Development of Tetrahydroquinoline-Based Inhibitors for Chronic Pain.

Chronic pain affects a substantial portion of the population, posing a significant health challenge. Current treatments often come with limitations and side effects, necessitating novel therapeutic approaches. Our study focuses on disrupting the Cav3.

Determinants of interactions of a novel next-generation gabapentinoid NVA1309 and mirogabalin with the Cavα2δ-1 subunit.

NVA1309 is a non-brain penetrant next-generation gabapentinoid shown to bind Cavα2δ at R243 within a triple Arginine motif forming the binding site for gabapentin and pregabalin. In this study we have compared the effects of NVA1309 with Mirogabalin, a gabapentinoid drug with higher affinity for the voltage-gated calcium channel subunit Cavα2δ-1 than pregabalin which is approved for post-herpetic neuralgia in Japan, Korea and Taiwan. Both NVA1309 and mirogabalin inhibit Cav2.

Prunin from (L.) Rafin Inhibits Aldose Reductase and Glucose-Fructose-Mediated Protein Glycation and Oxidation of Human Serum Albumin.

Diabetes complications are associated with aldose reductase (AR) and advanced glycation end products (AGEs). Using bioassay-guided isolation by column chromatography, 10 flavonoids and one coumarin were isolated from Rafin and tested in vitro for an inhibitory effect against human recombinant AR (HRAR) and rat lens AR (RLAR). Prunin, narirutin, and naringin inhibited RLAR (IC 0.

Discovery of Potent Angiotensin-Converting Enzyme Inhibitors in Pomegranate as a Treatment for Hypertension.

Pomegranate ( L.) is associated with numerous health benefits due to its high levels of antioxidant polyphenolic substances. Since pomegranate extract has been shown to inhibit angiotensin-converting enzyme (ACE), the potential inhibitory effect of most of its main constituents against ACE is unknown.

Icariside II, a Prenyl-Flavonol, Alleviates Inflammatory and Neuropathic Pain by Inhibiting T-Type Calcium Channels and USP5-Cav3.2 Interactions.

Cav3.2 channels play an important role in the afferent nociceptive pathway, which is responsible for both physiological and pathological pain transmission. Cav3.

An Arylbenzofuran, Stilbene Dimers, and Prenylated Diels-Alder Adducts as Potent Diabetic Inhibitors from Leaves.

has a long history of usage as a treatment for metabolic diseases, especially, diabetes mellitus (DM). Thus, we aimed to isolate and evaluate bioactive constituents derived from leaves for the treatment of DM. According to bioassay-guided isolation by column chromatography, eight compounds were obtained from leaves: two phenolic compounds, -coumaric acid () and chlorogenic acid methyl ester (), one stilbene, oxyresveratrol (), two stilbene dimers, macrourin B () and austrafuran C (), one 2-arylbenzofuran, moracin M (), and two Diels-Alder type adducts, mulberrofuran F () and chalcomoracin ().

Ursonic acid from Artemisia montana exerts anti-diabetic effects through anti-glycating properties, and by inhibiting PTP1B and activating the PI3K/Akt signaling pathway in insulin-resistant C2C12 cells.

Artemisia is one of the largest genera in the plant family Asteraceae and has long been used in traditional medicine for its antitussive, analgesic, antihypertensive, antitoxic, antiviral, antimalarial, and anti-inflammatory properties. However, the anti-diabetic activity of Artemisia montana has not been broadly studied. The goal of this study was to determine whether extracts of the aerial parts of A.

Differential regulation of Ca 3.2 and Ca 2.2 calcium channels by CB receptors and cannabidiol.

Background And Purpose: Cannabinoids are a promising therapeutic avenue for chronic pain. However, clinical trials often fail to report analgesic efficacy of cannabinoids. Inhibition of voltage gate calcium (Ca ) channels is one mechanism through which cannabinoids may produce analgesia.

Discovery of potent and selective dual cholinesterases and β-secretase inhibitors in pomegranate as a treatment for Alzheimer's disease.

Pomegranate (Punica granatum L.) extract has been reported to inhibit cholinesterase and the β-site amyloid precursor protein cleaving enzyme 1 (BACE1); however, most of its constituents' potential inhibition of these enzymes remains unknown. Thus, we investigated the anti-Alzheimer's disease (anti-AD) potential of 16 ellagitannin and gallotannin, and nine anthocyanin derivatives' inhibition of BACE1, AChE, and BChE, and gallagic acid inhibited both the best.

6-Formyl Umbelliferone, a Furanocoumarin from a L., Inhibits Key Diabetes-Related Enzymes and Advanced Glycation End-Product Formation.

Over the years, great attention has been paid to coumarin derivatives, a set of versatile molecules that exhibit a wide variety of biological activities and have few toxic side effects. In this study, we investigated the antidiabetic potential of 6-formyl umbelliferone (6-FU), a novel furanocoumarin isolated from . Numerous pharmacological activities of 6-FU have been previously reported; however, the mechanism of its antidiabetic activity is unknown.

Inhibition of Aldose Reductase by Ginsenoside Derivatives via a Specific Structure Activity Relationship with Kinetics Mechanism and Molecular Docking Study.

This present work is designed to evaluate the anti-diabetic potential of 22 ginsenosides via the inhibition against rat lens aldose reductase (RLAR), and human recombinant aldose reductase (HRAR), using -glyceraldehyde as a substrate. Among the ginsenosides tested, ginsenoside Rh2, (20) ginsenoside Rg3, (20) ginsenoside Rg3, and ginsenoside Rh1 inhibited RLAR significantly, with IC values of 0.67, 1.

A Synthetically Accessible Small-Molecule Inhibitor of USP5-Cav3.2 Calcium Channel Interactions with Analgesic Properties.

Cav3.2 calcium channels are important mediators of nociceptive signaling in the primary afferent pain pathway, and their expression is increased in various rodent models of chronic pain. Previous work from our laboratory has shown that this is in part mediated by an aberrant expression of deubiquitinase USP5, which associates with these channels and increases their stability.

Structural Bases for Hesperetin Derivatives: Inhibition of Protein Tyrosine Phosphatase 1B, Kinetics Mechanism and Molecular Docking Study.

In the present study, we investigated the structure-activity relationship of naturally occurring hesperetin derivatives, as well as the effects of their glycosylation on the inhibition of diabetes-related enzyme systems, protein tyrosine phosphatase 1B (PTP1B) and α-glycosidase. Among the tested hesperetin derivatives, hesperetin 5--glucoside, a single-glucose-containing flavanone glycoside, significantly inhibited PTP1B with an IC value of 37.14 ± 0.

Phytochemistry, Ethnopharmacological Uses, Biological Activities, and Therapeutic Applications of L.: A Comprehensive Review.

L., of the Leguminosae family, is used as a diuretic, laxative, tonic, purgative, and natural remedy for treating headache, dizziness, constipation, tophobia, and lacrimation and for improving eyesight. It is commonly used in tea in Korea.

Inhibition of Angiotensin-I Converting Enzyme by Ginsenosides: Structure-Activity Relationships and Inhibitory Mechanism.

Ginseng ( C. A. Meyer) extract has been reported to inhibit the angiotensin converting enzyme (ACE); however, the possible inhibitory action of most of its constituents (ginsenosides) against ACE remains unknown.

Ginsenoside derivatives inhibit advanced glycation end-product formation and glucose-fructose mediated protein glycation in vitro via a specific structure-activity relationship.

Ginseng (Panax ginseng and red ginseng) extract has been reported to inhibit the formation of advanced glycation end-products (AGEs); however, the potential inhibitory activity of its major constituents (ginsenosides) against AGE formation is still unknown. In the present study, we investigated the inhibitory effect of ginsenoside derivatives on AGE formation. Herein, we assessed the activity of 22 ginsenosides, most of which significantly inhibited fluorescent AGE formation.

Insulin-Mimetic Dihydroxanthyletin-Type Coumarins from with Protein Tyrosine Phosphatase 1B and α-Glucosidase Inhibitory Activities and Docking Studies of Their Molecular Mechanisms.

As a traditional medicine, has been used for the treatment of many diseases. The goal of this study was to evaluate the potential of four natural major dihydroxanthyletin-type coumarins-(+)--decursidinol, Pd-C-I, Pd-C-II, and Pd-C-III-to inhibit the enzymes, protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase. In the kinetic study of the PTP1B enzyme's inhibition, we found that (+)--decursidinol, Pd-C-I, and Pd-C-II led to competitive inhibition, while Pd-C-III displayed mixed-type inhibition.

Effect of Manure Application on Net Nitrification Rates, Heavy Metal Concentrations and Nitrifying Archaea/Bacteria in Soils.

In this study, we determined the effect of manure application on net nitrification rates (NNRs), heavy metal concentrations (HMCs), and abundance of ammonia-oxidizing archaea (AOA)/bacteria (AOB), and nitrite-oxidizing bacteria (NOB) in soil. HMCs were measured by atomic absorption spectroscopy. Abundance of AOA, AOB, and NOB was enumerated by q-PCR.

Poncirin, an orally active flavonoid exerts antidiabetic complications and improves glucose uptake activating PI3K/Akt signaling pathway in insulin resistant C2C12 cells with anti-glycation capacities.

Poncirin, a natural flavanone glycoside present abundantly in many citrus fruits, contains an extensive range of biological activities. However, the antidiabetic mechanism of poncirin is unexplored yet. In this study, we examined the anti-diabetic prospective of poncirin by evaluating its ability to inhibit protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, human recombinant AR (HRAR), rat lens aldose reductase (RLAR), and advanced glycation end-product (AGE) formation (IC = 7.

Angiotensin-I-Converting Enzyme Inhibitory Activity of Coumarins from .

The bioactivity of ten traditional Korean species were screened by angiotensin-converting enzyme (ACE) assay in vitro. Among the crude extracts, the methanol extract of whole plants exhibited potent inhibitory effects against ACE. In addition, the ACE inhibitory activity of coumarins -, - was evaluated, along with two phenolic acids (, ) obtained from .

Umbelliferone derivatives exert neuroprotective effects by inhibiting monoamine oxidase A, self-amyloidβ aggregation, and lipid peroxidation.

Umbelliferone has been demonstrated to have a wide range of biological activities. However, the effect of incorporating a formyl moiety in the umbelliferone scaffold has not been investigated. In this paper, we investigated the inhibitory activity of six coumarins, namely umbelliferone (1), 6-formyl umbelliferone (2), 8-formyl umbelliferone (3), umbelliferone-6-carboxylic acid (4), esculetin (5), and scopoletin (6) against human monoamine oxidases (hMAOs), self-amyloid β (Aβ) aggregation, and lipid peroxidation.

Flavanone glycosides inhibit β-site amyloid precursor protein cleaving enzyme 1 and cholinesterase and reduce Aβ aggregation in the amyloidogenic pathway.

Alzheimer's disease (AD) is a slow but progressive neurodegenerative disease. One of the pathological hallmarks of AD is the progressive accumulation of β-amyloid (Aβ) in the form of senile plaques, and Aβ insult to neuronal cells has been identified as one of the major causes of AD onset. In the present study, we investigated the anti-AD potential of four flavonoids, naringenin, didymin, prunin, and poncirin, by evaluating their ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein cleaving enzyme 1 (BACE1).

Didymin, a dietary citrus flavonoid exhibits anti-diabetic complications and promotes glucose uptake through the activation of PI3K/Akt signaling pathway in insulin-resistant HepG2 cells.

Didymin is a naturally occurring orally active flavonoid glycoside (isosakuranetin 7-O-rutinoside) found in various citrus fruits, which has been previously reported to possess a wide variety of pharmacological activities including anticancer, antioxidant, antinociceptive, neuroprotective, hepatoprotective, inflammatory, and cardiovascular. However, there have not been any reports concerning its anti-diabetic potential until now. Therefore, we evaluated the anti-diabetic potential of didymin via inhibition of α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), rat lens aldose reductase (RLAR), human recombinant AR (HRAR), and advanced glycation end-product (AGE) formation inhibitory assays.

Inhibition of β-site amyloid precursor protein cleaving enzyme 1 and cholinesterases by pterosins via a specific structure-activity relationship with a strong BBB permeability.

We extracted 15 pterosin derivatives from Pteridium aquilinum that inhibited β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and cholinesterases involved in the pathogenesis of Alzheimer's disease (AD). (2R)-Pterosin B inhibited BACE1, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with an IC of 29.6, 16.

Correction to: Dihydroxanthyletin-type coumarins from Angelica decursiva that inhibits the formation of advanced glycation end products and human recombinant aldose reductase.

The author would like to include conflict of interest statement of the online published article. The correct conflict of interest statement should read as: Conflict of interest The authors declare no conflict of interest.