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Metabolite variations and antioxidant activity of Muntingia calabura leaves in response to different drying methods and ethanol ratios elucidated by NMR-based metabolomics

Zolkeflee NKZ, Isamail NA, Maulidiani M, Abdul Hamid NA, Ramli NS, Azlan A, et al.

Phytochem Anal, 2021 Jan;32(1):69-83.
PMID: 31953888 DOI: 10.1002/pca.2917

INTRODUCTION: Muntingia calabura from the Muntingiaceae family has been documented for several medicinal uses. The combinations of drying treatment and extracting solvents for a plant species need to be determined and optimised to ensure that the extracts contain adequate amounts of the bioactive metabolites.
OBJECTIVE: Evaluate the metabolite variations and antioxidant activity among M. calabura leaves subjected to different drying methods and extracted with different ethanol ratios using proton nuclear magnetic resonance (1 H-NMR)-based metabolomics. Methodology The antioxidant activity of M. calabura leaves dried with three different drying methods and extracted with three different ethanol ratios was determined by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) scavenging assays. The metabolites variation among the extracts and correlation with antioxidant activity were analysed by 1 H-NMR-based metabolomics.
RESULTS: Muntingia calabura leaves extracted with 50% and 100% ethanol from air-drying and freeze-drying methods had the highest total phenolic content and the lowest IC50 value for the DPPH scavenging activity. Meanwhile, oven-dried leaves extracted with 100% ethanol had the lowest IC50 value for the NO scavenging activity. A total of 43 metabolites, including sugars, organic acids, amino acids, phytosterols, phenolics and terpene glycoside were tentatively identified. A noticeable discrimination was observed in the different ethanol ratios by the principal component analysis. The partial least-squares analysis suggested that 32 compounds out of 43 compounds identified were the contributors to the bioactivities.
CONCLUSION: The results established set the preliminary steps towards developing this plant into a high value product for phytomedicinal preparations.
Fulltext NMR and LCMS analytical platforms exhibited the nephroprotective effect of Clinacanthus nutans in cisplatin-induced nephrotoxicity in the in vitro condition

Mahmod II, Ismail IS, Alitheen NB, Normi YM, Abas F, Khatib A, et al.

BMC Complement Med Ther, 2020 Oct 22;20(1):320.
PMID: 33092571 DOI: 10.1186/s12906-020-03067-3

BACKGROUND: Clinacanthus nutans (C. nutans) Lind. locally known as Belalai Gajah or Sabah snake grass is a medicinal plant belonging to Acanthaceae family. In Asia, this plant is traditionally used for treating skin rashes, insects and snake bites, diabetes mellitus, fever and for diuretic effect. C. nutans has been reported to possess biological activities including anti-oxidant, anti-inflammation, anti-cancer, anti-diabetic and anti-viral activities.
METHODS: Proton Nuclear Magnetic Resonance (1H NMR) and Liquid Chromatography Mass Spectroscopy (LCMS) coupled with multivariate data analysis were employed to characterize the metabolic variations of intracellular metabolites and the compositional changes of the corresponding culture media in rat renal proximal tubular cells (NRK-52E).
RESULTS: NMR and LCMS analysis highlighted choline, creatine, phosphocholine, valine, acetic acid, phenylalanine, leucine, glutamic acid, threonine, uridine and proline as the main metabolites which differentiated the cisplatin-induced group of NRK-52E from control cells extract. The corresponding media exhibited lactic acid, glutamine, glutamic acid and glucose-1-phosphate as the varied metabolites. The altered pathways perturbed by cisplatin nephrotoxic on NRK-52E cells included changes in amino acid metabolism, lipid metabolism and glycolysis.
CONCLUSION: The C. nutans aqueous extract (1000 μg/mL) exhibited the most potential nephroprotective effect against cisplatin toxicity on NRK-52E cell lines at 89% of viability. The protective effect could be seen through the changes of the metabolites such as choline, alanine and valine in the C. nutans pre-treated samples with those of the cisplatin-induced group.
Fulltext Mechanistic Understanding of Curcumin's Therapeutic Effects in Lung Cancer

Wan Mohd Tajuddin WNB, Lajis NH, Abas F, Othman I, Naidu R

Nutrients, 2019 Dec 06;11(12).
PMID: 31817718 DOI: 10.3390/nu11122989

Lung cancer is among the most common cancers with a high mortality rate worldwide. Despite the significant advances in diagnostic and therapeutic approaches, lung cancer prognoses and survival rates remain poor due to late diagnosis, drug resistance, and adverse effects. Therefore, new intervention therapies, such as the use of natural compounds with decreased toxicities, have been considered in lung cancer therapy. Curcumin, a natural occurring polyphenol derived from turmeric (Curcuma longa) has been studied extensively in recent years for its therapeutic effects. It has been shown that curcumin demonstrates anti-cancer effects in lung cancer through various mechanisms, including inhibition of cell proliferation, invasion, and metastasis, induction of apoptosis, epigenetic alterations, and regulation of microRNA expression. Several invitro and invivo studies have shown that these mechanisms are modulated by multiple molecular targets such as STAT3, EGFR, FOXO3a, TGF-β, eIF2α, COX-2, Bcl-2, PI3KAkt/mTOR, ROS, Fas/FasL, Cdc42, E-cadherin, MMPs, and adiponectin. In addition, limitations, strategies to overcome curcumin bioavailability, and potential side effects as well as clinical trials were also reviewed.
Fulltext Effective refolding of a cysteine rich glycoside hydrolase family 19 recombinant chitinase from Streptomyces griseus by reverse dilution and affinity chromatography

Oyeleye AO, Mohd Yusoff SF, Abd Rahim IN, Leow ATC, Saidi NB, Normi YM

PLoS One, 2020;15(10):e0241074.
PMID: 33091044 DOI: 10.1371/journal.pone.0241074

Conventional refolding methods are associated with low yields due to misfolding and high aggregation rates or very dilute proteins. In this study, we describe the optimization of the conventional methods of reverse dilution and affinity chromatography for obtaining high yields of a cysteine rich recombinant glycoside hydrolase family 19 chitinase from Streptomyces griseus HUT6037 (SgChiC). SgChiC is a potential biocontrol agent and a reference enzyme in the study and development of chitinases for various applications. The overexpression of SgChiC was previously achieved by periplasmic localization from where it was extracted by osmotic shock and then purified by hydroxyapatite column chromatography. In the present study, the successful refolding and recovery of recombinant SgChiC (r-SgChiC) from inclusion bodies (IB) by reverse dilution and column chromatography methods is respectively described. Approximately 8 mg of r-SgChiC was obtained from each method with specific activities of 28 and 52 U/mg respectively. These yields are comparable to that obtained from a 1 L culture volume of the same protein isolated from the periplasmic space of E. coli BL21 (DE3) as described in previous studies. The higher yields obtained are attributed to the successful suppression of aggregation by a stepwise reduction of denaturant from high, to intermediate, and finally to low concentrations. These methods are straight forward, requiring the use of fewer refolding agents compared with previously described refolding methods. They can be applied to the refolding of other cysteine rich proteins expressed as inclusion bodies to obtain high yields of actively folded proteins. This is the first report on the recovery of actively folded SgChiC from inclusion bodies.
Fulltext Sex estimation using subpubic angle from reconstructed three-dimensional computed tomography pelvic model in a contemporary Malaysian population

Mohd Ali SH, Omar N, Shafie MS, Nik Ismail NA, Hadi H, Nor FM

Anat Cell Biol, 2020 Mar;53(1):27-35.
PMID: 32274246 DOI: 10.5115/acb.19.135

Research in forensic anthropology is recent in Malaysia due to limited access to documented skeletal collections. However, advanced imaging techniques provide virtual bone samples for use in morphometric studies to establish population-specific standards by virtual anthropology. This study examined sexual dimorphism in the subpubic angle using a three-dimensional computed tomography model of the pelvis, in a contemporary Malaysian population. The sample comprised multidetector computed tomography (MDCT) scans of 50 male and 50 female adults. Segmentation of the MDCT scans was performed using 3D Slicer, and four landmarks were acquired using Stratovan Checkpoint for the subpubic angle measurement. The technical error of measurement (TEM), relative TEM, and coefficient of reliability (R) exhibited high reliability in measurements. Results showed that the subpubic angle in males was 68.6°±7.6° and in females 87.4°±6.5°. The subpubic angle in females was significantly larger than in males (P<0.001). Inverse correlation was found between the subpubic angle and age, in both males (r=-0.449, P<0.01) and females (r=-0.385, P<0.01). The overall accuracy of sex estimation using the subpubic angle was 94% (P<0.001). The subpubic angle, with a demarcating point of 78.6°, showed a sensitivity and specificity of 94% in the classification of female individuals. In conclusion, sex estimation using the subpu bic angle is highly accurate, with a high degree of expected sensitivity and specificity in the Malaysian population.
Fulltext Mechanism of Anti-Cancer Activity of Curcumin on Androgen-Dependent and Androgen-Independent Prostate Cancer

Abd Wahab NA, Lajis NH, Abas F, Othman I, Naidu R

Nutrients, 2020 Mar 02;12(3).
PMID: 32131560 DOI: 10.3390/nu12030679

Prostate cancer (PCa) is a heterogeneous disease and ranked as the second leading cause of cancer-related deaths in males worldwide. The global burden of PCa keeps rising regardless of the emerging cutting-edge technologies for treatment and drug designation. There are a number of treatment options which are effectively treating localised and androgen-dependent PCa (ADPC) through hormonal and surgery treatments. However, over time, these cancerous cells progress to androgen-independent PCa (AIPC) which continuously grow despite hormone depletion. At this particular stage, androgen depletion therapy (ADT) is no longer effective as these cancerous cells are rendered hormone-insensitive and capable of growing in the absence of androgen. AIPC is a lethal type of disease which leads to poor prognosis and is a major contributor to PCa death rates. A natural product-derived compound, curcumin has been identified as a pleiotropic compound which capable of influencing and modulating a diverse range of molecular targets and signalling pathways in order to exhibit its medicinal properties. Due to such multi-targeted behaviour, its benefits are paramount in combating a wide range of diseases including inflammation and cancer disease. Curcumin exhibits anti-cancer properties by suppressing cancer cells growth and survival, inflammation, invasion, cell proliferation as well as possesses the ability to induce apoptosis in malignant cells. In this review, we investigate the mechanism of curcumin by modulating multiple signalling pathways such as androgen receptor (AR) signalling, activating protein-1 (AP-1), phosphatidylinositol 3-kinases/the serine/threonine kinase (PI3K/Akt/mTOR), wingless (Wnt)/ß-catenin signalling, and molecular targets including nuclear factor kappa-B (NF-κB), B-cell lymphoma 2 (Bcl-2) and cyclin D1 which are implicated in the development and progression of both types of PCa, ADPC and AIPC. In addition, the role of microRNAs and clinical trials on the anti-cancer effects of curcumin in PCa patients were also reviewed.
Fulltext The Potential of Insects as Alternative Sources of Chitin: An Overview on the Chemical Method of Extraction from Various Sources

Zainol Abidin NA, Kormin F, Zainol Abidin NA, Mohamed Anuar NAF, Abu Bakar MF

Int J Mol Sci, 2020 Jul 15;21(14).
PMID: 32679639 DOI: 10.3390/ijms21144978

Chitin, being the second most abundant biopolymer after cellulose, has been gaining popularity since its initial discovery by Braconot in 1811. However, fundamental knowledge and literature on chitin and its derivatives from insects are difficult to obtain. The most common and sought-after sources of chitin are shellfish (especially crustaceans) and other aquatic invertebrates. The amount of shellfish available is obviously restricted by the amount of food waste that is allowed; hence, it is a limited resource. Therefore, insects are the best choices since, out of 1.3 million species in the world, 900,000 are insects, making them the most abundant species in the world. In this review, a total of 82 samples from shellfish-crustaceans and mollusks (n = 46), insects (n = 23), and others (n = 13)-have been collected and studied for their chemical extraction of chitin and its derivatives. The aim of this paper is to review the extraction method of chitin and chitosan for a comparison of the optimal demineralization and deproteinization processes, with a consideration of insects as alternative sources of chitin. The methods employed in this review are based on comprehensive bibliographic research. Based on previous data, the chitin and chitosan contents of insects in past studies favorably compare and compete with those of commercial chitin and chitosan-for example, 45% in Bombyx eri, 36.6% in Periostracum cicadae (cicada sloughs), and 26.2% in Chyrysomya megacephala. Therefore, according to the data reported by previous researchers, demonstrating comparable yield values to those of crustacean chitin and the great interest in insects as alternative sources, efforts towards comprehensive knowledge in this field are relevant.
Fulltext Towards identification of important plant areas (IPA) for Peninsular Malaysia. Methodology and future directions

Hamidah M, Mohd Hasmadi I, Chua LSL, Lau KH, Faridah-Hanum I, Yong WSY, et al.

Heliyon, 2020 Jul;6(7):e04370.
PMID: 32642589 DOI: 10.1016/j.heliyon.2020.e04370

Malaysia is a megadiverse country and listed as one of the world's biodiversity hotspots. Land use changes and deforestation have led to the threat of, and extinction of plant species. In order to mitigate loss in population numbers, and to prevent species extinction events, Important Plant Areas (IPA) for Malaysia shall be identified. The identification of IPA is important to ensure that key natural areas are adequately protected and managed to preserve the species and its habitats. Currently, there are 1771 IPA identified globally and only seven tropical countries are actively involved excluding Malaysia. Inventory and biodiversity research are actively conducted in Malaysia, however, the initiative to identify IPA is still in its infancy. The first attempt for IPA identification was in the state of Terengganu by using herbarium database through scoring technique. In this paper, we discussed methods and criteria used in IPA identification globally. We also deliberated current IPA development in Terengganu and challenges such as collections biases and the need for a robust scoring technique to reduce judgement uncertainty. We suggested GIS based multi-criteria decision making, analytical hierarchy process and species distribution for Malaysian IPA. These strategies were considered to be effective tools in providing decision support for spatial planning aimed at plant conservation in Malaysia.
Fulltext Pharmacokinetics and Metabolism of Liposome-Encapsulated 2,4,6-Trihydroxygeranylacetophenone in Rats Using High-Resolution Orbitrap Liquid Chromatography Mass Spectrometry

Alkhateeb Y, Jarrar QB, Abas F, Rukayadi Y, Tham CL, Hay YK, et al.

Molecules, 2020 Jul 06;25(13).
PMID: 32640512 DOI: 10.3390/molecules25133069

2,4,6-trihydroxy-3-geranylacetophenone (tHGA) is a bioactive compound that shows excellent anti-inflammatory properties. However, its pharmacokinetics and metabolism have yet to be evaluated. In this study, a sensitive LC-HRMS method was developed and validated to quantify tHGA in rat plasma. The method showed good linearity (0.5-80 ng/mL). The accuracy and precision were within 10%. Pharmacokinetic investigations were performed on three groups of six rats. The first two groups were given oral administrations of unformulated and liposome-encapsulated tHGA, respectively, while the third group received intraperitoneal administration of liposome-encapsulated tHGA. The maximum concentration (Cmax), the time required to reach Cmax (tmax), elimination half-life (t1/2) and area under curve (AUC0-24) values for intraperitoneal administration were 54.6 ng/mL, 1.5 h, 6.7 h, and 193.9 ng/mL·h, respectively. For the oral administration of unformulated and formulated tHGA, Cmax values were 5.4 and 14.5 ng/mL, tmax values were 0.25 h for both, t1/2 values were 6.9 and 6.6 h, and AUC0-24 values were 17.6 and 40.7 ng/mL·h, respectively. The liposomal formulation improved the relative oral bioavailability of tHGA from 9.1% to 21.0% which was a 2.3-fold increment. Further, a total of 12 metabolites were detected and structurally characterized. The metabolites were mainly products of oxidation and glucuronide conjugation.
Fluorescence-based immunoassay for the detection of Xanthomonas oryzae pv. oryzae in rice leaf

Awaludin N, Abdullah J, Salam F, Ramachandran K, Yusof NA, Wasoh H

Anal Biochem, 2020 12 01;610:113876.
PMID: 32750357 DOI: 10.1016/j.ab.2020.113876

The identification of rice bacterial leaf blight disease requires a simple, rapid, highly sensitive, and quantitative approach that can be applied as an early detection monitoring tool in rice health. This paper highlights the development of a turn-off fluorescence-based immunoassay for the early detection of Xanthomonas oryzae pv. oryzae (Xoo), a gram-negative bacterium that causes rice bacterial leaf blight disease. Antibodies against Xoo bacterial cells were produced as specific bio-recognition molecules and the conjugation of these antibodies with graphene quantum dots and gold nanoparticles was performed and characterized, respectively. The combination of both these bio-probes as a fluorescent donor and metal quencher led to changes in the fluorescence signal. The immunoreaction between AntiXoo-GQDs, Xoo cells, and AntiXoo-AuNPs in the immuno-aggregation complex led to the energy transfer in the turn-off fluorescence-based quenching system. The change in fluorescence intensity was proportional to the logarithm of Xoo cells in the range of 100-105 CFU mL-1. The limit of detection was achieved at 22 CFU mL-1 and the specificity test against other plant disease pathogens showed high specificity towards Xoo. The detection of Xoo in real plant samples was also performed in this study and demonstrated satisfactory results.
Fulltext Correction to: An Evaluation of Malaysian Regulatory Process for New Active Substances Approved in 2017 Using the OpERA Methodology

Sani NM, McAuslane N, Kasbon SH, Ahmad R, Yusof FAM, Patel P

Ther Innov Regul Sci, 2020 Sep;54(5):1225-1226.
PMID: 32865806 DOI: 10.1007/s43441-020-00150-2

The authors have revised Figure 1. The revised figure is presented below.
Fulltext An Evaluation of Malaysian Regulatory Process for New Active Substances Approved in 2017 Using the OpERA Methodology

Sani NM, McAuslane N, Kasbon SH, Ahmad R, Yusof FAM, Patel P

Ther Innov Regul Sci, 2020 Sep;54(5):1215-1224.
PMID: 32865804 DOI: 10.1007/s43441-020-00140-4

INTRODUCTION: The National Pharmaceutical Regulatory Agency (NPRA) embarked on a regulatory-strengthening program and is evaluating its processes. Optimising Efficiencies in Regulatory Agencies (OpERA) is a regulatory-strengthening program that provides benchmarking data that can define performance targets and focus performance improvement. The objective of this study was to use OpERA methodology to determine where time is spent in the NPRA approval process and to form a baseline to measure the performance improvements.
METHODS: The OpERA tool was used to collect specific milestone data that identify time periods, review stages, and data points for new active substances and biosimilars approved by NPRA in 2017.
RESULTS: In 2017, 25 new active substances and 1 biosimilar were approved by NPRA in a median of 515 days, representing both agency and applicant time. The median time between dossier receipt and the initiation of NPRA scientific assessment was 135 days, but there was a wide variation in queuing time. The median total assessment time was 279 days (agency and applicant timing). NPRA took a median of 166 days; applicants took a median of 131 days to respond to deficiency questions, with up to 6 cycles of review required for approval and 65% of applications requiring 4-5 cycles to provide satisfactory responses.
CONCLUSIONS: As a result of these data, NPRA proposes three improvements: target start for scientific assessment 100 days after file acceptance, a maximum of 5 review cycles, and applicant response time limited to 6 months. These results will serve as a baseline for further assessment.
Complementary NMR- and MS-based metabolomics approaches reveal the correlations of phytochemicals and biological activities in Phyllanthus acidus leaf extracts

Abd Ghafar SZ, Mediani A, Maulidiani M, Rudiyanto R, Mohd Ghazali H, Ramli NS, et al.

Food Res Int, 2020 10;136:109312.
PMID: 32846521 DOI: 10.1016/j.foodres.2020.109312

Proton nuclear magnetic resonance (1H NMR)- and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS)-based analytical tools are frequently used in metabolomics studies. These complementary metabolomics platforms were applied to identify and quantify the metabolites in Phyllanthus acidus extracted with different ethanol concentrations. In total, 38 metabolites were tentatively identified by 1H NMR and 39 via UHPLC-MS, including 30 compounds are reported for the first time from this plant. The partial least square analysis (PLS) revealed the metabolites that contributed to α-glucosidase and nitric oxide (NO) inhibitory activities, including kaempferol, quercetin, myricetin, phyllanthusol A, phyllanthusol B, chlorogenic, catechin, cinnamic coumaric, caffeic, quinic, citric, ellagic and malic acids. This study shows the significance of combining 1H NMR- and UHPLC-MS-based metabolomics as the best strategies in identifying metabolites in P. acidus extracts and establishing an extract with potent antioxidant, anti-diabetic, and anti-inflammatory properties.
Fulltext The anti-neuroinflammatory effects of Clinacanthus nutans leaf extract on metabolism elucidated through 1H NMR in correlation with cytokines microarray

Ahmad Azam A, Ismail IS, Kumari Y, Shaikh MF, Abas F, Shaari K

PLoS One, 2020;15(9):e0238503.
PMID: 32925968 DOI: 10.1371/journal.pone.0238503

Clinacanthus nutans (CN) (Acanthaceae) is well-known for its anti-inflammatory properties among Asian communities; however, there are currently no data specifically focused on the anti-inflammatory effects of CN on the brain tissue. Neuroinflammation is a common consequence of toxin intrusion to any part of the central nervous system (CNS). As an innate immune response, the CNS may react through both protective and/or toxic actions due to the activation of neuron cells producing pro- and/or anti-inflammatory cytokines in the brain. The unresolved activation of the inflammatory cytokines' response is associated with the pathogenesis of neurological disorders. The present study aimed to decipher the metabolic mechanism on the effects of 14 days oral treatment with CN aqueous extract in induced-lipopolysaccharides (LPS) rats through 1H NMR spectroscopic biomarker profiling of the brain tissue and the related cytokines. Based on the principal component analysis (PCA) of the nuclear magnetic resonance (NMR) spectral data, twenty-one metabolites in the brain tissue were profiled as biomarkers for the LPS (10 μL)-induced neuroinflammation following intracerebroventricular injection. Among the twenty-one biomarkers in the neuroinflammed rats, CN treatment of 1000 and 500 mg/kg BW successfully altered lactate, pyruvate, phosphorylcholine, glutamine, and α-ketoglutarate when compared to the negative control. Likewise, statistical isolinear multiple component analysis (SIMCA) showed that treatments by CN and the positive control drug, dextromethorphan (DXM, 5 mg/kg BW), have anti-neuroinflammatory potential. A moderate correlation, in the orthogonal partial least squares (OPLS) regression model, was found between the spectral metabolite profile and the cytokine levels. The current study revealed the existence of high levels of pro-inflammatory cytokines, namely IL-1α, IL-1β, and TNF-α in LPS-induced rats. Both CN dose treatments lowered IL-1β significantly better than DXM Interestingly, DXM and CN treatments both exhibited the upregulation of the anti-inflammatory cytokines IL-2 and 4. However, DXM has an advantage over CN in that the former also increased the expression of IL-10 of anti-inflammatory cytokines. In this study, a metabolomics approach was successfully applied to discover the mechanistic role of CN in controlling the neuroinflammatory conditions through the modulation of complex metabolite interactions in the rat brain.
Metabolomic analysis reveals the valuable bioactive compounds of Ardisia elliptica

Wong PL, Ramli NS, Tan CP, Azlan A, Abas F

Phytochem Anal, 2021 Sep;32(5):685-697.
PMID: 33295100 DOI: 10.1002/pca.3015

INTRODUCTION: Ardisia elliptica Thunb. (Primulaceae) is a medicinal herb that is traditionally used for the treatment of fever, diarrhoea, measles and herpes. However, there is limited information regarding the correlation of its phytoconstituents with the bioactivity. Optimisation of solvent extraction is vital for maximising retention of bioactive molecules.
OBJECTIVE: This study investigated the metabolite variations in A. elliptica leaves and the correlation with antioxidant activities.
METHODOLOGY: Total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) radicals scavenging assays were performed on A. elliptica leaves extracted with four different ethanol ratios (0%, 50%, 70% and absolute ethanol). The correlation of metabolites with antioxidant activities was evaluated using a nuclear magnetic resonance (NMR)-based metabolomics approach.
RESULTS: The results showed that the 50% and 70% ethanolic extracts retained the highest TPC, and the 70% ethanolic extract was the most active, exhibiting half maximal inhibitory concentration (IC50 ) values of 10.18 ± 0.83 and 43.05 ± 1.69 μg/mL, respectively, in both radical scavenging assays. A total of 46 metabolites were tentatively identified, including flavonoids, benzoquinones, triterpenes and phenolic derivatives. The 50% and 70% ethanolic extracts showed similarities in metabolites content and were well discriminated from water and absolute ethanol extracts in a principal component analysis (PCA) model. Moreover, 31 metabolites were found to contribute significantly to the differentiation and antioxidant activity.
CONCLUSION: This study provides information on bioactive compounds in A. elliptica leaves, which is promising as a functional ingredient for food production or for the development of phytomedicinal products.
Fulltext Impact of Quercetin Encapsulation with Added Phytosterols on Bilayer Membrane and Photothermal-Alteration of Novel Mixed Soy Lecithin-Based Liposome

Toopkanloo SP, Tan TB, Abas F, Alharthi FA, Nehdi IA, Tan CP

Nanomaterials (Basel), 2020 Dec 05;10(12).
PMID: 33291386 DOI: 10.3390/nano10122432

This study used highly lipophilic agents with an aim to increase the oxidant inhibitory activity and enhance photothermal stability of a novel mixed soy lecithin (ML)-based liposome by changing the composition of formulation within the membrane. Specifically, the development and optimization of the liposome intended for improving Trolox equivalent antioxidant capacity (TEAC) value and %TEAC loss was carried out by incorporating a natural antioxidant, quercetin (QU). In this context, a focus was set on QU encapsulation in ML-based liposomes and the concentration-dependent solubility of QU was investigated and calculated as encapsulation efficiency (EE). To explore the combined effects of the incorporation of plant sterols on the integrity and entrapment capacity of mixed phospholipid vesicles, conjugation of two types of phytosterols (PSs), namely β-sitosterol (βS) and stigmasterol (ST), to mixed membranes at different ratios was also performed. The EE measurement revealed that QU could be efficiently encapsulated in the stable ML-based liposome using 0.15 and 0.1 g/100 mL of βS and ST, respectively. The aforementioned liposome complex exhibited a considerable TEAC (197.23%) and enhanced TEAC loss (30.81%) when exposed to ultraviolet (UV) light (280-320 nm) over a 6 h duration. It appeared that the presence and type of PSs affect the membrane-integration characteristics as well as photodamage transformation of the ML-based liposome. The association of QU with either βS or ST in the formulation was justified by their synergistic effects on the enhancement of the EE of liposomes. Parallel to this, it was demonstrated that synergistic PS effects could be in effect in the maintenance of membrane order of the ML-based liposome. The findings presented in this study provided useful information for the development and production of stable QU-loaded ML-based liposomes for food and nutraceutical applications and could serve as a potential mixed lipids-based delivery system in the disease management using antioxidant therapy.
Fulltext Improving Vesicular Integrity and Antioxidant Activity of Novel Mixed Soy Lecithin-Based Liposomes Containing Squalene and Their Stability against UV Light

Toopkanloo SP, Tan TB, Abas F, Azam M, Nehdi IA, Tan CP

Molecules, 2020 Dec 11;25(24).
PMID: 33322600 DOI: 10.3390/molecules25245873

In order to improve the membrane lipophilicity and the affinity towards the environment of lipid bilayers, squalene (SQ) could be conjugated to phospholipids in the formation of liposomes. The effect of membrane composition and concentrations on the degradation of liposomes prepared via the extrusion method was investigated. Liposomes were prepared using a mixture of SQ, cholesterol (CH) and Tween80 (TW80). Based on the optimal conditions, liposome batches were prepared in the absence and presence of SQ. Their physicochemical and stability behavior were evaluated as a function of liposome constituent. From the optimization study, the liposomal formulation containing 5% (w/w) mixed soy lecithin (ML), 0.5% (w/w) SQ, 0.3% (w/w) CH and 0.75% (w/w) TW80 had optimal physicochemical properties and displayed a unilamellar structure. Liposome prepared using the optimal formulation had a low particle size (158.31 ± 2.96 nm) and acceptable %increase in the particle size (15.09% ± 3.76%) and %trolox equivalent antioxidant capacity (%TEAC) loss (35.69% ± 0.72%) against UV light treatment (280-320 nm) for 6 h. The interesting outcome of this research was the association of naturally occurring substance SQ for size reduction without the extra input of energy or mechanical procedures, and improvement of vesicle stability and antioxidant activity of ML-based liposome. This study also demonstrated that the presence of SQ in the membrane might increase the acyl chain dynamics and decrease the viscosity of the dispersion, thereby limiting long-term stability of the liposome.
3D Rapid Prototyping Heart Model Validation for Teaching and Training - A Pilot Project in a Teaching Institution

Krishnasamy S, Mokhtar RAR, Singh R, Sivallingam S, Aziz YFA, Mathaneswaran V

Braz J Cardiovasc Surg, 2021 Oct 17;36(5):707-716.
PMID: 33438849 DOI: 10.21470/1678-9741-2020-0433

INTRODUCTION: Rapid prototyping is a process by which three-dimensional (3D) computerized surface models are converted into physical models. In this study, a 3D heart bio model was created using the rapid prototyping method and the accuracy of this heart model was assessed by clinicians.
METHODS: The two-dimensional images of normal heart from gated computed tomography scan datasets were used to create a 3D model of the heart. The slices were then processed using the software BioModroid and printed with the 3D printer. The evaluation of the model was performed by a questionnaire answered by four cardiothoracic surgeons, 12 cardiologists, five radiologists, and nine surgical registrars.
RESULTS: Eighty-six percent of the anatomy structures showed in this model scored 100% accuracy. Structures such as circumflex branch of left coronary artery, great cardiac vein, papillary muscle, and coronary sinus were each rated 77%, 70%, 70%, and 57% accurate. Among 30 clinicians, a total of 93% rated the model accuracy as good and above; 64% of the clinicians evaluated this model as an excellent teaching tool for anatomy class. As a visual aid for surgery or interventional procedures, the model was rated excellent (40%), good (50%), average (23%), and poor (3%); 70% of the clinicians scored the model as above average for training purpose. Overall, this 3D rapid prototyping cardiac model was rated as excellent (33%), good (50%), and average (17%).
CONCLUSION: This 3D rapid prototyping heart model will be a valuable source of anatomical education and cardiac interventional management.
NMR-based metabolomics for elucidating the bioactive compounds from Mangifera caesia Jack and Ficus auriculata lour

Mohamed Yunus SN, Abdul-Hamid NA, Jaafar AH, Lawal U, Abas F

J Food Biochem, 2021 02;45(2):e13610.
PMID: 33491203 DOI: 10.1111/jfbc.13610

Mangifera caesia and Ficus auriculata are neglected fruits found in Malaysia and are locally known as "buah binjai" and "buah ara", respectively. To profile the metabolites for both fruits, we conducted a robust 1 H-nuclear magnetic resonance (NMR)-based metabolomics approach. Principal component analysis (PCA) and partial least square (PLS) analyses were applied to distinguish the metabolites variations of M. caesia and F. auriculata fruits extracted with different ethanol ratios (0, 70, and 100%). In total, 34 metabolites were identified in M. caesia and F. auriculata fruits. The 70% ethanol extracts of both fruits displayed the highest antioxidant and α-glucosidase inhibitory activities, as well as notable with the highest phenolic content, compared with the other samples. The present metabolomics study shows that the polarities of solvent extractions play a crucial role in the assessment and recovery of the metabolites for the high value of natural antioxidants and α-glucosidase inhibitors in M. caesia and F. auriculata fruits. PRACTICAL APPLICATIONS: Antioxidant and antidiabetic agents from fruit sources are increasingly becoming popular due to its potential contributions to human health, by protecting against infections and degenerative diseases. However, some of these fruits were neglected where the scientific data on their potential benefits and biochemical contents are lacking. The information gained from this study provides valuable knowledge on M. caesia and F. auriculata fruits as natural antioxidant and α-glucosidase inhibitors agents that might be beneficial to consumers, further promote the usage of neglected fruits as functional food and natural supplements.
Solar radiation prediction using boosted decision tree regression model: A case study in Malaysia

Jumin E, Basaruddin FB, Yusoff YBM, Latif SD, Ahmed AN

Environ Sci Pollut Res Int, 2021 Jun;28(21):26571-26583.
PMID: 33484461 DOI: 10.1007/s11356-021-12435-6

Reliable and accurate prediction model capturing the changes in solar radiation is essential in the power generation and renewable carbon-free energy industry. Malaysia has immense potential to develop such an industry due to its location in the equatorial zone and its climatic characteristics with high solar energy resources. However, solar energy accounts for only 2-4.6% of total energy utilization. Recently, in developed countries, various prediction models based on artificial intelligence (AI) techniques have been applied to predict solar radiation. In this study, one of the most recent AI algorithms, namely, boosted decision tree regression (BDTR) model, was applied to predict the changes in solar radiation based on collected data in Malaysia. The proposed model then compared with other conventional regression algorithms, such as linear regression and neural network. Two different normalization techniques (Gaussian normalizer binning normalizer), splitting size, and different input parameters were investigated to enhance the accuracy of the models. Sensitivity analysis and uncertainty analysis were introduced to validate the accuracy of the proposed model. The results revealed that BDTR outperformed other algorithms with a high level of accuracy. The funding of this study could be used as a reliable tool by engineers to improve the renewable energy sector in Malaysia and provide alternative sustainable energy resources.

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