Search Results (24)

Antibiotic resistance has become a global health concern, driving the need for sustainable alternatives in animal husbandry. This study explores the potential of natural feed additives as a viable solution to enhance poultry growth and health while reducing reliance on antibiotics. Chinese herbal medicines and probiotics have been widely studied as green, healthy, and safe antibiotic alternatives in livestock and poultry production. A total of 120 chickens were randomly divided into four groups: a control group and three treatment groups supplemented with 1% Pulsatilla chinensis powder, 3% fresh Acer truncatum, or 1% Clostridium butyricum. The results showed that Pulsatilla chinensis powder significantly increased gamma-glutamylcysteine (p < 0.05), UDP-N-acetylglucosamine (p < 0.05), tyramine (p < 0.01), and leucine (p < 0.05). Acer truncatum notably altered cecal metabolites, including L-tyrosine (p < 0.05), α-ketoisovaleric acid (p < 0.01), myristoleic acid (p < 0.01), glutathione (p < 0.05), and PGA1 (p < 0.05). Clostridium butyricum modified cecal metabolites such as L-glutamine (p < 0.05), riboflavin (p < 0.05), L-Carnitine (p < 0.05), ergocalciferol (p < 0.01), and α-tocotrienol (p < 0.05). Full article

Gamma-tocopherol methyltransferase (γ-TMT), a key gene in the vitamin E biosynthesis pathway, significantly influences the accumulation of tocochromanols, thereby determining rice nutritional quality. In our study, we analyzed the γ-TMT gene in 475 Korean rice accessions, uncovering 177 genetic variants, including 138 SNPs and 39 InDels. Notably, two functional SNPs, tmt-E2-28,895,665-G/A and tmt-E4-28,896,689-A/G, were identified, causing substitutions from valine to isoleucine and arginine to glycine, respectively, across 93 accessions. A positive Tajima’s D value in the indica group suggests a signature of balancing selection. Haplotype analysis revealed 27 haplotypes, with two shared between cultivated and wild accessions, seven specific to cultivated accessions, and 18 unique to wild types. Further, profiling of vitamin E isomers in 240 accessions and their association with haplotypes revealed that Hap_2, distinguished by an SNP in the 3′ UTR (tmt-3UTR-28,897,360-T/A) exhibited significantly lower α-tocopherol (AT), α-tocotrienol (AT3), total tocopherol, and total tocotrienol, but higher γ-tocopherol (GT) in the japonica group. Additionally, in the indica group, Hap_2 showed significantly higher AT, AT3, and total tocopherol, along with lower GT and γ-tocotrienol, compared to Hap_19, Hap_20, and Hap_21. Overall, this study highlights the genetic landscape of γ-TMT and provides a valuable genetic resource for haplotype-based breeding programs aimed at enhancing nutritional profiles. Full article

Tocotrienols have powerful radioprotective properties in multiple organ systems and are promising candidates for development as clinically effective radiation countermeasures. To facilitate their development as clinical radiation countermeasures, it is crucial to understand the mechanisms behind their powerful multi-organ radioprotective properties. In this context, their antioxidant effects are recognized for directly preventing oxidative damage to cellular biomolecules from ionizing radiation. However, there is a growing body of evidence indicating that the radioprotective mechanism of action for tocotrienols extends beyond their antioxidant properties. This raises a new pharmacological paradigm that tocotrienols are uniquely efficacious radioprotectors due to a synergistic combination of antioxidant and other signaling effects. In this review, we have covered the wide range of multi-organ radioprotective effects observed for tocotrienols and the mechanisms underlying it. These radioprotective effects for tocotrienols can be characterized as (1) direct cytoprotective effects, characteristic of the classic antioxidant properties, and (2) other effects that modulate a wide array of critical signaling factors involved in radiation injury. Full article

BCR-ABL1 is a fusion protein as a result of a unique chromosomal translocation (producing the so-called Philadelphia chromosome) that serves as a clinical biomarker primarily for chronic myeloid leukemia (CML); the Philadelphia chromosome also occurs, albeit rather rarely, in other types of leukemia. This fusion protein has proven itself to be a promising therapeutic target. Exploiting the natural vitamin E molecule gamma-tocotrienol as a BCR-ABL1 inhibitor with deep learning artificial intelligence (AI) drug design, this study aims to overcome the present toxicity that embodies the currently provided medications for (Ph+) leukemia, especially asciminib. Gamma-tocotrienol was employed in an AI server for drug design to construct three effective de novo drug compounds for the BCR-ABL1 fusion protein. The AIGT’s (Artificial Intelligence Gamma-Tocotrienol) drug-likeliness analysis among the three led to its nomination as a target possibility. The toxicity assessment research comparing AIGT and asciminib demonstrates that AIGT, in addition to being more effective nonetheless, is also hepatoprotective. While almost all CML patients can achieve remission with tyrosine kinase inhibitors (such as asciminib), they are not cured in the strict sense. Hence it is important to develop new avenues to treat CML. We present in this study new formulations of AIGT. The docking of the AIGT with BCR-ABL1 exhibited a binding affinity of −7.486 kcal/mol, highlighting the AIGT’s feasibility as a pharmaceutical option. 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. Full article

Radiation exposure causes acute damage to hematopoietic and immune cells. To date, there are no radioprotectors available to mitigate hematopoietic injury after radiation exposure. Gamma-tocotrienol (GT3) has demonstrated promising radioprotective efficacy in the mouse and nonhuman primate (NHP) models. We determined GT3-mediated hematopoietic recovery in total-body irradiated (TBI) NHPs. Sixteen rhesus macaques divided into two groups received either vehicle or GT3, 24 h prior to TBI. Four animals in each treatment group were exposed to either 4 or 5.8 Gy TBI. Flow cytometry was used to immunophenotype the bone marrow (BM) lymphoid cell populations, while clonogenic ability of hematopoietic stem cells (HSCs) was assessed by colony forming unit (CFU) assays on day 8 prior to irradiation and days 2, 7, 14, and 30 post-irradiation. Both radiation doses showed significant changes in the frequencies of B and T-cell subsets, including the self-renewable capacity of HSCs. 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. Full article

Previous studies have demonstrated the anticancer activities of tocotrienol on several types of cancer, but its effects on chondrosarcoma have never been investigated. Therefore, this study aims to determine the anticancer properties of annatto tocotrienol (AnTT), γ-tocotrienol (γ-T3) and δ-tocotrienol (δ-T3) on human chondrosarcoma SW1353 cells. Firstly, the MTT assay was performed to determine the half-maximal inhibitory concentration (IC₅₀) of tocotrienol on SW1353 cells after 24 h treatment. The mode of cell death, cell cycle analysis and microscopic observation of tocotrienol-treated SW1353 cells were then conducted according to the respective IC₅₀ values. Subsequently, RNAs were isolated from tocotrienol-treated cells and subjected to RNA sequencing and transcriptomic analysis. Differentially expressed genes were identified and then verified with a quantitative PCR. The current study demonstrated that AnTT, γ-T3 and δ-T3 induced G1 arrest on SW1353 cells in the early phase of treatment (24 h) which progressed to apoptosis upon 48 h of treatment. Furthermore, tocotrienol-treated SW1353 cells also demonstrated large cytoplasmic vacuolation. The subsequent transcriptomic analysis revealed upregulated signalling pathways in endoplasmic reticulum stress, unfolded protein response, autophagy and transcription upon tocotrienol treatment. 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. Full article

Exposure to high doses of radiation, accidental or therapeutic, often results in gastrointestinal (GI) injury. To date, there are no therapies available to mitigate GI injury after radiation exposure. Gamma-tocotrienol (GT3) is a promising radioprotector under investigation in nonhuman primates (NHP). We have shown that GT3 has radioprotective function in intestinal epithelial and crypt cells in NHPs exposed to 12 Gy total-body irradiation (TBI). Here, we determined GT3 potential in accelerating the GI recovery in partial-body irradiated (PBI) NHPs using X-rays, sparing 5% bone marrow. Sixteen rhesus macaques were treated with either vehicle or GT3 24 h prior to 12 Gy PBI. Structural injuries and crypt survival were examined in proximal jejunum on days 4 and 7. Plasma citrulline was assessed using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Crypt cell proliferation and apoptotic cell death were evaluated using Ki-67 and TUNEL staining. PBI significantly decreased mucosal surface area and reduced villous height. Interestingly, GT3 increased crypt survival and enhanced stem cell proliferation at day 4; however, the effects seemed to be minimized by day 7. 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. Full article

The gastrointestinal (GI) system is highly susceptible to irradiation. Currently, there is no Food and Drug Administration (FDA)-approved medical countermeasures for GI radiation injury. The vitamin E analog gamma-tocotrienol (GT3) is a promising radioprotector in mice and nonhuman primates (NHP). We evaluated GT3-mediated GI recovery in total-body irradiated (TBI) NHPs. Sixteen rhesus macaques were divided into two groups; eight received vehicle and eight GT3 24 h prior to 12 Gy TBI. Proximal jejunum was assessed for structural injuries and crypt survival on day 4 and 7. Apoptotic cell death and crypt cell proliferation were assessed with TUNEL and Ki-67 immunostaining. Irradiation induced significant shortening of the villi and reduced mucosal surface area. GT3 induced an increase in crypt depth at day 7, suggesting that more stem cells survived and proliferated after irradiation. GT3 did not influence crypt survival after irradiation. GT3 treatment caused a significant decline in TUNEL-positive cells at both day 4 (p < 0.03) and 7 (p < 0.0003). Importantly, GT3 induced a significant increase in Ki-67-positive cells at day 7 (p < 0.05). 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. Full article

Nutrition can modulate host immune responses as well as promote anticancer effects. In this study, two nutritional supplements, namely gamma-tocotrienol (γT3) and Spirulina, were evaluated for their immune-enhancing and anticancer effects in a syngeneic mouse model of breast cancer (BC). Five-week-old female BALB/c mice were fed Spirulina, γT3, or a combination of Spirulina and γT3 (Spirulina + γT3) for 56 days. The mice were inoculated with 4T1 cells into their mammary fat pad on day 28 to induce BC. The animals were culled on day 56 for various analyses. A significant reduction (p < 0.05) in tumor volume was only observed on day 37 and 49 in animals fed with the combination of γT3 + Spirulina. There was a marked increase (p < 0.05) of CD4/CD127⁺ T-cells and decrease (p < 0.05) of T-regulatory cells in peripheral blood from mice fed with either γT3 or Spirulina. The breast tissue of the combined group showed abundant areas of necrosis, but did not prevent metastasis to the liver. Although there was a significant increase (p < 0.05) of MIG-6 and Cadherin 13 expression in tumors from γT3-fed animals, there were no significant (p > 0.05) differences in the expression of MIG-6, Cadherin 13, BIRC5, and Serpine1 upon combined feeding. This showed that combined γT3 + Spirulina treatment did not show any synergistic anticancer effects in this study model. Full article

Parkinson’s disease (PD) is a debilitating neurodegenerative disease, which progresses over time, causing pathological depigmentation of the substantia nigra (SN) in the midbrain due to loss of dopaminergic neurons. Emerging studies revealed the promising effects of some nutrient compounds in reducing the risk of PD. One such nutrient compound that possess neuroprotective effects and prevents neurodegeneration is tocotrienol (T3), a vitamin E family member. In the present study, a single dose intracisternal injection of 250 µg 6-hydroxydopamine (6-OHDA) was used to induce parkinsonism in male Sprague Dawley (SD) rats. Forty-eight hours post injection, the SD rats were orally supplemented with alpha (α)- and gamma (γ)-T3 for 28 days. The neuroprotective effects of α- and γ-T3 were evaluated using behavioural studies and immunohistochemistry (IHC). The findings from this study revealed that supplementation of α- and γ-T3 was able to ameliorate the motor deficits induced by 6-OHDA and improve the neuronal functions by reducing inflammation, reversing the neuronal degradation, and preventing further reduction of dopaminergic neurons in the SN and striatum (STR) fibre density. Full article

Cyclodextrins (CDs) are a group of cyclic oligosaccharides produced from starch or starch derivatives. They contain six (αCD), seven (βCD), eight (γCD), or more glucopyranose monomers linked via α-1,4-glycosidic bonds. CDs have a truncated cone shape with a hydrophilic outer wall and a less hydrophilic inner wall, the latter forming a more apolar internal cavity. Because of this special architecture, CDs are soluble in water and can simultaneously host lipophilic guest molecules. The major advantage of inclusion into CDs is increased aqueous solubility of such lipophilic substances. Accordingly, we present studies where the complexation of natural compounds such as propolis and dietary plant bioactives (e.g., tocotrienol, pentacyclic triterpenoids, curcumin) with γCD resulted in improved stability, bioavailability, and bioactivity in various laboratory model organisms and in humans. We also address safety aspects that may arise from increased bioavailability of plant extracts or natural compounds owing to CD complexation. When orally administered, α- and βCD—which are inert to intestinal digestion—are fermented by the human intestinal flora, while γCD is almost completely degraded to glucose units by α-amylase. Hence, recent reports indicate that empty γCD supplementation exhibits metabolic activity on its own, which may provide opportunities for new applications. Full article

Studies on tocotrienols have progressively revealed the benefits of these vitamin E isoforms on human health. Beta-tocotrienol (beta-T3) is known to be less available in nature compared to other vitamin E members, which may explain the restricted number of studies on beta-T3. In the present study, we aim to investigate the anti-proliferative effects and the pro-apoptotic mechanisms of beta-T3 on two human breast adenocarcinoma cell lines MDA-MB-231 and MCF7. To assess cell viability, both cell lines were incubated for 24 and 48 h, with different concentrations of beta-T3 and gamma-T3, the latter being a widely studied vitamin E isoform with potent anti-cancerous properties. Cell cycle progression and apoptosis induction upon treatment with various concentrations of the beta-T3 isoform were assessed. The effect of beta-T3 on the expression level of several apoptosis-related proteins p53, cytochrome C, cleaved-PARP-1, Bax, Bcl-2, and caspase-3, in addition to key cell survival proteins p-PI3K and p-GSK-3 α/β was determined using western blot analysis. Beta-tocotrienol exhibited a significantly more potent anti-proliferative effect than gamma-tocotrienol on both cell lines regardless of their hormonal receptor status. Beta-T3 induced a mild G1 arrest on both cell lines, and triggered a mitochondrial stress-mediated apoptotic response in MDA-MB-231 cells. Mechanistically, beta-T3′s anti-neoplastic activity involved the downregulation of phosphorylated PI3K and GSK-3 cell survival proteins. These findings suggest that vitamin E beta-T3 should be considered as a promising anti-cancer agent, more effective than gamma-T3 for treating human breast cancer and deserves to be further studied to investigate its effects in vitro and on other cancer types. Full article

Tocotrienol, an analogue of vitamin E has been known for its numerous health benefits and anti-cancer effects. Of the four isoforms of tocotrienols, gamma-tocotrienol (γT3) has been frequently reported for their superior anti-tumorigenic activity in both in vitro and in vivo studies, when compared to its counterparts. In this study, the effect of γT3 treatment in the cytoplasmic and nuclear fraction of MDA-MB-231 human breast cancer cells were assessed using the label-free quantitative proteomics analysis. The cytoplasmic proteome results revealed the ability of γT3 to inhibit a group of proteasome proteins such as PSMA, PSMB, PSMD, and PSME. The inhibition of proteasome proteins is known to induce apoptosis in cancer cells. As such, the findings from this study suggest γT3 as a potential proteasome inhibitor that can overcome deficiencies in growth-inhibitory or pro-apoptotic molecules in breast cancer cells. The nuclear proteome results revealed the involvement of important nuclear protein complexes which hardwire the anti-tumorigenesis mechanism in breast cancer following γT3 treatment. In conclusion, this study uncovered the advancing roles of γT3 as potential proteasomes inhibitor that can be used for the treatment of breast cancer. Full article

Acute myeloid leukemia (AML) is a blood cancer characterized by the formation of faulty defective myelogenous cells with morphological heterogeneity and cytogenic aberrations leading to a loss of their function. In an attempt to find an effective and safe AML treatment, vitamin E derivatives, including tocopherols were considered as potential anti-tumor compounds. Recently, other isoforms of vitamin E, namely tocotrienols have been proposed as potential potent anti-cancerous agents, displaying promising therapeutic effects in different cancer types. In this study we evaluated the anti-cancerous effects of γ-tocotrienol, on AML cell lines in vitro. For this purpose, AML cell lines incubated with γ-tocotrienol were examined for their viability, cell cycle status, apoptotic cell death, DNA fragmentation, production of reactive oxygen species and expression of proapoptotic proteins. Our results showed that γ-tocotrienol exhibits time and dose-dependent anti-proliferative, pro-apoptotic and antioxidant effects on U937 and KG-1 cell lines, through the upregulation of proteins involved in the intrinsic apoptotic pathway. Full article

Emerging evidence suggests that gamma-tocotrienol (γ-T3), a vitamin E isomer, has potent anti-cancer properties against a wide-range of cancers. γ-T3 not only inhibited the growth and survival of cancer cells in vitro, but also suppressed angiogenesis and tumour metastasis under in vivo conditions. Recently, γ-T3 was found to target cancer stem cells (CSCs), leading to suppression of tumour formation and chemosensitisation. Despite its promising anti-cancer potential, the exact mechanisms responsible for the effects of γ-T3 are still largely unknown. Here, we report the identification of Ang-1 (Angiopoietin-1)/Tie-2 as a novel γ-T3 downstream target. In prostate cancer cells, γ-T3 treatment leads to the suppression of Ang-1 at both the mRNA transcript and protein levels. Supplementing the cells with Ang-1 was found to protect them against the anti-CSC effect of γ-T3. Intriguingly, inactivation of Tie-2, a member receptor that mediates the effect of Ang-1, was found to significantly enhance the cytotoxic effect of γ-T3 through activation of AMP-activated protein kinase (AMPK) and subsequent interruption of autophagy. Our results highlighted the therapeutic potential of using γ-T3 in combination with a Tie-2 inhibitor to treat advanced prostate cancer. Full article