arecoline / Cogent Pharma - LARVOL DELTA

Drug Repurposing Targeting miRNA-mRNA Networks to Mitigate Areca Nut-Induced Head and Neck Cancer. (PubMed, Biomed J) - "This integrative approach elucidates areca nut-driven carcinogenesis through miRNA-mRNA interactions and highlights MK-2206 as a promising therapeutic strategy for areca nut-associated HNC."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • MIR410

Computer prediction and genetic analysis identifies retinoic acid modulation as a driver of conserved longevity pathways in genetically-diverse Caenorhabditis nematodes. (PubMed, bioRxiv) - "While eleven compounds (aldosterone, arecoline, bortezomib, dasatinib, decitabine, dexamethasone, erlotinib, everolimus, gefitinib, temsirolimus, and thalidomide) either had no effect on median lifespan or were toxic, five compounds (all-trans retinoic acid, berberine, fisetin, propranolol, and ritonavir) extended lifespan in Caenorhabditis elegans . Evolutionary conservation of retinoic acid as a signaling ligand and the structure of the downstream effector network of retinoic acid combine to suggest that the all-trans retinoic acid pathway is an ancient metabolic regulatory system that can modulate lifespan. Our results highlight the potential of combining computational prediction of longevity interventions with the power of nematode functional genetics and underscore that the manipulation of a conserved metabolic regulatory circuit by co-opting endogenous signaling molecules is a powerful approach for discovering aging interventions."

Journal • Acne Vulgaris • Acute Promyelocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • AKT1 • AKT2 • AMPK • HSF1

GAS5 decreased the arecoline-induced myofibroblasts activity in buccal mucosal fibroblasts via acting as a competing endogenous RNA for miR-21. (PubMed, J Dent Sci) - "Our findings suggest that GAS5 plays a crucial role in inhibiting myofibroblast activation in OSF by targeting the TGF-β/Smad2 signaling pathway and regulating the miR-21. GAS5 may represent a novel therapeutic target for the prevention and treatment of OSF."

Journal • Fibrosis • Head and Neck Cancer • Immunology • Oncology • Oral Cancer • Solid Tumor • GAS5 • MIR21 • TGFB1

miR-134-3p Deficiency-Induced Methionine Metabolism Promotes Fibrosis via SLC25A33 in OSF. (PubMed, J Oral Pathol Med) - "In summary, the findings suggested that miR-134-3p is underexpressed in fibroblasts, which directly binds to SLC25A33, leading to degradation of SLC25A33 mRNAs. SLC25A33 induces methionine metabolism reprogramming to promote collagen synthesis through the mTOR pathway in OSF."

Journal • Fibrosis • Immunology • MIR134 • SLC25A3

Elucidation of the arecoline catabolism by Arthrobacter sp. strain NyZ413. (PubMed, J Hazard Mater) - "In addition, detoxification experiments showed that biodegradation by strain NyZ413 completely eliminated the embryotoxic effects of arecoline on zebrafish, confirming its high biosafety and potential for bioremediation in arecoline-contaminated environments. This study fills the gap in our understanding of microbial degradation of arecoline and also provides a bacterial resource for bioremediation of arecoline-polluted sites."

Journal

Arecoline Triggers Psychostimulant Responses by Modulating the Intestinal Microbiota to Influence Neurotransmitter Levels and Digestive Enzyme Activity. (PubMed, Pharmaceuticals (Basel)) - " Arecoline administration altered multiple enzymatic activities and the microbial composition abundance in the mouse intestine, eliciting psychostimulant effects while maintaining neurotransmitter homeostasis. This study provides an experimental foundation for further pharmacological exploitation of arecoline."

Journal • BDNF

An in-vitro exploration of the antifibrotic activity of Naringenin: A potential therapeutic agent for oral submucous fibrosis management. (PubMed, J Oral Biol Craniofac Res) - "Naringenin exhibits promising antifibrotic activity in arecoline-induced fibrosis in HGFs, potentially through modulation of key fibrotic signaling pathways. These findings highlight its potential role as a therapeutic agent for OSMF management."

Journal • Preclinical • Fibrosis • Immunology • Oncology • MMP9 • TGFB1

Co-Transfection With Anti-Fibrotic microRNAs for Treating Oral Submucous Fibrosis. (PubMed, J Oral Pathol Med) - "Co-transfection of anti-fibrotic miRs can be a promising treatment for oral submucous fibrosis."

Journal • Fibrosis • Immunology • ACTA2 • COL1A1 • COL3A1 • COL5A1 • MIR29A • MMP1 • MMP7 • TGFB1 • TIMP1 • TIMP2

Arecoline Alleviates Autism Spectrum Disorder-like Behaviors and Cognition Disorders in a Valproic Acid Mouse Model by Activating the AMPK/CREB/BDNF Signaling Pathway. (PubMed, Brain Res Bull) - "These findings suggest that the AMPK/CREB/BDNF pathway may contribute to the therapeutic effects of arecoline, potentially through increased oligodendrocyte maturation and remyelination. This study provides preclinical evidence supporting arecoline as a potential myelination-targeting intervention, with implications for ASD and other neurological disorders involving myelination deficits."

Journal • Preclinical • Autism Spectrum Disorder • CNS Disorders • Cognitive Disorders • Genetic Disorders • Solid Tumor • BDNF • GSTP1

Arecoline regulates glycolipid and endoplasmic reticulum metabolisms in adult grass carp (Ctenopharyngodon idella). (PubMed, Anim Nutr) - "Finally, arecoline promoted close communication between the ER and mitochondria by increasing the expression of the mitochondria-associated endoplasmic reticulum membrane (MAM) tight junction proteins GRP75 and PACS2 as well as the calcium transporter proteins SERCA1 and IP3R, which in turn promoted lipid metabolism by increasing the protein expression of DGAT2 (P < 0.05). In conclusion, we found for the first time that dietary arecoline promoted GLU and fatty acid metabolism in hepatopancreas and muscle, which may be related to the regulatory effects of MAM on ER and mitochondria."

Journal • Metabolic Disorders • ATF4 • ERN1 • HSPA9 • XBP1

EGFRvIII-driven microenvironmental fibroblast activation and transformation accelerate oral cancer progression via lipocalin-2/STAT3 axis. (PubMed, Neoplasia) - "Furthermore, exposure to environmental carcinogens such as nicotine-derived nitrosamine ketone (NNK) and arecoline enhances EGFRvIII expression and downstream signaling, exacerbating tumor aggressiveness. These findings reveal a positive feedback loop in which EGFRvIII fosters OSCC progression by stimulating LCN2-STAT3-mediated fibroblast activation. Targeting EGFRvIII and its downstream effectors may therefore represent a promising strategy to mitigate OSCC progression and improve therapeutic outcomes."

Journal • Brain Cancer • Glioblastoma • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • LCN2 • PDGFRA • PDGFRB

Study on the mechanism of areca alkaloids against eimeria tenella. (PubMed, Poult Sci) - "this study elucidates the primary active ingredients and molecular targets of AAl against E.tenella, suggesting that arecoline and homoarecoline may serve as potential therapeutic agents for E.tenella infection."

Journal • Infectious Disease • CD9

Serological diagnosis and post-treatment monitoring of Echinococcus granulosus in experimentally infected dogs using crude and recombinant fibronectin antigens. (PubMed, Vet Immunol Immunopathol) - "Adult E. granulosus parasites were collected from experimentally infected dogs using arecoline hydrobromide purgation...The findings suggest that rEgFN162 is a promising candidate for the serodiagnosis of E. granulosus in dogs, with potential applications in epidemiological studies and post-treatment follow-up. Further validation with larger sample sizes is needed to confirm its diagnostic accuracy in natural infections."

Journal • Infectious Disease

Natural Alkaloid Arecoline-Derived Amino Acid Derivatives: Design, Synthesis, and Evaluation of Their Antifungal Activity in an Agricultural Context. (PubMed, J Agric Food Chem) - "Transcriptomic profiling further confirmed its significant suppression of chitin biosynthesis pathways, while molecular docking validated strong interactions with chitin synthase. These findings position amino acid-pyridine hybridized arecoline derivatives as promising eco-friendly antifungals targeted at chitin metabolism."

Journal

Anticancer potential of exosome-like nanoparticles isolated from Acorus calamus in breast cancer. (PubMed, 3 Biotech) - "Metabolomic profiling identified bioactive compounds such as arecoline, trigonelline, asarone, and gingerol, known for their anti-cancer properties...We propose to conduct future research focusing on in vivo validation and optimizing large-scale production for clinical translation. The online version contains supplementary material available at 10.1007/s13205-025-04349-8."

Journal • Breast Cancer • Oncology • Solid Tumor • ANXA5 • BAX • BCL2

Unraveling the Ties Between Betel Nut Chewing, Obstructive Airway Disease, Zenker Diverticulum, and Gastro-esophageal Reflux Disease (ATS 2025) - "Discussion Arecoline, a cholinergic alkaloid is one of the primary components of betel nut (Areca Catechu) and can cause increase in eotaxin-1 levels and chronic inflammatory changes leading to Asthma and COPD respectively. In patients with recurrent COPD exacerbations, a thorough search for culture-specific practices like betel nut chewing amongst others is warranted and abstinence from such practices can aid in reducing morbidity."

Asthma • Chronic Obstructive Pulmonary Disease • Cough • Esophageal Cancer • Fibrosis • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Immunology • Oncology • Pulmonary Disease • Pulmonary Emphysema • Respiratory Diseases • CCL11

The effect and mechanism of areca nut in ovarian cancer were investigated based on network pharmacology, molecular docking, and in vitro experiments. (PubMed, Biochem Biophys Res Commun) - "In conclusion, this study provides a solid scientific basis for exploring the action mechanism of areca nut."

Journal • Preclinical • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • PTEN

Zinc-alpha-2-glycoprotein overexpression and maintaining anti-apoptotic function in oral squamous cell carcinoma. (PubMed, Arch Oral Biol) - "HPV oncoproteins and high doses of arecoline are risk factors for an overexpressed ZAG protein that has an anti-apoptotic function in OSCC."

IO biomarker • Journal • Oncology • Oral Cancer • Squamous Cell Carcinoma • AZGP1 • BCL2 • NFKB1 • STAT3 • TP53

Molecular mechanisms of arecoline-induced oral cancer: a network toxicology and molecular docking techniques integrated analysis. (PubMed, Discov Oncol) - "Arecoline may induce oral cancer by acting on core targets including TP53, TNF, IL6, and CASP3, which interfere with normal cellular growth regulation, inflammatory responses, and apoptotic mechanisms. Therapeutic strategies targeting TP53, TNF, IL6, and CASP3 may represent novel research directions for clinical diagnosis and treatment of oral cancer."

Journal • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • CASP3 • CD8 • IL6 • SNAI1 • TP53

INHBA+ macrophages and Pro-inflammatory CAFs are associated with distinctive immunosuppressive tumor microenvironment in submucous Fibrosis-Derived oral squamous cell carcinoma. (PubMed, BMC Cancer) - "The classic OSF-inducing molecule arecoline significantly increases the expression of INHBA (p < 0.0001) in vitro experiments stimulating THP-1 cells...The increased INHBA+Mac and iCAF in ODSCC are associated with the observed more severe TISME. The upregulated INHBA in ODSCC and its interaction with INHBA-ACVR1/ACVR2A/ACVR2B may mediate the modulation effect of INHBA+ Mac and iCAF on Treg differentiation and functionality."

Biomarker • IO biomarker • Journal • Fibrosis • Immunology • Oncology • Oral Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ACVR1 • ACVR2A • ACVR2B • CD8 • DUSP4 • IDO1 • SPP1 • TDO2

Safety evaluation of Areca catechu L. extract powder in rats: acute and 180-day chronic toxicity test. (PubMed, J Ethnopharmacol) - "The acute toxicity test showed that the LD50 of BLTQS exceeded 15 g/kg bw. The no-observed-effect level (NOEL) for BLTQS in rats was calculated to be 0.32 g/kg bw. These findings support the safety of BLTQS for clinical use, provided that dosages adhere to clinically recommended guidelines."

Journal • Preclinical • Hematological Disorders

Intranasal delivery of drugs to the central nervous system of adult zebrafish. (PubMed, Lab Anim (NY)) - "Intranasally administered arecoline (10 mg/mL) and nicotine (5 and 10 mg/mL) demonstrated overt behavioral profiles, evoking characteristic anxiolytic-like effects in zebrafish similar to those observed here for a standard 20-min water immersion method (10 mg/L arecoline or 30 mg/L nicotine). Overall, we showed that neuroactive drugs can be delivered to adult zebrafish intranasally to exert central effects, which may (at least for some drugs) occur faster and can need smaller drug quantities than for the water immersion delivery."

Journal

Haplotype-resolved genome reveals haplotypic variation and the biosynthesis of medicinal ingredients in Areca catechu L. (PubMed, Mol Hortic) - "Further analyses tested the function of AcUGT71CE15, AcUGT74CJ38, AcUGT87EE5 and AcUGT83S982 as glucosyltransferases, and AcUGT78AP14 was identified as a rhamnosyltransferase involved in flavonol glycosylation. Our study provides a high-quality genome of A. catechu, characterizes the arecoline biosynthetic pathway and expands the understanding of the diversity of UDP-glucosyltransferase and UDP-rhamnosyltransferase, offering insights into the potential of A. catechu for the biosynthesis of bioactive compounds."

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Modulation of neural activity and gene expression by arecoline. (PubMed, Front Integr Neurosci) - "These results provide valuable insights into the addictive potential of arecoline and its underlying neurobiological mechanisms, offering crucial information for understanding its broader impact on CNS function. The study's findings hold significant implications for informing public health strategies aimed at addressing arecoline misuse and its potential role in addiction-related disorders."

Journal • CNS Disorders • Psychiatry

Application potential of arecoline hydrobromidefor anti-Toxoplasma gondii. (PubMed, Exp Parasitol) - "Furthemore, the survival and safety evaluation outcome indicated that AH can prolong survival period of mice infected with T. gondii at non-toxic and side-effect dose. Based on these advantages, AH is a candidate compound with great potential for the treatment of T. gondii infection and it may be used clinically in the future."

Journal • Infectious Disease • Oncology