Therapeutic targeting of neuroinflammation in methamphetamine use disorder.

Methamphetamine (METH) is a highly addictive illicit psychostimulant with a significant annual fatality rate. Emerging studies highlight its role in neuroinflammation and a range of neurological disorders. This review examines the current landscape of potential drug targets for managing neuroinflammation in METH use disorders (MUDs), with a particular focus on the rationale behind targeting Toll-like receptor 4 (TLR4), the NLR family pyrin domain containing 3 (NLRP3) inflammasome, and other promising targets.

Inhibitory Effect of (2)-Pinocembrin From on the Prostaglandin E Production in Macrophage Cell Lines: and Studies.

Pinocembrin (PCB), a flavonoid known for its anti-inflammatory properties, has been approved for various clinical trial applications. To evaluate deeper into the anti-inflammatory potential of the specific enantiomer of natural PCB, we conducted the first investigation into the efficacy of the pure enantiomer (2)-PCB in modulating inflammatory mediators induced by lipopolysaccharide (LPS) in both murine RAW 264.7 and human U937 macrophage cell lines.

Inhibitory effect of food-functioned phytochemicals on dysregulated inflammatory pathways triggered by SARS-CoV-2: a mechanistic review.

Inflammatory cascades of the dysregulated inflammatory pathways in COVID-19 can cause excessive production of pro-inflammatory cytokines and chemokines leading to cytokine storm syndrome (CSS). The molecular cascades involved in the pathways may be targeted for discovery of new anti-inflammatory agents. Many plant extracts have been used clinically in the management of COVID-19, however, their immunosuppressive activities were mainly investigated based on activity.

Curcumin piperidone derivatives induce caspase-dependent apoptosis and suppress miRNA-21 expression in LN-18 human glioblastoma cells.

Background: Previously, we have reported on the two curcuminoid analogues with piperidone derivatives, namely FLDP-5 and FLDP-8 have more potent anti-proliferative and anti-migration effects than curcumin. In this study, we further investigated the mode of cell death and the mechanism involved in the cell death process induced by these analogues on human glioblastoma LN-18 cells.

Results: The FLDP-5 and FLDP-8 curcuminoid analogues induced LN-18 cell death through apoptosis in a concentration-dependent manner following 24 h of treatment.

Flavonoid diversity and roles in the lipopolysaccharide-mediated inflammatory response of monocytes and macrophages.

Targeting lipopolysaccharide (LPS)/toll-like receptor 4 signaling in mononuclear phagocytes has been explored for the treatment of inflammation and inflammation-related disorders. However, only a few key targets have been translated into clinical applications. Flavonoids, a class of ubiquitous plant secondary metabolites, possess a privileged scaffold which serves as a valuable template for designing pharmacologically active compounds directed against diseases with inflammatory components.

A Study of the Interaction between Xanthine Oxidase and Its Inhibitors from Using Computational Simulation and Multispectroscopic Methods.

The current therapeutic approach for gout is through the inhibition of the xanthine oxidase (XO) enzyme. Allopurinol, a clinically used XO inhibitor, causes many side effects. This study aimed to investigate the interaction between XO and inhibitors identified from by using computational simulation and multispectroscopic methods.

Ensemble-based, high-throughput virtual screening of potential inhibitor targeting putative farnesol dehydrogenase of Metisa plana (Lepidoptera: Psychidae).

Metisa plana (Lepidoptera: Psychidae) bagworm is a leaf-eater caterpillar ubiquitously found as a damaging pest in oil palm plantations, specifically in Malaysia. Various strategies have been implemented, including the usage of chemical insecticides. However, the main challenges include the development of insecticide resistance and its detrimental effects on the environment and non-target organisms.

Isolation, purification and biochemical characterization of Conopomorpha cramerella farnesol dehydrogenase.

In Southeast Asia, Conopomorpha cramerella (Snellen) which is commonly known as the cocoa pod borer (CPB) moth has been identified as the most detrimental pest of Theobroma cacao L. Apart from the various side effects on human health and non-target organisms, heavily relying on synthetic pyrethroid insecticides to control CPB infestations also increases the environmental contamination risks. Thus, developing biorational insecticides that minimally affect the non-target organism and environment by targeting the insect growth regulation process is needed to manage the pest population.

Synthesis of 1-hydroxy-3--substituted xanthone derivatives and their structure-activity relationship on acetylcholinesterase inhibitory effect.

This study focused on the synthesis of 1,3-dihydroxyxanthone () and its new derivatives with alkyl (-), alkenyl (-), alkynyl (-), and alkylated phenyl (-) groups at C3 position. The structures of these compounds were confirmed by MS, NMR, and FTIR spectroscopic data. All the substituted xanthones (-) showed significantly stronger acetylcholinesterase (AChE) inhibitory activities than .

Curcumin piperidone derivatives induce anti-proliferative and anti-migratory effects in LN-18 human glioblastoma cells.

Curcumin has demonstrated potential cytotoxicity across various cell lines despite its poor bioavailability and rapid metabolism. Therefore, our group have synthesized curcuminoid analogues with piperidone derivatives, FLDP-5 and FLDP-8 to overcome these limitations. In this study, the analogues were assessed on LN-18 human glioblastoma cells in comparison to curcumin.

Genistein: A Review on its Anti-Inflammatory Properties.

Nowadays, non-resolving inflammation is becoming a major trigger in various diseases as it plays a significant role in the pathogenesis of atherosclerosis, asthma, cancer, obesity, inflammatory bowel disease, chronic obstructive pulmonary disease, neurodegenerative disease, multiple sclerosis, and rheumatoid arthritis. However, prolonged use of anti-inflammatory drugs is usually accompanied with undesirable effects and hence more patients tend to seek for natural compounds as alternative medicine. Considering the fact above, there is an urgency to discover and develop potential novel, safe and efficacious natural compounds as drug candidates for future anti-inflammatory therapy.

Synthesis, Molecular Docking, and Antimalarial Activity of Hybrid 4-Aminoquinoline-pyrano[2,3-c]pyrazole Derivatives.

Widespread resistance of to current artemisinin-based combination therapies necessitate the discovery of new medicines. Pharmacophoric hybridization has become an alternative for drug resistance that lowers the risk of drug-drug adverse interactions. In this study, we synthesized a new series of hybrids by covalently linking the scaffolds of pyrano[2,3-c]pyrazole with 4-aminoquinoline via an ethyl linker.

Purification, biochemical characterisation and bioinformatic analysis of recombinant farnesol dehydrogenase from Theobroma cacao.

The juvenile hormones (JH) in plants are suggested to act as a form of plant defensive strategy especially against insect herbivory. The oxidation of farnesol to farnesoic acid is a key step in the juvenile hormone biosynthesis pathway. We herein present the purification and characterisation of the recombinant Theobroma cacao farnesol dehydrogenase enzyme that catalyses oxidation of farnesol to farnesal.

New 3--substituted xanthone derivatives as promising acetylcholinesterase inhibitors.

A new series of 3--substituted xanthone derivatives were synthesised and evaluated for their anti-cholinergic activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The results indicated that the xanthone derivatives possessed good AChE inhibitory activity with eleven of them (, , , , , -, -) exhibited significant effects with the IC values ranged 0.88 to 1.

Mechanistic Studies of the Antiallergic Activity of Schum. & Thonn. and Its Compounds.

Schum. & Thonn. (Phyllanthaceae) is a medicinal plant that is commonly used to treat diseases such as asthma, diabetes, and anemia.

Recent progress in small molecule agents for the targeted therapy of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive type of cancer, with a high risk of death on recurrence. To date, there is a lack of approved targeted agents for the treatment of the disease. Patients with TNBC continue to depend on surgery, chemotherapy, and radiotherapy, all of which have a wide side effect profile.

Genetic diversity and in silico evidence of target-site mutation in the EPSPS gene in endowing glyphosate resistance in Eleusine indica (L.) from Malaysia.

Glyphosate-resistant populations of Eleusine indica are widespread in several states of Malaysia. A whole-plant bioassay confirmed that eight out of the 17 populations tested were resistant to glyphosate at double the recommended rate of 2.44 kg ha.

In vitro anti-allergic activity of Moringa oleifera Lam. extracts and their isolated compounds.

Background: Moringa oleifera Lam. is a commonly used plant in herbal medicine and has various reported bioactivities such as antioxidant, antimicrobial, anticancer and antidiabetes. It is rich in nutrients and polyphenols.

Insights on the synthesis of asymmetric curcumin derivatives and their biological activities.

Curcumin is a small organic molecule with pleiotropic biological activities. However, its multiple structural-pharmacokinetic challenges prevent its development into a clinical drug. Various structural modifications have been made to improve its drug profile.

Hits-to-Lead Optimization of the Natural Compound 2,4,6-Trihydroxy-3-geranyl-acetophenone (tHGA) as a Potent LOX Inhibitor: Synthesis, Structure-Activity Relationship (SAR) Study, and Computational Assignment.

A new series of 2,4,6-trihydroxy-3-geranyl-acetophenone (tHGA) analogues were synthesized and evaluated for their lipoxygenase (LOX) inhibitory activity. Prenylated analogues ⁻ (half maximal inhibitory concentration (IC) values ranging from 35 μ M to 95 μ M) did not exhibit better inhibitory activity than tHGA () (IC value: 23.6 μ M) due to the reduction in hydrophobic interaction when the alkyl chain length was reduced.

The Molecular Targets and Anti-Invasive Effects of 2,6-bis-(4-hydroxyl-3methoxybenzylidine) cyclohexanone or BHMC in MDA-MB-231 Human Breast Cancer Cells.

In order to metastasize, tumor cells need to migrate and invade the surrounding tissues. It is important to identify compound(s) capable of disrupting the metastasis of invasive cancer cells, especially for hindering invadopodia formation, so as to provide anti-metastasis targeted therapy. Invadopodia are thought to be specialized actin-rich protrusions formed by highly invasive cancer cells to degrade the extracellular matrix (ECM).

In vitro and in silico evaluations of diarylpentanoid series as α-glucosidase inhibitor.

A series of thirty-four diarylpentanoids derivatives were synthesized and evaluated for their α-glucosidase inhibitory activity. Eleven compounds (19, 20, 21, 24, 27, 28, 29, 31, 32, 33 and 34) were found to significantly inhibit α-glucosidase in which compounds 28, 31 and 32 demonstrated the highest activity with IC values ranging from 14.1 to 15.

Effects of Tocotrienols on Insulin Secretion-Associated Genes Expression of Rat Pancreatic Islets in a Dynamic Culture.

Tocotrienols (T3) are well-known for their antioxidant properties besides showing therapeutic potential in clinical complications such as hyperlipidemia induced by diabetes. The aim of this study was to determine the effects of δ-T3, γ-T3, and α-T3 on insulin secretion-associated genes expression of rat pancreatic islets in a dynamic culture. Pancreatic islets freshly isolated from male Wistar rats were treated with T3 for 1 h at 37°C in a microfluidic system with continuous operation.

2-Benzoyl-6-benzylidenecyclohexanone analogs as potent dual inhibitors of acetylcholinesterase and butyrylcholinesterase.

In the present study, a series of 2-benzoyl-6-benzylidenecyclohexanone analogs have been synthesized and evaluated for their anti-cholinesterase activity. Among the forty-one analogs, four compounds (38, 39, 40 and 41) have been identified as lead compounds due to their highest inhibition on both AChE and BChE activities. Compounds 39 and 40 in particular exhibited highest inhibition on both AChE and BChE with IC50 values of 1.

Synthesis of unsymmetrical monocarbonyl curcumin analogues with potent inhibition on prostaglandin E2 production in LPS-induced murine and human macrophages cell lines.

The syntheses and bioactivities of symmetrical curcumin and its analogues have been the subject of interest by many medicinal chemists and pharmacologists over the years. To improve our understanding, we have synthesized a series of unsymmetrical monocarbonyl curcumin analogues and evaluated their effects on prostaglandin E2 production in lipopolysaccharide-induced RAW264.7 and U937 cells.