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Pu L, Wang Y, Pang W, Wei J, Wu J, Guo C, Weina Gao. Propolis does not significantly modulate immune function in an older population: A preliminary study. Heliyon 2024; 10:e41056. [PMID: 39759320 PMCID: PMC11699101 DOI: 10.1016/j.heliyon.2024.e41056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Revised: 11/16/2024] [Accepted: 12/06/2024] [Indexed: 01/03/2025] Open
Abstract
Purpose The human trial aimed to study the influence of propolis on immune function in the elderly. Methods Non-institutionalized community-dwelling individuals aged 60-80 years were recruited from Tianjin, China. Participants were assigned randomly to either the Chinese propolis group (600 mg/day, n = 32) or the control group (n = 30). Serum antibodies and biochemical indices were measured using commercial kits; cytokines were detected using ELISA assay, and the functions of lymphocytes and neutrophils were assayed using the MTT and Staphylococcal methods, respectively. A dietary survey was conducted based on 24-h recall. Results The study lasted for 12 weeks. Immunoglobulin G (IgG) levels notably increased at week 6 although these levels returned to baseline by week 12 in the Chinese propolis group. No significant difference was detected in serum antibodies, cytokines, or lymphocyte and neutrophil functions between the two groups at any time point. Conclusions Chinese propolis could stimulate IgG secretion within a certain period, but it was restored to baseline levels over time. Propolis does not significantly affect other immune markers in the elderly.
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Affiliation(s)
| | | | - Wei Pang
- Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, China
| | - Jingyu Wei
- Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, China
| | - Jianquan Wu
- Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, China
| | - Changjiang Guo
- Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, China
| | - Weina Gao
- Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, China
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Zhang C, Tian Y, Yang A, Tan W, Liu X, Yang W. Antitumor Effect of Poplar Propolis on Human Cutaneous Squamous Cell Carcinoma A431 Cells. Int J Mol Sci 2023; 24:16753. [PMID: 38069077 PMCID: PMC10706191 DOI: 10.3390/ijms242316753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 11/22/2023] [Accepted: 11/23/2023] [Indexed: 12/18/2023] Open
Abstract
Propolis is a gelatinous substance processed by western worker bees from the resin of plant buds and mixed with the secretions of the maxillary glands and beeswax. Propolis has extensive biological activities and antitumor effects. There have been few reports about the antitumor effect of propolis against human cutaneous squamous cell carcinoma (CSCC) A431 cells and its potential mechanism. CCK-8 assays, label-free proteomics, RT-PCR, and a xenograft tumor model were employed to explore this possibility. The results showed that the inhibition rate of A431 cell proliferation by the ethanol extract of propolis (EEP) was dose-dependent, with an IC50 of 39.17 μg/mL. There were 193 differentially expressed proteins in the EEP group compared with the control group (p < 0.05), of which 103 proteins (53.37%) were upregulated, and 90 proteins (46.63%) were downregulated. The main three activated and suppressed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were extracellular matrix (ECM)-receptor interaction, amoebiasis, cell adhesion molecules (CAMs), nonalcoholic fatty liver disease (NAFLD), retrograde endocannabinoid signaling, and Alzheimer's disease. The tumor volume of the 100 mg/kg EEP group was significantly different from that of the control group (p < 0.05). These results provide a theoretical basis for the potential treatment of human CSCC A431 cell tumors using propolis.
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Affiliation(s)
- Chuang Zhang
- College of Animal Science (College of Bee Science), Fujian Agriculture and Forestry University, Fuzhou 350002, China; (C.Z.); (Y.T.); (A.Y.); (X.L.)
| | - Yuanyuan Tian
- College of Animal Science (College of Bee Science), Fujian Agriculture and Forestry University, Fuzhou 350002, China; (C.Z.); (Y.T.); (A.Y.); (X.L.)
- College of Juncao Science and Ecology, Fujian Agriculture and Forestry University, Fuzhou 350002, China
| | - Ao Yang
- College of Animal Science (College of Bee Science), Fujian Agriculture and Forestry University, Fuzhou 350002, China; (C.Z.); (Y.T.); (A.Y.); (X.L.)
| | - Weihua Tan
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China;
| | - Xiaoqing Liu
- College of Animal Science (College of Bee Science), Fujian Agriculture and Forestry University, Fuzhou 350002, China; (C.Z.); (Y.T.); (A.Y.); (X.L.)
| | - Wenchao Yang
- College of Animal Science (College of Bee Science), Fujian Agriculture and Forestry University, Fuzhou 350002, China; (C.Z.); (Y.T.); (A.Y.); (X.L.)
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China;
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Belmehdi O, El Menyiy N, Bouyahya A, El Baaboua A, El Omari N, Gallo M, Montesano D, Naviglio D, Zengin G, Skali Senhaji N, Goh BH, Abrini J. Recent Advances in the Chemical Composition and Biological Activities of Propolis. FOOD REVIEWS INTERNATIONAL 2022. [DOI: 10.1080/87559129.2022.2089164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Affiliation(s)
- Omar Belmehdi
- Biotechnology and Applied Microbiology Team, Department of Biology, Faculty of Sciences, Abdelmalek Essaadi University, Tetouan, Morocco
| | - Naoual El Menyiy
- Laboratory of Pharmacology, National Agency of Medicinal and Aromatic Plants, Taounate, Morocco
| | - Abdelhakim Bouyahya
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat, Morocco
| | - Aicha El Baaboua
- Biotechnology and Applied Microbiology Team, Department of Biology, Faculty of Sciences, Abdelmalek Essaadi University, Tetouan, Morocco
| | - Nasreddine El Omari
- Laboratory of Histology, Embryology, and Cytogenetic, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco
| | - Monica Gallo
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy
| | | | - Daniele Naviglio
- Department of Chemical Sciences, University of Naples Federico II, Naples, Italy
| | - Gokhan Zengin
- Department of Biology, Science Faculty, Selcuk University, Campus, Konya, Turkey
| | - Nadia Skali Senhaji
- Biotechnology and Applied Microbiology Team, Department of Biology, Faculty of Sciences, Abdelmalek Essaadi University, Tetouan, Morocco
| | - Bey Hing Goh
- Biofunctional Molecule Exploratory (BMEX) Research Group, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya, Malaysia
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Jamal Abrini
- Biotechnology and Applied Microbiology Team, Department of Biology, Faculty of Sciences, Abdelmalek Essaadi University, Tetouan, Morocco
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Tsuruta H, Mizuno-Kamiya M, Takahashi M, Ando M, Ikeno K, Ueno K, Takayama E, Kawaki H, Nakamura G, Nikaido T, Fujita H, Kondoh N. Enhanced production of IL-2 from anti-CD3 antibody-stimulated mouse spleen cells by artepillin C, a major component of Brazilian green propolis. J Oral Biosci 2022; 64:366-375. [PMID: 35667586 DOI: 10.1016/j.job.2022.05.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 05/25/2022] [Accepted: 05/30/2022] [Indexed: 11/19/2022]
Abstract
OBJECTIVES In this report, we attempt to clarify the immune modulatory effects of Brazilian green propolis (BGP) and its major component, artepillin C, on the cytokine production of anti-CD3 antibody-stimulated mouse spleen cells. We also estimate the physiological mechanism affecting artepillin C's upon the cells. METHODS Male C3H/HeN mouse spleen cells stimulated by antiCD3 monoclonal antibody were co-cultured with BGP, artepillin C, and HC030031, a transient receptor potential ankyrin 1 (TRPA1) Ca2+ channel antagonist. The synthesis of interferon (IFN)-γ, interleukin (IL)-6, IL-17, IL-4, IL-10, and IL-2 was assayed by enzyme-linked immunoassay. The expression of IL-2 mRNA and the protein product were examined by reverse transcription-quantitative polymerase chain reaction and Western blot analyses, respectively. RESULTS The production of IL-2 was markedly enhanced, while that of IL-4 and IL-10 was not significantly affected; by contrast, the production of IFN-γ, IL-6, and IL-17 was significantly reduced in the antibody-stimulated spleen cells treated with BGP at a non-cytostatic concentration. These effects were reproduced in the cells treated with artepillin C. The expression of IL-2 mRNA was unaffected; however, that of the protein was significantly enhanced in the artepillin C-treated cells compared to untreated control cells. The enhancement of protein expression and the production of IL-2 by artepillin C was significantly alleviated by adding HC030031. CONCLUSIONS Artepillin C is an important regulator of cytokine synthesis from activated spleen cells. The agent specifically augmented the expression of IL-2 via the Ca2+-permeable cation channel, TRPA1, at least in part, at the translational or secretion levels.
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Affiliation(s)
- Hanemi Tsuruta
- Department of Oral Biochemistry, Asahi University School of Dentistry, Mizuho, Gifu 501-0296, Japan; Department of Operative Dentistry, Asahi University School of Dentistry, Mizuho, Gifu 501-0296, Gifu 500-8471, Japan.
| | - Masako Mizuno-Kamiya
- Chemistry Laboratory, Department of Business Administration, Asahi University School of Business Administration, Mizuho, Gifu 501-0296, Japan.
| | - Moe Takahashi
- Department of Oral and Maxillofacial Surgery, Asahi University School of Dentistry, Mizuho, Gifu 501-0296, Japan.
| | - Megumi Ando
- Department of Oral Biochemistry, Asahi University School of Dentistry, Mizuho, Gifu 501-0296, Japan.
| | - Kumiko Ikeno
- AKITAYA HONTEN CO., LTD., R&D, Gifu 500-8471, Japan.
| | - Kyohei Ueno
- Department of Oral Biochemistry, Asahi University School of Dentistry, Mizuho, Gifu 501-0296, Japan.
| | - Eiji Takayama
- Department of Oral Biochemistry, Asahi University School of Dentistry, Mizuho, Gifu 501-0296, Japan.
| | - Harumi Kawaki
- Chemistry Laboratory, Asahi University School of Dentistry, Mizuho, Gifu 501-0296, Gifu 500-8471, Japan.
| | | | - Toru Nikaido
- Department of Operative Dentistry, Asahi University School of Dentistry, Mizuho, Gifu 501-0296, Gifu 500-8471, Japan.
| | - Hisakazu Fujita
- Department of Scientific and Linguistic Fundamentals for Nursing, Osaka City University Graduate School of Nursing, Osaka 558-8585, Japan.
| | - Nobuo Kondoh
- Department of Oral Biochemistry, Asahi University School of Dentistry, Mizuho, Gifu 501-0296, Japan.
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Han NR, Kim KC, Kim JS, Ko SG, Park HJ, Moon PD. A mixture of Panax ginseng and Scrophularia buergeriana improves immune function in an immunosuppressed murine model. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 99:153984. [PMID: 35189478 DOI: 10.1016/j.phymed.2022.153984] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 02/06/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Immunomodulatory drugs are currently used for immunosuppressed individuals, but adverse side effects have been reported. Although Panax ginseng and Scrophularia buergeriana are known to have respective pharmacological properties, the potential of a mixture of Panax ginseng and Scrophularia buergeriana (Isam-Tang, IST) as an immunomodulatory drug has not yet been studied. PURPOSE The present study was designed to assess the immunomodulatory activity of IST and p-coumaric acid (pCA), an active compound of IST, in the immune system. METHODS The levels of immunostimulatory cytokines, nitrite, inducible nitric oxide synthase (iNOS), NF-kB activation, and proliferation were examined in RAW264.7 cells, primary splenocytes and splenic NK cells isolated from normal mouse spleen, and in cyclophosphamide-induced immunosuppressed mice using ELISA, quantitative real-time PCR, Western blotting, and immunofluorescence staining. RESULTS IST or pCA treatment increased the production of immunostimulatory cytokines and nitrite and the expression of iNOS in RAW264.7 cells and splenocytes. IST or pCA also induced NF-κB signaling activation and promoted the phagocytic activity of RAW264.7 cells. In addition, the splenocyte proliferation and splenic NK activity were enhanced by IST or pCA. IST or pCA increased the levels of immunostimulatory cytokines in immunosuppressed mice and ameliorated splenic tissue damage. CONCLUSION These findings suggest that IST supplementation may be used to enhance immune function.
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Affiliation(s)
- Na-Ra Han
- College of Korean Medicine, Kyung Hee University, Seoul, South Korea; Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
| | - Kyeoung-Cheol Kim
- Majors in Plant Resource and Environment, College of Agriculture & Life Sciences, SARI, Jeju National University, Jeju 63243, South Korea
| | - Ju-Sung Kim
- Majors in Plant Resource and Environment, College of Agriculture & Life Sciences, SARI, Jeju National University, Jeju 63243, South Korea
| | - Seong-Gyu Ko
- Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul, South Korea; Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
| | - Hi-Joon Park
- Department of Anatomy & Information Sciences, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
| | - Phil-Dong Moon
- Center for Converging Humanities, Kyung Hee University, Seoul, South Korea.
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Magnavacca A, Sangiovanni E, Racagni G, Dell'Agli M. The antiviral and immunomodulatory activities of propolis: An update and future perspectives for respiratory diseases. Med Res Rev 2022; 42:897-945. [PMID: 34725836 PMCID: PMC9298305 DOI: 10.1002/med.21866] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 07/20/2021] [Accepted: 10/20/2021] [Indexed: 12/11/2022]
Abstract
Propolis is a complex natural product that possesses antioxidant, anti-inflammatory, immunomodulatory, antibacterial, and antiviral properties mainly attributed to the high content in flavonoids, phenolic acids, and their derivatives. The chemical composition of propolis is multifarious, as it depends on the botanical sources from which honeybees collect resins and exudates. Nevertheless, despite this variability propolis may have a general pharmacological value, and this review systematically compiles, for the first time, the existing preclinical and clinical evidence of propolis activities as an antiviral and immunomodulatory agent, focusing on the possible application in respiratory diseases. In vitro and in vivo assays have demonstrated propolis broad-spectrum effects on viral infectivity and replication, as well as the modulatory actions on cytokine production and immune cell activation as part of both innate and adaptive immune responses. Clinical trials confirmed propolis undeniable potential as an effective therapeutic agent; however, the lack of rigorous randomized clinical trials in the context of respiratory diseases is tangible. Since propolis is available as a dietary supplement, possible use for the prevention of respiratory diseases and their deleterious inflammatory drawbacks on the respiratory tract in humans is considered and discussed. This review opens up new perspectives on the clinical investigation of neglected propolis biological properties which, now more than ever, are particularly relevant with respect to the recent outbreaks of pandemic respiratory infections.
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Affiliation(s)
- Andrea Magnavacca
- Department of Pharmacological and Biomolecular SciencesUniversity of MilanMilanItaly
| | - Enrico Sangiovanni
- Department of Pharmacological and Biomolecular SciencesUniversity of MilanMilanItaly
| | - Giorgio Racagni
- Department of Pharmacological and Biomolecular SciencesUniversity of MilanMilanItaly
| | - Mario Dell'Agli
- Department of Pharmacological and Biomolecular SciencesUniversity of MilanMilanItaly
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Wieczorek PP, Hudz N, Yezerska O, Horčinová-Sedláčková V, Shanaida M, Korytniuk O, Jasicka-Misiak I. Chemical Variability and Pharmacological Potential of Propolis as a Source for the Development of New Pharmaceutical Products. Molecules 2022; 27:1600. [PMID: 35268700 PMCID: PMC8911684 DOI: 10.3390/molecules27051600] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 02/24/2022] [Accepted: 02/24/2022] [Indexed: 11/23/2022] Open
Abstract
This review aims to analyze propolis as a potential raw material for the development and manufacture of new health-promoting products. Many scientific publications were retrieved from the Scopus, PubMed, and Google Scholar databases via searching the word "propolis". The different extraction procedures, key biologically active compounds, biological properties, and therapeutic potential of propolis were analyzed. It was concluded that propolis possesses a variety of biological properties because of a very complex chemical composition that mainly depends on the plant species visited by bees and species of bees. Numerous studies found versatile pharmacological activities of propolis: antimicrobial, antifungal, antiviral, antioxidant, anticancer, anti-inflammatory, immunomodulatory, etc. In this review, the composition and biological activities of propolis are presented from a point of view of the origin and standardization of propolis for the purpose of the development of new pharmaceutical products on its base. It was revealed that some types of propolis, especially European propolis, contain flavonoids and phenolic acids, which could be markers for the standardization and quality evaluation of propolis and its preparations. One more focus of this paper was the overview of microorganisms' sensitivity to propolis for further development of antimicrobial and antioxidant products for the treatment of various infectious diseases with an emphasis on the illnesses of the oral cavity. It was established that the antimicrobial activity of different types of propolis is quite significant, especially to Gram-negative bacteria and lipophilic viruses. The present study could be also of interest to the pharmaceutical industry as a review for the appropriate design of standardized propolis preparations such as mouthwashes, toothpastes, oral drops, sprays, creams, ointments, suppositories, tablets, and capsules, etc. Moreover, propolis could be regarded as a source for the isolation of biologically active substances. Furthermore, this review can facilitate partially overcoming the problem of the standardization of propolis preparations, which is a principal obstacle to the broader use of propolis in the pharmaceutical industry. Finally, this study could be of interest in the area of the food industry for the development of nutritionally well-balanced products. The results of this review indicate that propolis deserves to be better studied for its promising therapeutic effects from the point of view of the connection of its chemical composition with the locality of its collection, vegetation, appropriate extraction methods, and standardization.
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Affiliation(s)
| | - Nataliia Hudz
- Department of Drug Technology and Biopharmacy, Danylo Halytsky Lviv National Medical University, 79010 Lviv, Ukraine; (N.H.); (O.Y.)
- Department of Pharmacy and Ecological Chemistry, University of Opole, 45-052 Opole, Poland;
| | - Oksana Yezerska
- Department of Drug Technology and Biopharmacy, Danylo Halytsky Lviv National Medical University, 79010 Lviv, Ukraine; (N.H.); (O.Y.)
| | | | - Mariia Shanaida
- Department of Pharmacognosy and Medical Botany, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine;
| | - Oleksii Korytniuk
- Department of Occupational and Facial Surgery and Dentistry, Ukrainian Military Medical Academy, 01015 Kyiv, Ukraine;
| | - Iza Jasicka-Misiak
- Department of Pharmacy and Ecological Chemistry, University of Opole, 45-052 Opole, Poland;
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Optimization of Emulsification Conditions on Ethanol Extract of Taiwanese Green Propolis Using Polysorbate and Its Immunomodulatory Effects in Broilers. Animals (Basel) 2022; 12:ani12040446. [PMID: 35203153 PMCID: PMC8868552 DOI: 10.3390/ani12040446] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 02/09/2022] [Accepted: 02/09/2022] [Indexed: 02/05/2023] Open
Abstract
Simple Summary Taiwanese green propolis (TGP) ethanol extract has been shown to have a wide range of biological activities, such as antimicrobial and anti-inflammatory properties. However, extraction using ethanol limits the use of TGP as an ingredient in animal feeds. In addition, the effect of TGP ethanol extract on immunomodulation in broilers is still unclear. In order to increase the utilization of TGP ethanol extract in poultry productivity, this study aimed to establish the optimal emulsification conditions for TGP ethanol extract using polysorbate and investigate its effectiveness in improving immune response in broilers. Abstract Beeswax and resin are the main components of propolis, both of which are hydrophobic. The use of emulsifiers helps to improve the extraction of active propolis compounds and makes them more widely used. In this study, we investigated the optimal parameters for the emulsification of Taiwanese green propolis (TGP) using different polysorbates (polysorbate-20, polysorbate-60, and polysorbate-80) and evaluated the effects on the immunomodulatory response in broilers. The results showed that 4 mg/mL of TGP in combination with 2% polysorbate-60 at 60 °C for 60 min significantly decreased the undissolved particle size of ethanol extract of TGP during the emulsification. The bioactive compounds of TGP, the propolins (C, D, F, G, and H), were also detected after emulsification. Supplementation of emulsified TGP (eTGP) in the drinking water of broilers before and after vaccination significantly enhanced the antibody titer response to infectious bronchitis virus at 28 days of age. In the lipopolysaccharide-challenged model, supplementation of eTGP in the drinking water of broilers decreased pro-inflammatory gene expression and increased anti-inflammatory gene expression. These results together suggested that the polysorbate-60 could effectively emulsify the ethanol extract of TGP. Moreover, eTGP could be used as a vaccine adjuvant and an immunomodulator to improve the immune response of broilers.
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Spanidi E, Karapetsas A, Voulgaridou GP, Letsiou S, Aligiannis N, Tsochantaridis I, Kynigopoulos S, Lambropoulou M, Mourtzinos I, Pappa A, Gardikis K. A New Controlled Release System for Propolis Polyphenols and Its Biochemical Activity for Skin Applications. PLANTS 2021; 10:plants10020420. [PMID: 33672417 PMCID: PMC7927051 DOI: 10.3390/plants10020420] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 02/17/2021] [Accepted: 02/19/2021] [Indexed: 01/05/2023]
Abstract
Propolis is a resinous substance produced by bees that exhibits antimicrobial, immunostimulatory and antioxidant activity. Its use is common in functional foods, cosmetics and traditional medicine despite the fact that it demonstrates low extraction yields and inconsistency in non-toxic solvents. In this work, a new encapsulation and delivery system consisting of liposomes and cyclodextrins incorporating propolis polyphenols has been developed and characterized. The antioxidant, antimutagenic and antiaging properties of the system under normal and UVB-induced oxidative stress conditions were investigated in cultured skin cells and/or reconstituted skin model. Furthermore, the transcript accumulation for an array of genes involved in many skin-related processes was studied. The system exhibits significant polyphenol encapsulation efficiency, physicochemical stability as well as controlled release rate in appropriate conditions. The delivery system can retain the anti-mutagenic, anti-oxidative and anti-ageing effects of propolis polyphenols to levels similar and comparable to those of propolis methanolic extracts, making the system ideal for applications where non-toxic solvents are required and controlled release of the polyphenol content is desired.
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Affiliation(s)
- Eleni Spanidi
- Research and Development Department, APIVITA SA, Industrial Park Markopoulo Mesogaias, 19003 Athens, Greece; (E.S.); (S.L.)
| | - Athanasios Karapetsas
- Department of Molecular Biology & Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.K.); (G.-P.V.); (I.T.); (A.P.)
| | - Georgia-Persephoni Voulgaridou
- Department of Molecular Biology & Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.K.); (G.-P.V.); (I.T.); (A.P.)
| | - Sophia Letsiou
- Research and Development Department, APIVITA SA, Industrial Park Markopoulo Mesogaias, 19003 Athens, Greece; (E.S.); (S.L.)
| | - Nektarios Aligiannis
- Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 11527 Athens, Greece;
| | - Ilias Tsochantaridis
- Department of Molecular Biology & Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.K.); (G.-P.V.); (I.T.); (A.P.)
| | - Spyridon Kynigopoulos
- Laboratory of Histology and Embryology, Faculty of Health Sciences, School of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (S.K.); (M.L.)
| | - Maria Lambropoulou
- Laboratory of Histology and Embryology, Faculty of Health Sciences, School of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (S.K.); (M.L.)
| | - Ioannis Mourtzinos
- Department of Food Science and Technology, Faculty of Agriculture, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Aglaia Pappa
- Department of Molecular Biology & Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (A.K.); (G.-P.V.); (I.T.); (A.P.)
| | - Konstantinos Gardikis
- Research and Development Department, APIVITA SA, Industrial Park Markopoulo Mesogaias, 19003 Athens, Greece; (E.S.); (S.L.)
- Correspondence: ; Tel.: +30-6974899959
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Moise AR, Bobiş O. Baccharis dracunculifolia and Dalbergia ecastophyllum, Main Plant Sources for Bioactive Properties in Green and Red Brazilian Propolis. PLANTS (BASEL, SWITZERLAND) 2020; 9:E1619. [PMID: 33233429 PMCID: PMC7700410 DOI: 10.3390/plants9111619] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 11/18/2020] [Accepted: 11/19/2020] [Indexed: 02/06/2023]
Abstract
Nowadays, propolis is used as a highly valuable product in alternative medicine for improving health or treating a large spectrum of pathologies, an ingredient in pharmaceutical products, and also as a food additive. Different vegetal materials are collected by honeybees and mixed with wax and other own substances in order to obtain the final product, called propolis. It is known as the bee product with the widest chemical composition due to the raw material collected by the bees. Different types are known worldwide: green Brazilian propolis (having Baccharis dracunculifolia as the major plant source), red Brazilian propolis (from Dalbergia ecastophyllum), European propolis (Populus nigra L.), Russian propolis (Betula verrucosa Ehrh), Cuban and Venezuelan red propolis (Clusia spp.), etc. An impressive number of scientific papers already demonstrate the pharmacological potential of different types of propolis, the most important activities being the antimicrobial, anti-inflammatory, antitumor, immunomodulatory, and antioxidant activities. However, the bioactive compounds responsible for each activity have not been fully elucidated. This review aims to collect important data about the chemical composition and bioactive properties of the vegetal sources and to compare with the chemical composition of respective propolis types, in order to determine the connection between the floral source and the propolis properties.
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Affiliation(s)
- Adela Ramona Moise
- Department of Apiculture and Sericulture, Faculty of Animal Breeding and Biotechnologies, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, 400372 Cluj-Napoca, Romania;
| | - Otilia Bobiş
- Life Science Institute “King Michael I of Romania”, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, 400372 Cluj-Napoca, Romania
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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: 138] [Impact Index Per Article: 27.6] [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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12
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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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Iqbal M, Fan TP, Watson D, Alenezi S, Saleh K, Sahlan M. Preliminary studies: the potential anti-angiogenic activities of two Sulawesi Island (Indonesia) propolis and their chemical characterization. Heliyon 2019; 5:e01978. [PMID: 31372523 PMCID: PMC6656927 DOI: 10.1016/j.heliyon.2019.e01978] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 04/23/2019] [Accepted: 06/17/2019] [Indexed: 12/14/2022] Open
Abstract
Several studies have previously reported propolis, or its constituents, to inhibit tumour angiogenesis. The anti-angiogenic activity of two Indonesian stingless bee propolis extracts from Sulawesi Island on vascular cells were assessed. Sample D01 was obtained from the outer side of bee hives, while D02 was from the inner side of the same hives. The extracts were profiled by using liquid chromatography coupled to high resolution mass spectrometry. The anti-angiogenic capacity was assessed on HUVECs and placenta-derived pericytes by cell viability, multi-channel wound healing, and CoCl2 based-hypoxia assays. The exact chemical composition has not been confirmed. The most abundant compounds in Indonesian sample D01 seem to be unusual since they do not immediately fall into a clear class. Two of the most abundant compounds have elemental compositions matching actinopyrones. Identification on the basis of elemental composition is not definitive but compounds in D01 are possibly due to unusually modified terpenoids. Sample D02 has abundant compounds which include four related diterpenes with differing degrees of oxygenation and some sesquiterpenes. However, again the profile is unusual. The anti-angiogenic assays demonstrated that D01 elicited a strong cytotoxic effect and a considerable anti-migratory activity on the vascular cells. Although D02 demonstrated a much weaker cytotoxic effect on the cell lines compared to D01, it elicited a substantial protective effect on the pericytes against CoCl2-induced dropout in an experiment to mimic a micro-environment commonly associated with angiogenesis and tumour growth. These results demonstrate modulatory effects of these propolis samples in vascular cells, which requires further investigation.
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Affiliation(s)
- Muhammad Iqbal
- Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom
| | - Tai-Ping Fan
- Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom
| | - David Watson
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
| | - Samya Alenezi
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
| | - Khaled Saleh
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
| | - Muhamad Sahlan
- Department of Chemical Engineering, Universitas Indonesia, Depok, Indonesia
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Abstract
With a concomitant increase in immune-related diseases such as allergic diseases, Type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis, psoriasis, inflammatory bowel disease and other immune-related responses such as immunodeficiency, various infectious, diseases, vaccines, and malignancies, it has become very important to have a well-balanced and properly functioning immune system for the maintenance of human health. Recent scientific research has strongly suggested propolis as one of the most promising immunomodulation agents. This review describes recent findings with respect to propolis and its ingredients that show potential in this respect and evaluate their potential mechanisms. The author believes that propolis or/and its ingredients alone and in combination could be promising in manipulating the immune response and inducing immunomodulation. Further exploratory studies are needed to support large clinical trials toward further development of propolis.
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Affiliation(s)
- Mohammed Al-Hariri
- Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
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15
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Woods N, Niwasabutra K, Acevedo R, Igoli J, Altwaijry N, Tusiimire J, Gray A, Watson D, Ferro V. Natural Vaccine Adjuvants and Immunopotentiators Derived From Plants, Fungi, Marine Organisms, and Insects. IMMUNOPOTENTIATORS IN MODERN VACCINES 2017. [PMCID: PMC7148613 DOI: 10.1016/b978-0-12-804019-5.00011-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Immunopotentiators derived from different natural sources are under investigation with varying success. This chapter gives an overview of developments from plants, fungi, marine organisms, and insects. Plant-derived immune stimulators consist of a diverse range of small molecules or large polysaccharides. Notable examples that have been assessed in both preclinical and clinical trials include saponins, tomatine, and inulin. Similarly, fungi produce a range of potential candidate molecules, with β-glucans showing the most promise. Other complex molecules that have established adjuvant activity include α-galactosylceramide (originally obtained from a marine sponge), chitosan (commonly produced from chitin from shrimps), and peptides (found in bee venom). Some organisms, for example, endophytic fungi and bees, produce immunostimulants using compounds obtained from plants. The main challenges facing this type of research and tools being developed to overcome them are examined.
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Affiliation(s)
- N. Woods
- University of Strathclyde, Glasgow, Scotland
| | | | | | - J. Igoli
- University of Strathclyde, Glasgow, Scotland,University of Agriculture, Makurdi, Benue State, Nigeria
| | | | | | - A.I. Gray
- University of Strathclyde, Glasgow, Scotland
| | - D.G. Watson
- University of Strathclyde, Glasgow, Scotland
| | - V.A. Ferro
- University of Strathclyde, Glasgow, Scotland
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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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Zhou W, Cai B, Shan J, Wang S, Di L. Discovery and Current Status of Evaluation System of Bioavailability and Related Pharmaceutical Technologies for Traditional Chinese Medicines--Flos Lonicerae Japonicae--Fructus Forsythiae Herb Couples as an Example. Int J Mol Sci 2015; 16:28812-40. [PMID: 26690115 PMCID: PMC4691079 DOI: 10.3390/ijms161226132] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Revised: 11/21/2015] [Accepted: 11/24/2015] [Indexed: 12/22/2022] Open
Abstract
Traditional Chinese medicines (TCMs) have attracted extensive interest throughout the world due to their long history of health protection and disease control, and the internalization of TCM preparations or patented drugs has been considered a wind vane in the process of TCM modernization. However, multi-target effects, caused by multiple components in TCMs, hinder not only the construction of the quality evaluation system (bioavailability), but also the application of pharmaceutical technologies, which results in the poor efficacy in clinical practice. This review describes the methods in the literature as well as in our thoughts about how to identify the marker components, establish the evaluation system of bioavailability, and improve the bioavailability in TCM preparations. We expect that the current study will be positive and informative.
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Affiliation(s)
- Wei Zhou
- College of pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
- Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing 210023, China.
- Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets, Nanjing 210023, China.
- Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Baochang Cai
- College of pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
- Nanjing Haichang Chinese Medicine Group Co., Ltd., Nanjing 210023, China.
| | - Jinjun Shan
- Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Shouchuan Wang
- Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Liuqing Di
- College of pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
- Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing 210023, China.
- Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets, Nanjing 210023, China.
- Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China.
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Bukovsky A. Novel methods of treating ovarian infertility in older and POF women, testicular infertility, and other human functional diseases. Reprod Biol Endocrinol 2015; 13:10. [PMID: 25889983 PMCID: PMC4414002 DOI: 10.1186/s12958-015-0001-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2014] [Accepted: 01/28/2015] [Indexed: 12/11/2022] Open
Abstract
In vitro maturation (IVM) and in vitro fertilization (IVF) technologies are facing with growing demands of older women to conceive. Although ovarian stem cells (OSCs) of older women are capable of producing in vitro fresh oocyte-like cells (OLCs), such cells cannot respond to IVM and IVF due to the lack of granulosa cells required for their maturation. Follicular renewal is also dependent on support of circulating blood mononuclear cells. They induce intermediary stages of meiosis (metaphase I chromosomal duplication and crossover, anaphase, telophase, and cytokinesis) in newly emerging ovarian germ cells, as for the first time demonstrated here, induce formation of granulosa cells, and stimulate follicular growth and development. A pretreatment of OSC culture with mononuclear cells collected from blood of a young healthy fertile woman may cause differentiation of bipotential OSCs into both developing germ and granulosa cells. A small blood volume replacement may enable treatment of ovarian infertility in vivo. The transferred mononuclear cells may temporarily rejuvenate virtually all tissues, including improvement of the function of endocrine tissues. Formation of new follicles and their development may be sufficient for IVM and IVF. The novel proposed in vitro approaches may be used as a second possibility. Infertility of human males affects almost a half of the infertility cases worldwide. Small blood volume replacement from young healthy fertile men may also be easy approach for the improvement of sperm quality in older or other affected men. In addition, body rejuvenation by small blood volume replacement from young healthy individuals of the same sex could represent a decline of in vitro methodology in favor of in vivo treatment for human functional diseases. Here we propose for the first time that blood mononuclear cells are essential for rejuvenation of those tissues, where immune system components participate in an appropriate division and differentiation of tissue stem cells. If needed, small blood volume replacement from distinct young healthy individuals could be utilized in six month intervals for repair of young altered or aged reproductive and other tissue functions. Systemic and local use of honey bee propolis tincture is an alternative option for functional rejuvenation of some tissues.
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Affiliation(s)
- Antonin Bukovsky
- The Institute of Biotechnology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
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