Identifying the Molecular Mechanism of the Medium Chain Triglyceride (Ketogenic) Diet

2016 ◽  
Author(s):  
Matthew C. Walker ◽  
Robin S.B. Williams
Keyword(s):  
Ketogenic Diet ◽  
Seizure Control ◽  
Medium Chain Triglyceride ◽  
Decanoic Acid ◽  
In Vivo Models ◽  
Principal Mechanism ◽  
Excitatory Neurotransmitter ◽  
Medium Chain

The medium chain triglyceride (MCT) ketogenic diet provides a highly effective and commonly used approach for treating drug-resistant epilepsy. It is associated with elevated levels of two MCT-derived fatty acids, decanoioc and octanoic acids. Researchers have identified a role for decanoic acid and a range of novel related chemicals in seizure control in multiple acute in vitro and in vivo models. A principal mechanism of decanoic acid is direct inhibition of AMPA receptors, key excitatory neurotransmitter receptors widely recognized as a target for seizure control. These data suggest a therapeutic mechanism of the MCT ketogenic diet through a direct fatty acid–dependent mechanism, independent of ketosis. This discovery will enable the development of an improved and, potentially, better-tolerated diet and the generation of a corresponding pharmaceutical approach. The diet should be termed the MCT diet, as the consequent ketosis may not be necessary for seizure control.

scholarly journals Medium Chain Triglyceride (MCT) Oil Affects the Immunophenotype via Reprogramming of Mitochondrial Respiration in Murine Macrophages

Foods ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 553 ◽  
Author(s):  
Yu ◽  
Go ◽  
Kim
Keyword(s):  
Inflammatory Responses ◽  
Medium Chain Triglyceride ◽  
Metabolic Reprogramming ◽  
Activation Markers ◽  
In Vivo Models ◽  
Medium Chain ◽  
Anti Inflammatory ◽  
Alternatively Activated

Medium chain triglyceride (MCT) oil has been postulated to modulate inflammatory responses, but the detailed mechanisms have not been fully elucidated. Based on recent studies demonstrating that mitochondrial metabolic reprogramming and immune responses are correlated, the current study sought to determine whether MCT oil controls inflammatory responses through modulation of mitochondria using both in vitro and in vivo models. The mitochondrial metabolic phenotypes of macrophages were assessed according to oxygen consumption rate (OCR). Inflammatory responses were assessed for production of cytokines and expression of activation markers. MCT oil was more rapidly oxidized as observed by increased OCR in macrophages. The production of pro-inflammatory cytokines was down-regulated and anti-inflammatory cytokine was elevated by MCT oil. In addition, classically activated M1 and alternatively activated M2 markers were reciprocally regulated by MCT intervention. Overall, up-regulated β-oxidation by MCT contributes to the anti-inflammatory M2-like status of macrophages, which may aid in the dietary prevention and/or amelioration of inflammation.

scholarly journals Inclusion of Medium-Chain Triglyceride in Lipid-Based Formulation of Cannabidiol Facilitates Micellar Solubilization In Vitro, but In Vivo Performance Remains Superior with Pure Sesame Oil Vehicle

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1349
Author(s):  
Wanshan Feng ◽  
Chaolong Qin ◽  
Elena Cipolla ◽  
Jong Bong Lee ◽  
Atheer Zgair ◽  
...  
Keyword(s):  
Medium Chain Triglyceride ◽  
Sesame Oil ◽  
Water Soluble ◽  
Lymphatic Transport ◽  
Micellar Solubilization ◽  
Micellar Phase ◽  
Medium Chain ◽  
Natural Oil

Oral sesame oil-based formulation facilitates the delivery of poorly water-soluble drug cannabidiol (CBD) to the lymphatic system and blood circulation. However, this natural oil-based formulation also leads to considerable variability in absorption of CBD. In this work, the performance of lipid-based formulations with the addition of medium-chain triglyceride (MCT) or surfactants to the sesame oil vehicle has been tested in vitro and in vivo using CBD as a model drug. The in vitro lipolysis has shown that addition of the MCT leads to a higher distribution of CBD into the micellar phase. Further addition of surfactants to MCT-containing formulations did not improve distribution of the drug into the micellar phase. In vivo, formulations containing MCT led to lower or similar concentrations of CBD in serum, lymph and MLNs, but with reduced variability. MCT improves the emulsification and micellar solubilization of CBD, but surfactants did not facilitate further the rate and extent of lipolysis. Even though addition of MCT reduces the variability, the in vivo performance for the extent of both lymphatic transport and systemic bioavailability remains superior with a pure natural oil vehicle.

scholarly journals Neuronal decanoic acid oxidation is markedly lower than that of octanoic acid: A mechanistic insight into the medium-chain triglyceride ketogenic diet

Epilepsia ◽  
2017 ◽  
Vol 58 (8) ◽  
pp. 1423-1429 ◽  
Author(s):  
Aziza Khabbush ◽  
Michael Orford ◽  
Yi-Chen Tsai ◽  
Tricia Rutherford ◽  
Maura O'Donnell ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Octanoic Acid ◽  
Medium Chain Triglyceride ◽  
Decanoic Acid ◽  
Acid Oxidation ◽  
Medium Chain ◽  
Mechanistic Insight ◽  
Insight Into

scholarly journals Novel Therapeutic Application of Self-Assembly Peptides Targeting the Mitochondria in In Vitro and In Vivo Experimental Models of Gastric Cancer

2020 ◽  
Vol 21 (17) ◽  
pp. 6126
Author(s):  
Dong Jin Kim ◽  
M. T. Jeena ◽  
Ok-Hee Kim ◽  
Ha-Eun Hong ◽  
Haeyeon Seo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Antioxidant Enzymes ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Self Assembly ◽  
Gastric Cancer Cells ◽  
In Vivo Models ◽  
Principal Mechanism

Here, we provide the possibility of a novel chemotherapeutic agent against gastric cancer cells, comprising the combination of 5-fluorouracil (5-FU) and a mitochondria-targeting self-assembly peptide, which is a phenylalanine dipeptide with triphenyl phosphonium (Mito-FF). The anticancer effects and mechanisms of 5-FU and Mito-FF, individually or in combination, were compared through both in vitro and in vivo models of gastric cancer. Our experiments consistently demonstrated that the 5-FU and Mito-FF combination therapy was superior to monotherapy with either, as manifested by both higher reduction of proliferation as well as an induction of apoptotic cell death. Interestingly, we found that combining 5-FU with Mito-FF leads to a significant increase of reactive oxygen species (ROS) and reduction of antioxidant enzymes in gastric cancer cells. Moreover, the inhibition of ROS abrogated the pro-apoptotic effects of combination therapy, suggesting that enhanced oxidative stress could be the principal mechanism of the action of combination therapy. We conclude that the combination of 5-FU and Mito-FF exerts potent antineoplastic activity against gastric cancer cells, primarily by promoting ROS generation and suppressing the activities of antioxidant enzymes.

Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

2019 ◽  
Vol 2 (4) ◽  
pp. 83-98 ◽  
Author(s):  
André De Lima Mota ◽  
Bruna Vitorasso Jardim-Perassi ◽  
Tialfi Bergamin De Castro ◽  
Jucimara Colombo ◽  
Nathália Martins Sonehara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Metabolism ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Carbonic Anhydrases ◽  
In Vivo Models ◽  
Ca Ix ◽  
Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression. 

Current Challenges in the Development of Vaccines and Drugs Against Emerging Vector-borne Diseases

2019 ◽  
Vol 26 (16) ◽  
pp. 2974-2986 ◽  
Author(s):  
Kwang-sun Kim
Keyword(s):  
New Host ◽  
In Vivo Models ◽  
Vector Borne Diseases ◽  
Novel Drugs ◽  
Huge Impact ◽  
Tick Borne Disease ◽  
Vector Borne ◽  
Living Organisms

Vectors are living organisms that transmit infectious diseases from an infected animal to humans or another animal. Biological vectors such as mosquitoes, ticks, and sand flies carry pathogens that multiply within their bodies prior to delivery to a new host. The increased prevalence of Vector-Borne Diseases (VBDs) such as Aedes-borne dengue, Chikungunya (CHIKV), Zika (ZIKV), malaria, Tick-Borne Disease (TBD), and scrub typhus has a huge impact on the health of both humans and livestock worldwide. In particular, zoonotic diseases transmitted by mosquitoes and ticks place a considerable burden on public health. Vaccines, drugs, and vector control methods have been developed to prevent and treat VBDs and have prevented millions of deaths. However, development of such strategies is falling behind the rapid emergence of VBDs. Therefore, a comprehensive approach to fighting VBDs must be considered immediately. In this review, I focus on the challenges posed by emerging outbreaks of VBDs and discuss available drugs and vaccines designed to overcome this burden. Research into promising drugs needs to be upgraded and fast-tracked, and novel drugs or vaccines being tested in in vitro and in vivo models need to be moved into human clinical trials. Active preventive tactics, as well as new and upgraded diagnostics, surveillance, treatments, and vaccination strategies, need to be monitored constantly if we are to manage VBDs of medical importance.

Potential for Treatment of Neurodegenerative Diseases with Natural Products or Synthetic Compounds that Stabilize Microtubules

2020 ◽  
Vol 26 (35) ◽  
pp. 4362-4372
Author(s):  
John H. Miller ◽  
Viswanath Das
Keyword(s):  
Natural Products ◽  
Neurodegenerative Diseases ◽  
In Vivo Models ◽  
Synthetic Compounds ◽  
Stabilizing Agents ◽  
Animal Models Of Disease ◽  
Model Studies ◽  
Models Of Disease

No effective therapeutics to treat neurodegenerative diseases exist, despite significant attempts to find drugs that can reduce or rescue the debilitating symptoms of tauopathies such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, or Pick’s disease. A number of in vitro and in vivo models exist for studying neurodegenerative diseases, including cell models employing induced-pluripotent stem cells, cerebral organoids, and animal models of disease. Recent research has focused on microtubulestabilizing agents, either natural products or synthetic compounds that can prevent the axonal destruction caused by tau protein pathologies. Although promising results have come from animal model studies using brainpenetrant natural product microtubule-stabilizing agents, such as paclitaxel analogs that can access the brain, epothilones B and D, and other synthetic compounds such as davunetide or the triazolopyrimidines, early clinical trials in humans have been disappointing. This review aims to summarize the research that has been carried out in this area and discuss the potential for the future development of an effective microtubule stabilizing drug to treat neurodegenerative disease.

A Review on Opuntia Species and its Chemistry, Pharmacognosy, Pharmacology and Bioapplications

2020 ◽  
Vol 16 (8) ◽  
pp. 1227-1244
Author(s):  
Dharmendra Kumar ◽  
Pramod K. Sharma
Keyword(s):  
Human Consumption ◽  
In Vivo Models ◽  
Sugar Amino Acids ◽  
Opuntia Species ◽  
Therapeutic Uses ◽  
Anti Inflammatory ◽  
Online Library ◽  
Different Parts

Background:: Opuntia species, locally known as prickly pear was used for various purposes as food, medicine, beverage, source of dye and animal food. Many studies have revealed its pharmacology activity from time to time. This review is a collection of chemistry, pharmacognosy, pharmacology and bioapplications of the cactus family. Methods: Many sources were used to collect information about Opuntia species such as Pub med, Google scholar, Agris, science direct, Embase, Merk index, Wiley online library, books and other reliable sources. This review contains studies from 1812 to 2019. Results: The plants from the cactus family offer various pharmacological active compounds including phenolic compounds, carotenoids, betalains, vitamins, steroids, sugar, amino acids, minerals and fibers. These bioactive compounds serve various pharmacological activities such as anticancer, antiviral, anti-diabetic, Neuroprotective, anti-inflammatory, antioxidant, Hepatoprotective, antibacterial, antiulcer and alcohol hangover. According to various studies, Opuntia species offer many bioapplications such as fodder for animal, soil erosion, prevention, human consumption and waste water decontamination. Finally, different parts of plants are used in various formulations that offer many biotechnology applications. Conclusion: Different parts of Opuntia plant (fruits, seeds, flowers and cladodes) are used in various health problems which include wound healing, anti-inflammatory and urinary tract infection from ancient times. Nowadays, researches have extended several pharmacological and therapeutic uses of Opuntia species as discussed in this review. Many in-vitro and in-vivo models are also discussed in this review as the proofs of research findings. Various research gaps have been observed in current studies that require attention in the future.

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