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Jonker PB, Sadullozoda M, Cognet G, Saab JJA, Sokol KH, Wu VX, Kumari D, Sheehan C, Ozgurses ME, Agovino D, Croley G, Patel SA, Bock-Hughes A, Macleod KF, Shah H, Coloff JL, Lien EC, Muir A. Microenvironmental arginine restriction sensitizes pancreatic cancers to polyunsaturated fatty acids by suppression of lipid synthesis. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.03.10.642426. [PMID: 40161789 PMCID: PMC11952453 DOI: 10.1101/2025.03.10.642426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
Nutrient limitation is a characteristic feature of poorly perfused tumors. In contrast to well-perfused tissues, nutrient deficits in tumors perturb cellular metabolic activity, which imposes metabolic constraints on cancer cells. The metabolic constraints created by the tumor microenvironment can lead to vulnerabilities in cancers. Identifying the metabolic constraints of the tumor microenvironment and the vulnerabilities that arise in cancers can provide new insight into tumor biology and identify promising antineoplastic targets. To identify how the microenvironment constrains the metabolism of pancreatic tumors, we challenged pancreatic cancer cells with microenvironmental nutrient levels and analyzed changes in cell metabolism. We found that arginine limitation in pancreatic tumors perturbs saturated and monounsaturated fatty acid synthesis by suppressing the lipogenic transcription factor SREBP1. Synthesis of these fatty acids is critical for maintaining a balance of saturated, monounsaturated, and polyunsaturated fatty acids in cellular membranes. As a consequence of microenvironmental constraints on fatty acid synthesis, pancreatic cancer cells and tumors are unable to maintain lipid homeostasis when exposed to polyunsaturated fatty acids, leading to cell death by ferroptosis. In sum, arginine restriction in the tumor microenvironment constrains lipid metabolism in pancreatic cancers, which renders these tumors vulnerable to polyunsaturatedenriched fat sources.
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Affiliation(s)
- Patrick B. Jonker
- Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA, 60637
| | - Mumina Sadullozoda
- Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA, 60637
| | - Guillaume Cognet
- Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA, 60637
| | - Juan J. Apiz Saab
- Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA, 60637
| | - Kelly H. Sokol
- Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, Michigan, USA, 49503
| | - Violet X. Wu
- Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA, 60637
| | - Deepa Kumari
- Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA, 60637
| | - Colin Sheehan
- Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA, 60637
| | - Mete E. Ozgurses
- Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, IL, USA, 60612
| | - Darby Agovino
- Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA, 60637
| | - Grace Croley
- Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA, 60637
| | - Smit A. Patel
- Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA, 60637
| | - Althea Bock-Hughes
- Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA, 60637
| | - Kay F. Macleod
- Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA, 60637
| | - Hardik Shah
- Metabolomics Platform, Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA, 60637
| | - Jonathan L. Coloff
- Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, IL, USA, 60612
| | - Evan C. Lien
- Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, Michigan, USA, 49503
| | - Alexander Muir
- Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA, 60637
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Clews AC, Whitehead PS, Zhang L, Lü S, Shockey JM, Chapman KD, Dyer JM, Xu Y, Mullen RT. Identification and Characterization of Lipid Droplet-Associated Protein (LDAP) Isoforms from Tung Tree ( Vernicia fordii). PLANTS (BASEL, SWITZERLAND) 2025; 14:814. [PMID: 40094817 PMCID: PMC11901875 DOI: 10.3390/plants14050814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Revised: 02/25/2025] [Accepted: 02/28/2025] [Indexed: 03/19/2025]
Abstract
Lipid droplets (LDs) are cytoplasmic organelles responsible primarily for the storage of neutral lipids, such as triacyclglycerols (TAGs). Derived from the endoplasmic reticulum bilayer, LDs are composed of a hydrophobic lipid core encased by a phospholipid monolayer and surface-associated proteins. To date, only a relatively few LD 'coat' proteins in plants have been identified and characterized, most of which come from studies of the model plant Arabidopsis thaliana. To expand our knowledge of the plant LD proteome, the LD-associated protein (LDAP) family from the tung tree (Vernicia fordii), whose seeds are rich in a commercially valuable TAG containing the conjugated fatty acid α-eleostearic acid (C18:3Δ9cis,11trans,13trans [α-ESA]), was identified and characterized. Based on the tung tree transcriptome, three LDAP isoforms (VfLDAP1-3) were elucidated and the encoded proteins distinctly clustered into three clades along with their respective isoforms from other angiosperm species. Ectopic expression of the VfLDAPs in Nicotiana benthamiana leaves revealed that they localized specifically to LDs and influenced LD numbers and sizes, as well as increasing TAG content and altering TAG fatty acid composition. Interestingly, in a partially reconstructed TAG-ESA biosynthetic pathway, the co-expression of VfLDAP3 and, to a lesser degree, VfLDAP2, significantly increased the content of α-ESA stored within the LDs. These results suggest that the VfLDAPs can influence the steady-state content and composition of TAG in plant cells and that certain LDAP isoforms may have evolved to more efficiently package TAGs into LDs containing unusual fatty acids, such as α-ESA.
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Affiliation(s)
- Alyssa C. Clews
- Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada;
| | - Payton S. Whitehead
- BioDiscovery Institute, Department of Biological Sciences, University of North Texas, Denton, TX 76203, USA; (P.S.W.); (K.D.C.)
| | - Lingling Zhang
- Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 430074, China;
| | - Shiyou Lü
- State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan 430062, China;
| | - Jay M. Shockey
- United States Department of Agriculture, Agricultural Research Service, Southern Regional Research Center, New Orleans, LA 70124, USA; (J.M.S.); (J.M.D.)
| | - Kent D. Chapman
- BioDiscovery Institute, Department of Biological Sciences, University of North Texas, Denton, TX 76203, USA; (P.S.W.); (K.D.C.)
| | - John M. Dyer
- United States Department of Agriculture, Agricultural Research Service, Southern Regional Research Center, New Orleans, LA 70124, USA; (J.M.S.); (J.M.D.)
| | - Yang Xu
- Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada;
| | - Robert T. Mullen
- Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada;
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Honma T. Discovery and Synthesis of Conjugated Fatty Acids from Natural Products. J Oleo Sci 2025; 74:241-249. [PMID: 40024778 DOI: 10.5650/jos.ess24282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/04/2025] Open
Abstract
Conjugated fatty acids are a promising ingredient for cancer prevention and treatment. Conjugated fatty acids are minor fatty acids that are rarely found in nature, although a wide variety of structures are known. In recent years, studies have been conducted to screen natural products containing conjugated fatty acids and to synthesize conjugated fatty acids using enzymes derived from natural products. As a result, it was found that the seed oils of Centranthus ruber and Valeriana officinalis, which belong to the Valerianaceae family, contain conjugated linolenic acid, which has a conjugated triene structure in the molecule. Furthermore, it was found that parinaric acid, a conjugated tetraenoic fatty acid, can be synthesized by adding α-linolenic acid to enzymes extracted from the brown alga Padina arborescens Holmes. These research results are expected to be useful in securing conjugated fatty acids in quantities that can withstand practical application. Recent studies have reported that the cytotoxic effect of conjugated fatty acids is due to a programmed cell death called "ferroptosis". Many anticancer drugs exhibit anticancer activity through DNA modification, cell cycle arrest, angiogenesis inhibition, and epidermal growth factor receptor inhibition. Conjugated fatty acids, however, induce cell death through a mechanism distinct from these mechanisms and are therefore expected to be effective against cancers resistant to currently used anticancer drugs. The results of these studies will help to promote research on the use of conjugated fatty acids to overcome intractable cancers in the future.
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Zhang S, Guo L, Tao R, Liu S. Ferroptosis-targeting drugs in breast cancer. J Drug Target 2025; 33:42-59. [PMID: 39225187 DOI: 10.1080/1061186x.2024.2399181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Revised: 07/07/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024]
Abstract
In 2020, breast cancer surpassed lung cancer as the most common cancer in the world for the first time. Due to the resistance of some breast cancer cell lines to apoptosis, the therapeutic effect of anti-breast cancer drugs is limited. According to recent report, the susceptibility of breast cancer cells to ferroptosis affects the progress, prognosis and drug resistance of breast cancer. For instance, roblitinib induces ferroptosis of trastuzumab-resistant human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells by diminishing fibroblast growth factor receptor 4 (FGFR4) expression, thereby augmenting the susceptibility of these cells to HER2-targeted therapies. In tamoxifen-resistant breast cancer cells, Fascin exacerbates their resistance by repressing solute carrier family 7 member 11 (SLC7A11) expression, which in turn heightens their responsiveness to tamoxifen. In recent years, Chinese herbs extracts and therapeutic drugs have been demonstrated to elicit ferroptosis in breast cancer cells by modulating a spectrum of regulatory factors pertinent to ferroptosis, including SLC7A11, glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long chain family member 4 (ACSL4), and haem oxygenase 1 (HO-1). Here, we review the roles and mechanisms of Chinese herbal extracts and therapeutic drugs in regulating ferroptosis in breast cancer, providing potential therapeutic options for anti-breast cancer.
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Affiliation(s)
- Shuxian Zhang
- Chronic Disease Research Center, Medical College, Dalian University, Dalian, China
| | - Lijuan Guo
- Chronic Disease Research Center, Medical College, Dalian University, Dalian, China
| | - Ran Tao
- Department of Anatomy, Medical College, Dalian University, Dalian, China
| | - Shuangping Liu
- Chronic Disease Research Center, Medical College, Dalian University, Dalian, China
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Amakhmakh M, Hajib A, Belmaghraoui W, Harhar H, Mohammed EA, Al Abdulmonem W, Goh KW, Bouyahya A, Meliani A. Assessment of the impact of microwave roasting on nutrient content, lipid profile, and oxidative stability of pomegranate seed oil. Food Chem X 2024; 24:101875. [PMID: 39974711 PMCID: PMC11838093 DOI: 10.1016/j.fochx.2024.101875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Revised: 09/30/2024] [Accepted: 10/03/2024] [Indexed: 02/21/2025] Open
Abstract
The pomegranate, Punica granatum L. (Punicaceae), stands as one of the most widely employed oils in the cosmetic industry. However, due to its higher content of conjugated linoleic acid, its susceptibility to oxidation is a major challenge, with the most prominent being punicic acid. This study aimed to evaluate the effects of traditional roasting in a microwave on the lipid content, nutritional value, and oxidative stability of Moroccan pomegranate seed oil. The findings indicated a rise in the amount of oil after 15 min of roasting at 650 W, the amount of oil rose from 27.03 to 30.10 (g/100 g). However, the protein content, UV absorbance values, iodine, and saponification values were not significantly affected by a longer roasting time. The peroxide value increases with roasting (1.00 to 5.00 M.eq. O2/kg oil). The roasting process under 350 W did not significantly alter the fatty acid composition. The total tocopherol content exhibits a decrease with increasing roasting time and power, ranging from 333.36 mg/100 g for unroasted seeds to 316.84 mg/100 g for seeds roasted under the conditions of 650 W for 15 min. The roasting process has proven to be critical for the immediate and long-term preservation of the nutritional and physico-chemical properties of pomegranate seed oil.
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Affiliation(s)
- Mohammed Amakhmakh
- Laboratory of Applied Organic Chemistry, Faculty of Sciences and technology, Sidi Mohamed Ben Abdelah University, Fez, Morocco
| | - Ahmed Hajib
- Biotechnology Analytical Sciences and Quality Control Team, Polydisciplinary Faculty of Taroudant, Université Ibn Zohr, Morocco
- Higher School of Education and Training (ESEF), Ibn Zohr University, Agadir, Morocco
| | | | - Hicham Harhar
- Laboratory of Nanotechnology, Materials and Environment, Department of Chemistry, Faculty of Science, Mohammed V University in Rabat, Av. Ibn Batouta, BP 1014, Rabat, Morocco
| | - El Asri Mohammed
- Laboratory of Applied Organic Chemistry, Faculty of Sciences and technology, Sidi Mohamed Ben Abdelah University, Fez, Morocco
| | - Waleed Al Abdulmonem
- Department of Pathology, College of Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Khang Wen Goh
- Faculty of Data Science and Information Technology, INTI International University, Nilai, Malaysia
- Faculty of Mathematics and Natural Sciences, Universitas Negeri Padang, Padang, Indonesia
| | - Abdelhakim Bouyahya
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Morocco
| | - Abdeslam Meliani
- Laboratory of Applied Organic Chemistry, Faculty of Sciences and technology, Sidi Mohamed Ben Abdelah University, Fez, Morocco
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Hirata Y, Yamada Y, Taguchi S, Kojima R, Masumoto H, Kimura S, Niijima T, Toyama T, Kise R, Sato E, Uchida Y, Ito J, Nakagawa K, Taguchi T, Inoue A, Saito Y, Noguchi T, Matsuzawa A. Conjugated fatty acids drive ferroptosis through chaperone-mediated autophagic degradation of GPX4 by targeting mitochondria. Cell Death Dis 2024; 15:884. [PMID: 39643606 PMCID: PMC11624192 DOI: 10.1038/s41419-024-07237-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 11/04/2024] [Accepted: 11/08/2024] [Indexed: 12/09/2024]
Abstract
Conjugated fatty acids (CFAs) have been known for their anti-tumor activity. However, the mechanism of action remains unclear. Here, we identify CFAs as inducers of glutathione peroxidase 4 (GPX4) degradation through chaperone-mediated autophagy (CMA). CFAs, such as (10E,12Z)-octadecadienoic acid and α-eleostearic acid (ESA), induced GPX4 degradation, generation of mitochondrial reactive oxygen species (ROS) and lipid peroxides, and ultimately ferroptosis in cancer cell lines, including HT1080 and A549 cells, which were suppressed by either pharmacological blockade of CMA or genetic deletion of LAMP2A, a crucial molecule for CMA. Mitochondrial ROS were sufficient and necessary for CMA-dependent GPX4 degradation. Oral administration of an ESA-rich oil attenuated xenograft tumor growth of wild-type, but not that of LAMP2A-deficient HT1080 cells, accompanied by increased lipid peroxidation, GPX4 degradation and cell death. Our study establishes mitochondria as the key target of CFAs to trigger lipid peroxidation and GPX4 degradation, providing insight into ferroptosis-based cancer therapy.
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Affiliation(s)
- Yusuke Hirata
- Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
| | - Yuto Yamada
- Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
| | - Soma Taguchi
- Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
| | - Ryota Kojima
- Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
| | - Haruka Masumoto
- Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
| | - Shinnosuke Kimura
- Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
| | - Takuya Niijima
- Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
| | - Takashi Toyama
- Laboratory of Molecular Biology and Metabolism, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
| | - Ryoji Kise
- Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
| | - Emiko Sato
- Division of Clinical Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
| | - Yasunori Uchida
- Laboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan
| | - Junya Ito
- Laboratory of Food Function Analysis, Graduate School of Agricultural Sciences, Tohoku University, Sendai, Japan
| | - Kiyotaka Nakagawa
- Laboratory of Food Function Analysis, Graduate School of Agricultural Sciences, Tohoku University, Sendai, Japan
| | - Tomohiko Taguchi
- Laboratory of Organelle Pathophysiology, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan
| | - Asuka Inoue
- Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
- Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan
| | - Yoshiro Saito
- Laboratory of Molecular Biology and Metabolism, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
| | - Takuya Noguchi
- Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
| | - Atsushi Matsuzawa
- Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
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Du M, Gong M, Wu G, Jin J, Wang X, Jin Q. Conjugated Linolenic Acid (CLnA) vs Conjugated Linoleic Acid (CLA): A Comprehensive Review of Potential Advantages in Molecular Characteristics, Health Benefits, and Production Techniques. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:5503-5525. [PMID: 38442367 DOI: 10.1021/acs.jafc.3c08771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/07/2024]
Abstract
Conjugated linoleic acid (CLA) has been extensively characterized due to its many biological activities and health benefits, but conjugated linolenic acid (CLnA) is still not well understood. However, CLnA has shown to be more effective than CLA as a potential functional food ingredient. Current research has not thoroughly investigated the differences and advantages between CLnA and CLA. This article compares CLnA and CLA based on molecular characteristics, including structural, chemical, and metabolic characteristics. Then, the in vivo research evidence of CLnA on various health benefits is comprehensively reviewed and compared with CLA in terms of effectiveness and mechanism. Furthermore, the potential of CLnA in production technology and product protection is analyzed. In general, CLnA and CLA have similar physicochemical properties of conjugated molecules and share many similarities in regulation effects and pathways of various health benefits as well as in the production methods. However, their specific properties, regulatory capabilities, and unique mechanisms are different. The superior potential of CLnA must be specified according to the practical application patterns of isomers. Future research should focus more on the advantageous characteristics of different isomers, especially the effectiveness and safety in clinical applications in order to truly exert the potential value of CLnA.
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Affiliation(s)
- Meijun Du
- State Key Laboratory of Food Science and Resources, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, International Joint Research Laboratory for Lipid Nutrition and Safety, School of Food Science and Technology, Jiangnan University, Wuxi 214122, P. R. China
| | - Mengyue Gong
- State Key Laboratory of Food Science and Resources, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, International Joint Research Laboratory for Lipid Nutrition and Safety, School of Food Science and Technology, Jiangnan University, Wuxi 214122, P. R. China
| | - Gangcheng Wu
- State Key Laboratory of Food Science and Resources, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, International Joint Research Laboratory for Lipid Nutrition and Safety, School of Food Science and Technology, Jiangnan University, Wuxi 214122, P. R. China
| | - Jun Jin
- State Key Laboratory of Food Science and Resources, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, International Joint Research Laboratory for Lipid Nutrition and Safety, School of Food Science and Technology, Jiangnan University, Wuxi 214122, P. R. China
| | - Xingguo Wang
- State Key Laboratory of Food Science and Resources, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, International Joint Research Laboratory for Lipid Nutrition and Safety, School of Food Science and Technology, Jiangnan University, Wuxi 214122, P. R. China
| | - Qingzhe Jin
- State Key Laboratory of Food Science and Resources, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, International Joint Research Laboratory for Lipid Nutrition and Safety, School of Food Science and Technology, Jiangnan University, Wuxi 214122, P. R. China
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Mohammadi F, Dikpati A, Bertrand N, Rudkowska I. Encapsulation of conjugated linoleic acid and ruminant trans fatty acids to study the prevention of metabolic syndrome-a review. Nutr Rev 2024; 82:262-276. [PMID: 37221703 DOI: 10.1093/nutrit/nuad047] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/25/2023] Open
Abstract
Studies have reported the potential benefits of consuming conjugated linoleic acid (CLA) and ruminant trans fatty acids (R-TFAs) in reducing the risk factors of metabolic syndrome (MetS). In addition, encapsulation of CLA and R-TFAs may improve their oral delivery and further decrease the risk factors of MetS. The objectives of this review were (1) to discuss the advantages of encapsulation; (2) to compare the materials and techniques used for encapsulating CLA and R-TFAs; and (3) to review the effects of encapsulated vs non-encapsulated CLA and R-TFAs on MetS risk factors. Examination of papers citing micro- and nano-encapsulation methods used in food sciences, as well as the effects of encapsulated vs non-encapsulated CLA and R-TFAs, was conducted using the PubMed database. A total of 84 papers were examined; of these, 18 studies were selected that contained information on the effects of encapsulated CLA and R-TFAs. The 18 studies that described encapsulation of CLA or R-TFAs indicated that micro- or nano-encapsulation processes stabilized CLA and prevented oxidation. CLA was mainly encapsulated using carbohydrates or proteins. So far, oil-in-water emulsification followed by spray-drying were the frequently used techniques for encapsulation of CLA. Further, 4 studies investigated the effects of encapsulated CLA on MetS risk factors compared with non-encapsulated CLA. A limited number of studies investigated the encapsulation of R-TFAs. The effects of encapsulated CLA or R-TFAs on the risk factors for MetS remain understudied; thus, additional studies comparing the effects of encapsulated and non-encapsulated CLA or R-TFAs are needed.
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Affiliation(s)
- Farzad Mohammadi
- Department of Kinesiology, Faculty of Medicine, Université Laval, Québec City, Québec, Canada
- Endocrinology and Nephrology Unit, CHU de Québec-Université Laval Research Center, Québec City, Québec, Canada
| | - Amrita Dikpati
- Endocrinology and Nephrology Unit, CHU de Québec-Université Laval Research Center, Québec City, Québec, Canada
- Faculty of Pharmacy, Pavillon Ferdinand-Vandry, Université Laval, Québec City, Québec, Canada
| | - Nicolas Bertrand
- Endocrinology and Nephrology Unit, CHU de Québec-Université Laval Research Center, Québec City, Québec, Canada
- Faculty of Pharmacy, Pavillon Ferdinand-Vandry, Université Laval, Québec City, Québec, Canada
| | - Iwona Rudkowska
- Department of Kinesiology, Faculty of Medicine, Université Laval, Québec City, Québec, Canada
- Endocrinology and Nephrology Unit, CHU de Québec-Université Laval Research Center, Québec City, Québec, Canada
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9
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Do Q, Zhang R, Hooper G, Xu L. Differential Contributions of Distinct Free Radical Peroxidation Mechanisms to the Induction of Ferroptosis. JACS AU 2023; 3:1100-1117. [PMID: 37124288 PMCID: PMC10131203 DOI: 10.1021/jacsau.2c00681] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 02/14/2023] [Accepted: 02/14/2023] [Indexed: 05/03/2023]
Abstract
Ferroptosis is a form of regulated cell death driven by lipid peroxidation of polyunsaturated fatty acids (PUFAs). Lipid peroxidation can propagate through either the hydrogen-atom transfer (HAT) or peroxyl radical addition (PRA) mechanism. However, the contribution of the PRA mechanism to the induction of ferroptosis has not been studied. In this study, we aim to elucidate the relationship between the reactivity and mechanisms of lipid peroxidation and ferroptosis induction. We found that while some peroxidation-reactive lipids, such as 7-dehydrocholesterol, vitamins D3 and A, and coenzyme Q10, suppress ferroptosis, both nonconjugated and conjugated PUFAs enhanced cell death induced by RSL3, a ferroptosis inducer. Importantly, we found that conjugated PUFAs, including conjugated linolenic acid (CLA 18:3) and conjugated linoleic acid (CLA 18:2), can induce or potentiate ferroptosis much more potently than nonconjugated PUFAs. We next sought to elucidate the mechanism underlying the different ferroptosis-inducing potency of conjugated and nonconjugated PUFAs. Lipidomics revealed that conjugated and nonconjugated PUFAs are incorporated into distinct cellular lipid species. The different peroxidation mechanisms predict the formation of higher levels of reactive electrophilic aldehydes from conjugated PUFAs than nonconjugated PUFAs, which was confirmed by aldehyde-trapping and mass spectrometry. RNA sequencing revealed that protein processing in the endoplasmic reticulum and proteasome are among the most significantly upregulated pathways in cells treated with CLA 18:3, suggesting increased ER stress and activation of unfolded protein response. These results suggest that protein damage by lipid electrophiles is a key step in ferroptosis.
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Affiliation(s)
- Quynh Do
- Department
of Medicinal Chemistry, University of Washington, Seattle, Washington 98195, United States
| | - Rutan Zhang
- Department
of Medicinal Chemistry, University of Washington, Seattle, Washington 98195, United States
| | - Gavin Hooper
- Department
of Medicinal Chemistry, University of Washington, Seattle, Washington 98195, United States
| | - Libin Xu
- Department
of Medicinal Chemistry, University of Washington, Seattle, Washington 98195, United States
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10
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Du M, Jin J, Wu G, Jin Q, Wang X. Metabolic, structure-activity characteristics of conjugated linolenic acids and their mediated health benefits. Crit Rev Food Sci Nutr 2023; 64:8203-8217. [PMID: 37021469 DOI: 10.1080/10408398.2023.2198006] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/07/2023]
Abstract
Conjugated linolenic acid (CLnA) is a mixture of octadecenoic acid with multiple positional and geometric isomers (including four 9, 11, 13-C18:3 isomers and three 8, 10, 12-C18:3 isomers) that is mainly present in plant seeds. In recent years, CLnA has shown many promising health benefits with the deepening of research, but the metabolic characteristics, physiological function differences and mechanisms of different isomers are relatively complex. In this article, the metabolic characteristics of CLnA were firstly reviewed, with focus on its conversion, catabolism and anabolism. Then the possible mechanisms of CLnA exerting biological effects were summarized and analyzed from its own chemical and physical characteristics, as well as biological receptor targeting characteristics. In addition, the differences and mechanisms of different isomers of CLnA in anticancer, lipid-lowering, anti-diabetic and anti-inflammatory physiological functions were compared and summarized. The current results show that the position and cis-trans conformation of conjugated structure endow CLnA with unique physical and chemical properties, which also makes different isomers have commonalities and particularities in the regulation of metabolism and physiological functions. Corresponding the metabolic characteristics of different isomers with precise nutrition strategy will help them to play a better role in disease prevention and treatment. CLnA has the potential to be developed into food functional components and dietary nutritional supplements. The advantages and mechanisms of different CLnA isomers in the clinical management of specific diseases need further study.
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Affiliation(s)
- Meijun Du
- State Key Lab of Food Science and Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, International Joint Research Laboratory for Lipid Nutrition and Safety, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Jun Jin
- State Key Lab of Food Science and Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, International Joint Research Laboratory for Lipid Nutrition and Safety, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Gangcheng Wu
- State Key Lab of Food Science and Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, International Joint Research Laboratory for Lipid Nutrition and Safety, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Qingzhe Jin
- State Key Lab of Food Science and Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, International Joint Research Laboratory for Lipid Nutrition and Safety, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Xingguo Wang
- State Key Lab of Food Science and Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, International Joint Research Laboratory for Lipid Nutrition and Safety, School of Food Science and Technology, Jiangnan University, Wuxi, China
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11
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Sunarwidhi AL, Hernawan A, Frediansyah A, Widyastuti S, Martyasari NWR, Abidin AS, Padmi H, Handayani E, Utami NWP, Maulana FA, Ichfa MSM, Prasedya ES. Multivariate Analysis Revealed Ultrasonic-Assisted Extraction Improves Anti-Melanoma Activity of Non-Flavonoid Compounds in Indonesian Brown Algae Ethanol Extract. Molecules 2022; 27:7509. [PMID: 36364336 PMCID: PMC9655947 DOI: 10.3390/molecules27217509] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 10/28/2022] [Accepted: 10/30/2022] [Indexed: 07/29/2023] Open
Abstract
Indonesia has high biodiversity of algae that are under-utilised due to limitations in the processing techniques. Here, we observed the effect of two different extraction methods (cold maceration and ultrasonic-assisted extraction (UAE)) on multiple variables of Indonesian brown algae ethanol extracts (Sargassum polycystum, Sargassum cristaefolium, Sargassum aquifolium and Turbinaria ornata). The variables observed included metabolites screening by untargeted metabolomics liquid chromatography-high-resolution mass spectrometry (LC-HRMS), observation of total phenolic content (TPC), total flavonoid content (TFC), anti-oxidant and B16-F10 melanoma cells cytotoxicity. UAE extracts had higher extraction yield and TPC, but no TFC difference was observed. UAE extract had more lipophilic compounds, such as fatty acids (Palmitic acid, Oleamide, Palmitoleic acid, Eicosapentaenoic acid, α-Linolenic acid, Arachidonic acid), lipid-derived mediators (11,12-Epoxyeicosatrienoic acid ((±)11(12)-EET)), steroid derivatives (Ergosterol peroxide), lipophilic metabolite (Fucoxanthin), and lipid-soluble vitamins (all-trans-retinol). Principle component analysis (PCA) revealed that TPC, not TFC, in the UAE extracts was correlated with the anti-oxidant activities and cytotoxicity of the extracts towards B16-F10 melanoma cells. This means other non-flavonoid phenolic and lipophilic compounds may have contributed to its bioactivity. These results suggest that out of the two methods investigated, UAE could be a chosen method to extract natural anti-melanogenic agents from brown algae.
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Affiliation(s)
| | - Ari Hernawan
- Department of Informatics Engineering, Faculty of Engineering, University of Mataram, Mataram 83115, Indonesia
| | - Andri Frediansyah
- PRTPP, National Research and Innovation Agency (BRIN), Yogyakarta 55861, Indonesia
| | - Sri Widyastuti
- Faculty of Food Technology and Agroindustry, University of Mataram, Mataram 83115, Indonesia
| | - Ni Wayan Riyani Martyasari
- Bioscience and Biotechnology Research Centre, Faculty of Mathematics and Natural Sciences, University of Mataram, Mataram 83115, Indonesia
| | - Angga Susmana Abidin
- Bioscience and Biotechnology Research Centre, Faculty of Mathematics and Natural Sciences, University of Mataram, Mataram 83115, Indonesia
| | - Hasriaton Padmi
- Bioscience and Biotechnology Research Centre, Faculty of Mathematics and Natural Sciences, University of Mataram, Mataram 83115, Indonesia
| | - Ervina Handayani
- Department of Pharmacy, Faculty of Medicine, University of Mataram, Mataram 83115, Indonesia
| | - Ni Wayan Putri Utami
- Department of Pharmacy, Faculty of Medicine, University of Mataram, Mataram 83115, Indonesia
| | - Farreh Alan Maulana
- Department of Pharmacy, Faculty of Medicine, University of Mataram, Mataram 83115, Indonesia
| | | | - Eka Sunarwidhi Prasedya
- Bioscience and Biotechnology Research Centre, Faculty of Mathematics and Natural Sciences, University of Mataram, Mataram 83115, Indonesia
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12
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Wang H, Shuai X, Ye S, Zhang R, Wu M, Jiang S, Li Y, Wu D, He J. Recent advances in the development of bitter gourd seed oil: from chemical composition to potential applications. Crit Rev Food Sci Nutr 2022; 63:10678-10690. [PMID: 35648048 DOI: 10.1080/10408398.2022.2081961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Non-conventional seed oils are being considered novelty foods due to the unique properties of their chemical constituents. Numerous such seed oils serve as nutritional and functional supplements, making them a point of interest for scholars. Bitter gourd (Momordica charantia L.) seed oil (BGSO) has been widely used in folk medicine worldwide for the treatment of different pathologies, such as diabetes, cancer, and several inflammatory diseases. Therefore, its nutritional and medicinal value has been extensively studied. Considering the potential use of BGSO, it is imperative to have a comprehensive understanding of this product to develop and use its biologically active ingredients in innovative food and pharmaceutical products. An extensive understanding of BGSO would also help improve the economic feasibility of the bitter gourd seed processing industry and help prevent environmental pollution associated with the raw waste produced during the processing of bitter gourd seeds. This review addresses the potential uses of BGSO in terms of food and pharmaceuticals industry perspectives and comprehensively summarizes the oil extraction process, chemical composition, biological activity, and the application prospects of BGSO in clinical medicine.
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Affiliation(s)
- Huiling Wang
- Key Laboratory for Deep Processing of Major Grain and Oil, Ministry of Education, Wuhan Polytechnic University, Wuhan, P.R. China
- National R&D Center for Se-rich Agricultural Products Processing, School of Modern Industry for Selenium Science and Engineering, Wuhan Polytechnic University, Wuhan, P.R. China
| | - Xiaoyan Shuai
- Key Laboratory for Deep Processing of Major Grain and Oil, Ministry of Education, Wuhan Polytechnic University, Wuhan, P.R. China
- National R&D Center for Se-rich Agricultural Products Processing, School of Modern Industry for Selenium Science and Engineering, Wuhan Polytechnic University, Wuhan, P.R. China
| | - Shuxin Ye
- China YunHong Holdings Co, Ltd, Wuxue, P.R. China
| | - Rui Zhang
- Key Laboratory for Deep Processing of Major Grain and Oil, Ministry of Education, Wuhan Polytechnic University, Wuhan, P.R. China
- National R&D Center for Se-rich Agricultural Products Processing, School of Modern Industry for Selenium Science and Engineering, Wuhan Polytechnic University, Wuhan, P.R. China
| | - Muci Wu
- Key Laboratory for Deep Processing of Major Grain and Oil, Ministry of Education, Wuhan Polytechnic University, Wuhan, P.R. China
- National R&D Center for Se-rich Agricultural Products Processing, School of Modern Industry for Selenium Science and Engineering, Wuhan Polytechnic University, Wuhan, P.R. China
| | - Sijia Jiang
- China YunHong Holdings Co, Ltd, Wuxue, P.R. China
| | - Yubao Li
- China YunHong Holdings Co, Ltd, Wuxue, P.R. China
| | - Dong Wu
- China YunHong Holdings Co, Ltd, Wuxue, P.R. China
| | - Jingren He
- Key Laboratory for Deep Processing of Major Grain and Oil, Ministry of Education, Wuhan Polytechnic University, Wuhan, P.R. China
- National R&D Center for Se-rich Agricultural Products Processing, School of Modern Industry for Selenium Science and Engineering, Wuhan Polytechnic University, Wuhan, P.R. China
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13
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Van Nieuwenhove CP, Del Huerto Moyano A, Van Nieuwenhove GA, Molina V, Luna Pizarro P. Jacaranda oil administration improves serum biomarkers and bioavailability of bioactive conjugated fatty acids, and alters fatty acid profile of mice tissues. Lipids 2021; 57:33-44. [PMID: 34741309 DOI: 10.1002/lipd.12327] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 10/13/2021] [Accepted: 10/14/2021] [Indexed: 11/12/2022]
Abstract
Jacaric acid, a conjugated linolenic acid (CLNA) present in jacaranda oil (JO), is considered a potent anticarcinogenic agent. Several studies have focused on its biological effects, but the metabolism once consumed is not clear yet. The aim of this work was to evaluate the effects of two different daily doses of JO on serum parameters and fatty acid (FA) profile of mice tissues after 4 weeks of feeding. No significant changes on body weight gain, food intake, or tissue weight were determined after 0.7 or 2 ml/kg of JO supplementation compared to control animals. Significantly lower blood low-density lipoproteins-cholesterol (20 mg/dl) and glucose (~147-148 mg/dl) levels were detected in both oil-treated groups compared to control (31.2 and 165 mg/dl, respectively). Moreover, jacaric acid was partially converted into cis9, trans11 conjugated linoleic acid (CLA) and thus further incorporated into tissues. Liver evidenced the highest total conjugated fatty acid content (1.1%-2.2%), followed by epididymal (0.7%-1.9%) and mesenteric (1.4%-1.8%) fat. Lower saturated and higher unsaturated fatty acid content was detected in both oil-treated groups compared to control. Our results support the safety of JO and its potential application with a functional or nutraceutical propose, by increasing human CLNA consumption and further availability of CLA.
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Affiliation(s)
- Carina P Van Nieuwenhove
- Laboratorio de Ecofisiología Tecnológica, Centro de Referencia para Lactobacilos (CERELA-CONICET), San Miguel de Tucumán, Argentina.,Facultad de Ciencias Naturales e IML, Universidad Nacional de Tucumán, San Miguel de Tucumán, Argentina
| | - Andrea Del Huerto Moyano
- Laboratorio de Investigaciones Ecoetológicas de Moscas de la Fruta y sus Enemigos Naturales (LIEMEN)., Planta Piloto de Procesos Industriales Microbiológicos (PROIMI-CONICET), San Miguel de Tucumán, Argentina
| | - Guido A Van Nieuwenhove
- Laboratorio de Investigaciones Ecoetológicas de Moscas de la Fruta y sus Enemigos Naturales (LIEMEN)., Planta Piloto de Procesos Industriales Microbiológicos (PROIMI-CONICET), San Miguel de Tucumán, Argentina.,Fundación Miguel Lillo, San Miguel de Tucumán, Argentina
| | - Verónica Molina
- Laboratorio de Ecofisiología Tecnológica, Centro de Referencia para Lactobacilos (CERELA-CONICET), San Miguel de Tucumán, Argentina
| | - Patricia Luna Pizarro
- Fundación Miguel Lillo, San Miguel de Tucumán, Argentina.,Facultad de Ingeniería, Universidad Nacional de Jujuy, San Salvador de Jujuy, Argentina
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14
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Punicic Acid Triggers Ferroptotic Cell Death in Carcinoma Cells. Nutrients 2021; 13:nu13082751. [PMID: 34444911 PMCID: PMC8399984 DOI: 10.3390/nu13082751] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 08/05/2021] [Accepted: 08/09/2021] [Indexed: 12/24/2022] Open
Abstract
Plant-derived conjugated linolenic acids (CLnA) have been widely studied for their preventive and therapeutic properties against diverse diseases such as cancer. In particular, punicic acid (PunA), a conjugated linolenic acid isomer (C18:3 c9t11c13) present at up to 83% in pomegranate seed oil, has been shown to exert anti-cancer effects, although the mechanism behind its cytotoxicity remains unclear. Ferroptosis, a cell death triggered by an overwhelming accumulation of lipid peroxides, has recently arisen as a potential mechanism underlying CLnA cytotoxicity. In the present study, we show that PunA is highly cytotoxic to HCT-116 colorectal and FaDu hypopharyngeal carcinoma cells grown either in monolayers or as three-dimensional spheroids. Moreover, our data indicate that PunA triggers ferroptosis in carcinoma cells. It induces significant lipid peroxidation and its effects are prevented by the addition of ferroptosis inhibitors. A combination with docosahexaenoic acid (DHA), a known polyunsaturated fatty acid with anticancer properties, synergistically increases PunA cytotoxicity. Our findings highlight the potential of using PunA as a ferroptosis-sensitizing phytochemical for the prevention and treatment of cancer.
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15
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Ranasinghe KNK, Premarathna AD, Mahakapuge TAN, Wijesundera KK, Ambagaspitiya AT, Jayasooriya AP, Kularatne SAM, Rajapakse RPVJ. In vivo anticancer effects of Momordica charantia seed fat on hepatocellular carcinoma in a rat model. J Ayurveda Integr Med 2021; 12:435-442. [PMID: 34275705 PMCID: PMC8377176 DOI: 10.1016/j.jaim.2021.03.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Revised: 02/26/2021] [Accepted: 03/01/2021] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Momordica charantia or bitter melon is a well-known vegetable with a number of therapeutic actions in Ayurvedic medicine. Alpha-eleostearic acid, a conjugated trienoic fatty acid present in bitter melon is proven to have anticancer properties. Crude seed oil from local bitter melon varieties could be an effective and economical anticancer therapy. OBJECTIVE(S) The study was conducted to evaluate the anticancer effect of the crude oil from the seeds of Matale green variety of bitter melon on a hepatocellular carcinoma-induced rat model. MATERIALS AND METHODS Hepatocellular carcinoma (HCC) was experimentally induced in Wistar rats. Crude seed oil of Matale green bitter melon (MGBM) was supplemented to one treatment group in concurrence with carcinoma induction and to another treatment group after the development of carcinoma. After 168 days, gross morphological, histopathological, biochemical, hematological and gene-expression analysis of treated and control groups were performed. RESULTS Oral supplementation of MGBM seed oil showed a statistically significant reduction (p < 0.05) in the average number, diameter and area of hepatic dysplastic nodules and a reduction in the size of histopathological neoplastic lesions in both treatment groups compared to the non-treated control group. The expression of tumor suppressor gene p53 and anti-apoptotic gene Bcl-2 were significantly increased while the expression of apoptotic gene caspase 3 was significantly reduced in the treatment group when MGBM supplementation was in concurrence with carcinogenesis (p < 0.05). CONCLUSION Crude seed oil from the MGBM has anticancer effects against experimentally induced HCC in Wistar rats, specially when supplemented in concurrence with carcinoma induction.
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Affiliation(s)
- K N K Ranasinghe
- Department of Veterinary Pathobiology, Faculty of Veterinary Medicine and Animal Science, University of Peradeniya, Peradeniya, Sri Lanka
| | - A D Premarathna
- Department of Veterinary Pathobiology, Faculty of Veterinary Medicine and Animal Science, University of Peradeniya, Peradeniya, Sri Lanka
| | - T A N Mahakapuge
- Department of Veterinary Pathobiology, Faculty of Veterinary Medicine and Animal Science, University of Peradeniya, Peradeniya, Sri Lanka
| | - K K Wijesundera
- Department of Veterinary Pathobiology, Faculty of Veterinary Medicine and Animal Science, University of Peradeniya, Peradeniya, Sri Lanka
| | - A T Ambagaspitiya
- Department of Veterinary Pathobiology, Faculty of Veterinary Medicine and Animal Science, University of Peradeniya, Peradeniya, Sri Lanka
| | - A P Jayasooriya
- Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine and Animal Science, University of Peradeniya, Peradeniya, Sri Lanka
| | - S A M Kularatne
- Department of Medicine, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - R P V J Rajapakse
- Department of Veterinary Pathobiology, Faculty of Veterinary Medicine and Animal Science, University of Peradeniya, Peradeniya, Sri Lanka.
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16
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Beatty A, Singh T, Tyurina YY, Tyurin VA, Samovich S, Nicolas E, Maslar K, Zhou Y, Cai KQ, Tan Y, Doll S, Conrad M, Subramanian A, Bayır H, Kagan VE, Rennefahrt U, Peterson JR. Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1. Nat Commun 2021; 12:2244. [PMID: 33854057 PMCID: PMC8046803 DOI: 10.1038/s41467-021-22471-y] [Citation(s) in RCA: 150] [Impact Index Per Article: 37.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 03/11/2021] [Indexed: 12/21/2022] Open
Abstract
Ferroptosis is associated with lipid hydroperoxides generated by the oxidation of polyunsaturated acyl chains. Lipid hydroperoxides are reduced by glutathione peroxidase 4 (GPX4) and GPX4 inhibitors induce ferroptosis. However, the therapeutic potential of triggering ferroptosis in cancer cells with polyunsaturated fatty acids is unknown. Here, we identify conjugated linoleates including α-eleostearic acid (αESA) as ferroptosis inducers. αESA does not alter GPX4 activity but is incorporated into cellular lipids and promotes lipid peroxidation and cell death in diverse cancer cell types. αESA-triggered death is mediated by acyl-CoA synthetase long-chain isoform 1, which promotes αESA incorporation into neutral lipids including triacylglycerols. Interfering with triacylglycerol biosynthesis suppresses ferroptosis triggered by αESA but not by GPX4 inhibition. Oral administration of tung oil, naturally rich in αESA, to mice limits tumor growth and metastasis with transcriptional changes consistent with ferroptosis. Overall, these findings illuminate a potential approach to ferroptosis, complementary to GPX4 inhibition.
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Affiliation(s)
| | - Tanu Singh
- Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Yulia Y Tyurina
- Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA
- Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Vladimir A Tyurin
- Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA
- Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Svetlana Samovich
- Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA
- Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA
| | | | - Kristen Maslar
- Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA
| | - Yan Zhou
- Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Kathy Q Cai
- Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Yinfei Tan
- Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Sebastian Doll
- Institute of Metabolism and Cell Death, Helmholtz Zentrum München, Neuherberg, Germany
| | - Marcus Conrad
- Institute of Metabolism and Cell Death, Helmholtz Zentrum München, Neuherberg, Germany
- National Research Medical University, Laboratory of Experimental Oncology, Ostrovityanova 1, Moscow, 117997, Russia
| | | | - Hülya Bayır
- Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA
- Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Critical Care Medicine, Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, USA
| | - Valerian E Kagan
- Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA
- Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Radiation Oncology, University of Pittsburgh, Pittsburgh, PA, USA
- Laboratory of Navigational Redox Lipidomics, IM Sechenov Moscow State Medical University, Moscow, Russia
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17
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Kung WM, Lin MS. Beneficial Impacts of Alpha-Eleostearic Acid from Wild Bitter Melon and Curcumin on Promotion of CDGSH Iron-Sulfur Domain 2: Therapeutic Roles in CNS Injuries and Diseases. Int J Mol Sci 2021; 22:3289. [PMID: 33804820 PMCID: PMC8037269 DOI: 10.3390/ijms22073289] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 03/20/2021] [Accepted: 03/21/2021] [Indexed: 02/05/2023] Open
Abstract
Neuroinflammation and abnormal mitochondrial function are related to the cause of aging, neurodegeneration, and neurotrauma. The activation of nuclear factor κB (NF-κB), exaggerating these two pathologies, underlies the pathogenesis for the aforementioned injuries and diseases in the central nervous system (CNS). CDGSH iron-sulfur domain 2 (CISD2) belongs to the human NEET protein family with the [2Fe-2S] cluster. CISD2 has been verified as an NFκB antagonist through the association with peroxisome proliferator-activated receptor-β (PPAR-β). This protective protein can be attenuated under circumstances of CNS injuries and diseases, thereby causing NFκB activation and exaggerating NFκB-provoked neuroinflammation and abnormal mitochondrial function. Consequently, CISD2-elevating plans of action provide pathways in the management of various disease categories. Various bioactive molecules derived from plants exert protective anti-oxidative and anti-inflammatory effects and serve as natural antioxidants, such as conjugated fatty acids and phenolic compounds. Herein, we have summarized pharmacological characters of the two phytochemicals, namely, alpha-eleostearic acid (α-ESA), an isomer of conjugated linolenic acids derived from wild bitter melon (Momordica charantia L. var. abbreviata Ser.), and curcumin, a polyphenol derived from rhizomes of Curcuma longa L. In this review, the unique function of the CISD2-elevating effect of α-ESA and curcumin are particularly emphasized, and these natural compounds are expected to serve as a potential therapeutic target for CNS injuries and diseases.
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Affiliation(s)
- Woon-Man Kung
- Department of Exercise and Health Promotion, College of Kinesiology and Health, Chinese Culture University, Taipei 11114, Taiwan;
| | - Muh-Shi Lin
- Division of Neurosurgery, Department of Surgery, Kuang Tien General Hospital, Taichung 43303, Taiwan
- Department of Biotechnology and Animal Science, College of Bioresources, National Ilan University, Yilan 26047, Taiwan
- Department of Biotechnology, College of Medical and Health Care, Hung Kuang University, Taichung 43302, Taiwan
- Department of Health Business Administration, College of Medical and Health Care, Hung Kuang University, Taichung 43302, Taiwan
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18
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Nischitha R, Shivanna MB. Antimicrobial activity and metabolite profiling of endophytic fungi in Digitaria bicornis (Lam) Roem. and Schult. and Paspalidium flavidum (Retz.) A. Camus. 3 Biotech 2021; 11:53. [PMID: 33489672 DOI: 10.1007/s13205-020-02590-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 12/03/2020] [Indexed: 11/29/2022] Open
Abstract
Endophytic fungal occurrences were studied in aerial regions of Digitaria bicornis and Paspalidium flavidum by three isolation methods: potato dextrose agar (PDA), malt extract agar (MEA), and moist blotters. Seventy species of 29 genera of endophytic fungi in D. bicornis and 71 species of 30 genera in P. flavidum were documented. Endophytic fungal communities were grouped into 40 and 43 anamorphic ascomycetes (21 and 23 genera) and 20 teleomorphic ascomycetes (6 and 7 genera) in D. bicornis and P. flavidum, respectively. PDA supported the expression of larger number of fungal communities than MEA and MB; and P. flavidum hosted more number of endophytic fungi than D. bicornis. Seasons played an important role in supporting the assemblage of fungal endophytes. Endophytic fungal species richness and assemblages in plant regions were determined for alpha, beta, and gamma diversities. The ethyl acetate followed by methanolic extracts of certain fungal species showed good antagonistic and antibacterial activities. Among fungal endophytes, Curvularia protuberata and Penicillium citrinum exhibited high antagonistic and antibacterial activities. The high-resolution orbitrap liquid chromatography-mass spectrometry of ethyl acetate crude extracts of C. protuberata and P. citrinum revealed the presence of antifungal and antimicrobial, besides a host of compounds in the extracts. The present study indicated that grass endophytes are the sources of compounds with antimicrobial and other pharmacological activities.
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Affiliation(s)
- R Nischitha
- Department of PG Studies and Research in Applied Botany, School of Biosciences, Kuvempu University, Jnana Sahyadri 577 451, Shimoga, Shankaraghatta India
| | - M B Shivanna
- Department of PG Studies and Research in Applied Botany, School of Biosciences, Kuvempu University, Jnana Sahyadri 577 451, Shimoga, Shankaraghatta India
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19
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Debieu S, Solier S, Colombeau L, Versini A, Sindikubwabo F, Forrester A, Müller S, Cañeque T, Rodriguez R. Small Molecule Regulators of Ferroptosis. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1301:81-121. [PMID: 34370289 DOI: 10.1007/978-3-030-62026-4_6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Ferroptosis is a dedicated mode of cell death involving iron, reactive oxygen species and lipid peroxidation. Involved in processes such as glutathione metabolism, lysosomal iron retention or interference with lipid metabolism, leading either to activation or inhibition of ferroptosis. Given the implications of ferroptosis in diseases such as cancer, aging, Alzheimer and infectious diseases, new molecular mechanisms underlying ferroptosis and small molecules regulators that target those mechanisms have prompted a great deal of interest. Here, we discuss the current scenario of small molecules modulating ferroptosis and critically assess what is known about their mechanisms of action.
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Affiliation(s)
- Sylvain Debieu
- Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France
- PSL Université Paris, Paris, France
- Chemical Biology of Cancer Laboratory, CNRS UMR 3666, INSERM U1143, Paris, France
| | - Stéphanie Solier
- Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France
- PSL Université Paris, Paris, France
- Chemical Biology of Cancer Laboratory, CNRS UMR 3666, INSERM U1143, Paris, France
| | - Ludovic Colombeau
- Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France
- PSL Université Paris, Paris, France
- Chemical Biology of Cancer Laboratory, CNRS UMR 3666, INSERM U1143, Paris, France
| | - Antoine Versini
- Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France
- PSL Université Paris, Paris, France
- Chemical Biology of Cancer Laboratory, CNRS UMR 3666, INSERM U1143, Paris, France
| | - Fabien Sindikubwabo
- Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France
- PSL Université Paris, Paris, France
- Chemical Biology of Cancer Laboratory, CNRS UMR 3666, INSERM U1143, Paris, France
| | - Alison Forrester
- Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France
- PSL Université Paris, Paris, France
- Chemical Biology of Cancer Laboratory, CNRS UMR 3666, INSERM U1143, Paris, France
| | - Sebastian Müller
- Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France
- PSL Université Paris, Paris, France
- Chemical Biology of Cancer Laboratory, CNRS UMR 3666, INSERM U1143, Paris, France
| | - Tatiana Cañeque
- Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France
- PSL Université Paris, Paris, France
- Chemical Biology of Cancer Laboratory, CNRS UMR 3666, INSERM U1143, Paris, France
| | - Raphaël Rodriguez
- Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
- PSL Université Paris, Paris, France.
- Chemical Biology of Cancer Laboratory, CNRS UMR 3666, INSERM U1143, Paris, France.
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Wu Q, Tsuduki T. CYP4F13 is the Major Enzyme for Conversion of alpha-Eleostearic Acid into cis-9, trans-11-Conjugated Linoleic Acid in Mouse Hepatic Microsomes. J Oleo Sci 2020; 69:1061-1075. [PMID: 32879197 DOI: 10.5650/jos.ess20080] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Our previous studies have shown that α-eleostearic acid (α-ESA; cis-9, trans-11, trans-13 (c9,t11,t13)-conjugated linolenic acid (CLnA)) is converted into c9,t11-conjugated linoleic acid (CLA) in rats. Furthermore, we have demonstrated that the conversion of α-ESA into CLA is a nicotinamide adenine dinucleotide phosphate (NADPH)-dependent enzymatic reaction, which occurs mostly in the rat liver. However, the precise metabolic pathway and enzyme involved have not been identified yet. Therefore, in this study we aimed to determine the role of cytochrome P450 (CYP) in the conversion of α-ESA into c9,t11-CLA using an in vitro reconstitution system containing mouse hepatic microsomes, NADPH, and α-ESA. The CYP4 inhibitors, 17-ODYA and HET0016, performed the highest level of inhibition of CLA formation. Furthermore, the redox partner cytochrome P450 reductase (CPR) inhibitor, 2-chloroethyl ethyl sulfide (CEES), also demonstrated a high level of inhibition. Thus, these results indicate that the NADPH-dependent CPR/CYP4 system is responsible for CLA formation. In a correlation analysis between the specific activity of CLA formation and Cyp4 family gene expression in tissues, Cyp4a14 and Cyp4f13 demonstrated the best correlations. However, the CYP4F substrate prostaglandin A1 (PGA1) exhibited the strongest inhibitory effect on CLA formation, while the CYP4A and CYP4B1 substrate lauric acid had no inhibitory effect. Therefore, we conclude that the CYP4F13 enzyme is the major enzyme involved in CLA formation. This pathway is a novel pathway for endogenous CLA synthesis, and this study provides insight into the potential application of CLnA in functional foods.
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Affiliation(s)
- Qiming Wu
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University
| | - Tsuyoshi Tsuduki
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University
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21
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He C, Wu Q, Hayashi N, Nakano F, Nakatsukasa E, Tsuduki T. Carbohydrate-restricted diet alters the gut microbiota, promotes senescence and shortens the life span in senescence-accelerated prone mice. J Nutr Biochem 2019; 78:108326. [PMID: 31952014 DOI: 10.1016/j.jnutbio.2019.108326] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Revised: 10/08/2019] [Accepted: 12/17/2019] [Indexed: 02/07/2023]
Abstract
This study examined the effects of a carbohydrate-restricted diet on aging, brain function, intestinal bacteria and the life span to determine long-term carbohydrate-restriction effects on the aging process in senescence-accelerated prone mice (SAMP8). Three-week-old male SAMP8 were divided into three groups after a week of preliminary feeding. One group was given a controlled diet, while the others fed on high-fat and carbohydrate-restricted diets, respectively. The mice in each group were further divided into two subgroups, of which one was the longevity measurement group. The other groups fed ad libitum until the mice were 50 weeks old. Before the test period termination, passive avoidance test evaluated the learning and memory abilities. Following the test period, serum and various mice organs were obtained and submitted for analysis. The carbohydrate-restricted diet group exhibited significant decrease in the survival rate as compared to the other two diet groups. The passive avoidance test revealed a remarkable decrease in the learning and memory ability of carbohydrate-restricted diet group as compared to the control-diet group. Measurement of lipid peroxide level in tissues displayed a marked increase in the brain and spleen of carbohydrate-restricted diet group than the control-diet and high-fat diet groups. Furthermore, notable serum IL-6 and IL-1β level (inflammation indicators) elevations, decrease in Enterobacteria (with anti-inflammatory action), increase in inflammation-inducing Enterobacteria and lowering of short-chain fatty acids levels in cecum were observed in the carbohydrate-restricted diet group. Hence, carbohydrate-restricted diet was revealed to promote aging and shortening of life in SAMP8.
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Affiliation(s)
- Chaoqi He
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, Sendai 981-8555, Japan
| | - Qiming Wu
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, Sendai 981-8555, Japan
| | - Nao Hayashi
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, Sendai 981-8555, Japan
| | - Fumika Nakano
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, Sendai 981-8555, Japan
| | - Eriko Nakatsukasa
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, Sendai 981-8555, Japan
| | - Tsuyoshi Tsuduki
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, Sendai 981-8555, Japan.
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22
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Comparative study of pomegranate and jacaranda seeds as functional components for the conjugated linolenic acid enrichment of yogurt. Lebensm Wiss Technol 2019. [DOI: 10.1016/j.lwt.2019.05.045] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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23
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Thakur K, Zhang YY, Mocan A, Zhang F, Zhang JG, Wei ZJ. 1-Deoxynojirimycin, its potential for management of non-communicable metabolic diseases. Trends Food Sci Technol 2019. [DOI: 10.1016/j.tifs.2019.05.010] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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24
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Honma T, Shiratani N, Banno Y, Kataoka T, Kimura R, Sato I, Endo Y, Kita K, Suzuki T, Takayanagi T. Seeds of Centranthus ruber and Valeriana officinalis Contain Conjugated Linolenic Acids with Reported Antitumor Effects. J Oleo Sci 2019; 68:481-491. [PMID: 31061266 DOI: 10.5650/jos.ess19007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Conjugated linolenic acids (CLNs) are naturally occurring fatty acids that are believed to have anticancer properties. In this study, we examined various plant seeds from herbs to discover seed oils containing CLNs. The ultraviolet spectra of total lipids from these seeds were measured. An absorption maximum around 270 nm was observed in seed oils belonging to the Valerianaceae family (Centranthus ruber and Valeriana officinalis). When the fatty acid compositions of these seed oils were measured, CLNs were detected. By silica column chromatography, neutral lipids (NLs), glycolipids, and phospholipids were eluted from seed oils of C. ruber and V. officinalis. Then, fatty acid compositions of these fractions were measured. This revealed that most of the CLNs in these seed oils existed in the NL fraction. When the NL fractions of these seed oils were reacted with lipase, CLNs showed good sensitivity to lipase hydrolysis. This suggested that the CLNs in the seed oils of C. ruber and V. officinalis existed predominantly at the sn-1,3 position of triacylglycerol and less at the sn-2 position. These results suggested that the CLNs from the seed oils of C. ruber and V. officinalis could easily be taken up by cancer cells as free fatty acids and had good potential as antitumor substances.
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Affiliation(s)
- Taro Honma
- Laboratory of Toxicology, Faculty of Pharma-Science, Teikyo University
| | | | - Yuki Banno
- School of Bioscience and Biotechnology, Tokyo University of Technology
| | - Tetsu Kataoka
- School of Bioscience and Biotechnology, Tokyo University of Technology
| | - Ryo Kimura
- School of Bioscience and Biotechnology, Tokyo University of Technology
| | - Ikumi Sato
- Laboratory of Toxicology, Faculty of Pharma-Science, Teikyo University
| | - Yasushi Endo
- School of Bioscience and Biotechnology, Tokyo University of Technology
| | - Kayoko Kita
- Laboratory of Toxicology, Faculty of Pharma-Science, Teikyo University
| | - Toshihide Suzuki
- Laboratory of Toxicology, Faculty of Pharma-Science, Teikyo University
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25
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Tsuduki T. Health Benefit of the Japanese Diet ～Exploring the Significance of Staple Food～. J JPN SOC FOOD SCI 2019. [DOI: 10.3136/nskkk.66.217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Affiliation(s)
- Tsuyoshi Tsuduki
- Laboratory of Food and Biomolecular Science, Graduate School of Agricultural Science, Tohoku University
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26
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Dhar Dubey KK, Sharma G, Kumar A. Conjugated Linolenic Acids: Implication in Cancer. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:6091-6101. [PMID: 31070027 DOI: 10.1021/acs.jafc.9b01379] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Conjugated fatty acids (CFAs) including both conjugated linoleic acids (CLAs) and conjugated linolenic acids (CLNAs) have various health promoting effects. These beneficial effects are comprised by their antioxidant, antiatherogenecity, anticarcinogenic activities, etc. Several reports indicate that CLNAs such as eleostearic acid, punicic acid, jacaric acid, and calendic acid possess anticancer properties. These CLNAs are produced and accumulated in seeds of certain commonly available plants. This review discusses their role in chemoprevention of cancer. Using in vitro as well as in vivo models of cancer, bioactivities of these CLNAs have been explored in detail. CLNAs have been shown to have potent anticancer activity as compared to the CLAs. Although the molecular basis of these effects has been summarized here, more detailed studies are needed to explore the underlying mechanisms. Further clinical trials are obligatory for assessing the safety and efficacy of CLNAs as an anticancer agent.
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Affiliation(s)
- Kaushik K Dhar Dubey
- Molecular Genetics Lab, Amity Institute of Biotechnology , Amity University Uttar Pradesh , Noida - 201303 , India
| | - Girish Sharma
- Molecular Genetics Lab, Amity Institute of Biotechnology , Amity University Uttar Pradesh , Noida - 201303 , India
- Amity Center for Cancer Epidemiology and Cancer Research , Amity University Uttar Pradesh , Noida - 201303 , India
| | - Aruna Kumar
- Molecular Genetics Lab, Amity Institute of Biotechnology , Amity University Uttar Pradesh , Noida - 201303 , India
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27
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Natalello A, Luciano G, Morbidini L, Valenti B, Pauselli M, Frutos P, Biondi L, Rufino-Moya PJ, Lanza M, Priolo A. Effect of Feeding Pomegranate Byproduct on Fatty Acid Composition of Ruminal Digesta, Liver, and Muscle in Lambs. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:4472-4482. [PMID: 30929432 DOI: 10.1021/acs.jafc.9b00307] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
This work investigated the effects of feeding whole pomegranate byproduct (WPB) to lambs on ruminal, liver, and intramuscular fatty acids (FA). Seventeen lambs, divided into two groups, were fed for 36 days with a cereal-based concentrate diet (CON) or with a concentrate diet containing 200 g/kg DM of WPB to partially replace barley and corn (WPB). The dietary treatment did not affect the final body and carcass weight, the dry matter intake, or the average daily gain. However, total polyunsaturated FA (PUFA), linolenic, rumenic (RA), and vaccenic (VA) acid were increased in liver (+15%, +32%, +344%, and +118%, respectively) and muscle (+46%, +38%, +169%, and +89%, respectively) of WPB lambs ( P < 0.05). Punicic acid and three isomers of conjugated linolenic acid were detected exclusively in the rumen and tissues of WPB-lambs. The C18:1 t10/ t11 ra tio in rumen digesta or in tissues was reduced by feeding WPB (-791%, -690%, and -456%, respectively, in rumen, liver and muscle; P < 0.001), suggesting that the WPB prevented the t10-shift rumen biohydrogenation pathway. In conclusion, the inclusion of WPB into a concentrate-based diet can be a strategy to improve the FA composition of meat, without effects on the animal performances.
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Affiliation(s)
- Antonio Natalello
- Dipartimento di Agricoltura, Alimentazione e Ambiente (Di3A) , University of Catania , Via Valdisavoia 5 , 95123 Catania , Italy
| | - Giuseppe Luciano
- Dipartimento di Agricoltura, Alimentazione e Ambiente (Di3A) , University of Catania , Via Valdisavoia 5 , 95123 Catania , Italy
| | - Luciano Morbidini
- Dipartimento di Scienze Agrarie, Alimentari e Ambientali (DSA3) , University of Perugia , Borgo XX Giugno 74 , 06123 Perugia , Italy
| | - Bernardo Valenti
- Dipartimento di Scienze Agrarie, Alimentari e Ambientali (DSA3) , University of Perugia , Borgo XX Giugno 74 , 06123 Perugia , Italy
| | - Mariano Pauselli
- Dipartimento di Scienze Agrarie, Alimentari e Ambientali (DSA3) , University of Perugia , Borgo XX Giugno 74 , 06123 Perugia , Italy
| | - Pilar Frutos
- Instituto de Ganadería de Montaña, CSIC-Universidad de León , Finca Marzanas s/n , 24346 Grulleros, León , Spain
| | - Luisa Biondi
- Dipartimento di Agricoltura, Alimentazione e Ambiente (Di3A) , University of Catania , Via Valdisavoia 5 , 95123 Catania , Italy
| | - Pablo J Rufino-Moya
- Centro de Investigación y Tecnología Agroalimentaria de Aragón (CITA) , Instituto Agroalimentario de Aragón-IA2 (CITA-Universidad de Zaragoza) , Avda. Montan ̃ana 930 , 50059 Zaragoza , Spain
| | - Massimiliano Lanza
- Dipartimento di Agricoltura, Alimentazione e Ambiente (Di3A) , University of Catania , Via Valdisavoia 5 , 95123 Catania , Italy
| | - Alessandro Priolo
- Dipartimento di Agricoltura, Alimentazione e Ambiente (Di3A) , University of Catania , Via Valdisavoia 5 , 95123 Catania , Italy
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28
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Okouchi R, E S, Yamamoto K, Ota T, Seki K, Imai M, Ota R, Asayama Y, Nakashima A, Suzuki K, Tsuduki T. Simultaneous Intake of Euglena gracilis and Vegetables Exerts Synergistic Anti-Obesity and Anti-Inflammatory Effects by Modulating the Gut Microbiota in Diet-Induced Obese Mice. Nutrients 2019; 11:nu11010204. [PMID: 30669573 PMCID: PMC6356467 DOI: 10.3390/nu11010204] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2018] [Revised: 01/16/2019] [Accepted: 01/18/2019] [Indexed: 01/03/2023] Open
Abstract
We determined whether the anti-obesity effect provided by the consumption of Euglena gracilis (Euglena), which is rich in insoluble dietary fiber, could be enhanced by the co-consumption of vegetables with an abundance of soluble dietary fiber. Nine-week-old male C57BL/6J mice were divided into five groups as follows: group 1 received a normal diet, group 2 received a high-fat diet, and groups 3, 4, and 5 received high fat diets containing 0.3% paramylon, 1.0% Euglena, or 1.0% Euglena plus 0.3% vegetables (barley leaf, kale, and ashitaba), respectively. Mice were fed ad libitum until 18 weeks of age. Euglena intake significantly reduced visceral fat accumulation in obese mice, and co-consumption of vegetables enhanced this effect. Consumption of Euglena with vegetables reduced adipocyte area, suppressed the expression of genes related to fatty acid synthesis, upregulated genes related to adipocyte lipolysis, and suppressed serum markers of inflammation. Notably, we also observed an increase in the fraction of short-chain fatty acid-producing beneficial bacteria, a reduction in harmful bacteria that cause inflammation, and an increase in short-chain fatty acid production. Therefore, the co-consumption of vegetables enhanced the anti-obesity and anti-inflammatory effects of Euglena, likely by modulating the gut microbiota composition.
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Affiliation(s)
- Ran Okouchi
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, Sendai 981-8555, Japan.
| | - Shuang E
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, Sendai 981-8555, Japan.
| | - Kazushi Yamamoto
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, Sendai 981-8555, Japan.
| | - Toshikuni Ota
- Takeda Consumer Healthcare Company Limited, Chiyoda-ku, Tokyo 100-0005, Japan.
| | - Kentarou Seki
- Takeda Consumer Healthcare Company Limited, Chiyoda-ku, Tokyo 100-0005, Japan.
| | - Mayumi Imai
- Takeda Consumer Healthcare Company Limited, Chiyoda-ku, Tokyo 100-0005, Japan.
| | - Ryuki Ota
- Takeda Consumer Healthcare Company Limited, Chiyoda-ku, Tokyo 100-0005, Japan.
| | - Yuta Asayama
- Euglena Co., Ltd, Minato-ku, Tokyo 108-0014, Japan.
| | | | - Kengo Suzuki
- Euglena Co., Ltd, Minato-ku, Tokyo 108-0014, Japan.
| | - Tsuyoshi Tsuduki
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, Sendai 981-8555, Japan.
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29
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Pereira de Melo IL, de Oliveira e Silva AM, Yoshime LT, Gasparotto Sattler JA, Teixeira de Carvalho EB, Mancini-Filho J. Punicic acid was metabolised and incorporated in the form of conjugated linoleic acid in different rat tissues. Int J Food Sci Nutr 2018; 70:421-431. [DOI: 10.1080/09637486.2018.1519528] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Affiliation(s)
- Illana Louise Pereira de Melo
- Department of Food and Experimental Nutrition Laboratory of Lipids Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
| | | | - Luciana Tedesco Yoshime
- Department of Food and Experimental Nutrition Laboratory of Lipids Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
| | - José Augusto Gasparotto Sattler
- Department of Food and Experimental Nutrition Laboratory of Lipids Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
| | | | - Jorge Mancini-Filho
- Department of Food and Experimental Nutrition Laboratory of Lipids Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
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30
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Wu Q, E S, Yamamoto K, Tsuduki T. Carbohydrate-restricted diet promotes skin senescence in senescence-accelerated prone mice. Biogerontology 2018; 20:71-82. [DOI: 10.1007/s10522-018-9777-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Accepted: 09/29/2018] [Indexed: 02/04/2023]
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31
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Sakanoi Y, E S, Yamamoto K, Ota T, Seki K, Imai M, Ota R, Asayama Y, Nakashima A, Suzuki K, Tsuduki T. Simultaneous Intake of Euglena Gracilis and Vegetables Synergistically Exerts an Anti-Inflammatory Effect and Attenuates Visceral Fat Accumulation by Affecting Gut Microbiota in Mice. Nutrients 2018; 10:E1417. [PMID: 30282906 PMCID: PMC6213005 DOI: 10.3390/nu10101417] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Revised: 09/22/2018] [Accepted: 09/27/2018] [Indexed: 02/06/2023] Open
Abstract
We determined whether the benefits provided by the consumption of Euglena gracilis (Euglena), which is a unicellular photosynthesizing green alga and rich in insoluble dietary fiber paramylon, can be enhanced by the co-consumption of vegetables that are rich in soluble dietary fiber. Nine-week-old male C57BL/6J mice were divided into four groups: group 1 received normal diet, whereas groups 2, 3 and 4 received normal diet containing 0.3% paramylon, 1.0% Euglena, or 1.0% Euglena plus 0.3% vegetables (barley leaf, kale and ashitaba), respectively. Mice were fed ad libitum until 18 weeks of age. Euglena intake significantly decreased serum markers of inflammation and co-consumption of vegetables enhanced this reduction. Notably, we observed an increase in the fraction of beneficial bacteria producing short-chain fatty acids, a reduction in harmful bacteria that cause inflammation and an increase in short-chain fatty acid production. Visceral fat accumulation was also reduced. Subsequent analyses showed that co-consumption of Euglena with vegetables reduced adipocyte area, suppressed the expression of genes related to fatty acid synthesis and increased the expression of genes related to adipocyte growth and lipolysis. Therefore, co-consumption of Euglena with vegetables enhanced its anti-inflammatory effect and the inhibitory effect on visceral fat accumulation likely by modulating the composition of gut microbiota.
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Affiliation(s)
- Yuto Sakanoi
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, Sendai 980-0845, Japan.
| | - Shuang E
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, Sendai 980-0845, Japan.
| | - Kazushi Yamamoto
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, Sendai 980-0845, Japan.
| | - Toshikuni Ota
- Takeda Consumer Healthcare Company Limited, Chiyoda-ku, Tokyo 100-0005, Japan.
| | - Kentarou Seki
- Takeda Consumer Healthcare Company Limited, Chiyoda-ku, Tokyo 100-0005, Japan.
| | - Mayumi Imai
- Takeda Consumer Healthcare Company Limited, Chiyoda-ku, Tokyo 100-0005, Japan.
| | - Ryuki Ota
- Takeda Consumer Healthcare Company Limited, Chiyoda-ku, Tokyo 100-0005, Japan.
| | - Yuta Asayama
- Euglena Co., Ltd., Minato-ku Tokyo 108-0014, Japan.
| | | | - Kengo Suzuki
- Euglena Co., Ltd., Minato-ku Tokyo 108-0014, Japan.
| | - Tsuyoshi Tsuduki
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, Sendai 980-0845, Japan.
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32
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Cui P, Lin Q, Fang D, Zhang L, Li R, Cheng J, Gao F, Shockey J, Hu S, Lü S. Tung Tree (Vernicia fordii, Hemsl.) Genome and Transcriptome Sequencing Reveals Co-Ordinate Up-Regulation of Fatty Acid β-Oxidation and Triacylglycerol Biosynthesis Pathways During Eleostearic Acid Accumulation in Seeds. PLANT & CELL PHYSIOLOGY 2018; 59:1990-2003. [PMID: 30137600 DOI: 10.1093/pcp/pcy117] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Accepted: 06/10/2018] [Indexed: 05/21/2023]
Abstract
The tung tree (Vernicia fordii) is one of only a few plant species that produces high oil-yielding seeds rich in α-eleostearic acid (α-ESA, 18:3Δ9cis, 11trans, 13trans), a conjugated trienoic fatty acid with valuable industrial and medical properties. Previous attempts have been made to engineer tung oil biosynthesis in transgenic oilseed crops, but these efforts have met with limited success. Here we present a high-quality genome assembly and developing seed transcriptomic data set for this species. Whole-genome shotgun sequencing generated 176 Gb of genome sequence data used to create a final assembled sequence 1,176,320 kb in size, with a scaffold N50 size of >474 kb, and containing approximately 47,000 protein-coding genes. Genomic and transcriptomic data revealed full-length candidate genes for most of the known and suspected reactions that are necessary for fatty acid desaturation/conjugation, acyl editing and triacylglycerol biosynthesis. Seed transcriptomic analyses also revealed features unique to tung tree, including unusual transcriptional profiles of fatty acid biosynthetic genes, and co-ordinated (and seemingly paradoxical) simultaneous up-regulation of both fatty acid β-oxidation and triacylglycerol biosynthesis in mid-development seeds. The precise temporal control of the expression patterns for these two pathways may account for α-ESA enrichment in tung seeds, while controlling the levels of potentially toxic by-products. Deeper understanding of these processes may open doors to the design of engineered oilseeds containing high levels of α-ESA.
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Affiliation(s)
- Peng Cui
- Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, Guangdong, China
| | - Qiang Lin
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
| | - Dongming Fang
- Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, Guangdong, China
| | - Lingling Zhang
- Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan, China
| | - Rongjun Li
- Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan, China
| | | | - Fei Gao
- Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, Guangdong, China
| | - Jay Shockey
- United States Department of Agriculture, Agricultural Research Service, Southern Regional Research Center, New Orleans, LA, USA
| | - Songnian Hu
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Shiyou Lü
- Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan, China
- Sino-Africa Joint Research Center, Chinese Academy of Sciences, Wuhan, China
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33
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Yamamoto K, Kushida M, Tsuduki T. The effect of dietary lipid on gut microbiota in a senescence-accelerated prone mouse model (SAMP8). Biogerontology 2018; 19:367-383. [DOI: 10.1007/s10522-018-9764-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Accepted: 07/30/2018] [Indexed: 12/26/2022]
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Yamamoto K, Iwagaki Y, Watanabe K, Nochi T, Aso H, Tsuduki T. Effects of a moderate-fat diet that is enriched with fish oil on intestinal lipid absorption in a senescence-accelerated prone mouse model. Nutrition 2018; 50:26-35. [DOI: 10.1016/j.nut.2017.10.015] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Revised: 10/10/2017] [Accepted: 10/29/2017] [Indexed: 12/13/2022]
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Effects of Dietary Intake of Japanese Mushrooms on Visceral Fat Accumulation and Gut Microbiota in Mice. Nutrients 2018; 10:nu10050610. [PMID: 29757949 PMCID: PMC5986490 DOI: 10.3390/nu10050610] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2018] [Revised: 05/07/2018] [Accepted: 05/11/2018] [Indexed: 12/27/2022] Open
Abstract
A lot of Japanese people are generally known for having a healthy diet, and consume a variety of mushrooms daily. Many studies have reported anti-obesity effects of mushrooms, but few have investigated the effects of consuming a variety of edible mushroom types together in realistic quantities. In this study, we investigated whether supplementation with a variety of mushroom types affects visceral fat accumulation and gut microbiota in mice. The most popular mushroom varieties in Japan were lyophilized and mixed according to their local production ratios. C57BL/6J mice were fed a normal diet, high-fat (HF) diet, HF with 0.5% mushroom mixture (equivalent to 100 g mushrooms/day in humans) or HF with 3% mushroom mixture (equivalent to 600 g mushrooms/day in humans) for 4 weeks. The mice were then sacrificed, and blood samples, tissue samples and feces were collected. Our results show that mushroom intake suppressed visceral fat accumulation and increased the relative abundance of some short chain fatty acid- and lactic acid-producing gut bacteria. These findings suggest that mushroom intake is an effective strategy for obesity prevention.
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Physicochemical interactions among α-eleostearic acid-loaded liposomes applied to the development of drug delivery systems. J Mol Struct 2018. [DOI: 10.1016/j.molstruc.2017.10.044] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Comparison of Separation of Seed Oil Triglycerides Containing Isomeric Conjugated Octadecatrienoic Acid Moieties by Reversed-Phase HPLC. SEPARATIONS 2017. [DOI: 10.3390/separations4040037] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Yeboah EMO, Kobue-Lekalake RI, Jackson JC, Muriithi EN, Matenanga O, Yeboah SO. Application of high resolution NMR, FTIR, and GC–MS to a comparative study of some indigenous seed oils from Botswana. INNOV FOOD SCI EMERG 2017. [DOI: 10.1016/j.ifset.2017.05.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Jia S, Shen M, Zhang F, Xie J. Recent Advances in Momordica charantia: Functional Components and Biological Activities. Int J Mol Sci 2017; 18:E2555. [PMID: 29182587 PMCID: PMC5751158 DOI: 10.3390/ijms18122555] [Citation(s) in RCA: 153] [Impact Index Per Article: 19.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Revised: 11/20/2017] [Accepted: 11/22/2017] [Indexed: 12/16/2022] Open
Abstract
Momordica charantia L. (M. charantia), a member of the Cucurbitaceae family, is widely distributed in tropical and subtropical regions of the world. It has been used in folk medicine for the treatment of diabetes mellitus, and its fruit has been used as a vegetable for thousands of years. Phytochemicals including proteins, polysaccharides, flavonoids, triterpenes, saponins, ascorbic acid and steroids have been found in this plant. Various biological activities of M. charantia have been reported, such as antihyperglycemic, antibacterial, antiviral, antitumor, immunomodulation, antioxidant, antidiabetic, anthelmintic, antimutagenic, antiulcer, antilipolytic, antifertility, hepatoprotective, anticancer and anti-inflammatory activities. However, both in vitro and in vivo studies have also demonstrated that M. charantia may also exert toxic or adverse effects under different conditions. This review addresses the chemical constituents of M. charantia and discusses their pharmacological activities as well as their adverse effects, aimed at providing a comprehensive overview of the phytochemistry and biological activities of M. charantia.
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Affiliation(s)
- Shuo Jia
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China.
| | - Mingyue Shen
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China.
| | - Fan Zhang
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China.
| | - Jianhua Xie
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China.
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Cheikhyoussef N, Kandawa-Schulz M, Böck R, de Koning C, Cheikhyoussef A, Hussein AA. Characterization of Acanthosicyos horridus and Citrullus lanatus seed oils: two melon seed oils from Namibia used in food and cosmetics applications. 3 Biotech 2017; 7:297. [PMID: 28868224 DOI: 10.1007/s13205-017-0922-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Accepted: 08/19/2017] [Indexed: 11/30/2022] Open
Abstract
The physicochemical characteristics, fatty acid, tocopherol, stigmasterol, β-sitosterol, and 1H NMR profiles of Citrullus lanatus and Acanthosicyos horridus melon seed oils were determined and compared among different extraction methods (cold pressing, traditional, and Soxhlet). The oil content was 40.2 ± 3.45 and 37.8 ± 7.26% for C. lanatus and A. horridus, respectively. Significant differences (p < 0.05) were observed among the different extraction methods in the characteristics studied. Physicochemical characteristics of the melon seed oils were saponification value, 180.48-189.86 mg KOH/g oil; iodine value, 108.27-118.62 g I2/100 g oil; acid value, 0.643-1.63 mg KOH/g oil; peroxide value; 1.69-2.98 mequiv/kg oil; specific gravity, 0.901-0.922; and refractive indices, 1.4676-1.4726. The dominant tocopherol was γ-tocopherol with total tocopherol in the range 27.61-74.39 mg/100 g. The dominant fatty acid was linoleic acid in the range 52.57-56.96%. The favorable oil yield, physicochemical characteristics, tocopherol, and fatty acid composition have the potential to replace or improve major commercial vegetable oils and to be used for various applications in the food industry and nutritive medicines.
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Affiliation(s)
- Natascha Cheikhyoussef
- Department of Chemistry and Biochemistry, University of Namibia, Windhoek, Namibia
- Ministry of Higher Education, Training and Innovation, Windhoek, Namibia
| | | | - Ronnie Böck
- Department of Biological Sciences, University of Namibia, Windhoek, Namibia
| | - Charles de Koning
- School of Chemistry, University of the Witwatersrand, Johannesburg, South Africa
| | - Ahmad Cheikhyoussef
- Science and Technology Division, Multidisciplinary Research Centre, University of Namibia, Windhoek, Namibia
| | - Ahmed A Hussein
- Department of Chemistry, Cape Peninsula University of Technology, Bellville Campus, Cape Town, South Africa
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Yin J, Wang B, Zhu X, Qu X, Huang Y, Lv S, Mu Y, Luo G. The Small Glutathione Peroxidase Mimic 5P May Represent a New Strategy for the Treatment of Liver Cancer. Molecules 2017; 22:E1495. [PMID: 28885589 PMCID: PMC6151655 DOI: 10.3390/molecules22091495] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Revised: 09/04/2017] [Accepted: 09/05/2017] [Indexed: 11/16/2022] Open
Abstract
Glutathione peroxidase (GPx) is an antioxidant protein containing selenium. Owing to the limitations of native GPx, considerable efforts have been made to develop GPx mimics. Here, a short 5-mer peptides (5P) was synthesized and characterized using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Enzyme coupled assays were used to evaluate GPx activity. The cell viability and apoptosis of H22 cells were tested, and mice bearing H22 cell-derived tumors were used to determine the effects of 5P on tumor inhibition. In comparison with other enzyme models, 5P provided a suitable substrate with proper catalytic site positions, resulting in enhanced catalytic activity. In our mouse model, 5P showed excellent inhibition of tumor growth and improved immunity. In summary, our findings demonstrated the design and synthesis of the small 5P molecule, which inhibited tumor growth and improved immunity. Notably, 5P could inhibit tumor growth without affecting normal growth. Based on these advantages, the novel mimic may have several clinical applications.
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Affiliation(s)
- Juxin Yin
- Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun 130000, China.
- Research Center for Analytical Instrumentation, Institute of Cyber-Systems and Control, State Key Laboratory of Industrial Control Technology, Zhejiang University, Hangzhou 310000, China.
| | - Bingmei Wang
- Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun 130000, China.
| | - Xuejun Zhu
- Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun 130000, China.
| | - Xiaonan Qu
- Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun 130000, China.
| | - Yi Huang
- Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun 130000, China.
| | - Shaowu Lv
- Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun 130000, China.
| | - Ying Mu
- Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun 130000, China.
- Research Center for Analytical Instrumentation, Institute of Cyber-Systems and Control, State Key Laboratory of Industrial Control Technology, Zhejiang University, Hangzhou 310000, China.
| | - Guimin Luo
- Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, College of Life Science, Jilin University, Changchun 130000, China.
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E S, Yamamoto K, Sakamoto Y, Mizowaki Y, Iwagaki Y, Kimura T, Nakagawa K, Miyazawa T, Tsuduki T. Intake of mulberry 1-deoxynojirimycin prevents colorectal cancer in mice. J Clin Biochem Nutr 2017; 61:47-52. [PMID: 28751809 PMCID: PMC5525018 DOI: 10.3164/jcbn.16-94] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Accepted: 11/23/2016] [Indexed: 12/21/2022] Open
Abstract
The effect of 1-deoxynojirimycin, a caloric restriction mimetic, was examined in ICR mice with azoxymethane dextran sodium sulfate-induced colorectal cancer. Azoxymethane is a carcinogen (10 mg/kg body weight), and 2% dextran sodium sulfate (w/v) used as a colitis-inducing agent. Mice were separated into 5 groups: a group without colorectal cancer fed a normal diet (CO– group), and groups with colorectal cancer fed a normal diet (CO+ group), a calorie-restricted diet (caloric restriction group), and diets including 0.02% and 0.1% 1-deoxynojirimycin (l-1-deoxynojirimycin and H-1-deoxynojirimycin groups). The tumor incidence and number were reduced significantly in the caloric restriction group compared to the CO+ group, and were also suppressed in a dose-dependent manner by 1-deoxynojirimycin. mRNA for anti-apoptotic Bcl-2 was decreased and that for pro-apoptotic Bax was increased in the carcinoma tissue of CR, l-1-deoxynojirimycin and H-1-deoxynojirimycin groups. These results suggest that caloric restriction and 1-deoxynojirimycin inhibit growth of colorectal cancer by inducing apoptosis in an induced cancer model in mice.
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Affiliation(s)
- Shuang E
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, 468-1 Aoba, Aramaki, Aoba-ku, Sendai 980-0845, Japan
| | - Kazushi Yamamoto
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, 468-1 Aoba, Aramaki, Aoba-ku, Sendai 980-0845, Japan
| | - Yu Sakamoto
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, 468-1 Aoba, Aramaki, Aoba-ku, Sendai 980-0845, Japan
| | - Yui Mizowaki
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, 468-1 Aoba, Aramaki, Aoba-ku, Sendai 980-0845, Japan
| | - Yui Iwagaki
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, 468-1 Aoba, Aramaki, Aoba-ku, Sendai 980-0845, Japan
| | - Toshiyuki Kimura
- Institute of Food Research, National Agriculture and Food Research Organization (NARO), 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan
| | - Kiyotaka Nakagawa
- Food and Biodynamic Chemistry Laboratory, Graduate School of Agriculture, Tohoku University, 468-1 Aoba, Aramaki, Aoba-ku, Sendai 980-0845, Japan
| | - Teruo Miyazawa
- Food and Biodynamic Chemistry Laboratory, Graduate School of Agriculture, Tohoku University, 468-1 Aoba, Aramaki, Aoba-ku, Sendai 980-0845, Japan
| | - Tsuyoshi Tsuduki
- Laboratory of Food and Biomolecular Science, Graduate School of Agriculture, Tohoku University, 468-1 Aoba, Aramaki, Aoba-ku, Sendai 980-0845, Japan
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Fontes AL, Pimentel LL, Simões CD, Gomes AMP, Rodríguez-Alcalá LM. Evidences and perspectives in the utilization of CLNA isomers as bioactive compounds in foods. Crit Rev Food Sci Nutr 2017; 57:2611-2622. [DOI: 10.1080/10408398.2015.1063478] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Affiliation(s)
- Ana L. Fontes
- CBQF – Centro de Biotecnologia e Química Fina – Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa/Porto, Porto, Portugal
| | - Lígia L. Pimentel
- CBQF – Centro de Biotecnologia e Química Fina – Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa/Porto, Porto, Portugal
| | - Catarina D. Simões
- CBQF – Centro de Biotecnologia e Química Fina – Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa/Porto, Porto, Portugal
| | - Ana M. P. Gomes
- CBQF – Centro de Biotecnologia e Química Fina – Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa/Porto, Porto, Portugal
| | - Luís M. Rodríguez-Alcalá
- CBQF – Centro de Biotecnologia e Química Fina – Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa/Porto, Porto, Portugal
- Centro de Investigación en Recursos Naturales y Sustentabilidad (CIRENYS), Universidad Bernardo O'Higgins, Santiago de Chile, Chile
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Wang L, Pang M, Wang X, Wang P, Xiao Y, Liu Q. Characteristics, composition, and antioxidant activities in vitro and in vivo of Gynostemma pentaphyllum (Thunb.) Makino seed oil. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2017; 97:2084-2093. [PMID: 27569782 DOI: 10.1002/jsfa.8013] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Revised: 08/07/2016] [Accepted: 08/25/2016] [Indexed: 06/06/2023]
Abstract
BACKGROUND In order to further develop and utilise Gynostemma pentaphyllum (Thunb.) Makino seeds, a detailed analysis of the characteristics of G. pentaphyllum seed oil (GPSO), including its physico-chemical parameters, fatty acid composition and unsaponifiable matter constituents, has been investigated in this study. The antioxidant potential of GPSO was evaluated by radical-scavenging activity and ferric-reducing antioxidant power assay in vitro, and the antioxidant activity in vivo was examined by using an aged mice model. RESULTS The main components of the seeds are lipids (485.54 g kg-1 ) and proteins (203.26 g kg-1 ). The GPSO obtained by supercritical CO2 fluid extraction was rich in polyunsaturated fatty acids (92.85%), especially conjugated linolenic acid (88.17%); and various useful compounds (squalene, tocopherol and phytosterols) were identified in the unsaponifiable matter. The overall antioxidant capacity of GPSO in vitro was shown to be comparable to that of Camellia seed oil as a positive control. GPSO could provide protection to the aged mice against oxidative stress and minimised the impact of ageing. CONCLUSION All the results suggest that GPSO has direct and potent antioxidant activities; it could be utilised as a functional food to supplement or replace some conventional oils. © 2016 Society of Chemical Industry.
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Affiliation(s)
- Lu Wang
- Key Laboratory of Medicinal Plant Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi'an, 710062, P.R. China
| | - Min Pang
- School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, 230009, P.R. China
| | - Xiaobing Wang
- Key Laboratory of Medicinal Plant Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi'an, 710062, P.R. China
| | - Pan Wang
- Key Laboratory of Medicinal Plant Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi'an, 710062, P.R. China
| | - Yaping Xiao
- Key Laboratory of Medicinal Plant Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi'an, 710062, P.R. China
| | - Quanhong Liu
- Key Laboratory of Medicinal Plant Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi'an, 710062, P.R. China
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Characterization of nutritionally important phytoconstituents in bitter melon (Momordica charantia L.) fruits by HPLC–DAD and GC–MS. JOURNAL OF FOOD MEASUREMENT AND CHARACTERIZATION 2016. [DOI: 10.1007/s11694-016-9378-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
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Korlesky NM, Stolp LJ, Kodali DR, Goldschmidt R, Byrdwell WC. Extraction and Characterization of Montmorency Sour Cherry (Prunus cerasus L.) Pit Oil. J AM OIL CHEM SOC 2016. [DOI: 10.1007/s11746-016-2835-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Hennessy AA, Ross P, Devery R, Stanton C. Bifidobacterially produced, C18:3 and C18:4 conjugated fatty acids exhibit in vitro anti-carcinogenic and anti-microbial activity. EUR J LIPID SCI TECH 2016. [DOI: 10.1002/ejlt.201500424] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Alan A. Hennessy
- Teagasc Food Research Centre; Moorepark; Fermoy Co. Cork Ireland
- National Institute for Cellular Biotechnology; Dublin City University; Ireland
| | - Paul Ross
- Teagasc Food Research Centre; Moorepark; Fermoy Co. Cork Ireland
| | - Rosaleen Devery
- National Institute for Cellular Biotechnology; Dublin City University; Ireland
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Sources and Bioactive Properties of Conjugated Dietary Fatty Acids. Lipids 2016; 51:377-97. [PMID: 26968402 DOI: 10.1007/s11745-016-4135-z] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2016] [Accepted: 02/17/2016] [Indexed: 12/11/2022]
Abstract
The group of conjugated fatty acids known as conjugated linoleic acid (CLA) isomers have been extensively studied with regard to their bioactive potential in treating some of the most prominent human health malignancies. However, CLA isomers are not the only group of potentially bioactive conjugated fatty acids currently undergoing study. In this regard, isomers of conjugated α-linolenic acid, conjugated nonadecadienoic acid and conjugated eicosapentaenoic acid, to name but a few, have undergone experimental assessment. These studies have indicated many of these conjugated fatty acid isomers commonly possess anti-carcinogenic, anti-adipogenic, anti-inflammatory and immune modulating properties, a number of which will be discussed in this review. The mechanisms through which these bioactivities are mediated have not yet been fully elucidated. However, existing evidence indicates that these fatty acids may play a role in modulating the expression of several oncogenes, cell cycle regulators, and genes associated with energy metabolism. Despite such bioactive potential, interest in these conjugated fatty acids has remained low relative to the CLA isomers. This may be partly attributed to the relatively recent emergence of these fatty acids as bioactives, but also due to a lack of awareness regarding sources from which they can be produced. In this review, we will also highlight the common sources of these conjugated fatty acids, including plants, algae, microbes and chemosynthesis.
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de Melo ILP, de Oliveira e Silva AM, de Carvalho EBT, Yoshime LT, Sattler JAG, Mancini-Filho J. Incorporation and effects of punicic acid on muscle and adipose tissues of rats. Lipids Health Dis 2016; 15:40. [PMID: 26922800 PMCID: PMC4769819 DOI: 10.1186/s12944-016-0214-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Accepted: 02/24/2016] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND This study evaluated the effect of pomegranate seed oil (PSO) supplementation, rich in punicic acid (55 %/C18:3-9c,11 t,13c/CLNA), on the lipid profile and on the biochemical and oxidative parameters in the gastrocnemius muscle and adipose tissues of healthy rats. Linseed oil (LO), rich in linolenic acid (52 %/C18:3-9c12c15c/LNA) was used for comparison. METHODS Male Wistar rats (n = 56) were distributed in seven groups: control (water); LNA 1 %, 2 % and 4 % (treated with LO); CLNA 1 %, 2 % and 4 % (treated with PSO), po for 40 days. The percentages were compared to the daily feed intake. Fatty acid profile were performed by gas chromatography, antioxidant enzymes activity by spectrophotometer and the adipocytes were isolated by collagenase tissue digestion. Analysis of variance (ANOVA) was applied to check for differences between the groups (control, LNAs and CLNAs) and principal component analysis (PCA) was used to project the groups in the factor-place (PC1 vs PC2) based on the biochemical responses assessed in the study. RESULTS The fatty acids profile of tissues showed that the LNA percentages were higher in the animals that were fed LO. However, PA was only detected in the adipose tissues. Conjugated linoleic acid (CLA) was present in all the tissues of the animals supplemented with PSO, in a dose dependent manner, and 9c11t-CLA was the predominant isomer. Nevertheless there were no changes in the total weight gain of the animals, the weights of the tissues, and the oxidative stress parameters in the muscle. In addition, there was an increase in the size of the epididymal fat cells in the groups treated with PSO. Principal component analysis (PCA) showed that the CLNAs groups were arranged separately with a cumulative variance of 68.47 %. CONCLUSIONS The results show that PSO can be used as a source of CLAs but that it does not cause changes in body modulation and does not interfere in the antioxidant activity of healthy rats.
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Affiliation(s)
- Illana Louise Pereira de Melo
- Department of Food and Experimental Nutrition, Laboratory of Lipids, Faculty of Pharmaceutical Sciences, São Paulo, University of São Paulo, Av. Prof. Lineu Prestes, 580 - Bloco 14, CEP: 05508-900, São Paulo, Brazil.
| | | | - Eliane Bonifácio Teixeira de Carvalho
- Department of Food and Experimental Nutrition, Laboratory of Lipids, Faculty of Pharmaceutical Sciences, São Paulo, University of São Paulo, Av. Prof. Lineu Prestes, 580 - Bloco 14, CEP: 05508-900, São Paulo, Brazil
| | - Luciana Tedesco Yoshime
- Department of Food and Experimental Nutrition, Laboratory of Lipids, Faculty of Pharmaceutical Sciences, São Paulo, University of São Paulo, Av. Prof. Lineu Prestes, 580 - Bloco 14, CEP: 05508-900, São Paulo, Brazil
| | - José Augusto Gasparotto Sattler
- Department of Food and Experimental Nutrition, Laboratory of Lipids, Faculty of Pharmaceutical Sciences, São Paulo, University of São Paulo, Av. Prof. Lineu Prestes, 580 - Bloco 14, CEP: 05508-900, São Paulo, Brazil
| | - Jorge Mancini-Filho
- Department of Food and Experimental Nutrition, Laboratory of Lipids, Faculty of Pharmaceutical Sciences, São Paulo, University of São Paulo, Av. Prof. Lineu Prestes, 580 - Bloco 14, CEP: 05508-900, São Paulo, Brazil
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50
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Production of conjugated dienoic and trienoic fatty acids by lactic acid bacteria and bifidobacteria. J Funct Foods 2015. [DOI: 10.1016/j.jff.2015.09.046] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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