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Background: KRAS and p53 are two of the most common genetic alterations associated with colorectal cancer. New drug development targeting these mutated genes in colorectal cancer may serve as a potential treatment avenue to the current regimen. Objective: The objective of the present study was to investigate the effects of alkoxy chain length and 1-hydroxy group on anticolorectal cancer activity of a series of 2-bromoalkoxyanthraquinones and corroborate it with their in silico properties. Methods: In vitro anticancer activity of 2-bromoalkoxyanthraquinones was evaluated against HCT116, HT29, and CCD841 CoN cell lines, respectively. Molecular docking was performed to understand the interactions of these compounds with putative p53 and KRAS targets (7B4N and 6P0Z). Results: 2-Bromoalkoxyanthraquinones with the 1-hydroxy group were proven to be more active than the corresponding counterparts in anticancer activity. Among the tested compounds, compound 6b with a C3 alkoxy chain exhibited the most promising antiproliferation activity against HCT116 cells (IC50 = 3.828 ± 0.05 µM) and showed high selectivity for HCT116 over CCD841 CoN cells (SI = 45.47). The molecular docking reveals additional hydrogen bonds between the 1-hydroxy group of 6b and the proteins. Compound 6b has adequate lipophilicity (cLogP = 3.27) and ligand efficiency metrics (LE = 0.34; LLE = 2.15) close to the proposed acceptable range for an initial hit. Conclusion: This work highlights the potential of the 1-hydroxy group and short alkoxy chain on anticolorectal cancer activity of 2-bromoalkoxyanthraquinones. Further optimisation may be warranted for compound 6b as a therapeutic agent against colorectal cancer. other: not applicable

Background: Platelet-activating factor (PAF) is an agonist mediator in the inflammatory process, which interacts with PAF receptor (PAFR) that eventually causes cancers, respiratory and neurodegenerative diseases. This interaction activates the mitogen-activated protein kinase (MAPK) pathway, leading to a pro-inflammatory cascade. The pathophysiological conditions due to activation of inflammatory cascade could be inhibited by PAF antagonists. Objectives: In this study, selected naturally derived flavonoids (flavone, biochanin A, and myricetin) with different functional groups were subjected to molecular modelling and experimental studies to investigate their potential as PAF antagonists. Method: Interactions of flavonoids and PAF were assessed via Autodock Vina for molecular docking and the AMBER program for molecular dynamic simulations. The experimentally antagonistic effects of the flavonoids were also conducted via PAF inhibitory assay to determine the IC50 values. Results: The findings of docking and dynamic simulations have revealed that all selected flavonoids interact with PAFR in the binding site with considerably good binding affinity up to - 9.8 kcal mol-1 as compared to cedrol (- 8.1 kcal mol-1) as a standard natural PAFR antagonist. The PAFR-flavonoid complexes exhibited four conserved active site residues, which included W73, F97, F174, and L279. The stability of all complexes was attained in a 30 ns simulation. The findings of in silico analyses were then compared to the experimental study on PAF inhibitory assay. Inhibitory effects of flavonoids against PAFR showed moderate activities, ranging from 27.8 – 30.8 μgM-1. Conclusion: All studied flavonoids could act as promising PAF antagonists with some enhancement in their structures to exhibit potent antagonistic activity. However, these naturally derived flavonoids demand further investigation at cellular and animal models to develop new PAF antagonist drug candidates for treating PAF-mediated diseases.

This study was performed to establish anti-diabetic and anti-oxidant properties, and to carry out phytochemical analysis of selected local plants which are traditionally used as medicinal plants. Local plants involved in this study were Lawsonia inermis, Punica granatum, Dryobalanops aromatica, Ziziphus mauritiana, and Ocimum basilicum. Solvent extraction was performed using maceration method with solvents of increasing polarity. Alpha-glucosidase inhibition assay was performed on all extracts to ascertain their anti-diabetic potentials. The extracts were screened for antioxidant activity using anti-oxidant assays (FRAP, DPPH, TAOC, ABTS, and BCB) and quantitative phytochemical analyses (TPC and TFC). Chemical profiling using LCMS and GCMS was performed on extracts with high biological activities. Methanol extracts of D. aromatica bark and leaves showed the most potent inhibition of alpha-glucosidase with IC50 values of 0.63 ± 0.03 µg/mL and 0.98 ± 0.02 µg/mL, respectively. Both extracts exhibited similar anti-oxidant activity on all five assays and possessed high phenolic contents with values of 266.79 and 261.69 GAE, respectively. The results obtained suggested that amongst the selected plants studied, D. aromatica showed high anti-oxidant activity and anti-diabetic activity (via inhibition of alpha-glucosidase). This is the first report that highlights the anti-diabetic potential of D. aromatica.

Diabetes mellitus is a prevalent metabolic syndrome that is associated with high blood glucose levels. The number of diabetic patients is increasing every year and the total number of cases is expected to reach more than 600 million worldwide by 2045. Modern antidiabetic drugs alleviate hyperglycaemia and complications that are caused by high blood glucose levels. However, due to the side effects of these drugs, plant extracts and bioactive compounds with antidiabetic properties have been gaining attention as alternative treatments for diabetes. Natural products are biocompatible, cheaper and expected to cause fewer side effects than the current antidiabetic drugs. In this review, various nanocarrier systems are discussed, such as liposomes, niosomes, polymeric nanoparticles, nanoemulsions, solid lipid nanoparticles and metallic nanoparticles. These systems have been applied to overcome the limitations of the current drugs and simultaneously improve the efficacy of plant-based antidiabetic drugs. The main challenges in the formulation of plant-based nanocarriers are the loading capacity of the plant extracts and the stability of the carriers. A brief review of lipid nanocarriers and the amphipathic properties of phospholipids and liposomes that encapsulate hydrophilic, hydrophobic and amphiphilic drugs is also described. A special emphasis is placed on metallic nanoparticles, with their advantages and associated complications being reported to highlight their effectiveness for treating hyperglycaemia. The present review could be an interesting paper for researchers who are working in the field of using plant extract-loaded nanoparticles as antidiabetic therapies.

The naturally derived flavonoids are well known to have anticarcinogenic effects. Flavonoids could be an alternative strategy for ovarian cancer treatment, due to existing platinum-based drugs are reported to develop resistance with low survival rates. Inhibition of antiapoptotic proteins, namely B-cell lymphoma (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl), is the key target to stimulate apoptosis process in cancer cells. This study aimed to determine the binding interaction of five naturally derived flavonoids (biochanin A, myricetin, apigenin, galangin, and fisetin) with potential antiapoptotic target proteins (Bcl-2 and Bcl-xl). The molecular docking study was conducted using AutoDock Vina program. The binding affinity and the presence of hydrogen bonds between the flavonoids and target proteins were predicted. Our findings showed that all the flavonoids showed better binding affinity with Bcl-xl than that of Bcl-2 proteins. The highest binding affinity was recorded in fisetin–Bcl-xl protein complex (−8.8 kcal/mol). Meanwhile, the other flavonoids docked with Bcl-xl protein showed binding affinities, ranging from –8.0 to –8.6 kcal/mol. A total of four hydrogen bonds, four hydrophobic contacts, and one electrostatic interaction were detected in the docked fisetin–Bcl-xl complex, explaining its high binding affinity with Bcl-xl. The present results indicate that all flavonoids could potentially serve as Bcl-xl protein inhibitors, which would consequently lead to apoptotic process in ovarian cancers.

Lawsonia inermis (Henna), (Lythraceae), contains a high amount of phenolic compounds which could activate antioxidants to help reduce free radicals. In this study, the compound content found in the ethanol:water (80:20) extract of local Lawsonia inermis was determined using HPLC-QTOFMS. The 1 H-NMR results were used to determine the peak that exists for the group compounds. Chromatographic peaks were detected and integrated by the MassHunter Acquisition B.07.00 for the Agilent TOF and QTOF and MassHunter Qualitative Analysis B.07.00. The ethanol:water (80:20) extract of L. inermis have shown, predominantly, the presence of phenolic compounds (coumarins, flavonoids, naphthalene, and gallic acid) which are highly glycosylated. The presence of compounds such as apiin, lawsone, apigenin, luteolin, cosmosiin, and p-coumaric acid were also found.

Sektor penternakan haiwan merupakan titik saringan awal dalam memastikan jaminan keselamatan makanan nasional. Walau bagaimanapun, terdapat pelbagai laporan salah laku dan sebaran wabak terhadap haiwan ternakan yang gagal diatasi dengan baik dalam kalangan pengusaha. Sehubungan dengan itu, objektif kertas kerja ini adalah memperincikan hadis-hadis yang menyebutkan mengenai isu keselamatan makanan dalam sektor penternakan berdasarkan ulasan para muhaddithin serta mengadaptasi hadis tersebut ke dalam satu bentuk instrumen yang praktikal dan mampu dimanfaatkan sama ada sebagai alternatif ataupun nilai tambah dalam prosedur keselamatan makanan semasa. Kajian ini mengguna pakai kaedah analisis data induktif, deduktif serta analisis kandungan dan tematik. Hasilnya, kajian membangunkan instrumen analisis hadis bagi menghindarkan pencemaran pada peringkat awal dalam penghasilan produk makanan daripada sumber haiwan. Food Safety Issues in Livestock Sector: An Analysis of the Development of An Instrument Based on Prophetic Tradition The animal farming or livestock sector is an initial screening point in ensuring national food safety. However, there have been numerous reports of misconduct and livestock outbreaks that farmers have not coped well with. In this regard, the objective of this study is to analyze the Prophetic tradition that addresses food safety issues in the livestock sector based on reviews of muhaddithin, in terms of adapting traditional practice into a modern practical instrument that can be used as an alternative or to add value to current food safety procedure. This study adopted the methods of inductive and deductive data analysis as well as content and thematic analysis. This study finds that a hadith-based analysis tool has been developed for the purpose of preventing contamination in the early stage of food production from animal sources.

There is an increasing demand in developing new, effective, and affordable anti-cancer against colon and rectal. In this study, our aim is to identify the potential anthraquinone compounds from the root bark of Morinda citrifolia to be tested in vitro against colorectal cancer cell lines. Eight potential anthraquinone compounds were successfully isolated, purified and tested for both in-silico and in-vitro analyses. Based on the in-silico prediction, two anthraquinones, morindone and rubiadin, exhibit a comparable binding affinity towards multitargets of β-catenin, MDM2-p53 and KRAS. Subsequently, we constructed a 2D interaction analysis based on the above results and it suggests that the predicted anthraquinones from Morinda citrifolia offer an attractive starting point for potential antiproliferative agents against colorectal cancer. In vitro analyses further indicated that morindone and damnacanthal have significant cytotoxicity effect and selectivity activity against colorectal cancer cell lines.

Selasih (nama saintifik; Ocimum basilicum Linn.) merupakan khazanah alam semulajadi yang istimewa. Penyebutan tentangnya yang dirakamkan dalam al-Quran dan al-Hadith telah menyerlahkan sisi istimewanya. Namun begitu, tidak ramai yang menyedari akan fakta ini. Malah, selasih dianggap tumbuhan yang kurang berharga kerana tidak bernilai komersial. Populariti selasih yang kurang berbanding delima, anggur dan kurma menjadikannya dipandang sepi. Kedangkalan manusia untuk mengenal, mengkaji dan memahami manfaat selasih menjadikannya tidak dikenali, kurang dikaji, tidak diyakini dan jarang digunakan. Oleh itu, kajian ini akan menonjolkan kelebihan dan manfaat yang boleh didapati daripada selasih. Kajian ini menggunapakai keutamaan perincian saintifik dalam menyenarai secara fakta manfaat-manfaat selasih. Dalil daripada al-Quran dan al-Hadith akan menjadi asas bagi menyatakan signifikan selasih daripada perspektif Islam. Kajian ini turut menggunapakai metodologi bibliometrik terhadap selasih. Ini penting bagi memperoleh data yang berautoriti. Hasilnya, didapati majoriti penyelidikan lepas mengenai selasih didominasi oleh artikel jurnal (65.7%) dan disertasi sarjana (13.1%). Kajian lepas berkenaan selasih kebanyakannya berkisar tentang perincian saintifik yang meliputi bidang Farmakologi, Bio-Teknologi, Food Science, Parasitologi and Pesticide, Sains Botani, Bio-Perubatan, Bio-Kimia dan Mikrobiologi. Hasil analisis kandungan turut menemui bahawa daun, minyak, biji dan keseluruhan bahagian pokok bahkan ekstrak daripada pokok selasih mempunyai pelbagai manfaat dari sudut kesihatan misalnya antioksida, antibakteria, antimikrob dan penghindar makhluk perosak. Melihatkan potensi sedia ada, lanjutan penyelidikan terhadap selasih penting bagi manfaat Malaysia. Basil (scientific name; Ocimum basilicum Linn.) is nature's special treasure. Recognition of basil in the Quran and Hadith has accentuated its special side. However, there is lack of awareness on this fact. Basil is even perceived as valueless due to its lack of commercial value. Its less popularity compared to pomegranate, grape and dates has made it seen deserted. Human ignorance to know, study and understand basil’s benefits had contributed to it being unrecognized, less studied, unconvincing and rerely consumed. Therefore, this study highlights the advantages and benefits of basil based on the scientific facts. Evidences from the Quran and the Hadith were also provided to proove its significance from the Islamic perspective. The study used bibliometric research methodology as it is important to get authoritative data. Findings showed that the majority of past studies on basil were found in journal articles (65.7%) and master dissertations (13.1%). Previous studies on basil mostly revolved around scientific details in areas such as pharmacology, bio-technology, food science, parasitology and pesticide, botanical sciences, bio-medical, bio-chemistry and microbiology. Content analysis of this study found that leaf, oil, seed and the whole parts of basil tree, even extracts from basil tree, have multiple benefits for health such as antioxidant, antibacterial, antimicrobial and pest deterrents. The various potentials of basil could justify the need for further research on the plant to give benefit to Malaysia.

Simple Summary Nanoparticulate systems have been extensively explored for the treatment of various diseases, including cancers. The outstanding characteristics of nanoparticles have made it possible to administer them via different routes such as intravenous or inhalation. This flexibility can improve the delivery of encapsulated drugs to the targeted cells for the treatment of lung-related diseases and cancers such as non-small cell lung cancers. The effectiveness of a treatment option needs to be validated in suitable in vitro and/or in vivo models. As the handling of in vivo models is a challenge, many researchers have turned towards in vitro models that use normal cells or specific cells from diseased tissues. This review focuses on the currently available nanoparticles for lung cancers and the type of cellular work that can be conducted to evaluate the effectiveness of a nanoparticulate system for this cancer type. Abstract Lung cancers, the number one cancer killer, can be broadly divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with NSCLC being the most commonly diagnosed type. Anticancer agents for NSCLC suffer from various limitations that can be partly overcome by the application of nanomedicines. Nanoparticles is a branch within nanomedicine that can improve the delivery of anticancer drugs, whilst ensuring the stability and sufficient bioavailability following administration. There are many publications available in the literature exploring different types of nanoparticles from different materials. The effectiveness of a treatment option needs to be validated in suitable in vitro and/or in vivo models. This includes the developed nanoparticles, to prove their safety and efficacy. Many researchers have turned towards in vitro models that use normal cells or specific cells from diseased tissues. However, in cellular works, the physiological dynamics that is available in the body could not be mimicked entirely, and hence, there is still possible development of false positive or false negative results from the in vitro models. This article provides an overview of NSCLC, the different nanoparticles available to date, and in vitro evaluation of the nanoparticles. Different types of cells suitable for in vitro study and the important precautions to limit the development of false results are also extensively discussed.

Oxidative stress and inflammation mostly contribute to aging and age-related conditions including skin aging. The potential of natural products in the form of naturally-derived cosmetics, cosmeceuticals, and nutricosmetics have, however, not been fully harnessed. This review, thus, critically analyzes the potential roles of natural products in inflammation-related skin aging diseases due to the increasing consumers' concerns and demands for efficacious, safe, natural, sustainable, and religiously permitted alternatives to synthetic products. The information and data were collated from various resources and literature databases such as PubMed, Science Direct, Wiley, Springer, Taylor and Francis, Scopus, Inflibnet, Google, and Google Scholar using relevant keywords and Medical Subject Headings (MeSH). The role of green extraction solvents as promising alternatives is also elucidated. The potential enhancements of the bioavailability, stability, solubility and controlled release profile of the bioactives using different delivery systems are also presented. The current potential global market value, motivators, drivers, trends, challenges, halal, and other regulatory certifications for cosmeceuticals and nutricosmetics are equally discussed. The adoption of the suggested extractions and delivery systems would enhance the stability, bioavailability, and target delivery of the bioactives.

A series of 2-aryl-3-(arylideneamino)-1,2-dihydroquinazoline-4(3H)-ones were evaluated as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and self-induced β-amyloid (Aβ) aggregation. All the compounds were found to inhibit both forms of cholinesterase (IC50 in the range 4–32 μM) with some selectivity for BuChE. Most of the compounds also showed self-induced Aβ aggregation inhibitory activities, which were comparable or higher than those obtained for reference compounds, curcumin and myricetin. Docking and molecular dynamics (MD) simulation experiments suggested that the compounds are able to disrupt the dimer form of Aβ.

Piper betle Linn is one of the most common ethnomedicinal plants with its extract being popularly used in the modern product to enhance functionality. However, extraction methods always lead to differences in biological activities. The objectives of this study were to evaluate the effects of the extraction methods on the yield and biological activities of hydroxychavicol from P. betle L. extracts and to determine the correlation between the hydroxychavicol content and biological activities of P. betle L. extracts such as antioxidant, antimicrobial, and anticancer properties. The purity of the hydroxychavicol and its concentration (quantitative) in the crude extracts were also evaluated using a reverse-phase HPLC while GC–MS was employed to determine other components (qualitative). The results showed that only certain extraction procedures gave high yields of hydroxychavicol as well as remarkable biological activities. The chloroform extract following boiling with water (M2) gave the highest percentage of hydroxychavicol content based on the HPLC analysis. M2 and pure hydroxychavicol actively inhibited all the five cancer cell lines studied except A549. M2 showed more effective inhibition activity against MCF 7 with an IC50 of 1.74 ug/mL. M2 extract also showed strong antibacterial activity against all the bacteria strains as well as a strong antifungal activity against Candida albicans. There was, however, a weak correlation between the hydroxychavicol content and the biological activities of P. betle L. extracts. In conclusion, extraction procedures greatly affect the yield and biological activities of hydroxychavicol from P. betle L. The designation of a single compound such as hydroxychavicol as a bioactive chemical marker compound in the P. betle L. extracts, however, is not enough to determine the biological activities of the extract.

Dengue is a potentially deadly disease with no effective drug. An in silico molecular docking was performed using Autodock 4.2.6 to investigate the molecular interactions between protease inhibitors, comprising antibiotic derivatives namely doxycycline (3), rolitetracycline (5) and a non-steroidal anti-inflammatory drug (NSAID), meclofenamic acid (4), against the NS2B-NS3 protease from dengue virus-2 (DENV-2). The non-competitive inhibitor (3) showed lower binding energy (-5.15 kcal/mol) than the predicted competitive inhibitors 4 and 5 (-3.64 and -3.21 kcal/mol, respectively). Structural analyses showed compound 3 that bound to a specific allosteric site, interacted with Lys74, a significant amino acid residue bonded to one of the catalytic triad, Asp75. Compounds 4 and 5 showed direct binding with two of the catalytic triad, His51 and Ser135, hence, predicted to be competitive inhibitors.

Effective novel peptide inhibitors which targeted the domain III of the dengue envelope (E) protein by blocking dengue virus (DENV) entry into target cells, were identified. The binding affinities of these peptides towards E-protein were evaluated by using a combination of docking and explicit solvent molecular dynamics (MD) simulation methods. The interactions of these complexes were further investigated by using the Molecular Mechanics-Poisson Boltzmann Surface Area (MMPBSA) and Molecular Mechanics Generalized Born Surface Area (MMGBSA) methods. Free energy calculations of the peptides interacting with the E-protein demonstrated that van der Waals (vdW) and electrostatic interactions were the main driving forces stabilizing the complexes. Interestingly, calculated binding free energies showed good agreement with the experimental dissociation constant (Kd) values. Our results also demonstrated that specific residues might play a crucial role in the effective binding interactions. Thus, this study has demonstrated that a combination of docking and molecular dynamics simulations can accelerate the identification process of peptides as potential inhibitors of dengue virus entry into host cells.

Structure-based virtual screening (SBVS) has served as a popular strategy for rational drug discovery. In this study, we aimed to discover novel benzopyran-based inhibitors that targeted the NS3 enzymes (NS3/4A protease and NS3 helicase) of HCV G3 using a combination of in silico and in vitro approaches. With the aid of SBVS, six novel compounds were discovered to inhibit HCV G3 NS3/4A protease and two phytochemicals (ellagic acid and myricetin) were identified as dual-target inhibitors that inhibited both NS3/4A protease and NS3 helicase in vitro (IC50 = 40.37 ± 5.47 nm and 6.58 ± 0.99 µm, respectively). Inhibitory activities against the replication of HCV G3 replicons were further assessed in a cell-based system with four compounds showed dose-dependent inhibition. Compound P8 was determined to be the most potent compound from the cell-based assay with an EC50 of 19.05 µm. The dual-target inhibitor, ellagic acid, was determined as the second most potent (EC50 = 32.37 µm) and the most selective in its inhibitory activity against the replication of HCV replicons, without severely affecting the viability of the host cells (selectivity index > 6.18).