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Synthesis, bioactivity and binding energy calculations of novel 3-ethoxysalicylaldehyde based thiosemicarbazone derivatives

Ishaq M, Taslimi P, Shafiq Z, Khan S, Ekhteiari Salmas R, Zangeneh MM, et al.

Bioorg Chem, 2020 07;100:103924.
PMID: 32442818 DOI: 10.1016/j.bioorg.2020.103924

In recent decade, the entrance of α-N-heterocyclic thiosemicarbazones derivates (Triapne, COTI-2 and DpC) in clinical trials for cancer and HIV-1 has vastly increased the interests of medicinal chemists towards this class of organic compounds. In the given study, a series of eighteen new (3a-r) 3-ethoxy salicylaldehyde-based thiosemicarbazones (TSC), bearing aryl and cycloalkyl substituents, were synthesized and assayed for their pharmacological potential against carbonic anhydrases (hCA I and hCA II), cholinesterases (AChE and BChE) and α-glycosidase. The hCA I isoform was inhibited by these novel 3-ethoxysalicylaldehyde thiosemicarbazone derivatives (3a-r) in low nanomolar levels, the Ki of which differed between 144.18 ± 26.74 and 454.92 ± 48.32 nM. Against the physiologically dominant isoform hCA II, the novel compounds demonstrated Kis varying from 110.54 ± 14.05 to 444.12 ± 36.08 nM. Also, these novel derivatives (3a-r) effectively inhibited AChE, with Ki values in the range of 385.38 ± 45.03 to 983.04 ± 104.64 nM. For BChE was obtained with Ki values in the range of 400.21 ± 35.68 to 1003.02 ± 154.27 nM. For α-glycosidase the most effective Ki values of 3l, 3n, and 3q were with Ki values of 12.85 ± 1.05, 16.03 ± 2.84, and 19.16 ± 2.66 nM, respectively. Moreover, the synthesized TCSs were simulated using force field methods whereas the binding energies of the selected compounds were estimated using MM-GBSA method. The findings indicate the present novel 3-ethoxy salicylaldehyde-based thiosemicarbazones to be excellent hits for pharmaceutical applications.
Fulltext Self-Fluxing Mechanism in Geopolymerization for Low-Sintering Temperature of Ceramic

Jamil NH, Abdullah MMAB, Pa FC, Mohamad H, Ibrahim WMAW, Amonpattaratkit P, et al.

Materials (Basel), 2021 Mar 10;14(6).
PMID: 33801862 DOI: 10.3390/ma14061325

Kaolin, theoretically known as having low reactivity during geopolymerization, was used as a source of aluminosilicate materials in this study. Due to this concern, it is challenging to directly produce kaolin geopolymers without pre-treatment. The addition of ground granulated blast furnace slag (GGBS) accelerated the geopolymerization process. Kaolin-GGBS geopolymer ceramic was prepared at a low sintering temperature due to the reaction of the chemical composition during the initial stage of geopolymerization. The objective of this work was to study the influence of the chemical composition towards sintering temperature of sintered kaolin-GGBS geopolymer. Kaolin-GGBS geopolymer was prepared with a ratio of solid to liquid 2:1 and cured at 60 °C for 14 days. The cured geopolymer was sintered at different temperatures: 800, 900, 1000, and 1100 °C. Sintering at 900 °C resulted in the highest compressive strength due to the formation of densified microstructure, while higher sintering temperature led to the formation of interconnected pores. The difference in the X-ray absorption near edge structure (XANES) spectra was related to the phases obtained from the X-ray diffraction analysis, such as akermanite and anothite. Thermal analysis indicated the stability of sintered kaolin-GGBS geopolymer when exposed to 1100 °C, proving that kaolin can be directly used without heat treatment in geopolymers. The geopolymerization process facilitates the stability of cured samples when directly sintered, as well as plays a significant role as a self-fluxing agent to reduce the sintering temperature when producing sintered kaolin-GGBS geopolymers.
Probing 4-(diethylamino)-salicylaldehyde-based thiosemicarbazones as multi-target directed ligands against cholinesterases, carbonic anhydrases and α-glycosidase enzymes

Hashmi S, Khan S, Shafiq Z, Taslimi P, Ishaq M, Sadeghian N, et al.

Bioorg Chem, 2021 02;107:104554.
PMID: 33383322 DOI: 10.1016/j.bioorg.2020.104554

With the fading of 'one drug-one target' approach, Multi-Target-Directed Ligands (MTDL) has become a central idea in modern Medicinal Chemistry. The present study aimed to design, develop and characterize a novel series of 4-(Diethylamino)-salicylaldehyde based thiosemicarbazones (3a-p) and evaluates their biological activity against cholinesterase, carbonic anhydrases and α-glycosidase enzymes. The hCA I isoform was inhibited by these novel 4-(diethylamino)-salicylaldehyde-based thiosemicarbazones (3a-p) in low nanomolar levels, the Ki of which differed between 407.73 ± 43.71 and 1104.11 ± 80.66 nM. Against the physiologically dominant isoform hCA II, the novel compounds demonstrated Kis varying from 323.04 ± 56.88 to 991.62 ± 77.26 nM. Also, these novel 4-(diethylamino)-salicylaldehyde based thiosemicarbazones (3a-p) effectively inhibited AChE, with Ki values in the range of 121.74 ± 23.52 to 548.63 ± 73.74 nM. For BChE, Ki values were obtained with in the range of 132.85 ± 12.53 to 618.53 ± 74.23 nM. For α-glycosidase, the most effective Ki values of 3b, 3k, and 3g were with Ki values of 77.85 ± 10.64, 96.15 ± 9.64, and 124.95 ± 11.44 nM, respectively. We have identified inhibition mechanism of 3b, 3g, 3k, and 3n on α-glycosidase AChE, hCA I, hCA II, and BChE enzyme activities. Hydrazine-1-carbothioamide and hydroxybenzylidene moieties of compounds play an important role in the inhibition of AChE, hCA I, and hCA II enzymes. Hydroxybenzylidene moieties are critical for inhibition of both BChE and α-glycosidase enzymes. The findings of in vitro and in silico evaluations indicate 4-(diethylamino)-salicylaldehyde-based thiosemicarbazone scaffold to be a promising hit for drug development for multifactorial diseases like Alzheimer's disease.
Fulltext Xylocarpus Moluccensis Induces Cytotoxicity in Human Hepatocellular Carcinoma HepG2 Cell Line via Activation of the Extrinsic Pathway

Chaudhry GE, Sohimi NKA, Mohamad H, Zafar MN, Ahmed A, Sung YY, et al.

Asian Pac J Cancer Prev, 2021 Feb 01;22(S1):17-24.
PMID: 33576208 DOI: 10.31557/APJCP.2021.22.S1.17

OBJECTIVE: Liver cancer is one of the most common causes of cancer death, with reduced survival rates. The development of new chemotherapeutic agents is essential to find effective cytotoxic drugs that give minimum side effects to the surrounding healthy tissues. The main objective of the present study was to evaluate the cytotoxic effects and mechanism of cell death induced by the crude and diethyl ether extract of Xylocarpus mouccensis on the human hepatocellular carcinoma cell line.
METHODS: The cytotoxicity activity was measured using the MTS assay. The mode of cell death determined by the apoptosis study, DNA fragmentation analysis done by using the TUNEL system. The pathway study or mechanism of apoptosis observed by study caspases 8, 9, 3/7 Glo-caspases method.
RESULTS: In this study, the methanol extracts prepared from leaf Xylocarpus mouccensis leaf produced cytotoxicity effect with IC50 (72hr) < 30µg/ml. The IC50 value at 72 hours exerted by diethyl ether extract of Xylocarpus moluccensis leaf was 0.22 µg/ml, which was more cytotoxic than to that of crude methanol extract. The results obtained by the colorimetric TUNEL system suggest that methanol crude extract of Xylocarpus moluccensis (leaf), diethyl ether extract of Xylocarpus moluccensis (leaf) and methanol extract of Xylocarpus granatum (bark) induced DNA fragmentation in the HepG2 cell line. Besides, the caspase-Glo assay demonstrated that diethyl ether leaf extract of Xylocarpus moluccensis triggered apoptotic cell death via activation of caspases -8, and -3/7 However, no visible activation was noticed for caspase -9. Furthermore, TLC indicates the presence of potential metabolites in an extract of Xylocarpus moluccensis.
CONCLUSION: Thus, the present study suggests the remarkable potential of active metabolites in the extract of Xylocarpus moluccensis as a future therapeutic agent for the treatment of cancer.
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Fulltext Street Food in Malaysia: What Are the Sodium Levels?

Haron H, Zainal Arifen ZN, Shahar S, Mohamad H, Mohd Yazid SFZ, Michael V, et al.

Foods, 2022 Nov 24;11(23).
PMID: 36496599 DOI: 10.3390/foods11233791

Street food is a major source of food in middle- and low-income countries as it is highly accessible and inexpensive. However, it is usually perceived as unhealthy due to the high levels of sodium, sugar, and fat content. However, there is little analytical data on the sodium levels in the street foods of Malaysia. This study started with a survey to determine the most frequently available street foods in every state in Malaysia, followed by food sampling and the analysis of sodium (reported mg/100 g sample). Street food in the snack category contained the highest amount of sodium (433 mg), followed by main meals (336.5 mg) and desserts (168 mg). Approximately 30% of the local street food in this study was deep-fried. Snacks from processed food (8%) contained high sodium content (500−815 mg). Fried noodles and noodle soup contained the highest amount of sodium (>2000 mg sodium) based on per serving. Most main dishes that use a variety of sauces contained high amounts of sodium. These findings were recorded in the Malaysian Food Composition Database. Moreover, this study could raise awareness and serve as baseline data for future interventions on the sodium content in the street foods of Malaysia.
Exploring chromone sulfonamides and sulfonylhydrazones as highly selective ectonucleotidase inhibitors: Synthesis, biological evaluation and in silico study

Younus HA, Saeed M, Mahmood A, Jadoon MSK, Hameed A, Asari A, et al.

Bioorg Chem, 2023 May;134:106450.
PMID: 36924652 DOI: 10.1016/j.bioorg.2023.106450

Ectonucleotidases, a well-known superfamily of plasma membrane located metalloenzymes plays a central role in mediating the process of purinergic cell signaling. Major functions performed by these enzymes include the hydrolysis of extracellular nucleosides and nucleotides which are considered as important cell-signaling molecules. Any (patho)-physiologically induced disruption in this purinergic cell signaling leads to several disorders, hence these enzymes are important drug targets for therapeutic purposes. Among the major challenges faced in the design of inhibitors of ectonucleotidases, an important one is the lack of selective inhibitors. Access to highly selective inhibitors via a facile synthetic route will not only be beneficial therapeutically, but will also lead to an increase in our understanding of intricate interplay between members of ectonucleotidase enzymes in relation to their selective activation and/or inhibition in different cells and tissues. Herein we describe synthesis of highly selective inhibitors of human intestinal alkaline phosphatase (h-IAP) and human tissue non-specific alkaline phosphatase (h-TNAP), containing chromone sulfonamide and sulfonylhydrazone scaffolds. Compound 1c exhibited highest (and most selective) h-IAP inhibition activity (h-IAP IC50 = 0.51 ± 0.20 µM; h-TNAP = 36.5%) and compound 3k showed highest activity and selective inhibition against h-TNAP (h-TNAP IC50 = 1.41 ± 0.10 µM; h-IAP = 43.1%). These compounds were also evaluated against another member of ectonucleotidase family, that is rat and human ecto-5'-nucleotidase (r-e5'NT and h-e5'NT). Some of the compounds exhibited excellent inhibitory activity against ecto-5'-nucleotidase. Compound 2 g exhibited highest inhibition against h-e5'NT (IC50 = 0.18 ± 0.02 µM). To rationalize the interactions with the binding site, molecular docking studies were carried out.
Fulltext The Effects of 4-Hydroxybenzoic Acid Identified from Bamboo (Dendrocalamus asper) Shoots on Kv1.4 Channel

Zhang J, Mohamad FH, Wong JH, Mohamad H, Ismail AH, Mohamed Yusoff AA, et al.

Malays J Med Sci, 2018 Feb;25(1):101-113.
PMID: 29599640 DOI: 10.21315/mjms2018.25.1.12

Background: Bamboo shoot has been used as a treatment for epilepsy in traditional Chinese medicine for generations to treat neuronal disorders such as convulsive, dizziness and headaches. 4-hydroxybenzoic acid (4-hba) is a non-flavonoid phenol found abundantly inDendrocalamus aspershoots (bamboo), fruits (strawberries and apples) and flowers. Kv1.4 is a rapidly inactivatingShaker-related member of the voltage-gated potassium channels with two inactivation mechanisms; the fast N-type and slow C-type. It plays vital roles in repolarisation, hyperpolarisation and signaling the restoration of resting membrane potential through the regulation of the movement of K+across the cellular membrane.
Methods: Chemical compounds fromDendrocalamus asperbamboo shoots were purified and identified as major palmitic acids mixed with other minor fatty acids, palmitic acid, 4-hydroxybenzaldehyde, lauric acid, 4-hydroxybenzoic acid and cholest-4-ene-3-one. The response of synthetic 4-hydroxybenzoic acid was tested on Kv1.4 potassium channel which was injected into viable oocytes that was extracted fromXenopus laevis. The current were detected by the two-microelectrode voltage clamp, holding potential starting from -80 mV with 20 mV step-up until +80 mV. Readings of treatments with 0.1% DMSO, 4-hba concentrations and K channel blockers were taken at +60 mV. The ratio of tail/peak amplitude is the index of the activity of the Kv1.4 channels withn≥ 6 (number of oocytes tested). The decreases of the ratios of five different concentrations (1 μM, 10 μM, 100 μM, 1 mM and 2.5 mM) were compared with 0.1% DMSO as the control.
Results: All concentration showed statistically significant results withP< 0.05 except for 100 μM. The normalised current of the 4-hba concentrations were compared with potassium channel blockers (TEA and 4-AP) and all groups showed statistically significant results. This study also showed that time taken for each concentration to affect Kv1.4 does not play any significant roles.
Conclusion: 4-hydroxybenzoic acid was found to be able to enhance the inactivation of Kv1.4 by lowering the membrane potential so that the abnormal neuronal firing can be inhibited. With IC50 slightly higher than 10 μM, increasing concentrations (100 μM, 1 mM and 2.5 mM) had shown to exhibit toxicity effects. The best concentration from this study is 10 μM with Hill slope of 0.1799.
Fulltext Hippocampal amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid GluA1 (AMPA GluA1) receptor subunit involves in learning and memory improvement following treatment with Centella asiatica extract in adolescent rats

Binti Mohd Yusuf Yeo NA, Muthuraju S, Wong JH, Mohammed FR, Senik MH, Zhang J, et al.

Brain Behav, 2018 09;8(9):e01093.
PMID: 30105867 DOI: 10.1002/brb3.1093

INTRODUCTION: Centella asiatica is an herbal plant that contains phytochemicals that are widely believed to have positive effects on cognitive function. The adolescent stage is a critical development period for the maturation of brain processes that encompass changes in physical and psychological systems. However, the effect of C. asiatica has not been extensively studied in adolescents. The aim of this study was therefore to investigate the effects of a C. asiatica extract on the enhancement of learning and memory in adolescent rats.
METHODS: The locomotor activity, learning, and memory were assessed by using open field test and water T-maze test. This study also examined changes in neuronal cell morphology using cresyl violet and apoptosis staining. We also performed immunohistochemical study to analyse the expression of the glutamate AMPA receptor (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) GluA1 subunit and the GABA receptor (γ-Aminobutyric Acid) subtype GABAA α1 subunit in the hippocampus of the same animals.
RESULTS: We found no significant changes in locomotor activity (p > 0.05). The water T-maze data showed that 30 mg/kg dose significantly (p 0.05). Histological data revealed no neuronal morphological changes. Immunohistochemical analysis revealed increased expression of the AMPA GluA1 receptor subunit but there was no effect on GABAA receptor α1 subunit expression in the CA1 and CA2 subregions of the hippocampus.
CONCLUSIONS: The C. asiatica extract therefore improved hippocampus-dependent spatial learning and memory in a dose-dependent manner in rats through the GluA1-containing AMPA receptor in the CA1 and CA2 sub regions of the hippocampus.
Sulfonylhydrazones: Design, synthesis and investigation of ectonucleotidase (ALP & e5'NT) inhibition activities

Younus HA, Hameed A, Mahmood A, Khan MS, Saeed M, Batool F, et al.

Bioorg Chem, 2020 07;100:103827.
PMID: 32402802 DOI: 10.1016/j.bioorg.2020.103827

Medicinal importance of the sulfonylhydrazones is well-evident owing to their binding ability with zinc containing metalloenzymes. In the present study, we have synthesized different series of sulfonylhydrazones by using facile synthetic methods in good to excellent yield. All the successfully prepared sulfonylhydrazones were screened for ectonucleotidase (ALP & e5'NT) inhibitory activity. Among the chromen-2-one scaffold based sulfonylhydrazones, the compounds 7 was found to be most potent inhibitor for h-TNAP (human tissue non-specific alkaline phosphatase) and h-IAP (human intestinal alkaline phosphatase) with IC50 values of 1.02 ± 0.13 and 0.32 ± 0.0 3 µM respectively, compared with levamisole (IC50 = 25.2 ± 1.90 µM for h-TNAP) and l-phenylalanine (IC50 = 100 ± 3.00 µM for h-IAP) as standards. Further, the chromen-2-one based molecule 5a showed excellent activity against h-ecto 5'-NT (human ecto-5'-nucleotidase) with IC50 value of 0.29 ± 0.004 µM compared to standard, sulfamic acid (IC50 = 42.1 ± 7.8 µM). However, among the series of phenyl ring based sulfonylhydrazones, compound 9d was found to be most potent against h-TNAP and h-IAP with IC50 values of 0.85 ± 0.08 and 0.52 ± 0.03 µM, respectively. Moreover, in silico studies were also carried to demonstrate their putative binding with the target enzymes. The potent compounds 5a, 7, and 9d against different ectonucleotidases (h-ecto 5'-NT, h-TNAP, h-IAP) could potentially serve as lead for the development of new therapeutic agents.
Fulltext Acute application of Centella asiatica extract enhanced AMPAR-mediated postsynaptic currents in rat entorhinal cortex

Wong JH, Reza F, Muthuraju S, Chuang HG, Zhang J, Senik MH, et al.

J Integr Neurosci, 2020 Jun 30;19(2):217-227.
PMID: 32706186 DOI: 10.31083/j.jin.2020.02.50

Centella asiatica is notable for its wide range of biological activities beneficial to human health, particularly its cognitive enhancement and neuroprotective effects. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors are ionotropic glutamate receptors mediating fast excitatory neurotransmission essential in long-term potentiation widely thought to be the cellular mechanism of learning and memory. The method of whole-cell patch-clamp was used to study the effect of the acute application of Centella asiatica extract on the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated spontaneous excitatory postsynaptic currents in the entorhinal cortex of rat brain slices. The respective low dose of test compounds significantly increased the amplitude of spontaneous excitatory postsynaptic currents while having no significant effects on the frequency. The findings suggested that Centella asiatica extract increased the response of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors at the postsynaptic level, revealing the potential role of Centella asiatica in modulating the glutamatergic responses in the entorhinal cortex of rat brain slices to produce cognitive enhancement effects.
Fulltext Antihypercholesterolemic and antiatherosclerotic potencies of Pandanus tectorius fruits via increasing scavenger receptor-B1 genes expression and inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity

Andriani Y, Chaudhry GE, Oksal E, Pangestika I, Ramli NM, Mohamad H, et al.

J Adv Pharm Technol Res, 2020 3 11;11(1):30-35.
PMID: 32154156 DOI: 10.4103/japtr.JAPTR_164_19

Atherosclerosis is a leading cause of death worldwide. The adverse side effects of currently available drugs urge to find more effective and safe remedial agents. Alternative candidates from natural resources are of great consequence in the emerging of new drugs. Pandanus tectorius (Pandanaceae) was traditionally used in Ayurvedic medicine to cure certain diseases. Thus, the current study conducted to elucidate the potency of P. tectorius fruit as antiatherosclerosis and antihypercholesterolemia agents through the regulation of high density lipoprotein (HDL) receptor (scavenger receptor [SR]-B1) gene expression and 3-hydroxy-3-methylglutaryl coenzyme A reductase reductase (HMGCR) in vitro, respectively. The P. tectorius fruit was noncytotoxic against the HepG2 cell line confirmed by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide assay. The P. tectorius fruit successfully upregulates the SR-B1 gene expression and downregulate the HMGCR. Moreover, anin vivo study showed that P. tectorius has good activity on the upregulation of HDL and subsequently downregulation of total cholesterol level. Moreover, P. tectorius fruit did not show any increase in toxicity biomarkers serum glutamic oxaloacetic transaminase and serum glutamate pyruvate transaminase in vivo. These results found that P. tectorius fruits have potency as the preventive agent for hypercholesterolemia and atherosclerosis via SR-B1 and HMGCR mechanisms of action.
Deep eutectic solvent mediated synthesis of 3,4-dihydropyrimidin-2(1H)-ones and evaluation of biological activities targeting neurodegenerative disorders

Saleem Khan M, Asif Nawaz M, Jalil S, Rashid F, Hameed A, Asari A, et al.

Bioorg Chem, 2022 01;118:105457.
PMID: 34798458 DOI: 10.1016/j.bioorg.2021.105457

Substitution of hazardous and often harmful organic solvents with "green" and "sustainable" alternative reaction media is always desirous. Ionic liquids (IL) have emerged as valuable and versatile liquids that can replace most organic solvents in a variety of syntheses. However, recently new types of low melting mixtures termed as Deep Eutectic Solvents (DES) have been utilized in organic syntheses. DES are non-volatile in nature, have sufficient thermal stability, and also have the ability to be recycled and reused. Hence DES have been used as alternative reaction media to perform different organic reactions. The availability of green, inexpensive and easy to handle alternative solvents for organic synthesis is still scarce, hence our interest in DES mediated syntheses. Herein we have investigated Biginelli reaction in different DES for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones. Monoamine oxidases and cholinesterases are important drug targets for the treatment of various neurological disorders such as Alzheimer's disease, Parkinson's disease, depression and anxiety. The compounds synthesized herein were evaluated for their inhibitory potential against these enzymes. Some of the compounds were found to be highly potent and selective inhibitors. Compounds 1 h and 1c were the most active monoamine oxidase A (MAO A) (IC50 = 0.31 ± 0.11 µM) and monoamine oxidase B (MAO B) (IC50 = 0.34 ± 0.04 µM) inhibitors respectively. All compounds were selective AChE inhibitors and did not inhibit BChE (<29% inhibition). Compound 1 k (IC50 = 0.13 ± 0.09 µM) was the most active AChE inhibitor.
Fulltext The Effect of 4-hydroxybenzaldehyde on the γ-aminobutyric Acid Type A Receptor

Zhang J, Mohamad H, Wong JH, Bilal M, Ismail AHB, Lloyd AJ, et al.

Malays J Med Sci, 2017 Mar;24(2):94-99.
PMID: 28894409 DOI: 10.21315/mjms2017.24.2.12

The α1β2γ2 subtype of GABAA receptors is the most commonly found GABAA receptor subtype in the mammalian cortex and hippocampus. It is expressed heterologously in the Xenopus laevis oocyte as a α1β2γ2S/L subtype for application as an in vitro model for the screening of compounds that modulate receptor activities. In fact, 4-hydroxybenzaldehyde (4-HB) has been identified as one of the major components in Dendrocalamus asper bamboo shoots in our previous study, and the current study showed that at 101.7 μM, 4-HB significantly reduced the GABA-induced chloride current of GABAA receptors expressed on Xenopus oocytes, indicating a possible GABAergic antagonistic effect at high concentrations.
Hydroxyproline determination for initial detection of halal-critical food ingredients (gelatin and collagen)

Yuswan MH, A Jalil NH, Mohamad H, Keso S, Mohamad NA, Tengku Md Yusoff TS, et al.

Food Chem, 2021 Feb 01;337:127762.
PMID: 32777563 DOI: 10.1016/j.foodchem.2020.127762

Gelatin and collagen are considered halal-critical ingredients as they are typically derived from either bovine or porcine animals. Current analytical methods for determining the sources of gelatin and collagen suffer from limitations in terms of robustness and false positives in peptide matching. Thus, the aim of this study was to investigate the utility of monitoring hydroxyproline, a signature amino acid for gelatin and collagen, for identifying potentially haram foodstuffs. To determine the hydroxyproline profiles among animal- and plant-based samples, one-way univariate analysis of variance followed by pair-wise comparison was used to establish statistical significance. Multivariate chemometric analysis through principal component analysis revealed a discrete distribution pattern among 59 samples due to hydroxyproline variability. Finally, inter- and intra-laboratory comparisons demonstrated the validity and robustness of hydroxyproline determination according to ISO 17025. Thus, this preliminary identification technique will aid the identification of potentially haram foodstuffs.
Fulltext Differential expression of entorhinal cortex and hippocampal subfields α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors enhanced learning and memory of rats following administration of Centella asiatica

Wong JH, Muthuraju S, Reza F, Senik MH, Zhang J, Mohd Yusuf Yeo NAB, et al.

Biomed Pharmacother, 2019 Feb;110:168-180.
PMID: 30469081 DOI: 10.1016/j.biopha.2018.11.044

Centella asiatica (CA) is a widely used traditional herb, notably for its cognitive enhancing effect and potential to increase synaptogenesis. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs) mediate fast excitatory neurotransmission with key roles in long-term potentiation which is believed to be the cellular mechanism of learning and memory. Improved learning and memory can be an indication to the surface expression level of these receptors. Our previous study demonstrated that administration of CA extract improved learning and memory and enhanced expression of AMPAR GluA1 subunit while exerting no significant effects on GABAA receptors of the hippocampus in rats. Hence, to further elucidate the effects of CA, this study investigated the effects of CA extract in recognition memory and spatial memory, and its effects on AMPAR GluA1 and GluA2 subunit and NMDAR GluN2 A and GluN2B subunit expression in the entorhinal cortex (EC) and hippocampal subfields CA1 and CA3. The animals were administered with saline, 100 mg/kg, 300 mg/kg, and 600 mg/kg of CA extract through oral gavage for 14 days, followed by behavioural analysis through Open Field Test (OFT), Novel Object Recognition Task (NORT), and Morris Water Maze (MWM) and lastly morphological and immunohistochemical analysis of the surface expression of AMPAR and NMDAR subunits were performed. The results showed that 14 days of administration of 600 mg/kg of CA extract significantly improved memory assessed through NORT while 300 mg/kg of CA extract significantly improved memory of the animals assessed through MWM. Immunohistochemical analysis revealed differential modulation effects on the expressions of receptor subunits across CA1, CA3 and EC. The CA extract at the highest dose (600 mg/kg) significantly enhanced the expression of AMPAR subunit GluA1 and GluA2 in CA1, CA3 and EC, and NMDAR subunit GluN2B in CA1 and CA3 compared to control. At 300 mg/kg, CA significantly increased expression of AMPAR GluA1 in CA1 and EC, and GluA2 in CA1, CA3 and EC while 100 mg/kg of CA significantly increased expression of only AMPAR subunit GluA2 in CA3 and EC. Expression of NMDAR subunit GluN2 A was significantly reduced in the CA3 (at 100, 300, and 600 mg/kg) while no significant changes of subunit expression was observed in CA1 and EC compared to control. The results suggest that the enhanced learning and memory observed in animals administered with CA was mainly mediated through increased expression of AMPAR GluA1 and GluA2 subunits and differential expression of NMDAR GluN2 A and GluN2B subunits in the hippocampal subfields and EC. With these findings, the study revealed a new aspect of cognitive enhancing effect of CA and its therapeutic potentials through modulating receptor subunit expression.
Fulltext Fatty Acid Composition of Selected Street Foods Commonly Available in Malaysia

Zainal Arifen ZN, Shahril MR, Shahar S, Mohamad H, Mohd Yazid SFZ, Michael V, et al.

Foods, 2023 Mar 14;12(6).
PMID: 36981160 DOI: 10.3390/foods12061234

Despite growing evidence of increased saturated and trans fat contents in street foods, little is known about their fatty acid (FA) compositions. This study aimed to analyse the saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and trans fatty acids (TFAs) content of 70 selected and most commonly available street foods in Malaysia. The street foods were categorised into main meals, snacks, and desserts. TFAs were not detected in any of the street foods. Descriptively, all three categories mainly contained SFAs, followed by MUFAs, and PUFAs. However, the one-way ANOVA testing showed that the differences between each category were insignificant (p > 0.05), and each FA was not significantly different (p > 0.05) from one to another. Nearly half of the deep-fried street foods contained medium to high SFAs content (1.7 g/100 g-24.3 g/100 g), while the MUFAs were also high (32.0-44.4%). The Chi-square test of association showed that the type of preparation methods (low or high fat) used was significantly associated (p < 0.05) with the number of SFAs. These findings provide valuable information about fat composition in local street foods for the Malaysian Food Composition Database and highlight the urgency to improve nutritional composition.
Salt reduction policy for out of home sectors: a supplementary document for the salt reduction strategy to prevent and control non-communicable diseases (NCDS) in Malaysia 2021-2025

Harun Z, Shahar S, You YX, Abdul Manaf Z, Abdul Majid H, Chin CY, et al.

Health Res Policy Syst, 2024 Apr 18;22(1):49.
PMID: 38637888 DOI: 10.1186/s12961-024-01124-8

Cardiovascular diseases (CVDs) are the major cause of death among Malaysians. Reduction of salt intake in populations is one of the most cost-effective strategies in the prevention of CVDs. It is very feasible as it requires low cost for implementation and yet could produce a positive impact on health. Thus, salt reduction initiatives have been initiated since 2010, and two series of strategies have been launched. However, there are issues on its delivery and outreach to the target audience. Further, strategies targeting out of home sectors are yet to be emphasized. Our recent findings on the perceptions, barriers and enablers towards salt reduction among various stakeholders including policy-makers, food industries, food operators, consumers and schools showed that eating outside of the home contributed to high salt intake. Foods sold outside the home generally contain a high amount of salt. Thus, this supplementary document is being proposed to strengthen the Salt Reduction Strategy to Prevent and Control Non-communicable Diseases (NCDs) for Malaysia 2021-2025 by focussing on the strategy for the out-of-home sectors. In this supplementary document, the Monitoring, Awareness and Product (M-A-P) strategies being used by the Ministry of Health (MOH) are adopted with a defined outline of the plan of action and indicators to ensure that targets could be achieved. The strategies will involve inter-sectoral and multi-disciplinary approaches, including monitoring of salt intake and educating consumers, strengthening the current enforcement of legislation on salt/sodium labelling and promoting research on reformulation. Other strategies included in this supplementary document included reformulation through proposing maximum salt targets for 14 food categories. It is hoped that this supplementary document could strengthen the current the Salt Reduction Strategy to Prevent and Control NCDs for Malaysia 2021-2025 particularly, for the out-of-home sector, to achieve a reduction in mean salt intake of the population to 6.0 g per day by 2025.

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