Molecular regulation and subtype-specific effects of naringenin and naringin on nicotinic acetylcholine receptors expressed in Xenopus oocytes.

Naringenin and naringin, bioactive flavonoids from citrus fruits, exhibit neuroprotective effects, showing promise for neurodegenerative diseases like Alzheimer's and Parkinson's. Additionally, they demonstrate significant anticancer potential, modulating key signaling pathways involved in tumor growth, apoptosis, and metastasis, thus expanding their therapeutic applications in cancer treatment. These compounds interact with nicotinic acetylcholine receptors (nAChRs), a class of ligand-gated ion channels critical for modulating neurotransmission within the central nervous system.

Phenethyl Acetate as an Agonist of Insect Odorant Receptor Co-Receptor (Orco): Molecular Mechanisms and Functional Insights.

The insect olfactory system is vital for survival, enabling the recognition and discrimination of a wide range of odorants present in the environment. This process is mediated by odorant receptors (Ors) and the highly conserved co-receptor Orco. Insect Ors are structurally distinct from mammalian olfactory receptors, a divergence that presents unique advantages for developing insect-specific pest control strategies.

Tripterygium-derived celastrol inhibits 5-HT3A receptors via key residue interactions: A comparative electrophysiological and docking study.

This study examines the effects of three Tripterygium wilfordii compounds-celastrol, triptolide, and triptonide-on 5-HT3A receptors. Using two-electrode voltage-clamp recordings, we found all three compounds reversibly and concentration-dependently inhibited 5-HT-induced inward currents (I), with celastrol showing the strongest inhibition (∼83 % at 100 µM) compared to triptolide (∼40 %) and triptonide (∼30 %) at 300 µM. Their voltage- and use-independent inhibition suggests they are not open-channel blockers.

Molecular investigation of ergot alkaloid ergotamine's modulatory effects on glycine receptors expressed in oocytes.

The relationship between oxidative stress and glycine receptors is complex, involving multiple mechanisms through which reactive oxygen species can modify glycine receptor function. Understanding these interactions is essential for developing therapeutic strategies to mitigate the effects of oxidative stress on inhibitory neurotransmission in various neurological disorders. Inhibitory glycine receptors play a critical role in regulating the final grand postsynaptic potential by attenuating excitatory postsynaptic potentials through inhibitory postsynaptic potentials in postsynaptic neurons.

Conformation-sensitive targeting of CD18 depletes M2-like tumor-associated macrophages resulting in inhibition of solid tumor progression.

Background: Tumor-associated macrophages (TAMs) primarily exist in the M2-like phenotype in the tumor microenvironment (TME). M2-TAMs contribute to tumor progression by establishing an immunosuppressive environment. However, TAM targeting is hindered, mainly owing to a lack of specific biomarkers for M2-TAMs.

Subtype-selective effect and molecular regulation of celastrol and triptolide at human nicotinic acetylcholine receptors.

Celastrol and triptolide, bioactive compounds isolated from Tripterygium wilfordii Hook F, have demonstrated significant pharmacological effects across various biological pathways, making them subjects of extensive research for potential therapeutic applications. Celastrol and triptolide are known to have therapeutic use in neurodegenerative diseases including Alzheimer's disease and Parkinson's disease through neuroprotective action. Nicotinic acetylcholine receptors (nAChRs) are a subtype of cholinergic receptors and are ligand-gated ion channels that play an essential role in regulating synaptic transmission in the central nervous system.

Molecular Mechanisms of Nicergoline from Ergot Fungus in Blocking Human 5-HT3A Receptor.

This study investigates the modulatory effects of nicergoline, a major bioactive compound derived from ergot fungus, on the 5-hydroxytryptamine 3A (5-HT3A) receptor. Utilizing a two-electrode voltage-clamp technique, we evaluated the impact of nicergoline on the 5-HT-induced inward current (I) in 5-HT3A receptors. Our findings reveal that nicergoline inhibits I in a reversible and concentration-dependent manner.

Molecular regulatory effect of the ergot alkaloid methylergometrine on the α3β4 nicotinic acetylcholine receptor.

Methylergometrine has widely been used pharmacologically to treat conditions such as pain, addiction, vasoconstriction, migraines, and Parkinson's disease. Despite its side effects, it is used as a therapeutic agent and research material for various diseases based on its natural potential; however, the regulatory effect of its interaction with the nicotinic acetylcholine receptor (nAChR) has not yet been investigated. The α3β4 nAChR is an ion channel essential for neurotransmission within the sympathetic, parasympathetic, and autonomic nervous systems.

Molecular Mechanism of L-Pyroglutamic Acid Interaction with the Human Sour Receptor.

Taste is classified into five types, each of which has evolved to play its respective role in mammalian survival. Sour taste is one of the important ways to judge whether food has gone bad, and the sour taste receptor (PKD2L1) is the gene behind it. Here, we investigated whether L-pyroglutamic acid interacts with sour taste receptors through electrophysiology and mutation experiments using oocytes.

DDX3 Upregulates Hydrogen Peroxide-Induced Melanogenesis in Sk-Mel-2 Human Melanoma Cells.

DDX3 is a DEAD-box RNA helicase with diverse biological functions through multicellular pathways. The objective of this study was to investigate the role of DDX3 in regulating melanogenesis by the exploring signaling pathways involved. Various concentrations of hydrogen peroxide were used to induce melanogenesis in SK-Mel-2 human melanoma cells.

The Application of the Neuroprotective and Potential Antioxidant Effect of Ergotamine Mediated by Targeting N-Methyl-D-Aspartate Receptors.

(1) Background: The N-methyl-D-aspartate receptors (NMDARs) mediate fast excitatory currents leading to depolarization. Postsynaptic NMDARs are ionotropic glutamate receptors that mediate excitatory glutamate or glycine signaling in the CNS and play a primary role in long-term potentiation, which is a major form of use-dependent synaptic plasticity. The overstimulation of NMDARs mediates excessive Ca influx to postsynaptic neurons and facilitates more production of ROS, which induces neuronal apoptosis.

Antioxidative and Analgesic Effects of Naringin through Selective Inhibition of Transient Receptor Potential Vanilloid Member 1.

Transient receptor potential vanilloid member 1 (TRPV1) is activated in response to capsaicin, protons, temperature, and free reactive oxygen species (ROS) released from inflammatory molecules after exposure to harmful stimuli. The expression level of TRPV1 is elevated in the dorsal root ganglion, and its activation through capsaicin and ROS mediates neuropathic pain in mice. Its expression is high in peripheral and central nervous systems.

Identification and molecular study on the interaction of Schisandrin C with human 5-HT receptor.

Schisandrin C (Sch C) is one of the main components of Schisandra chinensis (Schisandra). Since the olden times, Schisandra has been used as a traditional herbal medicine in Asia. Recent studies have shown that Schisandra is effective against irritable bowel syndrome (IBS) in an animal model and affects IBS through the 5-HT pathway in the IBS rat model.

Molecular Regulation of Betulinic Acid on α3β4 Nicotinic Acetylcholine Receptors.

Betulinic acid (BA) is a major constituent of Zizyphus seeds that have been long used as therapeutic agents for sleep-related issues in Asia. BA is a pentacyclic triterpenoid. It also possesses various anti-cancer and anti-inflammatory effects.

Differential Regulation of Human Serotonin Receptor Type 3A by Chanoclavine and Ergonovine.

Irritable bowel syndrome (IBS) is a chronic disease that causes abdominal pain and an imbalance of defecation patterns due to gastrointestinal dysfunction. The cause of IBS remains unclear, but intestinal-brain axis problems and neurotransmitters have been suggested as factors. In this study, chanoclavine, which has a ring structure similar to 5-hydroxytryptamine (5-HT), showed an interaction with the 5-HT receptor to regulate IBS.

Molecular Regulation of α3β4 Nicotinic Acetylcholine Receptors by Lupeol in Cardiovascular System.

Cardiovascular disease (CVD) occurs globally and has a high mortality rate. The highest risk factor for developing CVD is high blood pressure. Currently, natural products are emerging for the treatment of hypertension to avoid the side effects of drugs.

Subunit-specific effects of poricoic acid A on NMDA receptors.

Background: N-methyl-D-aspartate (NMDA) receptor is a tetrameric protein complex composed of glycine-linked NR1 subunits and glutamate-linked NR2 subunits. There are four NR2 subunits (A-D) that differ in development, anatomy, and function profiles. They play various roles in normal and neuropathologic conditions.

Molecular basis involved in the blocking effect of antidepressant metergoline on C-type inactivation of Kv1.4 channel.

Voltage-gated potassium channels (VGKCs) are transmembrane ion channels specific for potassium. Currently there are nine kinds of VGKCs. Kv1.

Molecular Determinants of α3β4 Nicotinic Acetylcholine Receptors Inhibition by Triterpenoids.

In a previous work, we reported the regulatory role of the triterpenoids on 5-hydroxytryptamine (5-HT)A receptors activity in Xenopus laevis oocytes (Eur. J. Pharmacol.

A Molecular Basis for the Inhibition of Transient Receptor Potential Vanilloid Type 1 by Gomisin A.

Transient receptor potential (TRP) channel has critical actions as conditional sensors in primary afferent neurons. We studied the regulatory action of gomisin A on TRPV1 channel current in this report. contains bioactive compounds such as the gomisin derivatives and their related compounds.

Regulation of Human Kv1.4 Channel Activity by the Antidepressant Metergoline.

Metergoline is an ergot-derived psychoactive drug that is a ligand for various serotonin and dopamine receptors. Little is known about the effect of metergoline on different types of receptors and ion channels. Potassium channels are the most diverse group of ion channels.