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Cho Y, Han EJ, Heo E, Jayasinghe AMK, Won J, Lee S, Kim T, Kim S, Lim S, Woo SO, Han G, Kang W, Ahn G, Byun S. Propolis suppresses atopic dermatitis through targeting the MKK4 pathway. Biofactors 2025; 51:e2119. [PMID: 39163569 PMCID: PMC11681297 DOI: 10.1002/biof.2119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 08/07/2024] [Indexed: 08/22/2024]
Abstract
Propolis is a natural resinous substance made by bees through mixing various plant sources. Propolis has been widely recognized as a functional food due to its diverse range of beneficial bioactivities. However, the therapeutic effects of consuming propolis against atopic dermatitis (AD) remain largely unknown. The current study aimed to investigate the potential efficacy of propolis against AD and explore the active compound as well as the direct molecular target. In HaCaT keratinocytes, propolis inhibited TNF-α-induced interleukin (IL)-6 and IL-8 secretion. It also led to a reduction in chemokines such as monocyte chemoattractant protein-1 (MCP-1) and macrophage-derived chemokine (MDC), while restoring the levels of barrier proteins, filaggrin and involucrin. Propolis exhibited similar effects in AD-like human skin, leading to the suppression of AD markers and the restoration of barrier proteins. In DNCB-induced mice, oral administration of propolis attenuated AD symptoms, improved barrier function, and reduced scratching frequency and transepidermal water loss (TEWL). In addition, propolis reversed the mRNA levels of AD-related markers in mouse dorsal skin. These effects were attributed to caffeic acid phenethyl ester (CAPE), the active compound identified by comparing major components of propolis. Mechanistic studies revealed that CAPE as well as propolis could directly and selectively target MKK4. Collectively, these findings demonstrate that propolis may be used as a functional food agent for the treatment of AD.
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Affiliation(s)
- Ye‐Ryeong Cho
- Department of BiotechnologyYonsei UniversitySeoulRepublic of Korea
| | - Eui Jeong Han
- Department of Food Technology and NutritionChonnam National UniversityYeosuRepublic of Korea
| | - Eun Heo
- Department of BiotechnologyYonsei UniversitySeoulRepublic of Korea
| | | | - Jihyun Won
- College of PharmacyChung‐Ang UniversitySeoulRepublic of Korea
| | - Soohwan Lee
- Department of Food Science and BiotechnologyGachon UniversitySeongnamRepublic of Korea
| | - Taegun Kim
- Department of BiotechnologyYonsei UniversitySeoulRepublic of Korea
| | - Sung‐Kuk Kim
- Department of Agrobiology, Division of ApicultureNational Institute of Agricultural SciencesWanjuRepublic of Korea
| | - Seokwon Lim
- Department of Food Science and BiotechnologyGachon UniversitySeongnamRepublic of Korea
| | - Soon Ok Woo
- Department of Agrobiology, Division of ApicultureNational Institute of Agricultural SciencesWanjuRepublic of Korea
| | - Gyoonhee Han
- Department of BiotechnologyYonsei UniversitySeoulRepublic of Korea
| | - Wonku Kang
- College of PharmacyChung‐Ang UniversitySeoulRepublic of Korea
| | - Ginnae Ahn
- Department of Food Technology and NutritionChonnam National UniversityYeosuRepublic of Korea
| | - Sanguine Byun
- Department of BiotechnologyYonsei UniversitySeoulRepublic of Korea
- POSTECH Biotech CenterPohang University of Science and Technology (POSTECH)PohangRepublic of Korea
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Cho YR, Jo KA, Park SY, Choi JW, Kim G, Kim TY, Lee S, Lee DH, Kim SK, Lee D, Lee S, Lim S, Woo SO, Byun S, Kim JY. Combination of UHPLC-MS/MS with context-specific network and cheminformatic approaches for identifying bioactivities and active components of propolis. Food Res Int 2023; 172:113134. [PMID: 37689898 DOI: 10.1016/j.foodres.2023.113134] [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: 04/09/2023] [Revised: 06/09/2023] [Accepted: 06/10/2023] [Indexed: 09/11/2023]
Abstract
Discovering new bioactivities and identifying active compounds of food materials are major fields of study in food science. However, the process commonly requires extensive experiments and can be technically challenging. In the current study, we employed network biology and cheminformatic approaches to predict new target diseases, active components, and related molecular mechanisms of propolis. Applying UHPLC-MS/MS analysis results of propolis to Context-Oriented Directed Associations (CODA) and Combination-Oriented Natural Product Database with Unified Terminology (COCONUT) systems indicated atopic dermatitis as a novel target disease. Experimental validation using cell- and human tissue-based models confirmed the therapeutic potential of propolis against atopic dermatitis. Moreover, we were able to find the major contributing compounds as well as their combinatorial effects responsible for the bioactivity of propolis. The CODA/COCONUT system also provided compound-associated genes explaining the underlying molecular mechanism of propolis. These results highlight the potential use of big data-driven network biological approaches to aid in analyzing the impact of food constituents at a systematic level.
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Affiliation(s)
- Ye-Ryeong Cho
- Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
| | - Kyeong Ah Jo
- Department of Food Science and Technology, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea
| | - Soo-Yeon Park
- Department of Food Science and Technology, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea
| | - Jae-Won Choi
- Department of Physical Education, Yonsei University, Seoul 03722, Republic of Korea
| | - Gwangmin Kim
- Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Republic of Korea
| | - Tae Yeon Kim
- Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Republic of Korea
| | - Soohwan Lee
- Department of Food Science and Biotechnology, Gachon University, Gyeonggi 13120, Republic of Korea
| | - Doo-Hee Lee
- National Instrumentation Center for Environmental Management, Seoul National University, Seoul, 08826, Republic of Korea
| | - Sung-Kuk Kim
- Department of Agrobiology, Division of Apiculture, National Institute of Agricultural Sciences, Wanju 55365, Republic of Korea
| | - Doheon Lee
- Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Republic of Korea
| | - Seungki Lee
- National Institute of Biological Resources, Incheon 22689, Republic of Korea
| | - Seokwon Lim
- Department of Food Science and Biotechnology, Gachon University, Gyeonggi 13120, Republic of Korea
| | - Soon Ok Woo
- Department of Agrobiology, Division of Apiculture, National Institute of Agricultural Sciences, Wanju 55365, Republic of Korea
| | - Sanguine Byun
- Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.
| | - Ji Yeon Kim
- Department of Food Science and Technology, Seoul National University of Science and Technology, Seoul 01811, Republic of Korea.
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Gravina C, Formato M, Piccolella S, Fiorentino M, Stinca A, Pacifico S, Esposito A. Lavandula austroapennina (Lamiaceae): Getting Insights into Bioactive Polyphenols of a Rare Italian Endemic Vascular Plant. Int J Mol Sci 2023; 24:ijms24098038. [PMID: 37175744 PMCID: PMC10178519 DOI: 10.3390/ijms24098038] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 04/23/2023] [Accepted: 04/26/2023] [Indexed: 05/15/2023] Open
Abstract
Lavandula austroapennina N.G. Passal., Tundis and Upon has recently been described as a new species endemic to the southern Apennines (Italy). Locally, this species has a long ethnobotanical tradition of use for curative and decoration purposes and has been the protagonist of a flourishing essential oil production chain. Currently, while this tradition has long since ended, attention to the species is necessary, with a view to enhancing marginal and rural areas, as a recovery of a precious resource to (i) get insights into its (poly)phenolic fraction and (ii) address new and innovative uses of all its organs in various application fields (e.g., cosmeceutical sector). Therefore, after field sampling and dissection of its organs (i.e., corolla, calyx, leaf, stem and root), the latter, previously deterpenated and defatted, were subjected to accelerated ultrasound extraction and the related alcoholic extracts were obtained. Chemical composition, explored by UHPLC-QqTOF-MS/MS, and the following multivariate data analysis showed that the hydroxycinnamoyl derivatives are abundant in the leaf, stem and root, while flavonoids are more present in corolla and calyx. In particular, coumaroyl flavonoids with glyconic portion containing also hexuronyl moieties differentiated corolla organ, while yunnaneic acid D isomers and esculin distinguished root. When antiradical and reducing properties were evaluated (by means of ABTS, DPPH and PFRAP tests), a similar clustering of organs was achieved and the marked antioxidant efficacy of leaf, stem and root extracts was found. Thus, following cytotoxicity screening by MTT test on HaCaT keratinocytes, the protective effects of the organ extracts were assessed by wound closure observed after the scratch test. In addition, the extracts from corolla, leaf and stem were particularly active at low doses inducing rapid wound closure on HaCaT cells at a concentration of 1 μg/mL. The diversity in (poly)phenols of each organ and the promising bioactivity preliminarily assessed suggest further investigation to be carried out to fully recover and valorize this precious endemic vascular plant.
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Affiliation(s)
- Claudia Gravina
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Via Vivaldi 43, 81100 Caserta, Italy
| | - Marialuisa Formato
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Via Vivaldi 43, 81100 Caserta, Italy
| | - Simona Piccolella
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Via Vivaldi 43, 81100 Caserta, Italy
| | - Marika Fiorentino
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Via Vivaldi 43, 81100 Caserta, Italy
| | - Adriano Stinca
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Via Vivaldi 43, 81100 Caserta, Italy
| | - Severina Pacifico
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Via Vivaldi 43, 81100 Caserta, Italy
| | - Assunta Esposito
- Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Via Vivaldi 43, 81100 Caserta, Italy
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Liu Y, Meng C, Li Y, Xia D, Lu C, Lai J, Zhang Y, Cao K, Gao X, Yuan Q. Peptide-Protected Gold Nanoclusters Efficiently Ameliorate Acute Contact Dermatitis and Psoriasis via Repressing the TNF-α/NF-κB/IL-17A Axis in Keratinocytes. NANOMATERIALS (BASEL, SWITZERLAND) 2023; 13:662. [PMID: 36839031 PMCID: PMC9963485 DOI: 10.3390/nano13040662] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 02/03/2023] [Accepted: 02/05/2023] [Indexed: 06/18/2023]
Abstract
Immune-mediated skin diseases have a high prevalence and seriously affect patients' quality of life. Gold compounds have been considered promising therapeutic agents in dermatology, but the high incidence of adverse reactions have limited their clinical application. There is a great need to develop more effective and less toxic gold-based drugs. Gold nanoclusters fabricated by using peptides (pep-AuNCs) have appeared as potential biomedical nanomaterials because of their excellent biocompatibility, ease of fabrication and unique physicochemical properties. Glutathione (GSH) is an endogenous tripeptide and has been used for lightening the skin color. Therefore, we fabricated a well-defined gold nanocluster with GSH as an example to explore the immunomodulatory effect of AuNCs on a TNF-α-treated human keratinocyte cell line (HaCaT) in vitro, the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced irritant contact dermatitis (ICD) model and the oxazolone (OXA)-induced psoriatic model in vivo. The results indicated that topically applied AuNCs successfully attenuated the severity of ICD and psoriasis-like lesions. In vitro and in vivo, AuNCs effectively inhibited the abnormal activation of the NF-κB pathway and the consequent overexpression of proinflammatory cytokines in keratinocytes. In particular, the transactivation of IL-17A, the most important cytokine in psoriasis pathology, was effectively inhibited by AuNCs treatment. In addition, AuNCs did not show any obvious cytotoxicity in HaCaT cells at doses even up to 100 µM and did not induce any irritation in the healthy skin and major organs, which indicated their favorable biosafety. These results indicate that biocompatible pep-AuNCs might be a promising gold-based nanomedicine for the treatment of inflammatory skin diseases.
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Affiliation(s)
- Yu Liu
- Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, Beijing 100124, China
| | - Cong Meng
- Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, Beijing 100124, China
| | - Yanggege Li
- Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, Beijing 100124, China
| | - Dongfang Xia
- College of Chemistry and Material Science, Shandong Agricultural University, Taian 271018, China
| | - Cao Lu
- Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, Beijing 100124, China
| | - Jing Lai
- Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, Beijing 100124, China
| | - Yulu Zhang
- Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, Beijing 100124, China
| | - Kai Cao
- Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, Beijing 100124, China
| | - Xueyun Gao
- Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, Beijing 100124, China
| | - Qing Yuan
- Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, Beijing 100124, China
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RNA Sequencing Reveals the Regulation Mechanism of Yunnan Baiyao in Treating Skin Infection Caused by Staphylococcus aureus. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:6348157. [PMID: 36276861 PMCID: PMC9581712 DOI: 10.1155/2022/6348157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 09/01/2022] [Accepted: 09/26/2022] [Indexed: 11/07/2022]
Abstract
Yunnan Baiyao is a well-known traditional Chinese medicine that can be formulated into a powder or capsule form. The mechanism by which it exerts its anti-inflammation effect, which is used in skin care products, needs to be further explored. In this study, we established the Staphylococcus aureus-induced mouse skin inflammatory model to investigate the effects of Yunnan Baiyao by the method of RNA-sequencing technology. The mice were randomly assigned to three groups, and those were control, model, and the Yunnan Baiyao-treated (YNtreated) group. Key genes and pathways were identified using bioinformatics analyses. In the study, we obtained 1,053 differentially expressed genes (DEGs) induced by Yunnan Baiyao. The 233 upregulated genes were enriched in 32 GO terms and 5 KEGG pathways, focused on the items, such as wound healing, cell metabolism, and proliferation, indicating the accelerating effects of Yunnan Baiyao on these aspects. The 820 downregulated genes were enriched mainly in the items, including the regulation of inflammation factor production, immune responses, and regulation of structure dermal components. Besides, Yunnan Baiyao reversed the expressions of 277 (201 decreased and 76 increased DEGs, respectively) induced by S. aureus. Ten key regulatory nodes (MMP2, PLK1, CCNB1, TLR4, CDK1, CCNA2, CDC25C, PDGFRA, MYOC, and KNG1) were identified by the construction of the protein interaction network, half of which were related to cell proliferation. VAV1 was another hub node that was affected by Yunnan Baiyao (Top 20). In the study, VAV1 and TLR4 can be considered key module genes in inflammation regulation. In conclusion, this study found that Yunnan Baiyao can significantly relieve inflammatory symptoms by regulating genes and pathways involved in the regulation of inflammation and immune response and also helped to deepen our understanding of the associated molecular mechanisms.
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Allergic Inflammation: Effect of Propolis and Its Flavonoids. Molecules 2022; 27:molecules27196694. [PMID: 36235230 PMCID: PMC9570745 DOI: 10.3390/molecules27196694] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 10/02/2022] [Accepted: 10/03/2022] [Indexed: 11/17/2022] Open
Abstract
The incidence of allergic diseases and their complications are increasing worldwide. Today, people increasingly use natural products, which has been termed a "return to nature". Natural products with healing properties, especially those obtained from plants and bees, have been used in the prevention and treatment of numerous chronic diseases, including allergy and/or inflammation. Propolis is a multi-component resin rich in flavonoids, collected and transformed by honeybees from buds and plant wounds for the construction and adaptation of their nests. This article describes the current views regarding the possible mechanisms and multiple benefits of flavonoids in combating allergy and allergy-related complications. These benefits arise from flavonoid anti-allergic, anti-inflammatory, antioxidative, and wound healing activities and their effects on microbe-immune system interactions in developing host responses to different allergens. Finally, this article presents various aspects of allergy pathobiology and possible molecular approaches in their treatment. Possible mechanisms regarding the antiallergic action of propolis on the microbiota of the digestive and respiratory tracts and skin diseases as a method to selectively remove allergenic molecules by the process of bacterial biotransformation are also reported.
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Molecular and Cellular Mechanisms of Propolis and Its Polyphenolic Compounds against Cancer. Int J Mol Sci 2022; 23:ijms231810479. [PMID: 36142391 PMCID: PMC9499605 DOI: 10.3390/ijms231810479] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Revised: 08/31/2022] [Accepted: 09/05/2022] [Indexed: 12/12/2022] Open
Abstract
In recent years, interest in natural products such as alternative sources of pharmaceuticals for numerous chronic diseases, including tumors, has been renewed. Propolis, a natural product collected by honeybees, and polyphenolic/flavonoid propolis-related components modulate all steps of the cancer progression process. Anticancer activity of propolis and its compounds relies on various mechanisms: cell-cycle arrest and attenuation of cancer cells proliferation, reduction in the number of cancer stem cells, induction of apoptosis, modulation of oncogene signaling pathways, inhibition of matrix metalloproteinases, prevention of metastasis, anti-angiogenesis, anti-inflammatory effects accompanied by the modulation of the tumor microenvironment (by modifying macrophage activation and polarization), epigenetic regulation, antiviral and bactericidal activities, modulation of gut microbiota, and attenuation of chemotherapy-induced deleterious side effects. Ingredients from propolis also "sensitize" cancer cells to chemotherapeutic agents, likely by blocking the activation of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). In this review, we summarize the current knowledge related to the the effects of flavonoids and other polyphenolic compounds from propolis on tumor growth and metastasizing ability, and discuss possible molecular and cellular mechanisms involved in the modulation of inflammatory pathways and cellular processes that affect survival, proliferation, invasion, angiogenesis, and metastasis of the tumor.
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An JY, Kim C, Park NR, Jung HS, Koo TS, Yuk SH, Lee EH, Cho SH. Clinical Anti-aging Efficacy of Propolis Polymeric Nanoparticles Prepared by a Temperature-induced Phase Transition Method. J Cosmet Dermatol 2022; 21:4060-4071. [PMID: 35001491 DOI: 10.1111/jocd.14740] [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: 09/08/2021] [Revised: 12/07/2021] [Accepted: 12/29/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND Collagen forms a dermal matrix in the skin. Biosynthesis and decomposition of collagen are the major processes in skin aging. Propolis is rich in flavonoids and phenolic compounds, which are known to be effective in preventing skin aging, including the enhancement of fibroblast proliferation, activation, and growth capacity. OBJECTIVES The aim of this study was to develop a poorly soluble propolis extract as an active ingredient in cosmetic products for anti-aging efficacy. METHODS & RESULTS Polymeric nanoparticles containing propolis extract, polyethylene glycol 400, and poloxamer 407 were prepared via a temperature-induced phase transition method. The particle size of the polymeric nanoparticles was approximately 20.75 nm. The results of an in vitro procollagen type I carboxy-terminal peptide assay and a matrix metalloproteinase-1 inhibition assay showed that the polymeric nanoparticles increased collagen production by 19.81%-24.59% compared to blank (p < 0.05), and significantly reduced intracellular collagenase activity by 7.46%-31.52% compared to blank (p < 0.05). In a clinical trial, polymeric nanoparticles in a cosmetic formulation were applied around the eyes of 24 female subjects for 8 weeks. Five skin parameters were significantly improved after the application of the test ampoule. Visual evaluation using the Global Photo Damage Score showed a significant reduction in wrinkles after the application of the test ampoules (p < 0.001). CONCLUSIONS This study outlines the development of stable polymeric nanoparticles containing poorly soluble propolis in a cosmetic formulation, and its efficacy in wrinkle improvement. The developed polymeric nanoparticles were effective for alleviating wrinkles and can be used for pharmaceutical applications that utilize propolis as antiseptic, anti-inflammatory, antimycotic, antifungal, antibacterial, antiulcer, anticancer, and immunomodulatory agents.
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Affiliation(s)
- Joo Young An
- College of Pharmacy, Korea University, Sejong-ro, Sejong, Republic of Korea.,Drug Discovery Platform Research Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea
| | - Chaejin Kim
- Drug Discovery Platform Research Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.,College of Pharmacy, Chungang University, Seoul, Republic of Korea
| | - Na Rae Park
- Drug Discovery Platform Research Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.,Graduate School of New Drug Discovery and Development, Chungnam National University, Yusung, Daejeon, Republic of Korea
| | - Han Soo Jung
- Hanstech, 1576-16, Chungui-ro, Jeongsan-myeon, Cheongyang-gun, Chungcheongnam-do, Republic of Korea
| | - Tae-Sung Koo
- Graduate School of New Drug Discovery and Development, Chungnam National University, Yusung, Daejeon, Republic of Korea
| | - Soon Hong Yuk
- College of Pharmacy, Korea University, Sejong-ro, Sejong, Republic of Korea
| | - Eun Hee Lee
- College of Pharmacy, Korea University, Sejong-ro, Sejong, Republic of Korea
| | - Sun Hang Cho
- Drug Discovery Platform Research Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea
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Rostami S, Tekkeşin AI, Ercan UK, Garipcan B. Biomimetic sharkskin surfaces with antibacterial, cytocompatible, and drug delivery properties. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 134:112565. [DOI: 10.1016/j.msec.2021.112565] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 11/02/2021] [Accepted: 11/21/2021] [Indexed: 11/29/2022]
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Melguizo-Rodríguez L, de Luna-Bertos E, Ramos-Torrecillas J, Illescas-Montesa R, Costela-Ruiz VJ, García-Martínez O. Potential Effects of Phenolic Compounds That Can Be Found in Olive Oil on Wound Healing. Foods 2021; 10:1642. [PMID: 34359512 PMCID: PMC8307686 DOI: 10.3390/foods10071642] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 07/08/2021] [Accepted: 07/13/2021] [Indexed: 01/03/2023] Open
Abstract
The treatment of tissue damage produced by physical, chemical, or mechanical agents involves considerable direct and indirect costs to health care systems. Wound healing involves a series of molecular and cellular events aimed at repairing the defect in tissue integrity. These events can be favored by various natural agents, including the polyphenols in extra virgin olive oil (EVOO). The objective of this study was to review data on the potential effects of different phenolic compounds that can also be found in EVOO on wound healing and closure. Results of in vitro and animal studies demonstrate that polyphenols from different plant species, also present in EVOO, participate in different aspects of wound healing, accelerating this process through their anti-inflammatory, antioxidant, and antimicrobial properties and their stimulation of angiogenic activities required for granulation tissue formation and wound re-epithelialization. These results indicate the potential usefulness of EVOO phenolic compounds for wound treatment, either alone or in combination with other therapies. Human studies are warranted to verify this proposition.
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Affiliation(s)
- Lucia Melguizo-Rodríguez
- Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences, University of Granada, Avda. Ilustración 60, 18016 Granada, Spain; (L.M.-R.); (E.d.L.-B.); (J.R.-T.); (R.I.-M.); (O.G.-M.)
- Institute of Biosanitary Research, ibs.Granada, C/Doctor Azpitarte 4, 4 planta, 18012 Granada, Spain
| | - Elvira de Luna-Bertos
- Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences, University of Granada, Avda. Ilustración 60, 18016 Granada, Spain; (L.M.-R.); (E.d.L.-B.); (J.R.-T.); (R.I.-M.); (O.G.-M.)
- Institute of Biosanitary Research, ibs.Granada, C/Doctor Azpitarte 4, 4 planta, 18012 Granada, Spain
| | - Javier Ramos-Torrecillas
- Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences, University of Granada, Avda. Ilustración 60, 18016 Granada, Spain; (L.M.-R.); (E.d.L.-B.); (J.R.-T.); (R.I.-M.); (O.G.-M.)
- Institute of Biosanitary Research, ibs.Granada, C/Doctor Azpitarte 4, 4 planta, 18012 Granada, Spain
| | - Rebeca Illescas-Montesa
- Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences, University of Granada, Avda. Ilustración 60, 18016 Granada, Spain; (L.M.-R.); (E.d.L.-B.); (J.R.-T.); (R.I.-M.); (O.G.-M.)
- Institute of Biosanitary Research, ibs.Granada, C/Doctor Azpitarte 4, 4 planta, 18012 Granada, Spain
| | - Victor Javier Costela-Ruiz
- Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences, University of Granada, Avda. Ilustración 60, 18016 Granada, Spain; (L.M.-R.); (E.d.L.-B.); (J.R.-T.); (R.I.-M.); (O.G.-M.)
- Institute of Biosanitary Research, ibs.Granada, C/Doctor Azpitarte 4, 4 planta, 18012 Granada, Spain
| | - Olga García-Martínez
- Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences, University of Granada, Avda. Ilustración 60, 18016 Granada, Spain; (L.M.-R.); (E.d.L.-B.); (J.R.-T.); (R.I.-M.); (O.G.-M.)
- Institute of Biosanitary Research, ibs.Granada, C/Doctor Azpitarte 4, 4 planta, 18012 Granada, Spain
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Lv L, Cui H, Ma Z, Liu X, Yang L. Recent progresses in the pharmacological activities of caffeic acid phenethyl ester. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2021; 394:1327-1339. [PMID: 33492405 DOI: 10.1007/s00210-021-02054-w] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Accepted: 01/14/2021] [Indexed: 12/16/2022]
Abstract
The past decades have seen a growing interest in natural products. Caffeic acid phenethyl ester (CAPE), a flavonoid isolated from honeybee propolis, has shown multiple pharmacological potentials, including anti-cancer, anti-inflammatory, antioxidant, antibacterial, antifungal, and protective effects on nervous systems and multiple organs, since it was found as a potent nuclear factor κB (NF-κB) inhibitor. This review summarizes the advances in these beneficial effects of CAPE, as well as the underlying mechanisms, and proposes that CAPE offers an opportunity for developing therapeutics in multiple diseases. However, clinical trials on CAPE are necessary and encouraged to obtain certain clinically relevant conclusions.
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Affiliation(s)
- Lili Lv
- Jilin University, Changchun, 130021, China
| | | | - Zhiming Ma
- Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, 130041, China
| | - Xin Liu
- Eye Center, The Second Hospital of Jilin University, Changchun, 130041, China.
| | - Longfei Yang
- Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, 130041, China.
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12
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Contardi M, Lenzuni M, Fiorentini F, Summa M, Bertorelli R, Suarato G, Athanassiou A. Hydroxycinnamic Acids and Derivatives Formulations for Skin Damages and Disorders: A Review. Pharmaceutics 2021; 13:999. [PMID: 34371691 PMCID: PMC8309026 DOI: 10.3390/pharmaceutics13070999] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 06/25/2021] [Accepted: 06/26/2021] [Indexed: 02/06/2023] Open
Abstract
Alterations of skin homeostasis are widely diffused in our everyday life both due to accidental injuries, such as wounds and burns, and physiological conditions, such as late-stage diabetes, dermatitis, or psoriasis. These events are locally characterized by an intense inflammatory response, a high generation of harmful free radicals, or an impairment in the immune response regulation, which can profoundly change the skin tissue' repair process, vulnerability, and functionality. Moreover, diabetes diffusion, antibiotic resistance, and abuse of aggressive soaps and disinfectants following the COVID-19 emergency could be causes for the future spreading of skin disorders. In the last years, hydroxycinnamic acids and derivatives have been investigated and applied in several research fields for their anti-oxidant, anti-inflammatory, and anti-bacterial activities. First, in this study, we give an overview of these natural molecules' current source and applications. Afterwards, we review their potential role as valid alternatives to the current therapies, supporting the management and rebalancing of skin disorders and diseases at different levels. Also, we will introduce the recent advances in the design of biomaterials loaded with these phenolic compounds, specifically suitable for skin disorders treatments. Lastly, we will suggest future perspectives for introducing hydroxycinnamic acids and derivatives in treating skin disorders.
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Affiliation(s)
- Marco Contardi
- Smart Materials, Italian Institute of Technology, 16163 Genoa, Italy; (M.L.); (F.F.); (G.S.)
| | - Martina Lenzuni
- Smart Materials, Italian Institute of Technology, 16163 Genoa, Italy; (M.L.); (F.F.); (G.S.)
- DIBRIS, University of Genoa, 16145 Genoa, Italy
| | - Fabrizio Fiorentini
- Smart Materials, Italian Institute of Technology, 16163 Genoa, Italy; (M.L.); (F.F.); (G.S.)
- DIBRIS, University of Genoa, 16145 Genoa, Italy
| | - Maria Summa
- Translational Pharmacology, Italian Institute of Technology, 16163 Genoa, Italy; (M.S.); (R.B.)
| | - Rosalia Bertorelli
- Translational Pharmacology, Italian Institute of Technology, 16163 Genoa, Italy; (M.S.); (R.B.)
| | - Giulia Suarato
- Smart Materials, Italian Institute of Technology, 16163 Genoa, Italy; (M.L.); (F.F.); (G.S.)
- Translational Pharmacology, Italian Institute of Technology, 16163 Genoa, Italy; (M.S.); (R.B.)
| | - Athanassia Athanassiou
- Smart Materials, Italian Institute of Technology, 16163 Genoa, Italy; (M.L.); (F.F.); (G.S.)
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13
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Cytokines and Water Distribution in Anorexia Nervosa. Mediators Inflamm 2021; 2021:8811051. [PMID: 33867858 PMCID: PMC8035023 DOI: 10.1155/2021/8811051] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 03/03/2021] [Accepted: 03/27/2021] [Indexed: 01/02/2023] Open
Abstract
In patients with anorexia nervosa (AN), decreased intracellular (ICW), extracellular (ECW), and total body water (TBW) as well as changes in serum cytokine concentrations have been reported. In this exploratory study, we measured body composition and serum cytokine levels in patients with AN (n = 27) and healthy controls (HCs; n = 13). Eating disorder symptom severity was assessed using the Eating Disorder Examination-Questionnaire (EDE-Q). Body composition was determined by bioimpedance analysis (BIA) which provided information on ICW, ECW, and TBW. Following blood collection, 27 cytokines and chemokines were quantified using multiplex ELISA-based technology: Eotaxin, Eotaxin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon- (IFN-) γ, interleukin- (IL-) 1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, interferon γ-induced protein- (IP-) 10, macrophage inflammatory protein- (MIP-) 1α, MIP-1β, monocyte chemoattractant protein- (MCP-) 1, MCP-4, thymus and activation-regulated chemokine (TARC), TNF-α, and TNF-β. ICW, ECW, and TBW volumes were significantly lower in patients with AN than in HCs. In the whole sample, GM-CSF, MCP-4, and IL-4 were positively, whereas IFN-γ, IL-6, and IL-10 were negatively associated with all three parameters of body water. In AN participants, we found a statistically significant negative correlation of IL-10 with ICW, ECW, and TBW. Our results suggest an interaction between body water and the cytokine system. Underlying mechanisms are unclear but may involve a loss of water from the gut, kidneys, or skin due to AN-associated inflammatory processes.
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14
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Wu BC, Skovbakke SL, Masoudi H, Hancock REW, Franzyk H. In vivo Anti-inflammatory Activity of Lipidated Peptidomimetics Pam-(Lys-βNspe) 6-NH 2 and Lau-(Lys-βNspe) 6-NH 2 Against PMA-Induced Acute Inflammation. Front Immunol 2020; 11:2102. [PMID: 32983167 PMCID: PMC7485003 DOI: 10.3389/fimmu.2020.02102] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 08/03/2020] [Indexed: 01/09/2023] Open
Abstract
Host Defense Peptides (HDPs) are key components of innate immunity that exert antimicrobial, antibiofilm, and immunomodulatory activities in all higher organisms. Synthetic peptidomimetic analogs were designed to retain the desirable pharmacological properties of HDPs while having improved stability toward enzymatic degradation, providing enhanced potential for therapeutic applications. Lipidated peptide/β-peptoid hybrids [e.g., Pam-(Lys-βNspe)6-NH2 (PM1) and Lau-(Lys-βNspe)6-NH2 (PM2)] are proteolytically stable HDP mimetics displaying anti-inflammatory activity and formyl peptide receptor 2 antagonism in human and mouse immune cells in vitro. Here PM1 and PM2 were investigated for their in vivo anti-inflammatory activity in a phorbol 12-myristate 13-acetate (PMA)-induced acute mouse ear inflammation model. Topical administration of PM1 or PM2 led to attenuated PMA-induced ear edema, reduced local production of the pro-inflammatory chemokines MCP-1 and CXCL-1 as well as the cytokine IL-6. In addition, diminished neutrophil infiltration into PMA-inflamed ear tissue and suppressed local release of reactive oxygen and nitrogen species were observed upon treatment. The obtained results show that these two peptidomimetics exhibit anti-inflammatory effects comparable to that of the non-steroidal anti-inflammatory drug indomethacin, and hence possess a potential for treatment of inflammatory skin conditions.
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Affiliation(s)
- Bing C Wu
- Center for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, The University of British Columbia, Vancouver, BC, Canada
| | - Sarah L Skovbakke
- Biotherapeutic Glycoengineering and Immunology, Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs Lyngby, Denmark
| | - Hamid Masoudi
- Faculty of Medicine, Department of Pathology and Laboratory Medicine, St. Paul's Hospital, Vancouver, BC, Canada
| | - Robert E W Hancock
- Center for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, The University of British Columbia, Vancouver, BC, Canada
| | - Henrik Franzyk
- Faculty of Health and Medical Sciences, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark
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15
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Protection against Ultraviolet A-Induced Skin Apoptosis and Carcinogenesis through the Oxidative Stress Reduction Effects of N-(4-bromophenethyl) Caffeamide, A Propolis Derivative. Antioxidants (Basel) 2020; 9:antiox9040335. [PMID: 32326032 PMCID: PMC7222364 DOI: 10.3390/antiox9040335] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 04/15/2020] [Accepted: 04/16/2020] [Indexed: 12/18/2022] Open
Abstract
Ultraviolet A (UVA) is a major factor in skin aging and damage. Antioxidative materials may ameliorate this UV damage. This study investigated the protective properties of N-(4-bromophenethyl) caffeamide (K36H) against UVA-induced skin inflammation, apoptosis and genotoxicity in keratinocytes. The protein expression or biofactor concentration related to UVA-induced skin damage were identified using an enzyme-linked immunosorbent assay and western blotting. K36H reduced UVA-induced intracellular reactive oxygen species generation and increased nuclear factor erythroid 2–related factor 2 translocation into the nucleus to upregulate the expression of heme oxygenase-1, an intrinsic antioxidant enzyme. K36H inhibited UVA-induced activation of extracellular-signal-regulated kinases and c-Jun N-terminal kinases, reduced the overexpression of matrix metalloproteinase (MMP)-1 and MMP-2 and elevated the expression of the metalloproteinase-1 tissue inhibitor. Moreover, K36H inhibited the phosphorylation of c-Jun and downregulated c-Fos expression. K36H attenuated UVA-induced Bax and caspase-3 expression and upregulated antiapoptotic protein B-cell lymphoma 2 expression. K36H reduced UVA-induced DNA damage. K36H also downregulated inducible nitric oxide synthase, cyclooxygenase-2 and interleukin-6 expression as well as the subsequent generation of prostaglandin E2 and nitric oxide. We observed that K36H ameliorated UVA-induced oxidative stress, inflammation, apoptosis and antiphotocarcinogenic activity. K36H can potentially be used for the development of antiphotodamage and antiphotocarcinogenic products.
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16
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Ferrer MD, Busquets-Cortés C, Capó X, Tejada S, Tur JA, Pons A, Sureda A. Cyclooxygenase-2 Inhibitors as a Therapeutic Target in Inflammatory Diseases. Curr Med Chem 2019; 26:3225-3241. [PMID: 29756563 DOI: 10.2174/0929867325666180514112124] [Citation(s) in RCA: 145] [Impact Index Per Article: 24.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Revised: 04/12/2017] [Accepted: 04/22/2017] [Indexed: 02/07/2023]
Abstract
Inflammation plays a crucial role in the development of many complex diseases and disorders including autoimmune diseases, metabolic syndrome, neurodegenerative diseases, and cardiovascular pathologies. Prostaglandins play a regulatory role in inflammation. Cyclooxygenases are the main mediators of inflammation by catalyzing the initial step of arachidonic acid metabolism and prostaglandin synthesis. The differential expression of the constitutive isoform COX-1 and the inducible isoform COX-2, and the finding that COX-1 is the major form expressed in the gastrointestinal tract, lead to the search for COX-2-selective inhibitors as anti-inflammatory agents that might diminish the gastrointestinal side effects of traditional non-steroidal anti-inflammatory drugs (NSAIDs). COX-2 isoform is expressed predominantly in inflammatory cells and decidedly upregulated in chronic and acute inflammations, becoming a critical target for many pharmacological inhibitors. COX-2 selective inhibitors happen to show equivalent efficacy with that of conventional NSAIDs, but they have reduced gastrointestinal side effects. This review would elucidate the most recent findings on selective COX-2 inhibition and their relevance to human pathology, concretely in inflammatory pathologies characterized by a prolonged pro-inflammatory status, including autoimmune diseases, metabolic syndrome, obesity, atherosclerosis, neurodegenerative diseases, chronic obstructive pulmonary disease, arthritis, chronic inflammatory bowel disease and cardiovascular pathologies.
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Affiliation(s)
- Miguel D Ferrer
- Laboratory for Physical Activity Sciences and Research Group in Community Nutrition and Oxidative Stress. Department of Basic Biology and Health Sciences, IUNICS, University of Balearic Islands, Palma, Spain.,CIBEROBN (Fisiopatología de la Obesidad y la Nutrición CB12/03/30038) Instituto de Salud Carlos III, Madrid, Spain
| | - Carla Busquets-Cortés
- Laboratory for Physical Activity Sciences and Research Group in Community Nutrition and Oxidative Stress. Department of Basic Biology and Health Sciences, IUNICS, University of Balearic Islands, Palma, Spain
| | - Xavier Capó
- Laboratory for Physical Activity Sciences and Research Group in Community Nutrition and Oxidative Stress. Department of Basic Biology and Health Sciences, IUNICS, University of Balearic Islands, Palma, Spain
| | - Silvia Tejada
- Laboratory of Neurophysiology, Biology Department, University of the Balearic Islands, Palma de Mallorca, Spain
| | - Josep A Tur
- Laboratory for Physical Activity Sciences and Research Group in Community Nutrition and Oxidative Stress. Department of Basic Biology and Health Sciences, IUNICS, University of Balearic Islands, Palma, Spain.,CIBEROBN (Fisiopatología de la Obesidad y la Nutrición CB12/03/30038) Instituto de Salud Carlos III, Madrid, Spain
| | - Antoni Pons
- Laboratory for Physical Activity Sciences and Research Group in Community Nutrition and Oxidative Stress. Department of Basic Biology and Health Sciences, IUNICS, University of Balearic Islands, Palma, Spain.,CIBEROBN (Fisiopatología de la Obesidad y la Nutrición CB12/03/30038) Instituto de Salud Carlos III, Madrid, Spain
| | - Antoni Sureda
- Laboratory for Physical Activity Sciences and Research Group in Community Nutrition and Oxidative Stress. Department of Basic Biology and Health Sciences, IUNICS, University of Balearic Islands, Palma, Spain.,CIBEROBN (Fisiopatología de la Obesidad y la Nutrición CB12/03/30038) Instituto de Salud Carlos III, Madrid, Spain
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17
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Milani GB, Camponogara C, Piana M, Silva CR, Oliveira SM. Cariniana domestica fruit peels present topical anti-inflammatory efficacy in a mouse model of skin inflammation. Naunyn Schmiedebergs Arch Pharmacol 2019; 392:513-528. [PMID: 30617548 DOI: 10.1007/s00210-018-1594-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2018] [Accepted: 11/22/2018] [Indexed: 12/30/2022]
Abstract
To investigate the topical anti-inflammatory activity of the crude extract of Cariniana domestica fruit peels (CdE), its dichloromethane, n-butanol, and ethyl acetate (EtAc) fractions, and steroids (β-sitosterol, lupeol, and stigmasterol) isolated from the EtAc fraction in models of irritant contact dermatitis (ICD) croton oil-induced in mice. We induced skin inflammation by single (acute; 1 mg/ear) and multiple (chronic; 0.4 mg/ear) croton oil application. We topically applied C. domestica (CdE, fractions, and gel formulations) and β-sitosterol, lupeol, and stigmasterol immediately after applying croton oil. HPLC-DAD chromatography of the EtAc fraction and stability of the gel formulations were verified. HPLC-DAD of the EtAc fraction revealed the stigmasterol, lupeol, and β-sitosterol presence. CdE and EtAc fraction gels showed no organoleptic or pH changes at room temperatures. CdE and dichloromethane, n-butanol, and EtAc (1 mg/ear) fractions decreased the acute ear edema with maximum inhibition (Imax) of 97 ± 2, 86 ± 1, 81 ± 4, and 95 ± 2%, respectively. CdE and EtAc fraction gel presented similar effects, with respective Imax of 85 ± 6% (3%;15 mg/ear) and 82 ± 2% (1%;15 mg/ear). β-sitosterol (7.5 μg/ear), lupeol (10 μg/ear), and stigmasterol (5.7 μg/ear) also reduced this parameter by 46 ± 8, 51 ± 7, and 62 ± 7%, respectively. All topical treatments reduced the inflammatory cells' infiltration in the acute ICD model. CdE reduced the ear edema by 77 ± 4% (1 mg/ear) and the inflammatory cell infiltration in the chronic ICD model. CdE's anti-inflammatory effect was accompanied by a minimum development of adverse effects. C. domestica demonstrates a promising potential for the development of a topical anti-inflammatory agent. Graphical abstract Cariniana domestica, popularly known as jequitibá-roxo, presented topical anti-inflammatory activity in an acute and chronic irritant contact dermatitis croton oil-induced in mice. The crude extract (solutions and gel formulations) and different fractions obtained from fruit peels of C. domestica showed topical antiinflammatory activity on skin inflammation models with minimum adverse effects in preliminary toxicological studies (behavior and biochemical parameters). Moreover, the HPLC analysis revealed the presence of β-sitosterol, stigmasterol and lupeol, which also presented topical anti-inflammatory effect in the acute irritant contact dermatitis croton oil-induced. Our findings support the use of this species as a promising topical antiinflammatory agent.
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Affiliation(s)
- Gessica Brum Milani
- Laboratory Neurotoxicity and Psychopharmacology, Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, Av. Roraima 1000, Camobi, Santa Maria, RS, 97105-900, Brazil
| | - Camila Camponogara
- Laboratory Neurotoxicity and Psychopharmacology, Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, Av. Roraima 1000, Camobi, Santa Maria, RS, 97105-900, Brazil
| | - Mariana Piana
- Phytochemical Research Laboratory, Graduate Program in Pharmaceutical Sciences, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Cássia Regina Silva
- Institute of Genetics and Biochemistry, Graduate Program in Genetics and Biochemistry, Federal University of Uberlandia, Uberlandia, MG, Brazil
| | - Sara Marchesan Oliveira
- Laboratory Neurotoxicity and Psychopharmacology, Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, Av. Roraima 1000, Camobi, Santa Maria, RS, 97105-900, Brazil.
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18
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Protective Effects and Mechanisms of N-Phenethyl Caffeamide from UVA-Induced Skin Damage in Human Epidermal Keratinocytes through Nrf2/HO-1 Regulation. Int J Mol Sci 2019; 20:ijms20010164. [PMID: 30621167 PMCID: PMC6337442 DOI: 10.3390/ijms20010164] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Revised: 12/24/2018] [Accepted: 12/27/2018] [Indexed: 02/07/2023] Open
Abstract
The skin provides an effective barrier against physical, chemical, and microbial invasion; however, overexposure to ultraviolet (UV) radiation causes excessive cellular oxidative stress, which leads to skin damage, DNA damage, mutations, and skin cancer. This study investigated the protective effects of N-phenethyl caffeamide (K36) from UVA damage on human epidermal keratinocytes. We found that K36 reduced UVA-induced intracellular reactive oxygen species (ROS) production and induced the expression of the intrinsic antioxidant enzyme heme oxygenase-1 (HO-1) by increasing the translocation of nuclear factor erythroid 2⁻related factor 2 (Nrf2). K36 could inhibit the phosphorylation of extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinases (JNK) and reduce UVA-induced matrix metalloproteinase (MMP)-1 and MMP-2 overexpression; it could also elevate the expression of tissue inhibitors of metalloproteinases (TIMP). In addition, K36 ameliorated 8-hydroxy-2'-deoxyguanosine (8-OHdG) induced by UVA irradiation. Furthermore, K36 could downregulate the expression of inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) and the subsequent production of nitric oxide (NO) and prostaglandin E₂ (PGE₂). Based on our findings, K36 possessed potent antioxidant, anti-inflammatory, antiphotodamage, and even antiphotocarcinogenesis activities. Thus, K36 has the potential to be used to multifunctional skin care products and drugs.
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19
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Romana-Souza B, Dos Santos JS, Monte-Alto-Costa A. Caffeic acid phenethyl ester promotes wound healing of mice pressure ulcers affecting NF-κB, NOS2 and NRF2 expression. Life Sci 2018; 207:158-165. [PMID: 29864436 DOI: 10.1016/j.lfs.2018.05.057] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Revised: 05/12/2018] [Accepted: 05/31/2018] [Indexed: 02/07/2023]
Abstract
AIMS In pressure ulcers, the synthesis of reactive oxygen species induced by ischemia and reperfusion leads to chronic inflammation and tissue damage, which impair the closure of these lesions. Caffeic acid phenethyl ester (CAPE), found in propolis, promotes cutaneous wound healing of acute lesions and severe burns. However, the effects of CAPE on wound healing of pressure ulcers have not been investigated. This study investigated the effects of CAPE administration in a murine model of pressure ulcers. MAIN METHODS To induce pressure ulcers, two cycles of ischemia and reperfusion by external application of two magnetic plates were performed in the skin dorsum of mice. After the last cycle, animals were treated daily with CAPE or vehicle until they were euthanized. KEY FINDINGS The nitric oxide synthesis, lipid peroxidation, macrophage migration, protein nuclear factor kappa B and nitric-oxide synthase-2 expression were increased 3 days after ulceration but decreased 7 days later, in pressure ulcers of the CAPE group compared to that of the control group. CAPE reduced the protein expression of nuclear factor-erythroid2-related factor 2 in pressure ulcers 3 days after ulceration, but increased 7 days later. Myofibroblast density was increased in the CAPE group 7 days after ulceration, but reduced 12 days later when compared to control group. In addition, CAPE promoted collagen deposition, re-epithelialization and wound closure of mice pressure ulcers 12 days after ulceration. SIGNIFICANCE CAPE brings forward inflammatory response and oxidative damage involved in injury by ischemia and reperfusion, promoting dermal reconstruction and closure of pressure ulcers.
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Affiliation(s)
- Bruna Romana-Souza
- Laboratory of Tissue Repair, Department of Histology and Embryology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
| | - Jeanine Salles Dos Santos
- Laboratory of Tissue Repair, Department of Histology and Embryology, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Andréa Monte-Alto-Costa
- Laboratory of Tissue Repair, Department of Histology and Embryology, State University of Rio de Janeiro, Rio de Janeiro, Brazil
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20
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da Silva JM, Conegundes JLM, Pinto NCC, Mendes RF, Castañon MCMN, Scio E. Comparative analysis of Lacistema pubescens and dexamethasone on topical treatment of skin inflammation in a chronic disease model and side effects. J Pharm Pharmacol 2018; 70:576-582. [DOI: 10.1111/jphp.12886] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2017] [Accepted: 01/03/2018] [Indexed: 12/20/2022]
Abstract
Abstract
Objectives
This study aimed to evaluate the chronic topical anti-inflammatory activity of the pharmaceutical formulation ProHLP containing the hexane fraction of Lacistema pubescens (HLP). It was also investigated the possible cutaneous and systemic adverse effects of HLP and ProHLP in mice when compared to dexamethasone.
Methods
The chronic topical anti-inflammatory activity was determined by croton oil multiple application-induced mouse ear oedema model. Histopathological analyses of ear tissue samples sensitized with croton oil were performed. Cutaneous atrophy induced by HLP and topical glucocorticoid treatments and excision skin wounds model to evidenced possible adverse reactions were also determined.
Key findings
ProHLP significantly reduced the mice ear oedema and considerably accelerated the wound-healing process. Also, HLP did not lead cutaneous atrophy and preserved the clinical aspect of the thymus, adrenal and spleen, unlike dexamethasone.
Conclusions
The results suggested that ProHLP is an efficient and safer pharmaceutical formulation to treat chronic inflammatory diseases.
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Affiliation(s)
- Josiane M da Silva
- Department of Biochemistry, Laboratory of Bioactive Natural Products, Biological Sciences Institute, Federal University of Juiz de Fora, Juiz De Fora, Brazil
| | - Jéssica L M Conegundes
- Department of Biochemistry, Laboratory of Bioactive Natural Products, Biological Sciences Institute, Federal University of Juiz de Fora, Juiz De Fora, Brazil
| | - Nícolas C C Pinto
- Department of Biochemistry, Laboratory of Bioactive Natural Products, Biological Sciences Institute, Federal University of Juiz de Fora, Juiz De Fora, Brazil
| | - Renata F Mendes
- Department of Biochemistry, Laboratory of Bioactive Natural Products, Biological Sciences Institute, Federal University of Juiz de Fora, Juiz De Fora, Brazil
| | - Maria Christina M N Castañon
- Department of Morphology, Biological Sciences Institute, Federal University of Juiz de Fora, Juiz de Fora, Brazil
| | - Elita Scio
- Department of Biochemistry, Laboratory of Bioactive Natural Products, Biological Sciences Institute, Federal University of Juiz de Fora, Juiz De Fora, Brazil
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21
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Li L, Sun W, Wu T, Lu R, Shi B. Caffeic acid phenethyl ester attenuates lipopolysaccharide-stimulated proinflammatory responses in human gingival fibroblasts via NF-κB and PI3K/Akt signaling pathway. Eur J Pharmacol 2016; 794:61-68. [PMID: 27832944 DOI: 10.1016/j.ejphar.2016.11.003] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2016] [Revised: 11/03/2016] [Accepted: 11/04/2016] [Indexed: 10/20/2022]
Abstract
Periodontal diseases often begin with chronic gingival inflammation, which causes the destruction of periodontal tissues. Inflammatory immune responses from host cells to bacteria, such as Porphyromonas gingivalis (P. gingivalis), cause periodontal degradation. Human gingival fibroblasts (HGFs) are the major cells in periodontal soft tissues. When stimulated by lipopolysaccharide (LPS), HGFs could secrete several pro-inflammatory cytokines and chemokines, such as interleukins (ILs) IL-6, IL-8, inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2). Caffeic acid phenethyl ester (CAPE) is the main active component of propolis, which is collected by honeybees from different plants and known for its anti-inflammatory effects. The anti-inflammatory effects of CAPE on the LPS-induced HGFs were demonstrated in this study. HGFs were pretreated with CAPE (10, 20, and 30µm) for 1h, followed by LPS stimulation (1μg/ml) for 24h. Enzyme-linked immunosorbent assay, Western blot analysis, and immunofluorescence staining were used to evaluate the production of IL-6, IL-8, iNOS, and COX-2, as well as the activation of TLR4-mediated NF-κB, PI3K/AKT, and MAPK signaling pathways. The results indicated that CAPE inhibits LPS-induced IL-6, IL-8, iNOS, and COX-2 production in a dose-dependent manner. Moreover, CAPE suppresses LPS-induced TLR4/MyD88 and nuclear factor kappa B (NF-κB) activation. In addition, phosphatidylinositol 3 kinase (PI3K) and protein kinase B (AKT) phosphorylation was inhibited by CAPE. These results demonstrated that CAPE could be effective for treating of periodontal diseases.
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Affiliation(s)
- Lei Li
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China
| | - Wei Sun
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China
| | - Tao Wu
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China
| | - Rui Lu
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China
| | - Bin Shi
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
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22
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Akram M, Shin I, Kim KA, Noh D, Baek SH, Chang SY, Kim H, Bae ON. A newly synthesized macakurzin C-derivative attenuates acute and chronic skin inflammation: The Nrf2/heme oxygenase signaling as a potential target. Toxicol Appl Pharmacol 2016; 307:62-71. [PMID: 27450019 DOI: 10.1016/j.taap.2016.07.013] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2016] [Revised: 07/11/2016] [Accepted: 07/19/2016] [Indexed: 11/26/2022]
Abstract
Impaired immune responses in skin play a pivotal role in the development and progression of chemical-associated inflammatory skin disorders. In this study, we synthesized new flavonoid derivatives from macakurzin C, and identified in vitro and in vivo efficacy of a potent anti-inflammatory flavonoid, Compound 14 (CPD 14), with its underlying mechanisms. In lipopolysaccharide (LPS)-stimulated murine macrophages and IFN-γ/TNF-α-stimulated human keratinocytes, CPD 14 significantly inhibited the release of inflammatory mediators including nitric oxide (NO), prostaglandins, and cytokines (IC50 for NO inhibition in macrophages: 4.61μM). Attenuated NF-κB signaling and activated Nrf2/HO-1 pathway were responsible for the anti-inflammatory effects of CPD 14. The in vivo relevance was examined in phorbol 12-myristate 13-acetate (TPA)-induced acute skin inflammation and oxazolone-induced atopic dermatitis models. Topically applied CPD 14 significantly protected both irritation- and sensitization-associated skin inflammation by suppressing the expression of inflammatory mediators. In summary, we demonstrated that a newly synthesized flavonoid, CPD 14, has potent inhibitory effects on skin inflammation, suggesting it is a potential therapeutic candidate to treat skin disorders associated with excessive inflammation.
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Affiliation(s)
- Muhammad Akram
- College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Republic of Korea
| | - Iljin Shin
- College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, Republic of Korea
| | - Kyeong-A Kim
- College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Republic of Korea
| | - Dabi Noh
- College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Republic of Korea
| | - Seung-Hoon Baek
- College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, Republic of Korea
| | - Sun-Young Chang
- College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, Republic of Korea
| | - Hyoungsu Kim
- College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, Republic of Korea.
| | - Ok-Nam Bae
- College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Republic of Korea.
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23
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Yoo SR, Seo CS, Lee NR, Shin HK, Jeong SJ. Phytochemical Analysis on Quantification and the Inhibitory Effects on Inflammatory Responses from the Fruit of Xanthii fructus. Pharmacogn Mag 2016; 11:S585-91. [PMID: 27013799 PMCID: PMC4787093 DOI: 10.4103/0973-1296.172966] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Objective: Xanthii fructus (Compositae) is a traditional herbal medicine used for treating headache, toothache, pruritus, empyema, and rhinitis. In this study of the quality control of X. fructus, we performed simultaneous analysis of nine marker compounds: Protocatechuic acid (1), chlorogenic acid (2), caffeic acid (3), 4,5-dicaffeoylquinic acid (4), ferulic acid (5), 3,5-dicaffeoylquinic acid (6), 1,3-dicaffeoylquinic acid (7), 1,4-dicaffeoylquinic acid (8), and 4,5-dicaffeoylquinic acid (9). Materials and Methods: Nine components were separated using reversed-phase SunFire™ C18 analytical column and analyzed using high-performance liquid chromatography. We examined the biological effects of the nine marker compounds by determining their anti-inflammatory activities in the murine macrophage cell line RAW 264.7. Results: Among the nine marker compounds, eight significantly inhibited lipopolysaccharide (LPS)-stimulated tumor necrosis factor-alpha (TNF-α) production. 1, 3, 5 had significant inhibitory effects on LPS-induced prostaglandin E2 (PGE2) production in RAW 264.7 cells. None of the tested marker compounds had a significant effect on interleukin-6 production in LPS-treated RAW 264.7 cells. Our data demonstrated that each marker compound from X. fructus exerts anti-inflammatory activity by targeting different inflammation-related pathways such as the TNF-α or PGE2 pathway. Conclusion: Further experiments using in vitro and in vivo models are needed to identify the mechanisms responsible for the anti-inflammatory properties of each marker compound. SUMMARY
Simultaneous analysis of nine phenylpropanoids in the Xanthii fructus was established using HPLC-PDA system. 1,4-dicaffeoylquinic acid significantly inhibited LPS-stimulated TNF-a production. Protocatechuic acid, caffeic acid and ferulic acid had significant inhibitory effects on LPS-induced PGE2 production in RAW 264.7 cells.
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Affiliation(s)
- Sae-Rom Yoo
- K-herb Research Center, Daejeon, Republic of Korea
| | | | - Na-Ri Lee
- K-herb Research Center, Daejeon, Republic of Korea
| | | | - Soo-Jin Jeong
- KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; Korean Medicine Life Science, University of Science and Technology, Daejeon, Republic of Korea
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