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Iijima S, Takeda K, Nagahiro T, Watanabe K, Ikegaya Y, Matsumoto N. Acute curcumin administration enhances delta oscillations in the hippocampus underlying object memory improvement. J Pharmacol Sci 2025; 158:95-102. [PMID: 40288828 DOI: 10.1016/j.jphs.2025.03.007] [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: 12/04/2024] [Revised: 03/10/2025] [Accepted: 03/14/2025] [Indexed: 04/29/2025] Open
Abstract
Curcumin mitigates memory deficits or improves memory when it is chronically administered to animals. Due to limited bioavailability of curcumin, it remains almost unknown whether acutely treated curcumin influences cognitive function and underlying neural activity. To address this question, we monitored behavior and neural activity in the hippocampus and medial prefrontal cortex of mice treated with vehicle or curcumin while they were engaged in a novel object recognition task. Object recognition memory performance in the novel object recognition task was increased in curcumin-treated mice. Moreover, delta oscillations in the hippocampus were enhanced in the curcumin-administered mice in the test trial. Altogether, acute curcumin treatment boosts delta oscillations for memory recognition possibly by neuromodulation.
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Affiliation(s)
- Sena Iijima
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan
| | - Kinjiro Takeda
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan
| | - Takeshi Nagahiro
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan
| | - Kisa Watanabe
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan
| | - Yuji Ikegaya
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan; Institute for AI and Beyond, The University of Tokyo, Tokyo, 113-0033, Japan; Center for Information and Neural Networks, National Institute of Information and Communications Technology, Suita City, Osaka, 565-0871, Japan
| | - Nobuyoshi Matsumoto
- Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan; Institute for AI and Beyond, The University of Tokyo, Tokyo, 113-0033, Japan.
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Xiao H, Ma W, Zha L, Xiao Y, Li H. Curcumin alleviates LPS-induced WI-38 cell inflammation injury by regulating PTGS2 expression. Hereditas 2025; 162:81. [PMID: 40380246 DOI: 10.1186/s41065-025-00441-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2025] [Accepted: 04/28/2025] [Indexed: 05/19/2025] Open
Abstract
BACKGROUND Infantile pneumonia is a common infectious disease affecting infants and young children, which can lead to severe complications such as heart failure, significantly increasing morbidity and mortality rates among affected populations. Curcumin (CUR), a prominent natural polyphenol found in turmeric and other species of Curcuma, exhibits anti-inflammatory, antioxidant, and anticancer properties. Consequently, CUR has been hoped to be a therapeutic or preventive agent for several main human diseases. This study aims to explore the effects of CUR on lipopolysaccharide (LPS)-treated Wistsar Institute (WI)-38 cells. METHODS The cell vitality, proliferation, and apoptosis were assessed by cell counting kit-8 (CCK8) assay, 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays. Inflammation and oxidative stress were examined by measuring interleukins (IL)-6, IL-1β, tumor necrosis factor α (TNF-α), malondialdehyde (MDA), and superoxide dismutase (SOD) levels using the corresponding enzyme-linked immunosorbent assay (ELISA) test kits. The network pharmacology and molecule docking were carried out to predict the critical targets and potential therapeutic mechanisms of CUR in infantile pneumonia. The key target genes were predicted using PPI in the CUR protected-infantile pneumonia effect. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to exhibit the biological function. The results of prediction were confirmed in vitro experiments. RESULTS LPS inhibited the vitality, proliferation, and SOD levels of WI-38 cells and facilitated the cell apoptosis, IL-6, IL-1β, TNF-α, and MDA levels. CUR abolished LPS-induced regulation WI-38 cell biological functions. Besides, the 16 hub genes from potential target genes of CUR and infantile pneumonia were screened. Moreover, six hub genes (enhanced green fluorescent protein (EGFP), v-akt murine thymoma viral oncogene homolog 1 (AKT1), prostaglandin endoperoxide synthase (PTGS2), signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase 9 (MMP9), and tumor necrosis factor (TNF)) in the CUR-protected-infantile pneumonia effect were identified by PPI analysis. The therapeutic effects of CUR on infantile pneumonia might relate to anti-viral and anti-inflammatory effects predicted by GO and KEGG enrichment analysis. Interestingly, CUR repressed LPS-stimulated facilitation of PTGS2 expression. The molecular docking demonstrated that PTGS2 could directly bind to CUR. The PTGS2 levels were inhibited by CUR treatment and negatively related to the time after WI-38 cells were treated with cycloheximide (CHX). PTGS2 knockdown could promote LPS-induced injury in WI-38 cells. CUR expedited cell vitality and proliferation and suppressed cell apoptosis, inflammation, and oxidative stress in LPS-induced WI-38 cells via down-regulating PTGS2. CONCLUSION CUR attenuates LPS-induced WI-38 cell injury by downregulating PTGS2. CUR may be the potential drug for alleviating LPS-induced WI-38 cell inflammation damage via regulating PTGS2 expression.
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Affiliation(s)
- Hongli Xiao
- Department of Pediatrics, Puren Hospital, Wuhan University of Science and Technology, No.1 Benxi Street, Heping Avenue, Qingshan District, Wuhan City, 430081, Hubei, China
| | - Wangsheng Ma
- Department of Pediatrics, Puren Hospital, Wuhan University of Science and Technology, No.1 Benxi Street, Heping Avenue, Qingshan District, Wuhan City, 430081, Hubei, China
| | - Lin Zha
- Department of Pediatrics, Puren Hospital, Wuhan University of Science and Technology, No.1 Benxi Street, Heping Avenue, Qingshan District, Wuhan City, 430081, Hubei, China
| | - Yanmin Xiao
- Department of Pediatrics, Puren Hospital, Wuhan University of Science and Technology, No.1 Benxi Street, Heping Avenue, Qingshan District, Wuhan City, 430081, Hubei, China
| | - Hui Li
- Department of Pediatrics, Puren Hospital, Wuhan University of Science and Technology, No.1 Benxi Street, Heping Avenue, Qingshan District, Wuhan City, 430081, Hubei, China.
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Huang X, Feng L, Lu X, Yang F, Liu S, Wei X, Huang J, Wang Y, Huang D, Huang T. Development and optimization of a self micro-emulsifying drug delivery system (SMEDDS) for co-administration of sorafenib and curcumin. Drug Deliv Transl Res 2025; 15:1609-1625. [PMID: 39207633 DOI: 10.1007/s13346-024-01699-3] [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] [Accepted: 08/06/2024] [Indexed: 09/04/2024]
Abstract
In this study, we developed a novel co-administration of curcumin and sorafenib using a Self micro-emulsifying Drug Delivery System (SMEDDS) called Sorafenib-Curcumin Self micro-emulsifying Drug Delivery System (SOR-CUR-SMEDDS). The formulation was optimized using star point design-response surface methodology, and in vitro cellular experiments were conducted to evaluate the delivery ratio and anti-tumor efficacy of the curcumin and sorafenib combination. The SOR-CUR-SMEDDS exhibited a small size distribution of 13.48 ± 0.61 nm, low polydispersity index (PDI) of 0.228 ± 0.05, and negative zeta potential (ZP) of - 12.4 mV. The half maximal inhibitory concentration (IC50) of the SOR-CUR-SMEDDS was 3-fold lower for curcumin and 5-fold lower for sorafenib against HepG2 cells (human hepatocellular carcinoma cells). Transmission electron microscopy (TEM) and particle size detection confirmed that the SOR-CUR-SMEDDS droplets were uniformly round and within the nano-emulsion particle size range of 10-20 nm. The SMEDDS were characterized then studied for drug release in vitro via dialysis membranes. Curcumin was released more completely in the combined delivery system, showing the largest in vitro drug release (79.20%) within 7 days in the medium, while the cumulative release rate of sorafenib in the release medium was low, reaching 58.96% on the 7 day. In vitro pharmacokinetic study, it demonstrated a significant increase in oral bioavailability of sorafenib (1239.88-fold) and curcumin (3.64-fold) when administered in the SMEDDS. These findings suggest that the SMEDDS formulation can greatly enhance drug solubility, improve drug absorption and prolong circulation in vivo, leading to increased oral bioavailability of sorafenib and curcumin.
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Affiliation(s)
- Xingzhen Huang
- School of Pharmacy, Guangxi Medical University, Nanning, Guangxi, 530000, PR China.
- Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Nanning, Guangxi, 530000, PR China.
| | - Lizhen Feng
- School of Pharmacy, Guangxi Medical University, Nanning, Guangxi, 530000, PR China
| | - Xuefang Lu
- Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530000, PR China
| | - Fan Yang
- Hechi Food and Drug Inspection Institute, Hechi, Guangxi, 547000, PR China
| | - Shengjun Liu
- School of Pharmacy, Guangxi Medical University, Nanning, Guangxi, 530000, PR China
| | - Xueqian Wei
- Hechi Food and Drug Inspection Institute, Hechi, Guangxi, 547000, PR China
| | - Jinping Huang
- School of Pharmacy, Guangxi Medical University, Nanning, Guangxi, 530000, PR China
| | - Yao Wang
- School of Pharmacy, Guangxi Medical University, Nanning, Guangxi, 530000, PR China
| | - Dongyi Huang
- School of Pharmacy, Guangxi Medical University, Nanning, Guangxi, 530000, PR China
| | - Tingting Huang
- School of Pharmacy, Guangxi Medical University, Nanning, Guangxi, 530000, PR China
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Gupta A, Jadhav SR, Colaco V, Saha M, Ghosh A, Sreedevi A, Datta D, Hebbar S, Moorkoth S, Ligade VS, Dhas N. Harnessing unique architecture and emerging strategies of solid lipid nanoparticles to combat colon cancer: A state-of-the-art review. Int J Pharm 2025; 675:125562. [PMID: 40194729 DOI: 10.1016/j.ijpharm.2025.125562] [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: 02/07/2025] [Revised: 03/30/2025] [Accepted: 04/02/2025] [Indexed: 04/09/2025]
Abstract
Cancer is a serious worldwide public health problem, ranking as the second leading cause of death in the United States. The third most prevalent tumor kind in the world is a colon or rectal tumor. Colon Cancer (CC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths globally. In the US, CC has become the 2nd most common cause of death after having different advancements like detection, surgery, and chemotherapy. The current strategies for treating colon cancer have several disadvantages, including higher toxicity, drug resistance, damage to healthy cells, solubility, specificity, a lower therapeutic index, and more. Solid lipid nanoparticles (SLNs) are a viable targeted treatment option for colon cancer to avoid this problem. This comprehensive review discussed the severity, pathophysiology, risk factors, and stages of colon cancer. The review covers the most effective colon cancer therapy and diagnostic procedures, including HSgFOBT, Fecal immunological test (FIT), Colonoscopy, FIT-DNA Test/mt-sDNA screening test, Colon capsule (CCE), Blood-based DNA Tests, and Flexible sigmoidoscopy. This reviewemphasizes the need for novel and specific approaches to colon cancer treatment to improve patient outcomes.
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Affiliation(s)
- Ashutosh Gupta
- Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104 Karnataka, India
| | - Sandesh Ramchandra Jadhav
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104 Karnataka, India
| | - Viola Colaco
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104 Karnataka, India
| | - Moumita Saha
- Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104 Karnataka, India
| | - Amartya Ghosh
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104 Karnataka, India
| | - Amatha Sreedevi
- Department of Pharmaceutical Regulatory Affairs, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104 Karnataka, India
| | - Deepanjan Datta
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104 Karnataka, India
| | - Srinivas Hebbar
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104 Karnataka, India
| | - Sudheer Moorkoth
- Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104 Karnataka, India
| | - Virendra S Ligade
- Department of Pharmaceutical Regulatory Affairs, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104 Karnataka, India
| | - Namdev Dhas
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104 Karnataka, India.
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Hong Q, Lyu W, Zhang C, Yao W, Han Y, Chen N. Research trajectory and future trends in curcumin related to immunity: a bibliometric analysis of publications from last two decades. Front Immunol 2025; 16:1559670. [PMID: 40196111 PMCID: PMC11973075 DOI: 10.3389/fimmu.2025.1559670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Accepted: 03/05/2025] [Indexed: 04/09/2025] Open
Abstract
Curcumin has a clear immunopharmacological effect and plays an important role as an immune agent in various immune diseases and tumor immunotherapy. To comprehensively and scientifically clarify and reflect the development process, current status, and research trends of curcumin in the field of immune regulation, and to provide reliable insights for discipline development strategies and future research expansion, this study systematically analyzes 3939 valid articles related to curcumin and immunity published between 2004 and 2024 from the Web of Science database. Using Citespace and R-bibliometrix software for bibliometric analysis, we create visual knowledge maps from multiple dimensions including overall publication output, influential research entities, highly cited papers, research topics and hotspots. The results indicate that the overall number of publications and citations is currently in a rapid development phase. China occupies a core position in this research field but has low collaboration intensity. The Egyptian Knowledge Bank (EKB) is the institution with the highest publication volume. Moreover, cluster analysis reveals that research hotspots are gradually shifting from fundamental pathology to topics involving broad social and environmental influences. The top five keywords with the most explosive citations-curcumin, inflammation, apoptosis, oxidative stress, and cancer-represent the most focused and influential research topics. Currently, curcumin immunology has developed a diversified research perspective, accumulating significant research in the areas of active substance basis, pharmacological activity, anti-inflammatory, and anti-cancer studies. The thematic evolution trends and keywords related to curcumin's immunological mechanisms summarized in this article provide insights and guidance for future research directions.
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Affiliation(s)
- Qing Hong
- Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Wei Lyu
- School of Economics and Management, Anhui Polytechnic University, Wuhu, China
| | - Chaowei Zhang
- Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Weiyi Yao
- Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Yuxuan Han
- Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Na Chen
- Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
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Eghbali A, Adibifar M, Ghasemi A, Afzal RR, Moradi K, Eghbali A, Faress F, Ghaffari K. The effect of oral curcumin on vincristine-induced neuropathy in pediatric acute lymphoblastic leukemia: A double-blind randomized controlled clinical trial. BMC Cancer 2025; 25:344. [PMID: 40000988 PMCID: PMC11853498 DOI: 10.1186/s12885-025-13751-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 02/17/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND Peripheral neuropathy is a major adverse effect of Vincristine (VCR) in pediatric acute lymphoblastic leukemia (ALL) patients. Curcumin can prevent the development of many neurological diseases. METHOD This clinical trial study was conducted on 141 pediatric ALL patients, all over 5 years old. The subjects were randomly divided into a curcumin-treatment group and a placebo group. In the curcumin-treatment group, patients received 3 mg/kg oral curcumin capsules twice a day for 3 months. In the placebo cohort, participants were administered placebo capsules twice a day for 3 months. Administration of VCR was started in all patients in both groups, with a weekly dose of 1.5 mg/m2. RESULT Overall, 39.4% of participants in the curcumin treatment group and 70.0% in the placebo group had VIPN. Thus, a significant difference in the incidence of VIPN was observed in the two groups (P < 0.001). A significantly higher frequency of motor nerve abnormalities in all types of nerves was observed in the placebo group than in the curcumin treatment group (P < 0.05). CONCLUSIONS The results of our study showed that curcumin is effective in preventing the development of VIPN and leads to the improvement of VIPN in these patients. Our findings indicate that the prevalence of VIPN was substantially lower in the curcumin-treated group compared to the placebo group, as confirmed by both NCS and EMG assessments. Furthermore, curcumin demonstrated a protective effect against motor and sensory nerve damage, with a significant reduction in motor nerve abnormalities. TRIAL REGISTRATION This study was registered at https://irct.behdasht.gov.ir/trial/73161 . TRIAL REGISTRATION NUMBER IRCT20201107049296N3. Date of registration: 2022-09-11.
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Affiliation(s)
- Aziz Eghbali
- Clinical Research Development Center of Aliasghar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Mahsa Adibifar
- Clinical Research Development Center of Aliasghar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Ghasemi
- Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran.
- Department of Biochemistry and Hematology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
- Abnormal Uterine Bleeding Research Center, Semnan University of Medical Sciences, Semnan, Iran.
| | - Roghayeh Rahimi Afzal
- Department of Pediatrics, Amir Kabir Hospital, Arak University of Medical Sciences, Arak, Iran
| | - Katayoun Moradi
- Neuromasculaoskeletal Research Center, Department of Physical Medicine and Rehabilitation, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Aygin Eghbali
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Foroozan Faress
- Department of Forensic Medicine and Toxicology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Kazem Ghaffari
- Department of Hematology and Blood Transfusion Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.
- Department of Basic and Laboratory Sciences, Khomein University of Medical Sciences, Khomein, Iran.
- Student's Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.
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7
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Meftahpour H, Leasan S, Jafariazar Z, Farrokhnia T. Comparative Antifungal Efficacy of Curcumin Plus Nystatin Versus Nystatin Monotherapy for Treatment of Denture Stomatitis: A Clinical Trial. Front Dent 2025; 22:8. [PMID: 40390830 PMCID: PMC12086465 DOI: 10.18502/fid.v22i8.17841] [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: 01/25/2023] [Accepted: 07/01/2024] [Indexed: 05/21/2025] Open
Abstract
Objectives: This study compared the antifungal efficacy of curcumin plus nystatin versus nystatin monotherapy for treatment of denture stomatitis. Materials and Methods: This single-blind clinical trial evaluated 32 patients with types II and III denture stomatitis. Microbial samples were collected from the patients' palate to count the Candida albicans (C. albicans) colonies. Erythema of the palate was quantified by measuring the surface area of the erythematous sites. The patients were randomly assigned to two groups (n=16). The control group received nystatin suspension while the test group received a curcumin mouthwash plus nystatin suspension. The number of C. albicans colony forming units (CFUs) and the surface area of the erythematous sites were calculated again after 14 days. Data were analyzed using t-test and Wilcoxon signed-rank test (alpha=0.05). Results: Both groups experienced a significant reduction in C. albicans colony count after the intervention (P<0.001). There was no significant difference in reduction of colony count between the two groups (P=0.341). Both groups experienced a significant reduction in the size of erythema (P=0.001 for the nystatin and P<0.001 for the nystatin plus curcumin). The two groups were not significantly different regarding the size of erythema at baseline (P=0.956) or after the intervention (P=0.491). Conclusion: Addition of curcumin to nystatin suspension did not add any significant advantage with regard to reduction of C. albicans colony count or erythema of the palate, and both interventions were equally effective.
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Affiliation(s)
| | - Simin Leasan
- Oral Medicine Department, Faculty of Dentistry, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Zahra Jafariazar
- Department of Pharmaceutics, Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Taraneh Farrokhnia
- Oral Medicine Department, Faculty of Dentistry, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
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EL-Rafei AM, Maurizii G, Aluigi A, Sotgiu G, Barbalinardo M, Posati T. Designing and Fabrication of Nano-Hydroxyapatite and Curcumin-Loaded Chitosan/PVA Nanofibrous Mats for Potential Use as Wound Dressing Biomaterials. NANOMATERIALS (BASEL, SWITZERLAND) 2025; 15:82. [PMID: 39852697 PMCID: PMC11767821 DOI: 10.3390/nano15020082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 12/23/2024] [Accepted: 12/24/2024] [Indexed: 01/26/2025]
Abstract
Chitosan/polyvinyl alcohol nanofibrous mats loaded with nano-hydroxyapatite and/or curcumin are successfully fabricated by the electrospinning method for the first time. Nano-hydroxyapatite is prepared by the co-precipitation method. The XRD pattern of calcined powder at 700 °C for 2 h reveals the presence of hydroxyapatite as a sole phase. FT-IR confirms its purity. The morphology of the hydroxyapatite is studied by HR-TEM. Nano-hydroxyapatite and curcumin are added at 5 wt% with respect to the polymer weight. XRD, FE-SEM, FT-IR, and HR-TEM are used to characterize the fabricated nanofibrous mats. The results confirm the successful loading of nano-hydroxyapatite and curcumin within the fabricated mats. The in vitro antimicrobial results show that most of mats have significant antimicrobial effects against E. coli and S. aureus. The fabricated matd are biocompatible with fibroblasts and the presence of curcumin increases cell viability. Curcumin release from both CS/PVA/Cur and CS/PVA/HA/Cur nanofiber mats principally follows the Korsmeyer-Peppas and Peppas-Salhin models.
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Affiliation(s)
- Amira M. EL-Rafei
- Refractories, Ceramics and Building Materials Department, National Research Centre, 33 EL Bohouth St., Dokki, Giza P.O. Box 12622, Egypt
| | - Giorgia Maurizii
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Piazza del Rinascimento, 6, 61029 Urbino, Italy; (G.M.); (A.A.)
| | - Annalisa Aluigi
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, Piazza del Rinascimento, 6, 61029 Urbino, Italy; (G.M.); (A.A.)
| | - Giovanna Sotgiu
- Consiglio Nazionale delle Ricerche (CNR), Istituto per la Sintesi Organica e Fotoreattività (ISOF), Via Piero Gobetti, 101, 40129 Bologna, Italy; (G.S.); (M.B.); (T.P.)
| | - Marianna Barbalinardo
- Consiglio Nazionale delle Ricerche (CNR), Istituto per la Sintesi Organica e Fotoreattività (ISOF), Via Piero Gobetti, 101, 40129 Bologna, Italy; (G.S.); (M.B.); (T.P.)
| | - Tamara Posati
- Consiglio Nazionale delle Ricerche (CNR), Istituto per la Sintesi Organica e Fotoreattività (ISOF), Via Piero Gobetti, 101, 40129 Bologna, Italy; (G.S.); (M.B.); (T.P.)
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Ebrahimzadeh A, Ebrahimzadeh A, Fooladshekan S, Mohseni S, Mohtashamian A, Babajafari S, Sohrabi Z. Therapeutic effects of curcumin supplementation on liver enzymes of nonalcoholic fatty liver disease patients: A systematic review and meta-analysis of randomized clinical trials. Food Sci Nutr 2025; 13:e4144. [PMID: 39803230 PMCID: PMC11716989 DOI: 10.1002/fsn3.4144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 03/08/2024] [Accepted: 03/18/2024] [Indexed: 01/05/2025] Open
Abstract
Curcumin, as an antioxidant agent, has been proposed as a potential treatment for nonalcoholic fatty liver disease (NAFLD). The aim of the current systematic review and meta-analysis was to summarize earlier findings regarding the effect of curcumin supplementation on liver enzymes and ALP in NAFLD patients. All studies published up to November 18, 2022, were searched through the PubMed, SCOPUS, and Web of Science databases to collect all randomized clinical trials (RCTs) on NAFLD patients in which curcumin was used as a treatment. A random-effects model was used to measure pooled effect sizes. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were used to report pooled effect sizes. Subgroup analysis was utilized to investigate heterogeneity. A total of 14 studies were included in this systematic review and meta-analysis. Our pooled meta-analysis indicated a significant decrease in alanine aminotransferase (ALT) following curcumin therapy by pooling 12 effect sizes (WMD: -8.72; 95% CI: -15.16, -2.27, I 2 = 94.1%) and in aspartate aminotransferase (AST) based on 13 effect sizes (WMD: -6.35; 95% CI: -9.81, -2.88, I 2 = 94.4%). However, the pooled analysis of five trials indicated that there was no significant association between curcumin therapy and alkaline phosphatase (ALP) in NAFLD patients (WMD: -4.71; 95% CI: -13.01, 3.58, I 2 = 64.2%). Nevertheless, subgroup analyses showed significant effects of curcumin on ALP with a longer duration of supplementation. The findings of this systematic review and meta-analysis support the potential effect of curcumin on the management of NAFLD. Further randomized controlled trials should be conducted in light of our findings.
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Affiliation(s)
- Armin Ebrahimzadeh
- Nutrition Research Center, School of Nutrition and Food SciencesShiraz University of Medical SciencesShirazIran
| | - Anahita Ebrahimzadeh
- Nutrition Research Center, School of Nutrition and Food SciencesShiraz University of Medical SciencesShirazIran
| | - Sara Fooladshekan
- Dental Research CenterGolestan University of Medical SciencesGorganIran
| | - Shokouh Mohseni
- Nutrition Research Center, School of Nutrition and Food SciencesShiraz University of Medical SciencesShirazIran
| | - Abbas Mohtashamian
- Student Research Committee, Department of Nutrition, Faculty of MedicineKashan University of Medical SciencesKashanIran
| | - Siavash Babajafari
- Nutrition Research Center, School of Nutrition and Food SciencesShiraz University of Medical SciencesShirazIran
| | - Zahra Sohrabi
- Nutrition Research Center, School of Nutrition and Food SciencesShiraz University of Medical SciencesShirazIran
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Gupta S, Chander NG, Bhatt A, Anitha K. Evaluation of osteoblast response to polyacrylonitrile infused nano-curcumin coated on titanium discs: Invitro study cell culture experimental study. J Oral Biol Craniofac Res 2025; 15:57-62. [PMID: 39734420 PMCID: PMC11681823 DOI: 10.1016/j.jobcr.2024.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 10/08/2024] [Accepted: 12/05/2024] [Indexed: 12/31/2024] Open
Abstract
Purpose The study evaluated the influence of titanium discs, coated with polyacrylonitrile infused curcumin nanofibers on osteoblast activity. Materials and methods The titanium discs were coated with polyacrylonitrile nanofibers infused with curcumin. MG-63 cell lines were utilized for cell culture to assess osteoblast morphology upon exposure of curcumin on titanium discs. SEM comparison was made. Lactate Dehydrogenase (LDH) activity was measured after 2 and 7 days and the Alkaline Phosphatase (ALP) activity of the cells was quantified. Results The results indicated that the coating had a notable impact on mineralization, LDH and ALP activities. Significant differences were observed between uncoated and coated samples. The SEM analysis indicated that curcumin enhanced bone growth when the Ti discs coated with curcumin are implanted in the bone. Conclusion Polyacrylonitrile infused nano-curcumin fibers coated on titanium discs potentially enhanced osteoblast response and mineralization.
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Affiliation(s)
- Shilpi Gupta
- Department of Prosthodontics, SRM Dental College, Bharathi Salai, Ramapuram, Chennai, 89, India
| | - N. Gopi Chander
- Department of Prosthodontics, SRM Dental College, Bharathi Salai, Ramapuram, Chennai, 89, India
| | - Aravind Bhatt
- Department of Prosthodontics, SRM Dental College, Bharathi Salai, Ramapuram, Chennai, 89, India
| | - K.V. Anitha
- Department of Prosthodontics, SRM Dental College, Bharathi Salai, Ramapuram, Chennai, 89, India
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11
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Moldoveanu CA, Tomoaia-Cotisel M, Sevastre-Berghian A, Tomoaia G, Mocanu A, Pal-Racz C, Toma VA, Roman I, Ujica MA, Pop LC. A Review on Current Aspects of Curcumin-Based Effects in Relation to Neurodegenerative, Neuroinflammatory and Cerebrovascular Diseases. Molecules 2024; 30:43. [PMID: 39795101 PMCID: PMC11722367 DOI: 10.3390/molecules30010043] [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: 11/06/2024] [Revised: 12/20/2024] [Accepted: 12/24/2024] [Indexed: 01/13/2025] Open
Abstract
Curcumin is among the most well-studied natural substances, known for its biological actions within the central nervous system, its antioxidant and anti-inflammatory properties, and human health benefits. However, challenges persist in effectively utilising curcumin, addressing its metabolism and passage through the blood-brain barrier (BBB) in therapies targeting cerebrovascular diseases. Current challenges in curcumin's applications revolve around its effects within neoplastic tissues alongside the development of intelligent formulations to enhance its bioavailability. Formulations have been discovered including curcumin's complexes with brain-derived phospholipids and proteins, or its liposomal encapsulation. These novel strategies aim to improve curcumin's bioavailability and stability, and its capability to cross the BBB, thereby potentially enhancing its efficacy in treating cerebrovascular diseases. In summary, this review provides a comprehensive overview of molecular pathways involved in interactions of curcumin and its metabolites, and brain vascular homeostasis. This review explores cellular and molecular current aspects, of curcumin-based effects with an emphasis on curcumin's metabolism and its impact on pathological conditions, such as neurodegenerative diseases, schizophrenia, and cerebral angiopathy. It also highlights the limitations posed by curcumin's poor bioavailability and discusses ongoing efforts to surpass these impediments to harness the full therapeutic potential of curcumin in neurological disorders.
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Affiliation(s)
- Claudia-Andreea Moldoveanu
- Department of Molecular Biology and Biotechnology, Babeș-Bolyai University, Clinicilor St., RO-400371 Cluj-Napoca, Romania;
- Department of Experimental Biology and Biochemistry, Institute of Biological Research from Cluj-Napoca, a Branch of NIRDBS Bucharest, 48 Republicii St., RO-400015 Cluj-Napoca, Romania;
| | - Maria Tomoaia-Cotisel
- Research Center of Excellence in Physical Chemistry, Faculty of Chemistry and Chemical Engineering, “Babes-Bolyai University”, 11 Arany Janos St., RO-400028 Cluj-Napoca, Romania or (M.T.-C.); (A.M.); (C.P.-R.); (M.-A.U.)
- Academy of Romanian Scientists, 3 Ilfov St., RO-050044 Bucharest, Romania;
| | - Alexandra Sevastre-Berghian
- Department of Physiology, Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 1 Clinicilor St., RO-400006 Cluj-Napoca, Romania;
| | - Gheorghe Tomoaia
- Academy of Romanian Scientists, 3 Ilfov St., RO-050044 Bucharest, Romania;
- Department of Orthopedics and Traumatology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 47 Gen. Traian Moșoiu St., RO-400132 Cluj-Napoca, Romania
| | - Aurora Mocanu
- Research Center of Excellence in Physical Chemistry, Faculty of Chemistry and Chemical Engineering, “Babes-Bolyai University”, 11 Arany Janos St., RO-400028 Cluj-Napoca, Romania or (M.T.-C.); (A.M.); (C.P.-R.); (M.-A.U.)
| | - Csaba Pal-Racz
- Research Center of Excellence in Physical Chemistry, Faculty of Chemistry and Chemical Engineering, “Babes-Bolyai University”, 11 Arany Janos St., RO-400028 Cluj-Napoca, Romania or (M.T.-C.); (A.M.); (C.P.-R.); (M.-A.U.)
| | - Vlad-Alexandru Toma
- Department of Molecular Biology and Biotechnology, Babeș-Bolyai University, Clinicilor St., RO-400371 Cluj-Napoca, Romania;
- Department of Experimental Biology and Biochemistry, Institute of Biological Research from Cluj-Napoca, a Branch of NIRDBS Bucharest, 48 Republicii St., RO-400015 Cluj-Napoca, Romania;
- Academy of Romanian Scientists, 3 Ilfov St., RO-050044 Bucharest, Romania;
- Centre for Systems Biology, Biodiversity and Bioresources “3B”, Babeș-Bolyai University, 44 Republicii St., RO-400347 Cluj-Napoca, Romania
| | - Ioana Roman
- Department of Experimental Biology and Biochemistry, Institute of Biological Research from Cluj-Napoca, a Branch of NIRDBS Bucharest, 48 Republicii St., RO-400015 Cluj-Napoca, Romania;
| | - Madalina-Anca Ujica
- Research Center of Excellence in Physical Chemistry, Faculty of Chemistry and Chemical Engineering, “Babes-Bolyai University”, 11 Arany Janos St., RO-400028 Cluj-Napoca, Romania or (M.T.-C.); (A.M.); (C.P.-R.); (M.-A.U.)
| | - Lucian-Cristian Pop
- Research Center of Excellence in Physical Chemistry, Faculty of Chemistry and Chemical Engineering, “Babes-Bolyai University”, 11 Arany Janos St., RO-400028 Cluj-Napoca, Romania or (M.T.-C.); (A.M.); (C.P.-R.); (M.-A.U.)
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Liu LY, He SJ, Luo J, Huang JK, Yuan JX, Yuan CJ, Zhang JL. Network pharmacology, molecular docking and experimental study on the mechanism of Curcumin's anti-ferroptosis in melanocytes. Biochem Biophys Res Commun 2024; 736:150871. [PMID: 39461013 DOI: 10.1016/j.bbrc.2024.150871] [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: 08/23/2024] [Revised: 10/02/2024] [Accepted: 10/21/2024] [Indexed: 10/28/2024]
Abstract
Ferroptosis is a form of regulated nonapoptotic cell death associated with iron-dependent lipid peroxidation, closely associated with Vitiligo. Although the impact of Curcumin (Cur), a polyphenolic compound derived from the plant Curcuma longa Linn, on vitiligo has been established, the specific role and potential mechanistic pathways through which Cur modulates ferroptosis in vitiligo remain elusive. In this study, the critical targets and potential mechanisms of Cur in treating vitiligo were predicted by network pharmacology and molecule docking. Then, the effects of Cur on Erastin-induced ferroptosis were investigated in melanocytes induced by Erastin in vitro. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of Cur acting on Vitiligo found that these intersection genes are associated with the vitiligo oxidative stress pathway, including nuclear factor erythroid 2-related factor 2(Nrf2)/Heme Oxygenase 1(HO-1) signaling pathway. Further molecular docking shows that Cur has a good binding effect with Nrf2(the binding energy of Cur and Nrf2 protein is -6 kcal/mol). Through the CCK8 assay, showed that 10 μM Cur treatment 24 h after Erastin significantly improved cell viability In vitro. Then we found that Erastin induced cell death, ROS production, the mitochondrial membrane potential(MMP) decreased, Superoxide dismutase (SOD) and Glutathione (GSH) levels reduced, Malonaldehyde (MDA) and iron ion accumulation in melanocytes. In addition, the expression of glutathione peroxidase 4(GPX4) mRNA and protein was inhibited, while the expression of acyl-CoA synthetase long-chain family member 4(ACSL4), Transferrin Receptor Protein 1(TFR1) mRNA and protein was increased. However, the damage induced by Erastin was significantly relieved by Cur and Fer-1 treatment. Mechanistically, Cur treatment significantly promoted nuclear translocation of transcriptional factor Nrf2 and HO-1 expression. Interestingly, pretreatment with ML385, a selective Nrf2 inhibitor, counteracted anti-ferroptosis effects induced by Cur treatment. Taken together, these results demonstrate that Cur inhibits ferroptosis by regulating the Nrf2/HO-1 pathway to protect melanocytes.
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Affiliation(s)
- Lyu-Ye Liu
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 300000, China
| | - Si-Jia He
- Department of Dermatology, Tianjin Public Security Hospital, Tianjin, 300000, China
| | - Jing Luo
- Department of Pathogen Biology and Immunology, Basic Medical College, Tianjin Medical University, Tianjin, 300000, China
| | - Jun-Kai Huang
- Department of Pathogen Biology and Immunology, Basic Medical College, Tianjin Medical University, Tianjin, 300000, China
| | - Jin-Xiang Yuan
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 300000, China
| | - Chuan-Jian Yuan
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 300000, China
| | - Jun-Ling Zhang
- Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, 300000, China.
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13
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Keshavarz Shahbaz S, Koushki K, Izadi O, Penson PE, Sukhorukov VN, Kesharwani P, Sahebkar A. Advancements in curcumin-loaded PLGA nanoparticle delivery systems: progressive strategies in cancer therapy. J Drug Target 2024; 32:1207-1232. [PMID: 39106154 DOI: 10.1080/1061186x.2024.2389892] [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: 04/23/2024] [Revised: 07/29/2024] [Accepted: 07/31/2024] [Indexed: 08/09/2024]
Abstract
Cancer is a leading cause of death worldwide, and imposes a substantial socioeconomic burden with little impact especially on aggressive types of cancer. Conventional therapies have many serious side effects including generalised systemic toxicity which limits their long-term use. Tumour resistance and recurrence is another main problem associated with conventional therapy. Purified or extracted natural products have been investigated as cost-effective cancer chemoprotective agents with the potential to reverse or delaying carcinogenesis. Curcumin (CUR) as a natural polyphenolic component, exhibits many pharmacological activities such as anti-cancer, anti-inflammatory, anti-microbial, activity against neurodegenerative diseases including Alzheimer, antidiabetic activities (type II diabetes), anticoagulant properties, wound healing effects in both preclinical and clinical studies. Despite these effective protective properties, CUR has several limitations, including poor aqueous solubility, low bioavailability, chemical instability, rapid metabolism and a short half-life time. To overcome the pharmaceutical problems associated with free CUR, novel nanomedicine strategies (including polymeric nanoparticles (NPs) such as poly (lactic-co-glycolic acid) (PLGA) NPs have been developed. These formulations have the potential to improve the therapeutic efficacy of curcuminoids. In this review, we comprehensively summarise and discuss recent in vitro and in vivo studies to explore the pharmaceutical significance and clinical benefits of PLGA-NPs delivery system to improve the efficacy of CUR in the treatment of cancer.
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Affiliation(s)
- Sanaz Keshavarz Shahbaz
- Cellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran
- USERN Office, Qazvin University of Medical Science, Qazvin, Iran
| | - Khadijeh Koushki
- Department of Neurosurgery, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA
| | - Omid Izadi
- Department of Industrial Engineering, ACECR Institute of Higher Education Kermanshah, Kermanshah, Iran
| | - Peter E Penson
- Clinical Pharmacy and Therapeutics Research Group, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK
- Liverpool Centre for Cardiovascular Science, Liverpool, UK
| | | | - Prashant Kesharwani
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
| | - Amirhossein Sahebkar
- Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
- Biotechnology Research Centre, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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14
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Leng T, Zhang L, Ma J, Qu X, Lei B. Intrinsically bioactive multifunctional Poly(citrate-curcumin) for rapid lung injury and MRSA infection therapy. Bioact Mater 2024; 41:158-173. [PMID: 39131630 PMCID: PMC11314446 DOI: 10.1016/j.bioactmat.2024.07.002] [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: 02/18/2024] [Revised: 07/01/2024] [Accepted: 07/02/2024] [Indexed: 08/13/2024] Open
Abstract
Dysregulated inflammation after trauma or infection could result in the further disease and delayed tissue reconstruction. The conventional anti-inflammatory drug treatment suffers to the poor bioavailability and side effects. Herein, we developed an amphiphilic multifunctional poly (citrate-polyglycol-curcumin) (PCGC) nano oligomer with the robust anti-inflammatory activity for treating acute lung injury (ALI) and Methicillin-resistant staphylococcus aureus (MRSA) infected wound. PCGC demonstrated the sustained curcumin release, inherent photoluminescence, good cellular compatibility, hemocompatibility, robust antioxidant activity and enhanced cellular uptake. PCGC could efficiently scavenge nitrogen-based free radicals, oxygen-based free radicals, and intracellular oxygen species, enhance the endothelial cell migration and reduce the expression of pro-inflammatory factors through the NF-κB signal pathway. Combined the anti-inflammation and antioxidant properties, PCGC can shortened the inflammatory process. In animal model of ALI, PCGC was able to reduce the pulmonary edema, bronchial cell infiltration, and lung inflammation, while exhibiting rapid metabolic behavior in vivo. The MRSA-infection wound model showed that PCGC significantly reduced the expression of pro-inflammatory factors, promoted the angiogenesis and accelerated the wound healing. The transcriptome sequencing and molecular mechanism studies further demonstrated that PCGC could inhibit multiple inflammatory related pathways including TNFAIP3, IL-15RA, NF-κB. This work demonstrates that PCGC is efficient in resolving inflammation and promotes the prospect of application in inflammatory diseases as the drug-loaded therapeutic system.
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Affiliation(s)
- Tongtong Leng
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China
| | - Long Zhang
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
| | - Junping Ma
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China
| | - Xiaoyan Qu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China
| | - Bo Lei
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
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15
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Acharya SS, Parida BB. Synthetic routes to access dicarbonylated aryls and heteroaryls. Org Biomol Chem 2024; 22:8209-8248. [PMID: 39319402 DOI: 10.1039/d4ob01278j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/26/2024]
Abstract
1,2-Dicarbonyl compounds are privileged functionalities found in natural products, pharmaceuticals, bioactive molecules, and food items, and are important precursors in catalysis, asymmetric synthesis, polymer chemistry and synthesizing functionalized heterocycles. Herein, this comprehensive review focuses on various approaches for synthesizing 1,2-dicarbonylated aryls and heteroaryls in both intermolecular and intramolecular fashion, covering the dicarbonylation of indoles, imidazoheterocycles, indolizines, aminopyrazoles, pyrroloisoquinolines, coumarins, furan, anilines, phenols, anthranils, and benzil synthesis over the last decade (since 2015). Also, the present review highlights the scope and future perspectives of the approach.
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Affiliation(s)
- Swadhin Swaraj Acharya
- Organic Synthesis Laboratory, P. G. Department of Chemistry, Berhampur University, Bhanja Bihar, Odisha, India 760007.
| | - Bibhuti Bhusan Parida
- Organic Synthesis Laboratory, P. G. Department of Chemistry, Berhampur University, Bhanja Bihar, Odisha, India 760007.
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16
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Tsou MH, Lin HY, Lin HM. Multifunctional and novelty green composite film containing sodium alginate, chitosan, rice husk and curcumin. Int J Biol Macromol 2024; 280:136298. [PMID: 39482136 DOI: 10.1016/j.ijbiomac.2024.136298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 08/26/2024] [Accepted: 10/03/2024] [Indexed: 11/03/2024]
Abstract
Foodborne diseases are a global public health issue, with their causes often originating from lapses in food production or transportation leading to food contamination. Therefore, food packaging plays a crucial role in preserving the safety and quality of food. In pursuit of sustainable development, this study aims to utilize agricultural waste-derived functional mesoporous silica nanoparticles in combination with biodegradable molecules to create food packaging films. Through recycling and the use of environmentally friendly green films, the goal is to achieve sustainability and the objectives of green chemistry. The study anticipates the production of biodegradable films and the testing of their antibacterial capabilities, antioxidant properties, biocompatibility, and film stress coefficients. This research will provide robust support for advancing green packaging technology to address the challenges of global food safety and environmental sustainability. The experiment is divided into two parts. The first part involves the synthesis of multifunctional mesoporous silica nanoparticles with antibacterial properties derived from rice husk (Rice husk mesoporous silica nanoparticles, rMSN) as nano-fillers. These nanoparticles are surface modified with a biodegradable polymer, chitosan (Chi), that interacts with the material. Natural extract curcumin (Cur), known for its antioxidant capabilities, is loaded into the pores, and the material's inherent antibacterial properties are utilized. The second part involves blending the material with the natural polymer sodium alginate (SA) to form a film (rMSN-Chi@Cur/Alg film). The film's thickness, stress strength, antibacterial, and antioxidant capabilities are tested to ensure the material possesses antibacterial and antioxidant properties.
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Affiliation(s)
- Min-Hsuan Tsou
- Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan
| | - Hsien-Yu Lin
- Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan
| | - Hsiu-Mei Lin
- Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan.
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17
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Bello ET, Awe S, Bale MI, Awosika A, Oladejo JM, Olaitan FJ, Ikibe JE. Antibacterial Activity of Phyto-Synthesized Silver Nanoparticles From Dryopteris cristata Against Staphylococcus aureus ATCC 28923 and Escherichia coli ATCC 28922. Cureus 2024; 16:e70856. [PMID: 39493097 PMCID: PMC11531801 DOI: 10.7759/cureus.70856] [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] [Accepted: 10/04/2024] [Indexed: 11/05/2024] Open
Abstract
Introduction Nanotechnology has emerged as a vital field, particularly in synthesizing nanoparticles. Silver nanoparticles (AgNPs) are recognized for their strong antimicrobial properties against various pathogens, including Staphylococcus aureus and Escherichia coli, due to their small size and high surface area. Green synthesis using plant extracts offers an eco-friendly alternative. The rise of multidrug-resistant bacteria underscores the urgent need for new antimicrobial agents. This study investigates the antibacterial activities of Dryopteris cristata AgNPs (DC-AgNPs) against S. aureus and E. coli, employing antimicrobial susceptibility testing (AST), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assessments, along with nanoparticle characterization. Materials and method The antimicrobial activity ofDC-AgNPs was evaluated using clinical isolates of E. coli and S. aureus. Bacterial inoculums were standardized to 0.5 MacFarlard (1.5 × 108 CFU/mL) and tested via a modified agar-well diffusion method. The MIC and MBC were determined using broth microdilution and sub-culturing methods, respectively. Characterization of the nanoparticles was conducted using Ultraviolet-visible (UV-Vis) spectroscopy, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Results and conclusion D. cristata was identified as the plant used to synthesize AgNPs, confirmed by the University of Ilorin, Nigeria. Phytochemical screening revealed the presence of tannins, flavonoids, glycosides, and phenolics. The AgNPs were synthesized by adding the aqueous extract to silver nitrate, resulting in a color change. Characterization via UV-Vis spectrophotometry confirmed nanoparticle formation. Antimicrobial testing showed that DC-AgNPs effectively inhibited S. aureus and E. coli, with minimum inhibitory concentrations of 125 μg and 250 μg, respectively, indicating their potential as antimicrobial agents.
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Affiliation(s)
- Emmanuel T Bello
- Department of Science Laboratory Technology (Microbiology Unit), Newland Polytechnic, Ilorin, NGA
| | - Sunday Awe
- Department of Microbiology, Kwara State University, Ilorin, NGA
| | - Muritala I Bale
- Department of Microbiology and Parasitology, School of Medicine and Pharmacy, University of Rwanda, Kigali, RWA
| | - Ayoola Awosika
- College of Medicine, University of Illinois Chicago, Chicago, USA
| | - Janet M Oladejo
- Department of Medical Microbiology and Parasitology, University of Ilorin Teaching Hospital, Ilorin, NGA
| | - Faith J Olaitan
- Department of Biological Sciences (Microbiology Unit), Thomas Adewumi University, Oko, NGA
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Paula S, Floruta S, Pajazetovic K, Sobota S, Almahmodi D. The molecular determinants of calcium ATPase inhibition by curcuminoids. BIOCHIMICA ET BIOPHYSICA ACTA. BIOMEMBRANES 2024; 1866:184367. [PMID: 38969202 PMCID: PMC11938986 DOI: 10.1016/j.bbamem.2024.184367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 06/04/2024] [Accepted: 07/01/2024] [Indexed: 07/07/2024]
Abstract
The natural product curcumin and some of its analogs are known inhibitors of the transmembrane enzyme sarco/endoplasmic reticulum calcium ATPase (SERCA). Despite their widespread use, the curcuminoids' binding site in SERCA and their relevant interactions with the enzyme remain elusive. This lack of knowledge has prevented the development of curcuminoids into valuable experimental tools or into agents of therapeutic value. We used the crystal structures of SERCA in its E1 conformation in conjunction with computational tools such as docking and surface screens to determine the most likely curcumin binding site, along with key enzyme/inhibitor interactions. Additionally, we determined the inhibitory potencies and binding affinities for a small set of curcumin analogs. The predicted curcumin binding site is a narrow cleft in the transmembrane section of SERCA, close to the transmembrane/cytosol interface. In addition to pronounced complementarity in shape and hydrophobicity profiles between curcumin and the binding pocket, several hydrogen bonds were observed that were spread over the entire curcumin scaffold, involving residues on several transmembrane helices. Docking-predicted interactions were compatible with experimental observations for inhibitory potencies and binding affinities. Based on these findings, we propose an inhibition mechanism that assumes that the presence of a curcuminoid in the binding site arrests the catalytic cycle of SERCA by preventing it from converting from the E1 to the E2 conformation. This blockage of conformational change is accomplished by a combination of steric hinderance and hydrogen-bond-based cross-linking of transmembrane helices that require flexibility throughout the catalytic cycle.
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Affiliation(s)
- Stefan Paula
- Department of Chemistry, California State University Sacramento, 6000 J Street, Sacramento, CA 95819, USA.
| | - Sergiu Floruta
- Department of Chemistry, California State University Sacramento, 6000 J Street, Sacramento, CA 95819, USA
| | - Karim Pajazetovic
- Department of Chemistry, California State University Sacramento, 6000 J Street, Sacramento, CA 95819, USA
| | - Sydni Sobota
- Department of Chemistry, California State University Sacramento, 6000 J Street, Sacramento, CA 95819, USA
| | - Dina Almahmodi
- Department of Chemistry, California State University Sacramento, 6000 J Street, Sacramento, CA 95819, USA
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Rahman M, Akter K, Ahmed KR, Fahim MMH, Aktary N, Park MN, Shin SW, Kim B. Synergistic Strategies for Castration-Resistant Prostate Cancer: Targeting AR-V7, Exploring Natural Compounds, and Optimizing FDA-Approved Therapies. Cancers (Basel) 2024; 16:2777. [PMID: 39199550 PMCID: PMC11352813 DOI: 10.3390/cancers16162777] [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: 07/01/2024] [Revised: 07/29/2024] [Accepted: 08/03/2024] [Indexed: 09/01/2024] Open
Abstract
Castration-resistant prostate cancer (CRPC) remains a significant therapeutic challenge due to its resistance to standard androgen deprivation therapy (ADT). The emergence of androgen receptor splice variant 7 (AR-V7) has been implicated in CRPC progression, contributing to treatment resistance. Current treatments, including first-generation chemotherapy, androgen receptor blockers, radiation therapy, immune therapy, and PARP inhibitors, often come with substantial side effects and limited efficacy. Natural compounds, particularly those derived from herbal medicine, have garnered increasing interest as adjunctive therapeutic agents against CRPC. This review explores the role of AR-V7 in CRPC and highlights the promising benefits of natural compounds as complementary treatments to conventional drugs in reducing CRPC and overcoming therapeutic resistance. We delve into the mechanisms of action underlying the anti-CRPC effects of natural compounds, showcasing their potential to enhance therapeutic outcomes while mitigating the side effects associated with conventional therapies. The exploration of natural compounds offers promising avenues for developing novel treatment strategies that enhance therapeutic outcomes and reduce the adverse effects of conventional CRPC therapies. These compounds provide a safer, more effective approach to managing CRPC, representing a significant advancement in improving patient care.
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Affiliation(s)
- Muntajin Rahman
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (M.R.); (K.R.A.); (M.M.H.F.); (N.A.); (M.N.P.)
| | - Khadija Akter
- Department of Plasma Bio Display, Kwangwoon University, Seoul 01897, Republic of Korea;
| | - Kazi Rejvee Ahmed
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (M.R.); (K.R.A.); (M.M.H.F.); (N.A.); (M.N.P.)
| | - Md. Maharub Hossain Fahim
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (M.R.); (K.R.A.); (M.M.H.F.); (N.A.); (M.N.P.)
| | - Nahida Aktary
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (M.R.); (K.R.A.); (M.M.H.F.); (N.A.); (M.N.P.)
| | - Moon Nyeo Park
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (M.R.); (K.R.A.); (M.M.H.F.); (N.A.); (M.N.P.)
| | - Sang-Won Shin
- Department of Humanities & Social Medicine, School of Korean Medicine, Pusan National University, 49 Busandaehak-ro, Mulgeum-eup, Yangsan-si 50612, Republic of Korea
| | - Bonglee Kim
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; (M.R.); (K.R.A.); (M.M.H.F.); (N.A.); (M.N.P.)
- Department of Plasma Bio Display, Kwangwoon University, Seoul 01897, Republic of Korea;
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20
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Yang Y, Du Y, Cui B. Polyphenols targeting multiple molecular targets and pathways for the treatment of vitiligo. Front Immunol 2024; 15:1387329. [PMID: 39119340 PMCID: PMC11306171 DOI: 10.3389/fimmu.2024.1387329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 07/11/2024] [Indexed: 08/10/2024] Open
Abstract
Vitiligo, a pigmentary autoimmune disorder, is marked by the selective loss of melanocytes in the skin, leading to the appearance of depigmented patches. The principal pathological mechanism is the melanocyte destruction mediated by CD8+ T cells, modulated by oxidative stress and immune dysregulation. Vitiligo affects both physical health and psychological well-being, diminishing the quality of life. Polyphenols, naturally occurring compounds with diverse pharmacological properties, including antioxidant and anti-inflammatory activities, have demonstrated efficacy in managing various dermatological conditions through multiple pathways. This review provides a comprehensive analysis of vitiligo and the therapeutic potential of natural polyphenolic compounds. We examine the roles of various polyphenols in vitiligo management through antioxidant and immunomodulatory effects, melanogenesis promotion, and apoptosis reduction. The review underscores the need for further investigation into the precise molecular mechanisms of these compounds in vitiligo treatment and the exploration of their combination with current therapies to augment therapeutic outcomes.
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Affiliation(s)
| | | | - Bingnan Cui
- Department of Dermatology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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21
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Mittal R, Keith G, Lacey M, Lemos JRN, Mittal J, Assayed A, Hirani K. Diabetes mellitus, hearing loss, and therapeutic interventions: A systematic review of insights from preclinical animal models. PLoS One 2024; 19:e0305617. [PMID: 38985787 PMCID: PMC11236185 DOI: 10.1371/journal.pone.0305617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 06/02/2024] [Indexed: 07/12/2024] Open
Abstract
OBJECTIVES The aim of this systematic review article is to evaluate the relationship between diabetes mellitus (DM) and sensorineural hearing loss (SNHL) utilizing preclinical animal models. The review focused on studies assessing SNHL in diabetic animal models, elucidating the mechanisms of DM-associated SNHL, and exploring the response of diabetic animal models to noise overexposure. We also discussed studies investigating the efficacy of potential therapeutic strategies for amelioration of DM-associated SNHL in the animal models. METHODS A protocol of this systematic review was designed a priori and was registered in the PROSPERO database (registration number: CRD42023439961). We conducted a comprehensive search on PubMed, Science Direct, Web of Science, Scopus, and EMBASE databases. A minimum of three reviewers independently screened, selected, and extracted data. The risk of bias assessment of eligible studies was conducted using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool. RESULTS Following the screening of 238 studies, twelve original articles were included in this systematic review. The studies revealed that hyperglycemia significantly affects auditory function, with various pathological mechanisms contributing to DM-induced hearing impairment, including cochlear synaptopathy, microangiopathy, neuropathy, oxidative stress, mitochondrial abnormalities, and apoptosis-mediated cell death. Emerging interventions, such as Asiaticoside, Trigonelline, Chlorogenic acid, and Huotanquyu granules, demonstrated efficacy in providing otoprotection for preserving cochlear hair cells and hearing function. CONCLUSIONS Our systematic review delves into the intricate relationship between DM and hearing impairment in animal models. Future research should focus on targeted therapies to enhance cochlear mitochondrial function, alleviate oxidative stress, and regulate apoptosis. The association between SNHL and social isolation as well as cognitive decline underscores the necessity for innovative therapeutic modalities addressing yet undiscovered mechanisms. Translating findings from animal models to human studies will validate these findings, offering a synergistic approach to effectively manage DM-associated co-morbidities such as hearing impairment.
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Affiliation(s)
- Rahul Mittal
- Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, Florida, United States of America
- Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, United States of America
| | - Grant Keith
- School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, United States of America
| | - Mitchel Lacey
- Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, United States of America
| | - Joana R. N. Lemos
- Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, Florida, United States of America
| | - Jeenu Mittal
- Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, United States of America
| | - Amro Assayed
- Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, Florida, United States of America
| | - Khemraj Hirani
- Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, Florida, United States of America
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22
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Fuster MG, Wang J, Fandiño O, Víllora G, Paredes AJ. Folic Acid-Decorated Nanocrystals as Highly Loaded Trojan Horses to Target Cancer Cells. Mol Pharm 2024; 21:2781-2794. [PMID: 38676649 DOI: 10.1021/acs.molpharmaceut.3c01186] [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] [Indexed: 04/29/2024]
Abstract
The nanocrystal (NC) technology has become one of the most commonly used strategies for the formulation of poorly soluble actives. Given their large specific surface, NCs are mainly used to enhance the oral absorption of poorly soluble actives. Differently from conventional nanoparticles, which require the use of carrier materials and have limited drug loadings, NCs' drug loading approaches 100% since they are formed of the pure drug and surrounded by a thin layer of a stabilizer. In this work, we report the covalent decoration of curcumin NCs with folic acid (FA) using EDC/NHS chemistry and explore the novel systems as highly loaded "Trojan horses" to target cancer cells. The decorated NCs demonstrated a remarkable improvement in curcumin uptake, exhibiting enhanced growth inhibition in cancer cells (HeLa and MCF7) while sparing healthy cells (J774A.1). Cellular uptake studies revealed significantly heightened entry of FA-decorated NCs into cancer cells compared to unmodified NCs while also showing reduced uptake by macrophages, indicating a potential for prolonged circulation in vivo. These findings underline the potential of NC highly loaded nanovectors for drug delivery and, in particular, for cancer therapies, effectively targeting folate receptor-overexpressing cells while evading interception by macrophages, thus preserving their viability and offering a promising avenue for precise and effective treatments.
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Affiliation(s)
- Marta G Fuster
- Department of Chemical Engineering, Faculty of Chemistry, University of Murcia (UMU), Campus de Espinardo, Murcia 30100, Spain
| | - Jiawen Wang
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, U.K
| | - Octavio Fandiño
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, U.K
| | - Gloria Víllora
- Department of Chemical Engineering, Faculty of Chemistry, University of Murcia (UMU), Campus de Espinardo, Murcia 30100, Spain
| | - Alejandro J Paredes
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, U.K
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23
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Xu X, Xu J, Sun Z, Tetiana D. Cyclodextrin-grafted redox-responsive hydrogel mediated by disulfide bridges for regulated drug delivery. Des Monomers Polym 2024; 27:21-34. [PMID: 38826495 PMCID: PMC11141310 DOI: 10.1080/15685551.2024.2358581] [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: 01/30/2024] [Accepted: 05/18/2024] [Indexed: 06/04/2024] Open
Abstract
In this paper, a novel mono-methacrylated β-cyclodextrin (β-CD) monomer mediated by disulfide bond was synthesized, and then thermal copolymerized with HEMA monomer in the presence of a little crosslinker to prepare redox-responsive hydrogel for regulated drug delivery. The structure of the monomer was confirmed by FTIR, 1H NMR, 13C NMR spectroscopy. The substitution degree of polymerizable methacrylated group grafted onto β-CD was about 1 by calculating by1H NMR (0.987) and element analysis (0.937). The mono-methacrylated β-CD monomer can well copolymerize with 2-hydroxyethyl methacrylate (HEMA) monomer with gel fraction over 80%. The hydrogel shows low cytotoxicity, and copolymerization of the mono-methacrylated β-CD monomer in the hydrogels increases its equilibrium swelling degree (ESD) and tensile strength, while its transmittance slightly decreases. Drug loading and release rate are dependent on the β-CD content. The hydrogel with high β-CD content of 13.83 wt% shows 1.8 and 8.5 folds puerarin (PUE) and curcumin (CUR) loading than pure pHEMA hydrogel, respectively. The incorporation of β-CD sustained drug release, especially CUR release was prolonged more than 24 h from 5 h of pure pHEMA hydrogel (80% release). The hydrogels are highly sensitive to reduced glutathione (GSH), and low concentration of GSH of 3 mM can significantly accelerate drug release rate. The higher of β-CD content, the more sensitive the hydrogels to GSH, resulting in rapider drug release rate.
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Affiliation(s)
- Xin Xu
- School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
| | - Jinku Xu
- School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
| | - Zeyuan Sun
- School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
- College of Pharmacy, Kyiv National University of Technologies and Design, Kyiv, Ukraine
| | - Derkach Tetiana
- College of Pharmacy, Kyiv National University of Technologies and Design, Kyiv, Ukraine
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24
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Chen L, Hua B, He Q, Han Z, Wang Y, Chen Y, Ni H, Zhu Z, Xu L, Yao M, Ni C. Curcumin analogue NL04 inhibits spinal cord central sensitization in rats with bone cancer pain by inhibiting NLRP3 inflammasome activation and reducing IL-1β production. Eur J Pharmacol 2024; 970:176480. [PMID: 38490468 DOI: 10.1016/j.ejphar.2024.176480] [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: 12/12/2023] [Revised: 02/08/2024] [Accepted: 03/04/2024] [Indexed: 03/17/2024]
Abstract
The management and therapy of bone cancer pain (BCP) remain formidable clinical challenges. Curcumin and its analogues have been shown to have anti-inflammatory and analgesic properties. In the present study, we investigated the efficacy of curcumin analogue NL04 (NL04) in modulating inflammation in spinal dorsal horn (SDH), thereby exploring its potential to reduce central sensitization of BCP in a rat model. Differing doses of NL04 and curcumin were administered intrathecally either once (on day 12 of BCP) or over seven consecutive days (from day 6-12 of BCP). Results indicated that the ED50 for NL04 and curcumin ameliorating BCP-induced mechanical hyperalgesia is 49.08 μg/kg and 489.6 μg/kg, respectively. The analgesic effects at various doses of NL04 lasted between 4 and 8 h, with sustained administration over a week maintaining pain relief for 1-4 days, while also ameliorating locomotor gait via gait analysis and reducing depressive and anxiety-like behaviors via open-field and light-dark transition tests. The analgesic effects at various doses of curcumin lasted 4 h, with sustained administration over a week maintaining pain relief for 0-2 days. ELISA, Western blotting, qPCR, and immunofluorescence assays substantiated that intrathecal administration of NL04 on days 6-12 of BCP dose-dependently lowered spinal IL-1β and IL-18 levels and significantly reduced the expression of IKKβ genes and proteins, as well as the downstream cleavage of the trans-Golgi network (TGN). Whole-cell patch-clamp results demonstrated that NL04 inhibits potassium ion efflux in rat primary spinal neurons. Thus, NL04 exhibits significant analgesic effects in a BCP rat model by downregulating IKKβ expression and inhibiting neuronal potassium ion efflux, which, in turn, suppresses the activation of NLRP3 inflammasomes and reduces IL-1β production, potentially ameliorating pain management in BCP.
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Affiliation(s)
- Liping Chen
- Department of Anesthesiology and Pain Research Center, Jiaxing University Affiliated Hospital, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China
| | - Bohan Hua
- Anesthesia Medicine, Jiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Qiuli He
- Department of Anesthesiology and Pain Research Center, Jiaxing University Affiliated Hospital, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China
| | - Zixin Han
- Department of Anesthesiology and Pain Research Center, Jiaxing University Affiliated Hospital, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China
| | - Yahui Wang
- Department of Anesthesiology and Pain Research Center, Jiaxing University Affiliated Hospital, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China
| | - Yujing Chen
- Department of Pathology, Jiaxing University Affiliated Hospital, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China
| | - Huadong Ni
- Department of Anesthesiology and Pain Research Center, Jiaxing University Affiliated Hospital, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China
| | - Zefeng Zhu
- Department of Radiology, Jiaxing University Affiliated Hospital, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China
| | - Longsheng Xu
- Department of Anesthesiology and Pain Research Center, Jiaxing University Affiliated Hospital, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China
| | - Ming Yao
- Department of Anesthesiology and Pain Research Center, Jiaxing University Affiliated Hospital, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China.
| | - Chaobo Ni
- Department of Anesthesiology and Pain Research Center, Jiaxing University Affiliated Hospital, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China.
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25
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Gogoi NG, Rahman A, Dutta P, Saikia J, Baruah A, Handique JG. Design, Synthesis, Biological Evaluation and in Silico Studies of Curcumin Pyrrole Conjugates. Chem Biodivers 2024; 21:e202301605. [PMID: 38488861 DOI: 10.1002/cbdv.202301605] [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] [Accepted: 03/13/2024] [Indexed: 04/12/2024]
Abstract
Curcumin conjugated heterocyclic compounds are potent candidates with drug likeness against various bacterial pathogens. A set of curcumin-based pyrrole conjugates (CPs) were synthesized and characterized by FT-IR, 1H and 13C NMR and HR-MS techniques. The results of free radical scavenging activity of the synthesized CPs, evaluated by FRAP and CUPRAC assays, showed the potency of these compounds as effective antioxidants. CP3 exhibits the highest antioxidant activity amongst the CPs. The bactericidal efficacy of CPs was screened against ESKAP bacterial pathogens, and CPs were found to possess better antibacterial property than curcumin, specifically against staphylococcus aureus bacteria. In addition, serum albumin (BSA and HSA) binding interaction of these CPs were determined by UV-visible and fluorescence spectrophotometric techniques. In-silico molecular docking study was performed to determine the binding patterns of molecular targets against Staphylococcus aureus tyrosyl tRNA synthetase, and serum albumin proteins. The structure-activity relationship showed that the presence of multiple phenolic hydroxyl groups, and electron withdrawing groups on the structure of CP molecule, enhances its antioxidant and antibacterial activity, respectively.
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Affiliation(s)
- Nishi Gandha Gogoi
- Department of Chemistry, Dibrugarh University, Dibrugarh, 786004, Assam, India
- Department of Chemistry, Manohari Devi Kanoi Girls College, Dibrugarh, 786001, Assam, India
| | - Aziza Rahman
- Department of Chemistry, Dibrugarh University, Dibrugarh, 786004, Assam, India
| | - Pankaj Dutta
- Department of Physics, Dibrugarh University, Dibrugarh, 786004, Assam, India
| | - Jiban Saikia
- Department of Chemistry, Dibrugarh University, Dibrugarh, 786004, Assam, India
| | - Anupaul Baruah
- Department of Chemistry, Dibrugarh University, Dibrugarh, 786004, Assam, India
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26
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Huang D, Wang Y, Xu C, Zou M, Ming Y, Luo F, Xu Z, Miao Y, Wang N, Lin Z, Weng Z. Colon-targeted hydroxyethyl starch-curcumin microspheres with high loading capacity ameliorate ulcerative colitis via alleviating oxidative stress, regulating inflammation, and modulating gut microbiota. Int J Biol Macromol 2024; 266:131107. [PMID: 38527677 DOI: 10.1016/j.ijbiomac.2024.131107] [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: 01/10/2024] [Revised: 03/08/2024] [Accepted: 03/21/2024] [Indexed: 03/27/2024]
Abstract
Curcumin (CUR) is a natural polyphenol that holds promise for treating ulcerative colitis (UC), yet oral administration of CUR exhibits limited bioavailability and existing formulations for oral delivery of CUR often suffer from unsatisfactory loading capacity. This study presents hydroxyethyl starch-curcumin microspheres (HC-MSs) with excellent CUR loading capacity (54.52 %), and the HC-MSs can further encapsulate anti-inflammatory drugs dexamethasone (DEX) to obtain a combination formulation (DHC-MSs) with high DEX loading capacity (19.91 %), for combination therapy of UC. The microspheres were successfully engineered, retaining the anti-oxidative and anti-inflammatory activities of parental CUR and demonstrating excellent biocompatibility and controlled release properties, notably triggered by α-amylase, facilitating targeted drug delivery to inflamed sites. In a mouse UC model induced by dextran sulfate sodium, the microspheres effectively accumulated in inflamed colons and both HC-MSs and DHC-MSs exhibited superior therapeutic efficacy in alleviating UC symptoms compared to free DEX. Moreover, mechanistic exploration uncovered the multifaceted therapeutic mechanisms of these formulations, encompassing anti-inflammatory actions, mitigation of spleen enlargement, and modulation of gut microbiota composition. These findings underscore the potential of HC-MSs and DHC-MSs as promising formulations for UC, with implications for advancing treatment modalities for various inflammatory bowel disorders.
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Affiliation(s)
- Da Huang
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China
| | - Yongming Wang
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China
| | - Chenlan Xu
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China
| | - Minglang Zou
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China
| | - Yangcan Ming
- Department of Pediatrics, Wuhan NO.1 Hospital, Wuhan, Hubei 430022, China
| | - Fang Luo
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China; Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection for Food Safety, College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, China
| | - Zhenjin Xu
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China
| | - Ying Miao
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China
| | - Na Wang
- Department of Pediatrics, Wuhan NO.1 Hospital, Wuhan, Hubei 430022, China.
| | - Zhenyu Lin
- Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection for Food Safety, College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, China
| | - Zuquan Weng
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China; Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection for Food Safety, College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, China.
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27
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Chen J, Luo A, Xu M, Zhang Y, Wang Z, Yu S, Zhu L, Wu W, Yang D. The application of phenylboronic acid pinacol ester functionalized ROS-responsive multifunctional nanoparticles in the treatment of Periodontitis. J Nanobiotechnology 2024; 22:181. [PMID: 38622641 PMCID: PMC11017612 DOI: 10.1186/s12951-024-02461-0] [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: 12/10/2023] [Accepted: 04/04/2024] [Indexed: 04/17/2024] Open
Abstract
Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases.
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Affiliation(s)
- Jinhong Chen
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 404100, China
| | - Aihua Luo
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 404100, China
| | - Mengmeng Xu
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 404100, China
| | - Yao Zhang
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 404100, China
| | - Zheng Wang
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 404100, China
| | - Shuang Yu
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 404100, China
| | - Li Zhu
- Key Laboratory of Biorheological Science and Technology, College of Bioengineering, Ministry of Education, Chongqing University, Chongqing, 400044, China.
| | - Wei Wu
- Key Laboratory of Biorheological Science and Technology, College of Bioengineering, Ministry of Education, Chongqing University, Chongqing, 400044, China.
| | - Deqin Yang
- Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 404100, China.
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28
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Xu Y, Xin J, Sun Y, Wang X, Sun L, Zhao F, Niu C, Liu S. Mechanisms of Sepsis-Induced Acute Lung Injury and Advancements of Natural Small Molecules in Its Treatment. Pharmaceuticals (Basel) 2024; 17:472. [PMID: 38675431 PMCID: PMC11054595 DOI: 10.3390/ph17040472] [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: 03/13/2024] [Revised: 04/02/2024] [Accepted: 04/05/2024] [Indexed: 04/28/2024] Open
Abstract
Sepsis-induced acute lung injury (ALI), characterized by widespread lung dysfunction, is associated with significant morbidity and mortality due to the lack of effective pharmacological treatments available clinically. Small-molecule compounds derived from natural products represent an innovative source and have demonstrated therapeutic potential against sepsis-induced ALI. These natural small molecules may provide a promising alternative treatment option for sepsis-induced ALI. This review aims to summarize the pathogenesis of sepsis and potential therapeutic targets. It assembles critical updates (from 2014 to 2024) on natural small molecules with therapeutic potential against sepsis-induced ALI, detailing their sources, structures, effects, and mechanisms of action.
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Affiliation(s)
- Yaxi Xu
- School of Pharmacy, Yantai University, Yantai 264005, China; (Y.X.); (Y.S.); (X.W.)
| | - Jianzeng Xin
- School of Life Sciences, Yantai University, Yantai 264005, China;
| | - Yupei Sun
- School of Pharmacy, Yantai University, Yantai 264005, China; (Y.X.); (Y.S.); (X.W.)
| | - Xuyan Wang
- School of Pharmacy, Yantai University, Yantai 264005, China; (Y.X.); (Y.S.); (X.W.)
| | - Lili Sun
- College of Pharmacy, University of Utah, Salt Lake City, UT 84108, USA;
| | - Feng Zhao
- School of Pharmacy, Yantai University, Yantai 264005, China; (Y.X.); (Y.S.); (X.W.)
| | - Changshan Niu
- College of Pharmacy, University of Utah, Salt Lake City, UT 84108, USA;
| | - Sheng Liu
- School of Pharmacy, Yantai University, Yantai 264005, China; (Y.X.); (Y.S.); (X.W.)
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29
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Thomas A, Shinde S, Wavhale R, Jadhav P, Tambe S, Lokhande K, Chitlange S. In-silico screening of phytomolecules against multiple targets for wound management. In Silico Pharmacol 2024; 12:19. [PMID: 38550524 PMCID: PMC10965871 DOI: 10.1007/s40203-024-00194-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Accepted: 02/07/2024] [Indexed: 03/28/2025] Open
Abstract
Chronic wound healing, especially in burns, is a major medical challenge with limited treatments. This study employs computational tools to identify phytomolecules that target multiple pathways involved in wound healing. By utilizing shape analysis, molecular docking, and binding energy calculations, potential compounds are pinpointed,to address the growing problem of chronic wounds. Initially, a set of phytomolecules from the ZINC database of natural molecules was screened to find compounds with shapes similar to well-known wound healing phytomolecules like curcumin, chromogenic acid, gallic acid, and quercetin. The most promising phytomolecules identified through shape similarity were further studied through molecular docking studies on several key targets involved in wound healing, including TNF-α, FGF, and TGF-β. Among the tested phytomolecules, a ligand known as Fluorophenyl(5-(5-chloro-1-(2-fluorophenyl)-2-oxopentyl)-4,5,6,7-tetrahydrothieno[3,2c]pyridine-2-yl acetate) exhibited a strong affinity with favourable binding interactions for TNF-α ( - 7.1 kcal/mole), FGF (-6.9 kcal/mole), and TGF-β (-5.1 kcal/mole). Another compound, 2,4 methoxybenzylidene-(-3)-oxo-2,3-dihydro-1-benzofuran-6-yl-4-methoxybenzoate, demonstrated a strong affinity with low binding energy for TNF-α ( - 6.8 kcal/mole) and FGF ( - 7.0 kcal/mole) targets. Isosakuranetin and Ermanin displayed moderate affinity for both TNF-α and FGF, with the highest affinity observed for the TGF-β target. These findings suggest that these identified phytomolecules hold promise as potential lead compounds for further structural modifications, with the goal of designing new molecules that can target multiple pathways involved in the wound healing process.
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Affiliation(s)
- Asha Thomas
- Department of Pharmaceutical Chemistry, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, Maharashtra 411 018 India
| | - Sheetal Shinde
- Department of Pharmaceutical Chemistry, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, Maharashtra 411 018 India
| | - Ravindra Wavhale
- Department of Pharmaceutical Chemistry, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, Maharashtra 411 018 India
| | - Pranali Jadhav
- Department of Pharmaceutical Chemistry, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, Maharashtra 411 018 India
| | - Sham Tambe
- Department of Pharmaceutical Chemistry, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, Maharashtra 411 018 India
| | - Kiran Lokhande
- Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D.Y. Patil Deemed to Be University, Pune, Maharashtra India
- Translational Bioinformatics and Computational Genomics Research Lab, Department of Life Sciences, Shiv Nadar Institution of Eminence, Gautam Buddha Nagar, UP India
| | - Sohan Chitlange
- Department of Pharmaceutical Chemistry, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, Maharashtra 411 018 India
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Rahbari S, Tavakolipour H, Kalbasi-Ashtari A. Application of electro-spraying technique and mathematical modelling for nanoencapsulation of curcumin. Heliyon 2024; 10:e25680. [PMID: 38390193 PMCID: PMC10881552 DOI: 10.1016/j.heliyon.2024.e25680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 01/30/2024] [Accepted: 01/31/2024] [Indexed: 02/24/2024] Open
Abstract
Electro-spraying Process (ESP) was used to coat extracted curcumin (CUR) with milk protein isolate (MPI) at equal concentration. The variables were applied voltage (AV), pumps flow rate ratio (PFRR) for coating (CUR with MPI), travelling distance (TD for coating and dehydration), ESE and MPI concentrations. They changed respectively from 7.5 to 27.5 kV, 2-10 times, and 5-25 cm, and 1.5-3.5% (w/w). When the MPI concentration, TD, PFRR, and AV of ESE reached respectively to 2.56 %, 16.64 cm, 6.77 times, and 19.06 kV; the resulting nanoparticle diameter and encapsulation efficiency of CUR coated (with MPI) became 232 nm (minimum) and 80.7% (maximum) values. The scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR) analysis confirmed that the produced nanoparticles were bead-free, homogeneous, smooth surfaces, and >50% uniformity. While the nanoparticles of CUR had >70% heat resistance (up to 10 min at 120 °C against degradation), it had more than 100% antioxidant capacity in aqueous solution than its free form (because of its appropriate and intact coating). In-vitro studies showed that the nano encapsulated particles released >80% of CUR into the intestinal tract without significant release in simulated gastric fluid.
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Affiliation(s)
- Siamak Rahbari
- Islamic Azad University (Tehran Campus), City of Tehran, Iran
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31
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Sebastian S, Rohila Y, Yadav E, Bhardwaj P, Sudheer Babu Y, Maruthi M, Ansari A, Gupta MK. Supramolecular Organo/hydrogel-Fabricated Long Alkyl Chain α-Amidoamides as a Smart Soft Material for pH-Responsive Curcumin Release. Biomacromolecules 2024; 25:975-989. [PMID: 38189243 DOI: 10.1021/acs.biomac.3c01074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2024]
Abstract
Low-molecular-mass gelators, due to their excellent biocompatibility, low toxicological profile, innate biodegradability and ease of fabrication have garnered significant interest as they self-assemble through non-covalent interactions. In this study, we have designed and synthesized a series of six α-amidoamides by varying the hydrophobic alkyl chain length (C12-C22), which were well characterized using different spectral techniques. These α-amidoamides formed self-assembled aggregates in a DMSO/water solvent system affording organo/hydrogels at 0.66% w/v, which is the minimum gelation concentration (MGC) making them as remarkable supergelators. The various functionalities present in these gelators such as amides and alkyl chain length pave the way toward excellent gelation mechanism through hydrogen bonding and van der Waals interaction as evidenced from FTIR spectroscopy. Notably, as the chain length increased, organo/hydrogels became more thermally stable. Rheological results showed that the stability and strength of these gelators were considerably impacted by variations in chain length. The SEM morphology revealed dense sheet architectures of the organo/hydrogel samples. Organo/hydrogels have a significant impact on the advancement of innovative drug delivery systems that respond to various stimuli, ushering in a new era in pharmaceutical technology. Inspired by this, we encapsulated curcumin, a chemopreventive medication, into the gel core and further released via gel-to-sol transition induced by pH variation at 37 °C, without any alteration in structure-activity relationship. The drug release behavior was observed by UV-vis spectroscopy. Moreover, cell viability and cell invasion experiments demonstrate that the gel formulations exhibit high biocompatibility and low cytotoxicity. Among the tested formulations, 5e+Cur exhibited remarkable efficacy in controlling A549 cell migration, suggesting significant potential for applications in the pharmaceutical industry.
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Affiliation(s)
- Sharol Sebastian
- Department of Chemistry, School of Basic Sciences, Central University of Haryana, Mahendergarh 123031, Haryana, India
| | - Yajat Rohila
- Department of Chemistry, School of Basic Sciences, Central University of Haryana, Mahendergarh 123031, Haryana, India
| | - Eqvinshi Yadav
- Department of Chemistry, School of Basic Sciences, Central University of Haryana, Mahendergarh 123031, Haryana, India
| | - Priya Bhardwaj
- Department of Biochemistry, School of Interdisciplinary and Applied Sciences, Central University of Haryana, Mahendergarh 123031, Haryana,India
| | - Yangala Sudheer Babu
- Department of Biochemistry, School of Interdisciplinary and Applied Sciences, Central University of Haryana, Mahendergarh 123031, Haryana,India
| | - Mulaka Maruthi
- Department of Biochemistry, School of Interdisciplinary and Applied Sciences, Central University of Haryana, Mahendergarh 123031, Haryana,India
| | - Azaj Ansari
- Department of Chemistry, School of Basic Sciences, Central University of Haryana, Mahendergarh 123031, Haryana, India
| | - Manoj K Gupta
- Department of Chemistry, School of Basic Sciences, Central University of Haryana, Mahendergarh 123031, Haryana, India
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Haloub K, McNamara E, Yahya RH. An Unusual Case of Dietary-Induced Liver Injury during Pregnancy: A Case Report of Probable Liver Injury due to High-Dose Turmeric Intake and Literature Review. Case Reports Hepatol 2024; 2024:6677960. [PMID: 38352658 PMCID: PMC10864038 DOI: 10.1155/2024/6677960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 01/23/2024] [Accepted: 01/29/2024] [Indexed: 02/16/2024] Open
Abstract
Turmeric-induced liver injury is a controversial topic, and turmeric is safe to consume during pregnancy in small amounts; however, it might be an uncommon cause of liver injury if consumed in large amounts. We hereby report a case of a pregnant patient who demonstrated atypical signs and symptoms of dietary-induced liver injury during pregnancy. She presented with itching at 23 weeks 4 days of pregnancy and had deranged liver function tests and was diagnosed with dietary-induced liver injury. The patient was managed with a strict diet during the pregnancy which resulted in a significant improvement in the clinical and biochemical findings during the pregnancy.
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Affiliation(s)
- Kareem Haloub
- The University of Melbourne, Parkville, VIC 3052, Australia
| | - Elly McNamara
- The University of Melbourne, Parkville, VIC 3052, Australia
| | - Rani Haj Yahya
- The University of Melbourne, Parkville, VIC 3052, Australia
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33
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Zhao YY, Li J, Wang HQ, Zheng HB, Ma SW, Zhou GZ. Activation of autophagy promotes the inhibitory effect of curcumin analog EF-24 against MDA-MB-231 cancer cells. J Biochem Mol Toxicol 2024; 38:e23642. [PMID: 38348710 DOI: 10.1002/jbt.23642] [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: 10/02/2023] [Revised: 12/20/2023] [Accepted: 01/08/2024] [Indexed: 02/15/2024]
Abstract
Breast cancer is the leading cause of cancer deaths in women worldwide. EF-24, an analog of curcumin, has been shown to possess promising anticancer effects. However, the underlying mechanism remains elusive. In the present study, the inhibitory effect of EF-24 against one breast cancer cell line, MDA-MB-231, and its anti-migration ability were assessed by MTT, wound healing, and Transwell assay. Furthermore, we found that EF-24 could induce initiation of autophagy as evidenced by fluorescence and electron microscope observation. EF-24 also induced mitochondrial apoptosis in MDA-MB-231 cells as detected by Hoechst 33342 staining, flow cytometry analysis, and western blot analysis. In addition, the early autophagy inhibitor 3-MA could reduce the cleavage of PARP protein and protect cells from EF-24-induced apoptosis, while the autophagy inducer (rapamycin) could enhance the anticancer effect of EF-24 in MDA-MB-231 cells, which suggest that EF-24 induces crosstalk between autophagy and apoptosis, which herein participate in the antiproliferative effect of EF-24 in breast cancer cells. Moreover, removal of EF-24-activated ROS with NAC significantly reversed migration ability of MDA-MB-231 cells, indicating that EF-24 exerted an inhibitory effect through a ROS-mediating pathway. These results will help to elucidate the antitumor mechanism of curcumin analogs and to explore future potential clinical applications.
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Affiliation(s)
- Yin-Yin Zhao
- College of Bioengineering, Henan University of Technology, Zhengzhou, China
| | - Jun Li
- College of Bioengineering, Henan University of Technology, Zhengzhou, China
| | - Hao-Qi Wang
- College of Bioengineering, Henan University of Technology, Zhengzhou, China
| | - Hao-Bo Zheng
- College of Bioengineering, Henan University of Technology, Zhengzhou, China
| | - Shi-Wei Ma
- College of Bioengineering, Henan University of Technology, Zhengzhou, China
| | - Guang-Zhou Zhou
- College of Bioengineering, Henan University of Technology, Zhengzhou, China
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Chatterjee P, Dutta SS, Agarwal M, Dey S, Chakraborty T. UV-A-Induced Photoisomerization and Photodimerization of Curcumin: An Ion Mobility Mass Spectrometry Study. J Phys Chem A 2024; 128:548-562. [PMID: 38206070 DOI: 10.1021/acs.jpca.3c05933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2024]
Abstract
Curcumin, the bioactive compound present in spice plant turmeric, has been shown to exhibit selective phototoxic activities toward mammalian cancer cells, and it is being used extensively as a photosensitizer (PS) in photodynamic therapies (PDT). However, so far, the fate of curcumin toward photochemical transformations is not well understood. Here we report our findings of a number of novel photochemical reaction channels of curcumin in water-methanol mixture, like photoisomerization, photodimerization, and photooxidation (H2-loss). The reaction was performed by irradiating the curcumin solution with ultraviolet (UV) light of wavelength 350 nm, which is abundant in the earth's troposphere. Product identification and structure elucidation are done by employing an integrated method of drift tube ion mobility mass spectrometry (DTIMS) in combination with high-performance liquid chromatography (HPLC) and collision-induced dissociation (CID) of the mass-selected molecular ions. Two photoisomers of curcumin produced as a result of trans-cis configurational changes about C═C double bonds in the excited state have been identified, and it has been shown that they could serve as the precursors for formation of isomeric dimers via [2 + 2] cycloaddition and H2-loss products. Comparisons of the experimentally measured collision cross-section (CCS) values of the reactant and product ions obtained by the DTIMS method with those predicted by the electronic structure theory are found to be very effective for the discrimination of the produced photoisomers. The observed photochemical reaction channels are potentially significant toward uses of curcumin as a photosensitizer in photodynamic therapy.
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Affiliation(s)
- Piyali Chatterjee
- School of Chemical Sciences, Indian Association for the Cultivation of Science, 2A Raja S C Mullick Road, Jadavpur, Kolkata 700032, India
| | - Subhra Sankar Dutta
- School of Chemical Sciences, Indian Association for the Cultivation of Science, 2A Raja S C Mullick Road, Jadavpur, Kolkata 700032, India
| | - Megha Agarwal
- School of Chemical Sciences, Indian Association for the Cultivation of Science, 2A Raja S C Mullick Road, Jadavpur, Kolkata 700032, India
| | - Supriyo Dey
- School of Chemical Sciences, Indian Association for the Cultivation of Science, 2A Raja S C Mullick Road, Jadavpur, Kolkata 700032, India
| | - Tapas Chakraborty
- School of Chemical Sciences, Indian Association for the Cultivation of Science, 2A Raja S C Mullick Road, Jadavpur, Kolkata 700032, India
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Tiwari P, Gupta A, Shivhare V, Ahuja R, Mandloi AS, Mishra A, Basu A, Konar AD. Stereogenic Harmony Fabricated Mechanoresponsive Homochiral Triphenylalanine Analogues with Synergistic Antibacterial Performances: A Potential Weapon for Dermal Wound Management. ACS APPLIED BIO MATERIALS 2024; 7:332-343. [PMID: 38116621 DOI: 10.1021/acsabm.3c00926] [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] [Indexed: 12/21/2023]
Abstract
The wound recovery phenomenon remains as one of the long challenging concerns worldwide. In search of user-friendly dressing materials, in this report, we fabricated a rational combinatorial strategy utilizing stereogenic harmony in a triphenylalanine fragment and appending it to δ-amino valeric acid at the N-terminus (hydrogelators I-VII) such that a potential scaffold could be fished out from the design. Our investigations revealed that all the hydrogelators displayed not only excellent self-healing performance as well as high mechanical strength at physiological pH but also mechanical stress-triggered gel-sol-gel transition properties. The structural and morphological investigation confirmed the presence of β-sheet-like assemblies stabilized by intermolecular H-bonding and π-π interactions. Moreover, these scaffolds showed substantial antibacterial as well as antifungal efficacy against common wound pathogens, i.e, four Gram-positive bacteria (Staphylococcus aureus, Streptococcus mutans, B. subtilis, E. fecalis), four Gram-negative bacteria (Escherichia coli, Klebsiella pneumonia, P. aerugonosa, Proteus spp.), and two fungal strains (C. albicans and A. niger). The manifestation of consistent antioxidant properties might be due to the enhancement of amphiphilicity in hydrogelators, which has led to the generation of reactive oxygen species (ROS) in a facile manner, a probable mechanism to damage the microbial membrane, the driving force behind the antimicrobial efficacy. Also, the constructs exhibited proteolytic resistance and remarkable biocompatibility toward mammalian cells. Thus, based on the above benchmarks, the homochiral hydrogelator IV was seived out from a pool of seven, and we proceeded toward its in vivo evaluation using full-thickness excisional wounds in Wister rats. The scaffolds also accentuated the re-epithelialization as well in comparison to the negative control, thereby facilitating the wound closure process in a very short span of time (10 days). Overall, our in vitro and in vivo analysis certifies hydrogelator IV as an ideal dressing material that might hold immense promise for future wound care management.
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Affiliation(s)
- Priyanka Tiwari
- Department of Applied Chemistry, Rajiv Gandhi Technological University, Bhopal, Madhya Pradesh 462033, India
| | - Arindam Gupta
- Department of Chemistry, IISER, Bhopal 462066, India
| | - Vaibhav Shivhare
- Department of Applied Chemistry, Rajiv Gandhi Technological University, Bhopal, Madhya Pradesh 462033, India
| | - Rishabh Ahuja
- Department of Applied Chemistry, Rajiv Gandhi Technological University, Bhopal, Madhya Pradesh 462033, India
| | - Avinash Singh Mandloi
- Faculty of Pharmacy, VNS Group of Institutions, Bhopal, Madhya Pradesh 462044, India
| | - Ankit Mishra
- Faculty of Pharmacy, VNS Group of Institutions, Bhopal, Madhya Pradesh 462044, India
| | - Anindya Basu
- School of Pharmaceutical Sciences, Rajiv Gandhi Technological University, Bhopal 462036, India
- University Grants Commission, New Delhi, New Delhi 110002, India
| | - Anita Dutt Konar
- Department of Applied Chemistry, Rajiv Gandhi Technological University, Bhopal, Madhya Pradesh 462033, India
- School of Pharmaceutical Sciences, Rajiv Gandhi Technological University, Bhopal 462036, India
- University Grants Commission, New Delhi, New Delhi 110002, India
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36
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Chong Y, Xu S, Liu T, Guo P, Wang X, He D, Zhu G. Curcumin Inhibits Vasculogenic Mimicry via Regulating ETS-1 in Renal Cell Carcinoma. Curr Cancer Drug Targets 2024; 24:1031-1046. [PMID: 38299401 DOI: 10.2174/0115680096277126240102060617] [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: 08/26/2023] [Revised: 11/07/2023] [Accepted: 11/13/2023] [Indexed: 02/02/2024]
Abstract
BACKGROUND Metastatic renal cell carcinoma (RCC) poses a huge challenge once it has become resistant to targeted therapy. Vasculogenic mimicry (VM) is a novel blood supply system formed by tumor cells that can circumvent molecular targeted therapies. As one of the herbal remedies, curcumin has been demonstrated to play antineoplastic effects in many different types of human cancers; however, its function and mechanism of targeting VM in RCC remains unknown. OBJECTIVE Here, in the work, we explored the role of curcumin and its molecular mechanism in the regulation of VM formation in RCC. METHODS RNA-sequencing analysis, immunoblotting, and immunohistochemistry were used to detect E Twenty Six-1(ETS-1), vascular endothelial Cadherin (VE-Cadherin), and matrix metallopeptidase 9 (MMP9) expressions in RCC cells and tissues. RNA sequencing was used to screen the differential expressed genes. Plasmid transfections were used to transiently knock down or overexpress ETS-1. VM formation was determined by tube formation assay and animal experiments. CD31-PAS double staining was used to label the VM channels in patients and xenograft samples. RESULTS Our results demonstrated that VM was positively correlated with RCC grades and stages using clinical patient samples. Curcumin inhibited VM formation in dose and time-dependent manner in vitro. Using RNA-sequencing analysis, we discovered ETS-1 as a potential transcriptional factor regulating VM formation. Knocking down or overexpression of ETS-1 decreased or increased the VM formation, respectively and regulated the expression of VE-Cadherin and MMP9. Curcumin could inhibit VM formation by suppressing ETS-1, VE-Cadherin, and MMP9 expression both in vitro and in vivo. CONCLUSION Our finding might indicate that curcumin could inhibit VM by regulating ETS-1, VE-Cadherin, and MMP9 expression in RCC cell lines. Curcumin could be considered as a potential anti-cancer compound by inhibiting VM in RCC progression.
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MESH Headings
- Carcinoma, Renal Cell/drug therapy
- Carcinoma, Renal Cell/pathology
- Carcinoma, Renal Cell/metabolism
- Humans
- Curcumin/pharmacology
- Proto-Oncogene Protein c-ets-1/metabolism
- Proto-Oncogene Protein c-ets-1/genetics
- Kidney Neoplasms/drug therapy
- Kidney Neoplasms/pathology
- Kidney Neoplasms/metabolism
- Animals
- Mice
- Neovascularization, Pathologic/drug therapy
- Neovascularization, Pathologic/metabolism
- Xenograft Model Antitumor Assays
- Mice, Nude
- Male
- Gene Expression Regulation, Neoplastic/drug effects
- Female
- Matrix Metalloproteinase 9/metabolism
- Matrix Metalloproteinase 9/genetics
- Cadherins/metabolism
- Cadherins/genetics
- Cell Line, Tumor
- Mice, Inbred BALB C
- Cell Proliferation/drug effects
- Antigens, CD
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Affiliation(s)
- Yue Chong
- Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
- Oncology Research Laboratory, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, 710061, China
- Key Laboratory for Tumor Precision Medicine of Shaanxi Province, Xi'an Jiaotong University, Xi'an, 710061, China
| | - Shan Xu
- Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
- Oncology Research Laboratory, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, 710061, China
- Key Laboratory for Tumor Precision Medicine of Shaanxi Province, Xi'an Jiaotong University, Xi'an, 710061, China
| | - Tianjie Liu
- Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
- Oncology Research Laboratory, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, 710061, China
- Key Laboratory for Tumor Precision Medicine of Shaanxi Province, Xi'an Jiaotong University, Xi'an, 710061, China
| | - Peng Guo
- Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
- Oncology Research Laboratory, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, 710061, China
- Key Laboratory for Tumor Precision Medicine of Shaanxi Province, Xi'an Jiaotong University, Xi'an, 710061, China
| | - Xinyang Wang
- Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
- Oncology Research Laboratory, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, 710061, China
- Key Laboratory for Tumor Precision Medicine of Shaanxi Province, Xi'an Jiaotong University, Xi'an, 710061, China
| | - Dalin He
- Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
- Oncology Research Laboratory, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, 710061, China
- Key Laboratory for Tumor Precision Medicine of Shaanxi Province, Xi'an Jiaotong University, Xi'an, 710061, China
| | - Guodong Zhu
- Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
- Oncology Research Laboratory, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, 710061, China
- Key Laboratory for Tumor Precision Medicine of Shaanxi Province, Xi'an Jiaotong University, Xi'an, 710061, China
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Islam MR, Rauf A, Akash S, Trisha SI, Nasim AH, Akter M, Dhar PS, Ogaly HA, Hemeg HA, Wilairatana P, Thiruvengadam M. Targeted therapies of curcumin focus on its therapeutic benefits in cancers and human health: Molecular signaling pathway-based approaches and future perspectives. Biomed Pharmacother 2024; 170:116034. [PMID: 38141282 DOI: 10.1016/j.biopha.2023.116034] [Citation(s) in RCA: 31] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Revised: 12/08/2023] [Accepted: 12/14/2023] [Indexed: 12/25/2023] Open
Abstract
The curry powder spices turmeric (Curcuma longa L.), which contains curcumin (diferuloylmethane), an orange-yellow chemical. Polyphenols are the most commonly used sources of curcumin. It combats oxidative stress and inflammation in diseases, such as hyperlipidemia, metabolic syndrome, arthritis, and depression. Most of these benefits are due to their anti-inflammatory and antioxidant properties. Curcumin consumption leads to decreased bioavailability, resulting in limited absorption, quick metabolism, and quick excretion, which hinders health improvement. Numerous factors can increase its bioavailability. Piperine enhances bioavailability when combined with curcumin in a complex. When combined with other enhancing agents, curcumin has a wide spectrum of health benefits. This review evaluates the therapeutic potential of curcumin with a specific emphasis on its approach based on molecular signaling pathways. This study investigated its influence on the progression of cancer, inflammation, and many health-related mechanisms, such as cell proliferation, apoptosis, and metastasis. Curcumin has a significant potential for the prevention and treatment of various diseases. Curcumin modulates several biochemical pathways and targets involved in cancer growth. Despite its limited tissue accumulation and bioavailability when administered orally, curcumin has proven useful. This review provides an in-depth analysis of curcumin's therapeutic applications, its molecular signaling pathway-based approach, and its potential for precision medicine in cancer and human health.
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Affiliation(s)
- Md Rezaul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka 1216, Bangladesh
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Anbar 23561, Khyber Pakhtunkhwa, Pakistan.
| | - Shopnil Akash
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka 1216, Bangladesh
| | - Sadiya Islam Trisha
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka 1216, Bangladesh
| | - Akram Hossain Nasim
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka 1216, Bangladesh
| | - Muniya Akter
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka 1216, Bangladesh
| | - Puja Sutro Dhar
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka 1216, Bangladesh
| | - Hanan A Ogaly
- Chemistry Department, College of Science, King Khalid University, Abha 61421, Saudi Arabia
| | - Hassan A Hemeg
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Taibah University, Al-Medinah Al-Monawara, Saudi Arabia
| | - Polrat Wilairatana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
| | - Muthu Thiruvengadam
- Department of Applied Bioscience, College of Life and Environmental Science, Konkuk University, Seoul 05029, Republic of Korea; Department of Microbiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai 600077, India.
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38
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Erzurumlu Y, Dogan HK, Catakli D. New mode of action of curcumin on prostate cancer cells: Modulation of endoplasmic reticulum-associated degradation mechanism and estrogenic signaling. J Biochem Mol Toxicol 2024; 38:e23636. [PMID: 38229314 DOI: 10.1002/jbt.23636] [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: 01/22/2023] [Revised: 11/25/2023] [Accepted: 12/20/2023] [Indexed: 01/18/2024]
Abstract
Prostate cancer is leading to cancer-related mortality in numerous men each year worldwide. While there are several treatment options, acquired drug resistance mostly limits the success of treatments. Therefore, there is a need for the development of innovative treatments. Curcumin is one of the bioactive polyphenolic ingredients identified in turmeric and has numerous biological activities, such as anti-inflammatory and anticancer. In the present study, we investigated the effect of curcumin on the ER-associated degradation (ERAD) and estrogenic signaling in prostate cancer cells. The antiproliferative effect of curcumin on human androgen-dependent prostate cancer cell lines LNCaP and VCaP was estimated by WST-1 assay. Morphological alterations were investigated with an inverted microscope. We investigated the effect of curcumin on ERAD and estrogen signaling proteins by immunoblotting assay. To evaluate the impact of curcumin on endoplasmic reticulum (ER) protein quality-related, the expression level of 32 genes was analyzed by quantitative reverse transcription polymerase chain reaction. The nuclear translocation of estrogen receptor was examined by nuclear fractionation and immunofluorescence microscopy. We found that curcumin effectively reduced the proliferation rates of LNCaP and VCaP cells. ERAD proteins; Hrd1, gp78, p97/VCP, Ufd1 and Npl4 were strongly induced by curcumin. Also, the steady-state level of polyubiquitin was increased in a dose-dependent manner in both cell lines. Curcumin administration remarkably decreased the protein levels of estrogen receptor-alfa (Erα), whereas estrogen receptor-beta unaffected. Additionally, curcumin strongly restricted the nuclear translocation of Erα. Present data suggest that curcumin may be effectively used in therapeutic approaches associated with the targeting ER protein quality control mechanism and modulation of estrogen signaling in prostate cancer.
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Affiliation(s)
- Yalcin Erzurumlu
- Department of Biochemistry, Faculty of Pharmacy, Suleyman Demirel University, Isparta, Turkey
| | - Hatice Kubra Dogan
- Department of Bioengineering, Institute of Science, Suleyman Demirel University, Isparta, Turkey
| | - Deniz Catakli
- Department of Pharmacology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
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39
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Eghbali A, Nourigheimasi S, Ghasemi A, Afzal RR, Ashayeri N, Eghbali A, Khanzadeh S, Ghaffari K. The effects of curcumin on hepatic T2*MRI and liver enzymes in patients with β-thalassemia major: a double-blind randomized controlled clinical trial. Front Pharmacol 2023; 14:1284326. [PMID: 38164474 PMCID: PMC10757948 DOI: 10.3389/fphar.2023.1284326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 12/05/2023] [Indexed: 01/03/2024] Open
Abstract
Background: Curcumin present in turmeric has been considered due to its cancer-preventive features, antioxidant and anti-inflammatory properties. This double-blind, randomized, controlled clinical trial with a reasonable sample size and longer intervention period was conducted to investigate how oral curcumin affected cardiac and hepatic T2*MRI and liver enzymes in patients with β-thalassemia major. Method: This clinical trial study was conducted on 171 patients over 5 years old. The subjects were randomly divided into a curcumin-treatment group and a placebo group to receive either curcumin capsules twice daily or placebo for 6 months. Patients were examined once a month for 6 months to receive capsules and measure the levels of alanine aminotransferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP), direct and total bilirubin, ferritin and cardiac and hepatic T2*MRI. Result: There was a significant decrease in levels of AST, ALT, ALP, and bilirubin (direct and total) in the curcumin group compared with the placebo group by the end of the study (p < 0.05). The levels of serum ferritin remained unchanged in both groups at the end of the follow-up period (p > 0.05). No significant differences were observed between the curcumin and placebo groups at baseline values or at the end of the study of cardiac and hepatic T2*MRI and serum magnesium. Conclusion: Administration of curcumin has some beneficial effects on liver function by reducing liver enzymes in patients with beta-thalassemia major.
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Affiliation(s)
- Aziz Eghbali
- Clinical Research Development Center of Aliasghar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Shima Nourigheimasi
- School of Medicine, Amir Kabir Hospital, Arak University of Medical Sciences, Arak, Iran
| | - Ali Ghasemi
- Department of Biochemistry and Hematology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Roghayeh Rahimi Afzal
- Department of Pediatrics, Amir Kabir Hospital, Arak University of Medical Sciences, Arak, Iran
| | - Neda Ashayeri
- Clinical Research Development Center of Aliasghar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Aygin Eghbali
- Clinical Research Development Center of Aliasghar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | | | - Kazem Ghaffari
- Department of Basic and Laboratory Sciences, Khomein University of Medical Sciences, Khomein, Iran
- Student Research Committee, Khomein University of Medical Sciences, Khomein, Iran
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Zhang C, Jahan SA, Zhang J, Bianchi MB, Volpe-Zanutto F, Baviskar SM, Rodriguez-Abetxuko A, Mishra D, Magee E, Gilmore BF, Singh TRR, Donnelly RF, Larrañeta E, Paredes AJ. Curcumin nanocrystals-in-nanofibres as a promising platform for the management of periodontal disease. Int J Pharm 2023; 648:123585. [PMID: 37952560 DOI: 10.1016/j.ijpharm.2023.123585] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 11/06/2023] [Accepted: 11/07/2023] [Indexed: 11/14/2023]
Abstract
It is estimated that nearly a half of the world's population over 30 years old suffer from some kind of periodontal disease (PD). Although preventable, PD can pose a significant health burden to patients, causing from pain and discomfort to disfigurement and death. The management of PD often requires surgical procedures accompanied of systemic antibiotic and anti-inflammatory treatments. Curcumin (CUR), a potent anti-inflammatory and antimicrobial active, has shown great promise in the management of PD; however, its effects are often limited by its low bioavailability. In this work, we report the development of electrospun nanofibres (NFs) loaded with CUR nanocrystals (NCs) for the management of PD. NCs of 100 nm were obtained by media milling and loaded into dissolving polyvinyl alcohol NFs using electrospinning. The resultant NCs-in-NFs dissolved in water spontaneously, releasing NCs with a particle size of ∼120 nm. The physiochemical characterisation of the systems indicated the absence of chemical interactions between drug and polymer, and nanofibres with an amorphous nature. In vitro release profiles demonstrated that the NCs had a significantly higher dissolution rate (∼100 % at day 40) than the control group (approximately 6 % at day 40), which consisted of NFs containing a physical mixture of the drug and stabiliser. Finally, mucosal deposition studies demonstrated a 10-fold higher capacity of the novel NCs-in-NFs system to deposit CUR ex vivo using excised neonatal porcine mucosal tissue, when compared to the control group.
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Affiliation(s)
- Chunyang Zhang
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK
| | - Subrin A Jahan
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK
| | - Jingru Zhang
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK
| | - Maria Beatrice Bianchi
- Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy
| | - Fabiana Volpe-Zanutto
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK
| | - Shubhamkumar M Baviskar
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK
| | | | - Deepakkumar Mishra
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK
| | - Erin Magee
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK
| | - Brendan F Gilmore
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK
| | - Thakur Raghu Raj Singh
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK
| | - Ryan F Donnelly
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK
| | - Eneko Larrañeta
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK
| | - Alejandro J Paredes
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
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Pshenichnyuk SA, Asfandiarov NL, Markova AV, Komolov AS, Timoshnikov VA, Polyakov NE. Elementary processes triggered in curcumin molecule by gas-phase resonance electron attachment and by photoexcitation in solution. J Chem Phys 2023; 159:214305. [PMID: 38051100 DOI: 10.1063/5.0180053] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Accepted: 11/14/2023] [Indexed: 12/07/2023] Open
Abstract
Electron-driven processes in isolated curcumin (CUR) molecules are studied by means of dissociative electron attachment (DEA) spectroscopy under gas-phase conditions. Elementary photostimulated reactions initiated in CUR molecules under UV irradiation are studied using the chemically induced dynamic nuclear polarization method in an acetonitrile solvent. Density functional theory is applied to elucidate the energetics of fragmentation of CUR by low-energy (0-15 eV) resonance electron attachment and to characterize various CUR radical forms. The adiabatic electron affinity of CUR molecule is experimentally estimated to be about 1 eV. An extra electron attachment to the π1* LUMO and π2* molecular orbitals is responsible for the most intense DEA signals observed at thermal electron energy. The most abundant long-lived (hundreds of micro- to milliseconds) molecular negative ions CUR- are detected not only at the thermal energy of incident electrons but also at 0.6 eV, which is due to the formation of the π3* and π4* temporary negative ion states predicted to lie around 1 eV. Proton-assisted electron transfer between CUR molecules is registered under UV irradiation. The formation of both radical-anions and radical-cations of CUR is found to be more favorable in its enol form. The present findings shed some light on the elementary processes triggered in CUR by electrons and photons and, therefore, can be useful to understand the molecular mechanisms responsible for a variety of biological effects produced by CUR.
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Affiliation(s)
- Stanislav A Pshenichnyuk
- Institute of Molecule and Crystal Physics, Ufa Federal Research Centre, Russian Academy of Sciences, Prospekt Oktyabrya 151, 450075 Ufa, Russia
| | - Nail L Asfandiarov
- Institute of Molecule and Crystal Physics, Ufa Federal Research Centre, Russian Academy of Sciences, Prospekt Oktyabrya 151, 450075 Ufa, Russia
| | - Angelina V Markova
- Institute of Molecule and Crystal Physics, Ufa Federal Research Centre, Russian Academy of Sciences, Prospekt Oktyabrya 151, 450075 Ufa, Russia
| | - Alexei S Komolov
- St. Petersburg State University, Universitetskaya nab. 7/9, 199034 St. Petersburg, Russia
| | - Viktor A Timoshnikov
- Voevodsky Institute of Chemical Kinetics and Combustion, Russian Academy of Sciences, Institutskaya str. 3, 630090 Novosibirsk, Russia
| | - Nikolay E Polyakov
- Voevodsky Institute of Chemical Kinetics and Combustion, Russian Academy of Sciences, Institutskaya str. 3, 630090 Novosibirsk, Russia
- Institute of Solid State Chemistry and Mechanochemistry, Russian Academy of Sciences, Kutateladze 18, 630128 Novosibirsk, Russia
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Mia MAR, Dey D, Sakib MR, Biswas MY, Prottay AAS, Paul N, Rimti FH, Abdullah Y, Biswas P, Iftehimul M, Paul P, Sarkar C, El-Nashar HAS, El-Shazly M, Islam MT. The efficacy of natural bioactive compounds against prostate cancer: Molecular targets and synergistic activities. Phytother Res 2023; 37:5724-5754. [PMID: 37786304 DOI: 10.1002/ptr.8017] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 08/17/2023] [Accepted: 09/05/2023] [Indexed: 10/04/2023]
Abstract
Globally, prostate cancer (PCa) is regarded as a challenging health issue, and the number of PCa patients continues to rise despite the availability of effective treatments in recent decades. The current therapy with chemotherapeutic drugs has been largely ineffective due to multidrug resistance and the conventional treatment has restricted drug accessibility to malignant tissues, necessitating a higher dosage resulting in increased cytotoxicity. Plant-derived bioactive compounds have recently attracted a great deal of attention in the field of PCa treatment due to their potent effects on several molecular targets and synergistic effects with anti-PCa drugs. This review emphasizes the molecular mechanism of phytochemicals on PCa cells, the synergistic effects of compound-drug interactions, and stem cell targeting for PCa treatment. Some potential compounds, such as curcumin, phenethyl-isothiocyanate, fisetin, baicalein, berberine, lutein, and many others, exert an anti-PCa effect via inhibiting proliferation, metastasis, cell cycle progression, and normal apoptosis pathways. In addition, multiple studies have demonstrated that the isolated natural compounds: d-limonene, paeonol, lanreotide, artesunate, and bicalutamide have potential synergistic effects. Further, a significant number of natural compounds effectively target PCa stem cells. However, further high-quality studies are needed to firmly establish the clinical efficacy of these phytochemicals against PCa.
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Affiliation(s)
- Md Abdur Rashid Mia
- Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh
| | - Dipta Dey
- Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalgonj, Bangladesh
| | - Musfiqur Rahman Sakib
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalgonj, Bangladesh
| | - Md Yeaman Biswas
- Department of Genetic Engineering and Biotechnology, Jashore University of Science and Technology (JUST), Jashore, Bangladesh
| | - Abdullah Al Shamsh Prottay
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalgonj, Bangladesh
| | - Niloy Paul
- Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalgonj, Bangladesh
| | - Fahmida Hoque Rimti
- Bachelor of Medicine and Surgery, Chittagong Medical College, Chawkbazar, Bangladesh
| | - Yusuf Abdullah
- Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalgonj, Bangladesh
| | - Partha Biswas
- Department of Genetic Engineering and Biotechnology, Jashore University of Science and Technology (JUST), Jashore, Bangladesh
| | - Md Iftehimul
- Department of Fisheries and Marine Bioscience, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalgonj, Bangladesh
| | - Priyanka Paul
- Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalgonj, Bangladesh
| | - Chandan Sarkar
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalgonj, Bangladesh
| | - Heba A S El-Nashar
- Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Mohamed El-Shazly
- Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Muhammad Torequl Islam
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalgonj, Bangladesh
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Abualhasan M, Jaradat N, Hawash M, Shraim N, Asaad M, Mousa A, Mousa Z, Tobeh R, Mlitat B. Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine. Open Life Sci 2023; 18:20220767. [PMID: 38027225 PMCID: PMC10668110 DOI: 10.1515/biol-2022-0767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 10/02/2023] [Accepted: 10/10/2023] [Indexed: 12/01/2023] Open
Abstract
Curcuma longa (turmeric) is a plant that has been extensively utilized in traditional medicine for centuries. Turmeric has a long history of use in both food and traditional medicine for the treatment of ailments such as diarrhea, cancer, flatulence, and dyspepsia. In Palestine, this plant was cultivated for the first time. The objective of this study was to characterize the extract of C. longa and assess its antimutagenic activity against a variety of cancer cells. Gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) methods were employed to identify the constituents of turmeric. The cytotoxic effects of C. longa were evaluated on cancer and normal cell lines using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. The results revealed the presence of 10 components in turmeric extract as identified by GC-MS. The major constituents comprising 78% of the total constituents were α-zingiberene (27.51%), tumeron (19.44%), β-sesquiphellandrene (19.40%), and aromatic-tumeron (11.63%). HPLC analysis successfully separated the main constituent, curcumin (1.78%), along with two other curcumin derivatives. The cytotoxicity results demonstrated potent anticancer activity of the C. longa extract against HeLa and LX2 cell lines, with IC50 values of 46.84 ± 2.12 and 29.77 ± 1 µg/mL, respectively. Furthermore, the plant extract at a concentration of 250 µg/mL exhibited over 95% inhibition against all tested cancer cell lines. These findings highlight the promising potential of turmeric as a natural source with powerful anticancer activities. Moreover, the extract may possess other biological activities such as antioxidant and antimicrobial properties, which could be explored in future studies.
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Affiliation(s)
- Murad Abualhasan
- Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine
| | - Nidal Jaradat
- Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine
| | - Mohammed Hawash
- Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine
| | - Naser Shraim
- Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine
| | - Mohammad Asaad
- Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine
| | - Ahmed Mousa
- Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine
| | - Zain Mousa
- Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine
| | - Reem Tobeh
- Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine
| | - Balsam Mlitat
- Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine
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Twum Y, Marshall K, Gao W. Caffeic acid phenethyl ester surmounts acquired resistance of AZD9291 in non-small cell lung cancer cells. Biofactors 2023; 49:1143-1157. [PMID: 37555475 DOI: 10.1002/biof.1983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 05/19/2023] [Indexed: 08/10/2023]
Abstract
Epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the first-line therapy for EGFR mutated non-small cell lung cancer (NSCLC); however, resistance rapidly develops. The objective of this study was therefore to establish and characterize a gefitinib resistant NSCLC line (HCC827GR) and evaluate the therapeutic effects of natural products in combination with third-generation EGFR-TKI, AZD9291. The IC50 of gefitinib and AZD9291 in HCC827GR were significantly higher than those of HCC827 (p < 0.05). Furthermore, anchorage-independent colony assay indicated that HCC827GR cells were more aggressive than their predecessors. This was reflected by the gene/protein expression changes observed in HCC827GR versus HCC827 profiled by cancer drug resistance real-time polymerase chain reaction (RT-PCR) array and Western blot. Three natural products were screened and caffeic acid phenethyl ester (CAPE) exhibited the most significant combinative cytotoxic effect with AZD9291. Specifically, flow cytometry revealed that AZD9291 + CAPE considerably increased the fraction of cell in pre-G1 of the cell cycle and caspase-Glo3/7 assay showed a dramatic increase in apoptosis when compared to AZD9291 alone. Furthermore, Western blot showed significant downregulation of p-EGFR/p-AKT in HCC827GR cells treated with AZD9291 + CAPE as compared to AZD9291. Moreover, it is evident that AZD9291 + CAPE specifically resulted in a marked reduction in the protein expressions of the cell-proliferation-related genes p21, cyclin D1, and survivin. Finally, refined RT-PCR/Western blot data indicated that AZD9291 + CAPE may at least partially exert its synergistic effects via the PLK2 pathway. Together, these results suggest that CAPE is a clinically relevant compound to aid AZD9291 in treating EGFR-TKI resistant cells through modulating critical genes/proteins involved in cancer resistance/therapy.
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Affiliation(s)
- Yaw Twum
- Department of Occupational and Environmental Health Sciences, School of Public Health, West Virginia University, Morgantown, West Virginia, USA
| | - Kent Marshall
- Department of Occupational and Environmental Health Sciences, School of Public Health, West Virginia University, Morgantown, West Virginia, USA
| | - Weimin Gao
- Department of Occupational and Environmental Health Sciences, School of Public Health, West Virginia University, Morgantown, West Virginia, USA
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Mamsharifi P, Farokhi B, Hajipoor-Taziani R, Alemi F, Hazegh P, Masoumzadeh S, Jafari L, Ghaderi A, Ghadami Dehkohneh S. Nano-curcumin effects on nicotine dependence, depression, anxiety and metabolic parameters in smokers: A randomized double-blind clinical study. Heliyon 2023; 9:e21249. [PMID: 37954269 PMCID: PMC10637885 DOI: 10.1016/j.heliyon.2023.e21249] [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: 06/15/2023] [Revised: 10/15/2023] [Accepted: 10/18/2023] [Indexed: 11/14/2023] Open
Abstract
Background Smoking is clearly associated with metabolic profiles/abnormalities, psychological dysfunction, and symptoms of nicotine dependence. Nano-Curcumin (Nano-CUR) is a medicinal herb with antianxiety, antioxidant antidepressant-like effects, and anti-inflammatory properties. This RCT aimed to determine the therapeutic effects of Nano-CUR in smokers on clinical symptoms and metabolic parameters. Methods This trial was conducted on 70 participants with cigarette smoking. Smokers in two arms received soft gel capsules Nano-CUR 80 mg/daily for 3 months (n = 35) and placebo (n = 35), respectively. Primary outcomes (Nicotine dependence syndrome scale, depression, and anxiety beck score), and secondary outcomes (glycemic, lipid, stress oxidative, and inflammation profiles) were analyzed before and 3-months after the intervention in smokers. Results Nano-CUR supplementation significantly decreased nitric oxide, malondialdehyde, and C-reactive protein levels (P < 0.05), compared to the control. Furthermore, no significant effect change was shown in nicotine dependence syndrome, depression, anxiety, and other metabolic parameters (p > 0.05). Conclusion Nano-CUR intake may have favorable effects on C-reactive protein, malondialdehyde, and nitric oxide in subjects with cigarette smoking. More RCT are required to evaluate the effectiveness of Nano-CUR supplementations in smokers in order to reject or support these conclude.
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Affiliation(s)
- Peyman Mamsharifi
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
- Department of Psychology, Allameh Tabataba'i University, Tehran, Iran
| | - Bahareh Farokhi
- Department of Clinical Psychology, Allameh Tabataba'i University, Tehran, Iran
| | - Raha Hajipoor-Taziani
- Department of General Psychology, Islamic Azad University of Qeshm Branch, Qeshm, Iran
| | - Fatemeh Alemi
- Department of Toxicology and Pharmacology, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
| | - Pooya Hazegh
- Department of Psychiatry, Kashan University of Medical Sciences, Kashan, Iran
| | | | - Leila Jafari
- Department of Addiction Studies, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Amir Ghaderi
- Clinical Research Development Unit-Matini/Kargarnejad Hospital, Kashan University of Medical Sciences, Kashan, Iran
- Department of Addiction Studies, School of Medical, Kashan University of Medical Sciences, Kashan, Iran
| | - Somayeh Ghadami Dehkohneh
- Department of Pharmacy, Acharya BM ready college of Pharmacy, Rajive Gandhi University of Health Sciences, Banglore Karnataka, India
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46
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Han JH, Lee EJ, Park W, Ha KT, Chung HS. Natural compounds as lactate dehydrogenase inhibitors: potential therapeutics for lactate dehydrogenase inhibitors-related diseases. Front Pharmacol 2023; 14:1275000. [PMID: 37915411 PMCID: PMC10616500 DOI: 10.3389/fphar.2023.1275000] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 09/27/2023] [Indexed: 11/03/2023] Open
Abstract
Lactate dehydrogenase (LDH) is a crucial enzyme involved in energy metabolism and present in various cells throughout the body. Its diverse physiological functions encompass glycolysis, and its abnormal activity is associated with numerous diseases. Targeting LDH has emerged as a vital approach in drug discovery, leading to the identification of LDH inhibitors among natural compounds, such as polyphenols, alkaloids, and terpenoids. These compounds demonstrate therapeutic potential against LDH-related diseases, including anti-cancer effects. However, challenges concerning limited bioavailability, poor solubility, and potential toxicity must be addressed. Combining natural compounds with LDH inhibitors has led to promising outcomes in preclinical studies. This review highlights the promise of natural compounds as LDH inhibitors for treating cancer, cardiovascular, and neurodegenerative diseases.
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Affiliation(s)
- Jung Ho Han
- Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu, Republic of Korea
| | - Eun-Ji Lee
- Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu, Republic of Korea
| | - Wonyoung Park
- Korean Convergence Medical Science Major, KIOM Campus, University of Science and Technology (UST), Daegu, Republic of Korea
| | - Ki-Tae Ha
- Korean Convergence Medical Science Major, KIOM Campus, University of Science and Technology (UST), Daegu, Republic of Korea
| | - Hwan-Suck Chung
- Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu, Republic of Korea
- Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea
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Virat G, Maiti KK, Amal Raj RB, Gowd EB. Impact of polymer chain packing and crystallization on the emission behavior of curcumin-embedded poly(L-lactide)s. SOFT MATTER 2023; 19:6671-6682. [PMID: 37609667 DOI: 10.1039/d3sm00853c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/24/2023]
Abstract
The development of biodegradable and biocompatible fluorescent materials with tunable emission in the solid state has become increasingly relevant for smart packaging and biomedical applications. Molecular packing and conformations play a critical role in tuning the solid-state photophysical properties of fluorescent materials. In this work, tunable emission of bioactive curcumin was achieved through the manipulation of the crystallization conditions and the polymorphic form of covalently linked poly(L-lactide) in the curcumin-embedded poly(L-lactide) (curcumin-PLLA). In the melt-crystallized curcumin-PLLA, with the increase in the isothermal crystallization temperature, a bathochromic shift in the fluorescence of curcumin-PLLA was observed due to the change in the intramolecular conjugation length of curcumin. The change in the isothermal crystallization temperature of curcumin-PLLA resulted in the rotation of the terminal phenyl rings of curcumin with respect to the central keto-enol group due to the covalently linked helical PLLA chains. In addition, solvent-induced single crystals and a gel of curcumin-PLLA were prepared and the influence of the polymorphic form of PLLA on the emission behavior of curcumin-PLLA was investigated. The results suggest that the polymer chain packing, crystallization conditions, morphology, and polymorphic form could play an influential role in dictating the fluorescence properties of fluorophore-embedded polymers.
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Affiliation(s)
- G Virat
- Materials Science and Technology Division CSIR-National Institute for Interdisciplinary Science and Technology, Trivandrum 695 019, Kerala, India.
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201 002, India
| | - Kaustabh Kumar Maiti
- Chemical Sciences and Technology Division CSIR-National Institute for Interdisciplinary Science and Technology, Trivandrum 695 019, Kerala, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201 002, India
| | - R B Amal Raj
- Materials Science and Technology Division CSIR-National Institute for Interdisciplinary Science and Technology, Trivandrum 695 019, Kerala, India.
| | - E Bhoje Gowd
- Materials Science and Technology Division CSIR-National Institute for Interdisciplinary Science and Technology, Trivandrum 695 019, Kerala, India.
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201 002, India
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Kaur Sandhu S, Raut J, Kumar S, Singh M, Ahmed B, Singh J, Rana V, Rishi P, Ganesh N, Dua K, Pal Kaur I. Nanocurcumin and viable Lactobacillus plantarum based sponge dressing for skin wound healing. Int J Pharm 2023; 643:123187. [PMID: 37394156 DOI: 10.1016/j.ijpharm.2023.123187] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 06/25/2023] [Accepted: 06/26/2023] [Indexed: 07/04/2023]
Abstract
Curcumin loaded solid lipid nanoparticles (CSLNs) and probiotic (Lactobacillus plantarum UBLP-40; L. plantarum) were currently co-incorporated into a wound dressing. The combination with manifold anti-inflammatory, anti-infective, analgesic, and antioxidant properties of both curcumin and L. plantarum will better manage complex healing process. Recent reports indicate that polyphenolics like curcumin improve probiotic effects. Curcumin was nanoencapsulated (CSLNs) to improve its bioprofile and achieve controlled release on the wound bed. Bacteriotherapy (probiotic) is established to promote wound healing via antimicrobial activity, inhibition of pathogenic toxins, immunomodulation, and anti-inflammatory actions. Combination of CSLNs with probiotic enhanced (560%) its antimicrobial effects against planktonic cells and biofilms of skin pathogen, Staphylococcus aureus 9144. The sterile dressing was devised with selected polymers, and optimized for polymer concentration, and dressing characteristics using a central composite design. It exhibited a swelling ratio of 412 ± 36%, in vitro degradation time of 3 h, optimal water vapor transmission rate of 1516.81 ± 155.25 g/m2/day, high tensile strength, low-blood clotting index, case II transport, and controlled release of curcumin. XRD indicated strong interaction between employed polymers. FESEM revealed a porous sponge like meshwork embedded with L. plantarum and CSLNs. It degraded and released L. plantarum, which germinated in the wound bed. The sponge was stable under refrigerated conditions for up to six months. No translocation of probiotic from wound to the internal organs confirmed safety. The dressing exhibited faster wound closure and lowered bioburden in the wound area in mice. This was coupled with a decrease in TNF-α, MMP-9, and LPO levels; and an increase in VEGF, TGF-β, and antioxidant enzymes such as catalase and GSH, establishing multiple healing pathways. Results were compared with CSLNs and probiotic-alone dressings. The dressing was as effective as the silver nanoparticle-based marketed hydrogel dressing; however, the cost and risk of developing resistance would be much lower currently.
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Affiliation(s)
- Simarjot Kaur Sandhu
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India
| | - Jayant Raut
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India
| | - Suneel Kumar
- Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08844, USA
| | - Mandeep Singh
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India
| | - Bakr Ahmed
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India
| | - Joga Singh
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India
| | - Vikas Rana
- Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India
| | - Praveen Rishi
- Department of Microbiology, Panjab University, Chandigarh 160014, India
| | - Narayanan Ganesh
- Jawaharlal Nehru Cancer Hospital & Research Centre, Bhopal 462001, India
| | - Kamal Dua
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, New South Wales 2007, Australia
| | - Indu Pal Kaur
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
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Jang SY, Kim J, Hong E, Lee K, Na Y, Yeom CH, Park S. Curcumin inhibits human cancer cell growth and migration through downregulation of SVCT2. Cell Biochem Funct 2023; 41:696-703. [PMID: 37322603 DOI: 10.1002/cbf.3824] [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: 04/21/2023] [Revised: 05/17/2023] [Accepted: 06/03/2023] [Indexed: 06/17/2023]
Abstract
Curcumin is a natural polyphenol that is extracted from the rhizomes of the turmeric plant (Curcuma longa), a member of the ginger family. It has been used for centuries in traditional Indian and Chinese medicine for its medicinal properties, including anti-inflammatory, antioxidant and antitumor effects. SVCT2 (Solute Carrier Family 23 Member 2, also known as SLC23A2) is a protein that plays a role in the transport of Vitamin C (Ascorbic Acid) into cells. SVCT2 plays an important role in tumor progression and metastasis, however, the molecular mechanisms of curcumin on SVCT2 have not been studied to date. Curcumin treatment inhibited proliferation and migration of cancer cells in a dose dependent manner. We found that curcumin reduced the expression of SVCT2 in cancer cells with a wild type p53, but not in those with a mutant type of p53. SVCT2 downregulation also reduced the MMP2 activity. Taken together, our results indicate that curcumin inhibited human cancer cell growth and migration by regulating SVCT2 through a downregulating p53. These findings provide new insights into the molecular mechanisms of curcumin's anticancer effects and potential therapeutic strategies for the treatment of metastatic migration.
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Affiliation(s)
- Soon Young Jang
- Department of Applied Chemistry, Dongduk Women's University, Seoul, Korea
- Rappeler Company, Anyang, Gyeonggi-do, Korea
| | - Jiyun Kim
- Department of Applied Chemistry, Dongduk Women's University, Seoul, Korea
| | - Eunbi Hong
- Department of Applied Chemistry, Dongduk Women's University, Seoul, Korea
| | - Kyuri Lee
- Department of Applied Chemistry, Dongduk Women's University, Seoul, Korea
| | - Yuran Na
- Rappeler Company, Anyang, Gyeonggi-do, Korea
| | | | - Seyeon Park
- Department of Applied Chemistry, Dongduk Women's University, Seoul, Korea
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50
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Shi M, Liu X, Pan W, Li N, Tang B. Anti-inflammatory strategies for photothermal therapy of cancer. J Mater Chem B 2023. [PMID: 37326239 DOI: 10.1039/d3tb00839h] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
High temperature generated by photothermal therapy (PTT) can trigger an inflammatory response at the tumor site, which not only limits the efficacy of PTT but also increases the risk of tumor metastasis and recurrence. In light of the current limitations posed by inflammation in PTT, several studies have revealed that inhibiting PTT-induced inflammation can significantly improve the efficacy of cancer treatment. In this review, we summarize the research progress made in combining anti-inflammatory strategies to enhance the effectiveness of PTT. The goal is to offer valuable insights for developing better-designed photothermal agents in clinical cancer therapy.
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Affiliation(s)
- Mingwan Shi
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.
| | - Xiaohan Liu
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.
| | - Wei Pan
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.
| | - Na Li
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.
| | - Bo Tang
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.
- Laoshan Laboratory, Qingdao 266237, P. R. China
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