 values of 0.08 μM, 0.05 μM, 1.18 μM, 3.11 μM, 0.65 μM, 0.26 μM, and 1.38 μM for cycleanine, 10-demethylxylopinine, reticuline, laurotetanine, bicuculine, α-hydrastine and anolobine, respectively, which are comparable with the reference standard, chloroquine. 10-Demethylxylopinine was found to be the most active of these compounds

Phytochemical and biological studies of the extracts of Pseuduvaria Monticola and Pseuduvaria Macrophylla / Hairin Taha

The chemical constituents of two Pseuduvaria species from the Annonaceae family; Pseuduvaria monticola and Pseuduvaria macrophylla have been investigated. The extraction of the compounds from the bark and leaves was carried out using n-hexane, dichloromethane and methanol followed by chromatographic techniques such as column chromatography (CC), preparative thin layer chromatography (PTLC) and high performance liquid chromatography (HPLC). Structural elucidations of the compounds were established through spectroscopic methods; 1D-NMR (1H,13C, DEPT 135 ), 2D-NMR (COSY, HMQC, HMBC), UV, IR and MS (LC-MS, GC-MS) and comparison from the published data. The leaf essential oils were extracted by Clavenger-type apparatus and analyzed by GC-MSTOF. A total of 29 chemical constituents ( 3, 39, 40, 4, 41, 42, 43, 14, 15, 32, 44, 45, 46, 47, 48, 39, 10, 5, 7, 16, 49, 26, 50, 52, 53, 54, 55) including 2 new compounds (32, 51) were isolated and elucidated from both species. 15 chemical compounds were isolated from the bark and leaves of Pseuduvaria monticola. They are four oxoaporphine alkaloids; liriodenine (3), lysicamine (39), oxoputerine (40), ouregidione (4), two phenanthrene alkaloids; atherosperminine (41) and argentinine (42), one sesquiterpene; tau cadinol (43), three benzopyran derivatives; oligandrol (14), (6E,10E) isopolycerasoidol (15), (6E,10E) isopolycerasoidol methyl ester (a new compound) (32), two phenolic acids; caffeic acid (44) and chlorogenic acid (45), two fatty acids; n-hexadecanoic acid (46), methyl oleate (47) and one sterol; stigmasterol (48). From Pseuduvaria macrophylla, 14 compounds were isolated from the leaves and bark. They are one new compound; 1,3,5,7-tetramethoxy-2-naphthoic acid (51), five oxoaporphine alkaloids; liriodinine (3), lysicamine (39) atherospermidine (10), N-methyl ouregidione (5) and O-methylmoschatoline (7), two benzopyran derivatives; polycerasoidol (16) and polycerasoidin (49), two phenyl propanoids; elimicin (26) and elimicin 6-methoxy (50), two sterols; β-sitosterol (52) and stigmasta-5,22-diene, 3 methoxy (53) and two fatty acids; oleic acid (54) and n-hexadecanoic acid methyl ester (55). The major compounds in the leaf essential oils of Pseuduvaria monticola were alpha cadinol (56) (13.0 %), cis-calamenene (57) (6.9 %) and alpha copaene (25) (4 %) whereas the major compounds in the leaf essential oils of Pseuduvaria macrophylla were caryophyllene oxide (29) (29.7 %) and elimicin (26) (28 %). In DPPH assay, polycerasoidol (16) and (6E,10E) isopolycerasoidol (15) demonstrated good antioxidant activity (IC50 of 18.89 μg/mL and 22.56 μg/mL) respectively, compared to quercetin (IC50 7.01 μg/mL ). Leaf essential oil of Pseuduvaria macrophylla exhibited slightly greater antioxidant activity than that of Pseuduvaria monticola. In anticancer activity, (6E, 10E) isopolycerasoidol (15) and (6E,10E) isopolycerasoidol methyl ester (32) demonstrated cytotoxic effects on MCF-7 and MDA-MB-231 human breast cancer cells (IC50 59 ± 5.1, 43 ± 2.4 and 76 ± 8.5, 58 ± 2.6 respectively) and induced apoptosis. In antidiabetic study, the bark methanolic extract of Pseuduvaria monticola induced the glucose uptake and insulin secretion of mouse pancreatic β-cell line (NIT-1) and upregulated insulin secretion and downregulated oxidative stress and hyperglycemia in STZ-nicotinamide-induced type 2 diabetic rats whereas the methanol extract of Pseuduvaria macrophylla upregulated insulin and C-peptide levels and down-regulated hyperglycemia and oxidative stress in STZ-nicotinamide-induced type 2 diabetic rats

Phytochemical and biological activity study on Pseuduvaria Rugosa (annonaceae) / Hairin Taha

The study of phytochemical constituents on the bark of Pseuduvaria Rugosa from the family Annonaceae has resulted in the isolation and characterization of aporphine alkaloids, benzo[7]annulene and tripenoids. Six aporphine alkaloids have been isolated from the dichloromethane and methanol crude extract of which three of them are new compounds. The known alkaloids were liriodenine 1, ouregidione 5, and Nmethylouregidione 11, whereas the new alkaloids were 3-amino-1,2-dimethoxy-4,5- dioxoaporphine (pseuduvarine A) 36, N-methyl-3-amino-1,2-dimethoxy-4,5- dioxoaporphine (pseuduvarine B) 37 and 3-hydroxy-1,2-dimethoxy-3,4-dioxoaporphine (pseuduvarine C) 38. The aporphine alkaloids with a substituted amino group at position C-3 in ring A have never been discovered in any plant species before. One compound with the benzo[7]annulene skeleton has been isolated from the methanol extract in very miniscule amount. The structural elucidation of this compound was done based on the mass spectroscopy spectrum and from the fragmentation pattern, this compound was identified as 1-hydroxy-2,3,9-trimethoxy-9-methyl-5H-benzo[7]annulene-5,6,7,8,(9H)- tetraone or Pseuduvarin 39. This compound is a novel compound and has never been isolated before. From the hexane extract, some of the compounds identified by GCMS were terpenoids and most of them were sesquiterpenes and diterpene including fatty acid esters. The major compounds found in the hexane extract were isoelemicin 40, 1,2,3,4-tetramethoxy- 5-(2-propenyl)benzene 41 and 3-hydroxy-1-propenyl-2- methoxyphenol 42. The other compounds are elemicin 24, spathulenol 29 and caryophyllene oxide 30. The sterol compounds found were stigmasterol 43 and gamma sitosterol 44.This thesis also investigated the antioxidant and cytotoxic activities of the crude extracts and isolated compounds from Pseuduvaria Rugosa. The crude extracts and isolated compounds with sufficient quantities were tested for their radical scavenging activity using DPPH method and cytotoxic activity against selected cancer cell lines using the MTS and MTT assay. Preliminary bioactivity screening showed that the hexane, dichloromethane and methanol extracts of Pseuduvaria rugosa displayed weak to moderate activities in the radical scavenging activity but exhibited significant cytotoxic activities against seven cancer cell lines with more than 80% of cell death at 100 μg/ml. Ouregidione, N-methylouregidione and pseuduvarine C showed moderate cytotoxic activity on seven cancer cell lines. Pseuduvarine A and pseuduvarine B showed potent cytotoxicity against human cancer cell lines, MCF7 (IC50 : 0.9 μM, >50.0 μM), HepG2 (IC50: 21.7 μM, 15.7 μM) and HL-60 cells (IC50 : >50 μM, 12.4 μM)

The energy charts for occupants’ behavioural improvement through BIM

BIM is an easy method to design sustainable buildings for professionals like architects and engineers. By using the real measurable environment, software tools can shape building concepts such as geometry, spatial relations, geographical details and the design of structural composites and buildings, and the usage of energy annual like energy costs and life-cycle costs can be estimated and calculated. This study revealed the findings of the energy consumption within one year can provide valuable insights into the projected resources in the UNITEN Administrative Building. The application of these data would simplify energy cost calculation, an essential component of the costs of operating a property. With the purpose of maximizing energy efficiency in green buildings, the outcomes can be used as guidance to advice occupant management in optimizing occupant actions

Characterization of carbonate rocks using seismic wave for tunnel design stability

The design and construction of a tunnel depends on the mechanical properties of the rock mass around the tunnel. Seismic method can be used to characterize the dynamic properties of rocks. The technique is mostly conducted in geophysical surveys and geotechnical investigations. The method utilizes reflected sound waves that can be used to describe the dynamic properties of rocks. Physical properties of carbonate rocks such as water content, density, hardness, permeability, porosity, wave velocity and abrasivity can be assessed and estimated using P-wave velocity. One of the important characteristics in rock is its ability to remain stable. In this research, seismic refraction survey was applied to measure the strength of carbonate rocks for tunnel stability design. The findings revealed that the regression between the primary velocity and the uniaxial compressive strength R2 was 0.8592, indicating that the rock was firm and solid. Observation by physical visual test showed that the rock samples with yellowish-grey and light grey colours were categorized in the weathering grade II and III, respectively. The results have concluded that the rocks in the proposed area met the full requirements for tunnelling construction

Factors influencing the compliance of workplace safety culture in the government linked company (GLC)

This research focused on five factors; the management commitments towards safety, availability of safety rules and procedures, safety communication and feedback, the effectiveness of safety training, and the acquisition of safety knowledge that contributes to compliance of safety culture in the government-linked companies (GLC), by exploring various dimensions by which converge into achieving organizational safety performance outcomes. The importance of safety performance in the GLC is to ensure the employees have the right safety culture, a safe working environment, and comply with safety rules and procedures. The contribution of the findings of this study may provide knowledge of existing safety management practices in Malaysia’s Government Linked Company (GLC) and facilitate the organizations in evaluating the importance of safety management on their performance. This study also emphasizes the relationship between the five factors mentioned towards the compliance of safety culture in the organization. Besides that, it also provides an empirical review on which components of safety management practices have a better relationship with the organizational safety culture. Based on the results obtained, there is a positive correlation between management commitments towards safety, availability of safety rules and procedures, safety communication and feedback, the effectiveness of safety training, and acquisition of safety knowledge with regards to employees’ safety compliance towards a better safety culture in the organization

Impact of employee age and work experience on safety culture at workplace

Occupational accidents can be caused by different factors and can have many consequences, such as minor or fatal injury, equipment damage, permanent disability, or, in some cases, fatality. Therefore, it is essential to identify the causes of accidents to prevent them from recurring in the future and minimize injury, ill-health, and business costs. It is crucial, by determining the causes of the incident in the workplace, to analyse those that happened and take practical preventive steps to minimize the likelihood of them occurring again. A safe and accident-free working environment can allow the company to function efficiently and effectively. This study examined whether the age and experience of the employees, as determined by the demographics, have significant differences in the mean scores of the compliance towards safety culture within the company

Persea declinata (Bl.) Kosterm Bark Crude Extract Induces Apoptosis in MCF-7 Cells via G0/G1 Cell Cycle Arrest, Bcl-2/Bax/Bcl-xl Signaling Pathways, and ROS Generation

Persea declinata (Bl.) Kosterm is a member of the Lauraceae family, widely distributed in Southeast Asia. It is from the same genus with avocado (Persea americana Mill), which is widely consumed as food and for medicinal purposes. In the present study, we examined the anticancer properties of Persea declinata (Bl.) Kosterm bark methanolic crude extract (PDM). PDM exhibited a potent antiproliferative effect in MCF-7 human breast cancer cells, with an IC50 value of 16.68 µg/mL after 48 h of treatment. We observed that PDM caused cell cycle arrest and subsequent apoptosis in MCF-7 cells, as exhibited by increased population at G0/G1 phase, higher lactate dehydrogenase (LDH) release, and DNA fragmentation. Mechanistic studies showed that PDM caused significant elevation in ROS production, leading to perturbation of mitochondrial membrane potential, cell permeability, and activation of caspases-3/7. On the other hand, real-time PCR and Western blot analysis showed that PDM treatment increased the expression of the proapoptotic molecule, Bax, but decreased the expression of prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner. These findings imply that PDM could inhibit proliferation in MCF-7 cells via cell cycle arrest and apoptosis induction, indicating its potential as a therapeutic agent worthy of further development

Quantitative LC/MS/MS analysis of acetaminophen–cysteine adducts (APAP–CYS) and its application in acetaminophen overdose patients

A more sensitive approach by liquid chromatography–tandem mass spectrometry (LC/MS/MS) method using the AB Sciex QTRAP 5500 was developed and validated for the detection and quantification of acetaminophen–cysteine adducts (APAP–CYS) in human plasma. Chromatographic separation was achieved using a Protecol P C18 column (2.1 mm i.d. × 100 mm, 3 microns). The mobile phase consists of A: 2 mM ammonium formate in water (0.2% formic acid) and B: 2 mM ammonium formate in acetonitrile (0.2% formic acid). The analysis was performed using positive and negative ion electrospray ionization (ESI) in multiple reaction monitoring mode (MRM) with a total run time of 7 min per assay. The MS/MS ion transitions monitored were m/z 271 → 140 for APAP–CYS (positive mode) and m/z 154 → 111 for acetaminophen-D4 (negative mode). The newly developed method showed good linearity in the range of 1.0 to 100 ng mL−1. Inter and intra batch precision and accuracy of the method ranged from 0.28 to 5.30% and 87.0 to 113% respectively. LOD was 0.5 ng mL−1 and LLOQ was 1.0 ng mL−1. Analytes were extracted from plasma samples by simple protein precipitation using acetonitrile. The method was successfully applied in a preliminary clinical study to determine APAP–CYS concentration from 46 acetaminophen overdose patients treated at outpatient clinic in the University Malaya Medical Centre