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Ullah A, Ullah N, Nawaz T, Aziz T. Molecular Mechanisms of Sanguinarine in Cancer Prevention and Treatment. Anticancer Agents Med Chem 2023; 23:765-778. [PMID: 36045531 DOI: 10.2174/1871520622666220831124321] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Revised: 07/08/2022] [Accepted: 07/19/2022] [Indexed: 11/22/2022]
Abstract
Historically, natural plant-derived drugs received a great impact of consideration in the treatment of several human-associated disorders. Cancer is a devastating disease and the second most cause of mortality. Sanguinarine (SANG), a naturally isolated plant alkaloidal agent, possesses chemo-preventive effects. Several studies have revealed that SANG impedes tumor metastasis and development by disrupting a wide range of cell signaling pathways and its molecular targets, such as BCL-2, MAPKs, Akt, NF-κB, ROS, and microRNAs (miRNAs). However, its low chemical stability and poor oral bioavailability remain key issues in its use as a medicinal molecule. A novel method (e.g., liposomes, nanoparticles, and micelles) and alternative analogs provide an exciting approach to alleviate these problems and broaden its pharmacokinetic profile. Cancer-specific miRNA expression is synchronized by SANG, which has also been uncertain. In this critical study, we review the utilization of SANG mimics and nano-technologies to improve its support in cancer. We focus on recently disclosed studies on SANG anti-cancer properties.
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Affiliation(s)
- Asmat Ullah
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China
| | - Najeeb Ullah
- School of Biochemistry and Molecular Biology, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China
| | - Touseef Nawaz
- Faculty of Pharmacy, Gomal University, D.I. Khan, Pakistan
| | - Tariq Aziz
- School of Engineering, Westlake University, Hangzhou, Zhejiang Province, 310024, China
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Natural Product Library Screens Identify Sanguinarine Chloride as a Potent Inhibitor of Telomerase Expression and Activity. Cells 2022; 11:cells11091485. [PMID: 35563795 PMCID: PMC9104802 DOI: 10.3390/cells11091485] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 04/12/2022] [Accepted: 04/26/2022] [Indexed: 02/04/2023] Open
Abstract
Reverse transcriptase hTERT is essential to telomerase function in stem cells, as well as in 85–90% of human cancers. Its high expression in stem cells or cancer cells has made telomerase/hTERT an attractive therapeutic target for anti-aging and anti-tumor applications. In this study, we screened a natural product library containing 800 compounds using an endogenous hTERT reporter. Eight candidates have been identified, in which sanguinarine chloride (SC) and brazilin (Braz) were selected due to their leading inhibition. SC could induce an acute and strong suppressive effect on the expression of hTERT and telomerase activity in multiple cancer cells, whereas Braz selectively inhibited telomerase in certain types of cancer cells. Remarkably, SC long-term treatment could cause telomere attrition and cell growth retardation, which lead to senescence features in cancer cells, such as the accumulation of senescence-associated β-galactosidase (SA-β-gal)-positive cells, the upregulation of p16/p21/p53 pathways and telomere dysfunction-induced foci (TIFs). Additionally, SC exhibited excellent capabilities of anti-tumorigenesis, both in vitro and in vivo. In the mechanism, the compound down-regulated several active transcription factors including p65, a subunit of NF-κB complex, and reintroducing p65 could alleviate its suppression of the hTERT/telomerase. Moreover, SC could directly bind hTERT and inhibit telomerase activity in vitro. In conclusion, we identified that SC not only down-regulates the hTERT gene’s expression, but also directly affects telomerase/hTERT. The dual function makes this compound an attractive drug candidate for anti-tumor therapy.
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Porras G, Chassagne F, Lyles JT, Marquez L, Dettweiler M, Salam AM, Samarakoon T, Shabih S, Farrokhi DR, Quave CL. Ethnobotany and the Role of Plant Natural Products in Antibiotic Drug Discovery. Chem Rev 2021; 121:3495-3560. [PMID: 33164487 PMCID: PMC8183567 DOI: 10.1021/acs.chemrev.0c00922] [Citation(s) in RCA: 183] [Impact Index Per Article: 45.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The crisis of antibiotic resistance necessitates creative and innovative approaches, from chemical identification and analysis to the assessment of bioactivity. Plant natural products (NPs) represent a promising source of antibacterial lead compounds that could help fill the drug discovery pipeline in response to the growing antibiotic resistance crisis. The major strength of plant NPs lies in their rich and unique chemodiversity, their worldwide distribution and ease of access, their various antibacterial modes of action, and the proven clinical effectiveness of plant extracts from which they are isolated. While many studies have tried to summarize NPs with antibacterial activities, a comprehensive review with rigorous selection criteria has never been performed. In this work, the literature from 2012 to 2019 was systematically reviewed to highlight plant-derived compounds with antibacterial activity by focusing on their growth inhibitory activity. A total of 459 compounds are included in this Review, of which 50.8% are phenolic derivatives, 26.6% are terpenoids, 5.7% are alkaloids, and 17% are classified as other metabolites. A selection of 183 compounds is further discussed regarding their antibacterial activity, biosynthesis, structure-activity relationship, mechanism of action, and potential as antibiotics. Emerging trends in the field of antibacterial drug discovery from plants are also discussed. This Review brings to the forefront key findings on the antibacterial potential of plant NPs for consideration in future antibiotic discovery and development efforts.
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Affiliation(s)
- Gina Porras
- Center for the Study of Human Health, Emory University, 1557 Dickey Dr., Atlanta, Georgia 30322
| | - François Chassagne
- Center for the Study of Human Health, Emory University, 1557 Dickey Dr., Atlanta, Georgia 30322
| | - James T. Lyles
- Center for the Study of Human Health, Emory University, 1557 Dickey Dr., Atlanta, Georgia 30322
| | - Lewis Marquez
- Molecular and Systems Pharmacology Program, Laney Graduate School, Emory University, 615 Michael St., Whitehead 115, Atlanta, Georgia 30322
| | - Micah Dettweiler
- Department of Dermatology, Emory University, 615 Michael St., Whitehead 105L, Atlanta, Georgia 30322
| | - Akram M. Salam
- Molecular and Systems Pharmacology Program, Laney Graduate School, Emory University, 615 Michael St., Whitehead 115, Atlanta, Georgia 30322
| | - Tharanga Samarakoon
- Emory University Herbarium, Emory University, 1462 Clifton Rd NE, Room 102, Atlanta, Georgia 30322
| | - Sarah Shabih
- Center for the Study of Human Health, Emory University, 1557 Dickey Dr., Atlanta, Georgia 30322
| | - Darya Raschid Farrokhi
- Center for the Study of Human Health, Emory University, 1557 Dickey Dr., Atlanta, Georgia 30322
| | - Cassandra L. Quave
- Center for the Study of Human Health, Emory University, 1557 Dickey Dr., Atlanta, Georgia 30322
- Emory University Herbarium, Emory University, 1462 Clifton Rd NE, Room 102, Atlanta, Georgia 30322
- Department of Dermatology, Emory University, 615 Michael St., Whitehead 105L, Atlanta, Georgia 30322
- Molecular and Systems Pharmacology Program, Laney Graduate School, Emory University, 615 Michael St., Whitehead 115, Atlanta, Georgia 30322
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Warnakulasuriya S, Kujan O, Aguirre-Urizar JM, Bagan JV, González-Moles MÁ, Kerr AR, Lodi G, Mello FW, Monteiro L, Ogden GR, Sloan P, Johnson NW. Oral potentially malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer. Oral Dis 2020; 27:1862-1880. [PMID: 33128420 DOI: 10.1111/odi.13704] [Citation(s) in RCA: 556] [Impact Index Per Article: 111.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 10/21/2020] [Accepted: 10/25/2020] [Indexed: 12/12/2022]
Abstract
Oral potentially malignant disorders (OPMDs) are associated with an increased risk of occurrence of cancers of the lip or oral cavity. This paper presents an updated report on the nomenclature and the classification of OPMDs, based predominantly on their clinical features, following discussions by an expert group at a workshop held by the World Health Organization (WHO) Collaborating Centre for Oral Cancer in the UK. The first workshop held in London in 2005 considered a wide spectrum of disorders under the term "potentially malignant disorders of the oral mucosa" (PMD) (now referred to as oral potentially malignant disorders: OPMD) including leukoplakia, erythroplakia, proliferative verrucous leukoplakia, oral lichen planus, oral submucous fibrosis, palatal lesions in reverse smokers, lupus erythematosus, epidermolysis bullosa, and dyskeratosis congenita. Any new evidence published in the intervening period was considered to make essential changes to the 2007 classification. In the current update, most entities were retained with minor changes to their definition. There is sufficient evidence for an increased risk of oral cancer among patients diagnosed with "oral lichenoid lesions" and among those diagnosed with oral manifestations of 'chronic graft-versus-host disease'. These have now been added to the list of OPMDs. There is, to date, insufficient evidence concerning the malignant potential of chronic hyperplastic candidosis and of oral exophytic verrucous hyperplasia to consider these conditions as OPMDs. Furthermore, due to lack of clear evidence of an OPMD in epidermolysis bullosa this was moved to the category with limited evidence. We recommend the establishment of a global research consortium to further study the natural history of OPMDs based on the classification and nomenclature proposed here. This will require multi-center longitudinal studies with uniform diagnostic criteria to improve the identification and cancer risk stratification of patients with OPMDs, link them to evidence-based interventions, with a goal to facilitate the prevention and management of lip and oral cavity cancer.
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Affiliation(s)
- Saman Warnakulasuriya
- The WHO Collaborating Centre for Oral Cancer and Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London, London, UK
| | - Omar Kujan
- UWA Dental School, The University of Western Australia, Perth, WA, Australia
| | - José M Aguirre-Urizar
- Oral and Maxillofacial Medicine & Pathology Unit, Department of Stomatology II, Faculty of Medicine and Nursery, University of the Basque Country/EHU, Bilbao, Spain
| | - José V Bagan
- Oral Medicine, Valencia University, Valencia, Spain.,Department of Oral and Maxillofacial Surgery, University General Hospital, Valencia, Spain
| | - Miguel Ángel González-Moles
- School of Dentistry, University of Granada, Granada, Spain.,Biohealth Research Institute (IBS), Granada, Spain
| | - Alexander R Kerr
- Department of Oral and Maxillofacial Pathology, Radiology, and Medicine, New York University College of Dentistry, New York, NY, USA
| | - Giovanni Lodi
- Dipartimento di Scienze Biomediche, Chirurgiche e Odontoiatriche, Università degli Studi di Milano, Milano, Italy
| | | | - Luis Monteiro
- CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde (IINFACTS), IUCS - Instituto Universitário de Ciências da Saúde, Gandra, Portugal
| | - Graham R Ogden
- Department of Oral Surgery, Dundee Dental School, Dundee, Scotland, UK
| | - Philip Sloan
- School of Dental Sciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Newell W Johnson
- Menzies Health Institute Queensland and School of Dentistry and Oral Health, Griffith University, Gold Coast, Qld, Australia.,Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London, London, UK
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Croaker A, King GJ, Pyne JH, Anoopkumar-Dukie S, Liu L. Black salve composition: An evaluation of the potential for normal tissue toxicity and treatment failure from black salve products. J Herb Med 2019. [DOI: 10.1016/j.hermed.2018.11.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Galadari S, Rahman A, Pallichankandy S, Thayyullathil F. Molecular targets and anticancer potential of sanguinarine-a benzophenanthridine alkaloid. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2017; 34:143-153. [PMID: 28899497 DOI: 10.1016/j.phymed.2017.08.006] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2016] [Revised: 07/06/2017] [Accepted: 08/06/2017] [Indexed: 05/03/2023]
Abstract
BACKGROUND Cancer is an enormous global health burden, and should be effectively addressed with better therapeutic strategies. Currently, over 60% of the clinically approved anticancer agents are either directly isolated from natural sources or are modified from natural lead molecules. Sanguinarine (SNG), a quaternary benzophenanthridine alkaloid has gained increasing attention in recent years as a potential anticancer agent. PURPOSE There is a large untapped source of phytochemical-based anticancer agents remaining to be explored. This review article aims to recapitulate different anticancer properties of SNG, and describes some of the molecular targets involved in exerting its effect. It also depicts the pharmacokinetic and toxicological properties of SNG, two parameters important in determining the druggability of a molecule. METHODS Numerous in vivo and in vitro published studies have signified the anticancer properties of SNG. In order to collate and decipher these properties, an extensive literature search was conducted in PubMed, ScienceDirect, and Scopus using keywords followed by the evaluation of the relevant articles where the relevant reports are integrated and analyzed. RESULTS Apart from inducing cell death, SNG inhibits pro-tumorigenic processes such as invasion, angiogenesis, and metastasis in different cancers. Moreover, SNG has been shown to synergistically enhance the sensitivity of several chemotherapeutic agents and is effective against a variety of multi-drug resistant cancers.
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Affiliation(s)
- Sehamuddin Galadari
- Cell Death Signaling Laboratory, Division of Science (Biology), Experimental Research Building, New York University Abu Dhabi, PO Box 129188, Saadiyat Island Campus, Abu Dhabi, UAE.
| | - Anees Rahman
- Cell Death Signaling Laboratory, Division of Science (Biology), Experimental Research Building, New York University Abu Dhabi, PO Box 129188, Saadiyat Island Campus, Abu Dhabi, UAE.
| | - Siraj Pallichankandy
- Cell Death Signaling Laboratory, Division of Science (Biology), Experimental Research Building, New York University Abu Dhabi, PO Box 129188, Saadiyat Island Campus, Abu Dhabi, UAE.
| | - Faisal Thayyullathil
- Cell Death Signaling Laboratory, Division of Science (Biology), Experimental Research Building, New York University Abu Dhabi, PO Box 129188, Saadiyat Island Campus, Abu Dhabi, UAE.
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Croaker A, King GJ, Pyne JH, Anoopkumar-Dukie S, Simanek V, Liu L. Carcinogenic potential of sanguinarine, a phytochemical used in 'therapeutic' black salve and mouthwash. MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH 2017; 774:46-56. [PMID: 29173498 DOI: 10.1016/j.mrrev.2017.09.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Revised: 08/17/2017] [Accepted: 09/02/2017] [Indexed: 02/07/2023]
Abstract
Black salves are escharotic skin cancer therapies in clinical use since the mid 19th century. Sanguinaria canadensis, a major ingredient of black salve formulations, contains a number of bioactive phytochemicals including the alkaloid sanguinarine. Despite its prolonged history of clinical use, conflicting experimental results have prevented the carcinogenic potential of sanguinarine from being definitively determined. Sanguinarine has a molecular structure similar to known polyaromatic hydrocarbon carcinogens and is a DNA intercalator. Sanguinarine also generates oxidative and endoplasmic reticulum stress resulting in the unfolded protein response and the formation of 8-hydroxyguanine genetic lesions. Sanguinarine has been the subject of contradictory in vitro and in vivo genotoxicity and murine carcinogenesis test results that have delayed its carcinogenic classification. Despite this, epidemiological studies have linked mouthwash that contains sanguinarine with the development of oral leukoplakia. Sanguinarine is also proposed as an aetiological agent in gallbladder carcinoma. This literature review investigates the carcinogenic potential of sanguinarine. Reasons for contradictory genotoxicity and carcinogenesis results are explored, knowledge gaps identified and a strategy for determining the carcinogenic potential of sanguinarine especialy relating to black salve are discussed. As patients continue to apply black salve, especially to skin regions suffering from field cancerization and skin malignancies, an understanding of the genotoxic and carcinogenic potential of sanguinarine is of urgent clinical relevance.
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Affiliation(s)
- Andrew Croaker
- Southern Cross Plant Science, Southern Cross University, Lismore, NSW, Australia; Wesley Medical Research Institute, Wesley Hospital, Auchenflower, QLD, Australia; Quality Use of Medicines Network, Queensland, Australia
| | - Graham J King
- Southern Cross Plant Science, Southern Cross University, Lismore, NSW, Australia
| | - John H Pyne
- School of Medicine, University of Queensland, St Lucia, QLD, Australia
| | - Shailendra Anoopkumar-Dukie
- Quality Use of Medicines Network, Queensland, Australia; School of Pharmacy and Pharmacology, Griffith University, Gold Coast Campus, Gold Coast, QLD, Australia
| | - Vilim Simanek
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic
| | - Lei Liu
- Southern Cross Plant Science, Southern Cross University, Lismore, NSW, Australia.
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Abstract
A wide spectrum of drugs can sometimes give rise to numerous adverse orofacial manifestations, particularly dry mouth, taste disturbances, oral mucosal ulceration, and/or gingival swelling. There are few relevant randomized double-blind controlled studies in this field, and therefore this paper reviews the data from case reports, small series, and non-peer-reviewed reports of adverse drug reactions affecting the orofacial region (available from a MEDLINE search to April, 2003). The more common and significant adverse orofacial consequences of drug therapy are discussed.
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Affiliation(s)
- C Scully
- Eastman Dental Institute for Oral Health Care Sciences, University College, University of London, 256 Gray's Inn Road, London WC1X 8LD, UK.
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Sanguinaria canadensis: Traditional Medicine, Phytochemical Composition, Biological Activities and Current Uses. Int J Mol Sci 2016; 17:ijms17091414. [PMID: 27618894 PMCID: PMC5037693 DOI: 10.3390/ijms17091414] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2016] [Revised: 08/11/2016] [Accepted: 08/12/2016] [Indexed: 12/26/2022] Open
Abstract
Sanguinaria canadensis, also known as bloodroot, is a traditional medicine used by Native Americans to treat a diverse range of clinical conditions. The plants rhizome contains several alkaloids that individually target multiple molecular processes. These bioactive compounds, mechanistically correlate with the plant’s history of ethnobotanical use. Despite their identification over 50 years ago, the alkaloids of S. canadensis have not been developed into successful therapeutic agents. Instead, they have been associated with clinical toxicities ranging from mouthwash induced leukoplakia to cancer salve necrosis and treatment failure. This review explores the historical use of S. canadensis, the molecular actions of the benzophenanthridine and protopin alkaloids it contains, and explores natural alkaloid variation as a possible rationale for the inconsistent efficacy and toxicities encountered by S.canadensis therapies. Current veterinary and medicinal uses of the plant are studied with an assessment of obstacles to the pharmaceutical development of S. canadensis alkaloid based therapeutics.
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Sandor R, Midlik A, Sebrlova K, Dovrtelova G, Noskova K, Jurica J, Slaninova I, Taborska E, Pes O. Identification of metabolites of selected benzophenanthridine alkaloids and their toxicity evaluation. J Pharm Biomed Anal 2016; 121:174-180. [DOI: 10.1016/j.jpba.2016.01.024] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Revised: 01/11/2016] [Accepted: 01/12/2016] [Indexed: 11/24/2022]
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Gaziano R, Moroni G, Buè C, Miele MT, Sinibaldi-Vallebona P, Pica F. Antitumor effects of the benzophenanthridine alkaloid sanguinarine: Evidence and perspectives. World J Gastrointest Oncol 2016; 8:30-39. [PMID: 26798435 PMCID: PMC4714144 DOI: 10.4251/wjgo.v8.i1.30] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2015] [Revised: 09/01/2015] [Accepted: 11/04/2015] [Indexed: 02/05/2023] Open
Abstract
Historically, natural products have represented a significant source of anticancer agents, with plant-derived drugs becoming increasingly explored. In particular, sanguinarine is a benzophenanthridine alkaloid obtained from the root of Sanguinaria canadensis, and from other poppy Fumaria species, with recognized anti-microbial, anti-oxidant and anti-inflammatory properties. Recently, increasing evidence that sanguinarine exibits anticancer potential through its capability of inducing apoptosis and/or antiproliferative effects on tumor cells, has been proved. Moreover, its antitumor seems to be due not only to its pro-apoptotic and inhibitory effects on tumor growth, but also to its antiangiogenic and anti-invasive properties. Although the precise mechanisms underlying the antitumor activity of this compound remain not fully understood, in this review we will focus on the most recent findings about the cellular and molecular pathways affected by sanguinarine, together with the rationale of its potential application in clinic. The complex of data currently available suggest the potential application of sanguinarine as an adjuvant in the therapy of cancer, but further pre-clinical studies are needed before such an antitumor strategy can be effectively translated in the clinical practice.
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Mortazavi H, Baharvand M, Mehdipour M. Oral potentially malignant disorders: an overview of more than 20 entities. J Dent Res Dent Clin Dent Prospects 2014; 8:6-14. [PMID: 25024833 PMCID: PMC4091702 DOI: 10.5681/joddd.2014.002] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2013] [Accepted: 08/07/2013] [Indexed: 12/13/2022] Open
Abstract
Cancer of the oral cavity accounts for approximately 3% of all malignancies diagnosed annually in 270,000 patients world-wide. Oral cancer is the 12th most common cancer in women and the 6th in men. Many oral squamous cell carcinomas develop from potentially malignant disorders (PMDs). Lack of awareness about the signs and symptoms of oralPMDs in the general population and even healthcare providers is believed to be responsible for the diagnostic delay of these entities. The aim of this article is to update and improve the knowledge of healthcare providers about oral PMDs.
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Affiliation(s)
- Hamed Mortazavi
- 1Associate Professor, Department of Oral and Maxillofacial Medicine, Faculty of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Baharvand
- 1Associate Professor, Department of Oral and Maxillofacial Medicine, Faculty of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Masoumeh Mehdipour
- 1Associate Professor, Department of Oral and Maxillofacial Medicine, Faculty of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Vlachojannis C, Magora F, Chrubasik S. Rise and fall of oral health products with Canadian bloodroot extract. Phytother Res 2012; 26:1423-6. [PMID: 22318955 DOI: 10.1002/ptr.4606] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2011] [Revised: 12/03/2011] [Accepted: 12/16/2011] [Indexed: 11/07/2022]
Abstract
The rhizome of Sanguinaria canadensis (SC, bloodroot) contains an active principle with antimicrobial, antiinflammatory, antioxidative and immunomodulatory effects. For this reason SC extract has been added to toothpastes and mouthwashes in various concentrations. When tested separately, neither the toothpastes nor the mouthwashes with SC extract had any demonstrable clinical effectiveness against dental plaque and gingivitis. Although using them together twice a day seemed more effective than using placebo, more recent studies have shown conflicting results. Preclinical safety studies up to 2000, which did not include studies longer than 6 months, were thought not to indicate any appreciable potential for harm - to the oral mucosa in particular. In 2003, the FDA Subcommittee on Oral Health Care Drug Products for Over-the-Counter Human Use concluded from a review that using SC-containing products is safe. However, for reasons unknown, the review failed to consider publications between 1999 and 2001 that suggested a possible link between the use of SC-containing products and the pre-neoplastic lesion, leukoplakia. As it happened, bloodroot had already been removed (in 2001) from the formula of one of the most widely used products in question and the brand has since then disappeared altogether from the worldwide market.
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Woo SB. Diseases of the oral mucosa. MCKEE'S PATHOLOGY OF THE SKIN 2012:362-436. [DOI: 10.1016/b978-1-4160-5649-2.00011-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
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Kosina P, Gregorova J, Gruz J, Vacek J, Kolar M, Vogel M, Roos W, Naumann K, Simanek V, Ulrichova J. Phytochemical and antimicrobial characterization of Macleaya cordata herb. Fitoterapia 2010; 81:1006-12. [PMID: 20600683 DOI: 10.1016/j.fitote.2010.06.020] [Citation(s) in RCA: 104] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2010] [Revised: 06/18/2010] [Accepted: 06/18/2010] [Indexed: 10/19/2022]
Abstract
Macleaya cordata (plume poppy) is a source of bioactive compounds, mainly isoquinoline alkaloids which are used in phytopreparations with anti-inflammatory and antimicrobial activities. In this study, the alkaloids sanguinarine, chelerythrine, their dihydro derivatives, protopine and allocryptopine and phenolics, gallic, protocatechuic, p-hydroxybenzoic, m-hydroxybenzoic, gentisic, p-coumaric, caffeic, ferulic and sinapic acids were determined in extracts prepared from M. cordata aerial part, seeds, and seed capsules using HPLC with UV detection and/or LC/MS with electrospray ionization. The highest content of sanguinarine and chelerythrine was found in capsules. Protopine and allocryptopine were major alkaloids in leaves including footstalks. The seed oil contained dihydrosanguinarine, dihydrochelerythrine and twelve fatty acids of which linoleic, oleic, palmitic and stearic acids predominated. In addition, sanguinarine reductase, a key enzyme in sanguinarine/dihydrosanguinarine equilibrium in plants, was found for the first time, in the soluble proteins of leaves. Finally, extracts were tested for antimicrobial activity using the microdilution method on standard reference bacterial strains.
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Affiliation(s)
- Pavel Kosina
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 3, 775 15 Olomouc, Czech Republic.
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Abstract
Sanguinarine is an alkaloid found in many medicinal plants. It has diverse biological activities, including modulation of nuclear factor-kappaB and of several enzymes. It is also known to induce apoptosis, perturb microtubules, and to have antimicrobial effects. This article reviews its cardiovascular properties, including hypotensive, antiplatelet, and positive inotropic effects. Its pharmacokinetics, and toxicology, including its carcinogenic potential, are also discussed. Further pharmacological and toxicological studies with sanguinarine are needed before its therapeutic use can be considered.
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Affiliation(s)
- I Mackraj
- Department of Human Physiology, Nelson R. Mandela School of Medicine, University of KwaZulu, Durban, South Africa.
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Matkar SS, Wrischnik LA, Hellmann-Blumberg U. Sanguinarine causes DNA damage and p53-independent cell death in human colon cancer cell lines. Chem Biol Interact 2008; 172:63-71. [PMID: 18243168 DOI: 10.1016/j.cbi.2007.12.006] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2007] [Revised: 12/07/2007] [Accepted: 12/18/2007] [Indexed: 12/14/2022]
Abstract
The benzophenanthridine alkaloid sanguinarine has antimicrobial and possibly anticancer properties but it is not clear to what extent these activities involve DNA damage. Thus, we studied its ability to cause DNA single and double strand breaks, as well as increased levels of 8-oxodeoxyguanosine, in human colon cancer cells and found DNA damage consistent with oxidation. Since the tumor suppressor p53 is frequently involved in inducing apoptosis following DNA damage we investigated the effect of sanguinarine in wild type, p53-mutant and p53-null colon cancer cell lines. We found them to be equally sensitive to this plant compound, indicating that cell death is not mediated by p53 in this case. In addition, our observation that apoptosis induced by sanguinarine is initiated very rapidly raised the question whether there is enough time for cellular signaling in response to DNA damage. Moreover, the abundance of double strand breaks is not consistent with only oxidative damage to DNA. We conclude that the majority of DNA double strand breaks in sanguinarine-treated cells are likely the result, rather than the cause, of apoptotic cell death and that apoptosis induced by sanguinarine is independent of p53 and most likely independent of DNA damage.
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Affiliation(s)
- Smita S Matkar
- Department of Chemistry, University of the Pacific, Stockton, CA 95211, USA
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Benign alveolar ridge keratosis (oral lichen simplex chronicus): A distinct clinicopathologic entity. J Am Acad Dermatol 2008; 58:151-7. [DOI: 10.1016/j.jaad.2007.07.011] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2007] [Revised: 07/02/2007] [Accepted: 07/09/2007] [Indexed: 11/21/2022]
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A Case-Control Study on Tobacco and Alcohol Addicted Subjects. ADDICTIVE DISORDERS & THEIR TREATMENT 2006. [DOI: 10.1097/01.adt.0000185137.58631.16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Simánek V, Dvorák Z, Kubán V, Klejdus B, Vicar J, Ulrichová J, Hlavac J. Quaternary Benzo[c]phenanthridines Sanguinarine and Chelerythrine: a Review of Investigations from Chemical and Biological Studies. HETEROCYCLES 2006. [DOI: 10.3987/rev-06-610] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Zdarilová A, Vrzal R, Rypka M, Ulrichová J, Dvorák Z. Investigation of sanguinarine and chelerythrine effects on CYP1A1 expression and activity in human hepatoma cells. Food Chem Toxicol 2005; 44:242-9. [PMID: 16115718 DOI: 10.1016/j.fct.2005.07.006] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2005] [Revised: 06/02/2005] [Accepted: 07/11/2005] [Indexed: 11/20/2022]
Abstract
Quaternary benzo[c]phenanthridine alkaloids (QBA) sanguinarine and chelerythrine exhibit a wide spectrum of biological activities whence they are used in dental care products. Recent studies indicated that cytochrome P450 CYP1A attenuates sanguinarine toxicity both in vivo [Williams, M.K., Dalvi, S., Dalvi, R.R., 2000. Influence of 3-methylcholanthrene pretreatment on sanguinarine toxicity in mice. Vet. Hum. Toxicol. 42, 196-198] and in vitro [Vrba, J., Kosina, P., Ulrichová, J., Modrianský, M., 2004. Involvement of cytochrome P450 1A in sanguinarine detoxication. Toxicol. Lett. 151, 375-387]. However, CYP1A converts sanguinarine to the products that form DNA adducts [Stiborová, M., Simánek, V., Frei, E., Hobza, P., Ulrichová, J., 2002. DNA adduct formation from quaternary benzo[c]phenanthridine alkaloids sanguinarine and chelerythrine as revealed by the 32P-postlabeling technique. Chem. Biol. Interact. 140, 231-242]. In our work we examined the effects of sanguinarine and chelerythrine on CYP1A1 expression and catalytic activity in human hepatoma cells-HepG2. Sanguinarine and chelerythrine did not affect basal and dioxin-inducible expression of CYP1A1 mRNA and protein in HepG2 cells. The enzymatic activity of CYP1A1 was assessed by the fluorescent measurement of 7-ethyxoresorufin-O-deethylase (EROD) activity. We observed a slight decrease of dioxin-induced EROD activity in HepG2 cells by sanguinarine and chelerythrine. This decrease was attributed to the inhibition of CYP1A1 catalytic activity, as revealed by enzyme kinetic studies on recombinant CYP1A1 protein. The IC50 values for the inhibition of CYP1A1 by sanguinarine and chelerythrine were 2.1 and 1.9muM, respectively. In conclusion, albeit the CYP1A modulates QBA cytotoxicity and genotoxicity, the QBA themselves do not affect CYP1A1 expression. The data indicate that studied alkaloids do not have specific cellular target and their biological effects are rather pleiotropic.
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Affiliation(s)
- A Zdarilová
- Institute of Medical Chemistry and Biochemistry, Faculty of Medicine, Palacký University, Hnĕvotínská 3, 775 15 Olomouc, Czech Republic
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Vlcková M, Kubán V, Vicar J, Simánek V. Capillary zone electrophoretic studies of interactions of some quaternary isoquinoline alkaloids with DNA constituents and DNA. Electrophoresis 2005; 26:1673-9. [PMID: 15812846 DOI: 10.1002/elps.200410193] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Capillary zone electrophoresis was applied for the investigation of interactions of some quaternary isoquinoline alkaloids, namely sanguinarine, chelerythrine, berberine, and jatrorrhizine, with DNA constituents and with DNA. None of these alkaloids attach covalently to nucleotides or to the whole DNA under physiological conditions. The interaction with DNA constituents is a noncovalent complexation based on weak intermolecular forces. Electrostatic attraction participates in the interaction but other types of intermolecular forces are involved as well. Cations were identified as the most probable interacting forms of the alkaloids. The interaction with compounds derived from purine was always stronger than those derived from pyrimidine. All alkaloids behaved analogously and similarly to ethidium bromide, the classic DNA intercalator. Stability constants K (in l.mol(-1)) for sanguinarine and chelerythrine in phosphate buffer of pH 7.4 (I(S) = 30 mM) ranged from tens to hundreds.
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Affiliation(s)
- Markéta Vlcková
- Department of Chemistry and Biochemistry, Mendel University of Agriculture and Forestry, Zemĕdĕlská 1, CZ-613 00 Brno, Czech Republic
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Anderson KM, Stoner GD, Fields HW, Chacon GE, Dohar AL, Gregg BR, Mallery SR. Immunohistochemical assessment of Viadent-associated leukoplakia. Oral Oncol 2005; 41:200-7. [PMID: 15695122 DOI: 10.1016/j.oraloncology.2004.08.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2004] [Accepted: 08/06/2004] [Indexed: 12/14/2022]
Abstract
Studies show an association between sanguinarine, the active ingredient in Viadent oral health care products, and oral premalignant lesions. The study was undertaken to quantitatively compare the staining profiles of sanguinarine-associated leukoplakia to normal and dysplastic specimens. Archived oral mucosal specimens were stained for tumor markers p16, p53, cyclin D1, Ki-67, and Bcl-x and analyzed through Simple PCI image analysis software. Quantitative analyses showed trends towards intermediate staining in Viadent-related specimens (Ki-67: normal: 18.12+/-2.15, Viadent: 16.12+/-2.16, dysplasia: 14.53+/-2.04, p>0.05; cyclin D1: normal: 15.65+/-3.68, Viadent: 12.52+/-3.57, dysplasia: 1.94+/-3.93, p<0.05; p16: normal: 55.04+/-4.16, Viadent: 49.74+/-4.16, dysplasia: 45.03+/-4.45; p>0.05; p53:normal: 2.65+/-1.37, Viadent: 4.64+/-1.52, dysplasia: 8.71+/-1.37; p<0.05 Kruskal Wallace, Tukey/Kramer). Our Viadent profiles, intermediate between normal and dysplasia, support a preneoplastic nature of this process.
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Affiliation(s)
- K Mark Anderson
- American Cancer Society, Ohio Division, 5555 Frantz Road, Dublin, OH 43017, USA.
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Noonan VL, Kabani S. Diagnosis and management of suspicious lesions of the oral cavity. Otolaryngol Clin North Am 2005; 38:21-35, vii. [PMID: 15649496 DOI: 10.1016/j.otc.2004.09.008] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Oral lesions associated with premalignant changes and malignancy present in diverse ways. This article discusses the clinical characteristics of such lesions enabling clinicians to identify classical features.Additionally, an effort is made to familiarize clinicians with the significance of red and white lesions, especially those having a high index of suspicion for oral cancer, and to alert clinicians when a biopsy is mandatory.
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Affiliation(s)
- Vikki L Noonan
- Oral and Maxillofacial Pathology, Boston University Goldman School of Dental Medicine, 100 East Newton Street, Boston, MA 02118, USA.
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Karp JM, Rodrigo KA, Pei P, Pavlick MD, Andersen JD, McTigue DJ, Fields HW, Mallery SR. Sanguinarine activates polycyclic aromatic hydrocarbon associated metabolic pathways in human oral keratinocytes and tissues. Toxicol Lett 2005; 158:50-60. [PMID: 15993743 DOI: 10.1016/j.toxlet.2005.02.007] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2004] [Revised: 02/25/2005] [Accepted: 02/28/2005] [Indexed: 12/14/2022]
Abstract
Sanguinarine's use in human clinical applications is currently controversial. While some studies have demonstrated sanguinarine's anti-inflammatory and anti-oxidant properties, other investigations reported sanguinarine's procarcinogenic effects. Like the tobacco-associated carcinogen, benzo(a)pyrene (B(a)P), sanguinarine is a polycyclic aromatic hydrocarbon (PAH). PAH exposure activates the aryl hydrocarbon transcription activating factor (AhR), resulting in nuclear translocation, binding to the aryl hydrocarbon nuclear translocator (ARNT), which thereby increases expression of a pool of carcinogen metabolizing enzymes. The goal of this study was to investigate whether sanguinarine activates this PAH-associated signaling cascade in human oral cells and tissues. Our results demonstrate that sanguinarine: (i) results in formation of the AhR-ARNT complex, (ii) induces AhR-associated gene expression, (iii) inhibits cytochrome P450 1A1 (CYP 1A1) microsomal oxidative activity and (iv) pretreatment upregulates CYP 1A1 function. Collectively, these data provide evidence that sanguinarine activates PAH-associated signaling and metabolic pathways. Notably, previous studies have demonstrated that mammalian hepatic microsomes metabolize sanguinarine to a mutagenic epoxide. Persons who respond to sanguinarine exposure with induction of primarily Phase I relative to Phase II enzymes are, therefore, at risk for sanguinarine bioactivation and its potential mutagenic effects.
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Affiliation(s)
- Jeffrey M Karp
- The Ohio State University College of Dentistry, Department of Pediatric Dentistry, Columbus, OH 43210, USA
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Fisher MA, Bouquot JE, Shelton BJ. Assessment of risk factors for oral leukoplakia in West Virginia. Community Dent Oral Epidemiol 2005; 33:45-52. [PMID: 15642046 DOI: 10.1111/j.1600-0528.2004.00195.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVE To assess risk factors associated with oral leukoplakia in a US population with high use of smoked tobacco and smokeless tobacco. METHODS The RJ Gorlin Leukoplakia Tissue Registry was used to identify individuals with oral leukoplakia in West Virginia, USA. This case-control study consisted of 90 cases with oral leukoplakia and 78 controls with periapical cysts. Univariate-univariable (one dependent variable and one independent variable) and univariate-multivariable (one dependent variable and multiple independent variables) logistic regression modeling quantified the association between oral leukoplakia and potential explanatory variables. RESULTS Unadjusted measures of association indicate that those with oral leukoplakia were more likely to be older [odds ratio of crude: OR(Crude) = 2.72; 95% confidence interval (CI): 1.45-5.11], more likely to currently use smokeless tobacco (OR(Crude) = 3.16; 95% CI: 1.10-9.07), and more likely to currently use snuff (OR(Crude) = 8.32; 95% CI: 1.83-37.80). Individuals currently using smokeless tobacco or currently using snuff were more likely to have oral leukoplakia [adjusted odds ratio, OR(Adj) = 9.21 and 30.08; 95% CI: 1.49-57.00 and 2.67-338.48, respectively], after simultaneously adjusting for age, gender, currently using smoked tobacco, currently using alcohol daily, and dental prostheses use. CONCLUSIONS Generalizability is an issue when studying risk factors associated with oral leukoplakia because of geographical variations in the composition of smokeless tobacco (i.e. betel, lime, ash, and N-nitrosamines) and cultural variations in the use of tobacco (i.e. reverse smoking). Snuff was the main smokeless tobacco product currently used in West Virginia, and was strongly associated with oral leukoplakia, after adjusting for potential explanatory variables.
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Affiliation(s)
- Monica A Fisher
- University of Alabama at Birmingham, Department of Diagnostic Sciences, SDB 219, 1530 3rd Avenue South, Birmingham, AL 35294-0007, USA.
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Ansari KM, Dhawan A, Khanna SK, Das M. In vivo DNA damaging potential of sanguinarine alkaloid, isolated from argemone oil, using alkaline Comet assay in mice. Food Chem Toxicol 2005; 43:147-53. [PMID: 15582207 DOI: 10.1016/j.fct.2004.09.005] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2004] [Accepted: 09/15/2004] [Indexed: 12/14/2022]
Abstract
Consumption of mustard oil contaminated with argemone oil is well known to cause clinical manifestation referred to as "Epidemic Dropsy". Our prior studies have shown that argemone oil produces genotoxic effects in mice [Ansari, K.M., et al., 2004. Int. J. Cancer 112, 890]. Since, sanguinarine alkaloid is the major component of argemone oil, the in vivo DNA damaging potential of the isolated alkaloid was investigated in blood and bone marrow cells of mice using alkaline Comet assay. Swiss albino male mice were given single intraperitoneal administration of 1.35, 2.70, 5.40, 10.80 and 21.60 mg sanguinarine alkaloid/kg b wt., while controls were treated with saline in the same manner. The results revealed a dose dependent increase in DNA damage in blood and bone marrow cells following 24 h treatment of sanguinarine alkaloid. All the three parameters of Comet assay including olive tail moment (OTM), tail length and tail DNA showed significant (p<0.05) increases in blood and bone marrow cells at respective doses of 10.80 and 5.40 mg alkaloid/kg b wt. However, some of the parameters were significantly increased even at lower doses of sanguinarine alkaloid (2.70 mg/kg b wt.). The frequency of cells exhibiting greater DNA damage were found to be increased by sanguinarine alkaloid in a concentration dependent manner. These results indicate that single exposure of sanguinarine alkaloid causes DNA damage in blood and bone marrow cells of mice, which could be responsible for the genotoxicity of argemone oil.
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Affiliation(s)
- Kausar M Ansari
- Food Toxicology Division, Industrial Toxicology Research Centre, Mahatma Gandhi Marg, P.O. Box No. 80, Lucknow 226001, India
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Elvin-Lewis M. Safety issues associated with herbal ingredients. ADVANCES IN FOOD AND NUTRITION RESEARCH 2005; 50:219-313. [PMID: 16263432 DOI: 10.1016/s1043-4526(05)50007-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]
Affiliation(s)
- Memory Elvin-Lewis
- Department of Biology, Washington University, St. Louis, Missouri 63130, USA
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Ansari KM, Chauhan LKS, Dhawan A, Khanna SK, Das M. Unequivocal evidence of genotoxic potential of argemone oil in mice. Int J Cancer 2004; 112:890-5. [PMID: 15386392 DOI: 10.1002/ijc.20319] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Consumption of mustard oil adulterated with argemone oil leads to a clinical condition, commonly referred to as "Epidemic Dropsy." Since in vitro studies have shown that sanguinarine, an active benzophenanthridine alkaloid of argemone oil, intercalates DNA molecule, the in vivo clastogenic and DNA damaging potential of argemone oil was investigated in mice. Swiss albino mice were intraperitoneally administered 0.5, 1.0, 2.0 and 4.0 ml/kg body wt. of argemone oil to analyze chromosome aberrations and micronucleus test, while 0.25, 0.5, 1.0 and 2.0 ml/kg body wt. were given for alkaline comet assay. The frequencies of chromosomal aberrations and micronucleated erythrocytes formation in mouse bone marrow cells increased in a dose-dependent manner following argemone oil treatment. However, significant induction in chromosomal aberrations (83%) and micronucleated erythrocytes formation (261%) were observed at a minimum dose of 1.0 ml/kg. The results of comet assay revealed DNA damage in blood, bone marrow and liver cells following argemone oil treatment. Olive tail moment (OTM) and tail DNA showed significant increase in bone marrow (35-44%) and blood cells (25-40%) even at a dose of 0.25 ml/kg body wt. of argemone oil. In liver cells, OTM was significantly increased (20%) at a dose of 0.25 ml/kg, while all the comet parameters including OTM, tail length and tail DNA showed significant increase (31-101%) at a dose of 0.5 ml/kg. These results clearly suggest that single exposure of argemone oil even at low doses produces genotoxic effects in mice.
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Affiliation(s)
- Kausar M Ansari
- Industrial Toxicology Research Centre, Mahatma Gandhi Marg, Lucknow, India
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Abstract
White lesions are frequently found during the examination of the oral cavity. Although some benign physiologic entities may present as white lesions, systemic conditions, infections, and malignancies may also present as white oral lesions. An appreciation of the many clinical entities that white lesions may represent is necessary if a differential diagnosis of white lesions is to be elucidated. The appreciation of subtle clinical findings associated with white lesions of the oral cavity permits clinicians to better care for their patients.
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Affiliation(s)
- Diana V Messadi
- Section of Oral Medicine, Division of Oral Biology and Medicine, School of Dentistry, University of California Los Angeles, Box 951668, Los Angeles, CA 90095-1668, USA
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Mascarenhas AK, Allen CM, Moeschberger ML. The association between Viadent use and oral leukoplakia--results of a matched case-control study. J Public Health Dent 2002; 62:158-62. [PMID: 12180043 DOI: 10.1111/j.1752-7325.2002.tb03437.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVES Several oral pathologists have described oral leukoplakia of the maxillary vestibule in patients with no traditional risk factors for the condition. On questioning these patients, it was determined that Viadent mouthrinse or Viadent toothpaste was commonly used by them. A hypothesis was developed that Viadent or a component of Viadent caused the lesions. This paper evaluates the association between oral leukoplakia and use of Viadent products. METHODS A matched case-control study was designed to test the hypothesis that use of Viadent products increases an individual's risk of oral leukoplakia. Cases included 58 patients diagnosed with oral leukoplakia identified through the biopsy service at the Ohio State University, College of Dentistry, Oral Pathology Section. The matched control was a friend or relative of the patient. Cases and controls were administered a questionnaire about their use of Viadent, and other known risk factors for leukoplakia such as tobacco and excessive alcohol use. RESULTS An age difference was seen between cases and controls, the cases being older (P < .001). After controlling for confounding factors, results of exact conditional logistic regression analyses showed that use of Viadent products was a risk indicator for oral leukoplakia (odds ratio = 10.0; 95% confidence interval = 2.0, 89.2). CONCLUSIONS Viadent use is a risk indicator for oral leukoplakia, confirming our previous findings.
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Stiborová M, Simánek V, Frei E, Hobza P, Ulrichová J. DNA adduct formation from quaternary benzo[c]phenanthridine alkaloids sanguinarine and chelerythrine as revealed by the 32P-postlabeling technique. Chem Biol Interact 2002; 140:231-42. [PMID: 12204579 DOI: 10.1016/s0009-2797(02)00038-8] [Citation(s) in RCA: 65] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Using the 32P-postlabeling assay, we investigated the ability of quaternary benzo[c]phenanthridine alkaloids, sanguinarine, chelerythrine and fagaronine, to form DNA adducts in vitro. Two enhanced versions of the assay (enrichment by nuclease P1 and 1-butanol extraction) were utilized in the study. Hepatic microsomes of rats pre-treated with beta-naphthoflavone or those of uninduced rats, used as metabolic activators, were incubated in the presence of calf thymus DNA and the alkaloids, with NADPH used as a cofactor. Under these conditions sanguinarine and chelerythrine, but not fagaronine, formed DNA adducts detectable by 32P-postlabeling. DNA adduct formation by both alkaloids was found to be concentration dependent. When analyzing different atomic and bond indices of the C11-C12 bond (ring B) in alkaloid molecules we found that fagaronine behaved differently from sanguinarine and chelerythrine. While sanguinarine and chelerythrine showed a preference for electrophilic attack indicating higher potential to be activated by cytochrome P450, fagaronine exhibited a tendency for nucleophilic attack. Our results demonstrate that sanguinarine and chelerythrine are metabolized by hepatic microsomes to species, which generate DNA adducts.
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Affiliation(s)
- Marie Stiborová
- Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, 128 40 2 Prague, Czech Republic.
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Wu CD, Savitt ED. Evaluation of the safety and efficacy of over-the-counter oral hygiene products for the reduction and control of plaque and gingivitis. Periodontol 2000 2002; 28:91-105. [PMID: 12013351 DOI: 10.1034/j.1600-0757.2002.280105.x] [Citation(s) in RCA: 67] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Affiliation(s)
- Christine D Wu
- Department of Periodontics, College of Dentistry, University of Illinois at Chicago, USA
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Sedo A, Vlasicová K, Barták P, Vespalec R, Vicar J, Simánek V, Ulrichová J. Quaternary benzo[c]phenanthridine alkaloids as inhibitors of aminopeptidase N and dipeptidyl peptidase IV. Phytother Res 2002; 16:84-7. [PMID: 11807974 PMCID: PMC7168101 DOI: 10.1002/ptr.969] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/1999] [Accepted: 06/15/2000] [Indexed: 11/20/2022]
Abstract
Chelerythrine, sanguinarine and an alkaloid extract from Macleaya cordata--sanguiritrin--were found to be inhibitors of aminopeptidase A and dipeptidyl peptidase IV, while fagaronine inhibited dipeptidyl peptidase IV only. At 50 microM, chelerythrine, sanguinarine and sanguiritrin inhibited aminopeptidase N by 82%, 82%, 88%, DPP IV by 38%, 62%, 57%, and fagaronine by 34%, respectively. When bovine serum albumin (500 microg/mL) was added, the inhibition of both proteases by quaternary benzo[c]phenanthridine alkaloids (QBA) (50 microM) was significantly diminished. Strong interaction of chelerythrine and sanguinarine with bovine and human serum albumin was proved by electrophoretic determination of their respective conditional binding constants.
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Affiliation(s)
- Aleksi Sedo
- Joint Laboratory of Cancer Cell Biology of the 1st Faculty of Medicine, Charles University and Institute of Physiology, Academy of Sciences, 121 08 Prague, Czech Republic
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Ulrichová J, Dvorák Z, Vicar J, Lata J, Smrzová J, Sedo A, Simánek V. Cytotoxicity of natural compounds in hepatocyte cell culture models. The case of quaternary benzo[c]phenanthridine alkaloids. Toxicol Lett 2001; 125:125-32. [PMID: 11701231 DOI: 10.1016/s0378-4274(01)00430-1] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
The quaternary benzo[c]phenanthridine alkaloids (QBA) produce a plethora of species- and tissue-specific effects but the molecular basis of their biological activities remain mysterious. The objective of the present study was to investigate the cytotoxicity of QBA alkaloids, sanguinarine (SA), chelerythrine (CHE), fagaronine (FA), and the extract from Macleaya cordata in primary cultures of human and porcine hepatocytes. The cellular damage was assessed by the MTT assay, lactate dehydrogenase (LDH) leakage and the determination of intracellular glutathione (GSH) levels. The results are summarised as follows: (i) The alkaloids tested in doses 0.1 and 10 microM did not display statistically significant cytotoxicity for 0-3 h incubation; (ii) SA and CHE showed the dose- and time-dependent toxicity within the range 25-100 microM whereas FA was not toxic; (iii) the LDH leakage into the medium was higher for SA than for CHE, thus revealing a potent potential of SA to disturb cell-membrane integrity; (iv) after 3 h incubation with 100 microM SA/CHE, mitochondrial dehydrogenase activity (MTT assay) and the cellular GSH levels decreased to residual values of about 40% suggesting that mitochondria are unlikely to be a primary target for SA/CHE in the cell; (v) no differences were found in the response to QBA application in human vs porcine hepatocyte.
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Affiliation(s)
- J Ulrichová
- Institute of Medical Chemistry and Biochemistry, Palacký University, 775 15, Olomouc, Czech Republic.
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Abstract
Recently, leukoplakia of the maxillary vestibule was described in patients with no traditional risk factors but who had used Viadent products. We designed a case-control study to evaluate the hypothesis that Viadent users were more likely to have lesions. One hundred and forty-eight cases and controls were identified through the Section of Oral and Maxillofacial Pathology. Cases and controls were administered a questionnaire about Viadent use and other known risks. Results of crude, stratified, and logistic regression analyses showed that use of Viadent products was a risk indicator for leukoplakia (adjusted OR = 9.7, 95% CI = 4.7-21.6), with a strong dose-response relation.
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Affiliation(s)
- A K Mascarenhas
- Section of Health Service Research, College of Dentistry, The Ohio State University, Columbus 43218-2357, USA
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40
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Abstract
During the latter part of this century the practice of herbalism has become mainstream throughout the world. This is due in part to the recognition of the value of traditional medical systems, particularly of Asian origin, and the identification of medicinal plants from indigenous pharmacopeias that have been shown to have significant healing power, either in their natural state or as the source of new pharmaceuticals. Generally these formulations are considered moderate in efficacy and thus less toxic than most pharmaceutical agents. In the Western world, in particular, the developing concept that 'natural' is better than 'chemical' or 'synthetic' has led to the evolution of Neo-Western herbalism that is the basis of an ever expanding industry. In the US, often guised as food, or food supplements, known as nutriceuticals, these formulations are readily available for those that wish to self-medicate. Within this system, in particular, are plants that lack ethnomedical verification of efficacy or safety. Unfortunately there is no universal regulatory system in place that insures that any of these plant remedies are what they say they are, do what is claimed, or most importantly are safe. Data will be presented in this context, outlining how adulteration, inappropriate formulation, or lack of understanding of plant and drug interactions have led to adverse reactions that are sometimes life-threatening or lethal.
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Affiliation(s)
- M Elvin-Lewis
- Department of Biology, Washington University, Box 1137, St. Louis, MO 63130-4899, USA.
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Fettig A, Pogrel MA, Silverman S, Bramanti TE, Da Costa M, Regezi JA. Proliferative verrucous leukoplakia of the gingiva. ORAL SURGERY, ORAL MEDICINE, ORAL PATHOLOGY, ORAL RADIOLOGY, AND ENDODONTICS 2000; 90:723-30. [PMID: 11113818 DOI: 10.1067/moe.2000.108950] [Citation(s) in RCA: 75] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
OBJECTIVE The purpose of this study was to describe the clinical-pathologic features of what appears to be a gingival form of proliferative verrucous leukoplakia. STUDY DESIGN Ten adult patients with recurrent and histologically progressive gingival leukoplakias who were diagnosed and treated at the University of California, San Francisco between 1994 and 1999, comprised the subject group for this investigation. Clinical and microscopic features were reviewed. Proliferation indices and p53 expression were evaluated immunohistochemically, and the presence of human papillomavirus (HPV) DNA was determined by using polymerase chain reaction (PCR) amplification. RESULTS Lesions presented as solitary or regional flat/papillary/verrucal leukoplakias of the free and attached gingiva (tooth-bearing areas only). With time, flat lesions developed a papillary or verruciform profile. Although lesions were recurrent, they were confined to the gingiva, and multiple lesions did not develop. Half the patients used tobacco, and HPV could not be detected by using PCR. Microscopically, 6 cases began as hyperkeratotic lesions, and 4 initially exhibited a psoriasiform pattern with a marked inflammatory component. With recurrences, the lesions became progressively atypical histologically. The proliferation indices for these lesions showed modest increases over normal epithelium, and positive p53 staining was evident in 4 of 10 cases, indicating a disruption of the keratinocyte cell cycle in these lesions. The mechanism associated with the positive p53 staining (protein binding to wild type p53 versus mutation of the p53 gene) was not determined. Lesions recurred after conservative scalpel or laser excision, and many developed into verrucous or squamous cell carcinoma. CONCLUSIONS Proliferative verrucous leukoplakia of the gingiva (PVLG) appears to be a subset of oral proliferative verrucous leukoplakia. It can be characterized as a solitary, recurring, progressive white patch that develops a verruciform architecture and may not be associated with HPV. PVLG has an unpredictable course and is at risk for development into verrucous or squamous cell carcinoma. Currently, there is no way to determine or predict which gingival white lesions will follow the clinical course described for this group of patients with PVLG.
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Affiliation(s)
- A Fettig
- University of California, Department of Oral and Maxillofacial Surgery, San Francisco 94143-0424, USA
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Scully C. Advances in oral medicine. PRIMARY DENTAL CARE : JOURNAL OF THE FACULTY OF GENERAL DENTAL PRACTITIONERS (UK) 2000; 7:55-8. [PMID: 11404968 DOI: 10.1308/135576100322732184] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
This paper reviews some of the more important areas of oral medicine where significant advances have been made in the past decade. There have been developments in the definition of new entities causing orofacial pain, and new therapies. Oral cancer has been recognised as increasing in incidence and the genetic basis is becoming clearer, along with improvements in early diagnostic techniques and treatment. The basis of aphthae is being unravelled and new therapies are appearing. There is greater understanding of the aetiopathogenesis and treatment of various dermatoses that present in the mouth. Treatment and prevention of leukoplakias is improving and the importance of candidosis has become evident.
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Affiliation(s)
- C Scully
- International Centres for Excellence in Dentistry, and Eastman Dental Institute for Oral Health Care Sciences, University College London, University of London
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Eversole LR, Eversole GM, Kopcik J. Sanguinaria-associated oral leukoplakia: comparison with other benign and dysplastic leukoplakic lesions. ORAL SURGERY, ORAL MEDICINE, ORAL PATHOLOGY, ORAL RADIOLOGY, AND ENDODONTICS 2000; 89:455-64. [PMID: 10760727 DOI: 10.1016/s1079-2104(00)70125-9] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVE This study was undertaken to compare and contrast biomarkers and ploidy data from maxillary gingiva leukoplakias associated with dentifrices and mouthrinses containing the herbal compound sanguinaria with other forms of oral benign and premalignant mucosal keratosis. STUDY DESIGN Representative archived specimens of benign keratosis, sanguinaria-associated keratosis, and keratosis with dysplasia were used for computerized image analysis and biomarker immunohistochemical assays to assess ploidy, DNA content, and p53 and proliferating cell nuclear antigen immunoreactivity of nuclei. RESULTS DNA content was significantly higher and higher numbers of cell populations with hyperploid nuclei were encountered in the dysplastic group than in the other two groups (P <.001). Sanguinaria-associated keratosis did not harbor significant numbers of p53-expressing nuclei, yet it showed a significant elevation in proliferating cell nuclear antigen-labeled nuclei in total, in the basal layer, and in the spinous layer in comparison with benign keratoses (P <.001). In addition, 1.5% of the sanguinaria-associated leukoplakia epithelial cell population was characterized by nuclei with a greater than 4-fold increase in DNA content. CONCLUSIONS Sanguinaria-associated keratoses show some marker and image analysis profiles similar to those of non-sanguinaria dysplastic lesions of the lip and mucosa. Preparations containing sanguinaria should be avoided until the risk for malignant transformation is determined.
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Affiliation(s)
- L R Eversole
- University of the Pacific and Pathology Consultants of New Mexico, Department of Pathology and Medicine, University of the Pacific School of Dentistry, San Francisco, CA 94115, USA
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Sevcík J, Vicar J, Ulrichová J, Válka I, Lemr K, Simánek V. Capillary electrophoretic determination of sanguinarine and chelerythrine in plant extracts and pharmaceutical preparations. J Chromatogr A 2000; 866:293-8. [PMID: 10670819 DOI: 10.1016/s0021-9673(99)01126-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Capillary electrophoresis was employed to determine the principal quaternary benzo[c]phenanthridine alkaloids, sanguinarine and chelerythrine, in two plant extracts and one oral hygiene product. Phosphate-Tris buffer of pH 2.5 was used as a background electrolyte, limits of detection were 3 micromol/l(-1) (sanguinarine) and 2.4 micromol,l(-1) (chelerythrine) using UV detection at 270 nm. The method, which correlated well with HPLC, is suitable for serial determination of sanguinarine and chelerythrine in plant products and pharmaceuticals.
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Affiliation(s)
- J Sevcík
- Department of Analytical Chemistry, Palacký University, Olomouc, Czech Republic
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Munro IC, Delzell ES, Nestmann ER, Lynch BS. Viadent usage and oral leukoplakia: a spurious association. Regul Toxicol Pharmacol 1999; 30:182-96. [PMID: 10620468 DOI: 10.1006/rtph.1999.1339] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Oral rinse and toothpaste products (Viadent) containing Sanguinaria extract have been shown through extensive clinical trials to be effective against plaque build-up and gingivitis. To establish safety, a comprehensive research program was conducted, including a series of clinical studies and a number of animal studies to evaluate acute, subchronic, and chronic toxicity, and the potential for irritation of mucosal tissues. In 1990 and 1993, an Expert Panel reported on reviews of these data and concluded that Viadent products are safe for their intended use. Despite the large database of information to support the safety of Viadent products, Damm et al. (1999) recently raised the possibility that their usage may be causally associated with development of oral leukoplakia. However, a critique of this recent report shows that it does not fulfil criteria for establishing causation. In particular, the study does not show that exposure to Viadent preceded the onset of leukoplakia, it does not demonstrate dose-response or biological plausibility, and it suffers from selection and information bias and from potential confounding. Furthermore, upon critical evaluation, the Damm et al. (1999) report on a case-series is inconsistent with the weight of available clinical evidence showing that Sanguinaria extract-containing oral health care products cause no cytotoxic or significant irritant effects in the oral mucosa in human studies of up to 6 months duration. The animal data similarly do not support a causal association between Viadent usage and oral leukoplakia in humans. These data demonstrate that Sanguinaria extract and whole Viadent formulations are without significant irritation potential and have no effects on the oral mucosa, even in studies with life-long dietary exposure to Sanguinaria extract. The mutagenicity and genotoxicity data do not indicate that Sanguinaria extract or its components are genotoxic in vivo. The results of 2 GLP-compliant rat oncogenicity studies provide no evidence of any carcinogenic effect of Sanguinaria extract. In conclusion, the available clinical and animal data provide no support for and in fact argue strongly against the hypothesis that the use of Viadent toothpaste and/or oral rinse products may be causally associated with the development of leukoplakia in humans.
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Affiliation(s)
- I C Munro
- CanTox Health Sciences International, Inc., Mississauga, Ontario, L5N 2X7, Canada
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Affiliation(s)
- C B Fowler
- Oral & Maxillofacial Pathology Services, Wilford Hall Medical Center, Lackland Air Force Base, San Antonio, Texas, USA
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47
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Slavkin HC. Learning, immunology and allergic responses. J Am Dent Assoc 1999; 130:863-7. [PMID: 10377646 DOI: 10.14219/jada.archive.1999.0312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Affiliation(s)
- H C Slavkin
- National Institute of Dental and Craniofacial Research, Bethesda, Md. 20892-2290, USA
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Allen CM. Viadent-related leukoplakia--the tip of the iceberg? ORAL SURGERY, ORAL MEDICINE, ORAL PATHOLOGY, ORAL RADIOLOGY, AND ENDODONTICS 1999; 87:393-4. [PMID: 10225617 DOI: 10.1016/s1079-2104(99)70256-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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