BR-DIM (oral microencapsulated diindolylmethane) / BioResponse - LARVOL DELTA

Employing cancer driver genes for the identification of immunological features in two esophageal cancer subtypes to facilitate immunotherapy. (PubMed, Immunopharmacol Immunotoxicol) - "Additionally, potential small-molecule drugs targeting DEGs in ESCA were investigated, such as 3,3'-diindolylmethane, SJ-172550, aminoglutethimide, nitrazepam, actarit, and epigallocatechin. The results of qRT-PCR showed that RUNX1, NONO, and TSC2 were not only significantly associated with the survival of esophageal squamous cell carcinoma (ESCC) but also significantly overexpressed in the ESCC cell lines (KYSE150 and KYSE450). This study is valuable for elucidating CDG functions in ESCA and for biomarker identification."

IO biomarker • Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • RUNX1 • TSC2

Evaluation of the mechanisms of the antiproliferative effect of therapy for high-grade squamous intraepithelial neoplasia (ESMO-GC 2025) - "Patients received Inosin pranobex (IP) orally and 3,3'-Diindolylmethane (DIM) intravaginally as "suppositories" for 3 months...Determination of VEGF, IL-10 and IL-17A followed by calculation of the immunoregulatory index of IL-10/IL-17A in cervical mucus may be useful for prognosis and evaluation of treatment efficacy. Legal entity responsible for the study A. Riger."

Cervical Cancer • Gynecologic Cancers • Oncology • CXCL8 • IL10 • IL17A • IL1R1

3,3'-Diindolylmethane improves pathology and neurological outcome following traumatic brain injury. (PubMed, Neurotherapeutics) - "BR4044 also decreased microbleeding and nuclear AhR at the contusion site. This translational study demonstrates that BR4044 ameliorates pathology and improves neurological outcomes following TBI by reducing brain edema, lowering acute extracellular vesicle release, modulating AhR, preserving cortical and hippocampal neurons, reducing red blood cell (RBC) extravasation into the injured brain, and promoting behavioral recovery."

Journal • Cardiovascular • CNS Disorders • Vascular Neurology

Implication of Let7b/AhR/ARNT/HMGB1/RAGE cascade in neuroplasticity disturbances induced by glucocorticoids and the promising reversible effect of 3,3 diindolymethane: Bidirectional crosstalk of Aryl hydrocarbon receptors. (PubMed, Biochem Pharmacol) - "Rats were divided into 4 groups; control, GC (20 mg/kg, S.C.), 3,3'-diindolylmethane (DIM) 50 mg/kg/day, and donepezil (DNZ) 4 mg/kg/day for 21 days. Certainly, these effects are responsible for the behavioral fluctuations, the brain's histological disruption, altered neuroplasticity, and neuroinflammation induced by GC. Moreover, DIM conquers GC-induced neuroinflammation due to its characteristic role in modulating AhR and its downstream targets."

Journal • Inflammation • GFAP • HMGB1 • KEAP1 • MIRLET7B • TNFA

NEUROPROTECTIVE EFFECT OF THE AHR MODULATORS IN A TRANSIENT MIDDLE CEREBRAL ARTERY OCCLUSION MODEL OF STROKE (WSC 2023) - "The goal of the current investigation was to evaluate the neuroprotective effect of the AhR modulators 3,3'-diindolylmethane (DIM) and -naphthoflavone (ANF) in a transient middle cerebral artery occlusion (MCAO)-based experimental model of stroke in Wistar rats... AhR pathway modulators using ANF and DIM may be taken as valuable therapeutic agents for acute ischemic stroke (AIS) treatment."

Cardiovascular • Ischemic stroke

Design, synthesis, and biological evaluation of 3,3'-diindolylmethane N-linked glycoconjugate as a leishmanial topoisomerase IB inhibitor with reduced cytotoxicity. (PubMed, RSC Med Chem) - "Molecular docking further displayed the better binding efficiency of glycoside 13 with the target enzyme, suggesting the involvement of more H-bond interactions in the case of glycosides as compared to free drugs. Therefore, this work helps in proposing the fact that the addition of sugar moieties adds some favorable characteristics to free inhibitors, making it a promising approach for future clinical diagnostic and therapeutic applications, which can prove to be a valuable arsenal in combating such neglected diseases."

Journal • Infectious Disease • Malaria

The lncRNAs UCA1 and CRNDE target miR-145/TLR4/NF-қB/TNF-α axis in acetic acid-induced ulcerative colitis model: The beneficial role of 3,3-Diindolylmethane. (PubMed, Int Immunopharmacol) - "The present study is the first to document the interrelated role of the lncRNAs UCA1 and CRNDE in UC via orchestrating miR-145/TLR4/ NF-κB /TNF-α inflammatory cascade. Furthermore, the study demonstrated a new molecular basis for the pleiotropic activities of DIM in relieving UC."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • MIR145 • TLR4 • TNFA • UCA1

3,3'-Diindolylmethane (DIM): A Potential Therapeutic Agent against Cariogenic Streptococcus mutans Biofilm. (PubMed, Antibiotics (Basel)) - "Additionally, treatment with DIM lowered extracellular polymeric substance (EPS) production and decreased its durability significantly under acidic conditions. Therefore, the anti-biofilm and anti-virulence properties of DIM against S. mutans bacteria in an "oral setting" provides evidence for its usefulness in reducing biofilm formation and potentially for caries attenuation."

Journal • Dental Disorders • Infectious Disease

Benzo[a]pyrene toxicokinetics in humans following dietary supplementation with 3,3'-diindolylmethane (DIM) or Brussels sprouts. (PubMed, Toxicol Appl Pharmacol) - "Significant amounts of metabolites in plasma were at the bay region of [C]-BaP irrespective of treatment. Although the number of subjects and large interindividual variation are limitations of this study, it represents the first human trial showing dietary intervention altering toxicokinetics of a defined dose of a known human carcinogen."

Journal

Diindolylmethane Ameliorates Ischemic Stroke-Induced Brain Injury by Peripheral and Central Mechanisms. (PubMed, Curr Neurovasc Res) - "This inhibition of platelet aggregation, platelet mediated oxidative stress, and inflammation, improved blood flow, and reduced neurological deficits, brain infarction, BBB leakage, brain water content, and histopathological abnormalities indicate the preservation of brain structural integrity. Therefore, these findings conclude that DIM exhibits neuroprotection by inhibiting platelet aggregation. Thus, the present study provided preclinical evidence of DIM neuroprotection against ischemic stroke."

Journal • Cardiovascular • CNS Disorders • Hematological Disorders • Immunology • Inflammation • Ischemic stroke • Oncology • Thrombosis • Vascular Neurology • IL10 • IL6 • TNFA

Dietary Diindolylmethane Enhances the Therapeutic Effect of Centchroman in Breast Cancer by Inhibiting Neoangiogenesis. (PubMed, Nutr Cancer) - "Interestingly, the DIM and CC combination also suppressed the lung metastasis of the highly metastatic 4T1 tumors through the downregulation of FAK/MMP9/2 signaling and reversal of epithelial-to-mesenchymal transition (EMT). Overall, these findings suggest that DIM-based nutraceuticals and functional foods can be developed as adjuvant therapy for treating TNBC."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • KDR • MMP9

Pharmacokinetic and Pharmacodynamic Properties of Indole-3-carbinol in Experimental Focal Ischemic Injury. (PubMed, Eur J Drug Metab Pharmacokinet) - "I3C pharmacokinetic parameters were similar in sham and MCAO rats, but I3C and DIM penetration in the brain and CSF was significantly higher in MCAO rats than in sham animals, and I3C oral intake significantly reduced MCAO-induced neurological impairments. Consequently, compared to intravenous treatment, I3C oral delivery is more effective in treating ischemic stroke."

Journal • PK/PD data • Cardiovascular • Ischemic stroke

Neuroprotective effect of 3,3'-diindolylmethane and ɑ-naphthoflavone, aryl hydrocarbon receptor modulators in an experimental model of ischemic stroke. (PubMed, CNS Neurol Disord Drug Targets) - "AhR pathway modulation may be taken as a valuable therapeutic target for treating acute ischemic stroke (AIS)."

Journal • Cardiovascular • Ischemic stroke

Efficacy evaluation of BR-9001, a SMEDDS formulation of 3,3’-diindolylmethane, as an inhibitor of preneoplastic and neoplastic lesion development in the prostate of Hi-Myc mice (AACR 2022) - "Despite the presence of measurable concentrations of DIM in the plasma and prostate in mice in both treated groups at all time points, BR-9001 demonstrated equivocal efficacy in preventing the development of preneoplastic and neoplastic lesions in the Hi-Myc mouse model of prostate cancer. [Supported by NCI HHSN261201500042I/HHSN26100003.]"

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Facile and Sensitive HPLC-MS/MS Method for Quantification of 3,3'-Diindolylmethane in Plasma Samples. (PubMed, Biomed Chromatogr) - "The method was successfully applied to the analysis of plasma samples after a single oral administration of the Indinol® Forto drug (200 mg) to Russian female healthy volunteers. Also, the developed method was used for the analysis of rabbit plasma samples after a single oral dose of DIM (20 mg/kg)."

Journal • Oncology

[VIRTUAL] 3,3'-Diindolylmethane (DIM): A nutritional intervention and its impact on breast density in healthy BRCA carriers compared to non-treated carriers—A prospective clinical trial. (ASCO 2020) - P=N/A | "One year’s supplementation with DIM 100 mgX1/d in BRCA carriers was associated with a significant decline in FGT amount on MRI. Larger randomized studies are warranted to corroborate these findings. Research Funding: Israel Cancer Association"

Clinical • Breast Cancer • Oncology • Solid Tumor • BRCA • MRI

3,3'-Diindolylmethane (BioResponse DIM) Exhibits Significant Metabolism Following Oral Dosing in Humans. (PubMed, Drug Metab Dispos) - "In marked contrast, we demonstrate rapid appearance of mono- and di-hydroxylated metabolites in human plasma and urine as well as sulfate and glucuronide conjugates. 2-Ox-DIM exhibited significant AHR agonist activity emphasizing the need for characterization of pharmacological properties of DIM metabolites."

Journal • Oncology

3,3'-Diindolylmethane Enhances Tumor Regression After Radiation Through Protecting Normal Cells to Modulate Antitumor Immunity. (PubMed, Adv Radiat Oncol) - "Transcriptomic profiling of cultured cells showed that DIM treatment mildly increased expression of some genes that are normally induced after radiation, such as genes involved in cell cycle arrest and apoptosis. In this study, using cultured cells and preclinical breast cancer models, we show that DIM protects normal cells from radiation-induced immediate cellular injury and combination treatment of DIM and radiation potentiates antitumor immune responses and enhances the efficacy of RT."

Journal • Breast Cancer • Immunology • Oncology • Solid Tumor

Enhanced oral bioavailability of 3,3-diindolylmethane administered in a self-microemulsifying drug delivery system (SMEDDS) (AACR 2018) - "Because the chemopreventive efficacy of DIM appears to be limited by poor oral bioavailability, the use of SMEDDS formulation technology may increase the efficacy of DIM for cancer chemoprevention. [HHSN261201500024I from the NCI, DHHS.]"

Oncology

Anti-inflammatory activity of diindolylmethane alleviates Riemerella anatipestifer infection in ducks. (PubMed, PLoS One) - "This study demonstrated the ameliorative effects of DIM in ducks infected with R. anatipestifer. Thus, DIM can potentially be used to prevent and/or treat R. anatipestifer infection via inhibition of inflammatory cytokine expression."

Journal • Inflammation • IL6

[VIRTUAL] 3,3'-diindolylmethane enhances tumor regression after radiation through protecting normal cells to modulate anti-tumor immunity (AACR-II 2020) - "As a result, DIM increases the efficacy of radiation treatment on tumor regression. This study supports the development of DIM as an adjunct agent for radiation treatment."

Breast Cancer • Oncology • Solid Tumor • CD74

3,3-Diindolylmethane (DIM): A nutritional intervention and its impact on breast density in healthy BRCA carriers. A prospective clinical trial. (PubMed, Carcinogenesis) - "In conclusion, one year's supplementation with DIM 100 mgX1/d in BRCA carriers was associated with a significant decline in FGT amount on MRI. Larger randomized studies are warranted to corroborate these findings."

Clinical • Journal • Breast Cancer • Oncology • Solid Tumor

Antiproliferative and anti-inflammatory properties of diindolylmethane and lupeol against N-butyl-N-(4-hydroxybutyl) nitrosamine induced bladder carcinogenesis in experimental rats. (PubMed) - "Preventive DIM and lupeol administration act as potent Cox-2 inhibitors, which activates the tumor suppressor protein PTEN against experimental bladder carcinogenesis by antiproliferative and anti-inflammatory properties."

Journal • Biosimilar • Oncology

Laquinimod and 3,3'-diindolylemethane alleviate neuropathological events and neurological deficits in a mouse model of intracerebral hemorrhage. (PubMed, J Neuroimmunol) - "Daily oral administration of laquinimod (25 mg/kg) or 3,3'-diindolylmethane (250 mg/kg) from 3 h after ICH induction improved motor functions, prevented the decrease of neurons within the hematoma, and attenuated activation of microglia/macrophages and astrocytes in the perihematomal region as well as infiltration of neutrophils into the hematoma. Elevated expression of AhR was detected in microglia and neutrophils, and both drugs inhibited upregulation of interleukin-6 and CXCL1. These results propose AhR as a therapeutic target for ICH."

Journal • Preclinical • AHR • CXCL1 • IL6

3,3'-Diindolylmethane nanoencapsulation improves its antinociceptive action: Physicochemical and behavioral studies. (PubMed, Colloids Surf B Biointerfaces) - "Importantly, the DIM nanoencapsulation promoted a rapid initiation and prolonged the bioactive antinociceptive action (up to 8 h) as well as reduced the effective dose in comparison to its free form. In summary, this study reported that the NCs had adequate nanometric size, increased DIM stability and its antinociceptive action in different animal models, suggesting that the formulation may be a possible therapeutic alternative to the management of pain and inflammatory-related pathologies."

Journal