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      In Vitro Evaluation of the Potential Use of Propolis as a Multitarget Therapeutic Product: Physicochemical Properties, Chemical Composition, and Immunomodulatory, Antibacterial, and Anticancer Properties

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          Abstract

          Propolis is a resin that honeybees produce by mixing saliva and beeswax with exudate gathered from botanical sources. The present in vitro study investigated the potential use of propolis as a multitarget therapeutic product and the physicochemical properties, chemical composition, and immunomodulatory, antioxidant, antibacterial, and anticancer properties of a propolis extract from the northern Morocco region (PNM). Pinocembrin, chrysin, and quercetin were the main phenolic compounds of PNM as measured in HPLC. The PNM showed significant inhibitory effects against all tested Gram-positive and Gram-negative strains and showed high antioxidant activities by scavenging free radicals with IC50 (DPPH = 0.02, ABTS = 0.04, and FRAP = 0.04 mg/ml). In addition, PNM induced a dose-dependent cytostatic effect in MCF-7, HCT, and THP-1 cell lines at noncytotoxic concentrations with IC50 values of 479.22, 108.88, and 50.54  μg/ml, respectively. The production of tumor necrosis factor- α (TNF- α) and interleukin-6 (IL-6) was decreased in a dose-dependent manner in LPS-stimulated human peripheral blood mononuclear cells (PBMNCs), whereas the production of the anti-inflammatory interleukin-10 (IL-10) was increased in a dose-dependent manner reaching 15-fold compared to the levels measured in untreated PBMNCs. Overall, the results showed that the traditionally known multitarget therapeutic properties of the PNM seem to be mediated, at least in part, through cytostatic, antibacterial, and immunomodulatory effects.

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          Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes

          In the present study we demonstrate that human monocytes activated by lipopolysaccharides (LPS) were able to produce high levels of interleukin 10 (IL-10), previously designated cytokine synthesis inhibitory factor (CSIF), in a dose dependent fashion. IL-10 was detectable 7 h after activation of the monocytes and maximal levels of IL-10 production were observed after 24-48 h. These kinetics indicated that the production of IL-10 by human monocytes was relatively late as compared to the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, tumor necrosis factor alpha (TNF alpha), and granulocyte colony-stimulating factor (G-CSF), which were all secreted at high levels 4-8 h after activation. The production of IL-10 by LPS activated monocytes was, similar to that of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), and G-CSF, inhibited by IL-4. Furthermore we demonstrate here that IL-10, added to monocytes, activated by interferon gamma (IFN-gamma), LPS, or combinations of LPS and IFN-gamma at the onset of the cultures, strongly inhibited the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, GM-CSF, and G-CSF at the transcriptional level. Viral-IL-10, which has similar biological activities on human cells, also inhibited the production of TNF alpha and GM-CSF by monocytes following LPS activation. Activation of monocytes by LPS in the presence of neutralizing anti-IL-10 monoclonal antibodies resulted in the production of higher amounts of cytokines relative to LPS treatment alone, indicating that endogenously produced IL-10 inhibited the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, GM-CSF, and G-CSF. In addition, IL-10 had autoregulatory effects since it strongly inhibited IL-10 mRNA synthesis in LPS activated monocytes. Furthermore, endogenously produced IL-10 was found to be responsible for the reduction in class II major histocompatibility complex (MHC) expression following activation of monocytes with LPS. Taken together our results indicate that IL-10 has important regulatory effects on immunological and inflammatory responses because of its capacity to downregulate class II MHC expression and to inhibit the production of proinflammatory cytokines by monocytes.
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            Recent Advances in the Chemical Composition of Propolis

            Propolis is a honeybee product with broad clinical applications. Current literature describes that propolis is collected from plant resins. From a systematic database search, 241 compounds were identified in propolis for the first time between 2000 and 2012; and they belong to such diverse chemical classes as flavonoids, phenylpropanoids, terpenenes, stilbenes, lignans, coumarins, and their prenylated derivatives, showing a pattern consistent with around 300 previously reported compounds. The chemical characteristics of propolis are linked to the diversity of geographical location, plant sources and bee species.
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              Botanical origin and chemical composition of Brazilian propolis.

              Brazilian propolis has been classified into 12 groups based on physicochemical characteristics: five in the southern Brazil group (group 3), one in the southeastern Brazil group (group 12), and six in the northeastern Brazil group (group 6). The plant origins of these groups were investigated using reversed-phase high-performance thin-layer chromatography (RPHPTLC), reversed-phase high-performance liquid chromatography (RPHPLC), and gas chromatography-mass spectrometry (GC-MS). It was concluded that the origins of propolis group 3, group 6, and group 12 are resins of the poplar tree, Hyptis divaricata, and Baccharis dracunculifolia, respectively.
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2019
                12 December 2019
                : 2019
                : 4836378
                Affiliations
                1Physiology-Pharmacology, University of Fez, P.O. Box 1796 Fez Atlas, Fez, Morocco
                2Faculty of Allied Medical Sciences, Arab American University Palestine, P.O. Box 240, Jenin, State of Palestine
                3Qasemi Research Center- Al-Qasemi Academic College and Faculty of Arts and Sciences, Arab American University Palestine, P.O. Box 240, Jenin, State of Palestine
                Author notes

                Guest Editor: Yearul Kabir

                Author information
                https://orcid.org/0000-0002-8410-3212
                https://orcid.org/0000-0002-1411-8953
                https://orcid.org/0000-0001-6090-6558
                https://orcid.org/0000-0003-4052-2279
                Article
                10.1155/2019/4836378
                6930758
                31915694
                390ca464-28e1-4fc9-9ad2-239c97850ccc
                Copyright © 2019 Soumaya Touzani et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 September 2019
                : 25 November 2019
                Funding
                Funded by: University Sidi Mohamed Ben Abdallah for Laboratory Physiology-Pharmacology & Environmental Health
                Award ID: USMBA/L08FSDM
                Categories
                Research Article

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