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Korkmaz K, Deger O, Yigit E, Uydu HA, Mercantepe T, Demir S. Effect of Propolis Extracts on OxLDL and LOX-1 Levels in ApoE Knockout Mice Fed a High Fat Diet. Life (Basel) 2025; 15:565. [PMID: 40283120 PMCID: PMC12028976 DOI: 10.3390/life15040565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Revised: 03/25/2025] [Accepted: 03/28/2025] [Indexed: 04/29/2025] Open
Abstract
Atherosclerosis, which has important effects on the development of cardiovascular diseases, is a widespread health problem with the highest mortality rate globally. In this study, we aimed to assess the impact of water and ethanolic extracts of propolis on oxidized low-density lipoprotein (OxLDL) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in the progression of the atherosclerotic process, which is characterized by oxidative stress, inflammation, and dyslipidemia. In our study, apolipoprotein E knockout (ApoE-/-) and C57BL/6J mice were used as study groups. Water (WEP) and ethanolic extracts (EEP) of propolis were administered intraperitoneally to ApoE-/- and C57BL/6J mice modeled with a high-fat diet. Under anesthesia, the animals were euthanized by decapitation, and serum, along with aortic tissues, was collected. Serum total cholesterol (TC), triglyceride (TG), OxLDL and LOX-1 levels, OxLDL levels in aortic tissue homogenate, and subendothelial lipid accumulation levels by histological staining were determined in mice and statistical analyses were performed. WEP and EEP supplementation significantly decreased serum TC, TG, OxLDL, LOX-1, and tissue OxLDL levels and reduced plaque burden in the aortic root, with statistically significant differences observed. Those results suggest that propolis extracts have a potential treatment option for atherosclerosis, as a food supplement or a complementary medical/functional food. However, further research is needed to elucidate their molecular mechanisms, evaluate clinical efficacy and safety, and explore possible synergistic effects with existing atherosclerosis treatments.
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Affiliation(s)
- Katip Korkmaz
- Department of Nutrition and Dietetics, Faculty of Health Science, Karadeniz Technical University, 61080 Trabzon, Turkey;
| | - Orhan Deger
- Department of Medical Biochemistry, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey; (O.D.); (E.Y.)
| | - Ertugrul Yigit
- Department of Medical Biochemistry, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey; (O.D.); (E.Y.)
| | - Hüseyin Avni Uydu
- Department of Medical Biochemistry, Faculty of Medicine, Samsun University, 55080 Samsun, Turkey;
| | - Tolga Mercantepe
- Department of Histology and Embryology, Faculty of Medicine, Recep Tayyip Erdogan University, 53020 Rize, Turkey;
| | - Selim Demir
- Department of Nutrition and Dietetics, Faculty of Health Science, Karadeniz Technical University, 61080 Trabzon, Turkey;
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Zhang Z, He Z, Wang X, Huang B, Zhang W, Sha Y, Pang W. A natural small molecule pinocembrin resists high-fat diet-induced obesity through GPR120-ERK1/2 pathway. J Nutr Biochem 2025; 135:109772. [PMID: 39313008 DOI: 10.1016/j.jnutbio.2024.109772] [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: 04/01/2024] [Revised: 09/16/2024] [Accepted: 09/19/2024] [Indexed: 09/25/2024]
Abstract
Obesity is a widely concerned health problem. Mobilizing white adipose tissue and reducing fat synthesis are considered as effective strategies in the treatment of obesity. Here, using Connectivity Map (CMap) approach, we identified the pinocembrin (PB), a natural flavonoid primarily found in propolis, as a potential anti-obesity drug. Therefore, high-fat-diet (HFD) mice were randomly divided into two groups and fed a HFD or HFD with PB in this study. In vivo experiments showed that supplementation of PB reduced the body weight gain and ameliorated insulin resistance in HFD-induced mice. More importantly, PB did not cause side effect through detecting the levels of alanine transaminase (ALT), aspartate aminotransferase (AST), creatinine (CRE) and blood urea nitrogen (BUN) in serum of mice. Additionally, PB reduced expansion of white adipose tissue with upregulation of genes related lipolysis and downregulation of genes related lipogenesis. Furthermore, in vitro experiments revealed that PB treatment dose-dependently inhibited lipid droplet formation with upregulation of genes related lipolysis and downregulation of genes related lipogenesis. Molecular docking analysis combined with cellular thermal shift assay (CETSA) suggested that PB has a high affinity to the G protein-coupled receptor 120 (GPR120). Meanwhile, we confirmed that PB efficiently inhibited adipogenic differentiation of preadipocytes by directly binding to GPR120 and subsequently activating the downstream phosphorylation extracellular regulated kinase 1/2 (ERK1/2). Collectively, PB exerted anti-obesity effect through GPR120-ERK1/2 signaling pathway, providing a novel and promising natural drug for the treatment of obesity.
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Affiliation(s)
- Ziyi Zhang
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Zhaozhao He
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Xinyi Wang
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Boyu Huang
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Wanrong Zhang
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Yiwen Sha
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China
| | - Weijun Pang
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
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Haruna NF, Berdnikovs S, Nie Z. Eosinophil biology from the standpoint of metabolism: implications for metabolic disorders and asthma. J Leukoc Biol 2024; 116:288-296. [PMID: 38700084 PMCID: PMC11288379 DOI: 10.1093/jleuko/qiae100] [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: 11/20/2023] [Revised: 03/15/2024] [Accepted: 04/01/2024] [Indexed: 05/05/2024] Open
Abstract
Eosinophils, recognized for their immune and remodeling functions and participation in allergic inflammation, have recently garnered attention due to their impact on host metabolism, especially in the regulation of adipose tissue. Eosinophils are now known for their role in adipocyte beiging, adipokine secretion, and adipose tissue inflammation. This intricate interaction involves complex immune and metabolic processes, carrying significant implications for systemic metabolic health. Importantly, the interplay between eosinophils and adipocytes is bidirectional, revealing the dynamic nature of the immune-metabolic axis in adipose tissue. While the homeostatic regulatory role of eosinophils in adipose tissue is appreciated, this relationship in the context of obesity or allergic inflammation is much less understood. Mechanistic details of eosinophil-adipose interactions, especially the direct regulation of adipocytes by eosinophils, are also lacking. Another poorly understood aspect is the metabolism of the eosinophils themselves, encompassing metabolic shifts during eosinophil subset transitions in different tissue microenvironments, along with potential effects of host metabolism on the programming of eosinophil hematopoiesis and the resulting plasticity. This review consolidates recent research in this emerging and fascinating frontier of eosinophil investigation, identifying unexplored areas and presenting innovative perspectives on eosinophil biology in the context of metabolic disorders and associated health conditions, including asthma.
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Affiliation(s)
- Nana-Fatima Haruna
- Division of Allergy and Immunology, Feinberg School of Medicine, Northwestern University, 240 East Huron, McGaw M309, Chicago, IL 60611, United States
| | - Sergejs Berdnikovs
- Division of Allergy and Immunology, Feinberg School of Medicine, Northwestern University, 240 East Huron, McGaw M309, Chicago, IL 60611, United States
| | - Zhenying Nie
- Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, United States
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Yigit E, Deger O, Korkmaz K, Huner Yigit M, Uydu HA, Mercantepe T, Demir S. Propolis Reduces Inflammation and Dyslipidemia Caused by High-Cholesterol Diet in Mice by Lowering ADAM10/17 Activities. Nutrients 2024; 16:1861. [PMID: 38931216 PMCID: PMC11206409 DOI: 10.3390/nu16121861] [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: 05/06/2024] [Revised: 06/04/2024] [Accepted: 06/06/2024] [Indexed: 06/28/2024] Open
Abstract
Atherosclerosis is one of the most important causes of cardiovascular diseases. A disintegrin and metalloprotease (ADAM)10 and ADAM17 have been identified as important regulators of inflammation in recent years. Our study investigated the effect of inhibiting these enzymes with selective inhibitor and propolis on atherosclerosis. In our study, C57BL/6J mice (n = 16) were used in the control and sham groups. In contrast, ApoE-/- mice (n = 48) were used in the case, water extract of propolis (WEP), ethanolic extract of propolis (EEP), GW280264X (GW-synthetic inhibitor), and solvent (DMSO and ethanol) groups. The control group was fed a control diet, and all other groups were fed a high-cholesterol diet for 16 weeks. WEP (400 mg/kg/day), EEP (200 mg/kg/day), and GW (100 µg/kg/day) were administered intraperitoneally for the last four weeks. Animals were sacrificed, and blood, liver, aortic arch, and aortic root tissues were collected. In serum, total cholesterol (TC), triglycerides (TGs), and glucose (Glu) were measured by enzymatic colorimetric method, while interleukin-1β (IL-1β), paraoxonase-1 (PON-1), and lipoprotein-associated phospholipase-A2 (Lp-PLA2) were measured by ELISA. Tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), myeloperoxidase (MPO), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-12 (IL-12) levels were measured in aortic arch by ELISA and ADAM10/17 activities were measured fluorometrically. In addition, aortic root and liver tissues were examined histopathologically and immunohistochemically (ADAM10 and sortilin primary antibody). In the WEP, EEP, and GW groups compared to the case group, TC, TG, TNF-α, IL-1β, IL-6, IL-12, PLA2, MPO, ADAM10/17 activities, plaque burden, lipid accumulation, ADAM10, and sortilin levels decreased, while IL-10 and PON-1 levels increased (p < 0.003). Our study results show that propolis can effectively reduce atherosclerosis-related inflammation and dyslipidemia through ADAM10/17 inhibition.
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Affiliation(s)
- Ertugrul Yigit
- Department of Medical Biochemistry, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey;
| | - Orhan Deger
- Department of Medical Biochemistry, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey;
| | - Katip Korkmaz
- Department of Nutrition and Dietetics, Faculty of Health Science, Karadeniz Technical University, 61080 Trabzon, Turkey; (K.K.); (S.D.)
| | - Merve Huner Yigit
- Department of Medical Biochemistry, Faculty of Medicine, Recep Tayyip Erdogan University, 53000 Rize, Turkey;
| | - Huseyin Avni Uydu
- Department of Medical Biochemistry, Faculty of Medicine, Samsun University, 55080 Samsun, Turkey;
| | - Tolga Mercantepe
- Department of Histology and Embryology, Faculty of Medicine, Recep Tayyip Erdogan University, 53000 Rize, Turkey;
| | - Selim Demir
- Department of Nutrition and Dietetics, Faculty of Health Science, Karadeniz Technical University, 61080 Trabzon, Turkey; (K.K.); (S.D.)
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Rocha Caldas G, do Amaral L, Munhoz Rodrigues D, Mayrink de Miranda A, Aparecida Guinaim Dos Santos N, Machado Rocha L, Tame Parreira RL, Cardozo Dos Santos A, Kenupp Bastos J. Brazilian Green Propolis' Artepillin C and Its Acetylated Derivative Activate the NGF-Signaling Pathways and Induce Neurite Outgrowth in NGF-Deprived PC12 Cells. Chem Biodivers 2023; 20:e202301294. [PMID: 37953436 DOI: 10.1002/cbdv.202301294] [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: 08/25/2023] [Revised: 11/10/2023] [Accepted: 11/12/2023] [Indexed: 11/14/2023]
Abstract
Artepillin C is the most studied compound in Brazilian Green Propolis and, along with its acetylated derivative, displays neurotrophic activity on PC12 cells. Specific inhibitors of the trkA receptor (K252a), PI3K/Akt (LY294002), and MAPK/ERK (U0126) signaling pathways were used to investigate the neurotrophic mechanism. The expression of proteins involved in axonal and synaptic plasticity (GAP-43 and Synapsin I) was assessed by western blotting. Additionally, physicochemical properties, pharmacokinetics, and drug-likeness were evaluated by the SwissADME web tool. Both compounds induced neurite outgrowth by activating the NGF-signaling pathways but through different neuronal proteins. Furthermore, in silico analyses showed interesting physicochemical and pharmacokinetic properties of these compounds. Therefore, these compounds could play an important role in axonal and synaptic plasticity and should be further investigated.
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Affiliation(s)
- Gabriel Rocha Caldas
- School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
| | - Lilian do Amaral
- School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
| | - Débora Munhoz Rodrigues
- School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
| | - Aline Mayrink de Miranda
- School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
| | | | - Leandro Machado Rocha
- Natural Products Technology Laboratory-Fluminense Federal University, Niterói, RJ, Brazil
| | | | | | - Jairo Kenupp Bastos
- School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
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Kitamura H. Flow cytometric detection of CD11b + Gr-1 + cells in nontumor-bearing mice: A propolis-elicited model. Methods Cell Biol 2023; 184:17-32. [PMID: 38555156 DOI: 10.1016/bs.mcb.2023.05.010] [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: 04/02/2024]
Abstract
Myeloid-derived suppressor cells (MDSCs) are a heterogenous myeloid lineage population whose conventional surface phenotype is CD11b+ Gr-1+. Due to their rarity and fragility, analyses using primary isolated MDSCs are extremely difficult. However, counting CD11b+ Gr-1+ cells in associated tissues such as tumors and inflammatory lesions provides critical information regarding MDSC involvement in immune disorders in the tissues. Specific MDSC markers have not been identified, limiting our ability to apply histochemical approaches during MDSCs research. However, profiling surface antigens using multi-colorimetric flow cytometry enables us to easily monitor the abundance of MDSCs in vivo. Monitoring of mouse MDSCs and their subpopulations using flow cytometry is well established. In this article, I exemplify a conventional method of monitoring CD11b+ Gr-1+ cells in mouse adipose tissue after administration of Brazilian propolis ethanol extract, which is a strong inducer of MDSCs.
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Affiliation(s)
- Hiroshi Kitamura
- Laboratory of Disease Models, College of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
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Taiwanese green propolis ameliorates metabolic syndrome via remodeling of white adipose tissue and modulation of gut microbiota in diet-induced obese mice. Biomed Pharmacother 2023; 160:114386. [PMID: 36773526 DOI: 10.1016/j.biopha.2023.114386] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 02/01/2023] [Accepted: 02/07/2023] [Indexed: 02/11/2023] Open
Abstract
Excessive energy intake leads to dysbiosis of intestinal microbiota and puts surrounding tissues under oxidative stress and inflammation, contributing to the development of metabolic syndrome. Taiwanese green propolis (TGP) exhibits a broad spectrum of biological activities, including anti-bacterial, anti-inflammatory, and antioxidant properties. However, the benefits of TGP on metabolic syndrome have not been explained in detail. In this study, we examined the preventive effects of TGP on high-fat diet (HFD)-induced obesity. The results showed that TGP supplementation at 1000 ppm improved condition such as hyperlipidemia, fat accumulation, liver steatosis, and whitening of brown adipose tissue (BAT) in mice. In addition, we observed more cold-induced non-shivering thermogenesis by BAT in TGP treatment with 1000 ppm group. At lower dose of 500 ppm, TGP improved glucose intolerance and insulin insensitivity in HFD mice and restructured the composition of gut microbiota to reduce dysbiosis, which involved an increase in the abundance of metabolism-related bacteria such as Lachnospiraceae NK4A136 group and the decrease in Desulfovibrio. The change of dominant microbiota was associated with the homeostasis of blood glucose and lipid. Transcriptome and micro-western array analysis revealed that TGP supplementation at 500 ppm promoted the browning and adipogenesis in white adipose tissue (WAT), blocked inflammation signaling and attenuated reactive oxygen species, contributing to healthy WAT remodeling and offsetting negative metabolic effects of obesity. We concluded that TGP modulated the function of BAT, WAT, and gut microbiota, bringing a balance to the glucose and lipid homeostasis in the body.
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Zhu L, Zhang J, Yang H, Li G, Li H, Deng Z, Zhang B. Propolis polyphenols: A review on the composition and anti-obesity mechanism of different types of propolis polyphenols. Front Nutr 2023; 10:1066789. [PMID: 37063322 PMCID: PMC10102383 DOI: 10.3389/fnut.2023.1066789] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 03/14/2023] [Indexed: 04/03/2023] Open
Abstract
Obesity, one of the most common nutritional diseases worldwide, can lead to dyslipidemia, high blood sugar, high blood pressure, and inflammation. Some drugs have been developed to ameliorate obesity. However, these drugs may cause serious side effects. Therefore, there is an urgent need for alternative “natural” remedies including propolis. Studies have found that propolis has excellent anti-obesity activity in in vitro and in vivo models during the past decades, of which polyphenols are the key component in regulating weight loss. This review focused on the different polyphenol compositions of propolis from different regions and plants, the evidence for the anti-obesity effects of different types of propolis and its derivatives, discussed the impact of propolis polyphenols on obesity related signal pathways, and proposed the molecular mechanism of how propolis polyphenols affect these signal pathways. For example, propolis and its derivatives regulate lipid metabolism related proteins, such as PPARα, PPARγ, SREBP-1&2, and HMG CoA etc., destroy the formation of CREB/CRTC2 transcription complex, activate Nrf2 pathway or inhibit protein kinase IKK ε/TBK1, thereby affecting fat production and lipid metabolism; The effects of propolis on adipokines (adiponectin, leptin and inflammatory factors) were discussed. Additionally, the mechanism of polyphenols in propolis promoting the browning of adipose tissues and the relationship between intestinal microorganisms was summarized. These information may be of value to better understand how specific propolis polyphenols interact with specific signaling pathways and help guide the development of new drugs to combat obesity and related metabolic diseases.
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Affiliation(s)
- Liuying Zhu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| | - Jinwu Zhang
- Nanchang Concentric Purple Nest Biological Engineering Co., Ltd., Nanchang, China
| | - Hui Yang
- Nanchang Concentric Purple Nest Biological Engineering Co., Ltd., Nanchang, China
| | - Guangyan Li
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
- Nanchang Concentric Purple Nest Biological Engineering Co., Ltd., Nanchang, China
| | - Hongyan Li
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| | - Zeyuan Deng
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| | - Bing Zhang
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
- *Correspondence: Bing Zhang,
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Chavda VP, Chaudhari AZ, Teli D, Balar P, Vora L. Propolis and Their Active Constituents for Chronic Diseases. Biomedicines 2023; 11:biomedicines11020259. [PMID: 36830794 PMCID: PMC9953602 DOI: 10.3390/biomedicines11020259] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Revised: 01/11/2023] [Accepted: 01/16/2023] [Indexed: 01/20/2023] Open
Abstract
Propolis is a mass of chemically diverse phytoconstituents with gummy textures that are naturally produced by honeybees upon collection of plant resins for utilization in various life processes in beehives. Since ancient times, propolis has been a unique traditional remedy globally utilized for several purposes, and it has secured value in pharmaceutical and nutraceutical areas in recent years. The chemical composition of propolis comprises diverse constituents and deviations in the precise composition of the honeybee species, plant source used for propolis production by bees, climate conditions and harvesting season. Over 300 molecular structures have been discovered from propolis, and important classes include phenolic acids, flavonoids, terpenoids, benzofurans, benzopyrene and chalcones. Propolis has also been reported to have diverse pharmacological activities, such as antidiabetic, anti-inflammatory, antioxidant, anticancer, immunomodulatory, antibacterial, antiviral, antifungal, and anticaries. As chronic diseases have risen as a global health threat, abundant research has been conducted to track propolis and its constituents as alternative therapies for chronic diseases. Several clinical trials have also revealed the potency of propolis and its constituents for preventing and curing some chronic diseases. This review explores the beneficial effect of propolis and its active constituents with credible mechanisms and computational studies on chronic diseases.
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Affiliation(s)
- Vivek P. Chavda
- Department of Pharmaceutics and Pharmaceutical Technology, L. M. College of Pharmacy, Ahmedabad 380008, India
- Correspondence: (V.P.C.); (L.V.)
| | - Amit Z. Chaudhari
- Department of Pharmaceutical Chemistry, L. M. College of Pharmacy, Ahmedabad 380009, India
| | - Divya Teli
- Department of Pharmaceutical Chemistry, L. M. College of Pharmacy, Ahmedabad 380009, India
| | - Pankti Balar
- Pharmacy Section, L. M. College of Pharmacy, Navrangpura, Ahmedabad 380009, India
| | - Lalitkumar Vora
- School of Pharmacy, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK
- Correspondence: (V.P.C.); (L.V.)
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Kanazashi M, Iida T, Nakanishi R, Tanaka M, Ikeda H, Takamiya N, Maeshige N, Kondo H, Nishigami T, Harada T, Fujino H. Brazilian Propolis Intake Decreases Body Fat Mass and Oxidative Stress in Community-Dwelling Elderly Females: A Randomized Placebo-Controlled Trial. Nutrients 2023; 15:nu15020364. [PMID: 36678234 PMCID: PMC9861743 DOI: 10.3390/nu15020364] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 12/25/2022] [Accepted: 01/05/2023] [Indexed: 01/13/2023] Open
Abstract
This study aimed to investigate the effects of Brazilian propolis on body fat mass and levels of adiponectin and reactive oxygen species among community-dwelling elderly females. This was a double-blind randomized placebo-controlled trial. Altogether, 78 females aged 66-84 years were randomly assigned to the propolis (PRO; n = 39) or placebo (PLA; n = 39) group. For 12 weeks, the PRO group were given three capsules containing 227 mg of propolis twice a day. Meanwhile, the PLA group were given daily placebo capsules. Of 78 participants, 53 (PLA group: n = 28, PRO group: n = 25) completed the study. Although no changes were observed in absolute or relative fat mass in the PLA group, they showed a significant decline in the PRO group. The level of serum adiponectin in the PLA group did not change, although that of the PRO group significantly increased. The level of d-ROMs in the PLA group significantly increased, whereas that of the PRO group significantly decreased. The serum SOD activity in the PLA group significantly decreased, whereas that of the PRO group tended to increase. These results suggest that propolis supplementation may decrease body fat mass and oxidative stress among community-dwelling elderly females.
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Affiliation(s)
- Miho Kanazashi
- Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima, Mihara 723-0053, Japan
| | - Tadayuki Iida
- Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima, Mihara 723-0053, Japan
| | - Ryosuke Nakanishi
- Department of Physical Therapy, Faculty of Rehabilitation, Kobe International University, Kobe 658-0032, Japan
| | - Masayuki Tanaka
- Department of Physical Therapy, Faculty of Health Sciences, Okayama Healthcare Professional University, Okayama 700-0913, Japan
| | - Hiromi Ikeda
- Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima, Mihara 723-0053, Japan
| | - Naomi Takamiya
- Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima, Mihara 723-0053, Japan
| | - Noriaki Maeshige
- Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences, Kobe 654-0142, Japan
| | - Hiroyo Kondo
- Department of Food Science and Nutrition, Nagoya Women’s University, Nagoya 467-8611, Japan
| | - Tomohiko Nishigami
- Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima, Mihara 723-0053, Japan
| | - Toshihide Harada
- Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima, Mihara 723-0053, Japan
| | - Hidemi Fujino
- Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences, Kobe 654-0142, Japan
- Correspondence: ; Tel.: +81-78-796-4542
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Rashvand F, Irandoust K, Taheri M, Gholamzadeh Khoei S, Gheibi N. The Effect of Four Weeks of Long-Term Endurance Training with and Without Propolis Supplementation on Serum Levels of Betatrophin/ANGPTL8 in Male Athletes. Asian J Sports Med 2022; 13. [DOI: 10.5812/asjsm-120515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 08/14/2022] [Accepted: 09/06/2022] [Indexed: 11/09/2023] Open
Abstract
Background: Betatrophin/angiopoietin-like protein (ANGPTL8) is defined as an adipokine that regulates blood glucose and triglyceride levels. Objectives: This study aimed to evaluate the effect of propolis supplementation for the first time on serum levels of the hormone betatrophin, as a drug target in the treatment of dyslipidemia, in male endurance athletes for four weeks. Methods: 44 male athletes with an average age of 22 ± 3 years, a height of 177.5 ± 6.5 cm, and a weight of 76 ± 6 kg were selected in Qazvin. They were randomly divided into four groups: Supplementation, placebo, physical activity, and control. The supplementation and placebo groups received two 500 mg tablets of propolis and cellulose (in terms of shape and color, are similar to the original supplement and have no properties, flavor, and aroma) once after lunch and once after dinner, respectively. The drug treatment lasted for four weeks. The athletes' weight and serum levels of betatrophin were measured at the beginning and the end of 4 weeks of treatment. The ELISA method was used to assess the serum concentration of betatrophin. Analyzes were performed by the ANCOVA method. Results: The results showed that the long-term endurance training plus propolis supplementation would result in significant changes in the betatrophin serum levels and weight in participants (P = 0.001), but in the athletes without supplementation, these changes were not significant (P > 0.05). Conclusions: The results indicated that betatrophin serum levels in endurance athletes are increased by propolis supplementation, and their weight is decreased.
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Tsuda T, Kumazawa S. Propolis: Chemical Constituents, Plant Origin, and Possible Role in the Prevention and Treatment of Obesity and Diabetes. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:15484-15494. [PMID: 34910481 DOI: 10.1021/acs.jafc.1c06194] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Honeybee products are not only beneficial to human health but also important to the food industry. One such product is propolis, a resinous substance that honeybees collect from certain trees and plants and store inside their hives. Although various health benefits of propolis have been reported, the chemical composition of propolis varies greatly depending on the growing region and plant origin. These differences have led to many misconceptions and conflicting research results. In this paper, we review research findings on how the growing region and plant origin of propolis affects its composition. We also discuss trends in research on the antiobesity and antidiabetes effects of propolis as well as recent findings that a major component of Brazilian green propolis modulates adipocyte function. Finally, we discuss challenges to be tackled in future research on the health benefits of propolis and share our perspective on the future of this field.
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Affiliation(s)
- Takanori Tsuda
- College of Bioscience and Biotechnology, Graduate School of Bioscience and Biotechnology, Chubu University, Kasugai, Aichi 487-8501, Japan
| | - Shigenori Kumazawa
- Department of Food and Nutritional Sciences, University of Shizuoka, Suruga-ku, Shizuoka 422-8526, Japan
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13
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Gheflati A, Dehnavi Z, Ghannadzadeh Yazdi A, Khorasanchi Z, Raeisi-Dehkordi H, Ranjbar G. The effects of propolis supplementation on metabolic parameters: A systematic review and meta-analysis of randomized controlled clinical trials. AVICENNA JOURNAL OF PHYTOMEDICINE 2021; 11:551-565. [PMID: 34804893 PMCID: PMC8588957 DOI: 10.22038/ajp.2021.18046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 03/03/2021] [Accepted: 03/06/2021] [Indexed: 12/16/2022]
Abstract
Objective: Propolis is a sticky, resinous substance produced by honeybees from various plants. Various biological properties of propolis and its extracts have been recognized in previous studies including the antiseptic, anti-inflammatory, antioxidant, antiviral, hepatoprotective, antitumor, antibacterial and antimycotic properties. This study aimed to summarize the effect of propolis on metabolic parameters in human adults using systematic review and meta-analysis. Materials and Methods: A comprehensive systematic search was performed in ISI Web of Science, PubMed, Scopus, and Google Scholar up to July 2020 for controlled clinical trials evaluating the impact of propolis on lipid profile and liver enzyme biomarkers. A random effects model was used to calculate the weighted mean difference (WMD) and 95% confidence interval (CI) as the difference between the mean for the intervention and control groups. Results: The present meta-analysis included six randomized controlled trials. There was significant reduction in Aspartate Aminotransferase (AST) in comparison to the control groups (WMD=-2.01; 95% CI: -3.93--0.10; p=0.039). However, a non-significant effect was observed in Triglycerides (TG), Total cholesterol (TC), low-density lipoprotein (LDL), High-density lipoprotein (HDL) (WMD=-0.05 mg/dl; 95% CI: -0.27-0.18; p=0.688; WMD=7.08 mg/dl; 95% CI: -37.31-51.46; p=0.755; WMD=-0.94 mg/dl; 95% CI: -6.64-4.77; p=0.747; WMD=3.14 mg/dl; 95% CI: -1.84-8.13; p=0.216, respectively). Conclusion: Current meta-analysis revealed that propolis supplementation can reduce AST; nevertheless, there was no significant effect on lipid profile indices and ALT.
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Affiliation(s)
- Alireza Gheflati
- Department of Nutrition, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Dehnavi
- Department of Nutrition, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Zahra Khorasanchi
- Department of Nutrition, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamidreza Raeisi-Dehkordi
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Golnaz Ranjbar
- Department of Nutrition, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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14
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Liu H, Li J, Yuan W, Hao S, Wang M, Wang F, Xuan H. Bioactive components and mechanisms of poplar propolis in inhibiting proliferation of human hepatocellular carcinoma HepG2 cells. Biomed Pharmacother 2021; 144:112364. [PMID: 34700230 DOI: 10.1016/j.biopha.2021.112364] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 10/17/2021] [Accepted: 10/19/2021] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND The aim of this study was to elucidate the bioactive components and anti-tumor mechanism of poplar propolis extract obtained from North China (CP) in human hepatocellular carcinoma HepG2 cells in vitro. METHODS Cell viability and proliferation were measured by SRB assay and EdU proliferation test kit, respectively. Cell migration was evaluated by scratching test. Reactive oxygen species (ROS) production and mitochondrial membrane potential were investigated with the fluorescent probes, DCHF and JC-1, respectively. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were inspected by measurement kits. Apoptosis was assessed by acridine orange (AO) and Hoechst 33258 staining. Levels of Bax, Bcl-2, caspase 9, caspase 3, PARP, MMP-2, MMP-9, PI3K/p-PI3K, AKT/p-AKT, p38MAPK/p-p38 MAPK, ERK/p-ERK, LATS2, YAP, TAZ and TEAD1 were assessed by western blotting, respectively. RESULTS The bioactive components of CP inhibiting HepG2 cells were mainly flavonoids, and esters. CP induced HepG2 apoptosis through a mitochondrial-dependent intrinsic pathway with elevated the levels of cleaved PARP, cleaved caspase 3, and Bax and decreased the expressions of Bcl-2 and procaspase 9. It seemed that CP triggered apoptosis by activation of the p38 MAPK and inactivation of p-ERK. More importantly, we found that CP suppressed the Hippo pathway, leading to inactivation of YAP/TAZ and TEAD1 and inhibition of PI3K/AKT signaling molecules. CONCLUSION CP exerted excellent anti-proliferation and pro-apoptosis actions in HepG2 cells by inactivation of the loop between the Hippo/YAP and PI3K/AKT pathways, and may be a promising therapy for HCC.
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Affiliation(s)
- Hui Liu
- School of Life Science, Liaocheng University, Liaocheng 252059, China
| | - Junya Li
- School of Life Science, Liaocheng University, Liaocheng 252059, China
| | - Wenwen Yuan
- School of Life Science, Liaocheng University, Liaocheng 252059, China
| | - Shengyu Hao
- School of Physical Science and Information Technology, Liaocheng University, Liaocheng 252059, China
| | - Meng Wang
- School of Life Science, Liaocheng University, Liaocheng 252059, China
| | - Fei Wang
- School of Life Science, Liaocheng University, Liaocheng 252059, China
| | - Hongzhuan Xuan
- School of Life Science, Liaocheng University, Liaocheng 252059, China.
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15
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Alassaf FA, Jasim MHM, Alfahad M, Qazzaz ME, Abed MN, Thanoon IAJ. Effects of Bee Propolis on FBG, HbA1c, and Insulin Resistance in Healthy Volunteers. Turk J Pharm Sci 2021; 18:405-409. [PMID: 34496480 DOI: 10.4274/tjps.galenos.2020.50024] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
Objectives Bee propolis is a natural substance that is used in traditional medicine due to its versatile pharmacological actions. This study evaluates whether short term use of bee propolis supplementation could have an impact on glycemic control in healthy individuals. Materials and Methods A single daily dose of 1000 mg of bee propolis was administered orally to a total of 34 healthy individuals for 60 days. Body weight, body mass index (BMI), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), and insulin resistance were measured in all participants before and after the use of bee propolis. Results The results of this study showed that bee propolis was associated with a significant increase in body weight and BMI of healthy volunteers. Bee propolis supplementation decreased FBG and HbA1c, but did not affect insulin resistance. Conclusion Based on these results, bee propolis supplementation has a potential effect on glycemic control in healthy individuals and this should be considered when using this supplement in medical conditions.
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Affiliation(s)
- Fawaz A Alassaf
- Mosul University College of Pharmacy, Department of Pharmacology and Toxicology, Mosul, Iraq
| | - Mahmood H M Jasim
- Mosul University College of Pharmacy, Department of Pharmaceutical Chemistry, Mosul, Iraq
| | - Mohanad Alfahad
- Mosul University College of Pharmacy, Department of Pharmaceutics, Mosul, Iraq
| | - Mohannad E Qazzaz
- Mosul University College of Pharmacy, Department of Pharmacognosy and Medicinal Plants, Mosul, Iraq
| | - Mohammed N Abed
- Mosul University College of Pharmacy, Department of Pharmaceutical Chemistry, Mosul, Iraq
| | - Imad A-J Thanoon
- Mosul University College of Medicine, Department of Pharmacology, Mosul, Iraq
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Wibowo I, Utami N, Anggraeni T, Barlian A, Putra RE, Indriani AD, Masadah R, Ekawardhani S. Propolis Can Improve Caudal Fin Regeneration in Zebrafish ( Danio rerio) Induced by The Combined Administration of Alloxan and Glucose. Zebrafish 2021; 18:274-281. [PMID: 34297614 DOI: 10.1089/zeb.2020.1969] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Hyperglycemia, a primary symptom in diabetes mellitus, is associated with difficulties in wound healing and regeneration. This condition is due to the length of the inflammatory phase and free radicals. Furthermore, there is evidence that molecular pathogenesis is involved in impaired wound healing in diabetics. As an animal model, zebrafish have many shared orthologous genes with human that are involved in protein regulation of wound healing and regeneration. Little is known about natural drugs that may be used to treat complications of wound healing in diabetes. Propolis, however, is known to consist of various organic compounds such as phenols and flavonoids with antioxidant and anti-inflammatory activities. This research aims to study propolis' effect on caudal fin regeneration and relative expression of several genes belonging to Hedgehog, bone morphogenetic protein (BMP), and Wnt signaling hyperglycemic (HG) zebrafish. GC-MS analysis and antioxidant activity testing were performed on ethanolic extract of propolis (EEP). Caudal fin regeneration was analyzed using ImageJ; blood glucose levels were measured; and relative gene expression analysis of shha, igf2a, bmp2b, and col1a2 was performed by the real-time polymerase chain reaction method with the β-actin housekeeping gene. Impairment of caudal fin regeneration in zebrafish hyperglycemia was characterized by a low percentage of regeneration and decreased relative gene expression. EEP at 15 ppm could increase the percentage of caudal fin regeneration and the expression of shha, igf2a, bmp2b, and col1a2. Based on the results, it appears that phenols and flavonoids from the EEP can improve the caudal fin regeneration of HG zebrafish.
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Affiliation(s)
- Indra Wibowo
- School of Life Sciences and Technology, Bandung Institute of Technology (ITB), Bandung, Indonesia
| | - Nuruliawaty Utami
- School of Life Sciences and Technology, Bandung Institute of Technology (ITB), Bandung, Indonesia
| | - Tjandra Anggraeni
- School of Life Sciences and Technology, Bandung Institute of Technology (ITB), Bandung, Indonesia
| | - Anggraini Barlian
- School of Life Sciences and Technology, Bandung Institute of Technology (ITB), Bandung, Indonesia
| | - Ramadhani Eka Putra
- School of Life Sciences and Technology, Bandung Institute of Technology (ITB), Bandung, Indonesia.,Biology Studi Program, Institut Teknologi Sumatera, Jalan Terusan Ryacudu, Way Hui, Indonesia
| | - Annisa Devi Indriani
- School of Life Sciences and Technology, Bandung Institute of Technology (ITB), Bandung, Indonesia
| | - Rina Masadah
- Department of Pathology Anatomy Faculty of Medicine Hasanuddin University, Makassar, Indonesia
| | - Savira Ekawardhani
- Parasitology Division, Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
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Effects of Baccharin Isolated from Brazilian Green Propolis on Adipocyte Differentiation and Hyperglycemia in ob/ob Diabetic Mice. Int J Mol Sci 2021; 22:ijms22136954. [PMID: 34203569 PMCID: PMC8267681 DOI: 10.3390/ijms22136954] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 06/18/2021] [Accepted: 06/22/2021] [Indexed: 01/04/2023] Open
Abstract
Propolis is a honeybee product with various biological activities, including antidiabetic effects. We previously reported that artepillin C, a prenylated cinnamic acid derivative isolated from Brazilian green propolis, acts as a peroxisome proliferator-activated receptor γ (PPARγ) ligand and promotes adipocyte differentiation. In this study, we examined the effect of baccharin, another major component of Brazilian green propolis, on adipocyte differentiation. The treatment of mouse 3T3-L1 preadipocytes with baccharin resulted in increased lipid accumulation, cellular triglyceride levels, glycerol-3-phosphate dehydrogenase activity, and glucose uptake. The mRNA expression levels of PPARγ and its target genes were also increased by baccharin treatment. Furthermore, baccharin enhanced PPARγ-dependent luciferase activity, suggesting that baccharin promotes adipocyte differentiation via PPARγ activation. In diabetic ob/ob mice, intraperitoneal administration of 50 mg/kg baccharin significantly improved blood glucose levels. Our results suggest that baccharin has a hypoglycemic effect on glucose metabolic disorders, such as type 2 diabetes mellitus.
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Michailidou Z, Gomez-Salazar M, Alexaki VI. Innate Immune Cells in the Adipose Tissue in Health and Metabolic Disease. J Innate Immun 2021; 14:4-30. [PMID: 33849008 DOI: 10.1159/000515117] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Accepted: 02/09/2021] [Indexed: 11/19/2022] Open
Abstract
Metabolic disorders, such as obesity, type 2 diabetes mellitus, and nonalcoholic fatty liver disease, are characterized by chronic low-grade tissue and systemic inflammation. During obesity, the adipose tissue undergoes immunometabolic and functional transformation. Adipose tissue inflammation is driven by innate and adaptive immune cells and instigates insulin resistance. Here, we discuss the role of innate immune cells, that is, macrophages, neutrophils, eosinophils, natural killer cells, innate lymphoid type 2 cells, dendritic cells, and mast cells, in the adipose tissue in the healthy (lean) and diseased (obese) state and describe how their function is shaped by the obesogenic microenvironment, and humoral, paracrine, and cellular interactions. Moreover, we particularly outline the role of hypoxia as a central regulator in adipose tissue inflammation. Finally, we discuss the long-lasting effects of adipose tissue inflammation and its potential reversibility through drugs, caloric restriction, or exercise training.
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Affiliation(s)
- Zoi Michailidou
- Centre for Cardiovascular Sciences, Edinburgh University, Edinburgh, United Kingdom
| | - Mario Gomez-Salazar
- Centre for Cardiovascular Sciences, Edinburgh University, Edinburgh, United Kingdom
| | - Vasileia Ismini Alexaki
- Institute for Clinical Chemistry and Laboratory Medicine, Medical Faculty, Technische Universität Dresden, Dresden, Germany
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Botanic Origin of Propolis Extract Powder Drives Contrasted Impact on Diabesity in High-Fat-Fed Mice. Antioxidants (Basel) 2021; 10:antiox10030411. [PMID: 33803136 PMCID: PMC8000394 DOI: 10.3390/antiox10030411] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 03/02/2021] [Accepted: 03/05/2021] [Indexed: 12/04/2022] Open
Abstract
Propolis extracts are considered as nutraceutical products with potentialities towards obesity and comorbidities management. Nevertheless, propolis extracts composition is highly variable and depends on the botanic origin of plants used by the bees to produce propolis. This study aims to evaluate the differential effect of poplar propolis extract powder (PPEP), Baccharis propolis extract powder (BPEP), and/ or Dalbergia propolis extract powder (DPEP) on obesity and glucose homeostasis in high-fat-fed mice. PPEP supplementation reduced high-fat (HF)-mediated body weight gain, adiposity index, and improved glucose homeostasis in male C57Bl/6J mice that were submitted to a high-fat diet for 12 weeks, whereas BPEP, DPEP, or a mix of the three PEPs did not modify those parameters. Adipose tissue (AT) gene expression profiling highlighted an induction of mRNA related to lipid catabolism and an inhibition of mRNA coding for inflammatory markers. Several Nrf2 target genes, coding for antioxidant enzymes, were induced in AT under PPEP effect, but not by other PEP. Interestingly, representative PPEP polyphenols mediated the induction of Nrf2 target genes cell-autonomously in adipocytes, suggesting that this induction may be related to the specific polyphenol content of PPEP. Whereas PPEP supplementation has demonstrated a clear potential to blunt the onset of obesity and associated comorbidities, other PEPs (from Baccharis and Dalbergia) were inefficient to support their role in preventive nutrition.
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20
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Hashimoto M, Kimura S, Kanno C, Yanagawa Y, Watanabe T, Okabe J, Takahashi E, Nagano M, Kitamura H. Macrophage ubiquitin-specific protease 2 contributes to motility, hyperactivation, capacitation, and in vitro fertilization activity of mouse sperm. Cell Mol Life Sci 2021; 78:2929-2948. [PMID: 33104844 PMCID: PMC11073191 DOI: 10.1007/s00018-020-03683-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 09/15/2020] [Accepted: 10/09/2020] [Indexed: 02/06/2023]
Abstract
Macrophages are innate immune cells that contribute to classical immune functions and tissue homeostasis. Ubiquitin-specific protease 2 (USP2) controls cytokine production in macrophages, but its organ-specific roles are still unknown. In this study, we generated myeloid-selective Usp2 knockout (msUsp2KO) mice and specifically explored the roles of testicular macrophage-derived USP2 in reproduction. The msUsp2KO mice exhibited normal macrophage characteristics in various tissues. In the testis, macrophage Usp2 deficiency negligibly affected testicular macrophage subpopulations, spermatogenesis, and testicular organogenesis. However, frozen-thawed sperm derived from msUsp2KO mice exhibited reduced motility, capacitation, and hyperactivation. In addition, macrophage Usp2 ablation led to a decrease in the sperm population exhibiting high intracellular pH, calcium influx, and mitochondrial membrane potential. Interrupted pronuclei formation in eggs was observed when using frozen-thawed sperm from msUsp2KO mice for in vitro fertilization. Administration of granulocyte macrophage-colony stimulating factor (GM-CSF), whose expression was decreased in testicular macrophages derived from msUsp2KO mice, restored mitochondrial membrane potential and total sperm motility. Our observations demonstrate a distinct role of the deubiquitinating enzyme in organ-specific macrophages that directly affect sperm function.
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Affiliation(s)
- Mayuko Hashimoto
- Laboratory of Veterinary Physiology, Department of Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan
| | - Shunsuke Kimura
- Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo, Japan
| | - Chihiro Kanno
- Laboratory of Theriogenology, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan
| | - Yojiro Yanagawa
- Laboratory of Theriogenology, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan
| | - Takafumi Watanabe
- Laboratory of Veterinary Anatomy, Department of Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan
| | - Jun Okabe
- Department of Diabetes, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia
| | - Eiki Takahashi
- Research Resources Centre, RIKEN Brain Science Institute, Wako, Japan
| | - Masashi Nagano
- Laboratory of Animal Reproduction, Department of Animal Science, School of Veterinary Medicine, Kitasato University, Towada, Japan
| | - Hiroshi Kitamura
- Laboratory of Veterinary Physiology, Department of Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
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21
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Propolis in Metabolic Syndrome and Its Associated Chronic Diseases: A Narrative Review. Antioxidants (Basel) 2021; 10:antiox10030348. [PMID: 33652692 PMCID: PMC7996839 DOI: 10.3390/antiox10030348] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 02/20/2021] [Accepted: 02/23/2021] [Indexed: 02/06/2023] Open
Abstract
Propolis is a resinous product collected by bees from plants to protect and maintain the homeostasis of their hives. Propolis has been used therapeutically by humans for centuries. This review article attempts to analyze the potential use of propolis in metabolic syndrome (MetS) and its associated chronic diseases. MetS and its chronic diseases were shown to be involved in at least seven out of the top 10 causes of death in 2019. Patients with MetS are also at a heightened risk of severe morbidity and mortality in the present COVID-19 pandemic. Propolis with its antioxidant and anti-inflammatory properties is potentially useful in ameliorating the symptoms of MetS and its associated chronic diseases. The aim of this article is to provide a comprehensive review on propolis and its therapeutic benefit in MetS and its chronic diseases, with an emphasis on in vitro and in vivo studies, as well as human clinical trials. Moreover, the molecular and biochemical mechanisms of action of propolis are also discussed. Propolis inhibits the development and manifestation of MetS and its chronic diseases by inhibiting of the expression and interaction of advanced glycation end products (AGEs) and their receptors (RAGEs), inhibiting pro-inflammatory signaling cascades, and promoting the cellular antioxidant systems.
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22
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[Body composition, mineral metabolism, and endocrine function of adipose tissue: influence of a nutritional supplement of propolis]. NUTR HOSP 2021; 38:585-591. [PMID: 33666089 DOI: 10.20960/nh.03438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
Introduction Introduction: propolis and its components influence lipid metabolism; however, its effect on body composition and mineral metabolism remains unknown. Objectives: to determine the effect of natural propolis supplementation on body composition, mineral metabolism, and the endocrine function of adipose tissue. Material and methods: twenty albino male Wistar rats (8 weeks old) were divided into two groups of 10 animals each. The rats were fed two different types of diet for 90 days: a standard diet for the control group (group C) and the same standard diet + 2 % propolis (group P). Thyroid hormones, ghrelin, leptin, adiponectin and insulin, non-esterified fatty acids (NEFA) in plasma, body composition (lean mass, fat mass and body water), and mineral deposition in target organs (spleen, brain, heart, lungs, testicles, kidneys and femur) were assessed. Results: thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4) did not show any differences after supplementation with propolis, while ghrelin and adiponectin decreased (p < 0.01 and p < 0.05, respectively) and insulin (p < 0.01), leptin (p < 0.05) and NEFA (p < 0.05) increased when 2 % propolis was supplied, while weight and body fat were reduced (p < 0.05) and lean mass increased. Lastly, the propolis supplement improves calcium deposition in the spleen, lungs, testes, and femur (p < 0.05). Conclusion: propolis supplementation of the diet (2 %) causes a decrease in the secretion of ghrelin and adiponectin, increasing the release of non-esterified fatty acids and the rate of insulin secretion. In addition, propolis supplementation induces an improvement in calcium deposition in target organs without affecting the rest of minerals, which improves body composition by inducing a reduction in weight and visceral adipose tissue, and improvement in lean mass.
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Boudreau A, Richard AJ, Harvey I, Stephens JM. Artemisia scoparia and Metabolic Health: Untapped Potential of an Ancient Remedy for Modern Use. Front Endocrinol (Lausanne) 2021; 12:727061. [PMID: 35211087 PMCID: PMC8861327 DOI: 10.3389/fendo.2021.727061] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 12/16/2021] [Indexed: 11/19/2022] Open
Abstract
Botanicals have a long history of medicinal use for a multitude of ailments, and many modern pharmaceuticals were originally isolated from plants or derived from phytochemicals. Among these, artemisinin, first isolated from Artemisia annua, is the foundation for standard anti-malarial therapies. Plants of the genus Artemisia are among the most common herbal remedies across Asia and Central Europe. The species Artemisia scoparia (SCOPA) is widely used in traditional folk medicine for various liver diseases and inflammatory conditions, as well as for infections, fever, pain, cancer, and diabetes. Modern in vivo and in vitro studies have now investigated SCOPA's effects on these pathologies and its ability to mitigate hepatotoxicity, oxidative stress, obesity, diabetes, and other disease states. This review focuses on the effects of SCOPA that are particularly relevant to metabolic health. Indeed, in recent years, an ethanolic extract of SCOPA has been shown to enhance differentiation of cultured adipocytes and to share some properties of thiazolidinediones (TZDs), a class of insulin-sensitizing agonists of the adipogenic transcription factor PPARγ. In a mouse model of diet-induced obesity, SCOPA diet supplementation lowered fasting insulin and glucose levels, while inducing metabolically favorable changes in adipose tissue and liver. These observations are consistent with many lines of evidence from various tissues and cell types known to contribute to metabolic homeostasis, including immune cells, hepatocytes, and pancreatic beta-cells. Compounds belonging to several classes of phytochemicals have been implicated in these effects, and we provide an overview of these bioactives. The ongoing global epidemics of obesity and metabolic disease clearly require novel therapeutic approaches. While the mechanisms involved in SCOPA's effects on metabolic, anti-inflammatory, and oxidative stress pathways are not fully characterized, current data support further investigation of this plant and its bioactives as potential therapeutic agents in obesity-related metabolic dysfunction and many other conditions.
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Affiliation(s)
- Anik Boudreau
- Adipocyte Biology Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, United States
| | - Allison J. Richard
- Adipocyte Biology Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, United States
| | - Innocence Harvey
- Adipocyte Biology Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, United States
| | - Jacqueline M. Stephens
- Adipocyte Biology Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, United States
- Department of Biological Sciences, Louisiana State University, Baton Rouge, LA, United States
- *Correspondence: Jacqueline M. Stephens,
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Rivera-Yañez N, Rivera-Yañez CR, Pozo-Molina G, Méndez-Catalá CF, Méndez-Cruz AR, Nieto-Yañez O. Biomedical Properties of Propolis on Diverse Chronic Diseases and Its Potential Applications and Health Benefits. Nutrients 2020; 13:E78. [PMID: 33383693 PMCID: PMC7823938 DOI: 10.3390/nu13010078] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 12/24/2020] [Accepted: 12/24/2020] [Indexed: 02/06/2023] Open
Abstract
The use of alternative medicine products has increased tremendously in recent decades and it is estimated that approximately 80% of patients globally depend on them for some part of their primary health care. Propolis is a beekeeping product widely used in alternative medicine. It is a natural resinous product that bees collect from various plants and mix with beeswax and salivary enzymes and comprises a complex mixture of compounds. Various biomedical properties of propolis have been studied and reported in infectious and non-infectious diseases. However, the pharmacological activity and chemical composition of propolis is highly variable depending on its geographical origin, so it is important to describe and study the biomedical properties of propolis from different geographic regions. A number of chronic diseases, such as diabetes, obesity, and cancer, are the leading causes of global mortality, generating significant economic losses in many countries. In this review, we focus on compiling relevant information about propolis research related to diabetes, obesity, and cancer. The study of propolis could generate both new and accessible alternatives for the treatment of various diseases and will help to effectively evaluate the safety of its use.
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Affiliation(s)
- Nelly Rivera-Yañez
- Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México 54090, Mexico; (N.R.-Y.); (C.R.R.-Y.)
| | - C. Rebeca Rivera-Yañez
- Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México 54090, Mexico; (N.R.-Y.); (C.R.R.-Y.)
| | - Glustein Pozo-Molina
- Laboratorio de Genética y Oncología Molecular, Laboratorio 5, Edificio A4, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México 54090, Mexico; (G.P.-M.); (C.F.M.-C.)
| | - Claudia F. Méndez-Catalá
- Laboratorio de Genética y Oncología Molecular, Laboratorio 5, Edificio A4, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México 54090, Mexico; (G.P.-M.); (C.F.M.-C.)
| | - Adolfo R. Méndez-Cruz
- Laboratorio de Inmunología, Unidad de Morfofisiología y Función, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México 54090, Mexico;
| | - Oscar Nieto-Yañez
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México 54090, Mexico
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25
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Berretta AA, Silveira MAD, Cóndor Capcha JM, De Jong D. Propolis and its potential against SARS-CoV-2 infection mechanisms and COVID-19 disease: Running title: Propolis against SARS-CoV-2 infection and COVID-19. Biomed Pharmacother 2020; 131:110622. [PMID: 32890967 PMCID: PMC7430291 DOI: 10.1016/j.biopha.2020.110622] [Citation(s) in RCA: 139] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 08/04/2020] [Accepted: 08/05/2020] [Indexed: 12/15/2022] Open
Abstract
Propolis, a resinous material produced by honey bees from plant exudates, has long been used in traditional herbal medicine and is widely consumed as a health aid and immune system booster. The COVID-19 pandemic has renewed interest in propolis products worldwide; fortunately, various aspects of the SARS-CoV-2 infection mechanism are potential targets for propolis compounds. SARS-CoV-2 entry into host cells is characterized by viral spike protein interaction with cellular angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2. This mechanism involves PAK1 overexpression, which is a kinase that mediates coronavirus-induced lung inflammation, fibrosis, and immune system suppression. Propolis components have inhibitory effects on the ACE2, TMPRSS2 and PAK1 signaling pathways; in addition, antiviral activity has been proven in vitro and in vivo. In pre-clinical studies, propolis promoted immunoregulation of pro-inflammatory cytokines, including reduction in IL-6, IL-1 beta and TNF-α. This immunoregulation involves monocytes and macrophages, as well as Jak2/STAT3, NF-kB, and inflammasome pathways, reducing the risk of cytokine storm syndrome, a major mortality factor in advanced COVID-19 disease. Propolis has also shown promise as an aid in the treatment of various of the comorbidities that are particularly dangerous in COVID-19 patients, including respiratory diseases, hypertension, diabetes, and cancer. Standardized propolis products with consistent bioactive properties are now available. Given the current emergency caused by the COVID-19 pandemic and limited therapeutic options, propolis is presented as a promising and relevant therapeutic option that is safe, easy to administrate orally and is readily available as a natural supplement and functional food.
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Affiliation(s)
- Andresa Aparecida Berretta
- Research, Development and Innovation Department, Apis Flora Indl. Coml. Ltda, Ribeirão Preto, São Paulo, Brazil.
| | | | - José Manuel Cóndor Capcha
- Interdisciplinary Stem Cell Institute at Miller School of Medicine, University of Miami, Miami, Florida, United States.
| | - David De Jong
- Genetics Department, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
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26
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Chen YW, Chien YH, Yu YH. Taiwanese green propolis ethanol extract promotes adipocyte differentiation and alleviates TNF-α-mediated downregulation of adiponectin expression. J Funct Foods 2020. [DOI: 10.1016/j.jff.2020.104135] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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27
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Bukovsky A. Immunology of tissue homeostasis, ovarian cancer growth and regression, and long lasting cancer immune prophylaxis - review of literature. Histol Histopathol 2020; 36:31-46. [PMID: 32896865 DOI: 10.14670/hh-18-261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Data on the substantial physiological role of the immune system in the organism's ability to manage proper differentiation and function of normal tissues (tissue homeostasis), and detailed causes of the immune system's essential role for the in-vivo stimulation of cancer growth, are severely lacking. This results in a lack of effective cancer immunotherapy without adverse events, and in the lack of long-lasting cancer immune prophylaxes, particularly in ovarian cancers. Elimination of blood auto-antibodies blocking anti-cancer T cell effectors by intermittent moderate doses of cyclophosphamide, facilitation of the immune system reactivity against alloantigens of cancer cells by two subsequent blood transfusions, and augmentation of anticancer immunity by weekly intradermal injections of bacterial toxins, caused during the subsequent treatment-free period, lasting for two to four weeks, regression of inoperable epithelial ovarian cancers and regeneration of the tremendously metastatically altered abdominal tissues into normal healthy conditions without multivisceral cytoreductive surgery, which can result in life-threatening consequences. An otherwise untreated rectal cancer, progressing over 3 years, regressed after severe toxic dermatitis lasting over one week. This was caused by an accidental consumption of a large raw shiitake mushroom. Subsequent daily consumptions of 2 g Metformin ER and honeybee propolis ethanol extract, and weekly single larger raw shiitake mushroom, which all stimulate immune system reactivity against cancer stem cells, prevented malignant recurrence over the next 29 years without recurring dermatitis, and maintained healthy organism's conditions. These observations indicate that regression of advanced inoperable cancers and long-lasting cancer immune prophylaxis can be reached by simple approaches.
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Affiliation(s)
- Antonin Bukovsky
- Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University, Vestec, Czech Republic.
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28
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Cardinault N, Tourniaire F, Astier J, Couturier C, Perrin E, Dalifard J, Seipelt E, Mounien L, Letullier C, Bonnet L, Karkeni E, Delbah N, Georgé S, Landrier JF. Poplar Propolis Ethanolic Extract Reduces Body Weight Gain and Glucose Metabolism Disruption in High-Fat Diet-Fed Mice. Mol Nutr Food Res 2020; 64:e2000275. [PMID: 32729164 DOI: 10.1002/mnfr.202000275] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 07/07/2020] [Indexed: 01/03/2023]
Abstract
SCOPE Current evidence supports the beneficial effect of polyphenols on the management of obesity and associated comorbidities. This is the case for propolis, a polyphenol-rich substance produced by bees. The aim of the present study is to evaluate the effect of a poplar propolis ethanolic extract (PPEE) on obesity and glucose homeostasis, and to unveil its putative molecular mechanisms of action. METHODS AND RESULTS Male high-fat (HF) diet-fed mice are administered PPEE for 12 weeks. PPEE supplementation reduces the HF-mediated adiposity index, adipocyte hypertrophy, and body weight gain. It also improves HOMA-IR and fasting glucose levels. Gene expression profiling of adipose tissue (AT) shows an induction of mRNA related to lipid catabolism and mitochondrial biogenesis and inhibition of mRNA coding for inflammatory markers. Interestingly, several Nrf2-target genes are induced in AT following administration of PPEE. The ability of PPEE to induce the expression of Nrf2-target genes is studied in adipocytes. PPEE is found to transactivate the Nrf2 response element and the Nrf2 DNA-binding, suggesting that part of the effect of PPEE can be mediated by Nrf2. CONCLUSION PPEE supplementation may represent an interesting preventive strategy to tackle the onset of obesity and associated metabolic disorders.
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Affiliation(s)
| | - Franck Tourniaire
- Aix-Marseille Université, C2VN, INRAE, INSERM, 27 Bd Jean Moulin, Marseille, cedex 5 13385, France.,CriBioM, Criblage Biologique Marseille, Faculté de Médecine de la Timone, 27 Bd Jean Moulin, Marseille, cedex 5 13385, France
| | - Julien Astier
- Aix-Marseille Université, C2VN, INRAE, INSERM, 27 Bd Jean Moulin, Marseille, cedex 5 13385, France
| | - Charlène Couturier
- Aix-Marseille Université, C2VN, INRAE, INSERM, 27 Bd Jean Moulin, Marseille, cedex 5 13385, France
| | - Estelle Perrin
- Aix-Marseille Université, C2VN, INRAE, INSERM, 27 Bd Jean Moulin, Marseille, cedex 5 13385, France
| | - Julie Dalifard
- Aix-Marseille Université, C2VN, INRAE, INSERM, 27 Bd Jean Moulin, Marseille, cedex 5 13385, France
| | - Eva Seipelt
- Aix-Marseille Université, C2VN, INRAE, INSERM, 27 Bd Jean Moulin, Marseille, cedex 5 13385, France
| | - Lourdes Mounien
- Aix-Marseille Université, C2VN, INRAE, INSERM, 27 Bd Jean Moulin, Marseille, cedex 5 13385, France
| | - Claire Letullier
- Pollenergie, La Grabère, Saint Hilaire de Lusignan, 47450, France
| | - Lauriane Bonnet
- Aix-Marseille Université, C2VN, INRAE, INSERM, 27 Bd Jean Moulin, Marseille, cedex 5 13385, France
| | - Esma Karkeni
- Aix-Marseille Université, C2VN, INRAE, INSERM, 27 Bd Jean Moulin, Marseille, cedex 5 13385, France
| | - Naïma Delbah
- CTCPA, 449 Avenue Clément Ader, Avignon, 84911, France
| | | | - Jean-François Landrier
- Aix-Marseille Université, C2VN, INRAE, INSERM, 27 Bd Jean Moulin, Marseille, cedex 5 13385, France.,CriBioM, Criblage Biologique Marseille, Faculté de Médecine de la Timone, 27 Bd Jean Moulin, Marseille, cedex 5 13385, France
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29
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Vohralik EJ, Psaila AM, Knights AJ, Quinlan KGR. EoTHINophils: Eosinophils as key players in adipose tissue homeostasis. Clin Exp Pharmacol Physiol 2020; 47:1495-1505. [PMID: 32163614 DOI: 10.1111/1440-1681.13304] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 02/24/2020] [Accepted: 03/09/2020] [Indexed: 12/22/2022]
Abstract
Eosinophils are granular cells of the innate immune system that are found in almost all vertebrates and some invertebrates. Knowledge of their wide-ranging roles in health and disease has largely been attained through studies in mice and humans. Although eosinophils are typically associated with helminth infections and allergic diseases such as asthma, there is building evidence that beneficial homeostatic eosinophils residing in specific niches are important for tissue development, remodelling and metabolic control. In recent years, the importance of immune cells in the regulation of adipose tissue homeostasis has been a focal point of research efforts. There is an abundance of anti-inflammatory innate immune cells in lean white adipose tissue, including macrophages, eosinophils and group 2 innate lymphoid cells, which promote energy homeostasis and stimulate the development of thermogenic beige adipocytes. This review will evaluate evidence for the role of adipose-resident eosinophils in local tissue homeostasis, beiging and systemic metabolism, highlighting where more research is needed to establish the specific effector functions that adipose eosinophils perform in response to different internal and external cues.
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Affiliation(s)
- Emily J Vohralik
- School of Biotechnology and Biomolecular Sciences, UNSW Sydney, Sydney, NSW, Australia
| | - Annalise M Psaila
- School of Biotechnology and Biomolecular Sciences, UNSW Sydney, Sydney, NSW, Australia
| | - Alexander J Knights
- School of Biotechnology and Biomolecular Sciences, UNSW Sydney, Sydney, NSW, Australia
| | - Kate G R Quinlan
- School of Biotechnology and Biomolecular Sciences, UNSW Sydney, Sydney, NSW, Australia
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30
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Cho H, Kim K, Kim N, Woo M, Kim HY. Effect of propolis phenolic compounds on free fatty acid receptor 4 activation. Food Sci Biotechnol 2020; 29:579-584. [PMID: 32296569 PMCID: PMC7142188 DOI: 10.1007/s10068-019-00688-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Revised: 09/15/2019] [Accepted: 09/20/2019] [Indexed: 12/12/2022] Open
Abstract
Propolis is known to have multiple biological and pharmacological properties including the regulation of energy homeostasis. Although phenolic compounds are considered to be the major active components in propolis, there is little information available about their mechanisms underlying the regulation of energy homeostasis. In this study, the effects of five phenolic compounds in propolis, chrysin, pinocembrin, galangin, pinobanksin, and caffeic acid phenethyl ester (CAPE) were evaluated on the activation of free fatty acid receptor 4 (FFA4), which are involved in the control of energy homeostasis by enhancing insulin signaling, increasing glucose uptake, and regulating adipogenesis. The results showed that three phenolic compounds exhibited the activation of FFA4, which were ranked in the order of pinocembrin, CAPE and pinobanksin in FFA4-expressing cells. These results suggest that some phenolic compounds in propolis, particularly pinocembrin, may affect the control of energy homeostasis via the activation of FFA4.
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Affiliation(s)
- Hyunnho Cho
- Division of Functional Food Research, Korea Food Research Institute, 245 Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365 Korea
| | - Kyong Kim
- Division of Functional Food Research, Korea Food Research Institute, 245 Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365 Korea
| | - Nayeon Kim
- Division of Functional Food Research, Korea Food Research Institute, 245 Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365 Korea
| | - Minji Woo
- Division of Functional Food Research, Korea Food Research Institute, 245 Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365 Korea
| | - Hye Young Kim
- Division of Functional Food Research, Korea Food Research Institute, 245 Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365 Korea
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31
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Calco GN, Fryer AD, Nie Z. Unraveling the connection between eosinophils and obesity. J Leukoc Biol 2020; 108:123-128. [PMID: 32170879 DOI: 10.1002/jlb.5mr0120-377r] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 01/31/2020] [Accepted: 02/14/2020] [Indexed: 12/23/2022] Open
Abstract
Obesity affects more than 650 million adults worldwide and is a major risk factor for a variety of serious comorbidities. The prevalence of obesity has tripled in the past forty years and continues to rise. Eosinophils have recently been implicated in providing a protective role against obesity. Decreasing eosinophils exacerbates weight gain and contributes to glucose intolerance in high fat diet-induced obese animals, while increasing eosinophils prevents high-fat diet-induced adipose tissue and body weight gain. Human studies, however, do not support a protective role for eosinophils in obesity. More recent animal studies have also reported conflicting results. Considering these contradictory findings, the relationship between eosinophils and obesity may not be unidirectional. In this mini-review, we summarize a recent debate regarding the role of adipose tissue eosinophils in metabolic disorders, and discuss local and systemic effects of eosinophils in obesity. Given that adipose eosinophils play a role in tissue homeostasis, more research is needed to understand the primary function of adipose tissue eosinophils in their microenvironment. Therapeutic interventions that target eosinophils in adipose tissue may have the potential to reduce inflammation and body fat, while improving metabolic dysfunction in obese patients.
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Affiliation(s)
- Gina N Calco
- Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon, USA
| | - Allison D Fryer
- Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon, USA
| | - Zhenying Nie
- Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon, USA
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32
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Effects of Propolis Extract and Propolis-Derived Compounds on Obesity and Diabetes: Knowledge from Cellular and Animal Models. Molecules 2019; 24:molecules24234394. [PMID: 31805752 PMCID: PMC6930477 DOI: 10.3390/molecules24234394] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 11/28/2019] [Accepted: 11/29/2019] [Indexed: 12/23/2022] Open
Abstract
Propolis is a natural product resulting from the mixing of bee secretions with botanical exudates. Since propolis is rich in flavonoids and cinnamic acid derivatives, the application of propolis extracts has been tried in therapies against cancer, inflammation, and metabolic diseases. As metabolic diseases develop relatively slowly in patients, the therapeutic effects of propolis in humans should be evaluated over long periods of time. Moreover, several factors such as medical history, genetic inheritance, and living environment should be taken into consideration in human studies. Animal models, especially mice and rats, have some advantages, as genetic and microbiological variables can be controlled. On the other hand, cellular models allow the investigation of detailed molecular events evoked by propolis and derivative compounds. Taking advantage of animal and cellular models, accumulating evidence suggests that propolis extracts have therapeutic effects on obesity by controlling adipogenesis, adipokine secretion, food intake, and energy expenditure. Studies in animal and cellular models have also indicated that propolis modulates oxidative stress, the accumulation of advanced glycation end products (AGEs), and adipose tissue inflammation, all of which contribute to insulin resistance or defects in insulin secretion. Consequently, propolis treatment may mitigate diabetic complications such as nephropathy, retinopathy, foot ulcers, and non-alcoholic fatty liver disease. This review describes the beneficial effects of propolis on metabolic disorders.
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33
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Patterson E, Ryan PM, Wiley N, Carafa I, Sherwin E, Moloney G, Franciosi E, Mandal R, Wishart DS, Tuohy K, Ross RP, Cryan JF, Dinan TG, Stanton C. Gamma-aminobutyric acid-producing lactobacilli positively affect metabolism and depressive-like behaviour in a mouse model of metabolic syndrome. Sci Rep 2019; 9:16323. [PMID: 31704943 PMCID: PMC6841999 DOI: 10.1038/s41598-019-51781-x] [Citation(s) in RCA: 108] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Accepted: 09/20/2019] [Indexed: 12/22/2022] Open
Abstract
Metabolic and neuroactive metabolite production represents one of the mechanisms through which the gut microbiota can impact health. One such metabolite, gamma-aminobutyric acid (GABA), can modulate glucose homeostasis and alter behavioural patterns in the host. We previously demonstrated that oral administration of GABA-producing Lactobacillus brevis DPC6108 has the potential to increase levels of circulating insulin in healthy rats. Therefore, the objective of this study was to assess the efficacy of endogenous microbial GABA production in improving metabolic and behavioural outcomes in a mouse model of metabolic dysfunction. Diet-induced obese and metabolically dysfunctional mice received one of two GABA-producing strains, L. brevis DPC6108 or L. brevis DSM32386, daily for 12 weeks. After 8 and 10 weeks of intervention, the behavioural and metabolic profiles of the mice were respectively assessed. Intervention with both L. brevis strains attenuated several abnormalities associated with metabolic dysfunction, causing a reduction in the accumulation of mesenteric adipose tissue, increased insulin secretion following glucose challenge, improved plasma cholesterol clearance and reduced despair-like behaviour and basal corticosterone production during the forced swim test. Taken together, this exploratory dataset indicates that intervention with GABA-producing lactobacilli has the potential to improve metabolic and depressive- like behavioural abnormalities associated with metabolic syndrome in mice.
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Affiliation(s)
- E Patterson
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
| | - P M Ryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
| | - N Wiley
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
| | - I Carafa
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland.,Department of Food Quality and Nutrition, Research and Innovation Centre-Fondazione Edmund Mach, San Michele all'Adige, Trento, Italy
| | - E Sherwin
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - G Moloney
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - E Franciosi
- Department of Food Quality and Nutrition, Research and Innovation Centre-Fondazione Edmund Mach, San Michele all'Adige, Trento, Italy
| | - R Mandal
- Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
| | - D S Wishart
- Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.,Department of Computing Science, University of Alberta, Edmonton, Alberta, Canada.,National Institute for Nanotechnology, Edmonton, Alberta, Canada
| | - K Tuohy
- Department of Food Quality and Nutrition, Research and Innovation Centre-Fondazione Edmund Mach, San Michele all'Adige, Trento, Italy
| | - R P Ross
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - J F Cryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - T G Dinan
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
| | - C Stanton
- APC Microbiome Ireland, University College Cork, Cork, Ireland. .,Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland.
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34
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Tani H, Hikami S, Takahashi S, Kimura Y, Matsuura N, Nakamura T, Yamaga M, Koshino H. Isolation, Identification, and Synthesis of a New Prenylated Cinnamic Acid Derivative from Brazilian Green Propolis and Simultaneous Quantification of Bioactive Components by LC-MS/MS. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:12303-12312. [PMID: 31597041 DOI: 10.1021/acs.jafc.9b04835] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
A new cinnamic acid derivative, (E)-3-[4-hydroxy-3-((E)-3-formyl-2-butenyl)phenyl]-2- propenoic acid (20) has been isolated from the ethanol extract of Brazilian green propolis along with three known cinnamic acid derivatives, 3,4-dihydroxy-5-prenyl-(E)-cinnamic acid (4), capillartemisin A (6), and 2,2-dimethylchromene-6-(E)-propenoic acid (8), and a flavonoid, dihydrokaempferide (16) by liquid-liquid participation, a series of column chromatography and preparative HPLC. Their structures have been determined by spectroscopic analyses and chemical synthesis of compound 20. The simultaneous quantification of 20 constituents, including 10 cinnamic acid derivatives, 7 flavonoids, and 3 caffeoylquinic acid derivatives, has also been developed and validated using LC-MS/MS. The new compound 20 was shown to activate PPAR α but not PPAR β or γ.
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Affiliation(s)
- Hiroko Tani
- Institute for Bee Products & Health Science, Yamada Bee Company, Incorporated , 194 Ichiba , Kagamino-cho, Okayama 708-0393 , Japan
| | - Susumu Hikami
- Institute for Bee Products & Health Science, Yamada Bee Company, Incorporated , 194 Ichiba , Kagamino-cho, Okayama 708-0393 , Japan
| | - Shunya Takahashi
- RIKEN Center for Sustainable Resource Science , Wako, Saitama , 351-0198 , Japan
| | - Yuka Kimura
- Institute for Bee Products & Health Science, Yamada Bee Company, Incorporated , 194 Ichiba , Kagamino-cho, Okayama 708-0393 , Japan
| | - Nobuyasu Matsuura
- Department of Life Science, Faculty of Science , Okayama University of Science , 1-1 Ridai-cho , Okayama 700-0005 , Japan
| | - Takemichi Nakamura
- RIKEN Center for Sustainable Resource Science , Wako, Saitama , 351-0198 , Japan
| | - Masayuki Yamaga
- Institute for Bee Products & Health Science, Yamada Bee Company, Incorporated , 194 Ichiba , Kagamino-cho, Okayama 708-0393 , Japan
| | - Hiroyuki Koshino
- RIKEN Center for Sustainable Resource Science , Wako, Saitama , 351-0198 , Japan
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35
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Bolus WR, Hasty AH. Contributions of innate type 2 inflammation to adipose function. J Lipid Res 2019; 60:1698-1709. [PMID: 29891508 PMCID: PMC6795076 DOI: 10.1194/jlr.r085993] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Revised: 05/25/2018] [Indexed: 12/17/2022] Open
Abstract
A critical contributor to the health consequences of the obesity epidemic is dysregulated adipose tissue (AT) homeostasis. While white, brown, and beige AT function is altered in obesity-related disease, white AT is marked by progressive inflammation and adipocyte dysfunction and has been the focus of extensive "immunometabolism" research in the past decade. The exact triggering events initiating and sustaining AT inflammation are still under study, but it has been shown that reducing inflammation improves insulin action in AT. Scientific efforts seeking interventions to mitigate obesity-associated AT inflammation continue, and many groups are now determining how lean healthy AT homeostasis is maintained in order to leverage these mechanisms as therapeutic targets. Such studies have revealed that an elaborate network of immune cells, cytokines, and other cellular mediators coordinate AT function. Recent studies elucidated the involvement of the innate immune system in AT homeostasis (e.g., beiging and insulin sensitivity), including M2-like macrophages, eosinophils, innate lymphoid type 2 cells, and several others. In this review, we summarize the existing literature on innate type 2 inflammation in AT; additionally, we draw attention to areas of debate where seemingly conflicting data promises to yield more surprising and elegant biology as studies continue to dissect AT physiology.
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Affiliation(s)
- W Reid Bolus
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville TN 37232
| | - Alyssa H Hasty
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville TN 37232
- Veterans Affairs Tennessee Valley Healthcare System, Nashville TN 37212
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36
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The Effect of Iranian Propolis on Glucose Metabolism, Lipid Profile, Insulin Resistance, Renal Function and Inflammatory Biomarkers in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blind Clinical Trial. Sci Rep 2019; 9:7289. [PMID: 31086222 PMCID: PMC6514000 DOI: 10.1038/s41598-019-43838-8] [Citation(s) in RCA: 84] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Accepted: 05/02/2019] [Indexed: 12/17/2022] Open
Abstract
Propolis is a natural product with many biological properties including hypoglycemic activity and modulating lipid profile. The present study was designed to evaluate the effect of Iranian propolis extract on glucose metabolism, Lipid profile, Insulin resistance, renal and liver function as well as inflammatory biomarkers in patients with type 2 diabetes mellitus (T2DM). A double-blind, placebo-controlled clinical trial was conducted. The duration of the study lasted 90 days. Patients with T2DM were recruited and randomly divided into an Iranian propolis group (1000 mg/day) (n = 50) and a placebo group (n = 44). There was a significant decrease in the serum levels of glycosylated hemoglobin (HbA1c), 2-hour post prandial (2hpp), insulin, homeostasis model assessment-insulin resistance (HOMA-IR), homeostasis model assessment of β-cell function (HOMA-β), High sensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α). However, there was a notable elevation in the serum HDL-C in the propolis group compared with the placebo group. In addition, a notable reduction in serum liver transaminase (ALT and AST) and blood urea nitrogen (BUN) concentrations in the propolis group was observed. Iranian propolis has beneficial effects on reducing post prandial blood glucose, serum insulin, insulin resistance, and inflammatory cytokines. It is also a useful treatment for preventing the liver and renal dysfunction, as well as, elevating HDL-C concentrations in patients with T2DM.
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Costa P, Almeida MO, Lemos M, Arruda C, Casoti R, Somensi LB, Boeing T, Mariott M, da Silva RDCMVDAF, Stein BDP, Souza PD, Dos Santos AC, Bastos JK, da Silva LM, Andrade SFD. Artepillin C, drupanin, aromadendrin-4'-O-methyl-ether and kaempferide from Brazilian green propolis promote gastroprotective action by diversified mode of action. JOURNAL OF ETHNOPHARMACOLOGY 2018; 226:82-89. [PMID: 30107246 DOI: 10.1016/j.jep.2018.08.006] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 07/29/2018] [Accepted: 08/09/2018] [Indexed: 06/08/2023]
Abstract
ETHOPHARMACOLOGICAL RELEVANCE The propolis is extensively used in folk medicine in natura or to prepare pharmaceutical formulations since ancient time to improve health or prevent diseases, among them gastrointestinal disorders. Aiming to contribute in the scientific validation about the popular use of Brazilian Green propolis (BGP) against gastritis and gastric ulcer, this work evaluated the antiulcer potential of isolated compounds from BGP, three prenylated p-coumaric acid derivatives and two flavonoids, respectively named: 3,5 diprenyl-4-hydroxycinnamic acid (artepillin C) (1), 3-prenyl-4-dihydroxycinnamoiloxy cinnamic acid (baccharin) (2), 3-prenyl-4-hydroxycinnamic acid (drupanin) (3), aromadendrin-4'-O-methyl-ether (4) and kaempferide (5). MATERIAL AND METHODS The compounds were characterized by nuclear magnetic resonance and mass spectrometry. Their gastroprotective effects were evaluated against ethanol/HCl- and indomethacin-induced ulcer in mice. Further, histological, histochemical, oxidative and inflammatory parameters were analyzed at ulcerated tissue. Acid antisecretory activities also were also assessed. RESULTS Compound 2 did not reduce the ethanol/HCl- induced ulcer at 30 mg/kg (p.o), whereas the minimum oral gastroprotective doses of 1, 3, 4 and 5 were 0.3, 0.3, 3 and 3 mg/kg, respectively. Besides, these compounds prevented ethanol/HCl-induced ulcer by intraperitoneal route, as well as indomethacin-induced ulcer by oral route. The gastroprotection was accompanied by normalization of superoxide dismutase, catalase and glutathione-S-transferase activities and reduction in myeloperoxidase activity. Moreover, the compounds 4 and 5 increased the gastric mucin content and 1 reduced TNF amount. Furthermore, 1, 3, 4 and 5 decreased volume, pH, total acidity and pepsin activity of the gastric juice from rats. CONCLUSIONS Together, our findings showed a diversified mode of action elicited by 1, 3, 4 and 5 on the gastroprotection and contribute to explain the anti-ulcer activity reported for BGP.
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Affiliation(s)
- Philipe Costa
- Programa de Pós Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajai (UNIVALI) - Campus Itajaí, Rua Uruguai, 458, Centro CEP: 88302-901, Santa Catarina, Brazil
| | - Marilia O Almeida
- School of Pharmaceutical Sciences of Ribeirão Preto of the University of São Paulo, Avenida do Café, s/n, 14040-903 Ribeirão Preto, SP, Brazil
| | - Marivane Lemos
- School of Pharmaceutical Sciences of Ribeirão Preto of the University of São Paulo, Avenida do Café, s/n, 14040-903 Ribeirão Preto, SP, Brazil
| | - Caroline Arruda
- School of Pharmaceutical Sciences of Ribeirão Preto of the University of São Paulo, Avenida do Café, s/n, 14040-903 Ribeirão Preto, SP, Brazil
| | - Rosana Casoti
- School of Pharmaceutical Sciences of Ribeirão Preto of the University of São Paulo, Avenida do Café, s/n, 14040-903 Ribeirão Preto, SP, Brazil
| | - Lincon Bordignon Somensi
- Programa de Pós Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajai (UNIVALI) - Campus Itajaí, Rua Uruguai, 458, Centro CEP: 88302-901, Santa Catarina, Brazil
| | - Thaise Boeing
- Programa de Pós Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajai (UNIVALI) - Campus Itajaí, Rua Uruguai, 458, Centro CEP: 88302-901, Santa Catarina, Brazil
| | - Marihá Mariott
- Programa de Pós Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajai (UNIVALI) - Campus Itajaí, Rua Uruguai, 458, Centro CEP: 88302-901, Santa Catarina, Brazil
| | - Rita de Cássia Melo Vilhena de Andrade Fonseca da Silva
- Programa de Pós Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajai (UNIVALI) - Campus Itajaí, Rua Uruguai, 458, Centro CEP: 88302-901, Santa Catarina, Brazil
| | - Bruna De Paoli Stein
- Programa de Pós Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajai (UNIVALI) - Campus Itajaí, Rua Uruguai, 458, Centro CEP: 88302-901, Santa Catarina, Brazil
| | - Priscila de Souza
- Programa de Pós Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajai (UNIVALI) - Campus Itajaí, Rua Uruguai, 458, Centro CEP: 88302-901, Santa Catarina, Brazil
| | - Ana Caroline Dos Santos
- Programa de Pós Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajai (UNIVALI) - Campus Itajaí, Rua Uruguai, 458, Centro CEP: 88302-901, Santa Catarina, Brazil
| | - Jairo K Bastos
- School of Pharmaceutical Sciences of Ribeirão Preto of the University of São Paulo, Avenida do Café, s/n, 14040-903 Ribeirão Preto, SP, Brazil
| | - Luísa Mota da Silva
- Programa de Pós Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajai (UNIVALI) - Campus Itajaí, Rua Uruguai, 458, Centro CEP: 88302-901, Santa Catarina, Brazil
| | - Sérgio Faloni de Andrade
- Programa de Pós Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajai (UNIVALI) - Campus Itajaí, Rua Uruguai, 458, Centro CEP: 88302-901, Santa Catarina, Brazil.
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Galangin and Pinocembrin from Propolis Ameliorate Insulin Resistance in HepG2 Cells via Regulating Akt/mTOR Signaling. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:7971842. [PMID: 30420897 PMCID: PMC6215570 DOI: 10.1155/2018/7971842] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Accepted: 10/16/2018] [Indexed: 01/19/2023]
Abstract
Insulin resistance has a critical role in type 2 diabetes. The aim of this study was to investigate the effect of pinobanksin, galangin, chrysin, and pinocembrin from propolis on insulin resistance. Our study shows that galangin and pinocembrin can ameliorate insulin resistance; on the contrary, pinobanksin and chrysin are ineffective. Galangin and pinocembrin treatments substantially increase glucose consumption and glycogen content by enhancing the activities of hexokinase and pyruvate kinase. Galangin treatment with 80 μM increased hexokinase and pyruvate kinase activities by 21.94% and 29.12%, respectively. Moreover, we hypothesize that galangin and pinocembrin may have a synergistic effect on the improvement of insulin resistance via Akt/mTOR signaling pathway, through distinctly upregulating the phosphorylation of IR, Akt, and GSK3β and remarkably downregulating the phosphorylation of IRS. Most notably, this is the first study to our knowledge to investigate pinocembrin about the alleviation of insulin resistance. Our results provide compelling evidence for the depth development of propolis products to ameliorate insulin resistance.
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Touri K, Belguendouz H, Medjeber O, Djeraba Z, Lahmar K, Touil-Boukoffa C. Propolis modulates NOS2/arginase-1 pathway in tropomyosin-induced experimental autoimmune uveitis. Inflammopharmacology 2018; 26:1293-1303. [DOI: 10.1007/s10787-018-0487-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2018] [Accepted: 04/20/2018] [Indexed: 11/24/2022]
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Kitamura H, Saito N, Fujimoto J, Nakashima KI, Fujikura D. Brazilian propolis ethanol extract and its component kaempferol induce myeloid-derived suppressor cells from macrophages of mice in vivo and in vitro. Altern Ther Health Med 2018; 18:138. [PMID: 29720160 PMCID: PMC5930496 DOI: 10.1186/s12906-018-2198-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2018] [Accepted: 04/10/2018] [Indexed: 02/05/2023]
Abstract
Background Brazilian green propolis is produced by mixing secretions from Africanized honey bees with exudate, mainly from Baccharis dracunculifolia. Brazilian propolis is especially rich in flavonoids and cinammic acid derivatives, and it has been widely used in folk medicine owing to its anti-inflammatory, anti-viral, tumoricidal, and analgesic effects. Moreover, it is applied to prevent metabolic disorders, such as type 2 diabetes and arteriosclerosis. Previously, we demonstrated that propolis ethanol extract ameliorated type 2 diabetes in a mouse model through the resolution of adipose tissue inflammation. The aims of this study were to identify the immunosuppressive cells directly elicited by propolis extract and to evaluate the flavonoids that induce such cells. Methods Ethanol extract of Brazilian propolis (PEE; 100 mg/kg i.p., twice a week) was injected into lean or high fat-fed obese C57BL/6 mice or C57BL/6 ob/ob mice for one month. Subsequently, immune cells in visceral adipose tissue and the peritoneal cavity were monitored using FACS analysis. Isolated macrophages and the macrophage-like cell line J774.1 were treated with PEE and its constituent components, and the expression of immune suppressive myeloid markers were evaluated. Finally, we injected one of the identified compounds, kaempferol, into C57BL/6 mice and performed FACS analysis on the adipose tissue. Results Intraperitoneal treatment of PEE induces CD11b+, Gr-1+ myeloid-derived suppressor cells (MDSCs) in visceral adipose tissue and the peritoneal cavity of lean and obese mice. PEE directly stimulates cultured M1 macrophages to transdifferentiate into MDSCs. Among twelve compounds isolated from PEE, kaempferol has an exclusive effect on MDSCs induction in vitro. Accordingly, intraperitoneal injection of kaempferol causes accumulation of MDSCs in the visceral adipose tissue of mice. Conclusion Brazilian PEE and its compound kaempferol strongly induce MDSCs in visceral adipose tissue at a relatively early phase of inflammation. Given the strong anti-inflammatory action of MDSCs, the induction of MDSCs by PEE and kaempferol is expected to be useful for anti-diabetic and anti-inflammatory therapies. Graphical Abstract ![]()
Electronic supplementary material The online version of this article (10.1186/s12906-018-2198-5) contains supplementary material, which is available to authorized users.
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Shimamoto Y, Nio-Kobayashi J, Watarai H, Nagano M, Saito N, Takahashi E, Higuchi H, Kobayashi A, Kimura T, Kitamura H. Generation and validation of novel anti-bovine CD163 monoclonal antibodies ABM-1A9 and ABM-2D6. Vet Immunol Immunopathol 2018; 198:6-13. [DOI: 10.1016/j.vetimm.2018.02.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Revised: 01/14/2018] [Accepted: 02/12/2018] [Indexed: 12/28/2022]
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Propolis reversed cigarette smoke-induced emphysema through macrophage alternative activation independent of Nrf2. Bioorg Med Chem 2017; 25:5557-5568. [DOI: 10.1016/j.bmc.2017.08.026] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Revised: 08/07/2017] [Accepted: 08/15/2017] [Indexed: 01/01/2023]
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Ubiquitin-Specific Protease 2 Modulates the Lipopolysaccharide-Elicited Expression of Proinflammatory Cytokines in Macrophage-like HL-60 Cells. Mediators Inflamm 2017; 2017:6909415. [PMID: 29138532 PMCID: PMC5613470 DOI: 10.1155/2017/6909415] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Revised: 07/21/2017] [Accepted: 07/30/2017] [Indexed: 12/13/2022] Open
Abstract
We investigated the regulatory roles of USP2 in mRNA accumulation of proinflammatory cytokines in macrophage-like cells after stimulation with a toll-like receptor (TLR) 4 ligand, lipopolysaccharide (LPS). Human macrophage-like HL-60 cells, mouse macrophage-like J774.1 cells, and mouse peritoneal macrophages demonstrated negative feedback to USP2 mRNA levels after LPS stimulation, suggesting that USP2 plays a significant role in LPS-stimulated macrophages. USP2 knockdown (KD) by short hairpin RNA in HL-60 cells promoted the accumulation of transcripts for 25 of 104 cytokines after LPS stimulation. In contrast, limited induction of cytokines was observed in cells forcibly expressing the longer splice variant of USP2 (USP2A), or in peritoneal macrophages isolated from Usp2a transgenic mice. An ubiquitin isopeptidase-deficient USP2A mutant failed to suppress LPS-induced cytokine expression, suggesting that protein ubiquitination contributes to USP2-mediated cytokine repression. Although USP2 deficiency did not accelerate TNF receptor-associated factor (TRAF) 6-nuclear factor-κB (NF-κB) signaling, it increased the DNA binding ratio of the octamer binding transcription factor (Oct)-1 to Oct-2 in TNF, CXCL8, CCL4, and IL6 promoters. USP2 decreased nuclear Oct-2 protein levels in addition to decreasing the polyubiquitination of Oct-1. In summary, USP2 modulates proinflammatory cytokine induction, possibly through modification of Oct proteins, in macrophages following TLR4 activation.
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Samadi N, Mozaffari-Khosravi H, Rahmanian M, Askarishahi M. Effects of bee propolis supplementation on glycemic control, lipid profile and insulin resistance indices in patients with type 2 diabetes: a randomized, double-blind clinical trial. JOURNAL OF INTEGRATIVE MEDICINE-JIM 2017; 15:124-134. [PMID: 28285617 DOI: 10.1016/s2095-4964(17)60315-7] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Propolis, a natural resinous substance made by bees from material extracted from plants, flowers and bee's wax, has shown great therapeutic effects and been widely used in food and drug industries. Recently, some researchers have studied the effect of this substance in the treatment of diabetes. OBJECTIVE The purpose of this trial was to determine the effect of bee propolis on glycemic control, serum lipid profile and insulin resistance indices in patients with type 2 diabetes (T2D). DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS This randomized clinical trial involved 66 patients with T2D, which were randomly divided into two groups of intervention (IG) and placebo (PG). IG received 300 mg three times a day for a total of 900 mg/d of propolis pills, while PG received similar pills, lacking propolis, on the same schedule for 12 weeks. MAIN OUTCOME MEASURES Fasting blood glucose (FBG), hemoglobin A1c (HbA1c), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), serum insulin and insulin resistance indices were the main outcome measures. RESULTS The mean change in FBG between the IG ((17.76 ± 27.72) mg/dL decrease) and the PG ((6.48 ± 42.77) mg/dL increase) was significantly different (P = 0.01). Change in mean HbA1c had a similar pattern to FBG. The mean change in TC between the IG ((5.16 ± 43.80) mg/dL increase) and the PG ((28.9 ± 27.4) mg/dL increase) was also significantly different (P = 0.01), showing the protective role of propolis against the increase in TC. The change in mean LDL was similar to mean TC. There was no significant difference in other lipids or insulin resistance indices between the two groups. CONCLUSION Based on this study, the daily intake of 900 mg of bee propolis supplement for 12 weeks results in improvement of glycemic and some serum lipid levels in patients with T2D. TRIAL REGISTRATION This study is registered on the website of Iranian Ministry of Health (www.irct.ir) with proprietary code of IRCT2014080218659N1.
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Affiliation(s)
- Nazli Samadi
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Hassan Mozaffari-Khosravi
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Yazd Diabetic Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Masoud Rahmanian
- Yazd Diabetic Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Department of Internal Medicine, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mohsen Askarishahi
- Department of Biostatistics and Epidemiology, Faculty of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Sakai T, Ohhata M, Fujii M, Oda S, Kusaka Y, Matsumoto M, Nakamoto A, Taki T, Nakamoto M, Shuto E. Brazilian Green Propolis Promotes Weight Loss and Reduces Fat Accumulation in C57BL/6 Mice Fed A High-Fat Diet. Biol Pharm Bull 2017; 40:391-395. [PMID: 28381793 DOI: 10.1248/bpb.b16-00577] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Propolis is a bee product with various biological properties. C57BL/6 mice were fed a high-fat diet and treated with propolis for 14 weeks. Body weight in mice treated with 2% propolis was less than that in control mice from 3 weeks after the start of treatment until 14 weeks except for the 7th week. Mice treated with propolis showed significantly lower epididymal fat weight and subcutaneous fat weight. Infiltration of epididymal fat by macrophages and T cells was reduced in the propolis group. Supplementation of propolis increased feces weight and fat content in feces, suggesting that mechanisms of weight reduction by propolis partly include a laxative effect and inhibition of fat absorption.
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Affiliation(s)
- Tohru Sakai
- Department of Public Health and Applied Nutrition, Institute of Biomedical Science, Tokushima University of Graduate School
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Alvarez-Suarez JM. The Chemical and Biological Properties of Propolis. BEE PRODUCTS - CHEMICAL AND BIOLOGICAL PROPERTIES 2017. [PMCID: PMC7123330 DOI: 10.1007/978-3-319-59689-1_7] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Saito N, Kimura S, Miyamoto T, Fukushima S, Amagasa M, Shimamoto Y, Nishioka C, Okamoto S, Toda C, Washio K, Asano A, Miyoshi I, Takahashi E, Kitamura H. Macrophage ubiquitin-specific protease 2 modifies insulin sensitivity in obese mice. Biochem Biophys Rep 2017; 9:322-329. [PMID: 28956020 PMCID: PMC5614627 DOI: 10.1016/j.bbrep.2017.01.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Revised: 12/24/2016] [Accepted: 01/23/2017] [Indexed: 12/17/2022] Open
Abstract
We previously reported that ubiquitin-specific protease (USP) 2 in macrophages down-regulates genes associated with metabolic diseases, suggesting a putative anti-diabetic role for USP2 in macrophages. In this study, we evaluate this role at both cellular and individual levels. Isolated macrophages forcibly expressing Usp2a, a longer splicing variant of USP2, failed to modulate the insulin sensitivity of 3T3-L1 adipocytes. Similarly, macrophage-selective overexpression of Usp2a in mice (Usp2a transgenic mice) had a negligible effect on insulin sensitivity relative to wild type littermates following a three-month high-fat diet. However, Usp2a transgenic mice exhibited fewer M1 macrophages in their mesenteric adipose tissue. Following a six-month high-fat diet, Usp2a transgenic mice exhibited a retarded progression of insulin resistance in their skeletal muscle and liver, and an improvement in insulin sensitivity at an individual level. Although conditioned media from Usp2a-overexpressing macrophages did not directly affect the insulin sensitivity of C2C12 myotubes compared to media from control macrophages, they did increase the insulin sensitivity of C2C12 cells after subsequent conditioning with 3T3-L1 cells. These results indicate that macrophage USP2A hampers obesity-elicited insulin resistance via an adipocyte-dependent mechanism.
USP2A controls macrophage population in mesenteric adipose tissue during obesity. Overexpression of USP2A in macrophages retards progression of insulin resistance. Overexpression of USP2A in macrophages represses high-fat diet-induced obesity. Macrophage USP2A controls insulin sensitivity of muscle dependent on adipocytes.
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Key Words
- DMEM, Dulbecco's modified Eagle medium
- Diabetes
- ELISA, enzyme-linked immunosorbent assay
- GAPDH, glyceraldehyde 3-phosphate dehydrogenase
- HFD, high-fat diet
- HOMA-IR, homeostatic model assessment as an index of insulin resistance
- IL, interleukin
- IR, insulin receptor
- IRS, insulin receptor substrate
- Insulin
- KD, knock down
- KO, knockout
- Macrophage
- NCD, normal chow diet
- NEFA, nonesterified fatty acid
- Obesity
- PDK, phosphoinositide-dependent kinase
- PI3K, phosphatidylinositol 3-phosphate kinase
- SOCS, suppressor of cytokine signaling
- T2DM, type 2 diabetes mellitus
- Tg, transgenic
- USP
- USP, ubiquitin-specific protease
- pAkt, phosphorylated Akt
- pIRβ, phosphorylated insulin receptor β chain
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Affiliation(s)
- Natsuko Saito
- Laboratory of Veterinary Physiology, Department of Veterinary Medicine, and Laboratory of Animal Therapeutics, Japan
| | - Shunsuke Kimura
- Laboratory of Histology and Cytology, Department of Functional Morphology, Graduate School of Medical Sciences, Hokkaido University, Kita15, Nishi7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan
| | - Tomomi Miyamoto
- Department of Comparative and Experimental Medicine, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan
| | - Sanae Fukushima
- Research Resources Center, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
| | - Misato Amagasa
- Laboratory of Veterinary Physiology, Department of Veterinary Medicine, and Laboratory of Animal Therapeutics, Japan
| | - Yoshinori Shimamoto
- Department of Veterinary Science, Rakuno Gakuen University, 582 Midorimachi, Bunkyodai, Ebetsu, Hokkaido 069-8501, Japan
| | - Chieko Nishioka
- Research Resources Center, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
| | - Shiki Okamoto
- Division of Endocrinology and Metabolism, National Institute for Physiological Sciences, 38 Nishigonaka Myodaiji, Okazaki, Aichi 444-8585, Japan
| | - Chitoku Toda
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8063, USA
| | - Kohei Washio
- Laboratory of Veterinary Physiology, Department of Veterinary Medicine, and Laboratory of Animal Therapeutics, Japan
| | - Atsushi Asano
- Laboratory of Laboratory Animal, Department of Basic Veterinary Science, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan
| | - Ichiro Miyoshi
- Department of Comparative and Experimental Medicine, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan
| | - Eiki Takahashi
- Research Resources Center, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
| | - Hiroshi Kitamura
- Laboratory of Veterinary Physiology, Department of Veterinary Medicine, and Laboratory of Animal Therapeutics, Japan.,Laboratory of Histology and Cytology, Department of Functional Morphology, Graduate School of Medical Sciences, Hokkaido University, Kita15, Nishi7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.,Department of Comparative and Experimental Medicine, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan
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Bukovsky A. Novel Immunological Aspects for the Treatment of Age-induced Ovarian and Testicular Infertility, Other Functional Diseases, and Early and Advanced Cancer Immunotherapy. Hum Reprod 2016. [DOI: 10.1002/9781118849613.ch4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Affiliation(s)
- Antonin Bukovsky
- The Laboratory of Reproductive Biology BIOCEV, Institute of Biotechnology; Academy of Sciences of the Czech Republic; Prague Czech Republic
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Bukovsky A. Involvement of blood mononuclear cells in the infertility, age-associated diseases and cancer treatment. World J Stem Cells 2016; 8:399-427. [PMID: 28074124 PMCID: PMC5183987 DOI: 10.4252/wjsc.v8.i12.399] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2016] [Revised: 08/19/2016] [Accepted: 09/21/2016] [Indexed: 02/06/2023] Open
Abstract
Blood mononuclear cells consist of T cells and monocyte derived cells. Beside immunity, the blood mononuclear cells belong to the complex tissue control system (TCS), where they exhibit morphostatic function by stimulating proliferation of tissue stem cells followed by cellular differentiation, that is stopped after attaining the proper functional stage, which differs among various tissue types. Therefore, the term immune and morphostatic system (IMS) should be implied. The TCS-mediated morphostasis also consists of vascular pericytes controlled by autonomic innervation, which is regulating the quantity of distinct tissues in vivo. Lack of proper differentiation of tissue cells by TCS causes either tissue underdevelopment, e.g., muscular dystrophy, or degenerative functional failures, e.g., type 1 diabetes and age-associated diseases. With the gradual IMS regression after 35 years of age the gonadal infertility develops, followed by a growing incidence of age-associated diseases and cancers. Without restoring an altered TCS function in a degenerative disease, the implantation of tissue-specific stem cells alone by regenerative medicine can not be successful. Transfused young blood could temporarily restore fertility to enable parenthood. The young blood could also temporarily alleviate aging diseases, and this can be extended by substances inducing IMS regeneration, like the honey bee propolis. The local and/or systemic use of honey bee propolis stopped hair and teeth loss, regressed varicose veins, improved altered hearing, and lowered high blood pressure and sugar levels. Complete regression of stage IV ovarian cancer with liver metastases after a simple elaborated immunotherapy is also reported.
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Affiliation(s)
- Antonin Bukovsky
- Antonin Bukovsky, Laboratory of Reproductive Biology BIOCEV, Institute of Biotechnology Czech Academy of Sciences, 25250 Vestec, Czech Republic
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Brazilian propolis mitigates impaired glucose and lipid metabolism in experimental periodontitis in mice. Altern Ther Health Med 2016; 16:329. [PMID: 27576340 PMCID: PMC5006533 DOI: 10.1186/s12906-016-1305-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Accepted: 08/19/2016] [Indexed: 11/24/2022]
Abstract
Background Periodontitis has been implicated as a risk factor for metabolic disorders associated with insulin resistance. Recently, we have demonstrated that orally administered Porphyromonas gingivalis, a representative periodontopathic bacterium, induces endotoxemia via reduced gut barrier function coupled with changes in gut microbiota composition, resulting in systemic inflammation and insulin resistance. Propolis, a resinous substance collected by honeybees from leaf buds and cracks in the bark of various plants, can positively affect metabolic disorders in various experimental models. In this study, we thus aimed to clarify the effect of propolis on impaired glucose and lipid metabolism induced by P. gingivalis administration. Methods Eight-week-old male C57BL/6 mice were orally administered P. gingivalis strain W83, propolis ethanol extract powder with P. gingivalis, or vehicle. We then analyzed the expression profile of glucose and lipid metabolism-related genes in the liver and adipose tissues. Serum endotoxin levels were also evaluated by a limulus amebocyte lysate test. In addition, we performed histological analysis of the liver and quantified alveolar bone loss by measuring the root surface area on the lower first molar. Results Oral administration of P. gingivalis induced downregulation of genes that improve insulin sensitivity in adipose tissue (C1qtnf9, Irs1, and Sirt1), but upregulation of genes associated with lipid droplet formation and gluconeogenesis (Plin2, Acox, and G6pc). However, concomitant administration of propolis abrogated these adverse effects of P. gingivalis. Consistent with gene expression, histological analysis showed that administered propolis suppressed hepatic steatosis induced by P. gingivalis. Furthermore, propolis inhibited the elevation of serum endotoxin levels induced by P. gingivalis administration. Contrary to the systemic effects, propolis had no beneficial effect on alveolar bone loss. Conclusion These results suggest that administration of propolis may be effective in suppressing periodontopathic bacteria-induced metabolic changes that increase the risk of various systemic diseases.
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