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Ding J, Gao T, Liu S, Li Z, Hu B, Zheng J, Yao X, Liu H, Hu H. Rhamnosidase from Parabacteroides distasonis exhibit the catabolism of epimedin C in the human gut microbiota. Int J Biol Macromol 2025; 309:142481. [PMID: 40157660 DOI: 10.1016/j.ijbiomac.2025.142481] [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: 10/02/2024] [Revised: 03/20/2025] [Accepted: 03/22/2025] [Indexed: 04/01/2025]
Abstract
Epimedin C, an anti-cardiovascular disease natural compound derived from Herba Epimedii, exhibits low oral bioavailability, with its metabolism closely related to the gut microbiota. In this study, we investigated the roles of intestinal bacteria in the catabolism of epimedin C. We discovered that a strain of Parabacteroides distasonis QZH 1201 (P. distasonis) from human fecal samples can convert epimedin C to 2"-O-rhamnosylicariside II and baohuoside I. More importantly, we identified an α-L-rhamnosidase enzyme from P. distasonis (PdRha), which plays a crucial role in this process by efficiently transforming epimedin C into icariside I. PdRha showed optimal activity at pH 6 and a temperature of 50 °C. Under the condition that the final concentration of epimedin C was 0.5 mM, its conversion efficiency reached 78.72 %. Additionally, we investigated the substrate profile of PdRha and discovered that it can hydrolyze rutin, naringin, and icariin, releasing isoquercitrin, prunin, and icariside I. Molecular docking was performed to gain insights into the enzymatic mechanism. This study provides valuable insights into how a common intestinal symbiotic bacterium processes an important natural flavonoid.
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Affiliation(s)
- Jiaojiao Ding
- School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China; College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China; School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China
| | - Tiexiang Gao
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China; Key Laboratory of Chinese Medicinal Resource and Chinese Herbal Compound of the Ministry of Education, Hubei University of Chinese Medicine, Wuhan 430065, China
| | - Songlin Liu
- Key Laboratory of Chinese Medicinal Resource and Chinese Herbal Compound of the Ministry of Education, Hubei University of Chinese Medicine, Wuhan 430065, China; Hubei Shizhen Laboratory, Wuhan 430061, China
| | - Zhezhe Li
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China
| | - Baifei Hu
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China; Key Laboratory of Chinese Medicinal Resource and Chinese Herbal Compound of the Ministry of Education, Hubei University of Chinese Medicine, Wuhan 430065, China; Hubei Shizhen Laboratory, Wuhan 430061, China
| | - Junping Zheng
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China; Key Laboratory of Chinese Medicinal Resource and Chinese Herbal Compound of the Ministry of Education, Hubei University of Chinese Medicine, Wuhan 430065, China; Hubei Shizhen Laboratory, Wuhan 430061, China
| | - Xiaowei Yao
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China; Key Laboratory of Chinese Medicinal Resource and Chinese Herbal Compound of the Ministry of Education, Hubei University of Chinese Medicine, Wuhan 430065, China; Hubei Shizhen Laboratory, Wuhan 430061, China
| | - Hongtao Liu
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China; Key Laboratory of Chinese Medicinal Resource and Chinese Herbal Compound of the Ministry of Education, Hubei University of Chinese Medicine, Wuhan 430065, China; Hubei Shizhen Laboratory, Wuhan 430061, China.
| | - Haiming Hu
- School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China; Key Laboratory of Chinese Medicinal Resource and Chinese Herbal Compound of the Ministry of Education, Hubei University of Chinese Medicine, Wuhan 430065, China; Hubei Shizhen Laboratory, Wuhan 430061, China.
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Beaver LM, Jamieson PE, Wong CP, Hosseinikia M, Stevens JF, Ho E. Promotion of Healthy Aging Through the Nexus of Gut Microbiota and Dietary Phytochemicals. Adv Nutr 2025; 16:100376. [PMID: 39832641 PMCID: PMC11847308 DOI: 10.1016/j.advnut.2025.100376] [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: 10/25/2024] [Revised: 12/20/2024] [Accepted: 01/14/2025] [Indexed: 01/22/2025] Open
Abstract
Aging is associated with the decline of tissue and cellular functions, which can promote the development of age-related diseases like cancer, cardiovascular disease, neurodegeneration, and disorders of the musculoskeletal and immune systems. Healthspan is the length of time an individual is in good health and free from chronic diseases and disabilities associated with aging. Two modifiable factors that can influence healthspan, promote healthy aging, and prevent the development of age-related diseases, are diet and microbiota in the gastrointestinal tract (gut microbiota). This review will discuss how dietary phytochemicals and gut microbiota can work in concert to promote a healthy gut and healthy aging. First, an overview is provided of how the gut microbiota influences healthy aging through its impact on gut barrier integrity, immune function, mitochondria function, and oxidative stress. Next, the mechanisms by which phytochemicals effect gut health, inflammation, and nurture a diverse and healthy microbial composition are discussed. Lastly, we discuss how the gut microbiota can directly influence health by producing bioactive metabolites from phytochemicals in food like urolithin A, equol, hesperetin, and sulforaphane. These and other phytochemical-derived microbial metabolites that may promote healthspan are discussed. Importantly, an individual's capacity to produce health-promoting microbial metabolites from cruciferous vegetables, berries, nuts, citrus, and soy products will be dependent on the specific bacteria present in the individual's gut.
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Affiliation(s)
- Laura M Beaver
- Linus Pauling Institute, Oregon State University, Corvallis, OR, United States; School of Nutrition and Public Health, Oregon State University, Corvallis, OR, United States
| | - Paige E Jamieson
- Linus Pauling Institute, Oregon State University, Corvallis, OR, United States; School of Nutrition and Public Health, Oregon State University, Corvallis, OR, United States
| | - Carmen P Wong
- Linus Pauling Institute, Oregon State University, Corvallis, OR, United States; School of Nutrition and Public Health, Oregon State University, Corvallis, OR, United States
| | - Mahak Hosseinikia
- Linus Pauling Institute, Oregon State University, Corvallis, OR, United States; School of Nutrition and Public Health, Oregon State University, Corvallis, OR, United States
| | - Jan F Stevens
- Linus Pauling Institute, Oregon State University, Corvallis, OR, United States; Department of Pharmaceutical Sciences, Oregon State University, Corvallis, Oregon, United States
| | - Emily Ho
- Linus Pauling Institute, Oregon State University, Corvallis, OR, United States; School of Nutrition and Public Health, Oregon State University, Corvallis, OR, United States.
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Wang C, Wang Y, Teng Y, Kong J, Dong F, Du J, Zhang Y. Cooperation mechanism of flavonoid transformation by Bifidobacterium animalis subsp. lactis and Lacticaseibacillus paracasei. Int J Food Microbiol 2025; 429:111019. [PMID: 39675163 DOI: 10.1016/j.ijfoodmicro.2024.111019] [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: 09/04/2024] [Revised: 12/01/2024] [Accepted: 12/09/2024] [Indexed: 12/17/2024]
Abstract
Elaeagnus moorcroftii Wall. ex Schlecht (EWS) as a suitable food matrix contains abundant flavonoids for promoting human health, this study aimed to use flavonoid-targeted metabolomics and transcriptome sequencing to investigate the transformation of flavonoids in EWS juice (EWSJ) by mono- and mixed-cultures fermentations of Bifidobacterium animalis subsp. lactis HN-3 (B.an3) and Lacticaseibacillus paracasei YL-29 (L.cp29). A total of 33 flavonoids were identified in mono- and mixed-cultures fermented EWSJ. Among them, fermentation by B.an3 produced specific deglycosylation products (kaempferol (17.6 mmol/L) and luteolin (4.5 mmol/L)) and methoxylation products (syringaldehyde (59.05 mmol/L)), and fermentation by L.cp29 resulted in a specific deglycosylation product (quercetin (9.2 mmol/L)). The co-culture fermentation further increased the levels of isorhamnetin (52.3 mmol/L), and produced a specific product (homoplantaginin (0.03 mmol/L)), which significantly increased the bioactive-form flavonoids. Moreover, we analyzed changes in different flavonoid metabolites and differential genes before and after fermentation. After L.cp29 fermentation the expression of glycoside hydrolases and oxidoreductases were increased compared to other groups. After B.an3 fermentation the expression of isomerases and synthetases were increased compared to other groups. In particular, 6-phosphogluconolactonase (Pgl) and glucose-6-phosphate isomerase (Pgi) were increased in B.an3 fermentation. Thus, we validated the predicted transformation reactions by the biotransformation of flavonoids by the collected strains and crude enzyme extracts of B.an3 and L.cp29. These findings provided a basis for the development of functional plant-based foods with enhanced bioactive flavonoids.
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Affiliation(s)
- Chenxi Wang
- School of Food Science and Technology, Shihezi University, Road Beisi, Shihezi, Xinjiang Province 832003, China; Key Laboratory of Agricultural Product Processing and Quality Control of Specialty (mixed-construction by Ministry and Province), School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang 832000, China
| | - Yixuan Wang
- School of Food Science and Technology, Shihezi University, Road Beisi, Shihezi, Xinjiang Province 832003, China; Key Laboratory of Agricultural Product Processing and Quality Control of Specialty (mixed-construction by Ministry and Province), School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang 832000, China
| | - Yingdi Teng
- School of Food Science and Technology, Shihezi University, Road Beisi, Shihezi, Xinjiang Province 832003, China; Key Laboratory of Agricultural Product Processing and Quality Control of Specialty (mixed-construction by Ministry and Province), School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang 832000, China
| | - Junkai Kong
- School of Food Science and Technology, Shihezi University, Road Beisi, Shihezi, Xinjiang Province 832003, China; Key Laboratory of Agricultural Product Processing and Quality Control of Specialty (mixed-construction by Ministry and Province), School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang 832000, China
| | - Fujin Dong
- School of Food Science and Technology, Shihezi University, Road Beisi, Shihezi, Xinjiang Province 832003, China; Key Laboratory of Agricultural Product Processing and Quality Control of Specialty (mixed-construction by Ministry and Province), School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang 832000, China
| | - Jie Du
- School of Food Science and Technology, Shihezi University, Road Beisi, Shihezi, Xinjiang Province 832003, China; Key Laboratory of Agricultural Product Processing and Quality Control of Specialty (mixed-construction by Ministry and Province), School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang 832000, China
| | - Yan Zhang
- School of Food Science and Technology, Shihezi University, Road Beisi, Shihezi, Xinjiang Province 832003, China; Key Laboratory of Agricultural Product Processing and Quality Control of Specialty (mixed-construction by Ministry and Province), School of Food Science and Technology, Shihezi University, Shihezi, Xinjiang 832000, China.
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Li X, Liu S, Wang F, Li X, Liu H, Lian T, Yan X, Yang L, Wei J, Li Y, Cai T. Dietary herbs that interact with gut microbiota: roles as anti-stroke agents. Food Sci Biotechnol 2025; 34:547-562. [PMID: 39958164 PMCID: PMC11822190 DOI: 10.1007/s10068-024-01698-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 08/08/2024] [Accepted: 08/12/2024] [Indexed: 02/18/2025] Open
Abstract
Growing evidence suggests that dietary herbs can prevent stroke by regulating the composition and structure of gut microbiota. The components of dietary herbs can also be metabolized or converted into bioactive molecules for treating stroke by gut microbiota, and exert therapeutic effects by inhibiting inflammation, oxidative stress, apoptosis, and other processes caused by stroke. A deep understanding of the mechanism of gut microbiota-mediated dietary herbal intervention in stroke is of great significance for the treatment and drug screening of stroke diseases. In this review, we summarise the complex bidirectional relationship between stroke and gut microbiota and provide a detailed introduction to the mechanism of the interaction between dietary herbs and gut microbiota in intervening in stroke. In addition, we also discuss the limitations of current research and potential directions in this field, hoping to provide ideas and references for the treatment and drug development of stroke diseases. Graphical abstract Dietary herbs and active ingredients can balance the intestinal microbiota disorders in stroke patients or models, and herbal ingredients can be converted into more easily absorbed active substances under the action of microorganisms, thereby exerting therapeutic effect on stroke diseases.
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Affiliation(s)
- Xia Li
- Ningbo No. 2 Hospital, Ningbo, 315099 China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, 315000 China
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Sijia Liu
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Fang Wang
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Xinyue Li
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
- Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Huiru Liu
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Tingting Lian
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Xingxu Yan
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Liu Yang
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Jinxia Wei
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Yubo Li
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617 People’s Republic of China
| | - Ting Cai
- Ningbo No. 2 Hospital, Ningbo, 315099 China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, 315000 China
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Wang Y, Wang C, Shi J, Zhang Y. Effects of derivatization and probiotic transformation on the antioxidative activity of fruit polyphenols. Food Chem X 2024; 23:101776. [PMID: 39280222 PMCID: PMC11402117 DOI: 10.1016/j.fochx.2024.101776] [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: 06/26/2024] [Revised: 08/15/2024] [Accepted: 08/24/2024] [Indexed: 09/18/2024] Open
Abstract
Fruits contain numerous polyphenols in the form of conjugates, which exhibit low antioxidant activity. Probiotic fermentation is a strategy to improve the antioxidant activity of these conjugated polyphenols by modifying their structure. However, the mechanisms underlying the effects of functional groups and derivatizations on the antioxidative activities of polyphenols and the antioxidation enhancement by probiotic biotransformation haven't been comprehensively explored. This review aimed to explore the structure-antioxidant activity relationships of four functional groups and three derivatizations in flavonoids and phenolic acids. Further, the review elucidated the antioxidant mechanisms underlying the biotransformation of flavonoids and phenolic acids as glycoside, methylated, and ester conjugates by probiotic biotransformation. Deglycosylation, demethylation, and hydrolysis catalyzed by enzymes produced by Bifidobacterium and Lactobacillus facilitated the conversion of conjugated polyphenols into flavonoids and phenolic acids with hydrolyzed forms and highly active functional groups, thereby increasing hydrogen supply and electron transfer capacity to enhance the antioxidant activity.
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Affiliation(s)
- Yixuan Wang
- School of food science and technology, Shihezi University, Road Beisi, Shihezi, Xinjiang Province 832003, China
| | - Chenxi Wang
- School of food science and technology, Shihezi University, Road Beisi, Shihezi, Xinjiang Province 832003, China
| | - Junling Shi
- Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Shaanxi, Xi'an Province 710072, People's Republic of China
| | - Yan Zhang
- School of food science and technology, Shihezi University, Road Beisi, Shihezi, Xinjiang Province 832003, China
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Kiriyama Y, Tokumaru H, Sadamoto H, Kobayashi S, Nochi H. Effects of Phenolic Acids Produced from Food-Derived Flavonoids and Amino Acids by the Gut Microbiota on Health and Disease. Molecules 2024; 29:5102. [PMID: 39519743 PMCID: PMC11548037 DOI: 10.3390/molecules29215102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 10/25/2024] [Accepted: 10/25/2024] [Indexed: 11/16/2024] Open
Abstract
The gut microbiota metabolizes flavonoids, amino acids, dietary fiber, and other components of foods to produce a variety of gut microbiota-derived metabolites. Flavonoids are the largest group of polyphenols, and approximately 7000 flavonoids have been identified. A variety of phenolic acids are produced from flavonoids and amino acids through metabolic processes by the gut microbiota. Furthermore, these phenolic acids are easily absorbed. Phenolic acids generally represent phenolic compounds with one carboxylic acid group. Gut microbiota-derived phenolic acids have antiviral effects against several viruses, such as SARS-CoV-2 and influenza. Furthermore, phenolic acids influence the immune system by inhibiting the secretion of proinflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α. In the nervous systems, phenolic acids may have protective effects against neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Moreover, phenolic acids can improve levels of blood glucose, cholesterols, and triglycerides. Phenolic acids also improve cardiovascular functions, such as blood pressure and atherosclerotic lesions. This review focuses on the current knowledge of the effects of phenolic acids produced from food-derived flavonoids and amino acids by the gut microbiota on health and disease.
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Affiliation(s)
- Yoshimitsu Kiriyama
- Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Shido 1314-1, Sanuki 769-2193, Kagawa, Japan (H.S.); (S.K.); (H.N.)
- Institute of Neuroscience, Tokushima Bunri University, Shido 1314-1, Sanuki 769-2193, Kagawa, Japan
| | - Hiroshi Tokumaru
- Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Shido 1314-1, Sanuki 769-2193, Kagawa, Japan (H.S.); (S.K.); (H.N.)
| | - Hisayo Sadamoto
- Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Shido 1314-1, Sanuki 769-2193, Kagawa, Japan (H.S.); (S.K.); (H.N.)
| | - Suguru Kobayashi
- Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Shido 1314-1, Sanuki 769-2193, Kagawa, Japan (H.S.); (S.K.); (H.N.)
- Institute of Neuroscience, Tokushima Bunri University, Shido 1314-1, Sanuki 769-2193, Kagawa, Japan
| | - Hiromi Nochi
- Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Shido 1314-1, Sanuki 769-2193, Kagawa, Japan (H.S.); (S.K.); (H.N.)
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Turck D, Bohn T, Castenmiller J, De Henauw S, Hirsch‐Ernst KI, Maciuk A, Mangelsdorf I, McArdle HJ, Naska A, Pentieva K, Siani A, Thies F, Tsabouri S, Vinceti M, Aguilera‐Gómez M, Cubadda F, Frenzel T, Heinonen M, Neuhäuser‐Berthold M, Poulsen M, Maradona MP, Schlatter JR, Siskos A, van Loveren H, Kouloura E, Matijević L, Knutsen HK. Safety of glucosyl hesperidin as a Novel food pursuant to Regulation (EU) 2015/2283. EFSA J 2024; 22:e8911. [PMID: 39119058 PMCID: PMC11306971 DOI: 10.2903/j.efsa.2024.8911] [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] [Indexed: 08/10/2024] Open
Abstract
Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on glucosyl hesperidin (GH) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF, which is produced from hesperidin and dextrin by enzymatic reactions, is a powder consisting mainly of monoglucosyl hesperidin (MGH) and unreacted hesperidin (flavonoid), which account in total for up to 92.8% (on dry basis) of the product. The applicant proposed to use the NF in specific drinks and food supplements leading to a maximum intake of up to 364 mg per day for adults. The target population is the general population, except for food supplements for which the proposed target population is children from 1 year onwards and adults. Taking into consideration the composition of the NF and the proposed uses, the consumption of the NF is not nutritionally disadvantageous. There are no concerns regarding genotoxicity of the NF. Based on a 90-day oral toxicity study conducted with the NF, the Panel considers the NOAEL at the mid-dose group, i.e. ~ 1000 mg/kg body weight (bw) per day. By applying an uncertainty factor of 200, the resulting intake providing sufficient margin of exposure for humans would be 5 mg/kg bw per day. The available human intervention studies did not report clinically relevant changes in haematological or clinical chemistry parameters following the administration of GH/MGH at supplemental doses of up to 3 g/day for 12 weeks. Overall, the Panel considers that the margin of exposure (~ 200) between the intake of the NF at the proposed uses and use levels and the NOAEL from the 90-day study is sufficient. The Panel concludes that the NF, glucosyl hesperidin, is safe for the target population at the proposed uses and use levels.
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Hu J, Mesnage R, Tuohy K, Heiss C, Rodriguez-Mateos A. (Poly)phenol-related gut metabotypes and human health: an update. Food Funct 2024; 15:2814-2835. [PMID: 38414364 DOI: 10.1039/d3fo04338j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/29/2024]
Abstract
Dietary (poly)phenols have received great interest due to their potential role in the prevention and management of non-communicable diseases. In recent years, a high inter-individual variability in the biological response to (poly)phenols has been demonstrated, which could be related to the high variability in (poly)phenol gut microbial metabolism existing within individuals. An interplay between (poly)phenols and the gut microbiota exists, with (poly)phenols being metabolised by the gut microbiota and their metabolites modulating gut microbiota diversity and composition. A number of (poly)phenol metabolising phenotypes or metabotypes have been proposed, however, potential metabotypes for most (poly)phenols have not been investigated, and the relationship between metabotypes and human health remains ambiguous. This review presents updated knowledge on the reciprocal interaction between (poly)phenols and the gut microbiome, associated gut metabotypes, and subsequent impact on human health.
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Affiliation(s)
- Jiaying Hu
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
| | - Robin Mesnage
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
- Buchinger Wilhelmi Clinic, Überlingen, Germany
| | - Kieran Tuohy
- School of Food Science and Nutrition, Faculty of Environment, University of Leeds, Leeds, UK
| | - Christian Heiss
- Department of Clinical and Experimental Medicine, Faculty of Health and Medical Sciences, University of Surrey, Surrey, UK
| | - Ana Rodriguez-Mateos
- Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
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Santa K, Kumazawa Y, Watanabe K, Nagaoka I. The Potential Use of Vitamin D3 and Phytochemicals for Their Anti-Ageing Effects. Int J Mol Sci 2024; 25:2125. [PMID: 38396804 PMCID: PMC10889119 DOI: 10.3390/ijms25042125] [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: 12/19/2023] [Revised: 02/02/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024] Open
Abstract
Unlike other vitamins, vitamin D3 is synthesised in skin cells in the body. Vitamin D3 has been known as a bone-related hormone. Recently, however, it has been considered as an immune vitamin. Vitamin D3 deficiency influences the onset of a variety of diseases. Vitamin D3 regulates the production of proinflammatory cytokines such as tumour necrosis factor-α (TNF-α) through binding to vitamin D receptors (VDRs) in immune cells. Since blood levels of vitamin D3 (25-OH-D3) were low in coronavirus disease 2019 (COVID-19) patients, there has been growing interest in the importance of vitamin D3 to maintaining a healthy condition. On the other hand, phytochemicals are compounds derived from plants with over 7000 varieties and have various biological activities. They mainly have health-promoting effects and are classified as terpenoids, carotenoids, flavonoids, etc. Flavonoids are known as the anti-inflammatory compounds that control TNF-α production. Chronic inflammation is induced by the continuous production of TNF-α and is the fundamental cause of diseases like obesity, dyslipidaemia, diabetes, heart and brain diseases, autoimmune diseases, Alzheimer's disease, and cancer. In addition, the ageing process is induced by chronic inflammation. This review explains the cooperative effects of vitamin D3 and phytochemicals in the suppression of inflammatory responses, how it balances the natural immune response, and its link to anti-ageing effects. In addition, vitamin D3 and phytochemicals synergistically contribute to anti-ageing by working with ageing-related genes. Furthermore, prevention of ageing processes induced by the chronic inflammation requires the maintenance of healthy gut microbiota, which is related to daily dietary habits. In this regard, supplementation of vitamin D3 and phytochemicals plays an important role. Recently, the association of the prevention of the non-disease condition called "ME-BYO" with the maintenance of a healthy condition has been an attractive regimen, and the anti-ageing effect discussed here is important for a healthy and long life.
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Affiliation(s)
- Kazuki Santa
- Department of Biotechnology, Tokyo College of Biotechnology, Ota-ku, Tokyo 114-0032, Japan;
| | - Yoshio Kumazawa
- Vino Science Japan Inc., Kawasaki 210-0855, Kanagawa, Japan
- Department of Biochemistry and Systems Biomedicine, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo 113-8421, Japan
| | - Kenji Watanabe
- Center for Kampo Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan
- Yokohama University of Pharmacy, Yokohama 245-0066, Kanagawa, Japan
| | - Isao Nagaoka
- Department of Biochemistry and Systems Biomedicine, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo 113-8421, Japan
- Faculty of Medical Science, Juntendo University, Urayasu 279-0013, Chiba, Japan
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Hao W, Gan H, Wang L, Huang J, Chen J. Polyphenols in edible herbal medicine: targeting gut-brain interactions in depression-associated neuroinflammation. Crit Rev Food Sci Nutr 2023; 63:12207-12223. [PMID: 35838146 DOI: 10.1080/10408398.2022.2099808] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Supplementing with edible herbal medicine is an important strategy because of its role in nutrition. Many polyphenols, which are universal components in edible herbal medicines, have low bioavailability. Therefore, gut microbiota is a key determinant of polyphenol bioactivity. Polyphenols can alter the abundance of flora associated with neuroinflammation by reversing intestinal microbiota dysbiosis. Intestinal flora-mediated chemical modification of polyphenols can result in their conversion into active secondary metabolites. The current review summarizes the main edible medicines used in anti-depression and details the interactions between polyphenols and gut microbiota; in addition, it provides insights into the mechanisms underlying the possible suppression of neuroinflammation associated with depression, by polyphenols in edible herbal medicine. A better understanding of polyphenols with bioactivities that are crucial in edible herbal medicine may facilitate their use in the prevention and treatment of neuroinflammation associated with depression.
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Affiliation(s)
- Wenzhi Hao
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Hua Gan
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Lu Wang
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Junqing Huang
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
| | - Jiaxu Chen
- Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
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11
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Ma Q, Noda M, Danshiitsoodol N, Sugiyama M. Fermented Stevia Improves Alcohol Poisoning Symptoms Associated with Changes in Mouse Gut Microbiota. Nutrients 2023; 15:3708. [PMID: 37686739 PMCID: PMC10489940 DOI: 10.3390/nu15173708] [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: 08/07/2023] [Revised: 08/21/2023] [Accepted: 08/23/2023] [Indexed: 09/10/2023] Open
Abstract
We previously found that the continuous feeding of ethanol caused mice dysbiosis, in which the cecal microbiota were significantly altered, as compared with those in the non-feeding control group, especially in some bacterial genera involved in gut inflammation. In the present study, we have found that the fermented extract of stevia (Stevia rebaudiana) leaves with plant-derived lactic acid bacteria (LABs), Pediococcus pentosaceus LY45, improves the trimethylamine (TMA) productivity of cecal content, which can be used as an indicator of dysbiosis. The following animal experiment also shows that the LY45-fermented stevia extract represses the typical increase in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, which decreased from 1106 to 210 IU/L (p < 0.05) and from 591 to 100 IU/L (p < 0.05), respectively, together with the simultaneously latent TMA productivity (from 1356 to 745 μM, p < 0.05) of cecal content in the ethanol-fed mice. The microbiota analyses have shown that the observed increased alterations in pro-inflammatory genera putative SMB53 (family Clostridiaceae) and Dorea are restored by the fermented stevia extract. Our result indicates that the preliminary bioconversion of herbal medicinal precursors by fermentation with safe microorganisms like LABs is expected to be a hopeful method of producing specific metabolites that may contribute to the reconstruction of gut microbiota.
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Affiliation(s)
| | | | | | - Masanori Sugiyama
- Department of Probiotic Science for Preventive Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8551, Japan; (Q.M.); (M.N.); (N.D.)
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12
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Bester A, O'Brien M, Cotter PD, Dam S, Civai C. Shotgun Metagenomic Sequencing Revealed the Prebiotic Potential of a Fruit Juice Drink with Fermentable Fibres in Healthy Humans. Foods 2023; 12:2480. [PMID: 37444219 DOI: 10.3390/foods12132480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 05/13/2023] [Accepted: 06/08/2023] [Indexed: 07/15/2023] Open
Abstract
Fibre-based dietary interventions are at the forefront of gut microbiome modulation research, with a wealth of 16S rRNA information to demonstrate the prebiotic effects of isolated fibres. However, there is a distinct lack of data relating to the effect of a combination of soluble and insoluble fibres in a convenient-to-consume fruit juice food matrix on gut microbiota structure, diversity, and function. Here, we aimed to determine the impact of the MOJU Prebiotic Shot, an apple, lemon, ginger, and raspberry fruit juice drink blend containing chicory inulin, baobab, golden kiwi, and green banana powders, on gut microbiota structure and function. Healthy adults (n = 20) were included in a randomised, double-blind, placebo-controlled, cross-over study, receiving 60 mL MOJU Prebiotic Shot or placebo (without the fibre mix) for 3 weeks with a 3-week washout period between interventions. Shotgun metagenomics revealed significant between-group differences in alpha and beta diversity. In addition, the relative abundance of the phyla Actinobacteria and Desulfobacteria was significantly increased as a result of the prebiotic intervention. Nine species were observed to be differentially abundant (uncorrected p-value of <0.05) as a result of the prebiotic treatment. Of these, Bifidobacterium adolescentis and CAG-81 sp900066785 (Lachnospiraceae) were present at increased abundance relative to baseline. Additionally, KEGG analysis showed an increased abundance in pathways associated with arginine biosynthesis and phenylacetate degradation during the prebiotic treatment. Our results show the effects of the daily consumption of 60 mL MOJU Prebiotic Shot for 3 weeks and provide insight into the functional potential of B. adolescentis.
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Affiliation(s)
- Adri Bester
- London Agri Food Innovation Clinic (LAFIC), School of Applied Sciences, London South Bank University, London SE1 0AA, UK
| | | | | | | | - Claudia Civai
- London Agri Food Innovation Clinic (LAFIC), School of Applied Sciences, London South Bank University, London SE1 0AA, UK
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13
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Wang J, Yu Z, Peng Y, Xu B. Insights into prevention mechanisms of bioactive components from healthy diets against Alzheimer's disease. J Nutr Biochem 2023:109397. [PMID: 37301484 DOI: 10.1016/j.jnutbio.2023.109397] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 05/01/2023] [Accepted: 05/30/2023] [Indexed: 06/12/2023]
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease in which senile plaques, neurofibrillary tangles, insulin resistance, oxidative stress, chronic neuroinflammation, and abnormal neurotransmission are the potential mechanisms involved in its onset and development. Although it is still an intractable disorder, diet intervention has been developed as an innovative strategy for AD prevention. Some bioactive compounds and micronutrients from food, including soy isoflavones, rutin, vitamin B1, etc., have exhibited numerous neuronal health-promoting effects in both in vivo and in vitro studies. It is well known that their antiapoptotic, antioxidative, and anti-inflammatory properties prevent the neuronal or glial cells from injury or death, minimize oxidative damage, inhibit the production of proinflammatory cytokines by modulating typical signaling pathways of MAPK, NF-kβ, and TLR, and further reduce Aβ genesis and tau hyperphosphorylation. However, parts of the dietary components trigger AD-related proteins productions and inflammasome as well as inflammatory gene upregulation. This review summarized the neuroprotective or nerve damage-promoting role and underlying molecular mechanisms of flavonoids, vitamins, and fatty acids via the data from library databases, PubMed, and journal websites, which provides a comprehensive analysis of the prevention potential of these dietary components against AD.
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Affiliation(s)
- Jingwen Wang
- Food Science and Technology Program, Department of Life Sciences, BNU-HKBU United International College, Zhuhai, Guangdong 519087, China
| | - Zhiling Yu
- Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
| | - Ye Peng
- Faculty of Medicine, Macau University of Science and Technology, Taipa, Macao SAR, China
| | - Baojun Xu
- Food Science and Technology Program, Department of Life Sciences, BNU-HKBU United International College, Zhuhai, Guangdong 519087, China.
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14
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Zhao Y, Yu S, Li L, Zhao H, Li Y, Jiang L, Liu M. Feeding citrus flavonoid extracts decreases bacterial endotoxin and systemic inflammation and improves immunometabolic status by modulating hindgut microbiome and metabolome in lactating dairy cows. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2023; 13:386-400. [PMID: 37214215 PMCID: PMC10196341 DOI: 10.1016/j.aninu.2023.03.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 01/09/2023] [Accepted: 03/01/2023] [Indexed: 05/24/2023]
Abstract
The objectives of this study were to determine the effects of dietary supplementation with citrus flavonoid extracts (CFE) on milk performance, serum biochemistry parameters, fecal volatile fatty acids, fecal microbial community, and fecal metabolites in dairy cows. Eight multiparous lactating Holstein cows were used in a replicated 4 × 4 Latin square design (21-day period). Cows were fed a basal diet without addition (CON) or basal diet with added CFE at 50 (CFE50), 100 (CFE10), and 150 g/d (CFE150). Feeding CFE up to 150 g/d increased milk yield and milk lactose percentage. Supplementary CFE linearly decreased milk somatic cell count. Serum cytokines interleukin-1β (IL-1β), IL-2, IL-6, and tumor necrosis factor-α (TNF-α) concentrations decreased linearly as the levels of CFE increased. Cows in CFE150 had lower serum lipopolysaccharide and lipopolysaccharide binding protein compared with CON. These results indicate feeding CFE decreased systemic inflammation and endotoxin levels in dairy cows. Furthermore, feeding CFE linearly increased the concentrations of total volatile fatty acids, acetate, and butyrate in feces. The relative abundances of beneficial bacteria Bifidobacterium spp., Clostridium coccoides-Eubacterium rectale group, and Faecalibacterium prausnitzii in feces increased linearly with increasing CFE supplementation. The diversity and community structure of fecal microbiota were unaffected by CFE supplementation. However, supplementing CFE reduced the relative abundances of genera Ruminococcus_torques_group, Roseburia, and Lachnospira, but increased genera Bacteroides and Phascolarctobacterium. Metabolomics analysis showed that supplementary CFE resulted in a significant modification in the fecal metabolites profile. Compared with CON, fecal naringenin, hesperetin, hippuric acid, and sphingosine concentrations were greater in CFE150 cows, while fecal GlcCer(d18:1/20:0), Cer(d18:0/24:0), Cer(d18:0/22:0), sphinganine, and deoxycholic acid concentrations were less in CFE150 cows. Predicted pathway analysis suggested that "sphingolipid metabolism" was significantly enriched. Overall, these results indicate that citrus flavonoids could exert health-promoting effects by modulating hindgut microbiome and metabolism in lactating cows.
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Affiliation(s)
- Yuchao Zhao
- Beijing Key Laboratory of Dairy Cow Nutrition, Animal Science and Technology College, Beijing University of Agriculture, Beijing, 102206, China
- Beijing Beinong Enterprise Management Co., Ltd., Beijing, 102206, China
| | - Shiqiang Yu
- Beijing Key Laboratory of Dairy Cow Nutrition, Animal Science and Technology College, Beijing University of Agriculture, Beijing, 102206, China
| | - Liuxue Li
- Beijing Key Laboratory of Dairy Cow Nutrition, Animal Science and Technology College, Beijing University of Agriculture, Beijing, 102206, China
| | - Huiying Zhao
- Beijing Key Laboratory of Dairy Cow Nutrition, Animal Science and Technology College, Beijing University of Agriculture, Beijing, 102206, China
| | - Yuqin Li
- Beijing Key Laboratory of Dairy Cow Nutrition, Animal Science and Technology College, Beijing University of Agriculture, Beijing, 102206, China
| | - Linshu Jiang
- Beijing Key Laboratory of Dairy Cow Nutrition, Animal Science and Technology College, Beijing University of Agriculture, Beijing, 102206, China
| | - Ming Liu
- Beijing Key Laboratory of Dairy Cow Nutrition, Animal Science and Technology College, Beijing University of Agriculture, Beijing, 102206, China
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15
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Ticinesi A, Nouvenne A, Cerundolo N, Parise A, Meschi T. Accounting Gut Microbiota as the Mediator of Beneficial Effects of Dietary (Poly)phenols on Skeletal Muscle in Aging. Nutrients 2023; 15:nu15102367. [PMID: 37242251 DOI: 10.3390/nu15102367] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 05/14/2023] [Accepted: 05/16/2023] [Indexed: 05/28/2023] Open
Abstract
Sarcopenia, the age-related loss of muscle mass and function increasing the risk of disability and adverse outcomes in older people, is substantially influenced by dietary habits. Several studies from animal models of aging and muscle wasting indicate that the intake of specific polyphenol compounds can be associated with myoprotective effects, and improvements in muscle strength and performance. Such findings have also been confirmed in a smaller number of human studies. However, in the gut lumen, dietary polyphenols undergo extensive biotransformation by gut microbiota into a wide range of bioactive compounds, which substantially contribute to bioactivity on skeletal muscle. Thus, the beneficial effects of polyphenols may consistently vary across individuals, depending on the composition and metabolic functionality of gut bacterial communities. The understanding of such variability has recently been improved. For example, resveratrol and urolithin interaction with the microbiota can produce different biological effects according to the microbiota metabotype. In older individuals, the gut microbiota is frequently characterized by dysbiosis, overrepresentation of opportunistic pathogens, and increased inter-individual variability, which may contribute to increasing the variability of biological actions of phenolic compounds at the skeletal muscle level. These interactions should be taken into great consideration for designing effective nutritional strategies to counteract sarcopenia.
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Affiliation(s)
- Andrea Ticinesi
- Department of Medicine and Surgery, University of Parma, Via Antonio Gramsci 14, 43126 Parma, Italy
- Microbiome Research Hub, University of Parma, Parco Area delle Scienze 11/1, 43124 Parma, Italy
- Geriatric-Rehabilitation Department, Azienda Ospedaliero-Universitaria di Parma, Via Antonio Gramsci 14, 43126 Parma, Italy
| | - Antonio Nouvenne
- Microbiome Research Hub, University of Parma, Parco Area delle Scienze 11/1, 43124 Parma, Italy
- Geriatric-Rehabilitation Department, Azienda Ospedaliero-Universitaria di Parma, Via Antonio Gramsci 14, 43126 Parma, Italy
| | - Nicoletta Cerundolo
- Geriatric-Rehabilitation Department, Azienda Ospedaliero-Universitaria di Parma, Via Antonio Gramsci 14, 43126 Parma, Italy
| | - Alberto Parise
- Geriatric-Rehabilitation Department, Azienda Ospedaliero-Universitaria di Parma, Via Antonio Gramsci 14, 43126 Parma, Italy
| | - Tiziana Meschi
- Department of Medicine and Surgery, University of Parma, Via Antonio Gramsci 14, 43126 Parma, Italy
- Microbiome Research Hub, University of Parma, Parco Area delle Scienze 11/1, 43124 Parma, Italy
- Geriatric-Rehabilitation Department, Azienda Ospedaliero-Universitaria di Parma, Via Antonio Gramsci 14, 43126 Parma, Italy
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16
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Guo Y, Liu Z, Wan Y, Zhang Y, Abdu HI, Yang M, Pei J, Yue T, Zhang X, Hacimuftuoglu A, Abd El-Aty AM. Literature analysis on asparagus roots and review of its functional characterizations. Front Nutr 2023; 9:1024190. [PMID: 37139102 PMCID: PMC10149932 DOI: 10.3389/fnut.2022.1024190] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Accepted: 12/05/2022] [Indexed: 05/05/2023] Open
Abstract
Asparagus root (AR) is utilized globally as a traditional herbal medicine because it contains various bioactive compounds, such as polyphenols, flavonoids, saponins, and minerals. The composition profiles of AR are strongly affected by its botanical and geographical origins. Although minerals and heavy metals are minor constituents of AR, they play a crucial role in determining its quality and efficacy. A comprehensive classification of AR, its phytochemistry, and its pharmacology were reviewed and interpreted herein. Potentially eligible articles (in English) were identified through an electronic search of the Web of Science database (2010-2022) and Google (2001-2022). We used the primary search term "Asparagus roots" combined with the words "pharmacology," "bioactive compounds," "physicochemical properties," and "health benefits" to find the relevant literature. We screened the titles, keywords, and abstracts of the publications obtained from the database. A full copy of the article was obtained for further assessment if deemed appropriate. Different asparagus species might potentially be used as herbal medicines and functional foods. Phytochemical studies have revealed the presence of various bioactive compounds as valuable secondary metabolites. The dominant class of bioactive compounds in AR is flavonoids. Furthermore, AR displayed significant pharmacological effects, such as antioxidant, antimicrobial, antiviral, anticancer, anti-inflammatory, and antidiabetic effects, as shown in animal and human studies. This review provides a valuable resource to enable a thorough assessment of the profile of Asparagus root as a functional ingredient for the pharmaceutical and food industries. In addition, it is anticipated that this review will provide information to healthcare professionals seeking alternative sources of critical bioactive compounds.
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Affiliation(s)
- Yaodong Guo
- College of Health Management, Shangluo University, Shangluo, Shaanxi, China
| | - Zhe Liu
- Shaanxi Key Laboratory of Bioresources, 2011 QinLing-Bashan Mountains Bioresources Comprehensive Development C. I. C., Qinba State Key Laboratory of Biological Resources and Ecological Environment, College of Bioscience and Bioengineering, Shaanxi University of Technology, Hanzhong, Shaanxi, China
| | - Yingjie Wan
- Shaanxi Key Laboratory of Bioresources, 2011 QinLing-Bashan Mountains Bioresources Comprehensive Development C. I. C., Qinba State Key Laboratory of Biological Resources and Ecological Environment, College of Bioscience and Bioengineering, Shaanxi University of Technology, Hanzhong, Shaanxi, China
| | - Yanyan Zhang
- Shaanxi Key Laboratory of Bioresources, 2011 QinLing-Bashan Mountains Bioresources Comprehensive Development C. I. C., Qinba State Key Laboratory of Biological Resources and Ecological Environment, College of Bioscience and Bioengineering, Shaanxi University of Technology, Hanzhong, Shaanxi, China
| | - Hassan Idris Abdu
- College of Health Management, Shangluo University, Shangluo, Shaanxi, China
- Shaanxi Key Laboratory of Bioresources, 2011 QinLing-Bashan Mountains Bioresources Comprehensive Development C. I. C., Qinba State Key Laboratory of Biological Resources and Ecological Environment, College of Bioscience and Bioengineering, Shaanxi University of Technology, Hanzhong, Shaanxi, China
| | - Meng Yang
- College of Society and Science, Tibet Cultural University, Xianyang, China
| | - Jinjin Pei
- Shaanxi Key Laboratory of Bioresources, 2011 QinLing-Bashan Mountains Bioresources Comprehensive Development C. I. C., Qinba State Key Laboratory of Biological Resources and Ecological Environment, College of Bioscience and Bioengineering, Shaanxi University of Technology, Hanzhong, Shaanxi, China
| | - Tianli Yue
- College of Food Science and Technology, Northwest University, Xi’an, Shaanxi, China
| | - Xianbin Zhang
- Department of General Surgery, Institute of Precision Diagnosis, Treatment of Digestive System Tumors, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong, China
| | - Ahmet Hacimuftuoglu
- Department of Medical Pharmacology, Faculty of Medicine, Atatürk University, Erzurum, Türkiye
| | - A. M. Abd El-Aty
- Department of Medical Pharmacology, Faculty of Medicine, Atatürk University, Erzurum, Türkiye
- State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences, Jinan, China
- Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
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17
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Gentile MT, Camerino I, Ciarmiello L, Woodrow P, Muscariello L, De Chiara I, Pacifico S. Neuro-Nutraceutical Polyphenols: How Far Are We? Antioxidants (Basel) 2023; 12:antiox12030539. [PMID: 36978787 PMCID: PMC10044769 DOI: 10.3390/antiox12030539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 02/09/2023] [Accepted: 02/17/2023] [Indexed: 02/25/2023] Open
Abstract
The brain, composed of billions of neurons, is a complex network of interacting dynamical systems controlling all body functions. Neurons are the building blocks of the nervous system and their impairment of their functions could result in neurodegenerative disorders. Accumulating evidence shows an increase of brain-affecting disorders, still today characterized by poor therapeutic options. There is a strong urgency to find new alternative strategies to prevent progressive neuronal loss. Polyphenols, a wide family of plant compounds with an equally wide range of biological activities, are suitable candidates to counteract chronic degenerative disease in the central nervous system. Herein, we will review their role in human healthcare and highlight their: antioxidant activities in reactive oxygen species-producing neurodegenerative pathologies; putative role as anti-acetylcholinesterase inhibitors; and protective activity in Alzheimer’s disease by preventing Aβ aggregation and tau hyperphosphorylation. Moreover, the pathology of these multifactorial diseases is also characterized by metal dyshomeostasis, specifically copper (Cu), zinc (Zn), and iron (Fe), most important for cellular function. In this scenario, polyphenols’ action as natural chelators is also discussed. Furthermore, the critical importance of the role exerted by polyphenols on microbiota is assumed, since there is a growing body of evidence for the role of the intestinal microbiota in the gut–brain axis, giving new opportunities to study molecular mechanisms and to find novel strategies in neurological diseases.
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18
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Hu H, Lan K, Liu H. Human symbiont Bacteroides xylanisolvens attenuates NASH through intestinal nicotine catabolism. Chin J Nat Med 2023; 21:81-82. [PMID: 36871984 DOI: 10.1016/s1875-5364(23)60387-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Indexed: 03/07/2023]
Affiliation(s)
- Haiming Hu
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China
| | - Ke Lan
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China
| | - Hongtao Liu
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China.
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19
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Zhang Y, Cheng L, Liu Y, Zhan S, Wu Z, Luo S, Zhang X. Dietary flavonoids: a novel strategy for the amelioration of cognitive impairment through intestinal microbiota. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2023; 103:488-495. [PMID: 35892267 DOI: 10.1002/jsfa.12151] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 07/23/2022] [Accepted: 07/27/2022] [Indexed: 06/15/2023]
Abstract
The chances of people suffering from cognitive impairments increase gradually with age. Diet and lifestyle are closely related to the occurrence and development of cognitive function. Dietary flavonoid supplementation has been shown to be one of the protective factors against cognitive decline. Flavonoids belong to a class of polyphenols that have been proposed for the treatment of cognitive decline. Recent evidence has shown that intestinal flora in the human body can interact with flavonoids. Intestinal microbiota can modify the chemical structure of flavonoids, producing new metabolites, the pharmacological activities of which may be different from those of the parent; meanwhile, flavonoids and their metabolites can, in turn, regulate the composition and structure of intestinal flora. Notably, intestinal flora affect host nervous system activity through the gut-brain axis, ultimately causing changes in cognitive function. This review therefore summarizes the interaction of dietary flavonoids and intestinal flora, and their protective effect against cognitive decline through the gut-brain axis, indicating that dietary flavonoids may ameliorate cognitive impairment through their interaction with intestinal microbiota. © 2022 Society of Chemical Industry.
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Affiliation(s)
- Yuting Zhang
- Department of Food Science and Engineering, Ningbo University, Ningbo, People's Republic of China
| | - Lu Cheng
- Department of Food Science, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
| | - Yanan Liu
- Department of Food Science and Engineering, Ningbo University, Ningbo, People's Republic of China
| | - Shengnan Zhan
- Department of Food Science and Engineering, Ningbo University, Ningbo, People's Republic of China
| | - Zufang Wu
- Department of Food Science and Engineering, Ningbo University, Ningbo, People's Republic of China
| | - Songmei Luo
- Department of Pharmacy, Lishui Central Hospital, Lishui, People's Republic of China
| | - Xin Zhang
- Department of Food Science and Engineering, Ningbo University, Ningbo, People's Republic of China
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20
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Polyphenols as Drivers of a Homeostatic Gut Microecology and Immuno-Metabolic Traits of Akkermansia muciniphila: From Mouse to Man. Int J Mol Sci 2022; 24:ijms24010045. [PMID: 36613488 PMCID: PMC9820369 DOI: 10.3390/ijms24010045] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 12/12/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022] Open
Abstract
Akkermansia muciniphila is a mucosal symbiont considered a gut microbial marker in healthy individuals, as its relative abundance is significantly reduced in subjects with gut inflammation and metabolic disturbances. Dietary polyphenols can distinctly stimulate the relative abundance of A. muciniphila, contributing to the attenuation of several diseases, including obesity, type 2 diabetes, inflammatory bowel diseases, and liver damage. However, mechanistic insight into how polyphenols stimulate A. muciniphila or its activity is limited. This review focuses on dietary interventions in rodents and humans and in vitro studies using different phenolic classes. We provide critical insights with respect to potential mechanisms explaining the effects of polyphenols affecting A. muciniphila. Anthocyanins, flavan-3-ols, flavonols, flavanones, stilbenes, and phenolic acids are shown to increase relative A. muciniphila levels in vivo, whereas lignans exert the opposite effect. Clinical trials show consistent findings, and high intervariability relying on the gut microbiota composition at the baseline and the presence of multiple polyphenol degraders appear to be cardinal determinants in inducing A. muciniphila and associated benefits by polyphenol intake. Polyphenols signal to the AhR receptor and impact the relative abundance of A. muciniphila in a direct and indirect fashion, resulting in the restoration of intestinal epithelial integrity and homeostatic crosstalk with the gut microbiota by affecting IL-22 production. Moreover, recent evidence suggests that A. muciniphila participates in the initial hydrolysis of some polyphenols but does not participate in their complete metabolism. In conclusion, the consumption of polyphenol-rich foods targeting A. muciniphila as a pivotal intermediary represents a promising precision nutritional therapy to prevent and attenuate metabolic and inflammatory diseases.
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21
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Ding S, Wang P, Pang X, Zhang L, Qian L, Jia X, Chen W, Ruan S, Sun L. The new exploration of pure total flavonoids extracted from Citrus maxima (Burm.) Merr. as a new therapeutic agent to bring health benefits for people. Front Nutr 2022; 9:958329. [PMID: 36276813 PMCID: PMC9582534 DOI: 10.3389/fnut.2022.958329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 08/25/2022] [Indexed: 11/13/2022] Open
Abstract
The peel and fruit of Citrus varieties have been a raw material for some traditional Chinese medicine (TCM). Pure total flavonoids from Citrus maxima (Burm.) Merr. (PTFC), including naringin, hesperidin, narirutin, and neohesperidin, have been attracted increasing attention for their multiple clinical efficacies. Based on existing in vitro and in vivo research, this study systematically reviewed the biological functions of PTFC and its components in preventing or treating liver metabolic diseases, cardiovascular diseases, intestinal barrier dysfunction, as well as malignancies. PTFC and its components are capable of regulating glycolipid metabolism, blocking peroxidation and persistent inflammation, inhibiting tumor progression, protecting the integrity of intestinal barrier and positively regulating intestinal microbiota, while the differences in fruit cultivation system, picking standard, manufacturing methods, delivery system and individual intestinal microecology will have impact on the specific therapeutic effect. Thus, PTFC is a promising drug for the treatment of some chronic diseases, as well as continuous elaborate investigations are necessary to improve its effectiveness and bioavailability.
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Affiliation(s)
- Shuning Ding
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Peipei Wang
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xi Pang
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Leyin Zhang
- Department of Medical Oncology, Hangzhou TCM Hospital of Zhejiang Chinese Medical University (Hangzhou Hospital of Traditional Chinese Medicine), Hangzhou, China
| | - Lihui Qian
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xinru Jia
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Wenqian Chen
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Shanming Ruan
- Department of Medical Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
| | - Leitao Sun
- Department of Medical Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
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22
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Candeliere F, Simone M, Leonardi A, Rossi M, Amaretti A, Raimondi S. Indole and p-cresol in feces of healthy subjects: Concentration, kinetics, and correlation with microbiome. FRONTIERS IN MOLECULAR MEDICINE 2022; 2:959189. [PMID: 39086966 PMCID: PMC11285674 DOI: 10.3389/fmmed.2022.959189] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 09/02/2022] [Indexed: 08/02/2024]
Abstract
Indole and p-cresol are precursors of the most important uremic toxins, generated from the fermentation of amino acids tryptophan and tyrosine by the proteolytic community of intestinal bacteria. The present study focused on the relationship between the microbiome composition, the fecal levels of indole and p-cresol, and their kinetics of generation/degradation in fecal cultures. The concentration of indole and p-cresol, the volatilome, the dry weight, and the amount of ammonium and carbohydrates were analyzed in the feces of 10 healthy adults. Indole and p-cresol widely differed among samples, laying in the range of 1.0-19.5 μg/g and 1.2-173.4 μg/g, respectively. Higher fecal levels of indole and p-cresol were associated with lower carbohydrates and higher ammonium levels, that are markers of a more pronounced intestinal proteolytic metabolism. Positive relationship was observed also with the dry/wet weight ratio, indicator of prolonged intestinal retention of feces. p-cresol and indole presented a statistically significant negative correlation with OTUs of uncultured Bacteroidetes and Firmicutes, the former belonging to Bacteroides and the latter to the families Butyricicoccaceae (genus Butyricicoccus), Monoglobaceae (genus Monoglobus), Lachnospiraceae (genera Faecalibacterium, Roseburia, and Eubacterium ventriosum group). The kinetics of formation and/or degradation of indole and p-cresol was investigated in fecal slurries, supplemented with the precursor amino acids tryptophan and tyrosine in strict anaerobiosis. The presence of the precursors bursted indole production but had a lower effect on the rate of p-cresol formation. On the other hand, supplementation with indole reduced the net rate of formation. The taxa that positively correlated with fecal levels of uremic toxins presented a positive correlation also with p-cresol generation rate in biotransformation experiments. Moreover other bacterial groups were positively correlated with generation rate of p-cresol and indole, further expanding the range of taxa associated to production of p-cresol (Bacteroides, Alistipes, Eubacterium xylanophylum, and Barnesiella) and indole (e.g., Bacteroides, Ruminococcus torques, Balutia, Dialister, Butyricicoccus). The information herein presented contributes to disclose the relationships between microbiota composition and the production of uremic toxins, that could provide the basis for probiotic intervention on the gut microbiota, aimed to prevent the onset, hamper the progression, and alleviate the impact of nephropaties.
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Affiliation(s)
- Francesco Candeliere
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Marta Simone
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Alan Leonardi
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Maddalena Rossi
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
- Biogest Siteia, University of Modena and Reggio Emilia, Reggio Emilia, Italy
| | - Alberto Amaretti
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
- Biogest Siteia, University of Modena and Reggio Emilia, Reggio Emilia, Italy
| | - Stefano Raimondi
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
- Biogest Siteia, University of Modena and Reggio Emilia, Reggio Emilia, Italy
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23
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Huang LL, Tang Y, Xie GZ, Tan ZJ. Progress in research of glycoside hydrolases in the intestine. Shijie Huaren Xiaohua Zazhi 2022; 30:555-561. [DOI: 10.11569/wcjd.v30.i13.555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Glycoside hydrolases are a class of enzymes that hydrolyze glycosides and play an important role in the metabolic transformation of glycosides in the intestine, but the number of glycoside hydrolases encoded and expressed in the body is limited, and most glycoside hydrolases are produced from intestinal bacteria genes. Gut microbiota and the secreted glycoside hydrolases participate in the deglycosylation of glycosides and improve their bioavailability. In this paper, we review the definition and types of glucoside hydrolases, their sources from the gut microbiota, and transformation of glycosides by the gut microbiota. We also discuss the relationship between the gut microbiota, glucoside hydrolases, and glucoside deglycosylation transformation products, with an aim to provide a reference for efficient production of enzymes and glycoside conversion products, and mining of new drug resources.
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Affiliation(s)
- Li-Li Huang
- Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Yuan Tang
- Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Guo-Zhen Xie
- Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Zhou-Jin Tan
- Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
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24
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Wdowiak K, Walkowiak J, Pietrzak R, Bazan-Woźniak A, Cielecka-Piontek J. Bioavailability of Hesperidin and Its Aglycone Hesperetin—Compounds Found in Citrus Fruits as a Parameter Conditioning the Pro-Health Potential (Neuroprotective and Antidiabetic Activity)—Mini-Review. Nutrients 2022; 14:nu14132647. [PMID: 35807828 PMCID: PMC9268531 DOI: 10.3390/nu14132647] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 06/23/2022] [Accepted: 06/24/2022] [Indexed: 12/19/2022] Open
Abstract
Hesperidin and hesperetin are polyphenols that can be found predominantly in citrus fruits. They possess a variety of pharmacological properties such as neuroprotective and antidiabetic activity. However, the bioavailability of these compounds is limited due to low solubility and restricts their use as pro-healthy agents. This paper described the limitations resulting from the low bioavailability of the presented compounds and gathered the methods aiming at its improvement. Moreover, this work reviewed studies providing pieces of evidence for neuroprotective and antidiabetic properties of hesperidin and hesperetin as well as providing a detailed look into the significance of reported modes of action in chronic diseases. On account of a well-documented pro-healthy activity, it is important to look for ways to overcome the problem of poor bioavailability.
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Affiliation(s)
- Kamil Wdowiak
- Department of Pharmacognosy, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland;
| | - Jarosław Walkowiak
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland;
| | - Robert Pietrzak
- Faculty of Chemistry, Adam Mickiewicz University in Poznań, Uniwersytetu Poznańskiego 8, 61-614 Poznań, Poland; (R.P.); (A.B.-W.)
| | - Aleksandra Bazan-Woźniak
- Faculty of Chemistry, Adam Mickiewicz University in Poznań, Uniwersytetu Poznańskiego 8, 61-614 Poznań, Poland; (R.P.); (A.B.-W.)
| | - Judyta Cielecka-Piontek
- Department of Pharmacognosy, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland;
- Correspondence:
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25
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Hesperidin Bioavailability Is Increased by the Presence of 2S-Diastereoisomer and Micronization-A Randomized, Crossover and Double-Blind Clinical Trial. Nutrients 2022; 14:nu14122481. [PMID: 35745211 PMCID: PMC9231284 DOI: 10.3390/nu14122481] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 06/07/2022] [Accepted: 06/09/2022] [Indexed: 12/13/2022] Open
Abstract
Hesperidin is a flavanone abundantly found in citrus fruits for which health beneficial effects have been reported. However, hesperidin shows a low bioavailability among individuals. The aim of this study was to evaluate the effects of the micronization process and 2R- and 2S-hesperidin diastereoisomers ratio on hesperidin bioavailability. In a first phase, thirty healthy individuals consumed 500 mL of orange juice with 345 mg of hesperidin, and the levels of hesperidin metabolites excreted in urine were determined. In the second phase, fifteen individuals with intermediate hesperidin metabolite levels excreted in urine were randomized in a crossover, postprandial and double-blind intervention study. Participants consumed 500 mg of the hesperidin-supplemented Hesperidin epimeric mixture (HEM), the micronized Hesperidin epimeric mixture (MHEM) and micronized 2S-Hesperidin (M2SH) in each study visit with 1 week of washout. Hesperidin metabolites and catabolites were determined in blood and urine obtained at different timepoints over a 24 h period. The bioavailability—relative urinary hesperidin excretion (% of hesperidin ingested)—of M2SH (70 ± 14%) formed mainly by 2S-diastereoisomer was significantly higher than the bioavailability of the MHEM (55 ± 15%) and HEM (43 ± 8.0%), which consisted of a mixture of both hesperidin diastereoisomers. Relative urinary excretion of hesperidin metabolites for MHEM (9.2 ± 1.6%) was significantly higher compared to the HEM (5.2 ± 0.81%) and M2SH (3.6 ± 1.0%). In conclusion, the bioavailability of 2S-hesperidin extract was higher compared to the standard mixture of 2S-/2R-hesperidin extract due to a greater formation of hesperidin catabolites. Furthermore, the micronization process increased hesperidin bioavailability.
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26
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Moreno-Ortega A, Di Pede G, Pereira-Caro G, Calani L, Mena P, Del Rio D, Moreno-Rojas JM. In Vitro Colonic Fermentation of (Poly)phenols and Organosulfur Compounds of Fresh and Black Garlic. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:3666-3677. [PMID: 35293213 DOI: 10.1021/acs.jafc.1c08081] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
The beneficial properties associated with garlic consumption have been related to the presence of bioactive compounds including (poly)phenols and organosulfur compounds (OSCs). This study aims to assess the effect of in vitro colonic fermentation on fresh and black garlic by determining the transformation of these compounds through ultrahigh-performance liquid chromatography coupled to mass spectrometry with a linear ion trap (uHPLC-LIT-MS). Colonic fermentation had a similar influence on the phenolic content of fresh and black garlic, with total respective decreases of 43.8% and 41.7%. Meanwhile, fermentation resulted in a significant decrease (33%) in OSCs in black garlic. Compounds such as 4-hydroxybenzoic acid, S-allylcysteine (SAC), and methionine sulfoxide were the phenolic compounds and OSCs with the highest concentration in fresh and black garlic after the in vitro fermentation. These compounds, potentially present at the colonic level, might be responsible for the systemic health benefits associated with the consumption of black and fresh garlic.
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Affiliation(s)
- Alicia Moreno-Ortega
- Departamento de Bromatología y Tecnología de los Alimentos, Campus Rabanales, Ed, Darwin-anexo Universidad de Córdoba, 14071 Córdoba, Spain
- Foods for Health Group, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), 14004 Córdoba, Spain
| | - Giuseppe Di Pede
- Human Nutrition Unit, Department of Food and Drugs, University of Parma, 43125 Parma, Italy
| | - Gema Pereira-Caro
- Foods for Health Group, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), 14004 Córdoba, Spain
- Department of Food Science and Health, Andalusian Institute of Agricultural and Fisheries Research and Training (IFAPA), Alameda del Obispo, Avda. Menéndez-Pidal, 14004 Córdoba, Spain
| | - Luca Calani
- Human Nutrition Unit, Department of Food and Drugs, University of Parma, 43125 Parma, Italy
| | - Pedro Mena
- Human Nutrition Unit, Department of Food and Drugs, University of Parma, 43125 Parma, Italy
- Microbiome Research Hub, University of Parma, 43124 Parma, Italy
| | - Daniele Del Rio
- Human Nutrition Unit, Department of Food and Drugs, University of Parma, 43125 Parma, Italy
- Microbiome Research Hub, University of Parma, 43124 Parma, Italy
| | - José Manuel Moreno-Rojas
- Foods for Health Group, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), 14004 Córdoba, Spain
- Department of Food Science and Health, Andalusian Institute of Agricultural and Fisheries Research and Training (IFAPA), Alameda del Obispo, Avda. Menéndez-Pidal, 14004 Córdoba, Spain
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27
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Davinelli S, Scapagnini G. Interactions between dietary polyphenols and aging gut microbiota: A review. Biofactors 2022; 48:274-284. [PMID: 34559427 DOI: 10.1002/biof.1785] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Accepted: 08/26/2021] [Indexed: 12/14/2022]
Abstract
Aging induces significant shifts in the composition of gut microbiota associated with decreased microbial diversity. Age-related changes in gut microbiota include a loss of commensals and an increase in disease-associated pathobionts. These alterations are accelerated by lifestyle factors, such as poor nutritional habits, physical inactivity, and medications. Given that diet is one of the main drivers shaping the gut microbiota, nutritional interventions for restoring gut homeostasis are of great importance to the overall health of older adults. Polyphenols, ubiquitously present in fruits and vegetables, have emerged as promising anti-aging candidates because of their ability to modulate some of the common denominators of aging, including gut dysbiosis. These compounds can influence the composition of the gut microbiota, and gut bacteria metabolize polyphenols into bioactive compounds that produce relevant health effects. Although the role of polyphenols on the aging gut has not been fully characterized, accumulating evidence suggests that these compounds exert selective effects on the gut microbial community. Here, we discuss the reciprocal interactions between polyphenols and gut microbiota and summarize the latest findings on the effects of polyphenols on modulating intestinal bacteria during aging.
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Affiliation(s)
- Sergio Davinelli
- Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Campobasso, Italy
| | - Giovanni Scapagnini
- Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Campobasso, Italy
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28
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Wang L, Gao M, Kang G, Huang H. The Potential Role of Phytonutrients Flavonoids Influencing Gut Microbiota in the Prophylaxis and Treatment of Inflammatory Bowel Disease. Front Nutr 2021; 8:798038. [PMID: 34970585 PMCID: PMC8713745 DOI: 10.3389/fnut.2021.798038] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 11/25/2021] [Indexed: 12/19/2022] Open
Abstract
Inflammatory bowel disease (IBD), characterized by the chronic inflammation of the gastrointestinal tract, is comprised of two idiopathic chronic intestinal inflammatory diseases. As the incidence of IBD increases, so does the need for safe and effective treatments. Trillions of microorganisms are colonized in the mammalian intestine, coevolve with the host in a symbiotic relationship. Gut microbiota has been reported to be involved in the pathophysiology of IBD. In this regard, phytonutrients flavonoids have received increasing attention for their anti-oxidant and anti-inflammatory activities. In this review, we address recent advances in the interactions among flavonoids, gut microbiota, and IBD. Moreover, their possible potential mechanisms of action in IBD have been discussed. We conclude that there is a complex interaction between flavonoids and gut microbiota. It is expected that flavonoids can change or reshape the gut microbiota to provide important considerations for developing treatments for IBD.
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Affiliation(s)
- Lina Wang
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China
- Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering, Ministry of Education, Tianjin University, Tianjin, China
| | - Mengxue Gao
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China
- Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering, Ministry of Education, Tianjin University, Tianjin, China
| | - Guangbo Kang
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China
- Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering, Ministry of Education, Tianjin University, Tianjin, China
| | - He Huang
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China
- Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering, Ministry of Education, Tianjin University, Tianjin, China
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29
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Sheik Abdul N, Marnewick JL. Rooibos, a supportive role to play during the COVID-19 pandemic? J Funct Foods 2021; 86:104684. [PMID: 34422116 PMCID: PMC8367744 DOI: 10.1016/j.jff.2021.104684] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 07/21/2021] [Accepted: 08/14/2021] [Indexed: 02/08/2023] Open
Abstract
This article presents the potential health benefits of Rooibos to be considered a support during the COVID-19 pandemic. The recent pandemic of COVID-19 has led to severe morbidity and mortality. The highly infectious SARS-CoV-2 is known to prime a cytokine storm in patients and progression to acute lung injury/acute respiratory distress syndrome. Based on clinical features, the pathology of acute respiratory disorder induced by SARS-CoV-2 suggests that excessive inflammation, oxidative stress, and dysregulation of the renin angiotensin system are likely contributors to the COVID-19 disease. Rooibos, a well-known herbal tea, consumed for centuries, has displayed potent anti-inflammatory, antioxidant, redox modulating, anti-diabetic, anti-cancer, cardiometabolic support and organoprotective potential. This article describes how Rooibos can potentially play a supportive role by modulating the risk of some of the comorbidities associated with COVID-19 in order to promote general health during infections.
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Affiliation(s)
- Naeem Sheik Abdul
- Applied Microbial and Health Biotechnology Institute, Cape Peninsula University of Technology, South Africa
| | - Jeanine L Marnewick
- Applied Microbial and Health Biotechnology Institute, Cape Peninsula University of Technology, South Africa
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30
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Agrawal PK, Agrawal C, Blunden G. Pharmacological Significance of Hesperidin and Hesperetin, Two Citrus Flavonoids, as Promising Antiviral Compounds for Prophylaxis Against and Combating COVID-19. Nat Prod Commun 2021. [DOI: 10.1177/1934578x211042540] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Hesperidin and hesperetin are flavonoids that are abundantly present as constituents of citrus fruits. These compounds have attracted attention as several computational methods, mostly docking studies, have shown that hesperidin may bind to multiple regions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (spike protein, angiotensin-converting enzyme 2, and proteases). Hesperidin has a low binding energy, both with the SARS-CoV-2 “spike” protein responsible for internalization, and also with the “PLpro” and “Mpro” responsible for transforming the early proteins of the virus into the complex responsible for viral replication. This suggests that these flavonoids could act as prophylactic agents by blocking several mechanisms of viral infection and replication, and thus helping the host cell to resist viral attack.
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Affiliation(s)
| | | | - Gerald Blunden
- School of Pharmacy & Biomedical Sciences, University of Portsmouth, Portsmouth, UK
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31
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Jing-Wei Z, Yi-Yuan S, Xin L, Hua Z, Hui N, Luo-Yun F, Ben-Hai X, Jin-Jin T, Lin-Shu J. Microbiome and Metabolic Changes of Milk in Response to Dietary Supplementation With Bamboo Leaf Extract in Dairy Cows. Front Nutr 2021; 8:723446. [PMID: 34595199 PMCID: PMC8476867 DOI: 10.3389/fnut.2021.723446] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 07/29/2021] [Indexed: 01/11/2023] Open
Abstract
Bamboo leaf extracts, with high content of flavonoids and diverse biological activities, are used in animal husbandry. Increasing evidence has suggested an association between the bovine physiology and the udder microbiome, yet whether the microbiota and the metabolites of milk affect the mammary gland health or the milk quality remains unknown. In this study, we provide a potential mechanism for the effects of bamboo leaf extracts on milk microbiota and metabolites of dairy cows. Twelve multiparous lactating Chinese Holstein dairy cows were randomly separated into two groups: basal diet as the control group (CON, n = 6) and a diet supplemented with 30 g/d bamboo leaf extract per head as antioxidants of bamboo leaf (AOB) group (AOB, n = 6) for 7 weeks (2-week adaptation, 5-week treatment). Milk samples were collected at the end of the trial (week 7) for microbiome and associated metabolic analysis by 16S ribosomal RNA (rRNA) gene sequencing and liquid chromatography-mass spectrometry (LC-MS). The results showed that the milk protein was increased (p < 0.0001) and somatic cell count (SCC) showed a tendency to decrease (p = 0.09) with AOB supplementation. The relative abundance of Firmicutes was significantly decreased (p = 0.04) while a higher relative abundance of Probacteria (p = 0.01) was seen in the group receiving AOB compared to the CON group. The AOB group had a significantly lower relative abundance of Corynebacterium_1 (p = 0.01), Aerococcus (p = 0.01), and Staphylococcus (p = 0.02). There were 64 different types of metabolites significantly upregulated, namely, glycerophospholipids and fatty acyls, and 15 significantly downregulated metabolites, such as moracetin, sphinganine, and lactulose in the AOB group. Metabolic pathway analysis of the different metabolites revealed that the sphingolipid signaling pathway was significantly enriched, together with glycerophospholipid metabolism, sphingolipid metabolism, and necroptosis in response to AOB supplementation. Several typical metabolites were highly correlated with specific ruminal bacteria, demonstrating a functional correlation between the milk microbiome and the associated metabolites. These insights into the complex mechanism and corresponding biological responses highlight the potential function of AOB, warranting further investigation into the regulatory role of specific pathways in the metabolism.
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Affiliation(s)
- Zhan Jing-Wei
- Beijing Key Laboratory for Dairy Cow Nutrition, Beijing University of Agriculture, Beijing, China
| | - Shen Yi-Yuan
- Beijing Key Laboratory for Dairy Cow Nutrition, Beijing University of Agriculture, Beijing, China
| | - Li Xin
- Beijing Key Laboratory for Dairy Cow Nutrition, Beijing University of Agriculture, Beijing, China
| | - Zhang Hua
- Beijing Key Laboratory for Dairy Cow Nutrition, Beijing University of Agriculture, Beijing, China
| | - Niu Hui
- Beijing Key Laboratory for Dairy Cow Nutrition, Beijing University of Agriculture, Beijing, China
| | - Fang Luo-Yun
- Beijing Key Laboratory for Dairy Cow Nutrition, Beijing University of Agriculture, Beijing, China
| | - Xiong Ben-Hai
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Tong Jin-Jin
- Beijing Key Laboratory for Dairy Cow Nutrition, Beijing University of Agriculture, Beijing, China
| | - Jiang Lin-Shu
- Beijing Key Laboratory for Dairy Cow Nutrition, Beijing University of Agriculture, Beijing, China
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32
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Screening of Human Gut Bacterial Culture Collection Identifies Species That Biotransform Quercetin into Metabolites with Anticancer Properties. Int J Mol Sci 2021; 22:ijms22137045. [PMID: 34208885 PMCID: PMC8269047 DOI: 10.3390/ijms22137045] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 06/23/2021] [Accepted: 06/25/2021] [Indexed: 12/19/2022] Open
Abstract
We previously demonstrated that flavonoid metabolites inhibit cancer cell proliferation through both CDK-dependent and -independent mechanisms. The existing evidence suggests that gut microbiota is capable of flavonoid biotransformation to generate bioactive metabolites including 2,4,6-trihydroxybenzoic acid (2,4,6-THBA), 3,4-dihydroxybenzoic acid (3,4-DHBA), 3,4,5-trihyroxybenzoic acid (3,4,5-THBA) and 3,4-dihydroxyphenylacetic acid (DOPAC). In this study, we screened 94 human gut bacterial species for their ability to biotransform flavonoid quercetin into different metabolites. We demonstrated that five of these species were able to degrade quercetin including Bacillus glycinifermentans, Flavonifractor plautii, Bacteroides eggerthii, Olsenella scatoligenes and Eubacterium eligens. Additional studies showed that B. glycinifermentans could generate 2,4,6-THBA and 3,4-DHBA from quercetin while F. plautii generates DOPAC. In addition to the differences in the metabolites produced, we also observed that the kinetics of quercetin degradation was different between B. glycinifermentans and F. plautii, suggesting that the pathways of degradation are likely different between these strains. Similar to the antiproliferative effects of 2,4,6-THBA and 3,4-DHBA demonstrated previously, DOPAC also inhibited colony formation ex vivo in the HCT-116 colon cancer cell line. Consistent with this, the bacterial culture supernatant of F. plautii also inhibited colony formation in this cell line. Thus, as F. plautii and B. glycinifermentans generate metabolites possessing antiproliferative activity, we suggest that these strains have the potential to be developed into probiotics to improve human gut health.
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33
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Rodríguez-Daza MC, Pulido-Mateos EC, Lupien-Meilleur J, Guyonnet D, Desjardins Y, Roy D. Polyphenol-Mediated Gut Microbiota Modulation: Toward Prebiotics and Further. Front Nutr 2021; 8:689456. [PMID: 34268328 PMCID: PMC8276758 DOI: 10.3389/fnut.2021.689456] [Citation(s) in RCA: 197] [Impact Index Per Article: 49.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 05/27/2021] [Indexed: 12/11/2022] Open
Abstract
The genome of gut microbes encodes a collection of enzymes whose metabolic functions contribute to the bioavailability and bioactivity of unabsorbed (poly)phenols. Datasets from high throughput sequencing, metabolome measurements, and other omics have expanded the understanding of the different modes of actions by which (poly)phenols modulate the microbiome conferring health benefits to the host. Progress have been made to identify direct prebiotic effects of (poly)phenols; albeit up to date, these compounds are not recognized as prebiotics sensu stricto. Interestingly, certain probiotics strains have an enzymatic repertoire, such as tannase, α-L-rhamnosidase, and phenolic acid reductase, involved in the transformation of different (poly)phenols into bioactive phenolic metabolites. In vivo studies have demonstrated that these (poly)phenol-transforming bacteria thrive when provided with phenolic substrates. However, other taxonomically distinct gut symbionts of which a phenolic-metabolizing activity has not been demonstrated are still significantly promoted by (poly)phenols. This is the case of Akkermansia muciniphila, a so-called antiobesity bacterium, which responds positively to (poly)phenols and may be partially responsible for the health benefits formerly attributed to these molecules. We surmise that (poly)phenols broad antimicrobial action free ecological niches occupied by competing bacteria, thereby allowing the bloom of beneficial gut bacteria. This review explores the capacity of (poly)phenols to promote beneficial gut bacteria through their direct and collaborative bacterial utilization and their inhibitory action on potential pathogenic species. We propose the term duplibiotic, to describe an unabsorbed substrate modulating the gut microbiota by both antimicrobial and prebiotic modes of action. (Poly)phenol duplibiotic effect could participate in blunting metabolic disturbance and gut dysbiosis, positioning these compounds as dietary strategies with therapeutic potential.
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Affiliation(s)
- Maria Carolina Rodríguez-Daza
- Faculty of Agriculture and Food Sciences, Institute of Nutrition and Functional Foods (INAF), Laval University, Québec, QC, Canada.,Department of Food Science, Faculty of Agriculture and Food Sciences, Laval University, Québec, QC, Canada
| | - Elena C Pulido-Mateos
- Faculty of Agriculture and Food Sciences, Institute of Nutrition and Functional Foods (INAF), Laval University, Québec, QC, Canada.,Department of Food Science, Faculty of Agriculture and Food Sciences, Laval University, Québec, QC, Canada
| | - Joseph Lupien-Meilleur
- Faculty of Agriculture and Food Sciences, Institute of Nutrition and Functional Foods (INAF), Laval University, Québec, QC, Canada.,Department of Food Science, Faculty of Agriculture and Food Sciences, Laval University, Québec, QC, Canada
| | - Denis Guyonnet
- Diana Nova, Symrise Nutrition, Clichy-la-Garenne, France
| | - Yves Desjardins
- Faculty of Agriculture and Food Sciences, Institute of Nutrition and Functional Foods (INAF), Laval University, Québec, QC, Canada.,Department of Plant Science, Faculty of Agriculture and Food Sciences, Laval University, Québec, QC, Canada
| | - Denis Roy
- Faculty of Agriculture and Food Sciences, Institute of Nutrition and Functional Foods (INAF), Laval University, Québec, QC, Canada.,Department of Food Science, Faculty of Agriculture and Food Sciences, Laval University, Québec, QC, Canada
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Biotransformation of Flavonoids by Newly Isolated and Characterized Lactobacillus pentosus NGI01 Strain from Kimchi. Microorganisms 2021; 9:microorganisms9051075. [PMID: 34067804 PMCID: PMC8157076 DOI: 10.3390/microorganisms9051075] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 05/13/2021] [Accepted: 05/14/2021] [Indexed: 12/17/2022] Open
Abstract
Lactic acid bacteria (LAB) are generally recognized as safe (GRAS) microorganisms. This study aimed to identify novel LAB strains that can transform flavonoids into aglycones to improve bioavailability. We isolated 34 LAB strains from kimchi. The biotransformation activity of these 34 LAB strains was investigated based on α-L-rhamnosidase and β-D-glucosidase activities. Among them, 10 LAB strains with high activities were identified by 16S rRNA sequencing analysis. All tested LAB strains converted hesperidin to hesperetin (12.5–30.3%). Of these, only the Lactobacillus pentosus NGI01 strain produced quercetin from rutin (3.9%). The optimal biotransformation conditions for the L. pentosus NGI01 producing hesperetin and quercetin were investigated. The highest final product concentrations of hesperetin and quercetin were 207 and 78 μM, respectively. Thus, the L. pentosus NGI01 strain can be a biocatalyst for producing flavonoid aglycones in the chemical and food industries.
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Tomás-Navarro M, Navarro JL, Vallejo F, Tomás-Barberán FA. Novel Urinary Biomarkers of Orange Juice Consumption, Interindividual Variability, and Differences with Processing Methods. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:4006-4017. [PMID: 33724826 DOI: 10.1021/acs.jafc.0c08144] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Untargeted metabolomics identified urinary biomarkers able to discriminate between the intake of fresh hand-squeezed and industrially processed orange juices. Processing led to an upregulation in the excretion of hydroxy-polymethoxyflavone sulfates, abscisic acid, and sinapic acid 4'-glucuronide. The demethylated polymethoxyflavone metabolites were produced with a significant interindividual variability suggesting that they could originate from gut microbiota metabolism. No correlation between the excretion levels of flavanone and polymethoxyflavone metabolites was observed, showing that gut microbiota metabolism differences could be behind the interindividual variability. Subjects with a high excretion level of hesperetin conjugates could be low or high polymethoxyflavone excretors. Flavanone phase II metabolites were primarily glucuronides, while those of demethylated polymethoxyflavones were mainly sulfates. A comparative study with the available demethylated polymethoxyflavone standards suggested that the metabolites produced in humans could be tentatively 4'-hydroxy- and/or 3'-hydroxy-polymethoxyflavone sulfates. This study is the first to describe the bioavailability and metabolism of citrus juice polymethoxyflavones in humans.
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Affiliation(s)
- María Tomás-Navarro
- Laboratory of Food & Health, Research Group on Quality, Safety, and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P. O. Box 164, 30100 Campus de Espinardo, Murcia, Spain
| | | | - Fernando Vallejo
- Laboratory of Food & Health, Research Group on Quality, Safety, and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P. O. Box 164, 30100 Campus de Espinardo, Murcia, Spain
| | - Francisco A Tomás-Barberán
- Laboratory of Food & Health, Research Group on Quality, Safety, and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P. O. Box 164, 30100 Campus de Espinardo, Murcia, Spain
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Vazhappilly CG, Amararathna M, Cyril AC, Linger R, Matar R, Merheb M, Ramadan WS, Radhakrishnan R, Rupasinghe HPV. Current methodologies to refine bioavailability, delivery, and therapeutic efficacy of plant flavonoids in cancer treatment. J Nutr Biochem 2021; 94:108623. [PMID: 33705948 DOI: 10.1016/j.jnutbio.2021.108623] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 01/21/2021] [Accepted: 02/28/2021] [Indexed: 02/06/2023]
Abstract
Over the last two decades, several advancements have been made to improve the therapeutic efficacy of plant flavonoids, especially in cancer treatment. Factors such as low bioavailability, poor flavonoid stability and solubility, ineffective targeted delivery, and chemo-resistance hinder the application of flavonoids in anti-cancer therapy. Many anti-cancer compounds failed in the clinical trials because of unexpected altered clearance of flavonoids, poor absorption after administration, low efficacy, and/or adverse effects. Hence, the current research strategies are focused on improving the therapeutic efficacy of plant flavonoids, especially by enhancing their bioavailability through combination therapy, engineering gut microbiota, regulating flavonoids interaction with adenosine triphosphate binding cassette efflux transporters, and efficient delivery using nanocrystal and encapsulation technologies. This review aims to discuss different methodologies with examples from reported dietary flavonoids that showed an enhanced anti-cancer efficacy in both in vitro and in vivo models. Further, the review discusses the recent progress in biochemical modifications of flavonoids to improve bioavailability, solubility, and therapeutic efficacy.
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Affiliation(s)
| | - Madumani Amararathna
- Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, Nova Scotia, Canada
| | - Asha Caroline Cyril
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE
| | - Rebecca Linger
- Department of Pharmaceutical and Administrative Sciences, University of Charleston, Charleston, West Virginia, USA
| | - Rachel Matar
- Department of Biotechnology, American University of Ras Al Khaimah, Ras Al Khaimah, UAE
| | - Maxime Merheb
- Department of Biotechnology, American University of Ras Al Khaimah, Ras Al Khaimah, UAE
| | - Wafaa S Ramadan
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah, UAE; College of Medicine, University of Sharjah, Sharjah, UAE
| | - Rajan Radhakrishnan
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE
| | - H P Vasantha Rupasinghe
- Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, Nova Scotia, Canada; Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
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Salehi B, Cruz-Martins N, Butnariu M, Sarac I, Bagiu IC, Ezzat SM, Wang J, Koay A, Sheridan H, Adetunji CO, Semwal P, Schoebitz M, Martorell M, Sharifi-Rad J. Hesperetin's health potential: moving from preclinical to clinical evidence and bioavailability issues, to upcoming strategies to overcome current limitations. Crit Rev Food Sci Nutr 2021; 62:4449-4464. [PMID: 33491467 DOI: 10.1080/10408398.2021.1875979] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Flavonoids are common in the plant kingdom and many of them have shown a wide spectrum of bioactive properties. Hesperetin (Hst), the aglycone form of hesperidin, is a great example, and is the most abundant flavonoid found in Citrus plants. This review aims to provide an overview on the in vitro, in vivo and clinical studies reporting the Hst pharmacological effects and to discuss the bioavailability-related issues. Preclinical studies have shown promising effects on cancer, cardiovascular diseases, carbohydrate dysregulation, bone health, and other pathologies. Clinical studies have supported the Hst promissory effects as cardioprotective and neuroprotective agent. However, further well-designed clinical trials are needed to address the other Hst effects observed in preclinical trials, as well as to a more in-depth understanding of its safety profile.
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Affiliation(s)
- Bahare Salehi
- Medical Ethics and Law Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Natália Cruz-Martins
- Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, Porto, Portugal
- Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal
- Laboratory of Neuropsychophysiology, Faculty of Psychology and Education Sciences, University of Porto, Portugal
| | - Monica Butnariu
- Banat's University of Agricultural Sciences and Veterinary Medicine "King Michael I of Romania" from Timisoara, Timisoara, Romania
| | - Ioan Sarac
- Banat's University of Agricultural Sciences and Veterinary Medicine "King Michael I of Romania" from Timisoara, Timisoara, Romania
| | - Iulia-Cristina Bagiu
- Timisoara, Discipline of Microbiology, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania
| | - Shahira M Ezzat
- Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
- Department of Pharmacognosy, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt
| | - Jinfan Wang
- Trinity College Dublin. NatPro (Natural Products Research Centre), School of Pharmacy and Pharmaceutical Science, Dublin, Ireland
| | - Aaron Koay
- Trinity College Dublin. NatPro (Natural Products Research Centre), School of Pharmacy and Pharmaceutical Science, Dublin, Ireland
| | - Helen Sheridan
- Trinity College Dublin. NatPro (Natural Products Research Centre), School of Pharmacy and Pharmaceutical Science, Dublin, Ireland
| | - Charles Oluwaseun Adetunji
- Applied Microbiology, Biotechnology and Nanotechnology Laboratory, Department of Microbiology, Edo University Iyamho, Auchi, Edo State, Nigeria
| | - Prabhakar Semwal
- Department of Biotechnology, Graphic Era University, Dehradun, Uttarakhand, India
- Uttarakhand State Council for Science and Technology, Dehradun, Uttarakhand, India
| | - Mauricio Schoebitz
- Departamento de Suelos y Recursos Naturales, Facultad de Agronomía, Universidad de Concepción, Concepción, Chile
| | - Miquel Martorell
- Department of Nutrition and Dietetics, Faculty of Pharmacy, and Centre for Healthy Living, University of Concepción, Concepción, Chile
- Unidad de Desarrollo Tecnológico, Universidad de Concepción UDT, Concepcion, Chile
| | - Javad Sharifi-Rad
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Facultad de Medicina, Universidad del Azuay, Cuenca, Ecuador
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Mouffouk C, Mouffouk S, Mouffouk S, Hambaba L, Haba H. Flavonols as potential antiviral drugs targeting SARS-CoV-2 proteases (3CL pro and PL pro), spike protein, RNA-dependent RNA polymerase (RdRp) and angiotensin-converting enzyme II receptor (ACE2). Eur J Pharmacol 2021; 891:173759. [PMID: 33249077 PMCID: PMC7691142 DOI: 10.1016/j.ejphar.2020.173759] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 11/01/2020] [Accepted: 11/23/2020] [Indexed: 12/12/2022]
Abstract
The novel coronavirus outbreak (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents the actual greatest global public health crisis. The lack of efficacious drugs and vaccines against this viral infection created a challenge for scientific researchers in order to find effective solutions. One of the promising therapeutic approaches is the search for bioactive molecules with few side effects that display antiviral properties in natural sources like medicinal plants and vegetables. Several computational and experimental studies indicated that flavonoids especially flavonols and their derivatives constitute effective viral enzyme inhibitors and possess interesting antiviral activities. In this context, the present study reviews the efficacy of many dietary flavonols as potential antiviral drugs targeting the SARS-CoV-2 enzymes and proteins including Chymotrypsin-Like Protease (3CLpro), Papain Like protease (PLpro), Spike protein (S protein) and RNA-dependent RNA polymerase (RdRp), and also their ability to interact with the angiotensin-converting enzyme II (ACE2) receptor. The relationship between flavonol structures and their SARS-CoV-2 antiviral effects were discussed. On the other hand, the immunomodulatory, the anti-inflammatory and the antiviral effects of secondary metabolites from this class of flavonoids were reported. Also, their bioavailability limitations and toxicity were predicted.
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Affiliation(s)
- Chaima Mouffouk
- Faculty of Nature and Life Sciences, Department of Organisms, University of Batna 2, Algeria.
| | - Soumia Mouffouk
- Laboratory of Chemistry and Environmental Chemistry (L.C.C.E), Department of Chemistry, Faculty of Sciences of the Matter, University of Batna 1, 05000, Batna, Algeria
| | - Sara Mouffouk
- Faculty of Nature and Life Sciences, Department of Organisms, University of Batna 2, Algeria
| | - Leila Hambaba
- Faculty of Nature and Life Sciences, Department of Organisms, University of Batna 2, Algeria
| | - Hamada Haba
- Laboratory of Chemistry and Environmental Chemistry (L.C.C.E), Department of Chemistry, Faculty of Sciences of the Matter, University of Batna 1, 05000, Batna, Algeria
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Orro A, Uggeri M, Rusnati M, Urbinati C, Pedemonte N, Pesce E, Moscatelli M, Padoan R, Cichero E, Fossa P, D'Ursi P. In silico drug repositioning on F508del-CFTR: A proof-of-concept study on the AIFA library. Eur J Med Chem 2021; 213:113186. [PMID: 33472120 DOI: 10.1016/j.ejmech.2021.113186] [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: 06/26/2020] [Revised: 01/07/2021] [Accepted: 01/07/2021] [Indexed: 12/14/2022]
Abstract
Computational drug repositioning is of growing interest to academia and industry, for its ability to rapidly screen a huge number of candidates in silico (exploiting comprehensive drug datasets) together with reduced development cost and time. The potential of drug repositioning has not been fully evaluated yet for cystic fibrosis (CF), a disease mainly caused by deletion of Phe 508 (F508del) of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. F508del-CFTR is thus withheld in the endoplasmic reticulum and rapidly degraded by the ubiquitin/proteasome system. CF is still a fatal disease. Nowadays, it is treatable by some CFTR-rescuing drugs, but new-generation drugs with stronger therapeutic benefits and fewer side effects are still awaited. In this manuscript we report about the results of a pilot computational drug repositioning screening in search of F508del-CFTR-targeted drugs performed on AIFA library by means of a dedicated computational pipeline and surface plasmon resonance binding assay to experimentally validate the computational findings.
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Affiliation(s)
- Alessandro Orro
- Institute for Biomedical Technologies, National Research Council (ITB-CNR), Segrate, MI, Italy
| | - Matteo Uggeri
- Institute for Biomedical Technologies, National Research Council (ITB-CNR), Segrate, MI, Italy; Department of Pharmacy, Section of Medicinal Chemistry, School of Medical and Pharmaceutical Sciences, University of Genova, Genova, Italy
| | - Marco Rusnati
- Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
| | - Chiara Urbinati
- Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
| | | | - Emanuela Pesce
- UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, Genova, Italy
| | - Marco Moscatelli
- Institute for Biomedical Technologies, National Research Council (ITB-CNR), Segrate, MI, Italy
| | - Rita Padoan
- Department of Pediatrics, Regional Support Centre for Cystic Fibrosis, Children's Hospital-ASST Spedali Civili, University of Brescia, Brescia, Italy
| | - Elena Cichero
- Department of Pharmacy, Section of Medicinal Chemistry, School of Medical and Pharmaceutical Sciences, University of Genova, Genova, Italy
| | - Paola Fossa
- Department of Pharmacy, Section of Medicinal Chemistry, School of Medical and Pharmaceutical Sciences, University of Genova, Genova, Italy
| | - Pasqualina D'Ursi
- Institute for Biomedical Technologies, National Research Council (ITB-CNR), Segrate, MI, Italy.
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Niu H, Zhang H, Wu F, Xiong B, Tong J, Jiang L. Proteomics study on the protective mechanism of soybean isoflavone against inflammation injury of bovine mammary epithelial cells induced by Streptococcus agalactiae. Cell Stress Chaperones 2021; 26:91-101. [PMID: 32865767 PMCID: PMC7736374 DOI: 10.1007/s12192-020-01158-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 08/21/2020] [Accepted: 08/25/2020] [Indexed: 01/14/2023] Open
Abstract
This study aimed to verify the anti-inflammatory effect of soybean isoflavones (SI) on the inflammatory response induced by Streptococcus agalactiae (S. agalactiae) of bovine mammary epithelial cells (bMECs) and to elucidate its possible mechanism. BMECs were pretreated with SI of different concentrations (20, 40, 60, 80, 100 μg/mL) for 0.5, 3, 6, 9, 12, 15, 18, 24 h. And then, S. agalactiae was used to infect bMECs for 6 h (MOI = 50:1) to establish the inflammation model. Cell viability, growth curves of S. agalactiae, cytotoxicity, and S. agalactiae invasion rate were determined. A proteomics technique was used to further detect differential proteins and enrichment pathways. SI (40 μg/mL) improved the viability of bMECs at 12 h (p < 0.05) and 60 and 80 μg/mL of SI greater (p < 0.01). Moreover, 60 μg/mL of SI protects cells from bacterial damage (p < 0.05). SI could inhibit S. agalactiae growth and internalization into bMECs in a time- and dose-dependent manner. In addition, proteomics results showed that 133 proteins were up-regulated and 89 proteins were down-regulated significantly. The differentially significantly expressed proteins (DSEPs) were mainly related to cell proliferation, differentiation, apoptosis, and migration. GO annotation showed that 222 DSEPs were divided into 23 biological processes (BP) terms, 14 cell components (CC) terms, and 12 molecular functions (MF) terms. DSEPs were significantly enriched in 10 pathways, of which the immune pathway was the main enrichment pathway.
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Affiliation(s)
- Hui Niu
- Department of Animal Science, Animal Science and Technology College, Beijing University of Agriculture, Beijing, 102206, China
| | - Hua Zhang
- Department of Animal Science, Animal Science and Technology College, Beijing University of Agriculture, Beijing, 102206, China
| | - Fuxin Wu
- Department of Animal Science, Animal Science and Technology College, Beijing University of Agriculture, Beijing, 102206, China
| | - Benhai Xiong
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China
| | - Jinjin Tong
- Department of Animal Science, Animal Science and Technology College, Beijing University of Agriculture, Beijing, 102206, China.
| | - Linshu Jiang
- Department of Animal Science, Animal Science and Technology College, Beijing University of Agriculture, Beijing, 102206, China.
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Riva A, Kolimár D, Spittler A, Wisgrill L, Herbold CW, Abrankó L, Berry D. Conversion of Rutin, a Prevalent Dietary Flavonol, by the Human Gut Microbiota. Front Microbiol 2020; 11:585428. [PMID: 33408702 PMCID: PMC7779528 DOI: 10.3389/fmicb.2020.585428] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 12/02/2020] [Indexed: 01/04/2023] Open
Abstract
The gut microbiota plays a pivotal role in the conversion of dietary flavonoids, which can affect their bioavailability and bioactivity and thereby their health-promoting properties. The ability of flavonoids to metabolically-activate the microbiota has, however, not been systematically evaluated. In the present study, we used a fluorescence-based single-cell activity measure [biorthogonal non-canonical ammino acid-tagging (BONCAT)] combined with fluorescence activated cell sorting (FACS) to determine which microorganisms are metabolically-active after amendment of the flavonoid rutin. We performed anaerobic incubations of human fecal microbiota amended with rutin and in the presence of the cellular activity marker L-azidohomoalanine (AHA) to detect metabolically-active cells. We found that 7.3% of cells in the gut microbiota were active after a 6 h incubation and 26.9% after 24 h. We then sorted BONCAT-positive cells and observed an enrichment of Lachnospiraceae (Lachnoclostridium and Eisenbergiella), Enterobacteriaceae, Tannerellaceae, and Erysipelotrichaceae species in the rutin-responsive fraction of the microbiota. There was marked inter-individual variability in the appearance of rutin conversion products after incubation with rutin. Consistent with this, there was substantial variability in the abundance of rutin-responsive microbiota among different individuals. Specifically, we observed that Enterobacteriaceae were associated with conversion of rutin into quercetin-3-glucoside (Q-glc) and Lachnospiraceae were associated with quercetin (Q) production. This suggests that individual microbiotas differ in their ability to metabolize rutin and utilize different conversion pathways.
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Affiliation(s)
- Alessandra Riva
- Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, Division of Microbial Ecology, University of Vienna, Vienna, Austria
| | - Ditta Kolimár
- Faculty of Food Science, Department of Applied Chemistry, Szent István University, Budapest, Hungary
| | - Andreas Spittler
- Core Facility Flow Cytometry, Department of Surgery, Research Lab, Medical University of Vienna, Vienna, Austria
| | - Lukas Wisgrill
- Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
| | - Craig W Herbold
- Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, Division of Microbial Ecology, University of Vienna, Vienna, Austria
| | - László Abrankó
- Faculty of Food Science, Department of Applied Chemistry, Szent István University, Budapest, Hungary
| | - David Berry
- Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, Division of Microbial Ecology, University of Vienna, Vienna, Austria.,Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna, Vienna, Austria
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Effects of 8 Weeks of 2S-Hesperidin Supplementation on Performance in Amateur Cyclists. Nutrients 2020; 12:nu12123911. [PMID: 33371483 PMCID: PMC7767530 DOI: 10.3390/nu12123911] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 12/10/2020] [Accepted: 12/18/2020] [Indexed: 12/12/2022] Open
Abstract
2S-Hesperidin is a flavanone (flavonoid) found in high concentrations in citrus fruits. It has an antioxidant and anti-inflammatory effects, improving performance in animals. This study investigated the effects of chronic intake of an orange extract (2S-hesperidin) or placebo on non-oxidative/glycolytic and oxidative metabolism markers and performance markers in amateur cyclists. A double-blind, randomized, placebo-controlled trial was carried out between late September and December 2018. Forty amateur cyclists were randomized into two groups: one taking 500 mg/day 2S-hesperidin and the other taking 500 mg/day placebo (microcellulose) for eight weeks. All participants completed the study. An incremental test was used to evaluate performance, and a step test was used to measure oxygen consumption, carbon dioxide, efficiency and oxidation of carbohydrates and fat by indirect calorimetry. The anaerobic power (non-oxidative) was determined using Wingate tests (30 s). After eight weeks supplementation, there was an increase in the incremental test in estimated functional threshold power (FTP) (3.2%; p ≤ 0.05) and maximum power (2.7%; p ≤ 0.05) with 2S-hesperdin compared to placebo. In the step test, there was a decrease in VO2 (L/min) (−8.3%; p ≤ 0.01) and VO2R (mL/kg/min) (−8.9%; p ≤ 0.01) at VT2 in placebo. However, there were no differences between groups. In the Wingate test, there was a significant increase (p ≤ 0.05) in peak and relative power in both groups, but without differences between groups. Supplementation with an orange extract (2S-hesperdin) 500 mg/day improves estimated FTP and maximum power performance in amateur cyclists.
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Kim DS, Lim SB. Kinetic study of subcritical water extraction of flavonoids from citrus unshiu peel. Sep Purif Technol 2020. [DOI: 10.1016/j.seppur.2020.117259] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Cherrak SA, Merzouk H, Mokhtari-Soulimane N. Potential bioactive glycosylated flavonoids as SARS-CoV-2 main protease inhibitors: A molecular docking and simulation studies. PLoS One 2020; 15:e0240653. [PMID: 33057452 PMCID: PMC7561147 DOI: 10.1371/journal.pone.0240653] [Citation(s) in RCA: 100] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 09/30/2020] [Indexed: 12/31/2022] Open
Abstract
A novel coronavirus responsible of acute respiratory infection closely related to SARS-CoV has recently emerged. So far there is no consensus for drug treatment to stop the spread of the virus. Discovery of a drug that would limit the virus expansion is one of the biggest challenges faced by the humanity in the last decades. In this perspective, to test existing drugs as inhibitors of SARS-CoV-2 main protease is a good approach. Among natural phenolic compounds found in plants, fruit, and vegetables; flavonoids are the most abundant. Flavonoids, especially in their glycosylated forms, display a number of physiological activities, which makes them interesting to investigate as antiviral molecules. The flavonoids chemical structures were downloaded from PubChem and protease structure 6LU7 was from the Protein Data Bank site. Molecular docking study was performed using AutoDock Vina. Among the tested molecules Quercetin-3-O-rhamnoside showed the highest binding affinity (-9,7 kcal/mol). Docking studies showed that glycosylated flavonoids are good inhibitors for the SARS-CoV-2 protease and could be further investigated by in vitro and in vivo experiments for further validation. MD simulations were further performed to evaluate the dynamic behavior and stability of the protein in complex with the three best hits of docking experiments. Our results indicate that the rutin is a potential drug to inhibit the function of Chymotrypsin-like protease (3CL pro) of Coronavirus.
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Affiliation(s)
- Sabri Ahmed Cherrak
- Laboratory of Physiology, Physiopathology and Biochemistry of Nutrition, Department of Biology, Faculty of Natural and Life Sciences, Earth and Universe, University of Tlemcen, Tlemcen, Algeria
| | - Hafida Merzouk
- Laboratory of Physiology, Physiopathology and Biochemistry of Nutrition, Department of Biology, Faculty of Natural and Life Sciences, Earth and Universe, University of Tlemcen, Tlemcen, Algeria
| | - Nassima Mokhtari-Soulimane
- Laboratory of Physiology, Physiopathology and Biochemistry of Nutrition, Department of Biology, Faculty of Natural and Life Sciences, Earth and Universe, University of Tlemcen, Tlemcen, Algeria
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Koudoufio M, Desjardins Y, Feldman F, Spahis S, Delvin E, Levy E. Insight into Polyphenol and Gut Microbiota Crosstalk: Are Their Metabolites the Key to Understand Protective Effects against Metabolic Disorders? Antioxidants (Basel) 2020; 9:E982. [PMID: 33066106 PMCID: PMC7601951 DOI: 10.3390/antiox9100982] [Citation(s) in RCA: 63] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 09/30/2020] [Accepted: 09/30/2020] [Indexed: 12/12/2022] Open
Abstract
Lifestyle factors, especially diet and nutrition, are currently regarded as essential avenues to decrease modern-day cardiometabolic disorders (CMD), including obesity, metabolic syndrome, type 2 diabetes, and atherosclerosis. Many groups around the world attribute these trends, at least partially, to bioactive plant polyphenols given their anti-oxidant and anti-inflammatory actions. In fact, polyphenols can prevent or reverse the progression of disease processes through many distinct mechanisms. In particular, the crosstalk between polyphenols and gut microbiota, recently unveiled thanks to DNA-based tools and next generation sequencing, unravelled the central regulatory role of dietary polyphenols and their intestinal micro-ecology metabolites on the host energy metabolism and related illnesses. The objectives of this review are to: (1) provide an understanding of classification, structure, and bioavailability of dietary polyphenols; (2) underline their metabolism by gut microbiota; (3) highlight their prebiotic effects on microflora; (4) discuss the multifaceted roles of their metabolites in CMD while shedding light on the mechanisms of action; and (5) underscore their ability to initiate host epigenetic regulation. In sum, the review clearly documents whether dietary polyphenols and micro-ecology favorably interact to promote multiple physiological functions on human organism.
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Affiliation(s)
- Mireille Koudoufio
- Research Centre, Sainte-Justine University Health Center, Montreal, QC H3T 1C5, Canada; (M.K.); (F.F.); (S.S.); (E.D.)
- Department of Nutrition, Université de Montréal, Montreal, QC H3T 1J4, Canada
- Institute of Nutrition and Functional Foods, Laval University, Quebec City, QC G1V 0A6, Canada;
| | - Yves Desjardins
- Institute of Nutrition and Functional Foods, Laval University, Quebec City, QC G1V 0A6, Canada;
| | - Francis Feldman
- Research Centre, Sainte-Justine University Health Center, Montreal, QC H3T 1C5, Canada; (M.K.); (F.F.); (S.S.); (E.D.)
- Department of Nutrition, Université de Montréal, Montreal, QC H3T 1J4, Canada
- Institute of Nutrition and Functional Foods, Laval University, Quebec City, QC G1V 0A6, Canada;
| | - Schohraya Spahis
- Research Centre, Sainte-Justine University Health Center, Montreal, QC H3T 1C5, Canada; (M.K.); (F.F.); (S.S.); (E.D.)
- Department of Nutrition, Université de Montréal, Montreal, QC H3T 1J4, Canada
- Institute of Nutrition and Functional Foods, Laval University, Quebec City, QC G1V 0A6, Canada;
| | - Edgard Delvin
- Research Centre, Sainte-Justine University Health Center, Montreal, QC H3T 1C5, Canada; (M.K.); (F.F.); (S.S.); (E.D.)
- Department of Biochemistry, Université de Montréal, Montreal, QC H3T 1J4, Canada
| | - Emile Levy
- Research Centre, Sainte-Justine University Health Center, Montreal, QC H3T 1C5, Canada; (M.K.); (F.F.); (S.S.); (E.D.)
- Department of Nutrition, Université de Montréal, Montreal, QC H3T 1J4, Canada
- Institute of Nutrition and Functional Foods, Laval University, Quebec City, QC G1V 0A6, Canada;
- Department of Pediatrics, Université de Montréal, Montreal, QC H3T 1J4, Canada
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Hou K, Tong J, Zhang H, Gao S, Guo Y, Niu H, Xiong B, Jiang L. Microbiome and metabolic changes in milk in response to artemisinin supplementation in dairy cows. AMB Express 2020; 10:154. [PMID: 32833065 PMCID: PMC7445214 DOI: 10.1186/s13568-020-01080-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 08/08/2020] [Indexed: 12/14/2022] Open
Abstract
This study aimed to explore the effects of artemisinin (ART) on the milk microbiome and metabolites of dairy cow. A total of 12 mid-lactation Holstein dairy cows with similar parity, days in milk were randomly divided into 2 groups receiving either a total mixed ration (TMR) as the control group or this TMR and 120 g/d/head ART as the ART group. The milk samples were collected weekly to determine the contents, and end-of-trial (week 8) milk samples were used to identify microbial species and metabolite profiles by 16S rRNA sequencing and LC–MS analyses, respectively. We observed that the milk fat content significantly increased by ART treatment (P < 0.05). The bacterial community richness was significantly lower in the ART group (P < 0.05), while the diversity showed no difference (P > 0.05). Compared with its abundance in the control (CON) group, Firmicutes was significantly decreased, whereas Proteobacteria was significantly increased. Furthermore, in the ART group, the relative abundances of the genera Aerococcus, Staphylococcus, Corynebacterium_1 and Facklamia were significantly lower (P < 0.01). Metabolomics analysis revealed that ART significantly increasing the concentrations of glycerophospholipids, glycerolipids and flavonoids compared with those in the CON group. An enrichment analysis of the different metabolites showed that ART mainly affected glycerophospholipid metabolism and the pantothenate and CoA biosynthesis pathways. These findings revealed that ART supplementation could affect the milk microbiota and metabolites, that glycerophospholipids and glycerolipids could be potential biomarkers in the milk response to ART feed in dairy cows, and that ART changes substances in milk by maintaining lipid metabolism in the mammary gland.
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Nazzaro F, Fratianni F, De Feo V, Battistelli A, Da Cruz AG, Coppola R. Polyphenols, the new frontiers of prebiotics. ADVANCES IN FOOD AND NUTRITION RESEARCH 2020; 94:35-89. [PMID: 32892838 DOI: 10.1016/bs.afnr.2020.06.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
There is a growing interest in the identification of molecules capable to promote health and with a concurrent potential for technological applications. Prebiotics are functional ingredients naturally occurring in some plant and animal foods that since many decades stimulated considerable attention from the pharmaceutical and food industries due to their positive health effects. Together the well-known biomolecules with ascertained prebiotic effect, in last year new molecules were finally recognized as prebiotics, so capable to improve the health of an organism, also through the positive effect exerted on host microbiota. Among the so-called prebiotics, a special mention should be given to polyphenols, probably the most important, or at least among the most important secondary metabolites produced by the vegetal kingdom. This short chapter wants to emphasize polyphenols and, after briefly describing the individual microbiome, to illustrate how polyphenols can, through their influence on the microbiome, have a positive effect on the health of the individual in general, and on some pathologies in particular, for which the role of a bad status of the individual microbiome has been definitively established.
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Affiliation(s)
| | | | - Vincenzo De Feo
- Department of Pharmacy, University of Salerno, Fisciano, Salerno, Italy
| | | | - Adriano Gomes Da Cruz
- Food Department, Federal Institute of Education, Science and Technology of Rio de Janeiro, Brazil
| | - Raffaele Coppola
- Department of Agricultural, Environmental and Food Sciences, DiAAA-University of Molise, Campobasso, Italy
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Okamoto T, Sugimoto S, Noda M, Yokooji T, Danshiitsoodol N, Higashikawa F, Sugiyama M. Interleukin-8 Release Inhibitors Generated by Fermentation of Artemisia princeps Pampanini Herb Extract With Lactobacillus plantarum SN13T. Front Microbiol 2020; 11:1159. [PMID: 32582099 PMCID: PMC7283739 DOI: 10.3389/fmicb.2020.01159] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 05/06/2020] [Indexed: 12/13/2022] Open
Abstract
Some glycosides, which are detected in water extracts from medicinal plants, have been reported to be degraded into their aglycones by incubating with some microorganisms producing β-glucosidase. We have shown that a plant-derived Lactobacillus plantarum SN13T harbors 11 open reading frames (ORFs) encoding the β-glucosidase enzyme and can grow vigorously in several herbal water extracts. In this study, we observed that the water extract from Artemisia princeps Pampanini (AP) fermented with the SN13T strain strongly inhibited the release of interleukin (IL)-8 from the HuH-7 cells, when compared to that without fermentation. Furthermore, we demonstrated that the SN13T strain produced at least two bioactive compounds from some compounds contained in AP extract. In addition, we determined that the two compounds were catechol and seco-tanapartholide C, which dose-dependently inhibited the release of IL-8. Because some sesquiterpene lactones are useful in pharmaceuticals, seco-tanapartholide C may be useful as an anti-inflammatory agent. This study suggests that the fermentation of medicinal herbs with Lb. plantarum SN13T is a significant technique to obtain bioactive compounds having therapeutic potential.
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Affiliation(s)
- Tomoko Okamoto
- Department of Probiotic Science for Preventive Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.,Department of Frontier Science for Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Sachiko Sugimoto
- Department of Pharmacognosy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Masafumi Noda
- Department of Probiotic Science for Preventive Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tomoharu Yokooji
- Department of Frontier Science for Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Narandalai Danshiitsoodol
- Department of Probiotic Science for Preventive Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Fumiko Higashikawa
- Department of Probiotic Science for Preventive Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Masanori Sugiyama
- Department of Probiotic Science for Preventive Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Tang HY, Fang Z, Ng K. Dietary fiber-based colon-targeted delivery systems for polyphenols. Trends Food Sci Technol 2020. [DOI: 10.1016/j.tifs.2020.04.028] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Mas-Capdevila A, Teichenne J, Domenech-Coca C, Caimari A, Del Bas JM, Escoté X, Crescenti A. Effect of Hesperidin on Cardiovascular Disease Risk Factors: The Role of Intestinal Microbiota on Hesperidin Bioavailability. Nutrients 2020; 12:E1488. [PMID: 32443766 PMCID: PMC7284956 DOI: 10.3390/nu12051488] [Citation(s) in RCA: 109] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 05/07/2020] [Accepted: 05/18/2020] [Indexed: 12/12/2022] Open
Abstract
Recently, hesperidin, a flavonone mainly present in citrus fruits, has emerged as a new potential therapeutic agent able to modulate several cardiovascular diseases (CVDs) risk factors. Animal and in vitro studies demonstrate beneficial effects of hesperidin and its derived compounds on CVD risk factors. Thus, hesperidin has shown glucose-lowering and anti-inflammatory properties in diabetic models, dyslipidemia-, atherosclerosis-, and obesity-preventing effects in CVDs and obese models, and antihypertensive and antioxidant effects in hypertensive models. However, there is still controversy about whether hesperidin could contribute to ameliorate glucose homeostasis, lipid profile, adiposity, and blood pressure in humans, as evidenced by several clinical trials reporting no effects of treatments with this flavanone or with orange juice on these cardiovascular parameters. In this review, we focus on hesperidin's beneficial effects on CVD risk factors, paying special attention to the high interindividual variability in response to hesperidin-based acute and chronic interventions, which can be partly attributed to differences in gut microbiota. Based on the current evidence, we suggest that some of hesperidin's contradictory effects in human trials are partly due to the interindividual hesperidin variability in its bioavailability, which in turn is highly dependent on the α-rhamnosidase activity and gut microbiota composition.
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Affiliation(s)
- Anna Mas-Capdevila
- Eurecat, Technology Centre of Catalunya, Nutrition and Health Unit, 43204 Reus, Spain; (A.M.-C.); (J.T.); (C.D.-C.); (A.C.); (J.M.D.B.)
- Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Campus Sescelades, 43007 Tarragona, Spain
| | - Joan Teichenne
- Eurecat, Technology Centre of Catalunya, Nutrition and Health Unit, 43204 Reus, Spain; (A.M.-C.); (J.T.); (C.D.-C.); (A.C.); (J.M.D.B.)
| | - Cristina Domenech-Coca
- Eurecat, Technology Centre of Catalunya, Nutrition and Health Unit, 43204 Reus, Spain; (A.M.-C.); (J.T.); (C.D.-C.); (A.C.); (J.M.D.B.)
| | - Antoni Caimari
- Eurecat, Technology Centre of Catalunya, Nutrition and Health Unit, 43204 Reus, Spain; (A.M.-C.); (J.T.); (C.D.-C.); (A.C.); (J.M.D.B.)
- Eurecat, Technology Centre of Catalunya, Biotechnology Area and Technological Unit of Nutrition and Health, 43204 Reus, Spain
| | - Josep M Del Bas
- Eurecat, Technology Centre of Catalunya, Nutrition and Health Unit, 43204 Reus, Spain; (A.M.-C.); (J.T.); (C.D.-C.); (A.C.); (J.M.D.B.)
| | - Xavier Escoté
- Eurecat, Technology Centre of Catalunya, Nutrition and Health Unit, 43204 Reus, Spain; (A.M.-C.); (J.T.); (C.D.-C.); (A.C.); (J.M.D.B.)
- Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Campus Sescelades, 43007 Tarragona, Spain
| | - Anna Crescenti
- Eurecat, Technology Centre of Catalunya, Nutrition and Health Unit, 43204 Reus, Spain; (A.M.-C.); (J.T.); (C.D.-C.); (A.C.); (J.M.D.B.)
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