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Villa de la Torre F, Tec Caamal EA, Rizo AM, Argáez RB, Pintor Romero VG, Yáñez-Barrientos E, Morales-Tirado DJ, Alonso-Castro AJ, Arana Argáez VE. In vivo and in vitro anti-inflammatory activity of the methanolic leaves extract of Gymnopodium floribundum Rolfe. JOURNAL OF ETHNOPHARMACOLOGY 2025; 347:119743. [PMID: 40204249 DOI: 10.1016/j.jep.2025.119743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 03/28/2025] [Accepted: 04/02/2025] [Indexed: 04/11/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Gymnopodium floribundum Rolfe, known locally as "Dzidzilche" or "Ts'its'ilche," is a native species from Mexico and Central America. In Mayan communities, this plant is used to relieve inflammation and diverse respiratory diseases such as colds, catarrh, bronchitis, and asthma. Usually, a decoction of leaves or flowers is prepared and administered orally. AIM This research explores the anti-inflammatory effects of the methanol extract of Gymnopodium floribundum Rolfe leaves (MGF) using in vitro and in vivo animal models of inflammation. METHODS MGF was characterized by GC-MS, and cytotoxicity was assessed using hemolysis and MTT assays. The antiphlogistic effect in vitro was measuring the release of cytokines, hydrogen peroxide, and nitric oxide in macrophages stimulated with LPS. Additionally, anti- and pro-inflammatory cytokines, prostaglandins, and leukotrienes in serum were quantified in carrageenan-induced mouse paw edema. Finally, 1-fluoro-2,4-dinitrobenzene (DNFB)-induced delayed-type hypersensitivity and TPA-induced ear edema models were analyzed. RESULTS Compounds found in MGF, such as D-pinitol and protocatechuic (3,4-dihydroxybenzoic) acid, are reported to exert anti-inflammatory effects. MGF showed no hemolytic or cytotoxic effects. Nevertheless, it displayed in vitro anti-inflammatory activity by decreasing the release of IL-6, IL-1β, TNF-α, hydrogen peroxide, and nitric oxide levels; on the other hand, it increased IL-10 production. Furthermore, the MGF significantly reduced inflammation in mouse models and reduced the release of leukotrienes, prostaglandins, and pro-inflammatory cytokines. CONCLUSION Gymnopodium floribundum Rolfe exhibits anti-inflammatory activity by suppressing pro-inflammatory mediators, altering cell migration mechanisms, and raising IL-10 production.
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Affiliation(s)
- Fabiola Villa de la Torre
- Faculty of Chemistry, Laboratory of Pharmacology, Autonomous University of Yucatan, Yucatan, Mexico.
| | | | - Abril Martínez Rizo
- Faculty of Chemistry, Laboratory of Pharmacology, Autonomous University of Yucatan, Yucatan, Mexico.
| | - Rocío Borges Argáez
- Biotechnology Unit, Scientific Research Center of Yucatan (CICY), Yucatan, Mexico.
| | | | - Eunice Yáñez-Barrientos
- Division of Natural and Exact Sciences, Department of Chemistry, University of Guanajuato, Guanajuato, Mexico.
| | | | - Angel Josabad Alonso-Castro
- Division of Natural and Exact Sciences, Department of Chemistry, University of Guanajuato, Guanajuato, Mexico.
| | - Víctor E Arana Argáez
- Faculty of Chemistry, Laboratory of Pharmacology, Autonomous University of Yucatan, Yucatan, Mexico.
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Du Y, Li S, Chen G, Mao Y, Zhu S, Zhang W, Kang M, Sui Y, Wang D. Sesquiterpene Lactone Lactucopicrin Boosts Apoptotic Cell Clearance by Colonic Epithelial Cells and Alleviates Colitis in Mice. Mol Nutr Food Res 2025:e70062. [PMID: 40249148 DOI: 10.1002/mnfr.70062] [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: 10/20/2024] [Revised: 02/03/2025] [Accepted: 03/27/2025] [Indexed: 04/19/2025]
Abstract
Boosting apoptotic cell clearance by phagocytes including colonic epithelial cells (CECs), a process named efferocytosis, inhibits colitis development. Lactucopicrin (LCP), one common bitter sesquiterpene lactone affluent in leafy vegetables possesses a significant antiinflammatory property. However, it remains unknown whether LCP could regulate CECs efferocytosis and colitis development in vivo. Methods and Results: LCP (0.25-1 µmol/L) does not appreciably change the efferocytic capacity of murine primary CECs to clear apoptotic CECs. Instead, LCP dose-dependently increases the efferocytic capacity of CECs treated with butyrate (But). This effect is reliant on efferocytic receptor brain-specific angiogenesis 1 (BAI1). Although LCP does not significantly affect BAI1 expression, it alters BAI1 distribution with an increase in lipid raft microdomains in plasma membrane, an effect responsible for the LCP effect on efferocytic capacity. Moreover, dietary supplementation with 0.012% wt/wt of LCP attenuates dextran sulfate sodium (DSS)-induced colitis in C57BL/6J mice, along with an increase in efferocytic capacity of CECs and fecal But content, a reduction in apoptotic cell accumulation and inflammation burden in colonic tissues. Conclusion: Dietary LCP could inhibit DSS-induced colitis in mice, likely through enhancing BAI1-mediated efferocytosis of CECs, thus providing a new candidate for the treatment of colitis.
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Affiliation(s)
- Yushi Du
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, PR China
| | - Shuangshuang Li
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, PR China
| | - Guanyu Chen
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, PR China
| | - Yihui Mao
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, PR China
| | - Shasha Zhu
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, PR China
| | - Wenyu Zhang
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, PR China
| | - Mengxi Kang
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, PR China
| | - Yi Sui
- Department of Clinical Nutrition, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, PR China
| | - Dongliang Wang
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, PR China
- Guangdong Provincial Key Laboratory for Food, Nutrition and Health, Guangzhou, Guangdong Province, PR China
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Du J, Wang H, Zhong L, Wei S, Min X, Deng H, Zhang X, Zhong M, Huang Y. Bioactivity and biomedical applications of pomegranate peel extract: a comprehensive review. Front Pharmacol 2025; 16:1569141. [PMID: 40206073 PMCID: PMC11979244 DOI: 10.3389/fphar.2025.1569141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Accepted: 03/07/2025] [Indexed: 04/11/2025] Open
Abstract
Pomegranate peel is a by-product generated during the processing of pomegranate (Punica granatum L.) fruit, accounting for approximately 50% of the total mass of the fruit. Although pomegranate peel is usually regarded as waste, it is rich in various bioactive metabolites such as polyphenols, tannins, and flavonoids, demonstrating significant medicinal and nutritional value. In recent years, Pomegranate peel extract (PPE) has shown broad application prospects in the biomedical field due to its multiple effects, including antioxidant, anti-inflammatory, antibacterial, anti-apoptotic properties, and promotion of cell regeneration. This review consolidates the major bioactive metabolites of PPE and explores its applications in biomedical materials, including nanodrug carriers, hydrogels, and tissue engineering scaffolds. By synthesizing the existing literature, we delve into the potential value of PPE in biomedicine, the challenges currently encountered, and the future directions for research. The aim of this review is to provide a scientific basis for optimizing the utilization of PPE and to facilitate its broader application in the biomedical field.
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Affiliation(s)
- Jinsong Du
- School of Health Management, Zaozhuang University, Zaozhuang, China
- Department of Teaching and Research, Shandong Coal Health School, Zaozhuang, China
| | - Heming Wang
- School of Nursing, Jilin University, Jilin, China
| | - Lingyun Zhong
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China
| | - Shujie Wei
- Image Center, Zaozhuang Municipal Hospital, Zaozhuang, China
| | - Xiaoqiang Min
- Department of Teaching and Research, Shandong Coal Health School, Zaozhuang, China
- Department of Geriatics, Shandong Healthcare Group Xinwen Central Hospital, Taian, China
| | - Hongyan Deng
- School of Health Management, Zaozhuang University, Zaozhuang, China
| | - Xiaoyan Zhang
- Magnetic Resonance Imaging Department, Shandong Healthcare Group Zaozhuang Central Hospital, Zaozhuang, China
| | - Ming Zhong
- Lanshu Cosmetics Co., Ltd., Huzhou, Zhejiang, China
| | - Yi Huang
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China
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Li S, Du Y, Chen G, Mao Y, Zhang W, Kang M, Zhu S, Wang D. Protocatechuic Acid Attenuates Inflammation in Macrophage-like Vascular Smooth Muscle Cells in ApoE -/- Mice. Nutrients 2025; 17:1090. [PMID: 40292571 PMCID: PMC11944442 DOI: 10.3390/nu17061090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2025] [Revised: 03/18/2025] [Accepted: 03/18/2025] [Indexed: 04/30/2025] Open
Abstract
Background/Objectives: Non-resolving inflammation in macrophage-like cells (MLCs) transdifferentiated from vascular smooth muscle cells and monocyte-derived macrophages aggravates atherosclerosis. We previously showed that polyphenolic protocatechuic acid (PCA) could reduce inflammation burden in monocyte-derived macrophages; however, it remains unknown how this compound affects MLCs inflammation. Methods: MLCs from the transdifferentiation of vascular smooth muscle cells induced by cholesterol and 30-week-old male ApoE-/- mice fed a semi-purified AIN-93G diet containing either 0.003% (wt:wt) of PCA for a duration of 20 weeks were used to examine the impact of PCA on the inflammatory response of MLCs. Results: Physiologically achievable doses of PCA (0.25-1 μM) dose-dependently inhibited lipopolysaccharide-induced NF-κB activation and simultaneously reduced pro-inflammatory cytokine levels. Mechanistically, this effect was mediated by effecting exportin-1 function, promoting nuclear export of phosphorylated-p65, independent of NF-κB kinase inhibitor α/β/γ, NF-κB inhibitor α, or importin-mediated nuclear import of p-p65. PCA reduced the nucleocytoplasmic ratio of exportin-1 (44%) without altering its abundance. Importantly, dietary supplementation with PCA reduced interleukin-1β content within MLCs in atherosclerotic plaques of ApoE-/- mice. In addition, dietary PCA reduced MLCs content in atherosclerotic plaques. Conclusions: PCA could attenuate inflammatory response in MLCs by targeting exportin-1 and also could inhibit the transdifferentiation of vascular smooth muscle cells into MLCs within atherosclerotic plaques, which might promote the translation from preclinical studies to clinical trials in patients with atherosclerosis.
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MESH Headings
- Animals
- Hydroxybenzoates/pharmacology
- Male
- Muscle, Smooth, Vascular/drug effects
- Muscle, Smooth, Vascular/cytology
- Apolipoproteins E/genetics
- Mice
- Macrophages/drug effects
- Macrophages/metabolism
- Inflammation/drug therapy
- Atherosclerosis/drug therapy
- NF-kappa B/metabolism
- Myocytes, Smooth Muscle/drug effects
- Myocytes, Smooth Muscle/metabolism
- Mice, Knockout, ApoE
- Mice, Knockout
- Cytokines/metabolism
- Mice, Inbred C57BL
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Affiliation(s)
- Shuangshuang Li
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Northern Campus, Guangzhou 510080, China; (S.L.); (Y.D.); (G.C.); (Y.M.); (W.Z.); (M.K.); (S.Z.)
| | - Yushi Du
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Northern Campus, Guangzhou 510080, China; (S.L.); (Y.D.); (G.C.); (Y.M.); (W.Z.); (M.K.); (S.Z.)
| | - Guanyu Chen
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Northern Campus, Guangzhou 510080, China; (S.L.); (Y.D.); (G.C.); (Y.M.); (W.Z.); (M.K.); (S.Z.)
| | - Yihui Mao
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Northern Campus, Guangzhou 510080, China; (S.L.); (Y.D.); (G.C.); (Y.M.); (W.Z.); (M.K.); (S.Z.)
| | - Wenyu Zhang
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Northern Campus, Guangzhou 510080, China; (S.L.); (Y.D.); (G.C.); (Y.M.); (W.Z.); (M.K.); (S.Z.)
| | - Mengxi Kang
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Northern Campus, Guangzhou 510080, China; (S.L.); (Y.D.); (G.C.); (Y.M.); (W.Z.); (M.K.); (S.Z.)
| | - Shasha Zhu
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Northern Campus, Guangzhou 510080, China; (S.L.); (Y.D.); (G.C.); (Y.M.); (W.Z.); (M.K.); (S.Z.)
| | - Dongliang Wang
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Northern Campus, Guangzhou 510080, China; (S.L.); (Y.D.); (G.C.); (Y.M.); (W.Z.); (M.K.); (S.Z.)
- Guangdong Provincial Key Laboratory for Food, Nutrition and Health, Guangzhou 510080, China
- Guangdong Engineering Technology Center of Nutrition Transformation, Sun Yat-sen University, Guangzhou 518107, China
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Zhang L, Yin Y, Jin S. Gut microbial metabolites: The bridge connecting diet and atherosclerosis, and next-generation targets for dietary interventions. Microbiol Res 2025; 292:128037. [PMID: 39752807 DOI: 10.1016/j.micres.2024.128037] [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: 10/08/2024] [Revised: 12/05/2024] [Accepted: 12/19/2024] [Indexed: 01/19/2025]
Abstract
Mounting evidence indicates that gut microbial metabolites are central hubs linking the gut microbiota to atherosclerosis (AS). Gut microbiota enriched with pathobiont bacteria responsible for producing metabolites like trimethylamine N-oxide and phenylacetylglutamine are related to an increased risk of cardiovascular events. Furthermore, gut microbiota enriched with bacteria responsible for producing short-chain fatty acids, indole, and its derivatives, such as indole-3-propionic acid, have demonstrated AS-protective effects. This study described AS-related gut microbial composition and how microbial metabolites affect AS. Summary findings revealed gut microbiota and their metabolites-targeted diets could benefit AS treatment. In conclusion, dietary interventions centered on the gut microbiota represent a promising strategy for AS treatment, and understanding diet-microbiota interactions could potentially be devoted to developing novel anti-AS therapies.
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Affiliation(s)
- Liyin Zhang
- Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Lake Road, East Lake Ecological Scenic, Wuhan, Hubei 430077, China
| | - Yao Yin
- Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Lake Road, East Lake Ecological Scenic, Wuhan, Hubei 430077, China
| | - Si Jin
- Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, 39 Lake Road, East Lake Ecological Scenic, Wuhan, Hubei 430077, China.
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Chen Y, Pan D, Zhu Q, Lu M, Zhang Y, Gao Z, Zhang L, Yi Y, Liu L, Liu Q, Li S, Shen C, Tang Q, Jiang C. Biomimetic metal-phenolic nanocarrier for co-delivery of multiple phytomedical bioactive components for anti-atherosclerotic therapy. Int J Pharm 2025; 671:125228. [PMID: 39832572 DOI: 10.1016/j.ijpharm.2025.125228] [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: 01/10/2025] [Revised: 01/10/2025] [Accepted: 01/14/2025] [Indexed: 01/22/2025]
Abstract
Atherosclerosis, a major cause of cardiovascular diseases, involves complex pathophysiological processes. The co-delivery of multiple bioactive components derived from phytomedicine to atherosclerotic plaque is challenging, especially for those with varied solubilities. This study introduces a novel metal-phenolic network-based core-shell recombinant high-density lipoprotein nanocarrier (SSPH-MPN@rHDL) for co-delivering multiple bioactive components from Salvia miltiorrhiza and Carthamus tinctorius, including salvianic acid A (SAA), salvianolic acid B (SAB), protocatechuic aldehyde (PCA), hydroxysafflor yellow A (HSYA), and tanshinone IIA (TS-IIA). These components have varied solubilities, presenting challenges for achieving synergistic therapeutic effects. The SSPH-MPN@rHDL system encapsulates the four hydrophilic components (i.e. SAA, SAB, PCA, HSYA) within a quaternary metal-phenolic network and a hydrophobic component (i.e. TS-IIA) in an outer lipid layer, facilitating targeted plaque delivery. In vitro and in vivo experimental results demonstrated that SSPH-MPN@rHDL enhanced anti-atherosclerotic efficacy through combined antioxidant, anti-inflammatory, and lipid-lowering actions. This approach offers new perspectives on using nanotechnology to optimize the delivery of phytomedicinal compounds for cardiovascular therapy.
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Affiliation(s)
- Yao Chen
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515 China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515 China
| | - Dongmei Pan
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515 China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515 China
| | - Qinglan Zhu
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515 China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515 China
| | - Meiting Lu
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515 China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515 China
| | - Ying Zhang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515 China
| | - Ziting Gao
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515 China
| | - Lu Zhang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515 China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515 China
| | - Yankui Yi
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515 China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515 China
| | - Li Liu
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515 China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515 China
| | - Qiang Liu
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515 China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515 China
| | - Shasha Li
- College of Pharmacy, Xinjiang Medical University, Urumqi, People's Republic of China
| | - Chunyan Shen
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515 China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515 China; Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou 510515 China.
| | - Qingfa Tang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515 China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515 China; Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou 510515 China.
| | - Cuiping Jiang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515 China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515 China; Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou 510515 China.
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Deveci G, Tek NA. Review on critical factor in monocyte adhesion: Nutrients. Cytokine 2025; 186:156845. [PMID: 39754794 DOI: 10.1016/j.cyto.2024.156845] [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: 10/14/2024] [Revised: 12/18/2024] [Accepted: 12/21/2024] [Indexed: 01/06/2025]
Abstract
Endogenous and exogenous factors play a role in endothelial dysfunction. Inflammation, leukocyte adhesion-aggregation, abnormal vascular proliferation, atherosclerosis, and hypertension are among the endogenous factors. Another factor that affects endothelial dysfunction is exogenous factors such as drug treatments, smoking, alcohol, and nutrition. According various studies on nutrition and endothelial function, it is supported that fatty acids, proteins, and phenolic compounds modulate this function. In vitro studies show that nutrients change the adhesion of monocytes to the endothelium. The pathways that play a role in the adhesion process of monocytes are also affected by nutrients. Particularly among these pathways, mTORC1, S6 plaques, monocyte chemotaxis protein, monocyte integrins, monocyte cytokines are transferred to the lesional area selectin protein. In this article, the effects of various nutrients on monocyte adhesion are examined. It explains the changes and possible mechanisms of nutrients such as fatty acids, protein, phenolic compounds, and other dietary components on monocyte adhesion, and examines the relationship between nutrients and monocyte adhesion in our country and allows us to look at our profession from a different perspective. Although not all nutritional elements are included, it is thought that our profession will play a role in taking the first step towards cell studies.
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Affiliation(s)
- Gülsüm Deveci
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Çankırı Kartekin University, Çankırı 18000, Türkiye.
| | - Nilüfer Acar Tek
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Gazi University, Ankara 06490, Türkiye
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8
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Safaeian L, Haghighatian Z, Zamani M. Cardioprotective potential of protocatechuic acid against doxorubicin-induced cardiotoxicity in rats. Res Pharm Sci 2025; 20:55-64. [PMID: 40190819 PMCID: PMC11972024 DOI: 10.4103/rps.rps_220_23] [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: 10/20/2023] [Revised: 04/07/2024] [Accepted: 06/01/2024] [Indexed: 04/09/2025] Open
Abstract
Background and purpose Chemotherapy with doxorubicin (DOX) is associated with toxicity in many organs including cardiac tissue. A large body of evidence has suggested that phenolic acids, such as protocatechuic acid (PCA), have beneficial effects on cardiovascular problems. This investigation was conducted to evaluate the ameliorative properties of PCA against DOX-induced cardiotoxicity in Wistar rats. Experimental approach Animals were treated with PCA (50, 100, and 200 mg/kg, orally) for 10 days. On the 7th day, a single injection of DOX (20 mg/kg/day, i.p.) was administered to induce cardiotoxicity. Electrocardiography, biochemical analysis of cardiac markers, and histological inspections were performed. Findings/Results Pretreatment with PCA, especially at the doses of 100 and 200 mg/kg for 7 days before the administration of DOX, significantly improved cardiac rhythm and pathological changes, reduced serum levels of creatine phosphokinase-MB, lactate dehydrogenase, aspartate aminotransferase, lipid peroxides and also prevented heart weight rise. Conclusions and implications The in-vivo findings of the current study revealed that PCA exhibits protective effects against DOX-induced cardiotoxicity. These results suggest that PCA, a natural phenolic acid, may serve as a promising candidate for cardioprotective interventions in clinical trials involving chemotherapy with DOX.
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Affiliation(s)
- Leila Safaeian
- Department of Pharmacology and Toxicology and Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran
| | - Zahra Haghighatian
- Department of Pathology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, I.R. Iran
| | - Mohammadreza Zamani
- Department of Pharmacology and Toxicology and Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran
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Mao Y, Huang J, Li S, Chen G, Du Y, Kang M, Zhu S, Zhang W, Xu Q, Wang Y, Ling W, Luo X, Wang D. Brussels Chicory Enhances Exhaustive Aerobic Exercise Performance and Post-Exercise Recovery, Possibly Through Promotion of Lactate Oxidation: A Pilot Randomized, Single-Blind, Placebo-Controlled, Two-Way Crossover Study. Nutrients 2025; 17:365. [PMID: 39861495 PMCID: PMC11769108 DOI: 10.3390/nu17020365] [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: 12/31/2024] [Revised: 01/18/2025] [Accepted: 01/18/2025] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND Brussels chicory affluent in phenolic acids could inhibit atherosclerosis; however, its effects on exercise performance and post-exercise recovery are unknown. We hypothesized that Brussels chicory could enhance exhaustive aerobic exercise performance and post-exercise recovery by promoting lactate oxidation. METHODS This is a single-blind, randomized, placebo-controlled two-way cross-over trial involving 32 untrained college students (men 18) who consumed either Brussels chicory juice (100 g of Brussels chicory containing ~130 mg phenolic acids and 180 mL fresh milk) or placebo (180 mL fresh milk) for 7 days with a 2-week washout period. On the 7th day, participants received a short-term, progressive workload, high-intensity, exhaustive aerobic exercise with the Bruce protocol. Time to exhaustion and blood lactate were evaluated after exercise. C2C12 myotubes were treated with Brussels chicory phenolic acids (0.625-10 μM) to evaluate these effects on lactate metabolism and lactate dehydrogenase A (LDHA) and B (LDHB), two enzymes responsible for lactate biosynthesis and oxidation, respectively. RESULTS Brussels chicory consumption increased time to exhaustion by 8.3% and 12.2% for men and women participants, respectively. This administration also promoted post-exercise recovery, evidenced by a reduction in blood lactate (14.5% for men and 10.6% for women). In C2C12 myotubes, Brussels chicory protocatechuic acid and caffeic acid did not affect LHDA-mediated lactate production, whereas these compounds dose-dependently promoted LDHB-mediated lactate oxidation through an enrichment of mitochondria LDHB. CONCLUSIONS Dietary supplementation with Brussels chicory may enhance short-term, progressive workload, high-intensity, exhaustive aerobic exercise performance and post-exercise recovery in humans, possibly by accelerating LDHB-mediated lactate oxidation.
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Affiliation(s)
- Yihui Mao
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), 74 Zhongshan Road II, Guangzhou 510080, China; (Y.M.); (S.L.); (G.C.); (Y.D.); (M.K.); (S.Z.); (W.Z.); (Q.X.); (Y.W.); (W.L.)
| | - Junhao Huang
- Guangdong Provincial Key Laboratory of Sports and Health Promotion, Scientific Research Center, Guangzhou Sport University, Guangzhou 510500, China;
| | - Shuangshuang Li
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), 74 Zhongshan Road II, Guangzhou 510080, China; (Y.M.); (S.L.); (G.C.); (Y.D.); (M.K.); (S.Z.); (W.Z.); (Q.X.); (Y.W.); (W.L.)
| | - Guanyu Chen
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), 74 Zhongshan Road II, Guangzhou 510080, China; (Y.M.); (S.L.); (G.C.); (Y.D.); (M.K.); (S.Z.); (W.Z.); (Q.X.); (Y.W.); (W.L.)
| | - Yushi Du
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), 74 Zhongshan Road II, Guangzhou 510080, China; (Y.M.); (S.L.); (G.C.); (Y.D.); (M.K.); (S.Z.); (W.Z.); (Q.X.); (Y.W.); (W.L.)
| | - Mengxi Kang
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), 74 Zhongshan Road II, Guangzhou 510080, China; (Y.M.); (S.L.); (G.C.); (Y.D.); (M.K.); (S.Z.); (W.Z.); (Q.X.); (Y.W.); (W.L.)
| | - Shasha Zhu
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), 74 Zhongshan Road II, Guangzhou 510080, China; (Y.M.); (S.L.); (G.C.); (Y.D.); (M.K.); (S.Z.); (W.Z.); (Q.X.); (Y.W.); (W.L.)
| | - Wenyu Zhang
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), 74 Zhongshan Road II, Guangzhou 510080, China; (Y.M.); (S.L.); (G.C.); (Y.D.); (M.K.); (S.Z.); (W.Z.); (Q.X.); (Y.W.); (W.L.)
| | - Qiuhui Xu
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), 74 Zhongshan Road II, Guangzhou 510080, China; (Y.M.); (S.L.); (G.C.); (Y.D.); (M.K.); (S.Z.); (W.Z.); (Q.X.); (Y.W.); (W.L.)
| | - Yihan Wang
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), 74 Zhongshan Road II, Guangzhou 510080, China; (Y.M.); (S.L.); (G.C.); (Y.D.); (M.K.); (S.Z.); (W.Z.); (Q.X.); (Y.W.); (W.L.)
| | - Wenhua Ling
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), 74 Zhongshan Road II, Guangzhou 510080, China; (Y.M.); (S.L.); (G.C.); (Y.D.); (M.K.); (S.Z.); (W.Z.); (Q.X.); (Y.W.); (W.L.)
- Guangdong Provincial Key Laboratory for Food, Nutrition and Health, Guangzhou 510080, China
| | - Xijuan Luo
- Department of Sports, Sun Yat-sen University, 135 West Xingang Road, Guangzhou 510275, China
| | - Dongliang Wang
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), 74 Zhongshan Road II, Guangzhou 510080, China; (Y.M.); (S.L.); (G.C.); (Y.D.); (M.K.); (S.Z.); (W.Z.); (Q.X.); (Y.W.); (W.L.)
- Guangdong Provincial Key Laboratory for Food, Nutrition and Health, Guangzhou 510080, China
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10
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Du L, Ding X, Tian Y, Chen J, Li W. Effect of anthocyanins on metabolic syndrome through interacting with gut microbiota. Pharmacol Res 2024; 210:107511. [PMID: 39577753 DOI: 10.1016/j.phrs.2024.107511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 10/22/2024] [Accepted: 11/16/2024] [Indexed: 11/24/2024]
Abstract
Metabolic syndrome, as a complex pathological condition, is caused by a series of pathogenic factors and has become a global public health challenge. Anthocyanins, a natural water-soluble flavonoid pigment, have attracted much attention due to their antioxidant, anti-inflammatory, and anticancer biological activities. After ingestion, a majority of anthocyanins is not directly absorbed but rather reaches the colon. Hence, the exertion of their biological benefits is closely intertwined with the role played by gut microbiota. In this review, we introduce the pathogenesis and intervention methods of metabolic syndrome, as well as the interaction between anthocyanins and gut microbiota. We also discuss the therapeutic potential of anthocyanins through gut microbiota in addressing a range of metabolic syndrome conditions, including obesity, type 2 diabetes mellitus, cardiovascular diseases, non-alcoholic fatty liver disease, inflammatory bowel disease, polycystic ovary syndrome, osteoporosis, and cancer.
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Affiliation(s)
- Lanlan Du
- State Key Laboratory of Tree Genetics and Breeding, Co-Innovation Center for Sustainable Forestry in Southern China, College of Forestry and Grassland, Nanjing Forestry University, Nanjing 210037, China
| | - Xiaoqin Ding
- Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China
| | - Yuwen Tian
- Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China
| | - Jian Chen
- Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
| | - Weilin Li
- State Key Laboratory of Tree Genetics and Breeding, Co-Innovation Center for Sustainable Forestry in Southern China, College of Forestry and Grassland, Nanjing Forestry University, Nanjing 210037, China.
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11
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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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12
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Sun M, Zhang Z, Xie J, Yu J, Xiong S, Xiang F, Ma X, Yang C, Lin L. Research Progress on the Mechanism for Improving Glucose and Lipid Metabolism Disorders Using Phenolic Acid Components from Medicinal and Edible Homologous Plants. Molecules 2024; 29:4790. [PMID: 39459158 PMCID: PMC11510019 DOI: 10.3390/molecules29204790] [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: 09/01/2024] [Revised: 10/04/2024] [Accepted: 10/08/2024] [Indexed: 10/28/2024] Open
Abstract
Glucose and lipid metabolism disorders are the core pathological mechanism of a variety of metabolic diseases, and the incidence of related diseases is increasing year by year, which seriously threatens human life and health. Traditional Chinese medicine with medicinal and edible properties refers to Chinese medicinal resources that have both medicinal and edible characteristics. Due to its safety and its health-promoting and medicinal functions, traditional Chinese medicine has received increasing attention in the development of functional health foods. Phenolic acids are important secondary metabolites that are ubiquitous in medicinal and edible homologous plants, and the regulation of glycolipid metabolism is an important activity and plays a key role in many diseases. In this paper, we focus on the alleviation of glycolipid disorders using MEHH phenolic acids, which regulate glucose metabolism and lipid metabolism, improve insulin resistance, inhibit inflammatory responses, alleviate oxidative stress, and regulate intestinal flora; additionally, we summarize the mechanism in order to provide a reference for MEHH phenolic acids in the treatment of glycolipid metabolism diseases.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Limei Lin
- Key Laboratory for Quality Evaluation of Bulk Herbs of Human Province, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China; (M.S.); (Z.Z.); (J.X.); (J.Y.); (S.X.); (F.X.); (X.M.); (C.Y.)
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13
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Flori L, Benedetti G, Martelli A, Calderone V. Microbiota alterations associated with vascular diseases: postbiotics as a next-generation magic bullet for gut-vascular axis. Pharmacol Res 2024; 207:107334. [PMID: 39103131 DOI: 10.1016/j.phrs.2024.107334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 07/11/2024] [Accepted: 07/29/2024] [Indexed: 08/07/2024]
Abstract
The intestinal microbiota represents a key element in maintaining the homeostasis and health conditions of the host. Vascular pathologies and other risk factors such as aging have been recently associated with dysbiosis. The qualitative and quantitative alteration of the intestinal microbiota hinders correct metabolic homeostasis, causing structural and functional changes of the intestinal wall itself. Impairment of the intestinal microbiota, combined with the reduction of the barrier function, worsen the pathological scenarios of peripheral tissues over time, including the vascular one. Several experimental evidence, collected in this review, describes in detail the changes of the intestinal microbiota in dysbiosis associated with vascular alterations, such as atherosclerosis, hypertension, and endothelial dysfunction, the resulting metabolic disorders and how these can impact on vascular health. In this context, the gut-vascular axis is considered, for the first time, as a merged unit involved in the development and progression of vascular pathologies and as a promising target. Current approaches for the management of dysbiosis such as probiotics, prebiotics and dietary modifications act mainly on the intestinal district. Postbiotics, described as preparation of inanimate microorganisms and/or their components that confers health benefits on the host, represent an innovative strategy for a dual management of intestinal dysbiosis and vascular pathologies. In this context, this review has the further purpose of defining the positive effects of the supplementation of bacterial strains metabolites (short‑chain fatty acids, exopolysaccharides, lipoteichoic acids, gallic acid, and protocatechuic acid) restoring intestinal homeostasis and acting directly on the vascular district through the gut-vascular axis.
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Affiliation(s)
- Lorenzo Flori
- Department of Pharmacy, University of Pisa, via Bonanno, Pisa 6-56120, Italy.
| | - Giada Benedetti
- Department of Pharmacy, University of Pisa, via Bonanno, Pisa 6-56120, Italy.
| | - Alma Martelli
- Department of Pharmacy, University of Pisa, via Bonanno, Pisa 6-56120, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, Pisa 56120, Italy; Interdepartmental Research Centre of Ageing Biology and Pathology, University of Pisa, Pisa 56120, Italy.
| | - Vincenzo Calderone
- Department of Pharmacy, University of Pisa, via Bonanno, Pisa 6-56120, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, Pisa 56120, Italy; Interdepartmental Research Centre of Ageing Biology and Pathology, University of Pisa, Pisa 56120, Italy.
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14
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Liang A, Leonard W, Beasley JT, Fang Z, Zhang P, Ranadheera CS. Anthocyanins-gut microbiota-health axis: A review. Crit Rev Food Sci Nutr 2024; 64:7563-7588. [PMID: 36927343 DOI: 10.1080/10408398.2023.2187212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Abstract
Anthocyanins are a subclass of flavonoids responsible for color in some fruits and vegetables with potent antioxidative capacity. During digestion, a larger proportion of dietary anthocyanins remains unabsorbed and reach the large intestine where they interact with the gut microbiota. Anthocyanins can modulate gut microbial populations to improve diversity and the proportion of beneficial populations, leading to alterations in short chain fatty acid and bile acid production. Some anthocyanins can be degraded into colonic metabolites, such as phenolic acids, which accumulate in the body and regulate a range of biological activities. Here we provide an overview of the effects of dietary anthocyanin consumption on gut microbial interactions, metabolism, and composition. Progression of chronic diseases has been strongly associated with imbalances in gut microbial populations. We therefore focus on the role of the gut microbiota as the 'mediator' that facilitates the therapeutic potential of anthocyanins against various chronic diseases, including obesity, type II diabetes, cardiovascular disease, neurodegenerative disease, inflammatory bowel disease, cancer, fatty liver disease, chronic kidney disease and osteoarthritis.
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Affiliation(s)
- Anqi Liang
- School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Victoria, Australia
| | - William Leonard
- School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Victoria, Australia
| | - Jesse T Beasley
- School of BioSciences, Faculty of Science, University of Melbourne, Parkville, Victoria, Australia
| | - Zhongxiang Fang
- School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Victoria, Australia
| | - Pangzhen Zhang
- School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Victoria, Australia
| | - Chaminda Senaka Ranadheera
- School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, Victoria, Australia
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15
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Sim WJ, Lee E, Lee G, Lim W, Lim TG. Inhibition of Photoaging by Anthocyanin Metabolites Derived from Rose Petal Extract. Mol Nutr Food Res 2024; 68:e2300611. [PMID: 38319040 DOI: 10.1002/mnfr.202300611] [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: 08/27/2023] [Revised: 12/06/2023] [Indexed: 02/07/2024]
Abstract
SCOPE Rose petal extract (RPE) shows a significant antioxidant effect through its anthocyanin content. However, the mechanism underlying the anti-aging effects of orally administered RPE remains unclear. This study aims to describe the anti-aging effect and mechanism of action of orally administered RPE in ultraviolet (UV)B-induced skin aging. METHODS AND RESULTS This study evaluates the protein expression of collagen type I alpha 1 (COL1A1) and matrix metalloproteinase 1 (MMP-1) and the mRNA expression of hyaluronic synthase 2 (HAS2) in human dermal fibroblasts. In addition, the hyaluronidase and collagenase inhibitory activities of RPE are confirmed. To evaluate the anti-aging effects of RPE, SKH-1 hairless mice are administered RPE daily for 12 weeks. Wrinkle formation, transepidermal water loss (TEWL), and skin moisture loss induced by UVB irradiation are suppressed in the dorsal skin of SKH-1 hairless mice orally administered RPE. Oral administration of RPE suppresses UVB irradiation-induced collagen disruption and reduction of hyaluronic acid. To find the bioactive compound in the RPE, serum protocatechuic acid (PCA), an anthocyanin metabolite, is analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). CONCLUSION Anthocyanins in RPE are metabolized to PCA in the body and circulated through the bloodstream to exhibit anti-aging effects on the skin.
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Affiliation(s)
- Woo-Jin Sim
- Department of Food Science & Biotechnology, Sejong University, Seoul, 05006, Republic of Korea
| | - Eunjung Lee
- Research Group of Traditional Food, Korea Food Research Institute, Wanju, 55365, Republic of Korea
| | - Gakyung Lee
- Department of Integrative Biological Sciences and Industry, Sejong University, Seoul, 05006, Republic of Korea
- Convergence Research Center for Natural Products, Sejong University, Seoul, 05006, Republic of Korea
| | - Wonchul Lim
- Department of Food Science & Biotechnology, and Carbohydrate Bioproduct Research Center, Sejong University, Seoul, 05006, Republic of Korea
| | - Tae-Gyu Lim
- Department of Food Science & Biotechnology, Sejong University, Seoul, 05006, Republic of Korea
- Department of Food Science & Biotechnology, and Carbohydrate Bioproduct Research Center, Sejong University, Seoul, 05006, Republic of Korea
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16
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Ding H, Liu J, Chen Z, Huang S, Yan C, Kwek E, He Z, Zhu H, Chen ZY. Protocatechuic acid alleviates TMAO-aggravated atherosclerosis via mitigating inflammation, regulating lipid metabolism, and reshaping gut microbiota. Food Funct 2024; 15:881-893. [PMID: 38165856 DOI: 10.1039/d3fo04396g] [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: 01/04/2024]
Abstract
Trimethylamine-N-oxide (TMAO) is a risk factor for atherosclerosis. As a natural phenolic acid, protocatechuic acid (PCA) is abundant in various plant foods. The present study investigated the effect of PCA on TMAO-aggravated atherosclerosis in ApoE-/- mice. The mice were randomly divided into five groups and fed one of the following five diets for 12 weeks: namely a low-fat diet (LFD), a western diet (WD), a WD + 0.2% TMAO diet (WDT), a WDT + 0.5% PCA diet (WDT + LPCA), and a WDT + 1.0% PCA diet (WDT + HPCA). Results demonstrated that dietary TMAO exacerbated the development of atherosclerosis by eliciting inflammation and disturbing lipid metabolism. The diet with PCA at 1% reduced TMAO-induced aortic plaque by 30% and decreased the levels of plasma pro-inflammatory cytokines. PCA also improved lipid metabolism by up-regulating the hepatic gene expression of peroxisome proliferator-activated receptor alpha (PPARα). In addition, PCA supplementation enhanced fecal excretion of fatty acids and decreased hepatic fat accumulation. PCA supplementation favorably modulated gut microbiota by increasing the α-diversity with an increase in the abundance of beneficial genera (Rikenella, Turicibacter, Clostridium_sensu_stricto and Bifidobacterium) and a decrease in the abundance of the harmful Helicobacter genus. In summary, PCA could alleviate the TMAO-exacerbated atherosclerosis and inflammation, improve the lipid metabolism, and modulate gut microbiota.
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Affiliation(s)
- Huafang Ding
- Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China.
| | - Jianhui Liu
- Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China.
- College of Food Science and Engineering, Nanjing University of Finance and Economics, Collaborative Innovation Center for Modern Grain Circulation and Safety, Jiangsu Province Engineering Research Center of Edible Fungus Preservation and Intensive Processing, Nanjing 210023, China
| | - Zixing Chen
- Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China.
| | - Shouhe Huang
- Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China.
| | - Chi Yan
- Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China.
| | - Erika Kwek
- Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China.
| | - Zouyan He
- Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China.
| | - Hanyue Zhu
- Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China.
| | - Zhen-Yu Chen
- Food & Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China.
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Lamenza FF, Upadhaya P, Roth P, Shrestha S, Jagadeesha S, Horn N, Pracha H, Oghumu S. Berries vs. Disease: Revenge of the Phytochemicals. Pharmaceuticals (Basel) 2024; 17:84. [PMID: 38256917 PMCID: PMC10818490 DOI: 10.3390/ph17010084] [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: 12/02/2023] [Revised: 01/03/2024] [Accepted: 01/05/2024] [Indexed: 01/24/2024] Open
Abstract
Secondary metabolites and phytochemicals in plant-based diets are known to possess properties that inhibit the development of several diseases including a variety of cancers of the aerodigestive tract. Berries are currently of high interest to researchers due to their high dietary source of phytochemicals. Black raspberries (BRB), Rubus occidentalis, are of special interest due to their rich and diverse composition of phytochemicals. In this review, we present the most up-to-date preclinical and clinical data involving berries and their phytochemicals in the chemoprevention of a variety of cancers and diseases. BRBs possess a variety of health benefits including anti-proliferative properties, anti-inflammatory activity, activation of pro-cell-death pathways, modulation of the immune response, microbiome modulation, reduction in oxidative stress, and many more. However, little has been done in both preclinical and clinical settings on the effects of BRB administration in combination with other cancer therapies currently available for patients. With the high potential for BRBs as chemopreventive agents, there is a need to investigate their potential in combination with other treatments to improve therapeutic efficacy.
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Affiliation(s)
- Felipe F. Lamenza
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (F.F.L.); (P.U.); (P.R.); (S.S.); (S.J.); (N.H.); (H.P.)
- Department of Microbiology, The Ohio State University, Columbus, OH 43210, USA
| | - Puja Upadhaya
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (F.F.L.); (P.U.); (P.R.); (S.S.); (S.J.); (N.H.); (H.P.)
| | - Peyton Roth
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (F.F.L.); (P.U.); (P.R.); (S.S.); (S.J.); (N.H.); (H.P.)
| | - Suvekshya Shrestha
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (F.F.L.); (P.U.); (P.R.); (S.S.); (S.J.); (N.H.); (H.P.)
- Department of Microbiology, The Ohio State University, Columbus, OH 43210, USA
| | - Sushmitha Jagadeesha
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (F.F.L.); (P.U.); (P.R.); (S.S.); (S.J.); (N.H.); (H.P.)
| | - Natalie Horn
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (F.F.L.); (P.U.); (P.R.); (S.S.); (S.J.); (N.H.); (H.P.)
| | - Hasan Pracha
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (F.F.L.); (P.U.); (P.R.); (S.S.); (S.J.); (N.H.); (H.P.)
| | - Steve Oghumu
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (F.F.L.); (P.U.); (P.R.); (S.S.); (S.J.); (N.H.); (H.P.)
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18
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Xiang P, Du Y, Chen G, Mao Y, Li S, Li Q, Yang Y, Li X, Wang D. Dietary Achievable Dose of Protocatechuic Acid, a Metabolite of Flavonoids, Inhibits High-Fat Diet-Induced Obesity in Mice. Mol Nutr Food Res 2024; 68:e2300451. [PMID: 37997172 DOI: 10.1002/mnfr.202300451] [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: 06/30/2023] [Revised: 09/11/2023] [Indexed: 11/25/2023]
Abstract
SCOPE Protocatechuic acid (PCA), a gut microbiota metabolite of flavonoids, inhibits dietary obesity and increases uncoupling protein 1 (UCP1), a critical regulator responsible for adipose thermogenesis; however, these effects are achieved at dietary unachievable (pharmacological) dose. It evaluates whether dietary achievable dose of PCA inhibits adiposity by activating adipose thermogenesis. METHODS AND RESULTS Six-week-old male C57BL/6J mice are fed a high-fat diet (HFD) alone (control) or supplemented with 0.003% PCA w/w for 16 weeks. PCA consumption does not affect food intake but appreciably reduces body weight gain, improves insulin sensitivity, and attenuates hepatic steatosis. These effects are associated with no significant changes in the abundance of UCP1 in adipose tissues. Instead, PCA consumption increases the abundance and enzymatic activity of carnitine palmitoyltransferase 1 (the first rate-limiting enzyme in fatty acid oxidation) in the livers, inguinal white, and brown adipose tissues. Surprisingly, PCA at physiologically achievable dose does not affect the abundance and enzymatic activity of carnitine acyltransferase-1 expression and the capacity of fatty acid oxidation in 3T3-L1-derived white or brown adipocytes and human hepatoma HepG2 cells. CONCLUSIONS Dietary achievable dose of PCA attenuates HFD-induced adiposity, which is likely achieved by increasing fatty acid oxidation other than activating adipose thermogenesis.
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Affiliation(s)
- Panyin Xiang
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510080, PR China
| | - Yushi Du
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510080, PR China
| | - Guanyu Chen
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510080, PR China
| | - Yihui Mao
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510080, PR China
| | - Shuangshuang Li
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510080, PR China
| | - Qing Li
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510080, PR China
| | - Yuting Yang
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510080, PR China
| | - Xueyu Li
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510080, PR China
| | - Dongliang Wang
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, 510080, PR China
- Guangdong Provincial Key Laboratory for Food, Nutrition and Health, Guangzhou, 510080, PR China
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Roney M, Issahaku AR, Huq AM, Soliman MES, Tajuddin SN, Aluwi MFFM. Exploring the potential of biologically active phenolic acids from marine natural products as anticancer agents targeting the epidermal growth factor receptor. J Biomol Struct Dyn 2023; 42:13564-13587. [PMID: 37909584 DOI: 10.1080/07391102.2023.2276879] [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: 06/26/2023] [Accepted: 10/22/2023] [Indexed: 11/03/2023]
Abstract
The epidermal growth factor receptor (EGFR) dimerizes upon ligand bindings to the extracellular domain that initiates the downstream signaling cascades and activates intracellular kinase domain. Thus, activation of autophosphorylation through kinase domain results in metastasis, cell proliferation, and angiogenesis. The main objective of this research is to discover more promising anti-cancer lead compound against EGRF from the phenolic acids of marine natural products using in-silico approaches. Phenolic compounds reported from marine sources are reviewed from previous literatures. Furthermore, molecular docking was carried out using the online tool CB-Dock. The molecules with good docking and binding energies scores were subjected to ADME, toxicity and drug-likeness analysis. Subsequently, molecules from the docking experiments were also evaluated using the acute toxicity and MD simulation studies. Fourteen phenolic compounds from the reported literatures were reviewed based on the findings, isolation, characterized and applications. Molecular docking studies proved that the phenolic acids have good binding fitting by forming hydrogen bonds with amino acid residues at the binding site of EGFR. Chlorogenic acid, Chicoric acid and Rosmarinic acid showed the best binding energies score and forming hydrogen bonds with amino acid residues compare to the reference drug Erlotinib. Among these compounds, Rosmarinic acid showed the good pharmacokinetics profiles as well as acute toxicity profile. The MD simulation study further revealed that the lead complex is stable and could be future drug to treat the cancer disease. Furthermore, in a wet lab environment, both in-vitro and in-vivo testing will be employed to validate the existing computational results.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Miah Roney
- Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang Al-Sultan Abdullah, Lebuhraya Tun Razak, Kuantan, Pahang Darul Makmur, Malaysia
- Centre for Bio-aromatic Research, Universiti Malaysia Pahang Al-Sultan Abdullah, Lebuhraya Tun Razak, Kuantan, Pahang Darul Makmur, Malaysia
| | - Abdul Rashid Issahaku
- Department of Chemistry, University of the Free State, Bloemfontein, South Africa
- Molecular Bio-computation and Drug Design Laboratory, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Akm Moyeenul Huq
- Centre for Bio-aromatic Research, Universiti Malaysia Pahang Al-Sultan Abdullah, Lebuhraya Tun Razak, Kuantan, Pahang Darul Makmur, Malaysia
- School of Medicine, Department of Pharmacy, University of Asia Pacific, Bangladesh
| | - Mahmoud E S Soliman
- Molecular Bio-computation and Drug Design Laboratory, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Saiful Nizam Tajuddin
- Centre for Bio-aromatic Research, Universiti Malaysia Pahang Al-Sultan Abdullah, Lebuhraya Tun Razak, Kuantan, Pahang Darul Makmur, Malaysia
| | - Mohd Fadhlizil Fasihi Mohd Aluwi
- Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang Al-Sultan Abdullah, Lebuhraya Tun Razak, Kuantan, Pahang Darul Makmur, Malaysia
- Centre for Bio-aromatic Research, Universiti Malaysia Pahang Al-Sultan Abdullah, Lebuhraya Tun Razak, Kuantan, Pahang Darul Makmur, Malaysia
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20
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Ijinu TP, De Lellis LF, Shanmugarama S, Pérez-Gregorio R, Sasikumar P, Ullah H, Buccato DG, Di Minno A, Baldi A, Daglia M. Anthocyanins as Immunomodulatory Dietary Supplements: A Nutraceutical Perspective and Micro-/Nano-Strategies for Enhanced Bioavailability. Nutrients 2023; 15:4152. [PMID: 37836436 PMCID: PMC10574533 DOI: 10.3390/nu15194152] [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] [Received: 09/07/2023] [Revised: 09/21/2023] [Accepted: 09/24/2023] [Indexed: 10/15/2023] Open
Abstract
Anthocyanins (ACNs) have attracted considerable attention for their potential to modulate the immune system. Research has revealed their antioxidant and anti-inflammatory properties, which play a crucial role in immune regulation by influencing key immune cells, such as lymphocytes, macrophages, and dendritic cells. Moreover, ACNs contribute towards maintaining a balance between proinflammatory and anti-inflammatory cytokines, thus promoting immune health. Beyond their direct effects on immune cells, ACNs significantly impact gut health and the microbiota, essential factors in immune regulation. Emerging evidence suggests that they positively influence the composition of the gut microbiome, enhancing their immunomodulatory effects. Furthermore, these compounds synergize with other bioactive substances, such as vitamins and minerals, further enhancing their potential as immune-supporting dietary supplements. However, detailed clinical studies must fully validate these findings and determine safe dosages across varied populations. Incorporating these natural compounds into functional foods or supplements could revolutionize the management of immune-related conditions. Personalized nutrition and healthcare strategies may be developed to enhance overall well-being and immune resilience by fully understanding the mechanisms underlying the actions of their components. Recent advancements in delivery methods have focused on improving the bioavailability and effectiveness of ACNs, providing promising avenues for future applications.
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Affiliation(s)
- Thadiyan Parambil Ijinu
- Naturæ Scientific, Kerala University-Business Innovation and Incubation Centre, Kariavattom Campus, University of Kerala, Thiruvananthapuram 695581, India;
- The National Society of Ethnopharmacology, VRA-179, Mannamoola, Peroorkada P.O., Thiruvananthapuram 695005, India
| | - Lorenza Francesca De Lellis
- Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy; (L.F.D.L.); (D.G.B.); (A.D.M.); (A.B.)
| | - Santny Shanmugarama
- Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA;
| | - Rosa Pérez-Gregorio
- Food and Health Omics Group, Institute of Agroecology and Food, Faculty of Sciences, University of Vigo, 32004 Ourense, Spain;
- LAQV-REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal
- Department of Analytical and Food Chemistry, Galicia Sur Health Research Institute (IISGS), SERGAS-UVIGO, 32002 Ourense, Spain
| | | | - Hammad Ullah
- Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy; (L.F.D.L.); (D.G.B.); (A.D.M.); (A.B.)
| | - Daniele Giuseppe Buccato
- Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy; (L.F.D.L.); (D.G.B.); (A.D.M.); (A.B.)
| | - Alessandro Di Minno
- Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy; (L.F.D.L.); (D.G.B.); (A.D.M.); (A.B.)
- CEINGE-Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Naples, Italy
| | - Alessandra Baldi
- Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy; (L.F.D.L.); (D.G.B.); (A.D.M.); (A.B.)
| | - Maria Daglia
- Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy; (L.F.D.L.); (D.G.B.); (A.D.M.); (A.B.)
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
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21
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Festa J, Hussain A, Al-Hareth Z, Singh H, Da Boit M. Anthocyanins and Vascular Health: A Matter of Metabolites. Foods 2023; 12:foods12091796. [PMID: 37174334 PMCID: PMC10178014 DOI: 10.3390/foods12091796] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/30/2023] [Accepted: 04/19/2023] [Indexed: 05/15/2023] Open
Abstract
Anthocyanins are a subgroup of flavonoid polyphenols previously investigated for improving cardiovascular health and preventing the development of endothelial dysfunction. However, their poor bioavailability raises the question of whether the observed biological activity is due to their metabolites. Phenolic metabolites can reach higher plasma concentrations and can persist in the circulation for periods much longer than their original anthocyanin form; therefore, the biological activity and health promoting effects of anthocyanins may differ from their metabolites. To address this, recent studies have facilitated different cell models, in vivo studies and explored physiologically relevant concentrations to better understand their mechanisms of action. The criteria were chosen based on previous reports demonstrating that anthocyanins can improve endothelial function via modulation of the Akt-endothelial nitric oxide synthase pathway and transcription factors Nrf2 and NF-κB, which made it critical to assess the phenolic metabolites' modes of action via these pathways. This review demonstrates how phenolic metabolites differ in bioactivity from their precursor anthocyanin, demonstrating improved endothelial function in response to inflammatory mediators at concentrations that are tolerated in vivo. The review highlights the crucial need for further studies to focus on improving the bioavailability of metabolites in isolation and explore the effect of metabolites in mixtures.
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Affiliation(s)
- Joseph Festa
- Leicester School of Allied Health Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, UK
| | - Aamir Hussain
- Leicester School of Allied Health Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, UK
| | - Zakia Al-Hareth
- Leicester School of Allied Health Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, UK
- Pandemic Sciences Institute, Old Road Campus, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7TY, UK
| | - Harprit Singh
- Leicester School of Allied Health Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, UK
| | - Mariasole Da Boit
- Leicester School of Allied Health Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, UK
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22
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Shafiee F, Safaeian L, Gorbani F. Protective effects of protocatechuic acid against doxorubicin- and arsenic trioxide-induced toxicity in cardiomyocytes. Res Pharm Sci 2023; 18:149-158. [PMID: 36873272 PMCID: PMC9976056 DOI: 10.4103/1735-5362.367794] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 08/31/2022] [Accepted: 10/23/2022] [Indexed: 01/21/2023] Open
Abstract
Background and purpose Some chemotherapeutic drugs are associated with an increased risk of cardiotoxicity in patients. Protocatechuic acid (PCA) is a phenolic acid with valuable cardiovascular, chemo-preventive, and anticancer activities. Recent studies have shown the cardioprotective effects of PCA in several pathological conditions. This investigation aimed to assess the possible protective effects of PCA on cardiomyocytes against toxicities caused by anti-neoplastic agents, doxorubicin (DOX), and arsenic trioxide (ATO). Experimental approach H9C2 cells were exposed to DOX (1 μM) or ATO (35 μM) after 24 h pretreatment with PCA (1-100 μM). MTT and lactate dehydrogenase (LDH) tests were used to define cell viability or cytotoxicity. Total oxidant and antioxidant capacities were evaluated by measuring hydroperoxides and ferric-reducing antioxidant power (FRAP) levels. Expression of the TLR4 gene was also quantitatively estimated by real-time polymerase chain reaction. Findings/Results PCA showed a proliferative effect on cardiomyocytes and significantly enhanced cell viability and reduced cytotoxicity of DOX and ATO during MTT and LDH assays. Pretreatment of cardiomyocytes with PCA significantly decreased hydroperoxide levels and elevated FRAP value. Moreover, PCA meaningfully decreased TLR4 expression in DOX-and ATO-treated cardiomyocytes. Conclusions and implications In conclusion, antioxidant and cytoprotective activities were found for PCA versus toxicities caused by DOX and ATO in cardiomyocytes. However, further in vivo investigations are recommended to assess its clinical value for the prevention and treatment of cardiotoxicity induced by chemotherapeutic agents.
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Affiliation(s)
- Fatemeh Shafiee
- Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran
| | - Leila Safaeian
- Department of Pharmacology and Toxicology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran
| | - Fatemeh Gorbani
- Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran
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23
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Wang J, Liu YM, Hu J, Chen C. Trained immunity in monocyte/macrophage: Novel mechanism of phytochemicals in the treatment of atherosclerotic cardiovascular disease. Front Pharmacol 2023; 14:1109576. [PMID: 36895942 PMCID: PMC9989041 DOI: 10.3389/fphar.2023.1109576] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 01/27/2023] [Indexed: 02/23/2023] Open
Abstract
Atherosclerosis (AS) is the pathology of atherosclerotic cardiovascular diseases (ASCVD), characterized by persistent chronic inflammation in the vessel wall, in which monocytes/macrophages play a key role. It has been reported that innate immune system cells can assume a persistent proinflammatory state after short stimulation with endogenous atherogenic stimuli. The pathogenesis of AS can be influenced by this persistent hyperactivation of the innate immune system, which is termed trained immunity. Trained immunity has also been implicated as a key pathological mechanism, leading to persistent chronic inflammation in AS. Trained immunity is mediated via epigenetic and metabolic reprogramming and occurs in mature innate immune cells and their bone marrow progenitors. Natural products are promising candidates for novel pharmacological agents that can be used to prevent or treat cardiovascular diseases (CVD). A variety of natural products and agents exhibiting antiatherosclerotic abilities have been reported to potentially interfere with the pharmacological targets of trained immunity. This review describes in as much detail as possible the mechanisms involved in trained immunity and how phytochemicals of this process inhibit AS by affecting trained monocytes/macrophages.
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Affiliation(s)
- Jie Wang
- Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing, China
| | - Yong-Mei Liu
- Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing, China
| | - Jun Hu
- Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing, China
| | - Cong Chen
- Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, Beijing, China
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24
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Effects of refining process on Camellia vietnamensis oil: Phytochemical composition, antioxidant capacity, and anti-inflammatory activity in THP-1 macrophages. FOOD BIOSCI 2023. [DOI: 10.1016/j.fbio.2023.102440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
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25
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Dietary Supplementation with Black Raspberries Altered the Gut Microbiome Composition in a Mouse Model of Colitis-Associated Colorectal Cancer, although with Differing Effects for a Healthy versus a Western Basal Diet. Nutrients 2022; 14:nu14245270. [PMID: 36558431 PMCID: PMC9786988 DOI: 10.3390/nu14245270] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 11/30/2022] [Accepted: 12/03/2022] [Indexed: 12/14/2022] Open
Abstract
Black raspberries (BRB) are rich in anthocyanins with purported anti-inflammatory properties. However, it is not known whether dietary supplementation would ameliorate Western-diet enhanced gut inflammation and colon tumorigenesis. We employed a mouse model of colitis-associated colorectal cancer (CAC) to determine the effects of dietary supplementation with 5 to 10% (w/w) whole, freeze-dried BRB in male C57BL/6J mice fed either a standard healthy diet (AIN93G) or the total Western diet (TWD). In a pilot study, BRB suppressed colitis and colon tumorigenesis while also shifting the composition of the fecal microbiome in favor of taxa with purported health benefits, including Bifidobacterium pseudolongum. In a follow-up experiment using a 2 × 2 factorial design with AIN and TWD basal diets with and without 10% (w/w) BRB, supplementation with BRB reduced tumor multiplicity and increased colon length, irrespective of the basal diet, but it did not apparently affect colitis symptoms, colon inflammation or mucosal injury based on histopathological findings. However, BRB intake increased alpha diversity, altered beta diversity and changed the relative abundance of Erysipelotrichaceae, Bifidobacteriaceae, Streptococcaceae, Rikenellaceae, Ruminococcaceae and Akkermansiaceae, among others, of the fecal microbiome. Notably, changes in microbiome profiles were inconsistent with respect to the basal diet consumed. Overall, these studies provide equivocal evidence for in vivo anti-inflammatory effects of BRB on colitis and colon tumorigenesis; yet, BRB supplementation led to dynamic changes in the fecal microbiome composition over the course of disease development.
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26
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Graton ME, Ferreira BHSH, Troiano JA, Potje SR, Vale GT, Nakamune ACMS, Tirapelli CR, Miller FJ, Ximenes VF, Antoniali C. Comparative study between apocynin and protocatechuic acid regarding antioxidant capacity and vascular effects. Front Physiol 2022; 13:1047916. [PMID: 36457305 PMCID: PMC9707364 DOI: 10.3389/fphys.2022.1047916] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 10/18/2022] [Indexed: 03/14/2024] Open
Abstract
Reactive oxygen species (ROS) derived from NOX enzymes activity play an important role in the development of cardiovascular diseases. Compounds able to decrease oxidative stress damage are potential candidates as drugs and/or supplements for hypertension treatment. Here, we aimed to compare in vitro ROS scavenging potency, effective NOX inhibition and effects on vascular reactivity of apocynin to another phenolic compound, protocatechuic acid, in vascular cells from spontaneously hypertensive rat (SHR), where redox signaling is altered and contributes to the development and/or maintenance of hypertension. We evaluated the in vitro antioxidant capacity and free radical scavenging capacity of both phenolic compounds. Moreover, we investigated the effect of both compounds on lipid peroxidation, lucigenin chemiluminescence, nitric oxide (NO•) levels and ROS concentration in vascular cells of SHR or human umbilical vein endothelial cell (HUVEC). Apocynin and protocatechuic acid presented antioxidant capacity and ability as free radical scavengers, decreased thiobarbituric acid reactive substances (TBARS) in aortic cells from SHR, and increased NO• concentration in isolated HUVEC. Both compounds were able to reduce lucigenin chemiluminescence and increased the potency of acetylcholine in aorta of SHR. However, in SHR aortas, only apocynin diminished the contraction induced by phenylephrine. In conclusion, these results strongly reinforce the potential application of substances such as apocynin and protocatechuic acid that combine abilities as scavenging and/or prevention of ROS generation, establishment of NO bioactivity and modulation of vascular reactivity. Due to its phytochemical origin and low toxicity, its potential therapeutic use in vascular diseases should be considered.
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Affiliation(s)
- Murilo E. Graton
- Programa de Pós-graduação Multicêntrico em Ciências Fisiológicas, SBFis, São Paulo State University (UNESP), Araçatuba, São Paulo, Brazil
- Department of Basic Sciences, School of Dentistry, São Paulo State University (UNESP), Araçatuba, São Paulo, Brazil
| | - Bruno H. S. H. Ferreira
- Department of Support, Production and Animal Health, School of Veterinary Medicine, São Paulo State University (UNESP), Araçatuba, São Paulo, Brazil
| | - Jéssica A. Troiano
- Programa de Pós-graduação Multicêntrico em Ciências Fisiológicas, SBFis, São Paulo State University (UNESP), Araçatuba, São Paulo, Brazil
- Department of Basic Sciences, School of Dentistry, São Paulo State University (UNESP), Araçatuba, São Paulo, Brazil
- Fundação Dracenense de Educação e Cultura (FUNDEC), Faculdades de Dracena (UNIFADRA), Dracena, São Paulo, Brazil
| | - Simone R. Potje
- Department of Biosciences, Minas Gerais State University (UEMG), Belo Horizonte, Minas Gerais, Brazil
| | - Gabriel T. Vale
- Department of Biosciences, Minas Gerais State University (UEMG), Belo Horizonte, Minas Gerais, Brazil
| | - Ana Cláudia M. S. Nakamune
- Programa de Pós-graduação Multicêntrico em Ciências Fisiológicas, SBFis, São Paulo State University (UNESP), Araçatuba, São Paulo, Brazil
- Department of Basic Sciences, School of Dentistry, São Paulo State University (UNESP), Araçatuba, São Paulo, Brazil
| | - Carlos R. Tirapelli
- Department of Psychiatry Nursing and Human Sciences, College of Nursing of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil
| | - Francis J. Miller
- Nashville VA Medical Center, Vanderbilt University, Nashville, TN, United States
| | - Valdecir F. Ximenes
- Department of Chemistry, Faculty of Sciences, São Paulo State University (UNESP), Bauru, São Paulo, Brazil
| | - Cristina Antoniali
- Programa de Pós-graduação Multicêntrico em Ciências Fisiológicas, SBFis, São Paulo State University (UNESP), Araçatuba, São Paulo, Brazil
- Department of Basic Sciences, School of Dentistry, São Paulo State University (UNESP), Araçatuba, São Paulo, Brazil
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27
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Johnson SA, Weir TL. Fresh Take on the Relationship between Diet, Gut Microbiota, and Atherosclerosis: A Food-Based Approach with Brussels Chicory. J Nutr 2022; 152:2181-2183. [PMID: 36054765 PMCID: PMC9535444 DOI: 10.1093/jn/nxac147] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Affiliation(s)
- Sarah A Johnson
- Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, CO, USA
| | - Tiffany L Weir
- Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, CO, USA
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28
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Tang Q, Yi Y, Chen Y, Zhuang Z, Wang F, Zhang L, Wei S, Zhang Y, Wang Y, Liu L, Liu Q, Jiang C. A green and highly efficient method to deliver hydrophilic polyphenols of Salvia miltiorrhiza and Carthamus tinctorius for enhanced anti-atherosclerotic effect via metal-phenolic network. Colloids Surf B Biointerfaces 2022; 215:112511. [PMID: 35483256 DOI: 10.1016/j.colsurfb.2022.112511] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 04/05/2022] [Accepted: 04/17/2022] [Indexed: 10/18/2022]
Abstract
Salvia miltiorrhiza and Carthamus tinctorius are traditional Chinese medicines that have been widely used for the treatment of cardiovascular disease. Salvianic acid A (SAA), salvianic acid B (SAB), protocatechuic aldehyde (PCA) and hydroxysafflor yellow A (HSYA) are the major hydrophilic polyphenols of Salvia miltiorrhiza and Carthamus tinctorius, all of which have been documented as active compounds for the prevention and treatment of atherosclerosis (AS). However, high aqueous solubility, low permeability and poor stability properties of the four hydrophilic polyphenols might influence their bioavailability and thus hinder their clinical potential. In this work, we introduced a green and highly efficient method for the efficient delivery of the four hydrophilic components via metal-phenolic network. The four coordination polymers of SAA, SAB, PCA and HSYA were successfully fabricated, and confirmed by UV-vis, FTIR, XPS, ICP-MS and dynamic light scattering analysis. We found all of them displayed potent antioxidant activity, good biocompatibility and stability. Impressively, the four coordination polymers showed remarkably enhanced anti-atherosclerotic effect compared with free drugs. Collectively, metal-phenolic network-based coordination polymer might show great potential for safe and efficient delivery of the hydrophilic polyphenols of Salvia miltiorrhiza and Carthamus tinctorius for anti-atherosclerotic therapy.
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Affiliation(s)
- Qingfa Tang
- Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou Avenue North 1838, Guangzhou 510515, PR China
| | - Yankui Yi
- Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou Avenue North 1838, Guangzhou 510515, PR China
| | - Yao Chen
- Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou Avenue North 1838, Guangzhou 510515, PR China
| | - Ziming Zhuang
- Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou Avenue North 1838, Guangzhou 510515, PR China
| | - Feng Wang
- Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou Avenue North 1838, Guangzhou 510515, PR China
| | - Lu Zhang
- Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou Avenue North 1838, Guangzhou 510515, PR China
| | - Shenkun Wei
- Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou Avenue North 1838, Guangzhou 510515, PR China
| | - Yusheng Zhang
- Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou Avenue North 1838, Guangzhou 510515, PR China
| | - Yueqiusha Wang
- Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou Avenue North 1838, Guangzhou 510515, PR China
| | - Li Liu
- Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou Avenue North 1838, Guangzhou 510515, PR China
| | - Qiang Liu
- Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou Avenue North 1838, Guangzhou 510515, PR China.
| | - Cuiping Jiang
- Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou Avenue North 1838, Guangzhou 510515, PR China; Zhujiang Hospital, Southern Medical University, 253 Gongye Middle Avenue, Haizhu District, Guangzhou, 510280, Guangdong, China.
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29
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Olędzka A, Cichocka K, Woliński K, Melzig MF, Czerwińska ME. Potentially Bio-Accessible Metabolites from an Extract of Cornus mas Fruit after Gastrointestinal Digestion In Vitro and Gut Microbiota Ex Vivo Treatment. Nutrients 2022; 14:nu14112287. [PMID: 35684087 PMCID: PMC9183047 DOI: 10.3390/nu14112287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 05/21/2022] [Accepted: 05/26/2022] [Indexed: 12/15/2022] Open
Abstract
Targeting pancreatic lipase and α-amylase by digestion-derived fractions of ethanolic-aqueous (60%, v/v) extract from Cornus mas fruit (CM) in relation to the control and prevention of metabolic disorders, including diabetes, was the first purpose of the present study. Taking into consideration the significance of bio-accessibility of compounds, we attempted to identify metabolites of CM after gastrointestinal digestion in vitro, as well as their kinetic changes upon gut microbiota treatment. The digestion of extract was simulated with digestive enzymes in vitro and human gut microbiota ex vivo (1 h, 3 h, 6 h, 24 h), followed by chromatographic analysis using the UHPLC-DAD-MSn method. The effect of fractions from gastrointestinal digestion in vitro on the activity of pancreatic lipase and α-amylase was studied with fluorescence-based assays. The gastric and intestinal fractions obtained after in vitro digestion of CM inhibited pancreatic lipase and α-amylase. Loganic acid as the main constituent of the extract was digested in the experimental conditions in contrast to cornuside. It was found in most analytes such as salivary, gastric, intestinal, and even colon (fecal slurry, FS) fractions. In all fractions, kaempferol hexoside and reduced forms of kaempferol, such as aromadendrin, and benzoic acid were assigned. The signals of tannins were detected in all fractions. Cornusiin A was tentatively assigned in the gastric fraction. The metabolites originating from kinetic analytes have been classified mainly as phenolic acids, hydrolyzable tannins, and flavonoids. Phenolic acids (protocatechuic acid, gallic acid), tannins (digalloylglucose, tri-O-galloyl-β-D-glucose), and flavonoids (aromadendrin, dihydroquercetin) were detected in the late phases of digestion in fecal slurry suspension. Cornuside was found in FS analyte after 3 h incubation. It was not detected in the samples after 6 and 24 h incubation with FS. In conclusion, cornuside, aromadendrin, and phenolic acids may be potentially bio-accessible compounds of CM. The presence of plants' secondary metabolites in the intestinal fractions allows us to indicate them as responsible for decreasing glucose and lipid absorption.
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Affiliation(s)
- Agata Olędzka
- Student Scientific Association “Farmakon”, Department of Biochemistry and Pharmacogenomics, Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland; (A.O.); (K.C.)
| | - Katarzyna Cichocka
- Student Scientific Association “Farmakon”, Department of Biochemistry and Pharmacogenomics, Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland; (A.O.); (K.C.)
| | - Konrad Woliński
- Polish Academy of Sciences Botanical Garden, Centre for Biological Diversity Conservation in Powsin, 2 Prawdziwka Street, 02-973 Warsaw, Poland;
| | - Matthias F. Melzig
- Institute of Pharmacy, Freie Universitaet Berlin, 2+4 Koenigin-Luise Street, 14195 Berlin, Germany;
| | - Monika E. Czerwińska
- Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland
- Centre for Preclinical Research, Medical University of Warsaw, 1B Banacha Street, 02-097 Warsaw, Poland
- Correspondence: ; Tel.: +48-22-116-61-85
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Mahfuz S, Mun HS, Dilawar MA, Ampode KMB, Yang CJ. Potential Role of Protocatechuic Acid as Natural Feed Additives in Farm Animal Production. Animals (Basel) 2022; 12:741. [PMID: 35327138 PMCID: PMC8944766 DOI: 10.3390/ani12060741] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 03/14/2022] [Accepted: 03/14/2022] [Indexed: 12/12/2022] Open
Abstract
Restriction on using antibiotics in animal feed that generates demand for antibiotics alternatives in animal breeding. Providing safe food to humans free from the residual effects of antibiotics is a great challenge to animal producers and food-producing industry owners. Medicinal plants and their extracts as feed supplements have been used to promote the growth and health of farm animals for centuries. Protocatechuic acid (PCA) is a phenolic compound that originated from natural plants. For years, the health-promoting role of PCA has been becoming an attraction of research in nutrition and pharmacy. Thus, it can be used as an active natural feed additive while synthetic antibiotics are illegal to use in animal breeding. However, the practical application of PCA in view of dosages in animal nutrition, together with its mode of action on animal health, is not well known. In this regard, this review study has explored the mode of action of PCA and the feasibility of using those compounds in animal nutrition. This review study concludes that phenolic-rich protocatechuic acid as a natural feed additive may be useful in enhancing antioxidant status, immune function, antimicrobial, intestinal health and growth performance of farm animals.
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Affiliation(s)
- Shad Mahfuz
- Animal Nutrition and Feed Science Laboratory, Department of Animal Science and Technology, Sunchon National University, Suncheon 57922, Korea; (S.M.); (H.-S.M.); (M.A.D.); (K.M.B.A.)
- Department of Animal Nutrition, Sylhet Agricultural University, Sylhet 3100, Bangladesh
| | - Hong-Seok Mun
- Animal Nutrition and Feed Science Laboratory, Department of Animal Science and Technology, Sunchon National University, Suncheon 57922, Korea; (S.M.); (H.-S.M.); (M.A.D.); (K.M.B.A.)
- Department of Multimedia Engineering, Sunchon National University, Suncheon 57922, Korea
| | - Muhammad Ammar Dilawar
- Animal Nutrition and Feed Science Laboratory, Department of Animal Science and Technology, Sunchon National University, Suncheon 57922, Korea; (S.M.); (H.-S.M.); (M.A.D.); (K.M.B.A.)
- Interdisciplinary Program in IT-Bio Convergence System (BK21 Plus), Sunchon National University, 255 Jungangno, Suncheon 57922, Korea
| | - Keiven Mark B. Ampode
- Animal Nutrition and Feed Science Laboratory, Department of Animal Science and Technology, Sunchon National University, Suncheon 57922, Korea; (S.M.); (H.-S.M.); (M.A.D.); (K.M.B.A.)
| | - Chul-Ju Yang
- Animal Nutrition and Feed Science Laboratory, Department of Animal Science and Technology, Sunchon National University, Suncheon 57922, Korea; (S.M.); (H.-S.M.); (M.A.D.); (K.M.B.A.)
- Interdisciplinary Program in IT-Bio Convergence System (BK21 Plus), Sunchon National University, 255 Jungangno, Suncheon 57922, Korea
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31
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Dietary ferulic acid and vanillic acid on inflammation, gut barrier function and growth performance in lipopolysaccharide-challenged piglets. ANIMAL NUTRITION (ZHONGGUO XU MU SHOU YI XUE HUI) 2022; 8:144-152. [PMID: 34977384 PMCID: PMC8683658 DOI: 10.1016/j.aninu.2021.06.009] [Citation(s) in RCA: 76] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 05/23/2021] [Accepted: 06/07/2021] [Indexed: 12/13/2022]
Abstract
Ferulic acid (FA) and vanillic acid (VA) are considered as major phenolic metabolites of cyanidin 3-glucoside, a polyphenol that widely exists in plants that possess a protective effect against oxidative stress and inflammation in our previous study. This study aimed to investigate the effect of FA and VA on inflammation, gut barrier function, and growth performance in a weaned piglet model challenged with lipopolysaccharide (LPS). Thirty-six piglets (PIC 337 × C48, 28 d of age) were randomly allocated into 3 treatments with 6 replicate pens (2 piglets per pen). They were fed with a basal diet or a diet containing 4,000 mg/kg of FA or VA. Dietary supplementation of VA significantly increased average daily gain (ADG) (P < 0.05). Both FA and VA decreased serum levels of thiobarbituric acid reactive substances (TBARS), interlukin (IL)-1β, IL-2, IL-6, and tumor necrosis factor (TNF)-α (P < 0.05), and enhanced the expression of tight junction protein oclaudin (P < 0.05). Analysis of gut microbiota indicated that both FA and VA increased the Firmicutes/Bacteroidetes ratio alongside reducing the relative abundance of the Prevotellaceae family including Prevotella 9 and Prevotella 2 genera, but enriched the Lachoiraceaea family including the Lachnospiraceae FCS020 group (P < 0.05). Moreover, VA reduced the relative abundance of Prevotella 7 and Prevotella 1 but enriched Lachnospira, Eubacterium eligens group, and Eubacterium xylanophilum group (P < 0.05), while FA showed a limited effect on these genera. The results demonstrated that both VA and FA could alleviate inflammation and oxidative stress, but only VA has a significant positive effect on the growth performance of LPS-challenged piglets potentially through modulating gut microbiota.
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Sayers B, Wijeyesekera A, Gibson G. Exploring the potential of prebiotic and polyphenol-based dietary interventions for the alleviation of cognitive and gastrointestinal perturbations associated with military specific stressors. J Funct Foods 2021. [DOI: 10.1016/j.jff.2021.104753] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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Osborn LJ, Claesen J, Brown JM. Microbial Flavonoid Metabolism: A Cardiometabolic Disease Perspective. Annu Rev Nutr 2021; 41:433-454. [PMID: 34633856 DOI: 10.1146/annurev-nutr-120420-030424] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Cardiometabolic disease (CMD) is a leading cause of death worldwide and encompasses the inflammatory metabolic disorders of obesity, type 2 diabetes mellitus, nonalcoholic fatty liver disease, and cardiovascular disease. Flavonoids are polyphenolic plant metabolites that are abundantly present in fruits and vegetables and have biologically relevant protective effects in a number of cardiometabolic disorders. Several epidemiological studies underscored a negative association between dietary flavonoid consumption and the propensity to develop CMD. Recent studies elucidated the contribution of the gut microbiota in metabolizing dietary intake as it relates to CMD. Importantly, the biological efficacy of flavonoids in humans and animal models alike is linked to the gut microbial community. Herein, we discuss the opportunities and challenges of leveraging flavonoid intake as a potential strategy to prevent and treat CMD in a gut microbe-dependent manner, with special emphasis on flavonoid-derived microbial metabolites.
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Affiliation(s)
- Lucas J Osborn
- Department of Cardiovascular and Metabolic Sciences and Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, Ohio 44195, USA; , , .,Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio 44195, USA
| | - Jan Claesen
- Department of Cardiovascular and Metabolic Sciences and Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, Ohio 44195, USA; , , .,Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio 44195, USA
| | - J Mark Brown
- Department of Cardiovascular and Metabolic Sciences and Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, Ohio 44195, USA; , , .,Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio 44195, USA
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Anghelache M, Turtoi M, Petrovici AR, Fifere A, Pinteala M, Calin M. Development of Dextran-Coated Magnetic Nanoparticles Loaded with Protocatechuic Acid for Vascular Inflammation Therapy. Pharmaceutics 2021; 13:pharmaceutics13091414. [PMID: 34575489 PMCID: PMC8468178 DOI: 10.3390/pharmaceutics13091414] [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: 08/02/2021] [Revised: 08/31/2021] [Accepted: 09/03/2021] [Indexed: 12/25/2022] Open
Abstract
Vascular inflammation plays a crucial role in the progression of various pathologies, including atherosclerosis (AS), and thus it has become an attractive therapeutic target. The protocatechuic acid (PCA), one of the main metabolites of complex polyphenols, is endowed with anti-inflammatory activity, but its formulation into nanocarriers may increase its bioavailability. In this study, we developed and characterized dextran shell‒iron oxide core nanoparticles loaded with PCA (MNP-Dex/PCA) and assessed their cytotoxicity and anti-inflammatory potential on cells acting as key players in the onset and progression of AS, namely, endothelial cells (EC) and monocytes/macrophages. The results showed that MNP-Dex/PCA exert an anti-inflammatory activity at non-cytotoxic and therapeutically relevant concentrations of PCA (350 μM) as supported by the reduced levels of inflammatory molecules such as MCP-1, IL-1β, TNF-α, IL-6, and CCR2 in activated EC and M1-type macrophages and functional monocyte adhesion assay. The anti-inflammatory effect of MNP-Dex/PCA was associated with the reduction in the levels of ERK1/2 and p38-α mitogen-activated protein kinases (MAPKs) and NF-kB transcription factor. Our data support the further development of dextran shell-magnetic core nanoparticles as theranostic nanoparticles for guidance, imaging, and therapy of vascular inflammation using PCA or other anti-inflammatory compounds.
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Affiliation(s)
- Maria Anghelache
- “Medical and Pharmaceutical Bionanotechnologies” Laboratory, Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, B.P. Hasdeu 8, 050568 Bucharest, Romania; (M.A.); (M.T.)
| | - Mihaela Turtoi
- “Medical and Pharmaceutical Bionanotechnologies” Laboratory, Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, B.P. Hasdeu 8, 050568 Bucharest, Romania; (M.A.); (M.T.)
| | - Anca Roxana Petrovici
- “Centre of Advanced Research in Bionanoconjugates and Biopolymers” Department, “Petru Poni” Institute of Macromolecular Chemistry, 41A Grigore Ghica-Voda Alley, 700487 Iasi, Romania; (A.R.P.); (M.P.)
| | - Adrian Fifere
- “Centre of Advanced Research in Bionanoconjugates and Biopolymers” Department, “Petru Poni” Institute of Macromolecular Chemistry, 41A Grigore Ghica-Voda Alley, 700487 Iasi, Romania; (A.R.P.); (M.P.)
- Correspondence: (A.F.); (M.C.)
| | - Mariana Pinteala
- “Centre of Advanced Research in Bionanoconjugates and Biopolymers” Department, “Petru Poni” Institute of Macromolecular Chemistry, 41A Grigore Ghica-Voda Alley, 700487 Iasi, Romania; (A.R.P.); (M.P.)
| | - Manuela Calin
- “Medical and Pharmaceutical Bionanotechnologies” Laboratory, Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, B.P. Hasdeu 8, 050568 Bucharest, Romania; (M.A.); (M.T.)
- Correspondence: (A.F.); (M.C.)
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Abdelmageed ME, Nader MA, Zaghloul MS. Targeting HMGB1/TLR4/NF-κB signaling pathway by protocatechuic acid protects against l-arginine induced acute pancreatitis and multiple organs injury in rats. Eur J Pharmacol 2021; 906:174279. [PMID: 34197778 DOI: 10.1016/j.ejphar.2021.174279] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 06/18/2021] [Accepted: 06/22/2021] [Indexed: 12/16/2022]
Abstract
Acute pancreatitis (AP) is a common pancreatic inflammation associated with substantial morbidity and mortality. AP may be mild or severe which can spread systemically causing multiple organs failure (MOF) and even death. In the current study, protocatechuic acid (PCA), a natural phenolic acid, was investigated for its possible protective potential against L-arginine induced AP and multiple organs injury (MOI) in rats. AP was induced by L-arginine (500 mg/100 g, ip). Two dose levels of PCA were tested (50 and 100 mg/kg, oral, 10 days before L-arginine injection). PCA successfully protected against L-arginine induced AP and MOI that was manifested by normalizing pancreatic, hepatic, pulmonary, and renal tissue architecture and restoring the normal values of pancreatic enzymes (amylase and lipase), serum total protein, liver enzymes (alanine transaminase (ALT) and aspartate transaminase (AST)) and kidney function biomarkers (blood urea nitrogen (BUN) and serum creatinine (Cr)) that were significantly elevated upon L-arginine administration. Additionally, PCA restored balanced oxidant/antioxidants status that was disrupted by L-arginine and normalized pancreatic levels of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) content. Moreover, PCA significantly decreased L-arginine induced elevation in pancreatic high motility group box protein 1 (HMGB1), toll like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF-κB), tumor necrosis factor- α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) expression. PCA significantly ameliorated L-arginine-induced AP and MOI through its anti-inflammatory and antioxidant effects. HMGB1/TLR4/NF-κB was the major pathway involved in the observed protective potential.
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Affiliation(s)
- Marwa E Abdelmageed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
| | - Manar A Nader
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt
| | - Marwa S Zaghloul
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt
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36
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Gao Y, Tian R, Liu H, Xue H, Zhang R, Han S, Ji L, Huang W, Zhan J, You Y. Research progress on intervention effect and mechanism of protocatechuic acid on nonalcoholic fatty liver disease. Crit Rev Food Sci Nutr 2021; 62:9053-9075. [PMID: 34142875 DOI: 10.1080/10408398.2021.1939265] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become a surge burden worldwide due to its high prevalence, with complicated deterioration symptoms such as liver fibrosis and cancer. No effective drugs are available for NALFD so far. The rapid growth of clinical demand has prompted the treatment of NAFLD to become a research hotspot. Protocatechuic acid (PCA) is a natural secondary metabolite commonly found in fruits, vegetables, grains, and herbal medicine. It is also the major internal metabolites of anthocyanins and other polyphenols. In the present manuscript, food sources, metabolic absorption, and efficacy of PCA were summarized while analyzing its role in improving NAFLD, as well as the mechanism involved. The results indicated that PCA could ameliorate NAFLD by regulating glucose and lipid metabolism, oxidative stress and inflammation, gut microbiota and metabolites. It was proposed for the first time that PCA might reduce NAFLD by enhancing the energy consumption of brown adipose tissue (BAT). However, the PCA administration mode and dose for NAFLD remain inconclusive. Fresh insights into the specific molecular mechanisms are required, while clinical trials are essential in the future. This review provides new targets and reasoning for the clinical application of PCA in the prevention and treatment of NAFLD.
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Affiliation(s)
- Yunxiao Gao
- College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing, China
| | - Rongrong Tian
- Department of Biomedicine, Beijing City University, Beijing, China
| | - Haiyue Liu
- College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing, China
| | - Huimin Xue
- College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing, China
| | - Ruizhe Zhang
- College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing, China
| | - Suping Han
- College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing, China
| | - Lin Ji
- College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing, China
| | - Weidong Huang
- College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing, China
| | - Jicheng Zhan
- College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing, China
| | - Yilin You
- College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Beijing, China
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Orabi D, Osborn LJ, Fung K, Massey W, Horak AJ, Aucejo F, Choucair I, DeLucia B, Wang Z, Claesen J, Brown JM. A surgical method for continuous intraportal infusion of gut microbial metabolites in mice. JCI Insight 2021; 6:145607. [PMID: 33986195 PMCID: PMC8262340 DOI: 10.1172/jci.insight.145607] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 03/24/2021] [Indexed: 12/12/2022] Open
Abstract
Gut microbe-derived metabolites influence human physiology and disease. However, establishing mechanistic links between gut microbial metabolites and disease pathogenesis in animal models remains challenging. The major route of absorption for microbe-derived small molecules is venous drainage via the portal vein to the liver. In the event of presystemic hepatic metabolism, the route of metabolite administration becomes critical. To our knowledge, we describe here a novel portal vein cannulation technique using a s.c. implanted osmotic pump to achieve continuous portal vein infusion in mice. We first administered the microbial metabolite trimethylamine (TMA) over 4 weeks, during which increased peripheral plasma levels of TMA and its host liver-derived cometabolite, trimethylamine-N-oxide, were observed when compared with a vehicle control. Next, 4-hydroxyphenylacetic acid (4-HPAA), a microbial metabolite that undergoes extensive presystemic hepatic metabolism, was administered intraportally to examine effects on hepatic gene expression. As expected, hepatic levels of 4-HPAA were elevated when compared with the control group while peripheral plasma 4-HPAA levels remained the same. Moreover, significant changes in the hepatic transcriptome were revealed by an unbiased RNA-Seq approach. Collectively, to our knowledge this work describes a novel method for administering gut microbe-derived metabolites via the portal vein, mimicking their physiologic delivery in vivo.
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Affiliation(s)
- Danny Orabi
- Department of Cardiovascular and Metabolic Sciences and
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, Ohio, USA
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA
- Department of General Surgery, Cleveland Clinic, Cleveland, Ohio, USA
| | - Lucas J. Osborn
- Department of Cardiovascular and Metabolic Sciences and
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, Ohio, USA
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA
| | - Kevin Fung
- Department of Cardiovascular and Metabolic Sciences and
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, Ohio, USA
| | - William Massey
- Department of Cardiovascular and Metabolic Sciences and
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, Ohio, USA
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA
| | - Anthony J. Horak
- Department of Cardiovascular and Metabolic Sciences and
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, Ohio, USA
| | - Federico Aucejo
- Department of General Surgery, Cleveland Clinic, Cleveland, Ohio, USA
| | - Ibrahim Choucair
- Department of Cardiovascular and Metabolic Sciences and
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, Ohio, USA
| | - Beckey DeLucia
- Department of Cardiovascular and Metabolic Sciences and
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, Ohio, USA
| | - Zeneng Wang
- Department of Cardiovascular and Metabolic Sciences and
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, Ohio, USA
| | - Jan Claesen
- Department of Cardiovascular and Metabolic Sciences and
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, Ohio, USA
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA
| | - J. Mark Brown
- Department of Cardiovascular and Metabolic Sciences and
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, Ohio, USA
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA
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Ouyang S, Chen W, Gaofeng Z, Changcheng L, Guoping T, Minyan Z, Yang L, Min Y, Luo J. Cyanidin‑3‑O‑β‑glucoside protects against pulmonary artery hypertension induced by monocrotaline via the TGF‑β1/p38 MAPK/CREB signaling pathway. Mol Med Rep 2021; 23:338. [PMID: 33760143 PMCID: PMC7974420 DOI: 10.3892/mmr.2021.11977] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 04/09/2020] [Indexed: 12/22/2022] Open
Abstract
Pulmonary artery hypertension (PAH) is a disease with high morbidity and mortality. Cyanidin‑3‑O‑β‑glucoside (Cy‑3‑g), a classical anthocyanin, has a variety of biological effects. The present study evaluated whether Cy‑3‑g attenuated PAH, and explored the potential mechanism of action. Rats were injected with monocrotaline (MCT; 60 mg per kg of body weight) and then treated with Cy‑3‑g (200 or 400 mg per kg of body weight) for 4 weeks. Protein expression was determined in vitro in transforming growth factor‑β1 (TGF‑β1)‑mediated human pulmonary arterial smooth muscle cells (SMCs). The results indicated that Cy‑3‑g significantly inhibited the mean pulmonary artery pressure, right ventricular systolic pressure and right ventricular hypertrophy index, as well as vascular remodeling induced by MCT in PAH rats. Further experiments showed that Cy‑3‑g suppressed the expression of pro‑-inflammatory factors and enhanced the levels of anti‑inflammatory factors. Cy‑3‑g blocked oxidative stress and improved vascular endothelial injury. Cy‑3‑g also reduced the proliferation of SMCs. Furthermore, the MCT‑ and TGF‑β1‑induced increase in TGF‑β1, phosphorylated (p)‑p38 mitogen‑activated protein kinase (MAPK) and p‑cAMP‑response element binding protein (CREB) expression was blocked by Cy‑3‑g treatment in vivo and in vitro. These results indicated that Cy‑3‑g could prevent vascular remodeling in PAH via inhibition of the TGF‑β1/p38 MAPK/CREB axis.
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Affiliation(s)
- Shao Ouyang
- Department of Cardiovascular Medicine, The Second Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China
| | - Wei Chen
- Department of Respiratory Medicine, The Second Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China
| | - Zeng Gaofeng
- Department of Cardiovascular Medicine, The Second Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China
| | - Lei Changcheng
- Department of Cardiovascular Medicine, The Second Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China
| | - Tian Guoping
- Department of Cardiovascular Medicine, The Second Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China
| | - Zhu Minyan
- Department of Cardiovascular Medicine, The Second Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China
| | - Liu Yang
- Department of Cardiovascular Medicine, The Second Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China
| | - Yang Min
- Department of Cardiovascular Medicine, The Second Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China
| | - Jiahao Luo
- Department of Cardiovascular Medicine, The Second Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China
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Weng H, He L, Liu X, Li Q, Du Y, Zheng J, Wang D. Natural lactucopicrin alleviates importin-α3-mediated NF-κB activation in inflammated endothelial cells and improves sepsis in mice. Biochem Pharmacol 2021; 186:114501. [PMID: 33684389 DOI: 10.1016/j.bcp.2021.114501] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 02/25/2021] [Accepted: 02/26/2021] [Indexed: 01/13/2023]
Abstract
Lactucopicrin, a bitter sesquiterpene lactone of leafy vegetables, such as chicory, curly escarole, and lettuce, possesses anti-malarial, anti-cancer and analgesic properties. However, it remains unknown whether lactucopicrin could inhibit vascular endothelial nuclear factor-κB (NF-κB) activation, a hallmark of vascular inflammatory diseases including sepsis. In tumor necrosis factor-α-stimulated human or mouse aortic endothelial cells, lactucopicrin dose-dependently inhibited NF-κB activation, and concomitantly repressed both vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1)-mediated monocyte adhesion. The lactucopicrin effect was not due to modulation of inhibitor of NF-κB kinases (IKK) α/β/γ, inhibitor of NF-κB alpha (IκBα), and NF-κB/p65 DNA binding activity. Instead, lactucopicrin inhibited importin-α3 expression by destabilization of its mRNA, an effect mediating the lactucopicrin effect on NF-κB activity. More importantly, in lipopolysaccharide (LPS)-elicited septic mice, oral gavage with lactucopicrin decreased mortality by 30.5% as compared with the control treatment. This effect was associated with inhibited importin-α3 expression, suppressed NF-κB activation and VCAM-1/ICAM-1 expression, and inhibited leukocyte influx in the vascular endothelium of both lung and aorta. Collectively, our novel data suggest that dietary supplementation with lactucopicrin inhibits endothelial NF-κB activation by down-regulation of importin-α3 and thereby improves sepsis.
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Affiliation(s)
- Hui Weng
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, China
| | - Luanying He
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, China
| | - Xiuping Liu
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, China
| | - Qing Li
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, China
| | - Yushi Du
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, China
| | - Jiakun Zheng
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, China
| | - Dongliang Wang
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, China; Guangdong Provincial Key Laboratory for Food, Nutrition and Health, Guangzhou 510080, China; Guangdong Engineering Technology Research Center for Nutrition Translation, Guangzhou 510080, China.
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He L, Weng H, Li Q, Shi G, Liu X, Du Y, Zheng J, Ling W, Wang D. Lactucopicrin Inhibits Cytoplasmic Dynein-Mediated NF-κB Activation in Inflammated Macrophages and Alleviates Atherogenesis in Apolipoprotein E-Deficient Mice. Mol Nutr Food Res 2021; 65:e2000989. [PMID: 33377310 DOI: 10.1002/mnfr.202000989] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 12/03/2020] [Indexed: 12/15/2022]
Abstract
SCOPE Nuclear factor-κB (NF-κB) activation in macrophages aggravates atherosclerosis. Dietary plant secondary metabolites including sesquiterpene lactone lactucopicrin target multiple organs. This study is focused on the impact of lactucopicrin on NF-κB activation in inflammed macrophages and atherogenesis in a mouse model of atherosclerosis. METHODS AND RESULTS In LPS-stimulated mouse bone marrow-derived macrophages, lactucopicrin inhibits NF-κB activation, and concomitantly represses the expression of IL-1β, IL-6, and tumor necrosis factor-alpha. This effect is not due to modulation of the inhibitor of NF-κB kinases (IKK) α/β/γ and NF-κB inhibitor α, and NF-κB/p65 DNA binding activity. Instead, the lactucopicrin effect is reliant on the inhibition of cytoplasmic dynein-mediated p65 transportation, a prerequisite step for p65 nuclear translocation. In high-fat diet-fed apolipoprotein E-deficient mice, lactucopicrin consumption dose-dependently reduces plaque area, inhibits plaque macrophage accumulation, attenuates plaque macrophage NF-κB activation, and reduces both plaque and serum inflammatory burden. However, lactucopicrin consumption does not affect the levels of serum lipids and anti-inflammatory cytokines (IL-4, IL-10, and transforming growth factor beta). CONCLUSION Dietary lactucopicrin inhibits atherogenesis in mice likely by its anti-inflammatory property. These findings suggest that dietary supplementation with lactucopicrin is a promising strategy to inhibit atherosclerotic cardiovascular disease.
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Affiliation(s)
- Luanying He
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, P. R. China
| | - Hui Weng
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, P. R. China
| | - Qing Li
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, P. R. China
| | - Guojun Shi
- Department of Endocrinology & Metabolism, Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China
| | - Xiuping Liu
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, P. R. China
| | - Yushi Du
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, P. R. China
| | - Jiakun Zheng
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, P. R. China
| | - Wenhua Ling
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, P. R. China
- Guangdong Provincial Key Laboratory for Food, Nutrition and Health, Guangzhou, P. R. China
- Guangdong Engineering Technology Research Center for Nutrition Translation, Guangzhou, P. R. China
| | - Dongliang Wang
- Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, P. R. China
- Guangdong Provincial Key Laboratory for Food, Nutrition and Health, Guangzhou, P. R. China
- Guangdong Engineering Technology Research Center for Nutrition Translation, Guangzhou, P. R. China
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Liu Y, Deng G, Wang X, Luo J, Qian X, Ling W. Cyanidin-3-O-β-glucoside polarizes LPS-induced M1 into M2 Macrophage in J774 cells via PPARγ-mediated NF-κB and STAT6 signaling pathway. J Funct Foods 2021. [DOI: 10.1016/j.jff.2020.104314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Soltani S, Boozari M, Cicero AFG, Jamialahmadi T, Sahebkar A. Effects of phytochemicals on macrophage cholesterol efflux capacity: Impact on atherosclerosis. Phytother Res 2021; 35:2854-2878. [PMID: 33464676 DOI: 10.1002/ptr.6991] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 10/19/2020] [Accepted: 12/11/2020] [Indexed: 12/24/2022]
Abstract
High-density lipoprotein cholesterol (HDL) is the major promoter of reverse cholesterol transport and efflux of excess cellular cholesterol. The functions of HDL, such as cholesterol efflux, are associated with cardiovascular disease rather than HDL levels. We have reviewed the evidence base on the major classes of phytochemicals, including polyphenols, alkaloids, carotenoids, phytosterols, and fatty acids, and their effects on macrophage cholesterol efflux and its major pathways. Phytochemicals show the potential to improve the efficiency of each of these pathways. The findings are mainly in preclinical studies, and more clinical research is warranted in this area to develop novel clinical applications.
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Affiliation(s)
- Saba Soltani
- Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Motahareh Boozari
- Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Arrigo F G Cicero
- Hypertension and Cardiovascular Risk Factors Research Center, Medical and Surgical Sciences Department, University of Bologna, Bologna, Italy
| | - Tannaz Jamialahmadi
- Department of Food Science and Technology, Quchan Branch, Islamic Azad University, Quchan, Iran.,Department of Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Halal Research Center of IRI, FDA, Tehran, Iran.,Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland
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Novel approaches in anthocyanin research - Plant fortification and bioavailability issues. Trends Food Sci Technol 2021. [DOI: 10.1016/j.tifs.2021.01.049] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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45
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Rafael FD, Isidro VM, Héctor-Gabriel AM, Abraham PO, Yolanda CU, Tania RG, Rosa-Isela GG, Lorena PC, Socorro HM. Berry Supplementation and Their Beneficial Effects on Some Central Nervous System Disorders. BEHAVIORAL PHARMACOLOGY - FROM BASIC TO CLINICAL RESEARCH 2020. [DOI: 10.5772/intechopen.90428] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Zhang J, Wang D, Zhang X, Yang J, Chai X, Wang Y. Application of "spider-web" mode in discovery and identification of Q-markers from Xuefu Zhuyu capsule. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2020; 77:153273. [PMID: 32663710 DOI: 10.1016/j.phymed.2020.153273] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 06/05/2020] [Accepted: 06/28/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND The selection of quality control indicators in a complex system is a key scientific issue for the study of Chinese materia medica (CMM), which is directly related to its safety and efficacy. In order to scientifically understand and control the quality of CMM, quality marker (Q-marker) has been recently raised as a new concept, which provided a novel research idea for the quality control and evaluation of CMM. PURPOSE By a new and integrated "spider-web" mode, Q-markers of Xuefu Zhuyu capsule (XZC) were comprehensively uncovered, conducing to great improvement of quality control of XZC. METHODS Mainly established by three dimensions derived from six variables including content, stability and activity, "spider-web" mode was constructed to evaluate Q-marker property of candidate compounds by taking regression area of the tested compounds into account. RESULTS The candidate compounds with larger regression area were preferentially adopted as Q-markers, which should possess the satisfactorily integrated properties of content, stability and activity. Six compounds, naringin, isoliquiritin, paeoniflorin, protocatechuic acid, neohesperidin and ferulic acid, were identified and preferred as Q-markers of XZC. CONCLUSION Based on "spider-web" mode, Q-markers from Xuefu Zhuyu capsule were successfully screened, which would substantially perform quality control of XZC and prove the feasibility of "spider-web" mode in solving the selection of quality control indicators from compound formulae.
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Affiliation(s)
- Jing Zhang
- Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Danni Wang
- Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Xiaoyu Zhang
- Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Jing Yang
- Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Xin Chai
- Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China.
| | - Yuefei Wang
- Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China.
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Liu J, Zhao M, Zhu Y, Zheng L, Yin Y. Plasma Metabolomic and Lipidomic Profiling of a Genetically Modified Mouse Model of Scavenger Receptor Class B Type I. Proteomics 2020; 20:e2000050. [PMID: 33090674 DOI: 10.1002/pmic.202000050] [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: 03/07/2020] [Revised: 08/31/2020] [Indexed: 11/06/2022]
Abstract
Atherosclerosis is a chronic inflammatory disease of the arterial wall and is becoming the principal cause of death globally. The reverse cholesterol transport (RCT) mediated by scavenger receptor class B type I (SR-BI) is a major protection mechanism against atherosclerosis. To investigate the metabolome changes and to find potential biomarkers involved in RCT, nontargeted metabolomics and nontargeted lipidomics are applied to SR-BI knockout mice that are fed a high fat and high cholesterol diet. SR-BI knockout mice and controls are told apart using multidimensional statistical analysis, and potential biomarkers are found and identified. The pathophysiological meaning of the biomarkers and the perturbed metabolic pathways are also addressed, which could provide new evidence for atherosclerosis studies.
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Affiliation(s)
- Jia Liu
- Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center for Life Sciences, Peking University Health Science Center, Beijing, 100191, China
| | - Mingming Zhao
- The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, Beijing, 100191, China
| | - Yizhang Zhu
- Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center for Life Sciences, Peking University Health Science Center, Beijing, 100191, China
| | - Lemin Zheng
- The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, Beijing, 100191, China
| | - Yuxin Yin
- Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center for Life Sciences, Peking University Health Science Center, Beijing, 100191, China
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Salehi B, Sharifi-Rad J, Cappellini F, Reiner Ž, Zorzan D, Imran M, Sener B, Kilic M, El-Shazly M, Fahmy NM, Al-Sayed E, Martorell M, Tonelli C, Petroni K, Docea AO, Calina D, Maroyi A. The Therapeutic Potential of Anthocyanins: Current Approaches Based on Their Molecular Mechanism of Action. Front Pharmacol 2020; 11:1300. [PMID: 32982731 PMCID: PMC7479177 DOI: 10.3389/fphar.2020.01300] [Citation(s) in RCA: 149] [Impact Index Per Article: 29.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 08/05/2020] [Indexed: 12/13/2022] Open
Abstract
Anthocyanins are natural phenolic pigments with biological activity. They are well-known to have potent antioxidant and antiinflammatory activity, which explains the various biological effects reported for these substances suggesting their antidiabetic and anticancer activities, and their role in cardiovascular and neuroprotective prevention. This review aims to comprehensively analyze different studies performed on this class of compounds, their bioavailability and their therapeutic potential. An in-depth look in preclinical, in vitro and in vivo, and clinical studies indicates the preventive effects of anthocyanins on cardioprotection, neuroprotection, antiobesity as well as their antidiabetes and anticancer effects.
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Affiliation(s)
- Bahare Salehi
- Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam, Iran
- Student Research Committee, School of Medicine, Bam University of Medical Sciences, Bam, Iran
| | - Javad Sharifi-Rad
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Željko Reiner
- Department of Internal Medicine, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Debora Zorzan
- Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Italy
| | - Muhammad Imran
- Faculty of Allied Health Sciences, University Institute of Diet and Nutritional Sciences, The University of Lahore, Lahore, Pakistan
| | - Bilge Sener
- Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Ankara, Turkey
| | - Mehtap Kilic
- Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Ankara, Turkey
| | - Mohamed El-Shazly
- Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt
- Department of Pharmaceutical Biology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt
| | - Nouran M. Fahmy
- Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt
| | - Eman Al-Sayed
- Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt
| | - Miquel Martorell
- Department of Nutrition and Dietetics, Faculty of Pharmacy, University of Concepcion, Concepcion, Chile
- Unidad de Desarrollo Tecnológico, Universidad de Concepción UDT, Concepcion, Chile
| | - Chiara Tonelli
- Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Italy
| | - Katia Petroni
- Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Italy
| | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Alfred Maroyi
- Department of Botany, University of Fort Hare, Alice, South Africa
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Mattioli R, Francioso A, Mosca L, Silva P. Anthocyanins: A Comprehensive Review of Their Chemical Properties and Health Effects on Cardiovascular and Neurodegenerative Diseases. Molecules 2020; 25:E3809. [PMID: 32825684 PMCID: PMC7504512 DOI: 10.3390/molecules25173809] [Citation(s) in RCA: 380] [Impact Index Per Article: 76.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 08/17/2020] [Accepted: 08/21/2020] [Indexed: 12/13/2022] Open
Abstract
Anthocyanins are a class of water-soluble flavonoids widely present in fruits and vegetables. Dietary sources of anthocyanins include red and purple berries, grapes, apples, plums, cabbage, or foods containing high levels of natural colorants. Cyanidin, delphinidin, malvidin, peonidin, petunidin, and pelargonidin are the six common anthocyanidins. Following consumption, anthocyanin, absorption occurs along the gastrointestinal tract, the distal lower bowel being the place where most of the absorption and metabolism occurs. In the intestine, anthocyanins first undergo extensive microbial catabolism followed by absorption and human phase II metabolism. This produces hybrid microbial-human metabolites which are absorbed and subsequently increase the bioavailability of anthocyanins. Health benefits of anthocyanins have been widely described, especially in the prevention of diseases associated with oxidative stress, such as cardiovascular and neurodegenerative diseases. Furthermore, recent evidence suggests that health-promoting effects attributed to anthocyanins may also be related to modulation of gut microbiota. In this paper we attempt to provide a comprehensive view of the state-of-the-art literature on anthocyanins, summarizing recent findings on their chemistry, biosynthesis, nutritional value and on their effects on human health.
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Affiliation(s)
- Roberto Mattioli
- Department of Sciences, RomaTre University, v.le G. Marconi 446, 00146 Rome, Italy;
| | - Antonio Francioso
- Department of Biochemical Sciences, Sapienza University, p.le Aldo Moro, 5, 00185 Rome, Italy;
| | - Luciana Mosca
- Department of Biochemical Sciences, Sapienza University, p.le Aldo Moro, 5, 00185 Rome, Italy;
| | - Paula Silva
- Laboratory of Histology and Embryology, Institute of Biomedical Sciences Abel Salazar (ICBAS), Rua de Jorge Viterbo Ferreira n°228, 4050-313 Porto, Portugal
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The Impact of Dietary Supplementation of Whole Foods and Polyphenols on Atherosclerosis. Nutrients 2020; 12:nu12072069. [PMID: 32664664 PMCID: PMC7400924 DOI: 10.3390/nu12072069] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 07/01/2020] [Accepted: 07/09/2020] [Indexed: 12/16/2022] Open
Abstract
The purpose of this review is to highlight current research on the benefits of supplementation with foods with a diverse polyphenol composition, including fruits, vegetables, nuts, grains, oils, spices, and teas in blunting atherosclerosis. We searched PubMed for publications utilizing whole food or polyphenols prepared from whole foods in Apolipoprotein E (ApoE) or Low-Density Lipoprotein Receptor (LDLR) knockout mice, and identified 73 studies in which plaque was measured. The majority of the studies reported a reduction in plaque. Nine interventions showed no effect, while three using Agaricus blazei mushroom, HYJA-ri-4 rice variety, and safrole-2', 3'-oxide (SFO) increased plaque. The mechanisms by which atherosclerosis was reduced include improved lipid profile, antioxidant status, and cholesterol clearance, and reduced inflammation. Importantly, not all dietary interventions that reduce plaque showed an improvement in lipid profile. Additionally, we found that, out of 73 studies, only 9 used female mice and only 6 compared both sexes. Only one study compared the two models (LDLR vs. ApoE), showing that the treatment worked in one but not the other. Not all supplementations work in both male and female animals, suggesting that increasing the variety of foods with different polyphenol compositions may be more effective in mitigating atherosclerosis.
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