gamma-tocotrienol / KLK OLEO - LARVOL DELTA

Serum Proteomic Signatures in Nonhuman Primates after Treatment with a Radiation Countermeasure and Exposure to a Partial- or Total-body Supralethal Radiation Dose. (PubMed, Radiat Res) - "One drug under advanced development, gamma-tocotrienol (GT3), has proved promising in terms of its antioxidant activity, accelerated hematopoietic recovery, and reduction of DNA damage in treated animals exposed to various doses of ionizing radiation...Notably, administration of GT3 offered significant protection against radiation-induced damage by either partial- or total-body irradiation in these pathways. Overall, this study offers insight into the biochemical mechanisms of the drug, pathways and proteins adversely affected by radiation, and potential biomarkers that can be further investigated to accurately assess absorbed radiation doses in exposed populations."

Journal

Spleen Transcriptome of Nonhuman Primates Exposed to High Doses of Total- or Partial-Body Radiation Comparisons with Jejunum and Lung. (PubMed, Radiat Res) - "In this study, we analyzed transcriptomic responses in irradiated nonhuman primate (NHP) tissues pretreated with gamma-tocotrienol (GT3) to evaluate GT3 efficacy and irradiation's tissue impact...In addition, a lower dose of GT3 pretreatment was ineffective in protecting against a supralethal 12 Gy radiation dose in either model. Overall, these findings provide important insights into the molecular changes induced by GT3 treatment and radiation, highlighting opportunities to identify biomarkers of radiation injury and to develop MCMs."

Journal

Delta- and Gamma-Tocotrienols Inhibit the Proliferation of HCC2998 Human Colorectal Carcinoma Cells via Modulation of Histone Modification Pathways Involved in DNA Damage Response. (PubMed, Cell Biol Int) - "These findings indicate that γT3 and δT3 inhibit HCC2998 cell proliferation by activating the DDR pathway, highlighting their potential as therapeutic agents to overcome cell cycle arrest resistance in CRC. This study provides critical insights into the molecular actions of γT3 and δT3, supporting their further investigation as promising candidates for CRC intervention."

Journal • Colorectal Cancer • Oncology • Solid Tumor • ATM • BRCA1 • CCNE2 • CDC25A • CDC25C • CDK2 • E2F1 • GNRP • PMAIP1 • RAD51 • SMC1A

Serum Metabolomic Signatures in Nonhuman Primates Treated with a Countermeasure and Exposed to Partial- or Total-Body Radiation. (PubMed, Metabolites) - "Gamma-tocotrienol (GT3) of vitamin E is a promising radioprotector under advanced development which has been tested for efficacy in both murine and nonhuman primate (NHP) models...The C21-steroid hormone biosynthesis and metabolism pathway was significantly dysregulated in both PBI and TBI groups, with minimal protection afforded by GT3 administration. GT3 offered a differential response in terms of protected metabolites and pathways in either group that was most effective at the early post-irradiation time points."

Journal

Mogroside-rich extract alleviates the inflammation state in polycystic ovary syndrome rats through modulating intestinal microbiota-metabolic axis and suppressing the NF-κB/NLRP3 pathway. (PubMed, J Steroid Biochem Mol Biol) - "Notably, MGE partially reversed letrozole-induced alterations in colonic metabolites, restoring levels of anti-inflammatory metabolites like butyric acid and gamma-tocotrienol. Furthermore, MGE significantly reduced ovarian pro-inflammatory cytokines and downregulated the expression of p-NF-κB and NLRP3 proteins. Collectively, these findings demonstrate that MGE ameliorates PCOS symptoms by coordinately regulating ovarian inflammation via suppressing the NF-κB/NLRP3 pathway and restoring intestinal microbiota-metabolic axis balance, highlighting its therapeutic potential for PCOS."

Journal • Preclinical • Inflammation • Metabolic Disorders • Polycystic Ovary Syndrome • NLRP3

Integrated microbiome and metabolome analysis reveals altered gut microbial communities and metabolite profiles in dairy cows with subclinical mastitis. (PubMed, BMC Microbiol) - "The intestinal microbial composition and metabolic profiles of healthy and SM cows were significantly distinct, that were characterized by decreased abundance of intestinal symbiotic bacteria, potential probiotics and anti-inflammatory, antioxidant compounds, along with increased abundance of potential pro-inflammatory bacteria, lipid metabolites, and the occurrence of oxidative stress in cows suffered from SM. The results of this study further enriched our understanding of the correlations between gut microbiota and metabolic profiles and SM, which provided insight into the formulation of management strategies for SM in cows."

Journal • Gastrointestinal Disorder • Infectious Disease • CAT

Chemical Profiling and Antioxidant, Anti-Inflammatory, Cytotoxic, Analgesic, and Antidiarrheal Activities from the Seeds of Commonly Available Red Grape (Vitis vinifera L.). (PubMed, Nutr Metab Insights) - "Several notable constituents, such as gamma-sitosterol, stigmasterol, paromomycin, 4,6-cholestadienol, gamma-tocotrienol, 24-Propylidenecholest-5-en-3beta-ol, and alpha-tocopherol acetate, are also present...Aqueous soluble fraction exerted inhibition of nearly 50% heat-induced hemolysis compared to the standard acetylsalicylic acid (42%)...The current findings endorsed the health benefits of V. vinifera by revealing potent antioxidant, anti-inflammatory, analgesic, and antidiarrheal effects. Nevertheless, further in-depth analysis of the plant's chemical constituents and pharmacological effects on health is warranted for novel drug discovery from V. vinifera."

Journal • Hematological Disorders • Inflammation • Pain

Gamma-Tocotrienol Inhibits Proliferation and Growth of HSD17B4-Overexpressing HepG2 Liver Cancer Cells. (PubMed, Curr Cancer Drug Targets) - "In conclusion, our study demonstrates that γ-T3 exhibits potent anti-proliferative and anti-tumor effects against HepG2 cells overexpressing HSD17B4. These findings highlight the therapeutic potential of γ-T3 in HCC treatment and suggest its role in targeting HSD17B4-associated pathways to inhibit tumor growth and enhance apoptosis."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • CCND1 • STAT3

Pathology of acute sub-lethal or near-lethal irradiation of nonhuman primates prophylaxed with the nutraceutical, gamma tocotrienol. (PubMed, Sci Rep) - "The prophylactic use of the test nutraceutical, GT3, appeared to limit the extent of irradiation-associated pathology within blood forming tissues and, to some extent, within the small intestine of the gastrointestinal tract. No distinct, global pattern of bodily protection was noted with the agent's use, although a hint of a possible radioprotective benefit was suggested not only by a lessening of apparent injury within select organ systems, but also by way of noting the lack of early onset of moribundity within select GT3-treated animals."

Journal • Gastrointestinal Disorder

Histopathological studies of nonhuman primates exposed to supralethal doses of total- or partial-body radiation: influence of a medical countermeasure, gamma-tocotrienol. (PubMed, Sci Rep) - "Results show that these supralethal radiation exposures induce severe injuries that manifest both clinically as well as pathologically, as evidenced by the noted functionally crippling lesions within various major organ systems of experimental NHPs. The MCM, GT3, has limited radioprotective efficacy against such supralethal radiation doses."

Journal

Validating a Four-gene Set for H-ARS Severity Prediction in Peripheral Blood Samples of Irradiated Rhesus Macaques. (PubMed, Radiat Res) - "Our earlier work identified a set of four genes (DDB2, FDXR, POU2AF1 and WNT3), which predicts severity of the hematological acute radiation syndrome (H-ARS) within the first three days postirradiation In this study of 41 Rhesus macaques (Macaca mulatta, 27 males, 14 females) irradiated with 5.8-7.2 Gy (LD29-50/60), including some treated with gamma-tocotrienol (GT3, a radiation countermeasure) we independently validated these genes as predictors in both sexes and examined them after three days...However, DDB2 showed higher GE values than FDXR. As shown in previous studies, the diagnostic significance of WNT3 could not be reproduced in Rhesus macaques; this could be due to the choice of animal model and methodological challenges."

Journal • Hematological Disorders • ACACA • DDB2 • FDXR • POU2AF1 • WNT3

Validating Radiosensitivity with Pre-Exposure Differential Gene Expression in Peripheral Blood Predicting Survival and Non-Survival in a Second Irradiated Rhesus Macaque Cohort. (PubMed, Radiat Res) - "Access to a second rhesus macaque cohort (males = 40, females = 23, total n = 63) irradiated with 5.8-7.2 Gy (LD29-50/60) and some treated with gamma-tocotrienol (GT3, a radiation countermeasure) allowed us to validate these gene expression changes independently...An associated odds ratio reflected a 62% elevated risk for dying or surviving per unit change (Ct-value) in gene expression, considering the before-mentioned CHD5 thresholds in RNA copy numbers. In conclusion, we identified two subsets of male animals characterized by increased (Ct values ≤ 11) and decreased (Ct values ≥ 14.4) CHD5 GE copy numbers before radiation exposure, which independently of the cohort, radiation exposure or treatment appeared to predict the death or survival in males."

Journal • CHI3L1 • IGF2BP1

Metabolomic Profiles in Tissues of Nonhuman Primates Exposed to Either Total- or Partial-Body Irradiation. (PubMed, Radiat Res) - "In this study, we report on changes in metabolomic and lipidomic profiles in multiple tissues of nonhuman primates (NHPs) that received either 4.0 Gy or 5.8 Gy total-body irradiation (TBI) of 60Co gamma rays, and 4.0 or 5.8 Gy partial-body irradiation (PBI) from LINAC-derived photons and treated with a promising radiation countermeasure, gamma-tocotrienol (GT3)...Taken together, the results of our study demonstrate that the prophylactic administration of GT3 results in metabolic and lipidomic shifts that likely provide an overall advantage against radiation injury. This investigation is among the first to highlight the use of a molecular phenotyping approach in a highly translatable NHP model of partial- and total-body irradiation to determine the underlying physiological mechanisms involved in the radioprotective efficacy of GT3."

Journal • Inflammation

Modulation of Hematopoietic Injury by a Promising Radioprotector, Gamma-Tocotrienol, in Rhesus Macaques Exposed to Partial-Body Radiation. (PubMed, Radiat Res) - "Additionally, GT3 treatment was shown to increase the percentage of CD34+ cells, including T and NK-cell subsets. Our data further affirm GT3's role in hematopoietic recovery and suggest the need for its further development as a prophylactic radiation medical countermeasure."

Journal • CD34

Transcriptome profile changes in the jejunum of nonhuman primates exposed to supralethal dose of total- or partial-body radiation. (PubMed, BMC Genomics) - "In this study, nonhuman primates were exposed to either 12.0 Gy cobalt-60 gamma (total-body irradiation, TBI) or X-ray (partial-body irradiation, PBI) 24 h after administration of a potential radiation medical countermeasure, gamma-tocotrienol (GT3)...Differential pathway activation was also identified across PBI and TBI, pointing towards altered molecular response for different degrees of bone marrow sparing and radiation doses. This study provides insight into radiation-induced changes in jejunal transcriptional profiles, supporting the investigation for the identification of biomarkers for radiation injury and countermeasure efficacy."

Journal • ER

Artificial Intelligence Assisted Pharmacophore Design for Philadelphia Chromosome-Positive Leukemia with Gamma-Tocotrienol: A Toxicity Comparison Approach with Asciminib. (PubMed, Biomedicines) - "Since current medical care only exclusively cures a small number of patients of CML with utter toxicity as a pressing consequence, a new possibility to tackle adverse instances is therefore presented in this study by new formulations of natural compounds of vitamin E, gamma-tocotrienol, thoroughly designed by AI. Even though AI-designed AIGT is effective and adequately safe as computed, in vivo testing is mandatory for the verification of the in vitro results."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • BCR

Metabolomics Reveals Novel Serum Metabolic Signatures in Gastric Cancer by a Mass Spectrometry Platform. (PubMed, J Proteome Res) - "Twelve differential metabolites (ethyl 2,4-dimethyl-1,3-dioxolane-2-acetate, D-urobilinogen, 14-HDoHE, 13-hydroxy-9-methoxy-10-oxo-11-octadecenoic acid, 5,6-dihydroxyprostaglandin F1a, 9'-carboxy-gamma-tocotrienol, glutaric acid, alanine, tyrosine, C18:2(FFA), adipic acid, and suberic acid) were identified to establish the diagnosis model for GAS...In conclusion, a diagnostic panel was established and validated, which could be used to further stage the early and advanced GAS patients from healthy controls. These findings may provide useful information for explaining the GAS metabolic alterations and try to facilitate the characterization of GAS patients in the early stage."

Journal • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Metabolic Disorders • Oncology • Solid Tumor

Development of gamma-tocotrienol as a radiation medical countermeasure for the acute radiation syndrome: Current status and future perspectives. (PubMed, Expert Opin Investig Drugs) - No abstract available

Journal

Gamma-Tocotrienol Modulates Total-Body Irradiation-Induced Hematopoietic Injury in a Nonhuman Primate Model. (PubMed, Int J Mol Sci) - "Importantly, GT3 accelerated the recovery in CD34 cells, increased HSC function as shown by improved recovery of CFU-granulocyte macrophages (CFU-GM) and burst-forming units erythroid (B-FUE), and aided the recovery of circulating neutrophils and platelets. These data elucidate the role of GT3 in hematopoietic recovery, which should be explored as a potential medical countermeasure to mitigate radiation-induced injury to the hematopoietic system."

Journal • Preclinical • CD34

Effects of Gamma-Tocotrienol on Partial-Body Irradiation-Induced Intestinal Injury in a Nonhuman Primate Model. (PubMed, Antioxidants (Basel)) - "GT3 did not ameliorate a radiation-induced decrease in citrulline levels. These data suggest that X-rays induce severe intestinal injury post-PBI and that GT3 has minimal radioprotective effect in this novel model."

Journal • Preclinical • Gastrointestinal Disorder

Transcriptomic Analysis of the Anticancer Effects of Annatto Tocotrienol, Delta-Tocotrienol and Gamma-Tocotrienol on Chondrosarcoma Cells. (PubMed, Nutrients) - "In addition, several cell proliferation and cancer-related pathways, such as Hippo signalling pathway and Wnt signalling pathway were also significantly downregulated upon treatment. In conclusion, AnTT, γ-T3 and δ-T3 possess promising anticancer properties against chondrosarcoma cells and further study is required to confirm their effectiveness as adjuvant therapy for chondrosarcoma."

Journal • Oncology • Sarcoma • Solid Tumor

Effects of Gamma-Tocotrienol on Intestinal Injury in a GI-Specific Acute Radiation Syndrome Model in Nonhuman Primate. (PubMed, Int J Mol Sci) - "These data suggest that GT3 has radioprotective function in intestinal epithelial and crypt cells. GT3 should be further explored as a prophylactic medical countermeasure for radiation-induced GI injury."

Journal • Gastrointestinal Disorder

Gamma-tocotrienol modifies methylation of HOXA10, IRF4 and RORα genes in CD4 T-lymphocytes: Evidence from a syngeneic mouse model of breast cancer. (PubMed, Curr Res Immunol) - "γT3 supplementation reduced tumour growth in the tumour-induced animals and modulated host immune system by inducing changes in DNA methylation patterns of the HOXA10, IRF4 and RORα genes, which are involved in differentiation and clonal expansion of CD4 T-cells. Results suggest that γT3 may enhance cell-mediated immune response in mice with breast cancer by inducing changes in DNA methylation pattern."

Journal • Preclinical • Breast Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • CD4 • IRF4

Gamma-tocotrienol, a radiation countermeasure, reverses proteomic changes in serum following total-body gamma irradiation in mice. (PubMed, Sci Rep) - "Of particular interest, significant expression changes in beta-2-glycoprotein 1, alpha-1-acid glycoprotein 1, alpha-2-macroglobulin, complement C3, mannose-binding protein C, and major urinary protein 6 were noted after TBI and reversed with GT3 treatment. This study reports the untargeted approach, the network, and specific serum proteins which could be translated as biomarkers of both radiation injury and protection by countermeasures."

Journal • Preclinical • Gastrointestinal Disorder • Inflammation • A2M • ORM1

In silico identification of the specific pathways in each stage of colorectal cancer and the association of their top genes with drug resistance and sensitivity. (PubMed, Med Oncol) - "GEO data revealed that gamma-tocotrienol (g-T3), NSC319726, and Casiopeina Cas-II-gly may reduce the expression of, NDUFAF1, CCNB1, DKK1 genes, respectively (P < 0.01). Specific pathways and TOP RANK genes could lead to cancer progression and malignancy, resistance to chemotherapy drugs, poor survival in patients, and metastasis. Therefore, identification and targeting these pathways at each stage could be crucial in inhibiting progression at different stages of CRC."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Inflammatory Arthritis • Oncology • Solid Tumor • CCNB1 • DKK1 • TNFRSF11A