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Indriyani N, Nur’aeny N. The Therapeutic Effects of Curcumin on Oral Disease: A Systematic Review. Clin Pharmacol 2025; 17:13-24. [PMID: 40034679 PMCID: PMC11874755 DOI: 10.2147/cpaa.s506396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 01/30/2025] [Indexed: 03/05/2025] Open
Abstract
Introduction Curcumin is an extract from herbal plants that has been implicated in the treatment of any disease, including oral disease. There are various types of curcumin formulation as the option of the therapy. The aim of this review is to describe the curcumin mechanism in reducing the severity, pain score, and oral lesion size as the therapeutic effects. Methods This systematic review used the Preferred Reporting Items for Systematic Review and Meta Analysis (PRISMA) guidelines. Databases used for articles include PubMed, Science Direct, and Scopus with inclusion criteria published from 2014 to 2024, full text, in English, and randomized controlled trial (RCT). Results The present study included 21 RCTs with a total of 1244 individuals. In this study, curcumin was most commonly used for oral submucous fibrosis, with 9 studies demonstrating that curcumin has anti-inflammatory properties and inhibits collagenase. All studies demonstrate that curcumin produces significant results in the management of oral disease. The remain studies showed curcumin has antioxidant, inhibit collagenase, antifungal, and wound healing properties for oral leukoplakia, recurrent aphthous stomatitis (RAS), oral lichen planus (OLP), and denture stomatitis. Conclusion Curcumin has anti inflammatory, antioxidant, inhibit collagenase, antifungal, and wound healing properties for reducing the severity of lesion, pain score and oral lesion size as the therapeutic effects in the patients with oral disease including OSMF, mucositis, leukoplakia, RAS, OLP, and denture stomatitis.
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Affiliation(s)
- Novi Indriyani
- Oral Medicine Residency, Faculty of Dentistry, Universitas Padjadjaran, Bandung, Indonesia
| | - Nanan Nur’aeny
- Oral Medicine Residency Program, Department of Oral Medicine, Faculty of Dentistry, Padjadjaran University, Bandung, Indonesia
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Zhang L, Tan J, Liu Y, Luo M. Curcumin relieves arecoline-induced oral submucous fibrosis via inhibiting the LTBP2/NF-κB axis. Oral Dis 2024; 30:2314-2324. [PMID: 37382472 DOI: 10.1111/odi.14656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 05/15/2023] [Accepted: 06/12/2023] [Indexed: 06/30/2023]
Abstract
BACKGROUND Submucosal fibrosis (OSF) of the oral cavity is a chronic scarring disease. Arecoline (Are) is the driving factor for the occurrence and deterioration of OSF. Curcumin plays a vital anti-inflammatory role in Are-induced OSF development. However, its potential pharmacological mechanism needs to be elucidated. METHODS The relative molecular level was measured via qRT-PCR or Western blot. MTT assay, transwell assay and flow cytometry detected cell proliferation, migration, and apoptosis. The correlation between hypoxia-inducible factor-1α (HIF-1α) and LTBP2 promoter was confirmed through dual-luciferase reporter assay. ELISA was performed to detect inflammatory cytokines levels. RESULTS Curcumin alleviated Are-induced oral mucosal fibroblast cells fibrosis by reducing oral mucosa fibroblasts viability, promoting cell apoptosis, suppressing cell migration, and down-regulating the levels of fibrosis markers and inflammatory factors. Curcumin relieved Are-induced OSF via inhibiting HIF-1α. Mechanically, HIF-1α bound to the promoter of LTBP2 to transcriptionally activated LTBP2. LTBP2 knockdown relieved Are-induced OSF, and curcumin down-regulated LTBP2 via inhibiting HIF-1α to relieve Are-induced OSF. Moreover, curcumin decreased NF-κB signal associated proteins via inhibiting LTBP2 to relieve Are-induced OSF. CONCLUSION Curcumin reduced the transcription level of LTBP2 by inhibiting HIF-1α, thereby inactivating NF-κB pathway to alleviate Are-induced OSF.
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Affiliation(s)
- Lin Zhang
- Department of Stomatology, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province, China
| | - Jin Tan
- Department of Stomatology, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province, China
| | - Yiping Liu
- Department of Stomatology, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province, China
| | - Mang Luo
- Hunan Changsha Maternal and Child Health Hospital, Changsha, Hunan Province, China
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Shao Y, Miao J, Wang Y. Curcumin in the treatment of oral submucous fibrosis: a systematic review and meta-analysis of randomized controlled trials. Int J Oral Maxillofac Surg 2024; 53:239-250. [PMID: 38057194 DOI: 10.1016/j.ijom.2023.11.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 11/17/2023] [Accepted: 11/22/2023] [Indexed: 12/08/2023]
Abstract
The objective was to evaluate the efficacy of curcumin in improving mouth opening (MO), burning sensation (BS), and tongue protrusion (TP) symptoms in patients with oral submucous fibrosis (OSF). An electronic search up to November 2022 was conducted in the PubMed, Web of Science, Embase, EBSCO, ProQuest, and Cochrane Library databases to identify studies using curcumin in the treatment of OSF with comparison to control groups (drugs previously proven to be effective for OSF treatment) or placebo. Only randomized controlled trials (RCTs) were considered. RevMan 5.3 software was used for the meta-analysis. Thirteen RCTs met the eligibility criteria and were included in the analysis. The results showed no significant improvement in MO (in millimetres) for curcumin when compared to control at 1 month (P = 0.91), 2 months (P = 0.54), 3 months (P = 0.56), or 6 months (P = 0.17) of treatment. There was no significant difference in BS (assessed using a visual analogue scale) between curcumin and control after 1 month (P = 0.05), 2 months (P = 0.64), 3 months (P = 0.13), or 6 months (P = 0.56) of treatment. Compared with the control groups, treatment with curcumin for 1 month (P = 0.32), 2 months (P = 0.07), and 3 months (P = 0.14) did not significantly improve the TP (in millimetres) of patients. The administration of curcumin, whether topically applied or taken orally, did not confer statistically significant improvements in MO, BS, or TP in comparison to the control treatments, among patients with OSF. The results of this meta-analysis showed that compared to placebo, the application of curcumin for 6 months markedly alleviated BS (P < 0.001). Curcumin treatment in OSF reaches a clinically effective range, but more bioavailability-centred outcomes should be reported. Robust multicentre RCTs are warranted to elucidate the efficacy of curcumin in improving specific outcomes like MO, BS, and TP in patients with this condition. Defining the therapeutic role of this natural compound may provide an effective botanical alternative for managing OSF.
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Affiliation(s)
- Y Shao
- Xiangya School of Stomatology, Central South University, Changsha, China
| | - J Miao
- Xiangya School of Public Health, Central South University, Changsha, China
| | - Y Wang
- Xiangya School of Stomatology, Central South University, Changsha, China.
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Meetam T, Angspatt A, Aramwit P. Evidence of Potential Natural Products for the Management of Hypertrophic Scars. J Evid Based Integr Med 2024; 29:2515690X241271948. [PMID: 39196306 PMCID: PMC11359448 DOI: 10.1177/2515690x241271948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 05/29/2024] [Accepted: 06/26/2024] [Indexed: 08/29/2024] Open
Abstract
Hypertrophic scarring is an aberrant wound-healing response to reestablish dermal integrity after an injury and can cause significant abnormalities in physical, aesthetic, functional, and psychological symptoms, impacting the patient's quality of life. There is currently no gold standard for preventing and treating hypertrophic scars. Therefore, many researchers have attempted to search for antihypertrophic scar agents with greater efficacy and fewer side effects. Natural therapeutics are becoming attractive as potential alternative anti-scarring agents because of their high efficacy, safety, biocompatibility, low cost, and easy accessibility. This review demonstrates various kinds of natural product-based therapeutics, including onion, vitamin E, Gotu kola, green tea, resveratrol, emodin, curcumin, and others, in terms of their mechanisms of action, evidence of efficacy and safety, advantages, and disadvantages when used as anti-scarring agents. We reviewed the literature based on data from in vitro, in vivo, and clinical trials. A total of 23 clinical trials were identified in this review; most clinical trials were ranked as having uncertain results (level of evidence 2b; n = 16). Although these natural products showed beneficial effects in both in vitro and in vivo studies of potential anti-scarring agents, there was limited clinical evidence to support their efficacy due to the limited quality of the studies, with individual flaws including small sample sizes, poor randomization, and blinding, and short follow-up durations. More robust and well-designed clinical trials with large-scale and prolonged follow-up durations are required to clarify the benefits and risks of these agents.
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Affiliation(s)
- Thunyaluk Meetam
- Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences and Center of Excellence in Bioactive Resources for Innovative Clinical Applications, Chulalongkorn University, Bangkok, Thailand
- Sirindhorn College of Public Health Trang, Faculty of Public Health and Allied Health Sciences, Praboromarajchanok Institute, Trang, Thailand
| | - Apichai Angspatt
- Department of Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Pornanong Aramwit
- Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences and Center of Excellence in Bioactive Resources for Innovative Clinical Applications, Chulalongkorn University, Bangkok, Thailand
- The Academy of Science, The Royal Society of Thailand, Dusit, Bangkok,
Thailand
- Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand
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Gao D, Fang L, Liu C, Yang M, Yu X, Wang L, Zhang W, Sun C, Zhuang J. Microenvironmental regulation in tumor progression: Interactions between cancer-associated fibroblasts and immune cells. Biomed Pharmacother 2023; 167:115622. [PMID: 37783155 DOI: 10.1016/j.biopha.2023.115622] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Revised: 09/20/2023] [Accepted: 09/28/2023] [Indexed: 10/04/2023] Open
Abstract
The tumor microenvironment (TME), the "soil" on which tumor cells grow, has an important role in regulating the proliferation and metastasis of tumor cells as well as their response to treatment. Cancer-associated fibroblasts (CAFs), as the most abundant stromal cells of the TME, can not only directly alter the immunosuppressive effect of the TME through their own metabolism, but also influence the aggregation and function of immune cells by secreting a large number of cytokines and chemokines, reducing the body's immune surveillance of tumor cells and making them more prone to immune escape. Our study provides a comprehensive review of fibroblast chemotaxis, malignant transformation, metabolic characteristics, and interactions with immune cells. In addition, the current small molecule drugs targeting CAFs have been summarized, including both natural small molecules and targeted drugs for current clinical therapeutic applications. A complete review of the role of fibroblasts in TME from an immune perspective is presented, which has important implications in improving the efficiency of immunotherapy by targeting fibroblasts.
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Affiliation(s)
- Dandan Gao
- College of Traditional Chinese Medicine, Weifang Medical University, Weifang 261000, China
| | - Liguang Fang
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Cun Liu
- College of Traditional Chinese Medicine, Weifang Medical University, Weifang 261000, China
| | - Mengrui Yang
- College of Traditional Chinese Medicine, Weifang Medical University, Weifang 261000, China
| | - Xiaoyun Yu
- College of Traditional Chinese Medicine, Weifang Medical University, Weifang 261000, China
| | - Longyun Wang
- State Key Laboratory of Quality Research in Chinese Medicine and Faculty of Chinese Medicine, Macau University of Science and Technology, 999078, Macao Special Administrative Region of China
| | - Wenfeng Zhang
- State Key Laboratory of Quality Research in Chinese Medicine and Faculty of Chinese Medicine, Macau University of Science and Technology, 999078, Macao Special Administrative Region of China
| | - Changgang Sun
- College of Traditional Chinese Medicine, Weifang Medical University, Weifang 261000, China; Department of Oncology, Weifang Traditional Chinese Hospital, Weifang 261000, China.
| | - Jing Zhuang
- Department of Oncology, Weifang Traditional Chinese Hospital, Weifang 261000, China.
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Eldesoqui M, Ahmed ME, Abdel-Kareem MA, Badawy MM, Dawood AF, Mohamed AS, Ibrahim AM, El-Mansi AA, El-Sherbiny M, Hendawy M. Curcumin Mitigates Malathion-Induced Renal Injury: Suppression of Apoptosis and Modulation of NF-κβ/TNF-α and Nrf2, and HO-1 Signaling. Metabolites 2023; 13:1117. [PMID: 37999213 PMCID: PMC10673029 DOI: 10.3390/metabo13111117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 10/23/2023] [Accepted: 10/24/2023] [Indexed: 11/25/2023] Open
Abstract
Malathion is one of the most used organophosphorus pesticides that is used for many reasons such as agriculture and industry. Human exposure to malathion may occur through various means, such as eating food that has been treated with it. Malathion not only increases oxidative stress but also decreases the antioxidant capacity. Curcumin is a powerful antioxidant with many pharmacological actions. Curcumin can act as a free radical scavenger and inhibit the activation and nuclear translocation of NF-κB. Curcumin could combat the lipid peroxidation and antioxidant depletion that trigger the apoptotic pathways. This study aims to examine the antioxidant, anti-inflammatory, and antiapoptotic effects of curcumin. Twenty-four Sprague Dawley rats were divided into four groups (six rats each): control, curcumin, malathion, and malathion + curcumin groups. At the assigned time, blood samples were used for the assessment of serum creatinine, and the kidneys were excised and washed; parts of them were used for the assessment of total oxidant status (TOS), oxidative stress index (OSI), the oxidative stress marker malondialdehyde (MDA), total antioxidant capacity (TAC), and glutathione (GSH) activity, other parts were fixed in formalin for further staining. Histopathological evaluation was performed for the fixed specimens after staining with H&E, sirus red, and the immunohistochemical staining for NF-κβ, TNF-α, Caspase-3, Nrf2, and HO-1. Curcumin significantly decreases the serum creatinine after malathion exposure and significantly restores the oxidant/antioxidant balance by increasing TAC and GSH and decreasing TOS, OSI, and MDA. Curcumin exerts its reno-protective effect and restores the histological architecture of the kidney by downregulating the immune expression of NF-κβ, TNF-α, and Caspase-3 and upregulating the expression of Nrf2 and HO-1. This study concluded that curcumin protects against nephrotoxicity caused by malathion by exerting its antioxidant, anti-inflammatory, and anti-apoptotic capabilities.
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Affiliation(s)
- Mamdouh Eldesoqui
- Department of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt; (M.E.); (M.E.A.); (M.H.)
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia;
| | - Magda E. Ahmed
- Department of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt; (M.E.); (M.E.A.); (M.H.)
| | - Mona A. Abdel-Kareem
- Department of Anatomy and Embryology, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh P.O. Box 33516, Egypt;
| | - Mohamed Moharram Badawy
- Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt;
- Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Delta University for Science and Technology, Gamasa 11152, Egypt
| | - Amal Fahmy Dawood
- Department of Basic Medical Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia;
| | - Abdelaty Shawky Mohamed
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia;
- Pathology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Ateya Megahed Ibrahim
- Department of Nursing, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia;
- Department of Family and Community Health Nursing, Faculty of Nursing, Port Said University, Port Said P.O. Box 42511, Egypt
| | - Ahmed A. El-Mansi
- Biology Department, College of Science, King Khalid University, Abha 61413, Saudi Arabia;
| | - Mohamad El-Sherbiny
- Department of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt; (M.E.); (M.E.A.); (M.H.)
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia;
| | - Mahmoud Hendawy
- Department of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt; (M.E.); (M.E.A.); (M.H.)
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Minhaco VMTR, Maquera Huacho PM, Mancim Imbriani MJ, Tonon CC, Chorilli M, Rastelli ANDS, Spolidorio DMP. Improving antimicrobial activity against endodontic biofilm after exposure to blue light-activated novel curcumin nanoparticle. Photodiagnosis Photodyn Ther 2023; 42:103322. [PMID: 36773754 DOI: 10.1016/j.pdpdt.2023.103322] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 12/29/2022] [Accepted: 02/03/2023] [Indexed: 02/12/2023]
Abstract
New therapies involving natural products and nanobiotechnology open additional perspectives to reduce endodontic infections. Curcumin is a natural polyphenol extracted from the dry rhizome of curcuma long Linn with therapeutic properties for application in nanobiotechnology and as a photosensitizer for photodynamic therapy. This study aimed to synthesize a novel polymeric nanoparticle of poly (lactic-co-glycolic acid) (PLGA) loaded with curcumin (NP+Cur), and evaluate its antimicrobial activity against endodontic biofilms. Additionally, its biocompatibility using oral keratinocytes was assessed. The polymeric NP+Cur was prepared by the nanoprecipitation method. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were calculated for the three endodontic bacteria (Enterococcus faecalis, Streptococcus oralis and Actinomyces viscosus). Antibacterial activity of NP+Cur against single- and multispecies biofilm pre-formed on the botton 24-well plate and into dentin tubules of bovine teeth were evaluated by colony forming units and confocal laser scanning microscopy. The pre-irradiation time was 5 min followed by exposure to blue light-emitting diode at 450 nm for the photodynamic treatment. Cell viability using oral keratinocytes was assessed by Alamar Blue assay. MIC and MBC showed antibacterial activity of NP+Cur against endodontic bacteria. A treatment of pre-formed biofilms of endodontic bacteria with NP+Cur also significantly decreased bacterial viability. The concentration of 325 μg/mL of photoactivated NP+Cur was the one that most reduced the viability of the endodontic bacteria evaluated. Regarding biocompatibility, NP+Cur 325 μg/mL and pure nanoparticles showed a cell viability greater than 80%. The novel polymeric nanoparticles loaded with curcumin may be a promising adjunct use to treatment of endodontic infections.
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Affiliation(s)
- Vivian Maria Tellaroli Rodrigues Minhaco
- Department of Physiology and Pathology, School of Dentistry, São Paulo State University (Unesp), Rua Humaitá, 1680, Araraquara, SP 14801-903, Brazil; Department of Oral Diagnosis and Surgery, School of Dentistry, São Paulo State University (Unesp), Rua Humaitá, 1680, Araraquara, SP 14801-903, Brazil
| | - Patricia Milagros Maquera Huacho
- Department of Physiology and Pathology, School of Dentistry, São Paulo State University (Unesp), Rua Humaitá, 1680, Araraquara, SP 14801-903, Brazil
| | - Maria Júlia Mancim Imbriani
- Department of Physiology and Pathology, School of Dentistry, São Paulo State University (Unesp), Rua Humaitá, 1680, Araraquara, SP 14801-903, Brazil; Department of Oral Diagnosis and Surgery, School of Dentistry, São Paulo State University (Unesp), Rua Humaitá, 1680, Araraquara, SP 14801-903, Brazil
| | - Caroline Coradi Tonon
- Wellman Center for Photomedicine, Massachusetts General Hospital, and Harvard Medical School, 40 Blossom St, Boston, MA 02114, United States
| | - Marlus Chorilli
- Department of Drugs and Medicines, International School of Pharmaceuticals Sciences, São Paulo State University (Unesp), Rodovia Araraquara Jaú, Km 01, Araraquara, SP 14800-903, Brazil
| | - Alessandra Nara de Souza Rastelli
- Department of Restorative Dentistry, School of Dentistry, São Paulo State University (Unesp), Rua Humaitá, 1680, Araraquara, SP 14801-903, Brazil
| | - Denise Madalena Palomari Spolidorio
- Department of Physiology and Pathology, School of Dentistry, São Paulo State University (Unesp), Rua Humaitá, 1680, Araraquara, SP 14801-903, Brazil.
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Ali FE, Abd El-Aziz MK, Sharab EI, Bakr AG. Therapeutic interventions of acute and chronic liver disorders: A comprehensive review. World J Hepatol 2023; 15:19-40. [PMID: 36744165 PMCID: PMC9896501 DOI: 10.4254/wjh.v15.i1.19] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 11/17/2022] [Accepted: 12/21/2022] [Indexed: 01/16/2023] Open
Abstract
Liver disorders are one of the most common pathological problems worldwide. It affects more than 1.5 billion worldwide. Many types of hepatic cells have been reported to be involved in the initiation and propagation of both acute and chronic liver diseases, including hepatocytes, Kupffer cells, sinusoidal endothelial cells, and hepatic stellate cells (HSCs). In addition, oxidative stress, cytokines, fibrogenic factors, microRNAs, and autophagy are also involved. Understanding the molecular mechanisms of liver diseases leads to discovering new therapeutic interventions that can be used in clinics. Recently, antioxidant, anti-inflammatory, anti-HSCs therapy, gene therapy, cell therapy, gut microbiota, and nanoparticles have great potential for preventing and treating liver diseases. Here, we explored the recent possible molecular mechanisms involved in the pathogenesis of acute and chronic liver diseases. Besides, we overviewed the recent therapeutic interventions that targeted liver diseases and summarized the recent studies concerning liver disorders therapy.
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Affiliation(s)
- Fares Em Ali
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt.
| | | | - Elham I Sharab
- Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt
| | - Adel G Bakr
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt
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Wang G, Zhu J, Liu L. Curcumin deactivates M2 macrophages to alleviate lung fibrosis in IgG4-related disease through activating the toll-like receptor 9 pathway. Immunopharmacol Immunotoxicol 2021; 44:I-X. [PMID: 34775900 DOI: 10.1080/08923973.2021.2001498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
OBJECTIVES To explore the effects and mechanism of Curcumin on pulmonary fibrosis in IgG4-related disease (IgG4-RD). METHODS The expression of fibrosis factors, inflammatory factors and markers of M1/M2 macrophages in lung tissue of IgG4-RD patients was detected by RT-qPCR or Western blotting. The macrophages of IgG4-RD patients were isolated and treated with different concentrations of Curcumin, and the markers of M1/M2 macrophages were detected by RT-qPCR, Western blotting or ELISA. Next, the pulmonary fibroblasts of IgG4-RD patients were isolated and cultured with the supernatant of macrophages treated with Curcumin. Cell proliferation and migration were detected by CCK-8 and Transwell assay, respectively. SOD activity and ROS content were detected by the xanthine oxidase method and flow cytometry, respectively. Then the expression of Toll-like Receptor 9 (TLR9) and its downstream proteins were detected by Western blotting. After treating the cells with TLR9 antagonist IRS869, the changes in the above indicators were further detected. RESULTS The collagen deposition, inflammatory factors secretion and M2 polarization of macrophages were increased in lung tissue of IgG4-RD patients. Curcumin decreased the macrophage M2 polarization and inhibited the proliferation and migration of fibroblasts, reduced the level of oxidative stress, and suppressed the occurrence of fibrosis. The TLR9 pathway was inhibited in IgG4-RD lung tissues, and Curcumin activated this pathway and reduced macrophage M2 polarization. And the inhibitory effect of Curcumin on pulmonary fibrosis could be reversed by IRS869. CONCLUSIONS Curcumin inhibited the occurrence of pulmonary fibrosis in IgG4-RD by inhibiting the TLR9 signaling pathway-mediated macrophage M2 polarization.
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Affiliation(s)
- Gang Wang
- School of Clinical Medicine, Tsinghua University, Beijing, China.,Department of Rheumatology and Immunology, Beijing Tsinghua Changgung Hospital, Beijing, China
| | - Jian Zhu
- Department of Rheumatology and Immunology, the First Medical Center of PLA General Hospital, Beijing, China
| | - LiPeng Liu
- Department of Rheumatology and Immunology, Zaozhuang Municipal Hospital of Shandong Province, Zaozhuang, Shandong Province, China
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Rajesh Kashyap R, Shanker Kashyap R. Herbal derivatives in the management of mouth opening in oral submucous fibrosis-A network meta-analysis. Oral Dis 2021; 27:1606-1615. [PMID: 32671872 DOI: 10.1111/odi.13544] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 06/08/2020] [Accepted: 06/19/2020] [Indexed: 11/26/2022]
Abstract
OBJECTIVES Oral submucous fibrosis is a potentially malignant disorder commonly seen in Asian countries. In this disease, the mucosa becomes stiff and patients have difficulty in mouth opening, thus affecting their quality of life. Recently, practitioners are focusing on herbal derivatives instead of commonly practiced intralesional steroids for the management of this disorder. Hence, we conducted a network meta-analysis of randomized clinical trials on herbal derivatives to identify the most effective treatment for oral submucous fibrosis. MATERIALS AND METHODS Electronic search for articles published in various journals was undertaken through various search engines till January 2020. 14 articles were selected which had performed randomized control trials of herbal derivatives against control/placebo. Frequentist network meta-analysis was performed using R studio software, and effective treatment ranking was derived. RESULTS The treatment ranking was generated, and relative to mouth opening, the most effective treatment was lycopene administered along with vitamin E and the second effective drug was aloe vera gel. CONCLUSION This network meta-analysis highlights the efficacy of some of the drugs of herbal origin which can be implemented by the practitioners in the management of initial stages of oral submucous fibrosis.
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Affiliation(s)
| | - Rajesh Shanker Kashyap
- Department of Periodontics, Yenepoya Dental College, Yenepoya University (Deemed to be), Mangalore, India
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Zoi V, Galani V, Lianos GD, Voulgaris S, Kyritsis AP, Alexiou GA. The Role of Curcumin in Cancer Treatment. Biomedicines 2021; 9:1086. [PMID: 34572272 PMCID: PMC8464730 DOI: 10.3390/biomedicines9091086] [Citation(s) in RCA: 104] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 08/19/2021] [Accepted: 08/23/2021] [Indexed: 12/24/2022] Open
Abstract
Curcumin is a polyphenol extracted from the rhizomes of the turmeric plant, Curcuma longa which has anti-inflammatory, and anticancer properties. Chronic inflammation is associated with the development of cancer. Curcumin acts on the regulation of various immune modulators, including cytokines, cyclooxygenase-2 (COX-2), and reactive oxygen species (ROS), which partly explains its anticancer effects. It also takes part in the downregulation of growth factors, protein kinases, oncogenic molecules and various signaling pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), c-Jun N-terminal kinase (JNK) and signal transducer and activator of transcription 3 (STAT3) signaling. Clinical trials of curcumin have been completed or are ongoing for various types of cancer. This review presents the molecular mechanisms of curcumin in different types of cancer and the evidence from the most recent clinical trials.
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Affiliation(s)
- Vasiliki Zoi
- Neurosurgical Institute, School of Medicine, University of Ioannina, 45500 Ioannina, Greece; (V.Z.); (S.V.); (A.P.K.)
- Department of Anatomy Histology-Embryology, School of Medicine, University of Ioannina, 45500 Ioannina, Greece;
| | - Vasiliki Galani
- Department of Anatomy Histology-Embryology, School of Medicine, University of Ioannina, 45500 Ioannina, Greece;
| | - Georgios D. Lianos
- Department of Surgery, University Hospital of Ioannina, 45500 Ioannina, Greece;
| | - Spyridon Voulgaris
- Neurosurgical Institute, School of Medicine, University of Ioannina, 45500 Ioannina, Greece; (V.Z.); (S.V.); (A.P.K.)
- Department of Neurosurgery, School of Medicine Ioannina, University of Ioannina, 45500 Ioannina, Greece
| | - Athanasios P. Kyritsis
- Neurosurgical Institute, School of Medicine, University of Ioannina, 45500 Ioannina, Greece; (V.Z.); (S.V.); (A.P.K.)
| | - George A. Alexiou
- Neurosurgical Institute, School of Medicine, University of Ioannina, 45500 Ioannina, Greece; (V.Z.); (S.V.); (A.P.K.)
- Department of Neurosurgery, School of Medicine Ioannina, University of Ioannina, 45500 Ioannina, Greece
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12
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Zhang L, Tan J, Liu YP, Liu X, Luo M. Curcumin relieves the arecoline-induced fibrosis of oral mucosal fibroblasts via inhibiting HIF-1α/TGF-β/CTGF signaling pathway: an in vitro study. Toxicol Res (Camb) 2021; 10:631-638. [PMID: 34141177 DOI: 10.1093/toxres/tfab046] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 04/19/2021] [Accepted: 04/27/2021] [Indexed: 11/14/2022] Open
Abstract
Oral submacosal fibrosis (OSF) has been recognized as one of the oral potentially malignant disorders. Areca nut chewing is implicated in this pathological fibrosis. The current treatments for OSF have failed to achieve the desired curative effect. Here, we propose that curcumin has excellent therapeutic effect on OSF and explore its specific mechanism. Transwell assay was performed to detected cell migration. Flow cytometry was used to measured apoptosis. And MTT assay was performed to test cell viability. Gene and protein levels were detected by quantitative real-time polymerase chain reaction (qPCR) and western blotting. Our results displayed that curcumin treatment reduced fibrosis-related molecules (collagen type I alpha 1, collagen type III alpha 1, tissue inhibitor of metalloprotease 2) in arecoline-treated oral mucosal fibroblasts and elevated matrix metalloproteinase 2 expression. Additionally, curcumin could suppress cell proliferation and migration, and enhance the apoptosis of arecoline-treated normal oral mucosal fibroblasts. Most importantly, the hypoxia-inducible factor-1α (HIF-1α), transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) expressions in arecoline-treated normal oral mucosal fibroblasts were reduced after exposure to curcumin, whereas the activation of HIF-1α/TGF-β/CTGF axis reversed curcumin's effect on improving fibrosis of arecoline-treated normal oral mucosal fibroblasts. Therefore, curcumin alleviated oral submucosal fibrosis via inhibiting HIF-1α/TGF-β/CTGF axis. In summary, curcumin effectively inhibited the migration and proliferation and promoted apoptosis in arecoline-induced normal oral mucosal fibroblasts by inactivating HIF-1α/TGF-β/CTGF pathway. And curcumin might be a potential therapeutic drug for OSF treatment.
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Affiliation(s)
| | - Jin Tan
- Department of Stomatology, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province 410007, P.R. China
| | - Yi-Ping Liu
- Department of Stomatology, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province 410007, P.R. China
| | - Xun Liu
- Department of Stomatology, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province 410007, P.R. China
| | - Mang Luo
- Department of Stomatology, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan Province 410007, P.R. China
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13
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Tang W, Du M, Zhang S, Jiang H. Therapeutic effect of curcumin on oral diseases: A literature review. Phytother Res 2021; 35:2287-2295. [PMID: 33205472 DOI: 10.1002/ptr.6943] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 10/13/2020] [Accepted: 10/20/2020] [Indexed: 02/06/2023]
Abstract
Curcumin (diferuloylmethane) is a polyphenol compound extracted from the rhizome of the plant Curcuma longa. It has the feature of being a yellow or orange pigment with a variety of biological properties, including anti-inflammation, antioxidation, anti-tumor, anti-bacteria, anti-fungus, and wound healing. Previous studies have reported the role of curcumin in treating different inflammatory diseases and tumors in vitro and in vivo. Recently, it has been demonstrated that curcumin has therapeutic benefits in oral mucosal diseases, periodontal diseases, and mouth neoplasms. In this review, we will focus on the therapeutic effects of curcumin on oral diseases.
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Affiliation(s)
- Weilong Tang
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST), Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Minquan Du
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST), Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Shuang Zhang
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST), Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China
| | - Han Jiang
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST), Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China
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14
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Girisa S, Kumar A, Rana V, Parama D, Daimary UD, Warnakulasuriya S, Kumar AP, Kunnumakkara AB. From Simple Mouth Cavities to Complex Oral Mucosal Disorders-Curcuminoids as a Promising Therapeutic Approach. ACS Pharmacol Transl Sci 2021; 4:647-665. [PMID: 33860191 PMCID: PMC8033761 DOI: 10.1021/acsptsci.1c00017] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Indexed: 02/08/2023]
Abstract
Oral diseases are among the most common encountered health issues worldwide, which are usually associated with anomalies of the oral cavity, jaws, and salivary glands. Despite the availability of numerous treatment modalities for oral disorders, a limited clinical response has been observed because of the inefficacy of the drugs and countless adverse side effects. Therefore, the development of safe, efficacious, and wide-spectrum therapeutics is imperative in the battle against oral diseases. Curcumin, extracted from the golden spice turmeric, is a well-known natural polyphenol that has been extensively studied for its broad pleiotropic attributes and its ability to modulate multiple biological processes. It is well-documented to target pro-inflammatory mediators like NF-κB, ROS, COX-2, IL-1, IL-2, TGF-β, growth factors, apoptotic proteins, receptors, and various kinases. These properties make curcumin a promising nutraceutical in the treatment of many oral diseases like oral submucous fibrosis, oral mucositis, oral leukoplakia, oral erythroplakia, oral candidiasis, aphthous stomatitis, oral lichen planus, dental caries, periodontitis, and gingivitis. Numerous in vitro and in vivo studies have shown that curcumin alleviates the symptoms of most of the oral complications, including the inhibition of the progression of oral cancer. In this regard, many clinical trials have been completed, and many are ongoing to investigate the "curcumin effect" in oral maladies. Therefore, the current review delineates the mechanistic framework of curcumin's propensity in curbing oral diseases and present outcomes of the clinical trials of curcumin-based therapeutics that can provide a breakthrough in the clinical management of these diseases.
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Affiliation(s)
- Sosmitha Girisa
- Cancer
Biology Laboratory and DBT-AIST International Center for Translational
and Environmental Research (DAICENTER), Department of Biosciences
and Bioengineering, Indian Institute of
Technology (IIT) Guwahati, Guwahati, Assam 781039, India
| | - Aviral Kumar
- Cancer
Biology Laboratory and DBT-AIST International Center for Translational
and Environmental Research (DAICENTER), Department of Biosciences
and Bioengineering, Indian Institute of
Technology (IIT) Guwahati, Guwahati, Assam 781039, India
| | - Varsha Rana
- Cancer
Biology Laboratory and DBT-AIST International Center for Translational
and Environmental Research (DAICENTER), Department of Biosciences
and Bioengineering, Indian Institute of
Technology (IIT) Guwahati, Guwahati, Assam 781039, India
| | - Dey Parama
- Cancer
Biology Laboratory and DBT-AIST International Center for Translational
and Environmental Research (DAICENTER), Department of Biosciences
and Bioengineering, Indian Institute of
Technology (IIT) Guwahati, Guwahati, Assam 781039, India
| | - Uzini Devi Daimary
- Cancer
Biology Laboratory and DBT-AIST International Center for Translational
and Environmental Research (DAICENTER), Department of Biosciences
and Bioengineering, Indian Institute of
Technology (IIT) Guwahati, Guwahati, Assam 781039, India
| | - Saman Warnakulasuriya
- Department
of Oral Medicine, King’s College
London and WHO Collaborating Centre for Oral Cancer and Precancer, London WC2R 2LS, United Kingdom
| | - Alan Prem Kumar
- Medical
Science Cluster, Cancer Translational Research Programme, Yong Loo
Lin School of Medicine, National University
of Singapore, Singapore 117600, Singapore
- Cancer
Science Institute of Singapore, National
University of Singapore, Singapore 117600, Singapore
- National
University Cancer Institute, National University
Health Systems, Singapore 117600, Singapore
| | - Ajaikumar B. Kunnumakkara
- Cancer
Biology Laboratory and DBT-AIST International Center for Translational
and Environmental Research (DAICENTER), Department of Biosciences
and Bioengineering, Indian Institute of
Technology (IIT) Guwahati, Guwahati, Assam 781039, India
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15
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Park CR, Lee JS, Son CG, Lee NH. A survey of herbal medicines as tumor microenvironment-modulating agents. Phytother Res 2021; 35:78-94. [PMID: 32658314 DOI: 10.1002/ptr.6784] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 05/24/2020] [Accepted: 06/06/2020] [Indexed: 12/18/2022]
Abstract
The tumor microenvironment (TME) is extremely complex, involving extensive interactions among stromal cells, immune cells, and signaling molecules. Therefore, an approach targeting the TME has emerged as a promising therapeutic strategy. Herbal medicines consist of multiple active compounds, which have multi-target effects. Therefore, they have been regarded as potential anticancer agents; multiple studies have explored their effects on the TME. In this review, we report the effects of 29 single herb medicines or herbal formulas on the TME, based on the findings of 64 published studies. Specifically, we describe the effects of these herbal medicines on cancer-associated fibroblasts/tumor-associated fibroblasts, tumor-associated endothelial cells, myeloid-derived suppressor cells, and tumor-associated macrophages. Among the reviewed herbal medicines, the most promising TME-modulating effects were exhibited by curcumin, DHA, EGCG, resveratrol, and silibinin; these medicines showed the ability to regulate two or more components of the TME. The findings of this review support the notion that the combination of herbal medicines with conventional anticancer therapies are likely to exhibit a clinical benefit, which should be further explored in clinical trials.
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Affiliation(s)
- Chan-Ran Park
- Dept. of Clinical Oncology, Cheonan Korean Medicine Hospital of Daejeon University, Cheonan-si, Republic of Korea
- Liver and Immunology Research Center, Dunsan Korean Medicine Hospital of Daejeon University, Daejeon-si, Republic of Korea
- Dept. of Internal Medicine, Graduated School of Korean Medicine, University of Daejeon, Daejeon-si, Republic of Korea
| | - Jin-Seok Lee
- Liver and Immunology Research Center, Dunsan Korean Medicine Hospital of Daejeon University, Daejeon-si, Republic of Korea
- Dept. of Internal Medicine, Graduated School of Korean Medicine, University of Daejeon, Daejeon-si, Republic of Korea
| | - Chang-Gue Son
- Liver and Immunology Research Center, Dunsan Korean Medicine Hospital of Daejeon University, Daejeon-si, Republic of Korea
- Dept. of Internal Medicine, Graduated School of Korean Medicine, University of Daejeon, Daejeon-si, Republic of Korea
| | - Nam-Hun Lee
- Dept. of Clinical Oncology, Cheonan Korean Medicine Hospital of Daejeon University, Cheonan-si, Republic of Korea
- Liver and Immunology Research Center, Dunsan Korean Medicine Hospital of Daejeon University, Daejeon-si, Republic of Korea
- Dept. of Internal Medicine, Graduated School of Korean Medicine, University of Daejeon, Daejeon-si, Republic of Korea
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16
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Rai A, Kaur M, Gombra V, Hasan S, Kumar N. Comparative evaluation of curcumin and antioxidants in the management of oral submucous fibrosis. ACTA ACUST UNITED AC 2019; 10:e12464. [PMID: 31605442 DOI: 10.1111/jicd.12464] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Accepted: 08/16/2019] [Indexed: 01/05/2023]
Abstract
AIM The present study aims to evaluate the efficacy and safety of curcumin in both topical and systemic forms for management of oral submucous fibrosis in comparison with the antioxidants. METHODS In this randomized parallel-group single-center trial, 119 patients were enrolled. Group I received antioxidants, group II received curcumin in systemic form and group III received curcumin in both systemic and topical forms. The primary outcomes assessed were interincisal mouth opening and burning sensation using a visual analog scale. The secondary outcomes were tongue protrusion and adverse reactions. The response to treatment was analyzed using ANOVA and Fisher's exact test. RESULTS Significant improvement in mouth opening, burning sensation and tongue protrusion was observed in all groups at 12 weeks. Mean improvement in burning sensation did not show statistical difference across the groups. A significant difference between groups II and III for improvement in mouth opening and groups I and III for improvement in tongue protrusion was noted. CONCLUSION When administrated in both systemic and topical forms together, curcumin showed better results in the management of oral submucous fibrosis as compared with the systemic form alone or antioxidants. Curcumin has the potential to emerge as an effective alternative to conventionally prescribed medications.
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Affiliation(s)
- Arpita Rai
- Oral Medicine and Radiology, Faculty of Dentistry, Jamia Millia Islamia, New Delhi, India
| | - Mandeep Kaur
- Oral Medicine and Radiology, Faculty of Dentistry, Jamia Millia Islamia, New Delhi, India
| | - Virender Gombra
- Oral Medicine and Radiology, Faculty of Dentistry, Jamia Millia Islamia, New Delhi, India
| | - Shamimul Hasan
- Oral Medicine and Radiology, Faculty of Dentistry, Jamia Millia Islamia, New Delhi, India
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17
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Enzyme-Catalyzed Glycosylation of Curcumin and Its Analogues by Glycosyltransferases from Bacillus subtilis ATCC 6633. Catalysts 2019. [DOI: 10.3390/catal9090734] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Curcumin is a naturally occurring polyphenolic compound that is commonly used in both medicine and food additives, but its low aqueous solubility and poor bioavailability hinder further clinical applications. For assessing the effect of the glycosylation of curcumin on its aqueous solubility, two glycosyltransferase genes (BsGT1 and BsGT2) were cloned from the genome of the strain Bacillus subtilis ATCC 6633 and over-expressed in Escherichia coli. Then, the two glycosyltransferases were purified, and their glycosylation capacity toward curcumin and its two analogues was verified. The results showed that both BsGT1 and BsGT2 could convert curcumin and its two analogues into their glucosidic derivatives. Then, the structures of the derivatives were characterized as curcumin 4′-O-β-D-glucoside and two new curcumin analogue monoglucosides namely, curcumoid-O-α-D-glucoside (2a) and 3-pentadienone-O-α-D-glucoside (3a) by nuclear magnetic resonance (NMR) spectroscopy. Subsequently, the dissolvability of curcumin 4′-O-β-D-glucoside was measured to be 18.78 mg/L, while its aglycone could not be determined. Furthermore, the optimal catalyzing conditions and kinetic parameters of BsGT1 and BsGT2 toward curcumin were determined, which showed that the Kcat value of BsGT1 was about 2.6-fold higher than that of BsGT2, indicating that curcumin is more favored for BsGT2. Our findings effectively apply the enzymatic approach to obtain glucoside derivatives with enhanced solubility.
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18
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Metformin Inhibits the Expression of Biomarkers of Fibrosis of EPCs In Vitro. Stem Cells Int 2019; 2019:9019648. [PMID: 31011335 PMCID: PMC6442487 DOI: 10.1155/2019/9019648] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Revised: 12/16/2018] [Accepted: 01/28/2019] [Indexed: 02/08/2023] Open
Abstract
Endothelial progenitor cells (EPCs) are a group of circulating cells with important functions in vascular repair and treatment of cardiovascular diseases. However, in patients with atrial fibrillation (AF), the number and function of EPCs reportedly are decreased. TGF-β is highly expressed in AF patients. In this study, we examined the effect of TGF-β1 on EPCs and the therapeutic outcome of metformin treatment on TGF-β1-induced EPCs. EPCs were induced with TGF-β1 at different concentrations (5 ng/ml, 10 ng/ml, and 20 ng/ml) for 48 h followed by western blot, qPCR, and immunofluorescence analyses to investigate changes in the levels of the fibrosis-related proteins, α-SMA, Col I, Col III, CTGF, and MMP-1. Live-dead cell staining was used to evaluate cell apoptosis. Compared with the control, TGF-β1 treatment significantly (p < 0.05) enhanced the levels of α-SMA, Col I, Col III, CTGF, and MMP-1 in a dose-dependent manner. The most effective concentration of TGF-β1 (20 ng/ml) was then used to induce fibrosis biomarker expression in EPCs, followed by treatment with metformin at different concentrations (0.5, 1, and 2 mmol/l). Metformin treatment suppressed TGF-β-induced expression of all above factors, with the effect at 2 mmol/l being significant (p < 0.05). Live-dead cell staining showed no difference among the control, TGF-β1-treated, and metformin-treated groups. In conclusion, our study showed that TGF-β1 induces the expression of fibrosis biomarkers in EPCs, which is attenuated by treatment with metformin. Thus, metformin may have therapeutic potential for improving EPC function in cardiovascular diseases.
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19
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Al-Maweri SA. Efficacy of curcumin for management of oral submucous fibrosis: a systematic review of randomized clinical trials. Oral Surg Oral Med Oral Pathol Oral Radiol 2019; 127:300-308. [PMID: 30745280 DOI: 10.1016/j.oooo.2019.01.010] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2018] [Revised: 12/11/2018] [Accepted: 01/11/2019] [Indexed: 01/20/2023]
Abstract
OBJECTIVES Oral submucous fibrosis (OSF) is a chronic debilitating disease that has a high risk of malignant transformation. Management of OSF is quite challenging, with no definitive cure being available. This systematic review assessed the available evidence for using curcumin for pain alleviation and clinical improvement in patients with OSF. STUDY DESIGN A comprehensive search of PubMed/Medline, Scopus, and ISI Web of Science databases was conducted to identify all relevant clinical trials comparing patients receiving curcumin treatment to active and/or nonactive controls for the treatment of OSF. RESULTS Six clinical trials comprising 298 patients were included. All studies found curcumin to be effective in the management of OSF. Three studies found significantly higher improvement in burning sensation in the curcumin group compared with controls, whereas 3 other studies found comparable results. With regard to clinical signs, 2 studies showed better improvement in mouth opening in the curcumin group; 3 studies reported no differences in effectiveness; and only 1 study found curcumin to be inferior to conventional therapy. CONCLUSIONS The available evidence remains inconclusive but suggests that curcumin is a promising effective treatment option for the management of patients with OSF. Further well-designed clinical trials with large sample sizes and adequate follow-up periods are warranted.
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Affiliation(s)
- Sadeq Ali Al-Maweri
- Department of Oral Medicine and Diagnostic Science, Al Farabi Colleges, Riyadh, Kingdom of Saudi Arabia.
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20
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Li X, Xu D, Sun D, Zhang T, He X, Xiao D. Curcumin ameliorates monosodium urate‐induced gouty arthritis through Nod‐like receptor 3 inflammasome mediation via inhibiting nuclear factor‐kappa B signaling. J Cell Biochem 2018; 120:6718-6728. [PMID: 30592318 DOI: 10.1002/jcb.27969] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Accepted: 10/02/2018] [Indexed: 02/02/2023]
Affiliation(s)
- Xiong Li
- Department of Sports Medicine Xiangya Hospital, Central South University Changsha China
| | - Da‐Qi Xu
- Department of Sports Medicine Xiangya Hospital, Central South University Changsha China
| | - De‐Yi Sun
- Department of Sports Medicine Xiangya Hospital, Central South University Changsha China
| | - Tao Zhang
- Department of Sports Medicine Xiangya Hospital, Central South University Changsha China
| | - Xi He
- Department of Sports Medicine Xiangya Hospital, Central South University Changsha China
| | - Dong‐Min Xiao
- Department of Orthopedics Yongzhou Central Hospital Yongzhou China
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21
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Kumar D, Yalamanchali S, New J, Parsel S, New N, Holcomb A, Gunewardena S, Tawfik O, Lominska C, Kimler BF, Anant S, Kakarala K, Tsue T, Shnayder Y, Sykes K, Padhye S, Thomas SM. Development and Characterization of an In Vitro Model for Radiation-Induced Fibrosis. Radiat Res 2018; 189:326-336. [PMID: 29351058 DOI: 10.1667/rr14926.1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Radiation-induced fibrosis (RIF) is a major side effect of radiotherapy in cancer patients with no effective therapeutic options. RIF involves excess deposition and aberrant remodeling of the extracellular matrix (ECM) leading to stiffness in tissues and organ failure. Development of preclinical models of RIF is crucial to elucidate the molecular mechanisms regulating fibrosis and to develop therapeutic approaches. In addition to radiation, the main molecular perpetrators of fibrotic reactions are cytokines, including transforming growth factor-β (TGF-β). We hypothesized that human oral fibroblasts would develop an in vitro fibrotic reaction in response to radiation and TGF-β. We demonstrate here that fibroblasts exposed to radiation followed by TGF-β exhibit a fibrotic phenotype with increased collagen deposition, cell proliferation, migration and invasion. In this in vitro model of RIF (RIFiv), the early biological processes involved in fibrosis are demonstrated, along with increased levels of several molecules including collagen 1α1, collagen XIα1, integrin-α2 and cyclin D1 mRNA in irradiated cells. A clinically relevant antifibrotic agent, pentoxifylline, and a curcumin analogue both mitigated collagen deposition in irradiated fibroblast cultures. In summary, we have established an in vitro model for RIF that facilitates the elucidation of molecular mechanisms in radiation-induced fibrosis and the development of effective therapeutic approaches.
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Affiliation(s)
- Dhruv Kumar
- Department of a Otolaryngology, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas
| | - Sreeya Yalamanchali
- Department of a Otolaryngology, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas
| | - Jacob New
- Department of a Otolaryngology, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas.,b Department of Anatomy and Cell Biology, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas
| | - Sean Parsel
- Department of a Otolaryngology, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas
| | - Natalie New
- Department of a Otolaryngology, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas
| | - Andrew Holcomb
- Department of a Otolaryngology, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas
| | - Sumedha Gunewardena
- c Department of Molecular and Integrative Physiology, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas
| | - Ossama Tawfik
- d Department of Pathology and Laboratory Medicine, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas
| | - Chris Lominska
- e Department of Radiation Oncology, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas
| | - Bruce F Kimler
- e Department of Radiation Oncology, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas
| | - Shrikant Anant
- f Department of Surgery, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas.,g Department of Cancer Biology, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas
| | - Kiran Kakarala
- Department of a Otolaryngology, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas
| | - Terance Tsue
- Department of a Otolaryngology, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas
| | - Yelizaveta Shnayder
- Department of a Otolaryngology, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas
| | - Kevin Sykes
- Department of a Otolaryngology, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas
| | - Subhash Padhye
- h Interdisciplinary Science and Technology Research Academy, University of Pune, Pune, India
| | - Sufi Mary Thomas
- Department of a Otolaryngology, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas.,b Department of Anatomy and Cell Biology, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas.,g Department of Cancer Biology, University of Kansas Medical Center and University of Kansas Cancer Center, Kansas City, Kansas
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22
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Park SA, Surh YJ. Modulation of tumor microenvironment by chemopreventive natural products. Ann N Y Acad Sci 2017. [DOI: 10.1111/nyas.13395] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Sin-Aye Park
- Tumor Microenvironment Global Core Research Center and Research Institute of Pharmaceutical Sciences; Seoul National University; Seoul South Korea
| | - Young-Joon Surh
- Tumor Microenvironment Global Core Research Center and Research Institute of Pharmaceutical Sciences; Seoul National University; Seoul South Korea
- Cancer Research Institute; Seoul National University; Seoul South Korea
- Department of Molecular Medicine and Biopharmaceutical Sciences, College of Pharmacy; Seoul National University; Seoul South Korea
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23
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Gupta S, Ghosh S, Gupta S, Sakhuja P. Effect of curcumin on the expression of p53, transforming growth factor-β, and inducible nitric oxide synthase in oral submucous fibrosis: A pilot study. ACTA ACUST UNITED AC 2016; 8. [PMID: 27989010 DOI: 10.1111/jicd.12252] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2016] [Accepted: 10/07/2016] [Indexed: 11/28/2022]
Abstract
AIM The purpose of the present study was to find out the expression of p53, transforming growth factor-β TGF-β), and inducible nitric oxide synthase (iNOS) in oral submucous fibrosis (OSMF), proteins implicated in its pathophysiology, as well as malignant transformation. We also sought to determine the effect of curcumin on the expression of these markers through immunohistochemistry. METHODS The expression of p53, TGF-β, and iNOS was evaluated through immunohistochemistry in 28 patients with OSMF before and after treatment with curcumin. Expression was evaluated semiquantitatively using a four-point scale based on the percentage of cells showing positive staining. RESULTS The expression of p53, TGF-β, and iNOS in OSMF was found to be statistically significant (P<.05). After therapy with curcumin, a decrease in the expression of p53, TGF-β, and iNOS was seen in 25%, 32.1%, and 32.1% of the samples, respectively; however, the difference in pretreatment and post-treatment expressions was not found to be statistically significant. CONCLUSION The present finding suggest that curcumin could have an effect on the expression of p53, iNOS, and TGF-β in OSMF, and thus, could prove to be an effective chemopreventive agent for its management. The increased expression of p53, TGF-β, and iNOS in OSMF is suggestive of the role of these markers in its pathophysiology.
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Affiliation(s)
- Shikha Gupta
- Department of Oral Medicine and Radiology, Maulana Azad Institute of Dental Sciences, New Delhi, India
| | - Sujoy Ghosh
- Department of Oral Medicine and Radiology, Maulana Azad Institute of Dental Sciences, New Delhi, India
| | - Sunita Gupta
- Department of Oral Medicine and Radiology, Maulana Azad Institute of Dental Sciences, New Delhi, India
| | - Puja Sakhuja
- Department of Pathology, Govind Ballabh Pant Hospital, New Delhi, India
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Kar S, Biswas S, Banerjee ER. Evaluating the ameliorative potential of plant flavonoids and their nanocomposites in bleomycin induced idiopathic pulmonary fibrosis. BIOMEDICAL RESEARCH AND THERAPY 2016. [DOI: 10.7603/s40730-016-0032-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Adtani PN, Narasimhan M, Punnoose AM, Kambalachenu HR. Antifibrotic effect of Centella asiatica Linn and asiatic acid on arecoline-induced fibrosis in human buccal fibroblasts. ACTA ACUST UNITED AC 2016; 8. [PMID: 26840561 DOI: 10.1111/jicd.12208] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Accepted: 11/24/2015] [Indexed: 12/28/2022]
Abstract
AIM The aim of the present study was to investigate the in vitro antifibrogenic effects of Centella asiatica Linn (CA) and its bioactive triterpene aglycone asiatic acid (AA) on arecoline-induced fibrosis in primary human buccal fibroblasts (HBF). METHODS An ethanolic extract of CA was prepared, and AA was purchased commercially. High-performance thin-layer chromatography (HPTLC) was performed to quantify AA in the CA extract; colorimetric assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) was performed to determine an half-maximal inhibitory concentration. HBF were cultured and stimulated with arecoline. The inhibitory effects of CA and AA at different concentrations were assessed using gene-expression studies on fibrosis-related markers: transforming growth factor-β1, collagen 1 type 2, and collagen 3 type 1. The stimulatory effect of arecoline and the inhibitory effect of AA on fibroblast morphology and extracellular matrix were assessed qualitatively using Masson trichrome stain. RESULTS The HPTLC analysis determined 1.2% AA per 100 g of CA extract. Arecoline produced a concentration-dependent increase in the fibrotic markers, treatment with CA significantly downregulated fibrotic markers at higher concentrations, and AA downregulated at lower concentrations. Arecoline altered fibroblast morphology and stained strongly positive for collagen, and AA treatment regained fibroblast morphology with faint collagen staining. CONCLUSION CA and AA can be used as antifibrotic agents.
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Affiliation(s)
- Pooja Narain Adtani
- Department of Oral Pathology and Microbiology, Faculty of Dental Sciences, Sri Ramachandra University and Research Institute, Chennai, India
| | - Malathi Narasimhan
- Department of Oral Pathology and Microbiology, Faculty of Dental Sciences, Sri Ramachandra University and Research Institute, Chennai, India
| | - Alan M Punnoose
- Center for Regenerative Medicine and Stem Cell Research, Central Research Facility, Sri Ramachandra University and Research Institute, Chennai, India
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Ganjre A, Kathariya R, Bagul N, Pawar V. Anti-carcinogenic and Anti-bacterial Properties of Selected Spices: Implications in Oral Health. Clin Nutr Res 2015; 4:209-15. [PMID: 26566515 PMCID: PMC4641982 DOI: 10.7762/cnr.2015.4.4.209] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2015] [Revised: 04/03/2015] [Accepted: 04/06/2015] [Indexed: 01/22/2023] Open
Abstract
"Let food be thy medicine and medicine be thy food", as said by the father of medicine, Hippocrates in 431 B.C. Nature has provided us with a variety of treatment modalities in the form of food. For the first 5,000 years of civilization, humans relied on herbs and foods for medicine. Only in the past 60 years have we forgotten our medicinal "roots" in favor of patented medicines. While pharmaceutical ingredients have their value, we should not overlook the well-documented, non-toxic and inexpensive healing properties of food. As an individual we consume food several times a day without a complete understanding of its innate qualities. As part of a daily diet, food plays a significant role in helping our bodies function at their best. There are hundreds of extremely nutritious foods, but the items in this article do more than providing healthy nutrients. Many of them consist of ingredients with hidden pharmaceutical qualities ranging from anti-inflammatory to anti-carcinogenic agent. They not only boost our innate immunity but also act as an adjunct to medicines for specific treatment. Prevention and management of symptoms can often be improved significantly through the foods we consume regularly. This paper overviews these beneficial traits of food ingredients, consumed on a daily basis, in various oral diseases.
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Affiliation(s)
- Anjali Ganjre
- Department of Oral Pathology and Microbiology, Dr. D. Y Patil Dental College and Hospital, Dr. D. Y Patil Vidyapeeth, Pimpri, Pune 411018 Maharashtra, India
| | - Rahul Kathariya
- Department of Periodontics and Oral Implantology, Dr. D. Y Patil Dental College and Hospital, Dr. D. Y Patil Vidyapeeth, Pimpri, Pune 411018 Maharashtra, India
| | - Neeta Bagul
- Department of Oral Pathology and Microbiology, Dr. D. Y Patil Dental College and Hospital, Dr. D. Y Patil Vidyapeeth, Pimpri, Pune 411018 Maharashtra, India
| | - Vivek Pawar
- Department of Oral and Maxillofacial Surgery, Dr. D. Y Patil Dental College and Hospital, Dr. D. Y Patil Vidyapeeth, Pimpri, Pune 411018 Maharashtra, India
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Alok A, Singh ID, Singh S, Kishore M, Jha PC. Curcumin - Pharmacological Actions And its Role in Oral Submucous Fibrosis: A Review. J Clin Diagn Res 2015; 9:ZE01-3. [PMID: 26557633 DOI: 10.7860/jcdr/2015/13857.6552] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2015] [Accepted: 07/05/2015] [Indexed: 01/18/2023]
Abstract
Turmeric has been in use for thousands of years as a dye, flavouring and a medicinal herb. Ancient Indian medicine has touted turmeric as an herb with the ability to provide glow and lustre to the skin as well as vigour and vitality to the entire body. Since curcumin has antimicrobial, antioxidant, astringents and other useful properties, it is quite useful in dentistry also. Curcumin, the most active polyphenolic constituent, is the active ingredient in the traditional herbal remedy and dietary spice turmeric. In gel form it is a component in local drugs delivery system. The objective of this article is to review the pharmacological action of turmeric and its use in treating oral submucous fibrosis.
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Affiliation(s)
- Abhijeet Alok
- Senior Lecturer, Department of Oral Medicine and Radiology, Sarjug Dental College and Hospital , Darbhanga, Bihar, India
| | - Indra Deo Singh
- Associate Professor and Head, Department of Psychiatry, Sri Krishna Medical College and Hospital , Muzaffarpur, Bihar, India
| | - Shivani Singh
- Post Graduate Student, Department of Public Health Dentistry, Institute of Dental Sciences , Bareilly, U.P, India
| | | | - Prakash Chandra Jha
- Senior Lecturer, Department of Oral Medicine and Radiology, Rama Dental College Hospital and Research Centre , Kanpur, U.P, India
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Lundvig DMS, Pennings SWC, Brouwer KM, Mtaya-Mlangwa M, Mugonzibwa E, Kuijpers-Jagtman AM, Wagener FADTG, Von den Hoff JW. Cytoprotective responses in HaCaT keratinocytes exposed to high doses of curcumin. Exp Cell Res 2015; 336:298-307. [PMID: 26071936 DOI: 10.1016/j.yexcr.2015.06.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Revised: 06/02/2015] [Accepted: 06/04/2015] [Indexed: 01/05/2023]
Abstract
Wound healing is a complex process that involves the well-coordinated interactions of different cell types. Topical application of high doses of curcumin, a plant-derived polyphenol, enhances both normal and diabetic cutaneous wound healing in rodents. For optimal tissue repair interactions between epidermal keratinocytes and dermal fibroblasts are essential. We previously demonstrated that curcumin increased reactive oxygen species (ROS) formation and apoptosis in dermal fibroblasts, which could be prevented by pre-induction of the cytoprotective enzyme heme oxygenase (HO)-1. To better understand the effects of curcumin on wound repair, we now assessed the effects of high doses of curcumin on the survival of HaCaT keratinocytes and the role of the HO system. We exposed HaCaT keratinocytes to curcumin in the presence or absence of the HO-1 inducers heme (FePP) and cobalt protoporphyrin (CoPP). We then assessed cell survival, ROS formation, and caspase activation. Curcumin induced caspase-dependent apoptosis in HaCaT keratinocytes via a ROS-dependent mechanism. Both FePP and CoPP induced HO-1 expression, but only FePP protected against curcumin-induced ROS formation and caspase-mediated apoptosis. In the presence of curcumin, FePP but not CoPP induced the expression of the iron scavenger ferritin. Together, our data show that the induction of ferritin, but not HO, protects HaCaT keratinocytes against cytotoxic doses of curcumin. The differential response of fibroblasts and keratinocytes to high curcumin doses may provide the basis for improving curcumin-based wound healing therapies.
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Affiliation(s)
- Ditte M S Lundvig
- Department of Orthodontics and Craniofacial Biology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, PO Box 9101, 6500 HB Nijmegen, The Netherlands
| | - Sebastiaan W C Pennings
- Department of Orthodontics and Craniofacial Biology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, PO Box 9101, 6500 HB Nijmegen, The Netherlands
| | - Katrien M Brouwer
- Department of Orthodontics and Craniofacial Biology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, PO Box 9101, 6500 HB Nijmegen, The Netherlands
| | - Matilda Mtaya-Mlangwa
- Department of Preventive and Community Dentistry, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Emeria Mugonzibwa
- Department of Preventive and Community Dentistry, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Anne Marie Kuijpers-Jagtman
- Department of Orthodontics and Craniofacial Biology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, PO Box 9101, 6500 HB Nijmegen, The Netherlands
| | - Frank A D T G Wagener
- Department of Orthodontics and Craniofacial Biology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, PO Box 9101, 6500 HB Nijmegen, The Netherlands
| | - Johannes W Von den Hoff
- Department of Orthodontics and Craniofacial Biology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
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Jia S, Xie P, Hong SJ, Galiano R, Singer A, Clark RAF, Mustoe TA. Intravenous curcumin efficacy on healing and scar formation in rabbit ear wounds under nonischemic, ischemic, and ischemia-reperfusion conditions. Wound Repair Regen 2015; 22:730-9. [PMID: 25230783 DOI: 10.1111/wrr.12231] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2013] [Accepted: 09/05/2014] [Indexed: 11/27/2022]
Abstract
Curcumin, a spice found in turmeric, is widely used in alternative medicine for its purported anti-inflammatory and antioxidant activities. The goal of this study was to test the curcumin efficacy on rabbit ear wounds under nonischemic, ischemic, and ischemia-reperfusion conditions. Previously described models were utilized in 58 New Zealand White rabbits. Immediately before wounding, rabbits were given intravenous crude or pure curcumin (6 μg/kg, 30 μg/kg, or 60 μg/kg) dissolved in 1% ethanol. Specimens were collected at 7-8 days to evaluate the effects on wound healing and at 28 days to evaluate the effects on hypertrophic scarring. Student's t test was applied to screen difference between any treatment and control group, whereas analysis of variance was applied to further analyze for all treatment groups in aggregate in some specific experiments. Treatment with crude curcumin suggested accelerated wound healing that reached significance for reepithelialization in lower and medium doses and granulation tissue formation in lower dose. Purified curcumin became available and was used for all later experiments. Treatment with pure curcumin suggested accelerated wound healing that reached significance for reepithelialization in lower and medium doses and granulation tissue formation in lower dose. Treatment with pure curcumin significantly promoted nonischemic wound healing in a dose-response fashion compared with controls as judged by increased reepithelialization and granulation tissue formation. Improved wound healing was associated with significant decreases in pro-inflammatory cytokines interleukin (IL)-1 and IL-6 as well as the chemokine IL-8. Curcumin also significantly reduced hypertrophic scarring. The effects of curcumin were examined under conditions of impaired healing including ischemic and ischemia-reperfusion wound healing, and beneficial effects were also seen, although the dose response was less clear. Systemically administrated pure curcumin significantly promotes nonischemic wound healing and reduces hypertrophic scarring. Improvements in wound healing were associated with decreased inflammatory markers in wounds. Further study is needed to optimize dosing in ischemic and ischemia-reperfusion wound healing. In aggregate, the studies strongly support the systemic administration of curcumin to improve wound healing.
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Affiliation(s)
- Shengxian Jia
- The Laboratory for Wound Healing and Regenerative Medicine, Department of Surgery, Northwestern University, Chicago, Illinois
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Lundvig DM, Pennings SW, Brouwer KM, Mtaya-Mlangwa M, Mugonzibwa EA, Kuijpers-Jagtman AM, Von den Hoff JW, Wagener FA. Curcumin induces differential expression of cytoprotective enzymes but similar apoptotic responses in fibroblasts and myofibroblasts. Exp Cell Res 2015; 330:429-441. [DOI: 10.1016/j.yexcr.2014.10.006] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2014] [Revised: 10/02/2014] [Accepted: 10/05/2014] [Indexed: 12/22/2022]
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Zhou X, Zhang J, Xu C, Wang W. Curcumin ameliorates renal fibrosis by inhibiting local fibroblast proliferation and extracellular matrix deposition. J Pharmacol Sci 2014; 126:344-50. [PMID: 25452269 DOI: 10.1254/jphs.14173fp] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
Abstract
Renal fibrosis is mainly characterized by activation and proliferation of interstitial fibroblasts and by excessive synthesis and accumulation of extracellular matrix (ECM) components, including fibronectin (FN) and collagen. This study investigated the effects of curcumin on proliferation of renal interstitial fibroblasts and their underlying mechanisms in vivo and in vitro. ECM components were visualized by Sirius red and immunohistochemistry staining and quantified by western blot analysis in mice with unilateral ureteral obstruction (UUO). Duplex staining for proliferating cell nuclear antigen and α-smooth muscle actin (α-SMA), as well as MTT and flow cytometry assays, were performed to measure fibroblast proliferation. Protein expression of phosphorylated Smad2/3 (p-Smad2/3) and peroxisome proliferator-activated receptor-γ (PPAR-γ) were assessed by western blotting. Curcumin treatment decreased the accumulation of type I collagen and FN in the kidney of animals with UUO. Activation of rat renal interstitial fibroblasts (NRK-49F) was induced by TGF-β1. Curcumin treatment inhibited fibroblast proliferation and the cell cycle was arrested in the G1 phase. Curcumin treatment upregulated the expression of PPAR-γ and downregulated the expression of p-Smad2/3. These results suggest that curcumin treatment ameliorates renal fibrosis by reducing fibroblast proliferation and ECM accumulation mediated by PPAR-γ and Smad-dependent TGF-β1 signaling.
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Affiliation(s)
- Xiangjun Zhou
- Department of Urology, Renmin Hospital of Wuhan University, China
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Raj GG, Varghese HS, Kotagiri S, Vrushabendra Swamy BM, Swamy A, Pathan RK. Anticancer Studies of Aqueous Extract of Roots and Leaves of Pandanus Odoratissimus f. ferreus (Y. Kimura) Hatus: An In Vitro Approach. J Tradit Complement Med 2014; 4:279-84. [PMID: 25379472 PMCID: PMC4220508 DOI: 10.4103/2225-4110.129199] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
A number of medicinal plant extracts are being used against various diseases in different systems of medicine such as Ayurveda, Unani, and Siddha, but only a few of them have been scientifically explored. The objective of the present study was to explore the dose-dependent in vitro anticancer effects of the extracts of Pandanus odoratissimus whose scientific documentation as an anticancer agent is lacking despite being used traditionally. The dried parts of roots and leaves were extracted with methanol (MEPO) and water (AEPO). The extracts were then subjected to in vitro cytotoxic and antimitotic screening by brine shrimp lethality assay and onion root tip method, respectively. Further, the behavior of the extracts on calu-6 (non-small cell lung cancer cell lines), PBMC (peripheral blood mononuclear cells) and WI (lung fibroblast cell lines) was studied using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay followed by flow cytometric analysis on calu-6 cell lines. AEPO showed significant cytotoxic and antimitotic activities. It showed 100% lethality of brine shrimps at 80 μg/ml and an LC50 of 33.33 μg/ml, which was eightfold higher than that of synthetic standard podophyllotoxin (4.16 μg/ml). AEPO at 10 mg/ml concentration showed significant antimitotic activity by showing 3% mitotic index. which was more than that of standard cyclophosphamide with 4% mitotic index in comparison to control. There was a significant reduction in cell proliferation of calu-6 cells, ranging from 56 to 35%, after 24-48 h of treatment with 200 μg/ml (P < 0.001) of AEPO, while AEPO remained unaffected on PBMC and WI-38 cel lines. Cell cycle analysis revealed that AEPO at 50 μg/ml and 100 μg/ml significantly increased the number of cells in sub G0–G1 phase, indicating the cells entering in to apoptotic phase. These results suggest that aqueous extract of P. odoratissimus possesses better anticancer activity. The plant has the potential to be used in anticancer therapy, and this study scientifically validated the folklore use of this plant.
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Affiliation(s)
- Gunti Gowtham Raj
- Department of Pharmacology and Toxicology, Gautham College of Pharmacy, Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka, India
| | - Hyma Sara Varghese
- Department of Pharmacology, Hillside College of Pharmacy and Research Centre, Bangalore, Karnataka, India
| | - Sarita Kotagiri
- Department of Pharmacology, East Point College of Pharmacy, Bangalore, Karnataka, India
| | | | - Archana Swamy
- Department of Pharmacology and Toxicology, Gautham College of Pharmacy, Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka, India
| | - Rafi Khan Pathan
- Department of Pharmacology, Prist University, Thanjavur, Tamilnadu, India
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Yadav M, Aravinda K, Saxena VS, Srinivas K, Ratnakar P, Gupta J, Sachdev AS, Shivhare P. Comparison of curcumin with intralesional steroid injections in Oral Submucous Fibrosis - A randomized, open-label interventional study. J Oral Biol Craniofac Res 2014; 4:169-73. [PMID: 25737939 PMCID: PMC4306996 DOI: 10.1016/j.jobcr.2014.11.003] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2014] [Accepted: 11/02/2014] [Indexed: 11/29/2022] Open
Abstract
INTRODUCTION Oral Submucous Fibrosis (OSMF) is precancerous condition caused by areca nut chewing characterized by restricted mouth opening, burning sensation and stiffness & blanching of oral mucosa. Complete regression of the condition had not been achieved in all cases with any of the present treatment regimens. Curcumin is (diferuloylmethane), a yellow pigment in curry powder, exhibits anti-oxidant, anti-inflammatory, and pro-apoptotic activities. Hence an interventional study was undertaken to establish the efficacy of curcumin in OSMF patients. SETTINGS & DESIGN A randomized open label, interventional study was conducted in forty patients with clinically and histologically proven Oral Submucous Fibrosis. MATERIALS & METHODS Forty patients with clinically and histologically proven Oral Submucous Fibrosis were selected for the study and were randomly divided into 2 groups. The first group was treated with weekly intralesional injection of 4 mg Dexamethasone & 1500 I.U Hyaluronidase and the second group by oral administration of two Curcumin tablets (Turmix 300 mg) per day for 3 months each. Improvement of burning sensation, interincisal distance and tongue protrusion was evaluated on a weekly basis. RESULTS Burning sensation improved in both the groups from early to late stages. Complete resolution of burning sensation was noted with turmix. The mean increase in interincisal distance was 3.13 mm and 1.25 mm respectively in groups 1 &2. The interincisal distance improved in both the groups, with significant results at the end of first month. Tongue protrusion showed greater recovery at the end of 1st month in group 1 when compared with group 2. CONCLUSION Turmix is beneficial and effective in reducing burning sensation in early OSMF patients.
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Affiliation(s)
- Monu Yadav
- Department of Oral Medicine & Radiology, Career Postgraduate Institute of Dental Sciences and Hospital, Lucknow, Uttar Pradesh, India
| | - K. Aravinda
- Department of Oral Medicine & Radiology, Swami Devi Dyal Hospital and Dental College, Barwala, Haryana, India
| | - Vasu S. Saxena
- Department of Oral Medicine & Radiology, Career Postgraduate Institute of Dental Sciences and Hospital, Lucknow, Uttar Pradesh, India
| | - K. Srinivas
- Department of Oral Medicine & Radiology, Career Postgraduate Institute of Dental Sciences and Hospital, Lucknow, Uttar Pradesh, India
| | - P. Ratnakar
- Department of Oral Medicine & Radiology, Career Postgraduate Institute of Dental Sciences and Hospital, Lucknow, Uttar Pradesh, India
| | - Jyothi Gupta
- Department of Oral Medicine & Radiology, Career Postgraduate Institute of Dental Sciences and Hospital, Lucknow, Uttar Pradesh, India
| | - Arti Saluja Sachdev
- Department of Oral Medicine & Radiology, Career Postgraduate Institute of Dental Sciences and Hospital, Lucknow, Uttar Pradesh, India
| | - Peeyush Shivhare
- Department of Oral Medicine & Radiology, Raja Rajeswari Dental College, Bangalore, Karnataka, India
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Siani A, Tirelli N. Myofibroblast differentiation: main features, biomedical relevance, and the role of reactive oxygen species. Antioxid Redox Signal 2014; 21:768-85. [PMID: 24279926 DOI: 10.1089/ars.2013.5724] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
SIGNIFICANCE Myofibroblasts are prototypical fibrotic cells, which are involved in a number of more or less pathological conditions, from foreign body reactions to scarring, from liver, kidney, or lung fibrosis to neoplastic phenomena. The differentiation of precursor cells (not only of fibroblastic nature) is characterized by a complex interplay between soluble factors (growth factors such as transforming growth factor β1, reactive oxygen species [ROS]) and material properties (matrix stiffness). RECENT ADVANCES The last 15 years have seen very significant advances in the identification of appropriate differentiation markers, in the understanding of the differentiation mechanism, and above all, the involvement of ROS as causative and persistence factors. CRITICAL ISSUES The specific mechanisms of action of ROS remain largely unknown, although evidence suggests that both intracellular and extracellular phenomena play a role. FUTURE DIRECTIONS Approaches based on antioxidant (ROS-scavenging) principles and on the potentiation of nitric oxide signaling hold much promise in view of a pharmacological therapy of fibrotic phenomena. However, how to make the active principles available at the target sites is yet a largely neglected issue.
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Affiliation(s)
- Alessandro Siani
- 1 School of Pharmacy and Pharmaceutical Sciences, University of Manchester , Manchester, United Kingdom
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Mo N, Li ZQ, Li J, Cao YD. Curcumin inhibits TGF-β1-induced MMP-9 and invasion through ERK and Smad signaling in breast cancer MDA- MB-231 cells. Asian Pac J Cancer Prev 2013; 13:5709-14. [PMID: 23317243 DOI: 10.7314/apjcp.2012.13.11.5709] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVE To evaluate the effects of curcumin on matrixmetalloproteinase-9 (MMP-9) and invasion ability induced by transforming growth factor-β1 (TGF-β1) in MDA-MB-231 cells and potential mechanisms. METHODS Human breast cancer MDA- MB-231 cells were used with the CCK-8 assay to measure the cytotoxicity of curcumin. After treatment with 10 ng/ml TGF-β1, with or without curcumin (≤10 μM), cell invasion was checked by transwell chamber. The effects of curcumin on TGF-β1-stimulated MMP-9 and phosphorylation of Smad2, extracellular-regulated kinase (ERK), and p38 mitogen activated protein kinases (p38MAPK) were examined by Western blotting. Supernatant liquid were collected to analyze the activity of MMP-9 via zymography. Following treatment with PD98059, a specific inhibitor of ERK, and SB203580, a specific inhibitor of p38MAPK, Western blotting and zymography were employed to examine MMP-9 expression and activity, respectively. RESULTS Low dose curcumin (≤10 μM) did not show any obvious toxicity to the cells, while 0~10 μmol/L caused a concentration-dependent reduction in cell invasion provoked by TGF-β1. Curcumin also markedly inhibited TGF-β1-regulated MMP-9 and activation of Smad2, ERK1/2 and p38 in a dose- and time-dependent manner. Additionally, PD98059, but not SB203580, showed a similar pattern of inhibition of MMP-9 expression. CONCLUSION Curcumin inhibited TGF-β1-stimulated MMP-9 and the invasive phenotype in MDA-MB-231 cells, possibly associated with TGF-β/Smad and TGF-β/ERK signaling.
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Affiliation(s)
- Na Mo
- Department of Pathology, Chongqing Medical University, Chongqing, China
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