Safety Evaluations of Single Dose of the Olive Secoiridoid S-(−)-Oleocanthal in Swiss Albino Mice

Siddique, Abu Bakar; King, Judy A.; Meyer, Sharon A.; Abdelwahed, Khaldoun S.; Busnena, Belnaser A.; Sayed, Khalid A. El

doi:10.3390/nu12020314

Cited by 10 publications

(11 citation statements)

References 46 publications

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“…Several studies suggested that the absorption of toxins in the gastrointestinal tract change the body, relative organs weight, and hematopoietic system as well. [73][74][75][76] The in vivo toxicological studies data revealed no clinical toxic sign of 5000 mg/kg FSE as revealed from behavioral pattern, mortality, body weight, relative vital organs weight, and biochemical analysis. According to the chemical labeling and classification of acute systemic toxicity recommended by OECD, the FSE was given class 5 status (LD50>5,000 mg/ kg) which was the lowest category of toxicity.…”

Section: Dovepressmentioning

confidence: 92%

Methanolic Fenugreek Seed Extract Induces p53-Dependent Mitotic Catastrophe in Breast Cancer Cells, Leading to Apoptosis

Khan¹,

Allemailem

Alsahli

et al. 2021

JIR

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Purpose The plant Trigonella foenum-graecum , well-known as fenugreek, has been shown to control type-2 diabetes, the level of cholesterol, inflammation of wounds, disorders related to gastrointestinal tracts, and cancer as well. The present study aimed to evaluate the anti-cancer potential of methanolic fenugreek seed extract (FSE) and its possible molecular mechanism of action in breast cancer cells. Methods The anticancer potential of FSE was evaluated in MCF-7 and SK-BR3 breast cancer cells through various cellular assays after selecting the IC 10 , IC 25 , IC 35 , and IC 50 doses by the cell cytotoxicity assay. Furthermore, the oral acute toxicity of FSE was examined in mice, according to the guidelines of the Organization for Economic Co-operation and Development (OECD). Results FSE exhibited dose-dependent cytotoxicity, as the IC 50 was found to be 150 and 40 μg/mL for MCF-7 and SK-BR3 breast cancer cells, respectively. The cytological observations showed the typical apoptotic morphology in both of the breast cancer cells upon treatment with FSE, as it inhibited the migration and adhesion, in a dose-dependent manner. The flow cytometry analysis revealed that FSE induced a significant shift from G 2 /M, and polyploidy (>G) at higher concentrations that suggested the activation of p53-mediated mitotic catastrophe, consequently leading to apoptosis. FSE induced a significant increase in the mitochondrial depolarization, ROS as well as a Bax/Bcl-2 ratio, and also exhibited the mitochondrial associated p53 signaling pathway. The in vivo acute toxicity data revealed that the oral administration of FSE did not induce any toxic effect in mice. Conclusion This study, for the first time, reports the mechanistic details of the anti-cancer potential of FSE. It requires a detailed analysis to understand the effect of FSE to induce the apoptosis through the multiple signaling pathways at varying concentrations. The nontoxic effect of FSE in mice suggests to utilize it safely for pharmaceutical formulations in different cancer systems.

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Section: Dovepressmentioning

confidence: 92%

Methanolic Fenugreek Seed Extract Induces p53-Dependent Mitotic Catastrophe in Breast Cancer Cells, Leading to Apoptosis

Khan¹,

Allemailem

Alsahli

et al. 2021

JIR

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“…All the sectioning and H&E staining has been done at the AML Laboratories (Jacksonville, FL, USA). Briefly, paraffin-embedded tissues were sliced into 5 µm sections and mounted on positively charged slides, dewaxed with xylene, rinsed with alcohol, rehydrated by water and finally, the tissue slides were stained with H&E. Tissues were then dehydrated through ethanol to xylene and coverslipped with Permount [59].…”

Section: Hematoxylin and Eosin Y (Hande) Stainingmentioning

confidence: 99%

“…OC showed high degree of selectivity to cancerous cells and exhibited modest or no cytotoxic effects against the non-tumorigenic cell lines, including the human adult dermal fibroblast HDFa cells [57], human mammary epithelial MCF10A cells [42], human liver LO2 cells [53], murine macrophages J774A.1 cells [55], human fibroblast BJ cells [58], rat fibroblast 3Y1 cells [58], human lung fibroblast IMR90 cells [58] and isolated primary human hepatocytes [52]. Recent single dose acute safety study further suggested the potential safety profile of OC single oral therapeutic dose (10 mg/kg) in Swiss albino mouse model over 14 days of administration [59]. OC inhibited the metastasis of melanoma and hepatocellular carcinoma to lung in mouse tail vein models after iv injection of A431 melanoma and HCCLM3 hepatocellular cancer cells, respectively [52,53].…”

Section: Introductionmentioning

confidence: 99%

(−)-Oleocanthal as a Dual c-MET-COX2 Inhibitor for the Control of Lung Cancer

et al. 2020

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Lung cancer (LC) represents the topmost mortality-causing cancer in the U.S. LC patients have overall poor survival rate with limited available treatment options. Dysregulation of the mesenchymal epithelial transition factor (c-MET) and cyclooxygenase 2 (COX2) initiates aggressive LC profile in a subset of patients. The Mediterranean extra-virgin olive oil (EVOO)-rich diet already documented to reduce multiple malignancies incidence. (-)-Oleocanthal (OC) is a naturally occurring phenolic secoiridoid exclusively occurring in EVOO and showed documented anti-breast and other cancer activities via targeting c-MET. This study shows the novel ability of OC to suppress LC progression and metastasis through dual targeting of c-MET and COX-2. Western blot analysis and COX enzymatic assay showed significant reduction in the total and activated c-MET levels and inhibition of COX1/2 activity in the lung adenocarcinoma cells A549 and NCI-H322M, in vitro. In addition, OC treatment caused a dose-dependent inhibition of the HGF-induced LC cells migration. Daily oral treatment with 10 mg/kg OC for 8 weeks significantly suppressed the LC A549-Luc progression and prevented metastasis to brain and other organs in a nude mouse tail vein injection model. Further, microarray data of OC-treated lung tumors showed a distinct gene signature that confirmed the dual targeting of c-MET and COX2. Thus, the EVOO-based OC is an effective lead with translational potential for use as a prospective nutraceutical to control LC progression and metastasis.

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“…On the other hand, interestingly, OC has been already exhibited in vitro and in vivo modulating β-amyloid, tau phosphorylation, and neuroinflammation activities in different models. A recent study showed the high safety profile of OC acute single oral dose in a Swiss albino mice model [ 47 ]. Unfortunately, one of the major obstacles for the application of OC as a prospective nutraceutical are its irritant, pharyngeal pungent, and astringent taste, similar to the NSAID drug-ibuprofen.…”

Section: Discussionmentioning

confidence: 99%

(-)-Oleocanthal Nutraceuticals for Alzheimer’s Disease Amyloid Pathology: Novel Oral Formulations, Therapeutic, and Molecular Insights in 5xFAD Transgenic Mice Model

et al. 2021

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Alzheimer’s disease (AD) is a complex progressive neurodegenerative disorder affecting humans mainly through the deposition of Aβ-amyloid (Aβ) fibrils and accumulation of neurofibrillary tangles in the brain. Currently available AD treatments only exhibit symptomatic relief but do not generally intervene with the amyloid and tau pathologies. The extra-virgin olive oil (EVOO) monophenolic secoiridoid S-(–)-oleocanthal (OC) showed anti-inflammatory activity through COX system inhibition with potency comparable to the standard non-steroidal anti-inflammatory drug (NSAID) like ibuprofen. OC also showed positive in vitro, in vivo, and clinical therapeutic effects against cardiovascular diseases, many malignancies, and AD. Due to its pungent, astringent, and irritant taste, OC should be formulated in acceptable dosage form before its oral use as a potential nutraceutical. The objective of this study is to develop new OC oral formulations, assess whether they maintained OC activity on the attenuation of β-amyloid pathology in a 5xFAD mouse model upon 4-month oral dosing use. Exploration of potential OC formulations underlying molecular mechanism is also within this study scope. OC powder formulation (OC-PF) and OC-solid dispersion formulation with erythritol (OC-SD) were prepared and characterized using FT-IR spectroscopy, powder X-ray diffraction, and scanning electron microscopy (SEM) analyses. Both formulations showed an improved OC dissolution profile. OC-PF and OC-SD improved memory deficits of 5xFAD mice in behavioral studies. OC-PF and OC-SD exhibited significant attenuation of the accumulation of Aβ plaques and tau phosphorylation in the brain of 5xFAD female mice. Both formulations markedly suppressed C3AR1 (complement component 3a receptor 1) activity by targeting the downstream marker STAT3. Collectively, these results demonstrate the potential for the application of OC-PF as a prospective nutraceutical or dietary supplement to control the progression of amyloid pathogenesis associated with AD.

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Safety Evaluations of Single Dose of the Olive Secoiridoid S-(−)-Oleocanthal in Swiss Albino Mice

Cited by 10 publications

References 46 publications

Methanolic Fenugreek Seed Extract Induces p53-Dependent Mitotic Catastrophe in Breast Cancer Cells, Leading to Apoptosis

Methanolic Fenugreek Seed Extract Induces p53-Dependent Mitotic Catastrophe in Breast Cancer Cells, Leading to Apoptosis

(−)-Oleocanthal as a Dual c-MET-COX2 Inhibitor for the Control of Lung Cancer

(-)-Oleocanthal Nutraceuticals for Alzheimer’s Disease Amyloid Pathology: Novel Oral Formulations, Therapeutic, and Molecular Insights in 5xFAD Transgenic Mice Model

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