arecoline / Cogent Pharma - LARVOL DELTA

Tropomyosin-1 positively regulates TGF-β/Smad3 signaling through STUB1 in arecoline-induced oral submucosal fibrosis. (PubMed, Odontology) - "In conclusion, activation of the TGF-β/Smad3 pathway upregulates TPM1, which in turn blocks STUB1-mediated ubiquitination of the same cascade, establishing a positive-feedback loop that exacerbates arecoline-induced OSF. These findings improve our understanding of OSF's molecular pathogenesis and offer a potential target for its prevention and treatment."

Journal • Fibrosis • Immunology • Oncology • Targeted Protein Degradation • SMAD3 • SMAD4 • TGFB1

Curcumin suppresses EMT to alleviate oral submucous fibrosis progression through XIST/miR-25-3p-mediated inactivation of the TGF-β1/Smads signalling pathway. (PubMed, Int Dent J) - "Curcumin effectively inhibits EMT by inactivating the TGF-β1/Smads pathway through regulating XIST/miR-25-3p, and thereby alleviating the progression ofOSF. The study results further reveal the mechanisms underlying the function of curcumin, and may provide novel targets and ideas for OSF therapy."

Journal • Fibrosis • Immunology • Oncology • CDH1 • CDH2 • MIR25 • TGFB1 • VIM • XIST

Arecoline stimulates the IL-33/13 axis and upregulates pro-fibrotic CTGF: A possible role in oral submucous fibrosis. (PubMed, Food Chem Toxicol) - "In conclusion, arecoline induces IL-33, IL-13 and CTGF release in HGF and mast cells, highlighting the importance of the IL-33/IL-13 axis in the progressive fibrosis of OSMF. These findings could support the approach of novel therapies targeting the IL-33/IL-13 axis for patients with OSMF."

Journal • Fibrosis • Immunology • Oncology • CTGF • IL13 • IL33

Panax notoginseng Saponins Alleviate OSF by Inhibiting Ferroptosis Through GPX4 Activation. (PubMed, J Oral Pathol Med) - "The research established OSF in vivo and in vitro, respectively, and the changes in the expression of fibrosis and ferroptosis-related markers in these models were studied to provide a theoretical and experimental basis for the clinical prevention and treatment of OSF."

Journal • Fibrosis • Immunology • GPX4

Immunological and molecular tools for environmental surveillance of canine echinococcosis: Steps toward a sustainable diagnostic algorithm. (PubMed, Vet Parasitol) - "Canine echinococcosis (CaEc) surveillance has evolved from necropsy and arecoline purgation to the detection of coproantigens (cELISA) and genomic copro-DNA (cPCR and cLAMP)...Using a BLCA model, both cPCR and cLAMPEGSL3.0 showed the best estimated sensitivity and specificity values. These results provide control programs with molecular tools suitable for use in medium- and low-complexity laboratories."

Journal

MicroRNA let-7a mitigates the progression of oral submucous fibrosis by targeting high-mobility group AT-hook 2. (PubMed, J Dent Sci) - "Moreover, let-7a expression declined in a dose-dependent manner during arecoline-induced myofibroblastic transdifferentiation of BMFs...The present study demonstrates that let-7a suppresses oral myofibroblast activation by directly targeting HMGA2. This finding first establishes the let-7a/HMGA2 axis as a promising therapeutic target for mitigating the progression of OSF."

Journal • Fibrosis • Immunology • HMGA2

Assessing adult zebrafish despair-like behaviors in the small vertical cylinder immobility test (VCIT). (PubMed, J Neurosci Methods) - "VCIT is sensitive to various stress-related manipulations and their bidirectional pharmacological modulation, hence emphasizing the growing relevance and potential of zebrafish in advancing neuropsychiatric research and identifying innovative treatments for neuropsychiatric disorders."

Journal • CNS Disorders • Depression • Mental Retardation • Psychiatry

YY1 lactylation promotes fibroblast senescence by targeting the PU.1-BTG2 axis to promote oral submucous fibrosis. (PubMed, Chem Biol Interact) - "In this study, we explored how arecoline, a key component of areca nut, influences fibroblast behavior...Overall, we demonstrate that lactylated YY1 promotes fibroblast senescence and collagen deposition by activating the PU.1-BTG2 axis. This newly identified mechanism highlights potential therapeutic targets for treating OSF."

Journal • Fibrosis • Immunology • BTG2 • SPI1 • YY1

The Areca Nut and Oral Submucosal Fibrosis: A Narrative Review. (PubMed, Dent J (Basel)) - "The active chemical ingredients of AN include alkaloids such as arecoline, flavonoids, and tannins...Consequently, treatment options for OSF are limited and primarily symptomatic. Collectively, evidence from human and animal studies establishes OSF as an AN-induced fibrotic disorder and underscores the urgent need for mechanism-focused research to identify reliable diagnostic markers and therapeutic targets to address its growing global burden."

Journal • Review • Fibrosis • Head and Neck Cancer • Immunology • Oncology • Oral Cancer • Solid Tumor • COL1A1 • CTGF • TGFB1

Low-dose nicotine enhances arecoline-induced human oral mucosa fibroblast proliferation by stabilizing Egr-1 protein. (PubMed, Odontology) - "Interestingly, Egr-1 exhibited enhanced stability in nicotine-treated cells, regardless of the presence of arecoline. Thus, it is evident that low-dose nicotine promotes arecoline-induced proliferation of human oral mucosa fibroblasts by enhancing the stability of the Egr-1 protein."

Journal • Fibrosis • Immunology • Oncology • Oral Cancer

Toxicological Impacts of Arecoline and Tobacco in Oral Submucous Fibrosis: Mechanisms and Therapeutic Insights. (PubMed, J Appl Toxicol) - "From a therapeutic perspective, intralesional administration of corticosteroids (such as dexamethasone, betamethasone, hydrocortisone, or triamcinolone) combined with hyaluronidase and antioxidants has shown improvements in mouth opening, burning sensations, and overall quality of life in OSMF patients. Additionally, herbal medicines such as curcumin and aloe vera have demonstrated efficacy, particularly in enhancing tongue protrusion and alleviating burning sensations, respectively. Lycopene and salvianolic acid B have also proven beneficial in relieving clinical symptoms and contributing to the long-term management of OSMF."

Journal • Review • Fibrosis • Immunology • ATF2 • TGFB1

Mechanistic Insights into Astragalus Membranaceus for Oral Submucosal Fibrosis: A Network Pharmacology and Experimental Approach. (PubMed, Curr Pharm Des) - "Astragalus membranaceus injection may suppress ARE-induced fibrosis by targeting EGFR and VEGFA, supporting its potential therapeutic role in the treatment of OSF."

Journal • Fibrosis • Immunology • Oncology • ACTA2 • EGFR • HRAS • MAPK3

Anthelmintic effects of Areca catechu L. (Arecaceae) and Piper betle L. (Piperaceae) combination on adult Haemonchus spp.: a scanning electron microscopy study. (PubMed, BMC Vet Res) - "The study results indicate that the methanolic extracts possess significant ability to inhibit the nematode motility and the morphological destruction caused the leakage of internal substances from circular furrows between the cuticular annuli. The cuticular damage along the entire body after the plant exposure, likely contributed to worm mortality. Taken together, these herbal effects warrant further investigation for controlling gastrointestinal nematode infections in livestock."

Journal • Infectious Disease

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

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