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Owczarek M, Herczyńska L, Sitarek P, Kowalczyk T, Synowiec E, Śliwiński T, Krucińska I. Chitosan Nanoparticles-Preparation, Characterization and Their Combination with Ginkgo biloba Extract in Preliminary In Vitro Studies. Molecules 2023; 28:4950. [PMID: 37446611 DOI: 10.3390/molecules28134950] [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: 04/11/2023] [Revised: 06/16/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
Nanoparticles (NPs), due to their size, have a key position in nanotechnology as a spectrum of solutions in medicine. NPs improve the ability of active substances to penetrate various routes: transdermal, but also digestive (active endocytosis), respiratory and injection. Chitosan, an N-deacetylated derivative of chitin, is a natural biodegradable cationic polymer with antioxidant, anti-inflammatory and antimicrobial properties. Cross-linked chitosan is an excellent matrix for the production of nanoparticles containing active substances, e.g., the Ginkgo biloba extract (GBE). Chitosan nanoparticles with the Ginkgo biloba extract (GBE) were obtained by ion gelation using TPP as a cross-linking agent. The obtained product was characterized in terms of morphology and size based on SEM and Zeta Sizer analyses as well as an effective encapsulation of GBE in nanoparticles-FTIR-ATR and UV-Vis analyses. The kinetics of release of the active substance in water and physiological saline were checked. Biological studies were carried out on normal and cancer cell lines to check the cytotoxic effect of GBE, chitosan nanoparticles and a combination of the chitosan nanoparticles with GBE. The obtained nanoparticles contained and released GBE encapsulated in research media. Pure NPs, GBE and a combination of NPs and the extract showed cytotoxicity against tumor cells, with no cytotoxicity against the physiological cell line.
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Affiliation(s)
- Monika Owczarek
- Łukasiewicz Research Network-Lodz Institute of Technology, Skłodowskiej-Curie 19/27, 90-570 Lodz, Poland
- Institute of Materials Science of Textiles and Polymer Composites, Faculty of Material Technologies and Textile Design, Lodz University of Technology, Żeromskiego 116, 90-924 Lodz, Poland
| | - Lucyna Herczyńska
- Institute of Materials Science of Textiles and Polymer Composites, Faculty of Material Technologies and Textile Design, Lodz University of Technology, Żeromskiego 116, 90-924 Lodz, Poland
| | - Przemysław Sitarek
- Department of Medical Biology, Medical University of Lodz, ul. Muszyńskiego 1, 90-151 Lodz, Poland
| | - Tomasz Kowalczyk
- Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland
| | - Ewelina Synowiec
- Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland
| | - Tomasz Śliwiński
- Department of Medical Biochemistry, Medical University of Lodz, 90-001 Lodz, Poland
| | - Izabella Krucińska
- Institute of Materials Science of Textiles and Polymer Composites, Faculty of Material Technologies and Textile Design, Lodz University of Technology, Żeromskiego 116, 90-924 Lodz, Poland
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Hu WH, Chan GKL, Duan R, Wang HY, Kong XP, Dong TTX, Tsim KWK. Synergy of Ginkgetin and Resveratrol in Suppressing VEGF-Induced Angiogenesis: A Therapy in Treating Colorectal Cancer. Cancers (Basel) 2019; 11:cancers11121828. [PMID: 31757048 PMCID: PMC6966653 DOI: 10.3390/cancers11121828] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 10/18/2019] [Accepted: 10/21/2019] [Indexed: 12/22/2022] Open
Abstract
Ginkgetin, a biflavone from Ginkgo biloba leaf, and resveratrol, a polyphenol found in grape and wine, are two phytochemicals being identified for its binding to vascular endothelial growth factor (VEGF): the binding, therefore, resulted in the alteration of the physiological roles of VEGF-mediated angiogenesis. The bindings of ginkgetin and resveratrol were proposed on different sites of VEGF, but both of them suppressed the angiogenic properties of VEGF. The suppressive activities of ginkgetin and resveratrol in VEGF-mediated angiogenesis were supported by several lines of evidence including (i) inhibiting the formation of sub-intestinal vessel in zebrafish embryos and microvascular sprouting in rat aortic ring; and (ii) suppressing the phosphorylations of VEGFR2, Akt, eNOS, and Erk as well as expressions of matrix metalloproteinases (MMPs), MMP-2, and MMP-9 in human umbilical vein endothelial cells (HUVECs). Here, we showed the synergy of ginkgetin and resveratrol in suppressing the VEGF-induced endothelial cell proliferation, migration, invasion, and tube formation. The synergy of ginkgetin and resveratrol was further illustrated in HT-29 colon cancer xenograft nude mice. Ginkgetin and resveratrol, when applied together, exerted a synergistic anti-tumor effect of 5-fluorouracil with decreasing microvessel density of tumors. In parallel, the combination of ginkgetin and resveratrol synergistically relieved the 5-fluorouracil-induced inflammatory response by suppressing expressions of COX-2 and inflammatory cytokines. Thus, the anti-angiogenic roles of ginkgetin and/or resveratrol could provide effective therapeutic strategy in cancer, similar to that of Avastin, in suppressing the VEGF-mediated angiogenesis during cancer development.
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Affiliation(s)
- Wei-Hui Hu
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Nanshan, Shenzhen 518057, China; (W.-H.H.); (G.K.-L.C.); (R.D.); (H.-Y.W.); (X.-P.K.); (T.T.-X.D.)
- Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong 999077, China
| | - Gallant Kar-Lun Chan
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Nanshan, Shenzhen 518057, China; (W.-H.H.); (G.K.-L.C.); (R.D.); (H.-Y.W.); (X.-P.K.); (T.T.-X.D.)
- Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong 999077, China
| | - Ran Duan
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Nanshan, Shenzhen 518057, China; (W.-H.H.); (G.K.-L.C.); (R.D.); (H.-Y.W.); (X.-P.K.); (T.T.-X.D.)
- Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong 999077, China
| | - Huai-You Wang
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Nanshan, Shenzhen 518057, China; (W.-H.H.); (G.K.-L.C.); (R.D.); (H.-Y.W.); (X.-P.K.); (T.T.-X.D.)
- Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong 999077, China
| | - Xiang-Peng Kong
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Nanshan, Shenzhen 518057, China; (W.-H.H.); (G.K.-L.C.); (R.D.); (H.-Y.W.); (X.-P.K.); (T.T.-X.D.)
- Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong 999077, China
| | - Tina Ting-Xia Dong
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Nanshan, Shenzhen 518057, China; (W.-H.H.); (G.K.-L.C.); (R.D.); (H.-Y.W.); (X.-P.K.); (T.T.-X.D.)
- Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong 999077, China
| | - Karl Wah-Keung Tsim
- Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Hi-Tech Park, Nanshan, Shenzhen 518057, China; (W.-H.H.); (G.K.-L.C.); (R.D.); (H.-Y.W.); (X.-P.K.); (T.T.-X.D.)
- Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong 999077, China
- Correspondence: ; Tel.: +852-2358-7332; Fax: +852-2358-1552
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Coelho MC, Sanchez PKV, Fernandes RR, Souza FPPD, Siéssere S, Bombonato-Prado KF. Effect of grape seed extract (GSE) on functional activity and mineralization of OD-21 and MDPC-23 cell lines. Braz Oral Res 2019; 33:e013. [PMID: 30758410 DOI: 10.1590/1807-3107bor-2019.vol33.0013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Accepted: 01/14/2019] [Indexed: 11/21/2022] Open
Abstract
Recent studies on functional tissue regeneration have focused on substances that favor cell proliferation and differentiation, including the bioactive phenolic compounds present in grape seed extract (GSE). The aim of this investigation was to evaluate the stimulatory potential of GSE in the functional activity of undifferentiated pulp cells and odontoblast-like cells. OD-21 and MDPC-23 cell lines were cultivated in odontogenic medium until subconfluence, seeded in 24-well culture plates in a concentration of 2x104/well and divided into: 1) OD-21 without GSE; 2) OD-21+10 µg/mL of GSE; 3) MDPC-23 without GSE; 4) MDPC-23+10 µg/mL of GSE. Cell proliferation, in situ detection of alkaline phosphatase (ALP) and total protein content were assessed after 3, 7 and 10 days, and mineralization was evaluated after 14 days. The data were analyzed by ANOVA statistical tests set at a 5% level of significance. Results revealed that cell proliferation increased after 10 days, and protein content, after 7 days of culture in MDPC-23 cells. In situ ALP staining intensity was higher in undifferentiated pulp cells and odontoblast-like cells after 7 and 10 days, respectively. A discrete increase in MDPC-23 mineralization after GSE treatment was observed despite OD-21 cells presenting a decrease in mineralized nodule deposits. Data suggest that GSE favors functional activity of differentiated cells more broadly than undifferentiated cells (OD-21). More studies with different concentrations of GSE must be conducted to confirm its benefits to cells regarding dentin regeneration.
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Affiliation(s)
- Maria Carolina Coelho
- Universidade de São Paulo - USP, School of Dentistry of Ribeirão Preto, Department of Basic and Oral Biology, Ribeirão Preto, SP, Brazil
| | - Paula Katherine Vargas Sanchez
- Universidade de São Paulo - USP, School of Dentistry of Ribeirão Preto, Department of Basic and Oral Biology, Ribeirão Preto, SP, Brazil
| | - Roger Rodrigo Fernandes
- Universidade de São Paulo - USP, School of Dentistry of Ribeirão Preto, Department of Oral and Maxillofacial Surgery and Periodontology, Ribeirão Preto, SP, Brazil
| | - Fernanda Panzeri Pires de Souza
- Universidade de São Paulo - USP, School of Dentistry of Ribeirão Preto, Department of Dental Materials and Prosthesis, Ribeirão Preto, SP, Brazil
| | - Selma Siéssere
- Universidade de São Paulo - USP, School of Dentistry of Ribeirão Preto, Department of Basic and Oral Biology, Ribeirão Preto, SP, Brazil
| | - Karina Fittipaldi Bombonato-Prado
- Universidade de São Paulo - USP, School of Dentistry of Ribeirão Preto, Department of Basic and Oral Biology, Ribeirão Preto, SP, Brazil
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Transdermal Hydrogel Composed of Polyacrylic Acid Containing Propolis for Wound Healing in a Rat Model. Macromol Res 2018. [DOI: 10.1007/s13233-019-7014-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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Yang S, Qu R, Zhu Z, Li W, Zhao C, Li L. Validated LC-MS/MS method for the quantification of sciadopitysin in rat plasma and its application to pharmacokinetic and bioavailability studies in vivo. Biomed Chromatogr 2018; 32:e4241. [PMID: 29575000 DOI: 10.1002/bmc.4241] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2017] [Revised: 03/06/2018] [Accepted: 03/12/2018] [Indexed: 11/08/2022]
Abstract
A sensitive and rapid LC-MS/MS method was developed and validated for quantitation of sciadopitysin in rat plasma using amentoflavone as an internal standard. Sample processing was accomplished after deproteinization with 150 μL aliquot of acetonitrile. Chromatographic separation was achieved using an Agela C18 column with an isocratic mobile phase comprising 2 mm ammonium acetate-acetonitrile (35:65, v/v) at a flow rate of 0.4 mL/min. Detection was performed by selection reaction monitoring on a triple-quadrupole mass spectrometer following the transitions m/z 579 → 547 and 537 → 375 for sciadopitysin and internal standard, respectively, in the negative ionization mode. The calibration curve was linear from 2.90 to 1160 ng/mL for sciadopitysin. Intra- and inter-day precisions were in the ranges 4.1-11.4 and 5.7-9.1% for sciadopitysin. Sciadopitysin was stable under different stability conditions. The validated assay was applied to pharmacokinetic and bioavailability studies in rats.
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Affiliation(s)
| | - Ruiying Qu
- Jiaozhou People's Hospital, Qingdao, China
| | - Zhe Zhu
- Hand and Foot Surgery and Reparative and Reconstruction Surgery Center, Department of Orthopaedics, the Second Hospital of Jilin University, Changchun, China
| | - Wei Li
- Department of Emergency, the First Hospital of Jilin University, Changchun, China
| | - Chengliang Zhao
- Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Liantai Li
- Affiliated Hospital of Chengde Medical University, Chengde, China
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Silva APPD, Gonçalves RS, Borges AFS, Bedran-Russo AK, Shinohara MS. Effectiveness of plant-derived proanthocyanidins on demineralization on enamel and dentin under artificial cariogenic challenge. J Appl Oral Sci 2015. [PMID: 26221925 PMCID: PMC4510665 DOI: 10.1590/1678-775720140304] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Dental caries is considered a disease of high prevalence and a constant problem in public health. Proanthocyanidins (PAs) are substances that have been the target of recent studies aiming to control or treat caries.
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Affiliation(s)
- Ana Paula Pereira da Silva
- Department of Restorative Dentistry, Araçatuba Dental School, Univ. Estadual Paulista, Araçatuba, SP, Brazil
| | - Rafael Simões Gonçalves
- Department of Dentistry, Endodontic and Dental Materials, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil
| | - Ana Flávia Sanches Borges
- Department of Dentistry, Endodontic and Dental Materials, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil
| | - Ana Karina Bedran-Russo
- Department of Restorative Dentistry, College of Dentistry, University of Illinois, Chicago, IL, USA
| | - Mirela Sanae Shinohara
- Department of Restorative Dentistry, Araçatuba Dental School, Univ. Estadual Paulista, Araçatuba, SP, Brazil
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Choi M, Oh JH, Shin MK, Lee SR, Lee DH, Jin SP, Cho S, Chung JH. Beneficial effects of blood group antigen synthesis-increasing natural plant extracts and monosaccharides on extracellular matrix protein production in vivo. J Dermatol Sci 2015; 80:152-5. [PMID: 26314866 DOI: 10.1016/j.jdermsci.2015.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Revised: 06/25/2015] [Accepted: 08/11/2015] [Indexed: 10/23/2022]
Affiliation(s)
- Mira Choi
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea
| | - Jang-Hee Oh
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea
| | - Min Kyeong Shin
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea
| | - Se-Rah Lee
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea
| | - Dong Hun Lee
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea
| | - Seon-Pil Jin
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea
| | - Soyun Cho
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea; Department of Dermatology, Seoul National University Boramae Hospital, Seoul, Republic of Korea.
| | - Jin Ho Chung
- Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea; SNU Institute on Aging, Seoul, Republic of Korea.
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Jeon YJ, Jung SN, Yun J, Lee CW, Choi J, Lee YJ, Han DC, Kwon BM. Ginkgetin inhibits the growth of DU-145 prostate cancer cells through inhibition of signal transducer and activator of transcription 3 activity. Cancer Sci 2015; 106:413-20. [PMID: 25611086 PMCID: PMC4409885 DOI: 10.1111/cas.12608] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2014] [Revised: 01/07/2015] [Accepted: 01/09/2015] [Indexed: 12/26/2022] Open
Abstract
Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in human cancers. Therefore, STAT3 is a therapeutic target of cancer drug discovery. We previously reported that natural products inhibited constitutively activated STAT3 in human prostate tumor cells. We used a dual-luciferase assay to screen 200 natural products isolated from herbal medicines and we identified ginkgetin obtained from the leaves of Ginkgo biloba L. as a STAT3 inhibitor. Ginkgetin inhibited both inducible and constitutively activated STAT3 and blocked the nuclear translocation of p-STAT3 in DU-145 prostate cancer cells. Furthermore, ginkgetin selectively inhibited the growth of prostate tumor cells stimulated with activated STAT3. Ginkgetin induced STAT3 dephosphorylation at Try705 and inhibited its localization to the nucleus, leading to the inhibition of expression of STAT3 target genes such as cell survival-related genes (cyclin D1 and survivin) and anti-apoptotic proteins (Bcl-2 and Bcl-xL). Therefore, ginkgetin inhibited the growth of STAT3-activated tumor cells. We also found that ginkgetin inhibited tumor growth in xenografted nude mice and downregulated p-STAT3(Tyr705) and survivin in tumor tissues. This is the first report that ginkgetin exerts antitumor activity by inhibiting STAT3. Therefore, ginkgetin is a good STAT3 inhibitor and may be a useful lead molecule for development of a therapeutic STAT3 inhibitor.
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Affiliation(s)
- Yoon Jung Jeon
- Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea; Korea University of Science and Technology, Daejeon, Korea
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Poon F, Kang S, Chien AL. Mechanisms and treatments of photoaging. PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE 2014; 31:65-74. [PMID: 25351668 DOI: 10.1111/phpp.12145] [Citation(s) in RCA: 145] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 10/20/2014] [Indexed: 01/16/2023]
Abstract
Photoaging is frequently encountered in a dermatologic practice. This systematic literature review aims to explore the etiology of photoaging and address the evidence behind its current management. A comprehensive search of MEDLINE, EMBASE, UpToDate, and the Cochrane Library was conducted. Articles were limited to those relating to photoaging. There are two major approaches in the current management of photoaging. This includes strategies to prevent against ultraviolet damage (e.g. sunscreen) and medications that attempt to reverse existing skin damage (topical retinoids and 5-fluorouracil). There has been a large growth in the variety of treatment options in recent years. While it is important for such growth to continue, prevention via sensible photoprotection methods still remains the best current management option.
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Affiliation(s)
- Flora Poon
- Department of Dermatology, Royal Melbourne Hospital, Melbourne, VIC, Australia; Department of Dermatology, Johns Hopkins Hospital, Baltimore, MD, USA
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Castangia I, Nácher A, Caddeo C, Valenti D, Fadda AM, Díez-Sales O, Ruiz-Saurí A, Manconi M. Fabrication of quercetin and curcumin bionanovesicles for the prevention and rapid regeneration of full-thickness skin defects on mice. Acta Biomater 2014; 10:1292-300. [PMID: 24239901 DOI: 10.1016/j.actbio.2013.11.005] [Citation(s) in RCA: 103] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2013] [Revised: 10/16/2013] [Accepted: 11/08/2013] [Indexed: 12/17/2022]
Abstract
In the present work biocompatible quercetin and curcumin nanovesicles were developed as a novel approach to prevent and restore skin tissue defects on chronic cutaneous pathologies. Stable and suitable quercetin- and curcumin-loaded phospholipid vesicles, namely liposomes and penetration enhancer-containing vesicles (PEVs), were prepared. Vesicles were made from a highly biocompatible mixture of phospholipids and alternatively a natural polyphenol, quercetin or curcumin. Liposomes were obtained by adding water, while PEVs by adding polyethylene glycol 400 and Oramix®CG110 to the water phase. Transmission electron microscopy, cryogenic-transmission electron microscopy and small- and wide-angle X-ray scattering showed that vesicles were spherical, oligo- or multilamellar and small in size (112-220 nm). In vitro and in vivo tests underlined a good effectiveness of quercetin and curcumin nanovesicles in counteracting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induced lesions and inflammation. Myeloperoxydase activity, used to gauge inflammation, was markedly inhibited by quercetin liposomes (59%) and curcumin liposomes and polyethylene glycol (PEG)-PEVs (∼ 68%). Histology showed that PEG-PEVs provided an extensive re-epithelization of the TPA-damaged skin, with multiple layers of thick epidermis. In conclusion, nanoentrapped polyphenols prevented the formation of skin lesions abrogating the various biochemical processes that cause epithelial loss and skin damage.
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Czemplik M, Kulma A, Bazela K, Szopa J. The biomedical potential of genetically modified flax seeds overexpressing the glucosyltransferase gene. Altern Ther Health Med 2012; 12:251. [PMID: 23228136 PMCID: PMC3640942 DOI: 10.1186/1472-6882-12-251] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2012] [Accepted: 12/07/2012] [Indexed: 11/10/2022]
Abstract
Background Flax (Linum usitatissimum) is a potential source of many bioactive components that can be found in its oil and fibers, but also in the seedcake, which is rich in antioxidants. To increase the levels of medically beneficial compounds, a genetically modified flax type (named GT) with an elevated level of phenylopropanoids and their glycoside derivatives was generated. In this study, we investigated the influence of GT seedcake extract preparations on human fibroblast proliferation and migration, and looked at the effect on a human skin model. Moreover, we verified its activity against bacteria of clinical relevance. Methods The GT flax used in this study is characterized by overexpression of the glucosyltransferase gene derived from Solanum sogarandinum. Five GT seedcake preparations were generated. Their composition was assessed using ultra pressure liquid chromatography and confirmed using the UPLC-QTOF method. For the in vitro evaluation, the influence of the GT seedcake preparations on normal human dermal fibroblast proliferation was assessed using the MTT test and the wound scratch assay. A human skin model was used to evaluate the potential for skin irritation. To assess the antimicrobial properties of GT preparations, the percentage of inhibition of bacterial growth was calculated. Results The GT seedcake extract had elevated levels of phenylopropanoid compounds in comparison to the control, non-transformed plants. Significant increases in the content of ferulic acid, p-coumaric acid and caffeic acid, and their glucoside derivatives, kaempferol, quercitin and secoisolariciresinol diglucoside (SDG) were observed in the seeds of the modified plants. The GT seedcake preparations were shown to promote the proliferation of normal human dermal fibroblasts and the migration of fibroblasts in the wound scratch assay. The superior effect of GT seedcake extract on fibroblast migration was observed after a 24-hour treatment. The skin irritation test indicated that GT seedcake preparations have no harmful effect on human skin. Moreover, GT seedcake preparations exhibited inhibitory properties toward two bacterial strains: Staphylococcus aureus and Escherichia coli. Conclusions We suggest that preparations derived from the new GT flax are an effective source of phenylopropanoids and that their glycoside derivatives and might be promising natural products with both healing and bacteriostatic effects. This flax-derived product is a good candidate for application in the repair and regeneration of human skin and might also be an alternative to antibiotic therapy for infected wounds.
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Effects of methanolic extracts from broad beans on cellular growth and antioxidant enzyme activity. Environ Health Prev Med 2012; 12:251-7. [PMID: 21432071 DOI: 10.1007/bf02898032] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2007] [Accepted: 09/18/2007] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE There are several reports of cellular-aging-dependent alterations in the antioxidant capacity of human fibroblasts. Fibroblasts show slower the growth rate at late passages (referred to hereafter as old cells) than at early passages (referred to hereafter as young cells). Antioxidants may control cellular growth by modulating reactive oxygen species (ROS). Methanolic extracts from broad beans (MEBB) contain phenolic compounds and have ROS-scavenging activities. In this study, we investigated the effects of MEBB on cellular growth and antioxidant levels in normal human lung fibroblasts. METHODS To determine cytosolic superoxide dismutase (SOD) activities, cytosolic glutathione peroxidase (GSH-Px) activities, catalase activities, reduced glutathione (GSH) concentrations, and growth rate, MEBB treatments were performed on young and old cells. RESULTS In young and old cells treated with 120 μg/ml MEBB, the growth rates increased by 28.1 and 15.2%, respectively, compared with controls. The MEBB treatment of young cells caused a 62.5% increase in SOD activity, but the treatment of old cells caused a 39.5% decrease. The catalase activities of the young and old cells treated with MEBB were equal to those of control cells. Young and old cells treated with MEBB were equal to the control cells in terms of GSH-Px activity. The GSH concentrations in the young and old cells treated with 120 μg/ml MEBB increased by 22.1 and 45.9%, respectively. CONCLUSION These studies elucidated a new cellular growth mechanism whereby human lung fibroblasts modulate intracellular GSH levels via the action of MEBB.
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Abstract
The need for cosmeceutical research is ever present. This article has tried to highlight the chemistry of botanic extracts in the current marketplace and review the best research available. In some ways, more questions have been raised than answered; yet, ideas for intellectual discourse have been provided. Herein lies the physician cosmeceutical challenge.
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Affiliation(s)
- Zoe Diana Draelos
- Department of Dermatology, Duke University School of Medicine, Durham, NC, USA.
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Adetutu A, Morgan WA, Corcoran O. Antibacterial, antioxidant and fibroblast growth stimulation activity of crude extracts of Bridelia ferruginea leaf, a wound-healing plant of Nigeria. JOURNAL OF ETHNOPHARMACOLOGY 2011; 133:116-119. [PMID: 20863876 DOI: 10.1016/j.jep.2010.09.011] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2010] [Revised: 08/18/2010] [Accepted: 09/15/2010] [Indexed: 05/29/2023]
Abstract
AIM OF THE STUDY Determination of pharmacological activity relevant to wound healing of Bridelia ferruginea leaf, a traditional medicine used to treat wounds in rural Nigeria. MATERIALS AND METHODS Aqueous and ethanolic leaf extracts were tested against bacterial species of relevance to wound infections: Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa. The ethanolic extracts were assessed for their ability to stimulate the growth of human dermal fibroblasts (FS5) and protect against damage induced by hydrogen peroxide. Antioxidant activity was also assessed using the DPPH assay. RESULTS Both aqueous and ethanolic extracts had weak antibacterial activity (MIC>470 μg/ml). A significant effect (p<0.001) on the growth of FS5 fibroblasts was observed only at a concentration of 5 μg/ml (28% increase), above which the extracts appeared toxic to the cells. The ethanolic extract offered the highest protection against H(2)O(2) damage to FS5 cells, comparable with catalase (82% at 250 μg/ml). The DPPH assay revealed antioxidant activity of the ethanolic leaf extract with IC(50) 12.5±0.3 μg/ml comparable to l-ascorbic acid (7.3±0.1 μg/ml). CONCLUSION The antibacterial, modest fibroblast stimulation activity and relatively strong antioxidant activity lend some support to the topical use of Bridelia ferruginea leaf for wound-healing in the traditional medicine of South-western Nigeria.
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Affiliation(s)
- Adewale Adetutu
- School of Health and Bioscience, University of East London, London, United Kingdom.
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15
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16
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van Patot MCT, Keyes LE, Leadbetter G, Hackett PH. Ginkgo bilobafor Prevention of Acute Mountain Sickness: Does It Work? High Alt Med Biol 2009; 10:33-43. [DOI: 10.1089/ham.2008.1085] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Affiliation(s)
- Martha C. Tissot van Patot
- Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado
- Altitude Research Center, Division of Emergency Medicine, Department of Surgery, University of Colorado, Denver Colorado
| | - Linda E. Keyes
- Altitude Research Center, Division of Emergency Medicine, Department of Surgery, University of Colorado, Denver Colorado
| | - Guy Leadbetter
- Department of Exercise Physiology, Mesa State College, Grand Junction, Colorado
| | - Peter H. Hackett
- Altitude Research Center, Division of Emergency Medicine, Department of Surgery, University of Colorado, Denver Colorado
- Institute for Altitude Medicine, Telluride, Colorado
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O'Brien K, Matlin AJ, Lowell AM, Moore MJ. The biflavonoid isoginkgetin is a general inhibitor of Pre-mRNA splicing. J Biol Chem 2008; 283:33147-54. [PMID: 18826947 PMCID: PMC2586251 DOI: 10.1074/jbc.m805556200] [Citation(s) in RCA: 156] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Membrane-permeable compounds that reversibly inhibit a particular step in
gene expression are highly useful tools for cell biological and
biochemical/structural studies. In comparison with other gene expression steps
where multiple small molecule effectors are available, very few compounds have
been described that act as general inhibitors of pre-mRNA splicing. Here we
report construction and validation of a set of mammalian cell lines suitable
for the identification of small molecule inhibitors of pre-mRNA splicing.
Using these cell lines, we identified the natural product isoginkgetin as a
general inhibitor of both the major and minor spliceosomes. Isoginkgetin
inhibits splicing both in vivo and in vitro at similar
micromolar concentrations. It appears to do so by preventing stable
recruitment of the U4/U5/U6 tri-small nuclear ribonucleoprotein, resulting in
accumulation of the prespliceosomal A complex. Like two other recently
reported general pre-mRNA splicing inhibitors, isoginkgetin has been
previously described as an anti-tumor agent. Our results suggest that splicing
inhibition is the mechanistic basis of the anti-tumor activity of
isoginkgetin. Thus, pre-mRNA splicing inhibitors may represent a novel avenue
for development of new anti-cancer agents.
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Affiliation(s)
- Kristine O'Brien
- Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA
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18
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Biochemical pharmacology of biflavonoids: Implications for anti-inflammatory action. Arch Pharm Res 2008; 31:265-73. [DOI: 10.1007/s12272-001-1151-3] [Citation(s) in RCA: 86] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2007] [Indexed: 11/26/2022]
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Chan PC, Xia Q, Fu PP. Ginkgo biloba leave extract: biological, medicinal, and toxicological effects. JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH. PART C, ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS 2007; 25:211-44. [PMID: 17763047 DOI: 10.1080/10590500701569414] [Citation(s) in RCA: 173] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/13/2023]
Abstract
Ginkgo biloba leave extract is among the most widely sold herbal dietary supplements in the United States. Its purported biological effects include: scavenging free radical; lowering oxidative stress; reducing neural damages, reducing platelets aggregation; anti-inflammation; anti-tumor activities; and anti-aging. Clinically, it has been prescribed to treat CNS disorders such as Alzheimer's disease and cognitive deficits. It exerts allergy and changes in bleeding time. While its mutagenicity or carcinogenic activity has not been reported, its components, quercetin, kaempferol and rutin have been shown to be genotoxic. There are no standards or guidelines regulating the constituent components of Ginkgo biloba leave extract nor are exposure limits imposed. Safety evaluation of Ginkgo biloba leave extract is being conducted by the U.S. National Toxicology Program.
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Affiliation(s)
- Po-Chuen Chan
- National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
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20
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Kisli E, Ozdemir H, Kösem M, Sürer H, Ciftçi A, Kanter M. Effect of Ginkgo biloba Extract (EGb 761) on the Healing of Left Colonic Anastomoses in Rat. World J Surg 2007; 31:1652-7. [PMID: 17578646 DOI: 10.1007/s00268-007-9049-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND The aim of this study was to assess the effect of Ginkgo biloba extract (EGb 761) on healing of experimental colonic anastomoses in a rat model. METHODS Rats were divided into four groups: postoperative day (POD) 3 untreated control group, POD 3 EGb 761 group, POD 7 untreated control group, and POD 7 EGb 761 group. In the oral EGb 761 groups, the agent was given at 9.6 mg daily per orogastric route using a 4-F fine feeding catheter. We measured bursting pressures and hydroxyproline content and histologically examined the resected anastomoses on POD 3 and POD 7. RESULTS The bursting pressures increased more in the EGb 761 group than in the untreated control group on POD 3, but this difference was not statistically significant. Hydroxyproline content was higher in the EGb 761 group than in the untreated control group on POD 3, and this difference was statistically significant. Anastomosis bursting pressure values and hydroxyproline contents were significantly higher in the EGb 761 group than in the untreated control group on POD 7. Histological examination showed greater fibroblastic activity in the EGb 761 group than in the untreated control group on POD 3. There was no significant difference in anastomotic polimorphonuclear leukocyte, mononuclear cells and blood vessel neodevelopment between the POD 3 groups, but there was significant difference in fibroblastic activity and blood vessel neodevelopment between the POD 7 groups. CONCLUSIONS These results showed us that EGb 761 administration resulted in enhanced stability of colonic anastomoses during the first postoperative week.
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Affiliation(s)
- Erol Kisli
- Department of General Surgery, School of Medicine, Yüzüncü Yil University, Van, Turkey.
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Tian YM, Tian HJ, Zhang GY, Dai YR. Effects of Ginkgo biloba extract (EGb 761) on hydroxyl radical-induced thymocyte apoptosis and on age-related thymic atrophy and peripheral immune dysfunctions in mice. Mech Ageing Dev 2004; 124:977-83. [PMID: 14499503 DOI: 10.1016/s0047-6374(03)00170-2] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
In this study, the effect of EGb 761, a standard extract of Ginkgo biloba leaf, on thymocyte apoptosis and age-related thymic atrophy and on peripheral immune dysfunctions was investigated in mice. When primary culture of thymocytes was preincubated with 100 microg/ml EGb 761 before their exposure to hydroxyl radicals (*OH) generated by Fe(2+)-mediated Fenton reaction, apoptotic cell death induced by *OH was distinctly prevented as determined by DNA laddering, the TUNEL assay and flow cytometric analysis. Furthermore, oral EGb 761 administration (about 1.5 mg/day/mouse) for 60 consecutive days led to a significant thymic regrowth in 22-month-old mice as revealed by the increment of thymus weight and total numbers of thymocytes. Partial recovery of peripheral immune capacities such as mitogen responsiveness and NK cell activity were also found in the old mice after 60 days of EGb 761 supplementation. Taken together, our study indicates that in addition to its protective and rescuing abilities on neurodegenerative disorders and cardiovascular diseases, EGb 761 was also found active in the rejuvenation of degenerated thymus and accordingly the strengthening of the immune system. These beneficial effects of EGb 761 on immune system are based on its antioxidant properties as well as the cell proliferation-stimulating effect.
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Affiliation(s)
- Yan-Mei Tian
- Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, PR China
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22
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Chao JCJ, Chu CC. Effects of Ginkgo biloba extract on cell proliferation and cytotoxicity in human hepatocellular carcinoma cells. World J Gastroenterol 2004; 10:37-41. [PMID: 14695765 PMCID: PMC4717074 DOI: 10.3748/wjg.v10.i1.37] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To study the effect of Ginkgo biloba extract (EGb 761) containing 22%-27% flavonoids (ginkgo-flavone glycosides) and 5%-7% terpenoids (ginkgolides and bilobalides) on cell proliferation and cytotoxicity in human hepatocellular carcinoma (HCC) cells.
METHODS: Human HCC cell lines (HepG2 and Hep3B) were incubated with various concentrations (0-1000 mg/L) of EGb 761 solution. After 24 h incubation, cell proliferation and cytotoxicity were determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and lactate dehydrogenase (LDH) release, respectively. After 48 h incubation, the expression of proliferating cell nuclear antigen (PCNA) and p53 protein was measured by Western blotting.
RESULTS: The results showed that EGb 761 (50-1000 mg/L) significantly suppressed cell proliferation and increased LDH release (P < 0.05) in HepG2 and Hep3B cells compared with the control group. The cell proliferation of HepG2 and Hep3B cells treated with EGb 761 (1000 mg/L) was 45% and 39% of the control group (P < 0.05), respectively. LDH release of HepG2 cells without and with EGb 761 (1000 mg/L) treatment was 6.7% and 37.7%, respectively, and that of Hep3B cells without and with EGb 761 (1000 mg/L) treatment was 7.2% and 40.3%, respectively. The expression of PCNA and p53 protein in HepG2 cells treated with EGb 761 (1000 mg/L) was 85% and 174% of the control group, respectively.
CONCLUSION: Ginkgo biloba extract significantly can suppress proliferation and increase cytotoxicity in HepG2 and Hep3B cells. Additionally, Ginkgo biloba extract can decrease PCNA and increase p53 expression in HepG2 cells.
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Affiliation(s)
- Jane C J Chao
- School of Nutrition and Health Sciences, Taipei Medical University, Taipei 110, Taiwan, China.
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23
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Chiu A, Kimball AB. Topical vitamins, minerals and botanical ingredients as modulators of environmental and chronological skin damage. Br J Dermatol 2003; 149:681-91. [PMID: 14616358 DOI: 10.1046/j.1365-2133.2003.05540.x] [Citation(s) in RCA: 92] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Ageing skin is characterized by fine lines, wrinkles, lentigines, dyspigmentation and increased coarseness. Topical preparations alleged to combat these changes abound in the over-the-counter market. Some of the most popular ingredients used in these products are vitamins, minerals and botanical extracts. Proposed mechanisms for antiageing effects on skin range from antioxidant properties to improved collagen synthesis or protection from collagen breakdown. Despite the media attention and consumer popularity that these ingredients have generated, there have been few scientific studies to support these claims. In this report, we review recent published studies on the most common of these ingredients for the topical photoprotection and the treatment of ageing skin.
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Affiliation(s)
- A Chiu
- Department of Dermatology, Stanford University School of Medicine, 900 Blake Wilbur Drive, RM W0024, Stanford, CA 94305-5334, U.S.A
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Parsad D, Pandhi R, Juneja A. Effectiveness of oral Ginkgo biloba in treating limited, slowly spreading vitiligo. Clin Exp Dermatol 2003; 28:285-7. [PMID: 12780716 DOI: 10.1046/j.1365-2230.2003.01207.x] [Citation(s) in RCA: 84] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
For effective treatment of vitiligo, it is as important to arrest the progression of the disease as it is to induce repigmentation. Recently, oxidative stress has been shown to play an important role in the pathogenesis of vitiligo. Ginkgo biloba extract has been shown to have antioxidant and immunomodulatory properties. In a double-blind placebo-controlled trial, we evaluated the efficacy of G. biloba extract in controlling the activity of the disease process in patients with limited and slow-spreading vitiligo and in inducing repigmentation of vitiliginous areas. Fifty-two patients were assigned to two treatment groups (A and B) in a double-blind fashion, but only 47 patients could be evaluated, because one patient in group A and four patients in group B withdrew for reasons unrelated to the study. Patients in group A were given G. biloba extract 40 mg three times daily whereas patients in group B received placebo in similar doses. A statistically significant cessation of active progression of depigmentation was noted in patients treated with G. biloba (P = 0.006). Marked to complete repigmentation was seen in 10 patients in group A, whereas only two patients in group B showed similar repigmentation. The G. biloba extract was well tolerated. G. biloba extract seems to be a simple, safe and fairly effective therapy for arresting the progression of the disease.
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Affiliation(s)
- D Parsad
- Department of Dermatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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25
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Han B, Jaurequi J, Tang BW, Nimni ME. Proanthocyanidin: a natural crosslinking reagent for stabilizing collagen matrices. J Biomed Mater Res A 2003; 65:118-24. [PMID: 12635161 DOI: 10.1002/jbm.a.10460] [Citation(s) in RCA: 264] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
While attempting to find a suitable crosslinking reagent for biopolymers, a naturally occurring proanthocyanidin (PA) obtained from grape seeds was selected to fix biological tissues. The cytotoxicity and crosslinking rate, reflected by the in vitro and in vivo degradation of fixed matrices has been studied. The shrinkage temperature of the fixed bovine pericardium increased from 66 to 86 degrees C. A cytotoxicity assay using fibroblast cultures revealed that PA is approximately 120 times less toxic than glutaraldehyde (GA), a currently used tissue stabilizer. In vitro degradation studies showed that fixed tissue was resistant to digestion by bacterial collagenase. Crosslinks between PA and tissues can be stabilized by decreasing the dielectric constant of the solution during storage. After subcutaneous implantation for periods ranging between 3 and 6 weeks, we found no apparent degradation of the GA- or PA-fixed tissues, whereas fresh tissue controls rapidly disintegrated. Beyond 6 weeks PA crosslinks began to degrade. More fibroblasts migrated and proliferated inside the PA-fixed implants compared with GA counterparts. Tissues crosslinked with PA manifested an enhanced collagen expression and deposition and did not calcify after implantation. GA, on the other hand, even after thorough rinsing continued to be cytotoxic, inhibited collagen synthesis and encouraged dystrophic calcification. Collagen matrices crosslinked with PA are expected to be of value in the design of matrices that will encourage cell ingrowth and proliferation, which are temporary in nature, and that are intended to regenerate or replace missing tissues, which can delay the biogradation of collagen. As such they should be of significant value in the emerging field of tissue engineering.
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Affiliation(s)
- Bo Han
- Tissue Engineering Laboratory, Department of Surgery, Biochemistry and Orthopaedics, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR-810, Los Angeles, CA 90033, USA
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Abstract
Flavonoids are plant pigments that are synthesised from phenylalanine, generally display marvelous colors known from flower petals, mostly emit brilliant fluorescence when they are excited by UV light, and are ubiquitous to green plant cells. The flavonoids are used by botanists for taxonomical classification. They regulate plant growth by inhibition of the exocytosis of the auxin indolyl acetic acid, as well as by induction of gene expression, and they influence other biological cells in numerous ways. Flavonoids inhibit or kill many bacterial strains, inhibit important viral enzymes, such as reverse transcriptase and protease, and destroy some pathogenic protozoans. Yet, their toxicity to animal cells is low. Flavonoids are major functional components of many herbal and insect preparations for medical use, e.g., propolis (bee's glue) and honey, which have been used since ancient times. The daily intake of flavonoids with normal food, especially fruit and vegetables, is 1-2 g. Modern authorised physicians are increasing their use of pure flavonoids to treat many important common diseases, due to their proven ability to inhibit specific enzymes, to simulate some hormones and neurotransmitters, and to scavenge free radicals.
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Affiliation(s)
- Bent H Havsteen
- Department of Biochemistry, University of Kiel, Olshausenstrasse 40, D-24098, Kiel, Germany.
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Abstract
AIM: To study the apoptosis of hepatoma cells SMMC-7721 induced by polysaccharide isolated from Ginkgo biloba seed.
METHODS: Ginkgo biloba seed polysaccharide (GBSP) was isolated by ethanol fractionation of Ginkgo biloba seed and purified by Sephadex G-200 chromatography. The purity of GBSP was verified by reaction with iodine-potassium iodide and ninhydrin and confirmed by UV spectrophotometer, cellulose acetate membrane electrophoresis and Sepharose 4B gel filtration chromatography. The Scanning Electron Microscope (SEM) and Flow Cytometry (FCM) were used to examine the SMMC-7721 cells with and without GBSP treatment at 500 mg/mL for 36 h.
RESULTS: GBSP product obtained was of high purity with the average molecular weight of 1.86 × 105. Quantitative analysis of SMMC-7721 cells in vitro with FCM showed that the percentages of G2-M cells without and with GBSP treatment were 17.01% ± 1.28% and 11.77% ± 1.50% (P < 0.05), the debris ratio of the cells were 0.46% ± 0.12% and 0.06% ± 0.06% (P < 0.01), and the apoptosis ratio of cells was 3.84% ± 0.55% and 9.13% ± 1.48% (P < 0.01) respectively. Following GBSP treatment, microvilli of SMMC-7721 cells appeared thinner and the number of spherical cells increased markedly. Most significantly, the apoptosis bodies were formed on and around the spherical cells treated with GBSP.
CONCLUSION: GBSP could potentially induce the apoptosis of SMMC-7721 cells.
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Affiliation(s)
- Qun Chen
- Department of Biology, Shandong Normal University, Jinan 250014, Shandong Province, China
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Affiliation(s)
- Z D Draelos
- Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
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Abstract
The effect of Ginkgo biloba extract on Ultraviolet B (UVB) irradiated fibroblasts was examined by using a neutral red dye uptake assay and a lactic dehydrogenase (LDH) release assay. Crude extract along with individual components, including flavone-glycosides and biflavones, were applied to cultured normal human skin fibroblasts for 12 hours, and 0, 20, 40 and 80 mJ/cm2 of UVB were irradiated. Two synthetic flavonoids, quercetin and rutin, which have polyphenol structures close to the flavonoids in Ginkgo biloba extract, were used to compare any structure-related activity under the same conditions. At the concentrations (from 0.25 to 2 mg/ml) treated with biflavone components (isoginkgetin/ginkgetin, sciadopitysin) and quercetin, high neutral red dye uptake was detected with gradual increases in UVB irradiation. The time-course release of LDH was determined as the cytotoxicity index (%) during 24 hours following a high dose UVB irradiation (200 mJ/cm2), and the pattern of this cytotoxicity index was similar to that of the neutral red dye uptake results. Sciadopitysin, isoginkgetin/ginkgetin and quercetin treatments lowered cytotoxicity indices to 50.81, 67.81 and 62.19%, respectively, compared to 95.38% for the untreated control. The antioxidant potential of biflavones of Ginkgo biloba could be explained on the basis of structure-related activity; hydroxy- and methyl-substitutions on the basic structure of these flavonoids played a role, as other reports have suggested.
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Affiliation(s)
- S J Kim
- Department of Dermatology, Chonnam National University Medical School, Kwangju 501-757, Korea
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Abstract
Glaucoma is becoming recognized as a condition for which not only elevated intraocular pressure, but also non-pressure-dependent risk factors are responsible. New avenues of treatment into which investigations are being initiated include agents which could possibly improve blood flow to the eye and neuroprotective drugs. Only calcium channel blockers are presently available for such treatment in glaucoma, and these have not been widely adopted, in contrast to clinical trials involving a number of neuroprotectants in other neurologic disorders. Ginkgo biloba extract is freely available and has several biological actions which combine to make it a potentially important agent in the treatment of glaucoma: improvement of central and peripheral blood flow, reduction of vasospasm, reduction of serum viscosity, antioxidant activity, platelet activating factor inhibitory activity, inhibition of apoptosis, and inhibition of excitotoxicity. The effect of Ginkgo biloba extract as a potential antiglaucoma therapy deserves intensive scrutiny.
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Affiliation(s)
- R Ritch
- Department of Ophthalmology, The New York Eye and Ear Infirmary, New York 10003, USA.
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