arecoline / Cogent Pharma - LARVOL DELTA

Arecoline upregulates CD155 expression to facilitate immune evasion in oral squamous cell carcinoma. (PubMed, J Immunother Cancer) - "This study unveils a novel mechanism by which arecoline promotes immune evasion in OSCC and highlights promising immune therapeutic targets and strategies for the treatment of areca nut-associated OSCC."

IO biomarker • Journal • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • CD8 • PVR • RHOA • TIGIT

TGF-β1 Directs TFAM-Mediated Mitochondrial Reprogramming in Oral Submucous Fibrosis. (PubMed, J Dent Res) - "TGF-β1 appears to modulate mitochondrial responses in arecoline-induced cytotoxicity, resulting in fibroblast survival, leading to a profibrotic phenotype. These observations suggest that selective targeting of the mitochondria driving these surviving myofibroblasts may serve as a novel therapeutic target for clinical translation."

Journal • Fibrosis • Immunology • TFAM • TGFB1 • VIM

Oxidative stress markers as a diagnostic tool in oral cancer and premalignant lesions: A systematic review. (PubMed, J Dent Res Dent Clin Dent Prospects) - "Standardized methodologies and therapeutic approaches targeting oxidative stress could enhance early detection and treatment, especially in resource-limited settings. However, the findings must be interpreted with caution due to methodological limitations, geographic bias, and the lack of inclusion of grey literature."

Journal • Review • Fibrosis • Head and Neck Cancer • Immunology • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma

High-fat diet exacerbates risk of prostate cancer in arecoline-induced prostatic hyperplasia via modulation of periprostatic adipose tissues in rats. (PubMed, Food Chem Toxicol) - "Our findings underscore that perilous synergy between arecoline and HFD drives an immune-metabolic remodelling in the prostate-adipose microenvironment. On a therapeutic standpoint, the study underscores lipid metabolism to be a potential target for prostate health intervention, reinforcing the necessity of lifestyle modifications to counteract diet- and habit-induced metabolic disruptions."

Journal • Preclinical • Genito-urinary Cancer • Metabolic Disorders • Oncology • Prostate Cancer • Solid Tumor • TGFB1

Stem Cell Secretome Reverse Areca Nut Extract Induced Fibrosis in Human Fibroblast and Patient-Derived Biopsies. (PubMed, J Oral Pathol Med) - "Secretome exhibited promising cytoprotective and anti-fibrotic properties, reduction in cell death, senescence, collagen expression, and oxidative stress. These findings support the potential of secretome as a novel therapeutic candidate for oral submucous fibrosis, meriting further investigation in preclinical and clinical trials."

Journal • Fibrosis • Immunology • TGFB1 • TGFB2

Neuroprotective Effects and Mechanisms of Arecoline Against H2O2-Induced Damage in SH-SY5Y Cells. (PubMed, Int J Mol Sci) - "Collectively, the findings suggest that arecoline safeguards neurons against oxidative stress by simultaneously activating antioxidant defenses and restraining apoptosis. This study adds novel molecular evidence supporting the potential neuroprotective relevance of arecoline in oxidative stress-related neuropathology."

IO biomarker • Journal • B Cell Lymphoma • CNS Disorders • Lymphoma • Neuroblastoma • Oncology • Solid Tumor • BAX • CASP3 • HMOX1 • KEAP1

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."

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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."

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