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Ligand expansion in ligand-based virtual screening using relevance feedback

Abdo A, Saeed F, Hamza H, Ahmed A, Salim N

J Comput Aided Mol Des, 2012 Mar;26(3):279-87.
PMID: 22249773 DOI: 10.1007/s10822-012-9543-4

Query expansion is the process of reformulating an original query to improve retrieval performance in information retrieval systems. Relevance feedback is one of the most useful query modification techniques in information retrieval systems. In this paper, we introduce query expansion into ligand-based virtual screening (LBVS) using the relevance feedback technique. In this approach, a few high-ranking molecules of unknown activity are filtered from the outputs of a Bayesian inference network based on a single ligand molecule to form a set of ligand molecules. This set of ligand molecules is used to form a new ligand molecule. Simulated virtual screening experiments with the MDL Drug Data Report and maximum unbiased validation data sets show that the use of ligand expansion provides a very simple way of improving the LBVS, especially when the active molecules being sought have a high degree of structural heterogeneity. However, the effectiveness of the ligand expansion is slightly less when structurally-homogeneous sets of actives are being sought.

Matched MeSH terms: Drug Evaluation, Preclinical/methods*
New fragment weighting scheme for the Bayesian inference network in ligand-based virtual screening

Abdo A, Salim N

J Chem Inf Model, 2011 Jan 24;51(1):25-32.
PMID: 21155550 DOI: 10.1021/ci100232h

Many of the conventional similarity methods assume that molecular fragments that do not relate to biological activity carry the same weight as the important ones. One possible approach to this problem is to use the Bayesian inference network (BIN), which models molecules and reference structures as probabilistic inference networks. The relationships between molecules and reference structures in the Bayesian network are encoded using a set of conditional probability distributions, which can be estimated by the fragment weighting function, a function of the frequencies of the fragments in the molecule or the reference structure as well as throughout the collection. The weighting function combines one or more fragment weighting schemes. In this paper, we have investigated five different weighting functions and present a new fragment weighting scheme. Later on, these functions were modified to combine the new weighting scheme. Simulated virtual screening experiments with the MDL Drug Data Report (23) and maximum unbiased validation data sets show that the use of new weighting scheme can provide significantly more effective screening when compared with the use of current weighting schemes.

Matched MeSH terms: Drug Evaluation, Preclinical/methods*
Fulltext Ligand-based virtual screening using Bayesian networks

Abdo A, Chen B, Mueller C, Salim N, Willett P

J Chem Inf Model, 2010 Jun 28;50(6):1012-20.
PMID: 20504032 DOI: 10.1021/ci100090p

A Bayesian inference network (BIN) provides an interesting alternative to existing tools for similarity-based virtual screening. The BIN is particularly effective when the active molecules being sought have a high degree of structural homogeneity but has been found to perform less well with structurally heterogeneous sets of actives. In this paper, we introduce an alternative network model, called a Bayesian belief network (BBN), that seeks to overcome this limitation of the BIN approach. Simulated virtual screening experiments with the MDDR, WOMBAT and MUV data sets show that the BIN and BBN methods allow effective screening searches to be carried out. However, the results obtained are not obviously superior to those obtained using a much simpler approach that is based on the use of the Tanimoto coefficient and of the square roots of fragment occurrence frequencies.

Matched MeSH terms: Drug Evaluation, Preclinical/methods*
Fulltext Knowledge-Based Methods To Train and Optimize Virtual Screening Ensembles

Swift RV, Jusoh SA, Offutt TL, Li ES, Amaro RE

J Chem Inf Model, 2016 05 23;56(5):830-42.
PMID: 27097522 DOI: 10.1021/acs.jcim.5b00684

Ensemble docking can be a successful virtual screening technique that addresses the innate conformational heterogeneity of macromolecular drug targets. Yet, lacking a method to identify a subset of conformational states that effectively segregates active and inactive small molecules, ensemble docking may result in the recommendation of a large number of false positives. Here, three knowledge-based methods that construct structural ensembles for virtual screening are presented. Each method selects ensembles by optimizing an objective function calculated using the receiver operating characteristic (ROC) curve: either the area under the ROC curve (AUC) or a ROC enrichment factor (EF). As the number of receptor conformations, N, becomes large, the methods differ in their asymptotic scaling. Given a set of small molecules with known activities and a collection of target conformations, the most resource intense method is guaranteed to find the optimal ensemble but scales as O(2(N)). A recursive approximation to the optimal solution scales as O(N(2)), and a more severe approximation leads to a faster method that scales linearly, O(N). The techniques are generally applicable to any system, and we demonstrate their effectiveness on the androgen nuclear hormone receptor (AR), cyclin-dependent kinase 2 (CDK2), and the peroxisome proliferator-activated receptor δ (PPAR-δ) drug targets. Conformations that consisted of a crystal structure and molecular dynamics simulation cluster centroids were used to form AR and CDK2 ensembles. Multiple available crystal structures were used to form PPAR-δ ensembles. For each target, we show that the three methods perform similarly to one another on both the training and test sets.

Matched MeSH terms: Drug Evaluation, Preclinical/methods*
Fulltext Rapid-response RNA-fluorescence in situ hybridization (FISH) assay platform for coronavirus antiviral high-throughput screening

Chan R, Mugisha CS, Chuenchob V, Moquin SA, Manjunatha UH, Jarrousse N, et al.

SLAS Discov, 2024 Dec;29(8):100189.
PMID: 39499968 DOI: 10.1016/j.slasd.2024.100189

Over the past 25 years, the global community has faced challenges posed by three distinct outbreaks of coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The identification of a novel alphacoronavirus canine CoV (CCoV-HuPn2018) in human patients in Malaysia underscores the potential for crossover infections to humans. The threat of the ever-evolving nature of viral infections as well as the lingering health and socioeconomic effects of the recent SARS-CoV-2 pandemic emphasize the urgent need for advanced antiviral drug screening tools that can be quickly implemented to strengthen preparedness and preventive measures against future outbreaks. Here, we present the development and validation of a novel RNA-fluorescence in situ hybridization (FISH) imaging assay as a 384-well, high-throughput rapid response platform for antiviral drug discovery. RNA-FISH is a powerful tool to visualize specific mRNA in cultured cells using a high-content imaging platform. The flexibility of RNA-FISH probe sets allows for the rapid design of viral genome-specific probes, enabling in vitro assay development to test for inhibition of viral replication by either biologic or small molecule inhibitors. Screening of 170 antiviral compounds in concentration-response demonstrates a strong correlation between the RNA-FISH assay and an immunofluorescence assay (IFA) for both human coronaviruses HCoV-OC43 and HCoV-229E. Additionally, we successfully applied this methodology in the context of CCoV strain 1-71, proving rapid development and deployment, opening new avenues for the evaluation of antiviral drugs to potential future emerging threats.

Matched MeSH terms: Drug Evaluation, Preclinical/methods
Rethinking zebrafish anxiety models in drug discovery and precision psychiatry

Abdul Basit NS, Yap MMC, Mah YK, Ogawa S

Expert Opin Drug Discov, 2026 Nov;21(11):1227-1241.
PMID: 42847163 DOI: 10.1080/17460441.2026.2743766

INTRODUCTION: Anxiety disorders are among the most prevalent psychiatric conditions worldwide, yet the development of novel anxiolytic therapies remains limited by poor translational success and the complexity of anxiety neurobiology. Zebrafish (Danio rerio) have emerged as a valuable vertebrate model bridging high-throughput in vitro screening and mammalian preclinical studies by combining whole-organism physiology with scalable phenotypic screening.
AREAS COVERED: This review evaluates advances in zebrafish models for anxiolytic drug discovery, focusing on features supporting their construct and predictive validity. Larval zebrafish enable high-throughput behavioral and imaging-based screening, whereas adults provide more complex behavioral phenotypes and translational validation. Genetically engineered models, automated behavioral tracking, functional imaging, and molecular profiling further support mechanism-based drug discovery. A targeted search of PubMed/MEDLINE, Web of Science, and Scopus identified current and foundational studies on zebrafish anxiety models, neurobiology, behavioral assays, and drug discovery.
EXPERT OPINION: Integration of behavioral phenotyping with genetics, multi-omics, functional imaging, and artificial intelligence could transform zebrafish from a screening organism into an integrated platform for precision psychiatry and personalized neuropsychopharmacological drug discovery, and improving translation across experimental scales. Zebrafish are best positioned as an efficient intermediate translational model that accelerates mechanism-based anxiolytic discovery while complementing, rather than replacing, mammalian preclinical studies.

Matched MeSH terms: Drug Evaluation, Preclinical/methods
A screening method for cardiovascular active compounds in marine algae

Agatonovic-Kustrin S, Kustrin E, Angove MJ, Morton DW

J Chromatogr A, 2018 May 18;1550:57-62.
PMID: 29615323 DOI: 10.1016/j.chroma.2018.03.054

The interaction of bioactive compounds from ethanolic extracts of selected marine algae samples, separated on chromatographic plates, with nitric/nitrous acid was investigated. The nature of bioactive compounds in the marine algae extracts was characterised using UV absorption spectra before and after reaction with diluted nitric acid, and from the characteristic colour reaction after derivatization with anisaldehyde. It was found that diterpenes from Dictyota dichotoma, an edible brown algae, and sterols from green algae Caulerpa brachypus, bind nitric oxide and may act as a nitric oxide carrier. Although the carotenoid fucoxanthin, found in all brown marine algae also binds nitric oxide, the bonds between nitrogen and the fucoxanthin molecule are much stronger. Further studies are required to evaluate the effects of diterpenes from Dictyota dichotoma and sterols from green algae Caulerpa brachypus to see if they have beneficial cardiovascular effects. The method reported here should prove useful in screening large numbers of algae species for compounds with cardiovascular activity.

Matched MeSH terms: Drug Evaluation, Preclinical/methods*
An evaluation of crude palm oil (CPO) and tocotrienol rich fraction (TRF) of palm oil as percutaneous permeation enhancers using full-thickness human skin

Singh I, Nair RS, Gan S, Cheong V, Morris A

Pharm Dev Technol, 2019 Apr;24(4):448-454.
PMID: 30084268 DOI: 10.1080/10837450.2018.1509347

The drawbacks associated with chemical skin permeation enhancers such as skin irritation and toxicity necessitated the research to focus on potential permeation enhancers with a perceived lower toxicity. Crude palm oil (CPO) is obtained by direct compression of the mesocarp of the fruit of the oil palm belonging to the genus Elaeis. In this research, CPO and tocotrienol-rich fraction (TRF) of palm oil were evaluated for the first time as skin permeation enhancers using full-thickness human skin. The in vitro permeation experiments were conducted using excised human skin mounted in static upright 'Franz-type' diffusion cells. The drugs selected to evaluate the enhancing effects of these palm oil derivatives were 5-fluorouracil, lidocaine and ibuprofen: compounds covering a wide range of Log p values. It was demonstrated that CPO and TRF were capable of enhancing the percutaneous permeation of drugs across full-thickness human skin in vitro. Both TRF and CPO were shown to significantly enhance the permeation of ibuprofen with flux values of 30.6 µg/cm2 h and 23.0 µg/cm2 h respectively, compared to the control with a flux of 16.2 µg/cm2 h. The outcome of this research opens further scope for investigation on the transdermal penetration enhancement activity of pure compounds derived from palm oil.

Matched MeSH terms: Drug Evaluation, Preclinical/methods
Aphrodisiac evaluation in non-copulator male rats after chronic administration of Eurycoma longifolia Jack

Ang HH, Ngai TH

Fundam Clin Pharmacol, 2001 Aug;15(4):265-8.
PMID: 11564133 DOI: 10.1046/j.1472-8206.2001.00038.x

The aphrodisiac effect of Eurycoma longifolia Jack (0.5 g/kg) was evaluated in noncopulator male rats using an electrical cage. Fractions of E. longifolia Jack decreased the hesitation time of noncopulator male rats, throughout the investigation period. Furthermore, it possessed a transient increase in the percentage of the male rats responding to the right choice, more than 50% of the male rats scored "right choice" after 3 weeks post-treatment and the effect became more prominent after 8 weeks post-treatment (only 40-50% of the control male rats responded to the right choice) using the electrical copulation cage. Hence, this study lends further support to the use of the plant by indigenous populations as a traditional medicine for its aphrodisiac property.

Matched MeSH terms: Drug Evaluation, Preclinical/methods
Evaluation of superabsorbent linseed-polysaccharides as a novel stimuli-responsive oral sustained release drug delivery system

Haseeb MT, Hussain MA, Bashir S, Ashraf MU, Ahmad N

Drug Dev Ind Pharm, 2017 Mar;43(3):409-420.
PMID: 27808567 DOI: 10.1080/03639045.2016.1257017

CONTEXT: Advancement in technology has transformed the conventional dosage forms to intelligent drug delivery systems. Such systems are helpful for targeted and efficient drug delivery with minimum side effects. Drug release from these systems is governed and controlled by external stimuli (pH, enzymes, ions, glucose, etc.). Polymeric biomaterial having stimuli-responsive properties has opened a new area in drug delivery approach.
OBJECTIVE: Potential of a polysaccharide (rhamnogalacturonan)-based hydrogel from Linseeds (Linum usitatissimum L.) was investigated as an intelligent drug delivery material.
MATERIALS AND METHODS: Different concentrations of Linseed hydrogel (LSH) were used to prepare caffeine and diacerein tablets and further investigated for pH and salt solution-responsive swelling, pH-dependent drug release, and release kinetics. Morphology of tablets was observed using SEM.
RESULTS: LSH tablets exhibited dynamic swelling-deswelling behavior with tendency to swell at pH 7.4 and in deionized water while deswell at pH 1.2, in normal saline and ethanol. Consequently, pH controlled release of the drugs was observed from tablets with lower release (<10%) at pH 1.2 and higher release at pH 6.8 and 7.4. SEM showed elongated channels in swollen then freeze-dried tablets.
DISCUSSION: The drug release was greatly influenced by the amount of LSH in the tablets. Drug release from LSH tablets was governed by the non-Fickian diffusion.
CONCLUSIONS: These finding indicates that LSH holds potential to be developed as sustained release material for tablet.

Matched MeSH terms: Drug Evaluation, Preclinical/methods
Fulltext Antinociceptive activities of a novel diarylpentanoid analogue, 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol, and its possible mechanisms of action in mice

Ong HM, Azmi AFA, Leong SW, Abas F, Perimal EK, Farouk AAO, et al.

Sci Rep, 2021 12 16;11(1):24121.
PMID: 34916536 DOI: 10.1038/s41598-021-02961-1

A novel synthetic compound from the 2-benzoyl-6-benzylidenecyclohexanone analogue, namely 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol (BBHC), showed pronounced nitric oxide inhibition in IFN-γ/LPS-induced RAW 264.7 cells. Based on this previous finding, our present study aimed to investigate the antinociceptive effects of BBHC via chemical and thermal stimuli in vivo. The investigation of the antinociceptive activity of BBHC (0.1, 0.3, 1.0 and 3.0 mg/kg, i.p.) was initiated with 3 preliminary screening tests, then BBHC was subjected to investigate its possible involvement with excitatory neurotransmitters and opioid receptors. The potential acute toxicity of BBHC administration was also studied. Administration of BBHC significantly inhibited acetic acid-induced abdominal constrictions, formalin-induced paw licking activity and developed notable increment in the latency time. BBHC's ability to suppress capsaicin- and glutamate-induced paw licking activities, as well as to antagonise the effect of naloxone, had indicated the possible involvement of its antinociception with TRPV1, glutamate and opioid receptors, respectively. The antinociceptive activities of BBHC was not related to any sedative action and no evidence of acute toxic effect was detected. The present study showed that BBHC possessed significant peripheral and central antinociceptive activities via chemical- and thermal-induced nociceptive murine models without any locomotor alteration and acute toxicity.

Matched MeSH terms: Drug Evaluation, Preclinical/methods
Fulltext Ligand-based virtual screening using Bayesian inference network and reweighted fragments

Ahmed A, Abdo A, Salim N

ScientificWorldJournal, 2012;2012:410914.
PMID: 22623895 DOI: 10.1100/2012/410914

Many of the similarity-based virtual screening approaches assume that molecular fragments that are not related to the biological activity carry the same weight as the important ones. This was the reason that led to the use of Bayesian networks as an alternative to existing tools for similarity-based virtual screening. In our recent work, the retrieval performance of the Bayesian inference network (BIN) was observed to improve significantly when molecular fragments were reweighted using the relevance feedback information. In this paper, a set of active reference structures were used to reweight the fragments in the reference structure. In this approach, higher weights were assigned to those fragments that occur more frequently in the set of active reference structures while others were penalized. Simulated virtual screening experiments with MDL Drug Data Report datasets showed that the proposed approach significantly improved the retrieval effectiveness of ligand-based virtual screening, especially when the active molecules being sought had a high degree of structural heterogeneity.

Matched MeSH terms: Drug Evaluation, Preclinical/methods*
Design, synthesis, in vitro cytotoxicity evaluation and structure-activity relationship of goniothalamin analogs

Mohideen M, Zulkepli S, Nik-Salleh NS, Zulkefeli M, Weber JF, Weber JF, et al.

Arch Pharm Res, 2013 Jul;36(7):812-31.
PMID: 23543632 DOI: 10.1007/s12272-013-0099-1

A series of six/five member (E/Z)-Goniothalamin analogs were synthesized from commercially available (3,4-dihydro-2H-pyran-2-yl)methanol/5-(hydroxymethyl)dihydrofuran-2(3H)-one in three steps with good to moderate overall yields and their cytotoxicity against lymphoblastic leukemic T cell line (Jurkat E6.1) have been evaluated. Among the synthesized analogs, (Z)-Goniothalamin appeared to be the most active in cytotoxicity (IC50 = 12 μM). Structure-activity relationship study indicates that introducing substituent in phenyl ring or replacing phenyl ring by pyridine/naphthalene, or decreasing the ring size of lactones (from six to five member) do not increase the cytotoxicity.

Matched MeSH terms: Drug Evaluation, Preclinical/methods
Drug-like and non drug-like pattern classification based on simple topology descriptor using hybrid neural network

Wan-Mamat WM, Isa NA, Wahab HA, Wan-Mamat WM

Annu Int Conf IEEE Eng Med Biol Soc, 2009;2009:6424-7.
PMID: 19964424 DOI: 10.1109/IEMBS.2009.5333747

An intelligent prediction system has been developed to discriminate drug-like and non drug-like molecules pattern. The system is constructed by using the application of advanced version of standard multilayer perceptron (MLP) neural network called Hybrid Multilayer Perceptron (HMLP) neural network and trained using Modified Recursive Prediction Error (MRPE) training algorithm. In this work, a well understood and easy excess Rule of Five + Veber filter properties are selected as the topological descriptor. The main idea behind the selection of this simple descriptor is to assure that the system could be used widely, beneficial and more advantageous regardless at all user level within a drug discovery organization.

Matched MeSH terms: Drug Evaluation, Preclinical/methods*
In vitro and in vivo evaluation of self-microemulsifying drug delivery system of buparvaquone

Venkatesh G, Majid MI, Mansor SM, Nair NK, Croft SL, Navaratnam V

Drug Dev Ind Pharm, 2010 Jun;36(6):735-45.
PMID: 20136493 DOI: 10.3109/03639040903460446

The aim of this study was to prepare a lipid-based self-microemulsifying drug delivery system (SMEDDS) to increase the solubility and oral bioavailability of a poorly water-soluble compound, buparvaquone (BPQ).

Matched MeSH terms: Drug Evaluation, Preclinical/methods
Synthesis of new oxadiazole derivatives as α-glucosidase inhibitors

Taha M, Ismail NH, Imran S, Rokei MQB, Saad SM, Khan KM

Bioorg Med Chem, 2015 Aug 01;23(15):4155-4162.
PMID: 26183542 DOI: 10.1016/j.bmc.2015.06.060

Oxadiazole derivatives (6-28) having hydrazone linkage, were synthesized through condensation reaction between benzohydrazide 5 with various benzaldehydes. The oxadiazoles derivatives (6-28) were evaluated for their α-glucosidase inhibitory activity. The IC50 values for inhibition activity vary in the range between 2.64 ± 0.05 and 460.14 ± 3.25 μM. The IC50 values were being compared to the standard acarbose (IC50=856.45 ± 5.60 μM) and it was found that compounds 6-9, 12, 13, 16, 18, 20, 22-28 were found to be more active than acarbose, while other compounds showed no activity. Structure-activity relationship (SAR) studies suggest that oxadiazole benzohydrazones (6-28) inhibitory potential is dependent on substitution of the N-benzylidene part. Compound 18 (IC50=2.64 ± 0.05 μM), which has trihydroxy substitution at C-2', C-4', and C-5' on N-benzylidene moiety, recorded the highest inhibition activity that is three-hundred times more active than the standard drug, acarbose (IC50=856.45 ± 5.60 μM). Compound 23 (IC50=34.64 ± 0.35 μM) was found to be the most active among compounds having single hydroxyl substitution. Shifting hydroxyl from C-2' to C-4' (6) and C-3' (7) reduces inhibitory activity significantly. Compounds with chlorine substituent (compounds 16, 28, and 27) showed potent activities but lower as compared to hydroxyl analogs. Substituent like nitro or methyl groups at any position suppresses enzyme inhibition activity. This reveals the important presence of hydroxyl and halo groups to have enzyme inhibitory potential.

Matched MeSH terms: Drug Evaluation, Preclinical/methods
A bioactive cycloartane triterpene from Garcinia hombroniana

Jamila N, Khan N, Khan I, Khan AA, Khan SN

Nat Prod Res, 2016 Jun;30(12):1388-97.
PMID: 26158779 DOI: 10.1080/14786419.2015.1060594

The dichloromethane bark extract of Garcinia hombroniana yielded one new cycloartane triterpene; (22Z,24E)-3β-hydroxycycloart-14,22,24-trien-26-oic acid (1) together with five known compounds: garcihombronane G (2), garcihombronane J (3), 3β acetoxy-9α-hydroxy-17,14-friedolanostan-14,24-dien-26-oic acid (4), (22Z, 24E)-3β, 9α-dihydroxy-17,14-friedolanostan-14,22,24-trien-26-oic acid (5) and 3β, 23α-dihydroxy-17,14-friedolanostan-8,14,24-trien-26-oic acid (6). Their structures were established by the spectral techniques of NMR and ESI-MS. These compounds together with some previously isolated compounds; garcihombronane B (7), garcihombronane D (8) 2,3',4,5'-tetrahydroxy-6-methoxybenzophenone (9), volkensiflavone (10), 4''-O-methyll-volkensiflavone (11), volkensiflavone-7-O-glucopyranoside (12), volkensiflavone-7-O-rhamnopyranoside (13), Morelloflavone (14), 3''-O-methyl-morelloflavone (15) and morelloflavone-7-O-glucopyranoside (16) were evaluated for cholinesterase enzymes inhibitory activities using acetylcholinesterase and butyrylcholinesterase. In these activities, compounds 1-9 showed good dual inhibition on both the enzymes while compounds 10-16 did not reasonably contribute to both the cholinesterases inhibitory effects.

Matched MeSH terms: Drug Evaluation, Preclinical/methods
Acetyl- and O-alkyl- derivatives of β-mangostin from Garcinia mangostana and their anti-inflammatory activities

Karunakaran T, Ee GCL, Ismail IS, Mohd Nor SM, Zamakshshari NH

Nat Prod Res, 2018 Jun;32(12):1390-1394.
PMID: 28715912 DOI: 10.1080/14786419.2017.1350666

Pure β-mangostin (1) was isolated from the stem bark of Garcinia mangostana L. One monoacetate (2) and five O-alkylated β-mangostin derivatives (3-7) were synthesised from β-mangostin. The structures of these compounds were elucidated and determined using spectroscopic techniques such as 1D NMR and MS. The cytotoxicities and anti-inflammatory activities of these five compounds against RAW cell 264.7 were tested. The structural-activity relationship studies indicated that β-mangostin showed a significant activity against the LPS-induced RAW cell 264.7, while the acetyl- as well as the O-alkyl- β-mangostin derivatives did not give good activity. Naturally occurring β-mangostin demonstrated comparatively better anti-inflammatory activity than its synthetic counterparts.

Matched MeSH terms: Drug Evaluation, Preclinical/methods
Fulltext Life-span extension by pigmented rice bran in the model yeast Saccharomyces cerevisiae

Sunthonkun P, Palajai R, Somboon P, Suan CL, Ungsurangsri M, Soontorngun N

Sci Rep, 2019 12 02;9(1):18061.
PMID: 31792269 DOI: 10.1038/s41598-019-54448-9

Benefits of whole grains as dietary supplements and active ingredients in health products have been promoted. Despite being neglected as an agricultural byproduct of polished rice, pigmented rice bran has emerged as a promising source of natural anti-aging compounds. Indeed, the extract of red rice bran Hom Dang cultivar contained rich phenolic acids and flavonoids. It displayed high antioxidant activities in vitro and in vivo assays. Using yeast model, extract and bioactive compounds, quercetin and protocatechuic acid found in the rice bran pericarp, effectively reduced levels of intracellular reactive oxygen species (ROS), restored plasma membrane damages and prolonged life-span of pre-treated wild-yeast cells. Importantly, these molecules modulated life span-extension through a mechanism of ROS reduction that resembles to that operated under the highly conserved Tor1- and Sir2-dependent signaling pathways, with the human homologs TORC1 and SIRT1, respectively. The key longevity factors Sch9 and Rim15 kinases, Msn2/4 regulators and a novel transcription factor Asg1, the antioxidant enzymes superoxide dismutases and glutathione peroxidases played important role in mediating longevity. Yeast clearly provides an instrumental platform for rapid screening of compounds with anti-aging efficacies and advances knowledge in the molecular study of ageing.

Matched MeSH terms: Drug Evaluation, Preclinical/methods
Fulltext Metabolic profiling and in vitro assessment of anthelmintic fractions of Picria fel-terrae Lour

Kumarasingha R, Karpe AV, Preston S, Yeo TC, Lim DSL, Tu CL, et al.

Int J Parasitol Drugs Drug Resist, 2016 12;6(3):171-178.
PMID: 27639945 DOI: 10.1016/j.ijpddr.2016.08.002

Anthelmintic resistance is widespread in gastrointestinal nematode populations, such that there is a consistent need to search for new anthelmintics. However, the cost of screening for new compounds is high and has a very low success rate. Using the knowledge of traditional healers from Borneo Rainforests (Sarawak, Malaysia), we have previously shown that some traditional medicinal plants are a rich source of potential new anthelmintic drug candidates. In this study, Picria fel-terrae Lour. plant extract, which has previously shown promising anthelmintic activities, was fractionated via the use of a solid phase extraction cartridge and each isolated fraction was then tested on free-living nematode Caenorhabditis elegans and the parasitic nematode Haemonchus contortus. We found that a single fraction was enriched for nematocidal activity, killing ≥90% of C. elegans adults and inhibiting the motility of exsheathed L3 of H. contortus, while having minimal cytotoxic activity in mammalian cell culture. Metabolic profiling and chemometric analysis of the effective fraction indicated medium chained fatty acids and phenolic acids were highly represented.

Matched MeSH terms: Drug Evaluation, Preclinical/methods*

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