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Almeida PSD, Barão K, Forones NM. SARCOPENIA AND GASTROINTESTINAL CANCER: NUTRITIONAL APPROACH FOCUSING ON CURCUMIN SUPPLEMENTATION. ARQUIVOS DE GASTROENTEROLOGIA 2025; 62:e24068. [PMID: 40197883 PMCID: PMC12043197 DOI: 10.1590/s0004-2803.24612024-068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Accepted: 11/15/2024] [Indexed: 04/10/2025]
Abstract
BACKGROUND Sarcopenia is a syndrome characterized by decreased strength, quantity and/or quality of skeletal muscle mass. When associated with cancer, it correlates with poorer clinical outcomes. Cancers of the gastrointestinal tract, prevalent globally and in Brazil, are associated with a greater nutritional risk. Early detection and intervention for nutritional risks are critical in this population. Recent studies on turmeric/curcumin have demonstrated beneficial effects in cancer patients. Specifically, curcumin have shown promise in reducing muscle depletion, oxidative stress, and improving strength and fatigue, factors related to sarcopenia. This review aims to elucidate sarcopenia and sarcopenia secondary to cancer, emphasizing nutritional management and the role of curcumin supplementation. Effective cancer management, whether with or without sarcopenia, demands comprehensive public health strategies and multimodal interventions within healthcare institutions. Nutrition is pivotal across the cancer care journey, encompassing screening, guidance, and provision of nutrients that support maintaining or recovering body composition. Curcumin supplementation emerges as a potential adjuvant to the standard cancer treatment and sarcopenia management. Nevertheless, further clinical studies are warranted to substantiate these findings. BACKGROUND • Sarcopenia is a syndrome characterized by decreased strength, quantity and/or quality of skeletal muscle mass. BACKGROUND • Sarcopenia when associated with cancer, it correlates with poorer clinical outcomes. BACKGROUND • Curcumin has shown promise in reducing muscle depletion, oxidative stress, and improving strength and fatigue, factors related to sarcopenia. BACKGROUND • Curcumin supplementation emerges as a potential adjuvant to the standard cancer treatment and sarcopenia management.
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Affiliation(s)
- Pamela S de Almeida
- Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Medicina, Divisão de Gastroenterologia, São Paulo, SP, Brasil
| | - Katia Barão
- Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Medicina, Divisão de Gastroenterologia, São Paulo, SP, Brasil
| | - Nora M Forones
- Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Medicina, Divisão de Gastroenterologia, São Paulo, SP, Brasil
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Gonçalves S, Fernandes L, Caramelo A, Martins M, Rodrigues T, Matos RS. Soothing the Itch: The Role of Medicinal Plants in Alleviating Pruritus in Palliative Care. PLANTS (BASEL, SWITZERLAND) 2024; 13:3515. [PMID: 39771213 PMCID: PMC11677410 DOI: 10.3390/plants13243515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 12/09/2024] [Accepted: 12/11/2024] [Indexed: 01/05/2025]
Abstract
Chronic pruritus, or persistent itching, is a debilitating condition that severely impacts quality of life, especially in palliative care settings. Traditional treatments often fail to provide adequate relief or are associated with significant side effects, prompting interest in alternative therapies. This review investigates the antipruritic potential of eight medicinal plants: chamomile (Matricaria chamomilla), aloe vera (Aloe barbadensis), calendula (Calendula officinalis), curcumin (Curcuma longa), lavender (Lavandula angustifolia), licorice (Glycyrrhiza glabra), peppermint (Mentha piperita), and evening primrose (Oenothera biennis). These plants are analyzed for their traditional applications, active bioactive compounds, mechanisms of action, clinical evidence, usage, dosage, and safety profiles. Comprehensive searches were conducted in databases including PubMed, Web of Science, Scopus, and b-on, focusing on in vitro, animal, and clinical studies using keywords like "plant", "extract", and "pruritus". Studies were included regardless of publication date and limited to English-language articles. Findings indicate that active compounds such as polysaccharides in aloe vera, curcuminoids in turmeric, and menthol in peppermint exhibit significant anti-inflammatory, antioxidant, and immune-modulating properties. Chamomile and calendula alleviate itching through anti-inflammatory and skin-soothing effects, while lavender and licorice offer antimicrobial benefits alongside antipruritic relief. Evening primrose, rich in gamma-linolenic acid, is effective in atopic dermatitis-related itching. Despite promising preclinical and clinical results, challenges remain in standardizing dosages and formulations. The review highlights the necessity of further clinical trials to ensure efficacy and safety, advocating for integrating these botanical therapies into complementary palliative care practices. Such approaches emphasize holistic treatment, addressing chronic pruritus's physical and emotional burden, thereby enhancing patient well-being.
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Affiliation(s)
- Sara Gonçalves
- Academic Clinical Center of Trás-os-Montes and Alto Douro (CACTMAD), University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
- School of Health, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
- Associação Internacional de Aromaterapeutas Profissionais (IAAP-Portugal), 4445-088 Alfena, Portugal;
| | - Lisete Fernandes
- Centro de Química-Vila Real (CQ-VR), UME-CIDE Unidade de Microscopia Eletrónica-Centro de Investigação e Desenvolvimento, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
- Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
| | - Ana Caramelo
- Academic Clinical Center of Trás-os-Montes and Alto Douro (CACTMAD), University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
- School of Health, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
- RISE-Health Research Network, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
| | - Maria Martins
- Academic Clinical Center of Trás-os-Montes and Alto Douro (CACTMAD), University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
- Palliative Medicine, Local Health Unit of Trás-os-Montes and Alto Douro EPE, 5400-261 Chaves, Portugal
| | - Tânia Rodrigues
- Associação Internacional de Aromaterapeutas Profissionais (IAAP-Portugal), 4445-088 Alfena, Portugal;
| | - Rita S. Matos
- Academic Clinical Center of Trás-os-Montes and Alto Douro (CACTMAD), University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
- Local Health Unit of Trás-os-Montes and Alto Douro (ULSTMAD), 5050-275 Peso da Régua, Portugal
- Palliative Medicine, Local Health Unit of Nordeste, 5370-210 Mirandela, Portugal
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Wang L, Wei Z, Xue C. Co-encapsulation of curcumin and fucoxanthin in solid-in-oil-in-water multilayer emulsions: Characterization, stability and programmed sequential release. Food Chem 2024; 456:139975. [PMID: 38852456 DOI: 10.1016/j.foodchem.2024.139975] [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: 11/26/2023] [Revised: 05/20/2024] [Accepted: 06/02/2024] [Indexed: 06/11/2024]
Abstract
To enhance the bioavailability of bioactives with varying efficacy in the gastrointestinal tract (GIT), a co-delivery system of solid-in-oil-in-water (S/O/W) emulsion was designed for the co-encapsulation of two bioactives in this paper. S/O/W emulsions were fabricated utilizing fucoxanthin (FUC)-loaded nanoparticles (NPs) as the solid phase, coconut oil containing curcumin (Cur) as the oil phase, and carboxymethyl starch (CMS)/propylene glycol alginate (PGA) complex as the aqueous phase. The high entrapment efficiency of Cur (82.3-91.3%) and FUC (96.0-96.1%) was found in the CMS/PGA complex-stabilized S/O/W emulsions. Encapsulation of Cur and FUC within S/O/W emulsions enhanced their UV and thermal stabilities. In addition, S/O/W emulsions prepared with CMS/PGA complexes displayed good stability. More importantly, the formed S/O/W emulsion possessed programmed sequential release characteristics, delivering Cur and FUC to the small intestine and colon, respectively. These results contributed to designing co-delivery systems for the programmed sequential release of two hydrophobic nutrients in the GIT.
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Affiliation(s)
- Luhui Wang
- College of Food Science and Engineering, Ocean University of China, Qingdao 266400, China
| | - Zihao Wei
- College of Food Science and Engineering, Ocean University of China, Qingdao 266400, China.
| | - Changhu Xue
- College of Food Science and Engineering, Ocean University of China, Qingdao 266400, China; Qingdao National Laboratory for Marine Science and Technology, Qingdao 266235, China.
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Kar S, Tudu B, Bandyopadhyay R. Statistical machine learning techniques applied to NIR spectral data for rapid detection of sudan dye-I in turmeric powders with optimized pre-processing and wavelength selection. JOURNAL OF FOOD SCIENCE AND TECHNOLOGY 2024; 61:1955-1964. [PMID: 39285995 PMCID: PMC11401802 DOI: 10.1007/s13197-024-05971-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Revised: 11/23/2023] [Accepted: 03/09/2024] [Indexed: 09/19/2024]
Abstract
Machine learning techniques were applied systematically to the spectral data of near-infrared (NIR) spectroscopy to find out the sudan dye I adulterants in turmeric powders. Turmeric powder is one of the most commonly used spice and a simple target for adulteration. Pure turmeric powder was prepared at the laboratory and spiked with sudan dye I adulterants. The spectral data of these adulterated mixtures were obtained by NIR spectrometer and investigated accordingly. The concentrations of the adulterants were 1%, 5%, 10%, 15%, 20%, 25%, 30% (w/w) respectively. Exploratory data analysis was done for the visualization of the adulterant classes by principal component analysis (PCA). Optimization of the pre-processing and wavelength selection was done by cross-validation techniques using a partial least squares regression (PLSR) model. For quantitative analysis four different regression techniques were applied namely ensemble tree regression (ENTR), support vector regression (SVR), principal component regression (PCR), and PLSR, and a comparative analysis was done. The best method was found to be PLSR. The accuracy of the PLSR analysis was determined with the coefficients of determination (R2) of greater than 0.97 and with root mean square error (RMSE) of less than 0.93 respectively. For the verification of the robustness of the model, the Figure of merit (FOM) of the model was derived with the help of the Net analyte signal (NAS) theory. The current study established that the NIR spectroscopy can be applied to detect and quantify the amount of sudan dye I adulterants added to the turmeric powders with satisfactory accuracy. Supplementary Information The online version contains supplementary material available at 10.1007/s13197-024-05971-9.
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Affiliation(s)
- Saumita Kar
- Department of Instrumentation and Electronics Engineering, Jadavpur University, Salt Lake Campus, Block LB, Sector III, Plot 8, Salt Lake, Kolkata, 700 098 India
| | - Bipan Tudu
- Department of Instrumentation and Electronics Engineering, Jadavpur University, Salt Lake Campus, Block LB, Sector III, Plot 8, Salt Lake, Kolkata, 700 098 India
| | - Rajib Bandyopadhyay
- Department of Instrumentation and Electronics Engineering, Jadavpur University, Salt Lake Campus, Block LB, Sector III, Plot 8, Salt Lake, Kolkata, 700 098 India
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Wang L, Wei Z, Xue C, Yang L. Co-delivery system based on multilayer structural nanoparticles for programmed sequential release of fucoxanthin and curcumin. Food Hydrocoll 2023. [DOI: 10.1016/j.foodhyd.2023.108729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/03/2023]
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Jian S, Yang K, Zhang L, Zhang L, Xin Z, Wen C, He S, Deng J, Deng B. The modulation effects of plant‐derived bioactive ingredients on chronic kidney disease: Focus on the gut–kidney axis. FOOD FRONTIERS 2023. [DOI: 10.1002/fft2.209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Affiliation(s)
- Shiyan Jian
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University Guangzhou China
| | - Kang Yang
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University Guangzhou China
| | - Lingna Zhang
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University Guangzhou China
| | - Limeng Zhang
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University Guangzhou China
| | - Zhongquan Xin
- Faculty of Food Science and Engineering Kunming University of Science and Technology Kunming China
| | - Chaoyu Wen
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University Guangzhou China
| | - Shansong He
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University Guangzhou China
| | - Jinping Deng
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University Guangzhou China
| | - Baichuan Deng
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University Guangzhou China
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De AK, Chakraborty D, Ponraj P, Sawhney S, Banik S, Chakurkar EB, Bhattacharya D. Supplementing turmeric rhizome powder in growing Andaman local pigs: a conflated approach for therapy evaluation. Trop Anim Health Prod 2023; 55:45. [PMID: 36692602 DOI: 10.1007/s11250-023-03459-w] [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: 04/27/2022] [Accepted: 01/04/2023] [Indexed: 01/25/2023]
Abstract
This paper examined the pluripotent effect of supplementation of turmeric rhizome powder (TRP) (Curcuma longa) in growing Andaman local pigs. A total of 48 pigs were randomly allotted into four groups and fed diets containing TRP at 4 concentrations, that is, 0 (control group), 0.05 (treatment 1), 0.1 (treatment 2), and 0.2% (treatment 3) for 30 days. The mean body weight of pigs supplemented with 0.1% and 0.2% TRP was significantly higher than that of the control group (41.66 ± 0.44, 42.59 ± 0.33 vs 40.38 ± 0.30 kg; p ≤ 0.05) which indicated the effect of TRP as growth enhancer. A significant (p ≤ 0.05) decrease in serum concentration of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) was recorded in supplemented groups as compared to the control group. Creatinine kinase (U/l) decreased in all the treatment groups as compared to the control group. Total cholesterol, triglyceride, and low-density lipoprotein cholesterol decreased significantly after supplementation with 0.1% and 0.2% TRP in comparison to the control group. However, there was marked increase in high-density lipoprotein cholesterol (mg/dl) in all TRP-supplemented groups than the control group (27.67 ± 0.60 in T1, 32.76 ± 0.32 in T2, and 34.58 ± 0.37 in T3 vs. 23.73 ± 0.69 in control; p ≤ 0.05). Further, there was increase in antioxidant profile after TRP supplementation. Anti-inflammatory potentiality of TRP could also be appreciated since TRP supplementation downregulated (p ≤ 0.05) expression of IL-6, IL-1β, and IFN-γ. Therefore, we perceive that this conflated approach is an example of its own kind to focus on modification of health status of pigs for more productivity and augmentation of immune response.
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Affiliation(s)
- Arun Kumar De
- Animal Science Division, ICAR-Central Island Agricultural Research Institute, Port Blair, Andaman and Nicobar Islands, 744101, India.
| | - Dibyendu Chakraborty
- Division of Animal Genetics and Breeding, Sher-e-Kashmir University of Agricultural Sciences and Technology of Jammu, R.S. Pura, Jammu, 181102, India
| | - Perumal Ponraj
- Animal Science Division, ICAR-Central Island Agricultural Research Institute, Port Blair, Andaman and Nicobar Islands, 744101, India
| | - Sneha Sawhney
- Animal Science Division, ICAR-Central Island Agricultural Research Institute, Port Blair, Andaman and Nicobar Islands, 744101, India
| | - Santanu Banik
- Department of Animal Genetics and Breeding, ICAR-National Research Centre on Pig, Guwahati, Assam, 781131, India
| | - Eaknath B Chakurkar
- Animal Science Division, ICAR-Central Island Agricultural Research Institute, Port Blair, Andaman and Nicobar Islands, 744101, India
| | - Debasis Bhattacharya
- Animal Science Division, ICAR-Central Island Agricultural Research Institute, Port Blair, Andaman and Nicobar Islands, 744101, India.
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Smirnova E, Moniruzzaman M, Chin S, Sureshbabu A, Karthikeyan A, Do K, Min T. A Review of the Role of Curcumin in Metal Induced Toxicity. Antioxidants (Basel) 2023; 12:antiox12020243. [PMID: 36829803 PMCID: PMC9952547 DOI: 10.3390/antiox12020243] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 01/17/2023] [Accepted: 01/19/2023] [Indexed: 01/26/2023] Open
Abstract
Metal toxicity poses a potential global threat to the environment and living beings. Their numerous agricultural, medical, industrial, domestic, and technological applications result in widespread distribution in the environment which raises concern on the potential effects of metals in terms of health hazards and environmental pollution. Chelation therapy has been the preferred medical treatment for metal poisoning. The chelating agent bounds metal ions to form complex cyclic structures known as 'chelates' to intensify their excretion from the body. The main disadvantage of synthetic chelators is that the chelation process removes vital nutrients along with toxic metals. Natural compounds are widely available, economical, and have minimal adverse effects compared to classical chelators. Herbal preparations can bind to the metal, reduce its absorption in the intestines, and facilitate excretion from the body. Curcumin, a bioactive substance in turmeric, is widely used as a dietary supplement. Most studies have shown that curcumin protects against metal-induced lipid peroxidation and mitigates adverse effects on the antioxidant system. This review article provides an analysis to show that curcumin imparts promising metal toxicity-ameliorative effects that are related to its intrinsic antioxidant activity.
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Affiliation(s)
- Elena Smirnova
- Department of Animal Biotechnology, Jeju International Animal Research Center (JIA) & Sustainable Agriculture Research Institute (SARI), Jeju National University, Jeju 63243, Republic of Korea
| | - Mohammad Moniruzzaman
- Department of Animal Biotechnology, Jeju International Animal Research Center (JIA) & Sustainable Agriculture Research Institute (SARI), Jeju National University, Jeju 63243, Republic of Korea
- Correspondence: (M.M.); (T.M.)
| | - Sungyeon Chin
- Department of Animal Biotechnology, Jeju International Animal Research Center (JIA) & Sustainable Agriculture Research Institute (SARI), Jeju National University, Jeju 63243, Republic of Korea
| | - Anjana Sureshbabu
- Department of Animal Biotechnology, Jeju International Animal Research Center (JIA) & Sustainable Agriculture Research Institute (SARI), Jeju National University, Jeju 63243, Republic of Korea
| | - Adhimoolam Karthikeyan
- Subtropical Horticulture Research Institute, Jeju National University, Jeju 63243, Republic of Korea
| | - Kyoungtag Do
- Department of Animal Biotechnology, Jeju International Animal Research Center (JIA) & Sustainable Agriculture Research Institute (SARI), Jeju National University, Jeju 63243, Republic of Korea
| | - Taesun Min
- Department of Animal Biotechnology, Jeju International Animal Research Center (JIA) & Sustainable Agriculture Research Institute (SARI), Jeju National University, Jeju 63243, Republic of Korea
- Correspondence: (M.M.); (T.M.)
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Siripruekpong W, Issarachot O, Kaewkroek K, Wiwattanapatapee R. Development of Gastroretentive Carriers for Curcumin-Loaded Solid Dispersion Based on Expandable Starch/Chitosan Films. MOLECULES (BASEL, SWITZERLAND) 2023; 28:molecules28010361. [PMID: 36615555 PMCID: PMC9822339 DOI: 10.3390/molecules28010361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/24/2022] [Accepted: 12/27/2022] [Indexed: 01/03/2023]
Abstract
Curcumin, a polyphenolic extract from the rhizomes of turmeric, exhibits antioxidant, anti-inflammatory, and anticancer activities, which are beneficial for the treatment of gastric diseases. However, curcumin's therapeutic usefulness is restricted by its low aqueous solubility and short gastric residence time. In this study, curcumin-loaded solid dispersion (ratio 1:5) was prepared using Eudragit® EPO (Cur EPO-SD), resulting in an approximately 12,000-fold increase in solubility to 6.38 mg/mL. Expandable films incorporating Cur EPO-SD were subsequently prepared by solvent casting using different types of starch (banana, corn, pregelatinized, and mung bean starch) in combination with chitosan. Films produced from banana, corn, pregelatinized and mung bean starch unfolded and expanded upon exposure to simulated gastric medium, resulting in sustained release of 80% of the curcumin content within 8 h, whereas films based on pregelatinized starch showed immediate release characteristics. Curcumin-loaded expandable films based on different types of starch exhibited similar cytotoxic effects toward AGS cells and more activity than unformulated curcumin. Furthermore, the films resulted in increased anti-inflammatory activity against RAW 264.7 macrophage cells compared with the NSAID, indomethacin. These findings demonstrate the potential of expandable curcumin-loaded films as gastroretentive dosage forms for the treatment of gastric diseases and to improve oral bioavailability.
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Affiliation(s)
- Worrawee Siripruekpong
- Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hatyai 90112, Songkhla, Thailand
- Phytomedicine and Pharmaceutical Biotechnology Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hatyai 90112, Songkhla, Thailand
| | - Ousanee Issarachot
- Pharmacy Technician Department, Sirindhron College of Public Health of Suphanburi, Mueang Suphan Buri District 72000, Suphan Buri, Thailand
| | - Kanidta Kaewkroek
- Faculty of Integrative Medicine, Rajamangala University of Technology Thanyaburi, Thanyaburi, Khlong Luang 12130, Pathum Thani, Thailand
| | - Ruedeekorn Wiwattanapatapee
- Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hatyai 90112, Songkhla, Thailand
- Phytomedicine and Pharmaceutical Biotechnology Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hatyai 90112, Songkhla, Thailand
- Correspondence: ; Tel.: +66-0897328989 or +66-074288801
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Rahman MM, Sarker MT, Alam Tumpa MA, Yamin M, Islam T, Park MN, Islam MR, Rauf A, Sharma R, Cavalu S, Kim B. Exploring the recent trends in perturbing the cellular signaling pathways in cancer by natural products. Front Pharmacol 2022; 13:950109. [PMID: 36160435 PMCID: PMC9498834 DOI: 10.3389/fphar.2022.950109] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 08/15/2022] [Indexed: 12/12/2022] Open
Abstract
Cancer is commonly thought to be the product of irregular cell division. According to the World Health Organization (WHO), cancer is the major cause of death globally. Nature offers an abundant supply of bioactive compounds with high therapeutic efficacy. Anticancer effects have been studied in a variety of phytochemicals found in nature. When Food and Drug Administration (FDA)-approved anticancer drugs are combined with natural compounds, the effectiveness improves. Several agents have already progressed to clinical trials based on these promising results of natural compounds against various cancer forms. Natural compounds prevent cancer cell proliferation, development, and metastasis by inducing cell cycle arrest, activating intrinsic and extrinsic apoptosis pathways, generating reactive oxygen species (ROS), and down-regulating activated signaling pathways. These natural chemicals are known to affect numerous important cellular signaling pathways, such as NF-B, MAPK, Wnt, Notch, Akt, p53, AR, ER, and many others, to cause cell death signals and induce apoptosis in pre-cancerous or cancer cells without harming normal cells. As a result, non-toxic "natural drugs" taken from nature's bounty could be effective for the prevention of tumor progression and/or therapy of human malignancies, either alone or in combination with conventional treatments. Natural compounds have also been shown in preclinical studies to improve the sensitivity of resistant cancers to currently available chemotherapy agents. To summarize, preclinical and clinical findings against cancer indicate that natural-sourced compounds have promising anticancer efficacy. The vital purpose of these studies is to target cellular signaling pathways in cancer by natural compounds.
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Affiliation(s)
- Md. Mominur Rahman
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Md. Taslim Sarker
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Mst. Afroza Alam Tumpa
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Md. Yamin
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Tamanna Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Moon Nyeo Park
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
| | - Md. Rezaul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Swabi, Anbar, Pakistan
| | - Rohit Sharma
- Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Simona Cavalu
- Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania
| | - Bonglee Kim
- Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
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Hafez Ghoran S, Calcaterra A, Abbasi M, Taktaz F, Nieselt K, Babaei E. Curcumin-Based Nanoformulations: A Promising Adjuvant towards Cancer Treatment. Molecules 2022; 27:molecules27165236. [PMID: 36014474 PMCID: PMC9414608 DOI: 10.3390/molecules27165236] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Revised: 08/10/2022] [Accepted: 08/13/2022] [Indexed: 02/06/2023] Open
Abstract
Throughout the United States, cancer remains the second leading cause of death. Traditional treatments induce significant medical toxic effects and unpleasant adverse reactions, making them inappropriate for long-term use. Consequently, anticancer-drug resistance and relapse are frequent in certain situations. Thus, there is an urgent necessity to find effective antitumor medications that are specific and have few adverse consequences. Curcumin is a polyphenol derivative found in the turmeric plant (Curcuma longa L.), and provides chemopreventive, antitumor, chemo-, and radio-sensitizing properties. In this paper, we summarize the new nano-based formulations of polyphenolic curcumin because of the growing interest in its application against cancers and tumors. According to recent studies, the use of nanoparticles can overcome the hydrophobic nature of curcumin, as well as improving its stability and cellular bioavailability in vitro and in vivo. Several strategies for nanocurcumin production have been developed, each with its own set of advantages and unique features. Because the majority of the curcumin-based nanoformulation evidence is still in the conceptual stage, there are still numerous issues impeding the provision of nanocurcumin as a possible therapeutic option. To support the science, further work is necessary to develop curcumin as a viable anti-cancer adjuvant. In this review, we cover the various curcumin nanoformulations and nanocurcumin implications for therapeutic uses for cancer, as well as the current state of clinical studies and patents. We further address the knowledge gaps and future research orientations required to develop curcumin as a feasible treatment candidate.
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Affiliation(s)
- Salar Hafez Ghoran
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran 16666-63111, Iran
- Medicinal Plant Breeding and Development Research Institute, University of Kurdistan, Sanandaj 66177-15175, Iran
- Correspondence: (S.H.G.); or (E.B.); Tel.: +98-9144425047 (S.H.G.); Tel.: +98-4133392686 (E.B.)
| | - Andrea Calcaterra
- Department of Chemistry and Technology of Drugs, Sapienza–University of Rome, P. le Aldo Moro 5, 00185 Rome, Italy
| | - Milad Abbasi
- Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz 71336-54361, Iran
| | - Fatemeh Taktaz
- Department of Biology, Faculty of Sciences, University of Hakim Sabzevari, Sabzevar 96179-76487, Iran
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Kay Nieselt
- Interfaculty Institute for Bioinformatics and Medical Informatics (IBMI), University of Tübingen, 72076 Tübingen, Germany
| | - Esmaeil Babaei
- Interfaculty Institute for Bioinformatics and Medical Informatics (IBMI), University of Tübingen, 72076 Tübingen, Germany
- Department of Biology, Faculty of Natural Science, University of Tabriz, Tabriz 51666-16471, Iran
- Correspondence: (S.H.G.); or (E.B.); Tel.: +98-9144425047 (S.H.G.); Tel.: +98-4133392686 (E.B.)
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12
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Celani LMS, Egito EST, Azevedo ÍM, Oliveira CN, Dourado D, Medeiros AC. Treatment of colitis by oral negatively charged nanostructured curcumin in rats. Acta Cir Bras 2022; 37:e370602. [PMID: 35976279 PMCID: PMC9377652 DOI: 10.1590/acb370602] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Revised: 04/08/2022] [Accepted: 05/03/2022] [Indexed: 12/05/2022] Open
Abstract
PURPOSE To examine the effects of a negatively charged nanostructured curcumin microemulsion in experimental ulcerative colitis (UC) in rats. METHODS Four percent acetic acid was used to induce UC. The animals were treated for seven days and randomly assigned to four groups: normal control (NC), colitis/normal saline (COL/NS), colitis/curcumin (COL/CUR), and colitis/mesalazine (COL/MES). The nanostructured curcumin was formulated with a negative zeta potential (-16.70 ± 1.66 mV). Dosage of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin 1-β (IL-1β), interleukin 6 (IL-6), and antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase), macro and microscopic evaluation of the colon tissue were analyzed. RESULTS The COL/CUR group had a higher level of antioxidant enzymes compared to the COL/MESgroup. The levels of TNF-α, IL-1β and IL-6 were significantly lower in the colonic tissue of the COL/CUR group rats, when compared to the COL/NS and COL/MES groups (p < 0.001). The presence of ulcers in the colonic mucosa in rats of the COL/NSgroup was significantly higher than in the COL/MES group (p < 0.001). In the NC and COL/CUR groups, there were no ulcers in the colonic mucosa. CONCLUSIONS The nanostructured microemulsion of curcumin, used orally, positively influenced the results of the treatment of UC in rats. The data also suggests that nanostructured curcumin with negative zeta potential is a promising phytopharmaceutical oral delivery system for UC therapy. Further research needs to be done to better understand the mechanisms of the negatively charged nanostructured curcumin microemulsion in UC therapy.
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Affiliation(s)
- Lívia Medeiros Soares Celani
- Fellow master degree. Universidade Federal do Rio Grande do Norte – Postgraduate Program in Health Sciences – Natal (RN), Brazil
| | - Eryvaldo Sócrates Tabosa Egito
- PhD, full professor, chairman. Universidade Federal do Rio Grande do Norte – Laboratory of Dispersed Systems – Natal (RN), Brazil
| | | | - Cláudia Nunes Oliveira
- PhD. Universidade Federal do Rio Grande do Norte – Pathology Department – Health Sciences – Natal (RN), Brazil
| | - Douglas Dourado
- Fellow PhD degree. Universidade Federal do Rio Grande do Norte – Postgraduate Program in Health Sciences – Natal (RN), Brazil
| | - Aldo Cunha Medeiros
- PhD, full professor, chairman. Universidade Federal do Rio Grande do Norte – Nucleus of Experimental Surgery – Natal (RN), Brazil
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13
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Wang L, Wei Z, Xue C. The presence of propylene glycol alginate increased the stability and intestine-targeted delivery potential of carboxymethyl starch-stabilized emulsions. Food Res Int 2022; 157:111387. [PMID: 35761643 DOI: 10.1016/j.foodres.2022.111387] [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: 03/05/2022] [Revised: 05/06/2022] [Accepted: 05/17/2022] [Indexed: 12/31/2022]
Abstract
Propylene glycol alginate (PGA) was added to improve the stability and delivery performance of carboxymethyl starch (CMS)-stabilized emulsion. In the first instance, the CMS/PGA complexes were characterized, which proved that the formation of CMS/PGA complexes mainly depended on hydrogen bonding, and the CMS/PGA complexes showed porous networks. The CMS/PGA complexes were more hydrophobic than CMS, and the interaction of CMS with PGA enhanced the thermal stability of CMS. Next, the effects of CMS/PGA complexes on the properties of emulsions were investigated, and the intestine-targeted delivery potential of emulsions was evaluated through the in vitro release study as well. The droplet size of CMS/PGA complex-stabilized emulsions gradually decreased and the encapsulation efficiency (EE) improved with increasing the PGA content in CMS/PGA complexes. The addition of PGA also greatly improved the physical stability of emulsions, including anti-flocculation and anti-coalescence stabilities. All emulsions exhibited non-Newtonian pseudoplastic properties. Furthermore, the emulsions stabilized by CMS/PGA complexes showed reduced curcumin (Cur) release in the simulated gastric fluid (SGF), whereas exhibited sustained release in the α-amylase-containing simulated intestinal fluid (SIF). These results demonstrated that the emulsion stabilized by CMS/PGA complex was able to control and modulate the release of Cur in the gastrointestinal tract, and was therefore a promising intestine-targeted delivery system for Cur.
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Affiliation(s)
- Luhui Wang
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
| | - Zihao Wei
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China.
| | - Changhu Xue
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China; Qingdao National Laboratory for Marine Science and Technology, Qingdao 266235, China.
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14
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Ismail OI, El-Meligy MMS. Curcumin ameliorated low dose-Bisphenol A induced gastric toxicity in adult albino rats. Sci Rep 2022; 12:10201. [PMID: 35715475 PMCID: PMC9206026 DOI: 10.1038/s41598-022-14158-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 06/02/2022] [Indexed: 11/16/2022] Open
Abstract
Bisphenol A (BPA) is one of the most common worldwide chemicals involved in the industry of polycarbonate plastics, medical devices, and pharmaceuticals. Forty three-month-old albino rats were randomly classified into four groups. Group Ӏ received a daily corn oil dose (5 mL/kg/ body weight, BW) through a gastric tube for one month, Group ӀӀ received a daily dose of Curcumin (200 mg/kg body weight (B.W.) through a gastric tube for one month, Group ӀӀӀ received a daily dose of BPA (0.5 μg/kg B.W.) through a gastric tube for one month and Group ӀV received concomitant daily doses of Bisphenol A and Curcumin as the regimen described in groups ӀӀ and ӀӀӀ. The rats were sacrificed, and glandular portion of stomach was dissected and processed for light, immunohistochemical and ultrastructural study. BPA induced destructed gastric glands, dilated congested blood vessels, submucosal oedema, decreased PAS-positive reactivity, increased collagen fibres deposition, decrease in the positive BCL2 immunoexpression, increased positive PCNA immunoexpression, reduction in the gastric mucosal height and destructive changes in the enteroendocrine, chief and parietal cells. Curcumin coadministration provoked an obvious improvement in the gastric structure. BPA exposure has toxic effects on the glandular portion of the stomach in rats. Otherwise, Curcumin coadministration has exhibited protective impact on the architecture of the stomach.
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Affiliation(s)
- Omnia Ibrahim Ismail
- Human Anatomy and Embryology Department, Faculty of Medicine, Assiut University, Assiut, Egypt.
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15
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Nakagawa Y, Mori K, Yamada S, Mukai S, Hirose A, Nakamura R. The Oral Administration of Highly-Bioavailable Curcumin for One Year Has Clinical and Chondro-Protective Effects: A Randomized, Double-Blinded, Placebo-Controlled Prospective Study. Arthrosc Sports Med Rehabil 2022; 4:e393-e402. [PMID: 35494290 PMCID: PMC9042777 DOI: 10.1016/j.asmr.2021.10.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 10/23/2021] [Indexed: 12/17/2022] Open
Abstract
Purpose The purpose of this study was to determine the clinical and chondroprotective efficacy and safety of orally administered Theracurmin in patients who underwent mosaicplasty for knee chondral or osteochondral diseases over 12 months of treatment. Methods We enrolled 50 patients, older than 20 years of age, who underwent mosaicplasty for their knee joint diseases. Theracurmin at 180 mg of curcumin per day or placebo was administered orally every day for 12 months. Because 7 patients dropped out of the study, 43 patients were examined; they included 14 men and 29 women and 24 right and 19 left knees. The mean operative age was 59.5 years (range, 24-84 years). We evaluated the Japanese Orthopaedic Association knee osteoarthritis score (JOA), visual analog scale (VAS), and Japanese Knee Osteoarthritis Measure (JKOM) as clinical symptoms; T2 mapping values using magnetic resonance imaging as an indication of the chondroprotective effect; and blood concentration of curcumin at 0, 3, 6, and 12 months after the operations. We performed intraoperative acoustic evaluation of articular cartilage as a measure of chondroprotective effect during the operations and second-look arthroscopy. Results The JOA, VAS and JKOM at 3, 6, and 12 months were significantly better than those during the preoperative period. However, the values of JOA, VAS and JKOM and T2 mapping were not significantly different between the Theracurmin and placebo groups. The blood concentration of curcumin in the Theracurmin group was significantly higher than that in the placebo group at 3, 6, and 12 months after the operations. Cartilage stiffness and surface roughness were significantly better in the Theracurmin group than in the placebo group at second-look arthroscopy. Conclusions The oral administration of Theracurmin for 1 year demonstrated significantly better chondroprotective effects and no worse clinical effects and adverse events than the placebo. Level of Evidence Level I, double-blinded, placebo-controlled, prospective study.
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16
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Dibba P, Kothari M, Grosman I. Prebiotics, Probiotics, and Dietary Supplements. NUTRITION, WEIGHT, AND DIGESTIVE HEALTH 2022:169-192. [DOI: 10.1007/978-3-030-94953-2_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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17
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Elkhamesy A, Refaat M, Gouida MSO, Alrdahe SS, Youssef MM. Diminished CCl 4 -induced hepatocellular carcinoma, oxidative stress, and apoptosis by co-administration of curcumin or selenium in mice. J Food Biochem 2021; 46:e13845. [PMID: 34231234 DOI: 10.1111/jfbc.13845] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 06/16/2021] [Accepted: 06/18/2021] [Indexed: 01/24/2023]
Abstract
Hepatocellular carcinoma (HCC) is a lethal disease, and in HCC advanced stages, there is limited therapeutic efficacy. HCC results in a complication of fibrosis or cirrhosis. In this study, the protective effect of curcumin and selenium versus hepatocellular carcinoma caused by CCl4 in experimental animals was investigated. In all, 70 mice were divided into seven groups to study the effect of curcumin and selenium on CCl4 -induced hepatocellular carcinoma. After treatment time, different animal groups were sacrificed, serum and liver samples were collected and processed for assay of biochemical and molecular parameters. Our results showed that CCl4 administration induced various alterations such as significant elevation in the serum levels of ALT, AST, and hepatic contents of malondialdehyde (MDA), and depletion in the levels of antioxidant parameters. CCl4 induced apoptosis in the hepatic cells indicated by an increased level of p53, CD4, CD8, Bax, and Annexin V/PI in addition to significant decrease in the level of Bcl-2. Administration of curcumin and selenium restored this abnormal variation in these biochemical parameters to normal values. Our study addressed that curcumin or selenium may be helpful in the protection against liver damage induced by CCl4 . The hepatoprotective impact of curcumin or selenium might be mediated primarily by its potent antioxidant activity. PRACTICAL APPLICATIONS: Hepatocellular carcinoma (HCC) ranked third common cause of death, primary liver cancer. Exposure to CCl4 was found to induce significant hepatotoxicity, characterized by fibrosis, bile duct proliferation, cirrhosis, and reduced hepatic function The work was prepared to investigate the protecting capacity of curcumin, selenium alone, and in combination against HCC induced by CCl4 in the experimental animal model. This study proved the protective effect of curcumin and selenium, alone and in combination with each other, where curcumin showed multiple pharmacological activities, including anti-inflammation and antioxidant, and have an essential role in inhibiting the progression of HCC.
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Affiliation(s)
- Asmaa Elkhamesy
- Department of Biochemistry, Faculty of Science, Mansoura University, Mansoura, Egypt
| | - Manar Refaat
- Department of Biochemistry, Faculty of Science, Mansoura University, Mansoura, Egypt
| | - Mona S O Gouida
- Genetics Unit, Faculty of Medicine, Children Hospital, Mansoura University, Mansoura, Egypt
| | - Salma S Alrdahe
- Department of Biology, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia
| | - Magdy M Youssef
- Department of Biochemistry, Faculty of Science, Mansoura University, Mansoura, Egypt
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18
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Akbari A, Sedaghat M, Heshmati J, Tabaeian SP, Dehghani S, Pizarro AB, Rostami Z, Agah S. Molecular mechanisms underlying curcumin-mediated microRNA regulation in carcinogenesis; Focused on gastrointestinal cancers. Biomed Pharmacother 2021; 141:111849. [PMID: 34214729 DOI: 10.1016/j.biopha.2021.111849] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 06/08/2021] [Accepted: 06/24/2021] [Indexed: 02/07/2023] Open
Abstract
Curcumin is a bioactive ingredient found in the Rhizomes of Curcuma longa. Curcumin is well known for its chemopreventive and anti-cancer properties. Recent findings have demonstrated several pharmacological and biological impacts of curcumin, related to the control and the management of gastrointestinal cancers. Mechanistically, curcumin exerts its biological impacts via antioxidant and anti-inflammatory effects through the interaction with various transcription factors and signaling molecules. Moreover, epigenetic modulators such as microRNAs (miRNAs) have been revealed as novel targets of curcumin. Curcumin was discovered to regulate the expression of numerous pathogenic miRNAs in gastric, colorectal, esophageal and liver cancers. The present systematic review was performed to identify miRNAs that are modulated by curcumin in gastrointestinal cancers.
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Affiliation(s)
- Abolfazl Akbari
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Meghdad Sedaghat
- Department of Internal Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Javad Heshmati
- Songhor Healthcare Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Seidamir Pasha Tabaeian
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Sadegh Dehghani
- Radiation Sciences Department, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Zahra Rostami
- Department of Genetics, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.
| | - Shahram Agah
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran.
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19
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Morshedi K, Borran S, Ebrahimi MS, Masoud Khooy MJ, Seyedi ZS, Amiri A, Abbasi-Kolli M, Fallah M, Khan H, Sahebkar A, Mirzaei H. Therapeutic effect of curcumin in gastrointestinal cancers: A comprehensive review. Phytother Res 2021; 35:4834-4897. [PMID: 34173992 DOI: 10.1002/ptr.7119] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 02/18/2021] [Accepted: 03/26/2021] [Indexed: 12/11/2022]
Abstract
Gastrointestinal (GI) cancers with a high global prevalence are a leading cause of morbidity and mortality. Accordingly, there is a great need to develop efficient therapeutic approaches. Curcumin, a naturally occurring agent, is a promising compound with documented safety and anticancer activities. Recent studies have demonstrated the activity of curcumin in the prevention and treatment of different cancers. According to systematic studies on curcumin use in various diseases, it can be particularly effective in GI cancers because of its high bioavailability in the gastrointestinal tract. Nevertheless, the clinical applications of curcumin are largely limited because of its low solubility and low chemical stability in water. These limitations may be addressed by the use of relevant analogues or novel delivery systems. Herein, we summarize the pharmacological effects of curcumin against GI cancers. Moreover, we highlight the application of curcumin's analogues and novel delivery systems in the treatment of GI cancers.
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Affiliation(s)
- Korosh Morshedi
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Sarina Borran
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | | | - Zeynab Sadat Seyedi
- Department of Cell and Molecular Biology, Faculty of Chemistry, University of Kashan, Kashan, Iran
| | - Atefeh Amiri
- Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Abbasi-Kolli
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Maryam Fallah
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakistan
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
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Kabir MT, Rahman MH, Akter R, Behl T, Kaushik D, Mittal V, Pandey P, Akhtar MF, Saleem A, Albadrani GM, Kamel M, Khalifa SA, El-Seedi HR, Abdel-Daim MM. Potential Role of Curcumin and Its Nanoformulations to Treat Various Types of Cancers. Biomolecules 2021; 11:392. [PMID: 33800000 PMCID: PMC8001478 DOI: 10.3390/biom11030392] [Citation(s) in RCA: 81] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 02/27/2021] [Accepted: 03/03/2021] [Indexed: 12/17/2022] Open
Abstract
Cancer is a major burden of disease globally. Each year, tens of millions of people are diagnosed with cancer worldwide, and more than half of the patients eventually die from it. Significant advances have been noticed in cancer treatment, but the mortality and incidence rates of cancers are still high. Thus, there is a growing research interest in developing more effective and less toxic cancer treatment approaches. Curcumin (CUR), the major active component of turmeric (Curcuma longa L.), has gained great research interest as an antioxidant, anticancer, and anti-inflammatory agent. This natural compound shows its anticancer effect through several pathways including interfering with multiple cellular mechanisms and inhibiting/inducing the generation of multiple cytokines, enzymes, or growth factors including IκB kinase β (IκKβ), tumor necrosis factor-alpha (TNF-α), signal transducer, and activator of transcription 3 (STAT3), cyclooxygenase II (COX-2), protein kinase D1 (PKD1), nuclear factor-kappa B (NF-κB), epidermal growth factor, and mitogen-activated protein kinase (MAPK). Interestingly, the anticancer activity of CUR has been limited primarily due to its poor water solubility, which can lead to low chemical stability, low oral bioavailability, and low cellular uptake. Delivering drugs at a controlled rate, slow delivery, and targeted delivery are other very attractive methods and have been pursued vigorously. Multiple CUR nanoformulations have also been developed so far to ameliorate solubility and bioavailability of CUR and to provide protection to CUR against hydrolysis inactivation. In this review, we have summarized the anticancer activity of CUR against several cancers, for example, gastrointestinal, head and neck, brain, pancreatic, colorectal, breast, and prostate cancers. In addition, we have also focused on the findings obtained from multiple experimental and clinical studies regarding the anticancer effect of CUR in animal models, human subjects, and cancer cell lines.
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Affiliation(s)
- Md. Tanvir Kabir
- Department of Pharmacy, Brac University, 66 Mohakhali, Dhaka 1212, Bangladesh;
| | - Md. Habibur Rahman
- Department of Pharmacy, Southeast University, Banani, Dhaka 1213, Bangladesh
| | - Rokeya Akter
- Department of Pharmacy, Jagannath University, Sadarghat, Dhaka 1100, Bangladesh;
| | - Tapan Behl
- Chitkara College of Pharmacy, Chitkara University, Punjab 140401, India;
| | - Deepak Kaushik
- Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak 124001, India; (D.K.); (V.M.)
| | - Vineet Mittal
- Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak 124001, India; (D.K.); (V.M.)
| | - Parijat Pandey
- Shri Baba Mastnath Institute of Pharmaceutical Sciences and Research, Baba Mastnath University, Rohtak 124001, India;
| | - Muhammad Furqan Akhtar
- Riphah Institute of Pharmaceutical Sciences, Lahore Campus, Riphah International University, Lahore 54000, Pakistan;
| | - Ammara Saleem
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan;
| | - Ghadeer M. Albadrani
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh 11474, Saudi Arabia;
| | - Mohamed Kamel
- Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt;
| | - Shaden A.M. Khalifa
- Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, S-10691 Stockholm, Sweden
| | - Hesham R. El-Seedi
- Pharmacognosy Group, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Box 574, 751 23 Uppsala, Sweden;
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
- Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Kom 32512, Egypt
| | - Mohamed M. Abdel-Daim
- Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt
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21
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A Systematic Review of the Clinical Use of Curcumin for the Management of Gastrointestinal Diseases. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1291:295-326. [PMID: 34331698 DOI: 10.1007/978-3-030-56153-6_18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Gastrointestinal (GI) diseases are highly prevalent worldwide, with considerable morbidity and mortality. Curcumin has been used for many years as a plant-derived product for the management of various conditions such as abdominal pain and poor digestion. This systematic review was undertaken with the aim of investigating the effect of curcumin or turmeric supplementation on GI diseases. A comprehensive systematic search was conducted in PubMed, Scopus, Web of Science and Google Scholar up to March 2020 to identify clinical trials assessing the effect of curcumin/turmeric alone or in combination with other herbs or nutrients on GI diseases. Twenty-one studies comprising 1478 GI patients were included in the study. Four out of seven studies showed a beneficial effect of curcumin/turmeric supplementation on irritable bowel syndrome (IBS) and six out of seven showed positive effects of these herbs on ulcerative colitis. Two out of four studies highlighted the potential role of curcumin/turmeric in eradication of H. pylori infection. Both studies conducted on peptic ulcer disease and two out of four studies performed on Crohn's disease demonstrated positive effects of curcumin/turmeric supplementation. One study showed curcumin supplementation had no effect on familial adenomatous polyposis. However, in another study, curcumin had favorable effects on proctosigmoiditis. Nine studies reported some minor adverse effects. The results of this systematic review suggest a beneficial effect of curcumin/turmeric supplementation on the management of GI diseases. More randomized clinical controlled trials are needed to confirm these results.
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22
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Salehi E, Mashayekh M, Taheri F, Gholami M, Motaghinejad M, Safari S, Sepehr A. Curcumin Can be Acts as Effective agent for Prevent or Treatment of Alcohol-induced Toxicity in Hepatocytes: An Illustrated Mechanistic Review. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH : IJPR 2021; 20:418-436. [PMID: 34400970 PMCID: PMC8170768 DOI: 10.22037/ijpr.2020.112852.13985] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Previous studies have shown that alcohol abuse can cause serious liver damage and cirrhosis. The main pathway for these types of hepatocellular cell neurodegeneration is mitochondrial dysfunction, which causes lipid peroxidation and dysfunction of the glutathione ring and the defect of antioxidant enzymes in alcoholic hepatic cells. Alcohol can also initiate malicious inflammatory pathways and trigger the initiation and activation of intestinal and extrinsic apoptosis pathways in hepatocellular tissues that lead to cirrhosis. Previous studies have shown that curcumin may inhibit lipid peroxidation, glutathione dysfunction and restore antioxidant enzymes. Curcumin also modulates inflammation and the production of alcohol-induced biomarkers. Curcumin has been shown to play a critical role in the survival of alcoholic hepatocellular tissue. It has been shown that curcumin can induce and trigger mitochondrial biogenesis and, by this mechanism, prevent the occurrence of both intrinsic and extrinsic apoptosis pathways in liver cells that have been impaired by alcohol. According to this mechanism, curcumin may protect hepatocellular tissue from alcohol-induced cell degeneration and may therefore survive alcoholic hepatocellular tissue. . Based on these mechanisms, the protective functions of curcumin against alcohol-induced cell degeneration due to oxidative stress, inflammation, and apoptosis events in hepatocellular tissue have been recorded. Hence, in this research, we have attempted to evaluate and analyze the main contribution mechanism of curcumin cell defense properties against alcohol-induced hepatocellular damage, according to previous experimental and clinical studies, and in this way we report findings from major studies.
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Affiliation(s)
- Elham Salehi
- Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University (IUAPS), Tehran, Iran.
| | - Mohammad Mashayekh
- Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University (IUAPS), Tehran, Iran.
| | - Fereshteh Taheri
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
| | - Mina Gholami
- Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
| | - Majid Motaghinejad
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
| | - Sepideh Safari
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
| | - Afrah Sepehr
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
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23
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Fallahi F, Borran S, Ashrafizadeh M, Zarrabi A, Pourhanifeh MH, Khaksary Mahabady M, Sahebkar A, Mirzaei H. Curcumin and inflammatory bowel diseases: From in vitro studies to clinical trials. Mol Immunol 2020; 130:20-30. [PMID: 33348246 DOI: 10.1016/j.molimm.2020.11.016] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Accepted: 11/17/2020] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel diseases (IBDs) may result from mutations in genes encoding for innate immunity, which can lead to exacerbated inflammatory response. Although some mono-targeted treatments have developed in recent years, IBDs are caused through several pathway perturbations. Therefore, targeting all these pathways is difficult to be achieved by a single agent. Moreover, those mono-targeted therapies are usually expensive and may cause side-effects. These limitations highlight the significance of an available, inexpensive and multi-targeted dietary agents or natural compounds for the treatment and prevention of IBDs. Curcumin is a multifunctional phenolic compound that is known for its anti-inflammatory and immunomodulatory properties. Over the past decades, mounting experimental investigations have revealed the therapeutic potential of curcumin against a broad spectrum of inflammatory diseases including IBDs. Furthermore, it has been reported that curcumin directly interacts with many signaling mediators implicated in the pathogenesis of IBDs. These preclinical findings have created a solid basis for the assessment of the efficacy of curcumin in clinical practice. In clinical trials, different dosages e.g., 550 mg /three times daily-1month, and 1 g /twice times daily-6month of curcumin were used for patients with IBDs. Taken together, these findings indicated that curcumin could be employed as a therapeutic candidate in the treatment of IBDs. Moreover, it seems that overcome to current limitations of curcumin i.e., poor oral bioavailability, and poor oral absorption with using nanotechnology and others, could improve the efficacy of curcumin both in pre-clinical and clinical studies.
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Affiliation(s)
- Farzaneh Fallahi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Sarina Borran
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Milad Ashrafizadeh
- Faculty of Engineering and Natural Sciences, Sabanci University, Orta Mahalle, Istanbul, Turkey
| | - Ali Zarrabi
- Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, 34956, Istanbul, Turkey
| | | | - Mahmood Khaksary Mahabady
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Amirhossein Sahebkar
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
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Alikiaii B, Bagherniya M, Askari G, Sathyapalan T, Sahebkar A. Evaluation of the effect of curcumin on pneumonia: A systematic review of preclinical studies. Phytother Res 2020; 35:1939-1952. [PMID: 33155336 DOI: 10.1002/ptr.6939] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 08/28/2020] [Accepted: 10/18/2020] [Indexed: 12/12/2022]
Abstract
Pneumonia is a major cause of morbidity and mortality worldwide and causes a significant burden on the healthcare systems. Curcumin is a natural phytochemical with anti-inflammatory and anti-neoplastic characteristics. The aim of this study was to conduct a systematic review of published studies on the effect of curcumin on preclinical models of pneumonia. A comprehensive search was conducted in PubMed/Medline, Scopus, Web of Science and Google Scholar from inception up to March 1, 2020 to recognize experimental or clinical trials assessing the effects of curcumin on pneumonia. We identified 17 primary citations that evaluated the effects of curcumin on pneumonia. Ten (58.8%) studies evaluated the effect of curcumin on mouse models of pneumonia, generated by intranasal inoculation of viruses or bacteria. Seven (41.2%) studies evaluated the inhibitory effects of curcumin on the pneumonia-inducing bacteria. Our results demonstrated that curcumin ameliorated the pneumonia-induced lung injury, mainly through a reduction of the activity and infiltration of neutrophils and the inhibition of inflammatory response in mouse models. Curcumin ameliorates the severity of pneumonia through a reduction in neutrophil infiltration and by amelioration of the exaggerated immune response in preclinical pneumonia models.
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Affiliation(s)
- Babak Alikiaii
- Department of Anesthesiology and Critical Care, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Bagherniya
- Food Security Research Center, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Gholamreza Askari
- Food Security Research Center, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Thozhukat Sathyapalan
- Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull, UK
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland.,Halal Research Center of IRI, FDA, Tehran, Iran
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25
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Gupta T, Singh J, Kaur S, Sandhu S, Singh G, Kaur IP. Enhancing Bioavailability and Stability of Curcumin Using Solid Lipid Nanoparticles (CLEN): A Covenant for Its Effectiveness. Front Bioeng Biotechnol 2020; 8:879. [PMID: 33178666 PMCID: PMC7593682 DOI: 10.3389/fbioe.2020.00879] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 07/09/2020] [Indexed: 12/17/2022] Open
Abstract
Curcumin, very rightly referred to as "a wonder drug" is proven to be efficacious in a variety of inflammatory disorders including cancers. Antiaging, anti-inflammatory, antioxidant, antitumor, chemosensitizing, P-gp efflux inhibiting, and antiproliferative activity are some of the striking features of curcumin, highlighting its importance in chemotherapy. Curcumin inhibits Bcl-2, Bcl-XL, VEGF, c-Myc, ICAM-1, EGFR, STAT3 phosphorylation, and cyclin D1 genes involved in the various stages of breast, prostate, and gastric cancer proliferation, angiogenesis, invasion, and metastasis. The full therapeutic potential of curcumin however remains under explored mainly due to poor absorption, rapid metabolism and systemic elimination culminating in its poor bioavailability. Furthermore, curcumin is insoluble, unstable at various pH and is also prone to undergo photodegradation. Nanotechnology can help improve the therapeutic potential of drug molecules with compromised biopharmaceutical profiles. Solid lipid nanoparticles (SLNs) are the latest offshoot of nanomedicine with proven advantages of high drug payload, longer shelf life, biocompatibility and biodegradability, and industrial amenability of the production process. We successfully developed CLEN (Curcumin encapsulated lipidic nanoconstructs) containing 15 mg curcumin per ml of the SLN dispersion with highest (till date, to our knowledge) increase in solubility of curcumin in an aqueous system by 1.4 × 106 times as compared to its intrinsic solubility of 11 ng/ml and high drug loading (15% w/v with respect to lipid matrix). Zero-order release kinetics observed for CLEN versus first order release for free curcumin establish controlled release nature of the developed CLEN. It showed 69.78 times higher oral bioavailability with respect to free curcumin; 9.00 times higher than a bioavailable marketed formulation (CurcuWIN®). The formulation showed 104, 13.3, and 10-times enhanced stability at pH 6.8, 1.2, and 7.4, respectively. All these factors ensure the efficacy of CLEN in treating cancer and other inflammatory diseases.
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Affiliation(s)
| | | | | | | | | | - Indu Pal Kaur
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
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Nakagawa Y, Mukai S, Yamada S, Murata S, Yabumoto H, Maeda T, Akamatsu S. The Efficacy and Safety of Highly-Bioavailable Curcumin for Treating Knee Osteoarthritis: A 6-Month Open-Labeled Prospective Study. CLINICAL MEDICINE INSIGHTS-ARTHRITIS AND MUSCULOSKELETAL DISORDERS 2020; 13:1179544120948471. [PMID: 32848491 PMCID: PMC7425263 DOI: 10.1177/1179544120948471] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 06/24/2020] [Indexed: 11/16/2022]
Abstract
Background We previously developed a surface-controlled water-dispersible form of curcumin that we called Theracurmin®. The area under the blood concentration-time curve (AUC) of Theracurmin in humans was 27-fold higher than that of curcumin powder. Previously, we reported on the anti-inflammatory effects of Theracurmin for knee osteoarthritis. Hypothesis/Purpose We determined the clinical effects of orally administered Theracurmin in patients with knee osteoarthritis over a 6-month period. Study Design Open prospective study. Methods Fifty patients Kellgren-Lawrence grade II, III, or IV knee osteoarthritis who were above 40 years old were enrolled in this clinical study. Theracurmin containing 180 mg/day of curcumin was administered orally every day for 6 months. To monitor for adverse events, blood biochemistry analyses were performed before and after 6 months of each intervention. The patients' knee symptoms were evaluated at 0, 1, 2, 3, 4, 5, and 6 months based on the Japanese Knee Osteoarthritis Measure, the knee pain visual analog scale, and the knee scoring system of the Japanese Orthopedic Association. Results Five cases dropped out during the study, but no cases dropped out because of major problems. No major side effects were observed with Theracurmin treatment, including the blood biochemistry analysis results. The effective group included 34 cases (75.6%), while the not-effective group included 11 cases. Conclusion This study demonstrates the safety and good efficacy of Theracurmin for various types of knee osteoarthritis. Theracurmin shows great potential for the treatment of human knee osteoarthritis.
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Affiliation(s)
- Yasuaki Nakagawa
- Department of Orthopedic Surgery, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan
| | - Shogo Mukai
- Department of Orthopedic Surgery, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan
| | - Shigeru Yamada
- Department of Orthopedic Surgery, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan
| | - Satoru Murata
- Department of Orthopedic Surgery, Goshohigashi Clinic, Kyoto, Japan
| | - Hiromitsu Yabumoto
- Department of Orthopedic Surgery, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan
| | - Takahiro Maeda
- Department of Orthopedic Surgery, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan
| | - Shota Akamatsu
- Department of Orthopedic Surgery, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan
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Jiang T, Liao W, Charcosset C. Recent advances in encapsulation of curcumin in nanoemulsions: A review of encapsulation technologies, bioaccessibility and applications. Food Res Int 2020; 132:109035. [PMID: 32331634 DOI: 10.1016/j.foodres.2020.109035] [Citation(s) in RCA: 147] [Impact Index Per Article: 29.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 01/22/2020] [Accepted: 01/25/2020] [Indexed: 12/27/2022]
Abstract
Curcumin is widely acknowledged for its beneficial activities. However, its application has remained challenging due to its low aqueous solubility, biochemical/structural degradation and poor bioavailability. For these reasons, many researches are aimed at overcoming these limitations using lipid-based nanosystems to encapsulate curcumin, especially nanoemulsions. This review highlights the theoretical aspects and recent advances of preparation technologies (phase inversion temperature, phase inversion composition, ultrasonication, high pressure homogenization and microfluidization) for encapsulation of curcumin in nanoemulsions. Additionally, the specific factors in designing nanoemulsions systems that affect the chemical stability and in vitro bioaccessibility of the encapsulated curcumin are discussed. Also, the importance of nanoemulsions in improving antioxidant, anti-inflammatory and anticancer activities of curcumin is underlined. Curcumin-loaded nanoemulsions preparation technologies have been proposed to provide efficient, systematic, and practical protocols for improved applications of curcumin. Additionally, key factors that influence curcumin delivery include the nature of emulsifier, the type and the amount of carrier oil and emulsifier-curcumin interactions. The pharmacological activities of curcumin including antioxidant, anti-inflammatory and anticancer activities can be improved by nanoemulsions.
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Affiliation(s)
- Tian Jiang
- Univ Lyon, Université Claude Bernard Lyon 1, CNRS, LAGEPP UMR 5007, 43 boulevard du 11 novembre 1918, F-69100 Villeurbanne, France
| | - Wei Liao
- Univ Lyon, Université Claude Bernard Lyon 1, CNRS, LAGEPP UMR 5007, 43 boulevard du 11 novembre 1918, F-69100 Villeurbanne, France
| | - Catherine Charcosset
- Univ Lyon, Université Claude Bernard Lyon 1, CNRS, LAGEPP UMR 5007, 43 boulevard du 11 novembre 1918, F-69100 Villeurbanne, France.
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Karthikeyan A, Senthil N, Min T. Nanocurcumin: A Promising Candidate for Therapeutic Applications. Front Pharmacol 2020; 11:487. [PMID: 32425772 PMCID: PMC7206872 DOI: 10.3389/fphar.2020.00487] [Citation(s) in RCA: 188] [Impact Index Per Article: 37.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2020] [Accepted: 03/27/2020] [Indexed: 12/12/2022] Open
Abstract
Curcuma longa is an important medicinal plant and a spice in Asia. Curcumin (diferuloylmethane) is a hydrophobic bioactive ingredient found in a rhizome of the C. longa. It has drawn immense attention in recent years for its variety of biological and pharmacological action. However, its low water solubility, poor bioavailability, and rapid metabolism represent major drawbacks for its successful therapeutic applications. Hence, researchers have attempted to enhance the biological and pharmacological activity of curcumin and overcome its drawbacks by efficient delivery systems, particularly nanoencapsulation. Research efforts so far and data from the available literature have shown a satisfactory potential of nanorange formulations of curcumin (Nanocurcumin), it increases all the biological and pharmacological benefits of curcumin, which was not significantly possible earlier. For the synthesis of nanocurcumin, an array of techniques has been developed and each technique has its own advantages and individual characteristics. The two most popular and effective techniques are ionic gelation and antisolvent precipitation. So far, many curcumin nanoformulations have been developed to enhance curcumin delivery, thereby overcoming the low therapeutic effects. However, most of the nanoformulation of curcumin remained at the concept level evidence, thus, several questions and challenges still exist to recommend the nanocurcumin as a promising candidate for therapeutic applications. In this review, we discuss the different curcumin nanoformulation and nanocurcumin implications for different therapeutic applications as well as the status of ongoing clinical trials and patents. We also discuss the research gap and future research directions needed to propose curcumin as a promising therapeutic candidate.
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Affiliation(s)
- Adhimoolam Karthikeyan
- Subtropical Horticulture Research Institute, Jeju National University, Jeju, South Korea
| | - Natesan Senthil
- Department of Plant Molecular Biology and Bioinformatics, Center for Plant Molecular Biology and Biotechnology, Tamil Nadu Agricultural University, Coimbatore, India
| | - Taesun Min
- Faculty of Biotechnology, College of Applied Life Science, Sustainable Agriculture Research Institute (SARI) and Jeju International Animal Research Center (JIA), Jeju National University, Jeju, South Korea
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29
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Rathaur P, SR KJ. Metabolism and Pharmacokinetics of Phytochemicals in the Human Body. Curr Drug Metab 2020; 20:1085-1102. [DOI: 10.2174/1389200221666200103090757] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 08/27/2019] [Accepted: 11/14/2019] [Indexed: 12/12/2022]
Abstract
Background:Phytochemicals are obtained from various plants and used for the treatment of diseases as both traditional and modern medicines. Poor bioavailability of phytochemicals is a major concern in applying phytochemicals as a therapeutic agent. It is, therefore, necessary to understand the metabolism and pharmacokinetics of phytochemicals for its implication as a therapeutic agent.Methods:Articles on the metabolism of phytochemicals from the PubMed database. The articles were classified into the digestion, absorption, metabolism, excretion, toxicity, and bioavailability of phytochemicals and the effect of gut microbiota on the metabolism of phytochemicals.Results:The metabolism of each phytochemical is largely dependent on the individual's digestive ability, membrane transporters, metabolizing enzymes and gut microbiota. Further, the form of the phytochemical and genetic make-up of the individual greatly influences the metabolism of phytochemicals.Conclusion:The metabolism of phytochemicals is mostly depended on the form of phytochemicals and individualspecific variations in the metabolism of phytochemicals. Understanding the metabolism and pharmacokinetics of phytochemicals might help in applying plant-based medicines for the treatment of various diseases.
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Affiliation(s)
- Pooja Rathaur
- Department of Life Science, School of Sciences, Gujarat University, Ahmedabad, India
| | - Kaid Johar SR
- Department of Zoology, Biomedical Technology and Human Genetics, School of Sciences, Gujarat University, Ahmedabad, India
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Nouri-Vaskeh M, Afshan H, Malek Mahdavi A, Alizadeh L, Fan X, Zarei M. Curcumin ameliorates health-related quality of life in patients with liver cirrhosis: A randomized, double-blind placebo-controlled trial. Complement Ther Med 2020; 49:102351. [PMID: 32147077 DOI: 10.1016/j.ctim.2020.102351] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Revised: 02/16/2020] [Accepted: 02/18/2020] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVES Current study aimed to find the effects of curcumin on quality of life (QoL) in liver cirrhotic patients. DESIGN In this randomized double-masked placebo-controlled trial, 70 cases with liver cirrhosis aged 20-70 years were randomly divided into two groups to receive 1000 mg/day curcumin (n = 35) or placebo (n = 35) for 12 weeks. The health-related QoL (HRQoL) was assessed by CLDQ, LDSI 2.0, and SF-36. RESULTS Fifty-eight patients (28 in curcumin and 30 in placebo groups) finished the research. Compared with baseline, overall scores as well as most of CLDQ domains (e.g. Fatigue, Emotional Function, Worry, Abdominal Symptoms, and Systemic Symptoms) and the Physical and Mental health (Total) scores and most of SF-36 domains (e.g. Physical Functioning, Bodily Pain, Vitality, Social Functioning, and Mental Health) increased considerably (P < 0.05) after curcumin administration. Furthermore, curcumin reduced most of LDSI 2.0 domains (e.g. Itch, Joint pain, Pain in the right upper abdomen, Sleeping during the day, Decreased appetite, Depression, Fear of complication, Jaundice, Hindrance in Financial Affairs, Change in use of time, Decreased sexual interest, and Decreased sexual activity) significantly (P < 0.05). Significant differences were noticed between two groups in CLDQ domains and overall scores, LDSI 2.0 domains and overall scores, SF-36 Physical and Mental health (total) scores and all its domains scores (P < 0.05), adjusting for baseline values and disease duration. CONCLUSIONS Curcumin improved QoL in liver cirrhotic patients according to CLDQ, LDSI 2.0, and SF-36 domains. Additional studies are warranted to consider curcumin as a safe, accessible, and low-cost complementary therapeutic option in cirrhosis.
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Affiliation(s)
- Masoud Nouri-Vaskeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Afshan
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Aida Malek Mahdavi
- Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Leila Alizadeh
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Xiude Fan
- Department of Infectious Diseases, The First Affiliated Hospital of Xi 'an Jiaotong University, Xi'an, 710061 China; Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, 44195, USA
| | - Mohammad Zarei
- Departrment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA; Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, USA
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Hatab HM, Abdel Hamid FF, Soliman AF, Al-Shafie TA, Ismail YM, El-Houseini ME. A combined treatment of curcumin, piperine, and taurine alters the circulating levels of IL-10 and miR-21 in hepatocellular carcinoma patients: a pilot study. J Gastrointest Oncol 2019; 10:766-776. [PMID: 31392057 PMCID: PMC6657326 DOI: 10.21037/jgo.2019.03.07] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Accepted: 03/14/2019] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Investigating and evaluating possible alternative therapeutic strategies to control hepatocellular carcinoma (HCC) is a critical need because of its high prevalence and being one of the most lethal cancers. Curcumin and taurine showed potent anti-tumor activities in pre-clinical and clinical studies by targeting multiple pathways. Thus, this study was designed to assess the effect of a combined treatment consisted of curcumin, piperine, and taurine on circulating levels of interleukin-10 (IL-10), and microRNAs miR-141 and miR-21. METHODS Twenty eligible HCC patients administrated an oral dose of 4 g curcumin, 40 mg piperine, and 500 mg taurine daily for three successive treatment cycles, each was a 30-day. The level of IL-10 along with the expression levels of miR-141, and miR-21 were monitored in serum before starting the treatment and after each cycle. Patients were followed-up for a period of 24 months. RESULTS The combined treatment was able to produce a significant decrease in the levels of serum IL-10, and miR-21 while it resulted in a non-significant up-regulation of serum miR-141 expression level. At the end of the follow-up period, the median overall survival (OS) rate was found to be 17.00 months with a worse OS in patients with high baseline levels of circulating IL-10 and miR-21 compared to those with low levels. In contrast, a low baseline level of circulating miR-141 was associated with poor prognosis. CONCLUSIONS The combined treatment may be able to increase the OS rate by altering the circulating level of IL-10 and miR-21.
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Affiliation(s)
- Hala M. Hatab
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | | | - Ahmed F. Soliman
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Tamer A. Al-Shafie
- Pharmacology and Therapeutics Department, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Alexandria, Egypt
| | - Yahia M. Ismail
- Medical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Motawa E. El-Houseini
- Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt
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Abou El Dahab MM, Shahat SM, Mahmoud SSM, Mahana NA. In vitro effect of curcumin on Schistosoma species viability, tegument ultrastructure and egg hatchability. Exp Parasitol 2019; 199:1-8. [PMID: 30790572 DOI: 10.1016/j.exppara.2019.02.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2018] [Revised: 01/01/2019] [Accepted: 02/16/2019] [Indexed: 12/12/2022]
Abstract
Schistosomiasis remains a severe problem of public health in developing countries. The development of resistance to praziquantel (PZQ) has justified the search for new alternative chemotherapies with new formulations, more effective, and without adverse effects. Curcumin (CUR), the major phenolic compound present in rhizome of turmeric (Curcuma longa L.), has been traditionally used against various diseases including parasitic infections. Here, the antischistosomal activity of CUR (50-500 μM), evaluated in parallel against S. mansoni and S. haematobium adult worms, appeared significant (P < 0.05 to < 0.0001) in a time- and dose-dependent manner. Two h incubation with CUR (500 μM) caused 100% irreversible killing of both schistosomal species. CUR (250 μM) caused the death of S. haematobium and S. mansoni worms after 2 h and 4 h, respectively. As CUR concentration decreases (50 μM), all coupled adult worms were separated into individual male and female but the worms remained viable up to 4 h. Scanning and transmission electron microscopy revealed that S. haematobium are more sensitive than S. mansoni to CUR schistosomicidal effects. In support, CUR was found to affect the antigenicity of surface membrane molecules of S. haematobium, but not S. mansoni. Of importance, CUR significantly (P < 0.05 to < 0.0001) affected S. mansoni eggs hatchability and viability, a ground for its use in chemotherapy of schistosomiasis mansoni and japonicum because of its increased bioavailability in the gastrointestinal tract. The data together emphasize that CUR is a promising potential schistosomicidal drug.
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MESH Headings
- Animals
- Antigens, Helminth/immunology
- Antigens, Helminth/isolation & purification
- Antigens, Surface/immunology
- Antigens, Surface/isolation & purification
- Cricetinae
- Curcumin/pharmacology
- Dose-Response Relationship, Drug
- Enzyme-Linked Immunosorbent Assay
- Female
- Intestine, Small/parasitology
- Liver/parasitology
- Male
- Mesocricetus
- Mice
- Mice, Inbred BALB C
- Microscopy, Electron, Scanning
- Microscopy, Electron, Transmission
- Ovum/drug effects
- Ovum/physiology
- Schistosoma haematobium/drug effects
- Schistosoma haematobium/immunology
- Schistosoma haematobium/physiology
- Schistosoma haematobium/ultrastructure
- Schistosoma mansoni/drug effects
- Schistosoma mansoni/immunology
- Schistosoma mansoni/physiology
- Schistosoma mansoni/ultrastructure
- Schistosomicides/pharmacology
- Time Factors
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Affiliation(s)
- Marwa M Abou El Dahab
- Zoology Department, Faculty of Science, Cairo University, Giza, 12613, Egypt; Zoology Department, Faculty of Science, Ain Shams University, Cairo, 11566, Egypt
| | - Sondos M Shahat
- Zoology Department, Faculty of Science, Cairo University, Giza, 12613, Egypt
| | | | - Noha A Mahana
- Zoology Department, Faculty of Science, Cairo University, Giza, 12613, Egypt.
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Di Ciaula A, Portincasa P, Maes N, Albert A. Efficacy of bio-optimized extracts of turmeric and essential fennel oil on the quality of life in patients with irritable bowel syndrome. Ann Gastroenterol 2018; 31:685-691. [PMID: 30386118 PMCID: PMC6191874 DOI: 10.20524/aog.2018.0304] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2018] [Accepted: 07/16/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The use of herbal products to treat irritable bowel syndrome (IBS), a disease that frequently affects the quality of life (QoL), is still under evaluation. This open pilot study assessed the efficacy of bio-optimized extracts of turmeric and essential fennel oil (Enterofytol®) in IBS patients. METHODS A total of 211 patients (14% diarrhea-predominant, IBS-D; 24% constipation-predominant, IBS-C; 62% mixed, IBS-M) were enrolled by general practitioners and completed questionnaires measuring symptom severity and QoL before and after Enterofytol®, two capsules b.i.d. for one month, followed by two capsules q.d. for another month. RESULTS IBS severity index and QoL were inversely related. A significant reduction in the severity index and an improvement in QoL were evident following treatment in all IBS subgroups. IBS-D patients showed the worst clinical picture at entry, with the highest IBS severity index and the lowest QoL score, compared with IBS-C and IBS-M subtypes. IBS-D patients, however, also showed the most pronounced response to therapy, considering both scores. The improvement in the IBS severity index was independent of age and sex. CONCLUSIONS Results from this "real-life" study show that the combination of turmeric and essential fennel oil over two months improves both symptoms and QoL in IBS patients, irrespectively of age, sex, initial severity of symptoms and IBS-subtypes, suggesting a potential role for the natural treatment of IBS.
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Affiliation(s)
- Agostino Di Ciaula
- Division of Internal Medicine, Hospital of Bisceglie, ASL-BAT, Italy (Agostino Di Ciaula)
| | - Piero Portincasa
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, Bari, Italy (Piero Portincasa)
| | - Nathalie Maes
- Biostatistics, University Hospital of Liège, Belgium (Nathalie Maes, Adelin Albert)
| | - Adelin Albert
- Biostatistics, University Hospital of Liège, Belgium (Nathalie Maes, Adelin Albert)
- Department of Public Health, University of Liège, Belgium (Adelin Albert)
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Mazieiro R, Frizon RR, Barbalho SM, Goulart RDA. Is Curcumin a Possibility to Treat Inflammatory Bowel Diseases? J Med Food 2018; 21:1077-1085. [PMID: 29957091 DOI: 10.1089/jmf.2017.0146] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
The inflammatory bowel diseases (IBDs) are mainly represented by Crohn's disease and Ulcerative colitis that are characterized by chronic and relapsing inflammatory processes of the gastrointestinal system. Curcuma longa L. is a plant with several medicinal properties, including anti-inflammatory effects, and curcumin is the most important compound derived from its rhizomes. As curcumin has remarkable anti-inflammatory actions, the aim of this work is to review the potential use of this compound in IBD patients. We consulted MEDLINE (PubMed/PMC), and the literature search was performed with the following combinations of terms "Inflammatory Bowel Diseases" and "Curcumin," "Crohn's Disease" and "Curcumin," "Ulcerative colitis" and "Curcumin." The inclusion criteria were articles that showed original studies with human models and the exclusion criteria were not full-text articles, articles not in English, poster presentations, letters, editorials, and articles not available. Curcumin interacts with receptors, growth and transcription factors, cytokines, enzymes, and genes leading to inhibitory effects on cyclooxygenase-1, tumor necrosis factor-α, interferon-γ, inducible nitric oxide synthase, transcriptional nuclear factor kappa B, and many other molecules associated with inflammatory processes. These molecules are critical factors in the positive regulation of inflammatory cytokines in inflammatory diseases, suggesting that curcumin may be considered as a new therapeutic agent for patients with IBD. Curcumin is a natural anti-inflammatory agent that represents an attractive, safe and inexpensive alternative for the treatment of IBD. Nevertheless, it is necessary to know the efficient and safe dose and consider its poor absorption.
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Affiliation(s)
- Rafaela Mazieiro
- 1 Department of Biochemistry and Pharmacology, Medical School of Marília, UNIMAR, Marília , São Paulo, Brazil
| | - Renata Reis Frizon
- 1 Department of Biochemistry and Pharmacology, Medical School of Marília, UNIMAR, Marília , São Paulo, Brazil
| | - Sandra Maria Barbalho
- 1 Department of Biochemistry and Pharmacology, Medical School of Marília, UNIMAR, Marília , São Paulo, Brazil .,2 Department of Biochemistry and Nutrition, Food Technology School , Marília, São Paulo, Brazil
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Cunha Neto F, Marton LT, de Marqui SV, Lima TA, Barbalho SM. Curcuminoids from Curcuma Longa: New adjuvants for the treatment of crohn's disease and ulcerative colitis? Crit Rev Food Sci Nutr 2018; 59:2136-2143. [PMID: 29565637 DOI: 10.1080/10408398.2018.1456403] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Crohn's Disease (CD) and Ulcerative Colitis (UC) result from an overreaction of the bowel to multifactorial stimuli leading to discomfort, pain, and it is associated with high morbidity and lethality. The medications commonly used are expensive and associated with multiple side effects. Curcuma longa exerts anti-inflammatory and antioxidant actions and has shown positive effects on CD and UC treatment, possibly due to the presence of curcuminoids. The objective of this review was to evaluate the role of curcuminoids in the treatment of IBD. A search for articles associating curcuminoids and CD and UC was performed using MEDLINE-PubMed. It has been found that curcumin can reduce oxidative stress and inhibit the migration of neutrophils and inducible nitric oxide synthase in the intestine. It may also improve micro and macroscopic lesions, prevent apoptosis of intestinal cells and also induce the restoration of the mitogen-activated protein kinase immune reaction. As the incidence of CD and UC is growing in many populations, there is an urgency to find an appropriate and accessible therapeutic approach to improve quality of life of patients. The use of curcumin is cheap, efficient and associated with no side effects, and may become an alternative to the IBD treatment.
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Affiliation(s)
| | | | | | | | - Sandra Maria Barbalho
- b Medical School of Marília - UNIMAR - Marília , São Paulo.,c Food Technology School , Marília, São Paulo , Brazil
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Ramirez CN, Li W, Zhang C, Wu R, Su S, Wang C, Gao L, Yin R, Kong ANT. Correction to: In Vitro-In Vivo Dose Response of Ursolic Acid, Sulforaphane, PEITC, and Curcumin in Cancer Prevention. AAPS JOURNAL 2018; 20:27. [PMID: 29411155 DOI: 10.1208/s12248-018-0190-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The citation of the author name "Ah-Ng Tony Kong" in PubMed is not the author's preference. Instead of "Kong AT", the author prefers "Kong AN".
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Affiliation(s)
- Christina N Ramirez
- Center for Phytochemicals Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA.,Cellular and Molecular Pharmacology Program, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey, 08854, USA
| | - Wenji Li
- Center for Phytochemicals Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA.,Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
| | - Chengyue Zhang
- Center for Phytochemicals Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA.,Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA.,Graduate Program in Pharmaceutical Sciences, Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
| | - Renyi Wu
- Center for Phytochemicals Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA.,Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
| | - Shan Su
- Center for Phytochemicals Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA.,Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
| | - Chao Wang
- Center for Phytochemicals Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA.,Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
| | - Linbo Gao
- Center for Phytochemicals Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA.,Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
| | - Ran Yin
- Center for Phytochemicals Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA.,Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
| | - Ah-Ng Tony Kong
- Center for Phytochemicals Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA. .,Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA. .,Graduate Program in Pharmaceutical Sciences, Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA. .,Ernest Mario School of Pharmacy, Room 228, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey, 08854, USA.
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Bisdemethoxycurcumin exerts pro-apoptotic effects in human pancreatic adenocarcinoma cells through mitochondrial dysfunction and a GRP78-dependent pathway. Oncotarget 2018; 7:83641-83656. [PMID: 27845899 PMCID: PMC5347794 DOI: 10.18632/oncotarget.13272] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2016] [Accepted: 10/14/2016] [Indexed: 12/27/2022] Open
Abstract
Pancreatic cancer is a highly aggressive malignancy, which is intrinsically resistant to current chemotherapies. Herein, we investigate whether bisdemethoxycurcumin (BDMC), a derivative of curcumin, potentiates gemcitabine in human pancreatic cancer cells. The result suggests that BDMC sensitizes gemcitabine by inducing mitochondrial dysfunctions and apoptosis in PANC-1 and MiaPaCa-2 pancreatic cancer cells. Utilizing two-dimensional gel electrophoresis and mass spectrometry, we identify 13 essential proteins with significantly altered expressions in response to gemcitabine alone or combined with BDMC. Protein-protein interaction network analysis pinpoints glucose-regulated protein 78 (GRP78) as the key hub activated by BDMC. We then reveal that BDMC upregulates GRP78 and facilitates apoptosis through eIF2α/CHOP pathway. Moreover, DJ-1 and prohibitin, two identified markers of chemoresistance, are increased by gemcitabine in PANC-1 cells. This could be meaningfully reversed by BDMC, suggesting that BDMC partially offsets the chemoresistance induced by gemcitabine. In summary, these findings show that BDMC promotes apoptosis through a GRP78-dependent pathway and mitochondrial dysfunctions, and potentiates the antitumor effect of gemcitabine in human pancreatic cancer cells.
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Ramirez CN, Li W, Zhang C, Wu R, Su S, Wang C, Gao L, Yin R, Kong AN. In Vitro-In Vivo Dose Response of Ursolic Acid, Sulforaphane, PEITC, and Curcumin in Cancer Prevention. AAPS J 2017; 20:19. [PMID: 29264822 PMCID: PMC6021020 DOI: 10.1208/s12248-017-0177-2] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Accepted: 11/29/2017] [Indexed: 02/07/2023] Open
Abstract
According to the National Center of Health Statistics, cancer was the culprit of nearly 600,000 deaths in 2016 in the USA. It is by far one of the most heterogeneous diseases to treat. Treatment for metastasized cancers remains a challenge despite modern diagnostics and treatment regimens. For this reason, alternative approaches are needed. Chemoprevention using dietary phytochemicals such as triterpenoids, isothiocyanates, and curcumin in the prevention of initiation and/or progression of cancer poses a promising alternative strategy. However, significant challenges exist in the extrapolation of in vitro cell culture data to in vivo efficacy in animal models and to humans. In this review, the dose at which these phytochemicals elicit a response in vitro and in vivo of a multitude of cellular signaling pathways will be reviewed highlighting Nrf2-mediated antioxidative stress, anti-inflammation, epigenetics, cytoprotection, differentiation, and growth inhibition. The in vitro-in vivo dose response of phytochemicals can vary due, in part, to the cell line/animal model used, the assay system of the biomarker used for the readout, chemical structure of the functional analog of the phytochemical, and the source of compounds used for the treatment study. While the dose response varies across different experimental designs, the chemopreventive efficacy appears to remain and demonstrate the therapeutic potential of triterpenoids, isothiocyanates, and curcumin in cancer prevention and in health in general.
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Affiliation(s)
- Christina N Ramirez
- Center for Phytochemicals Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
- Cellular and Molecular Pharmacology Program, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey, 08854, USA
| | - Wenji Li
- Center for Phytochemicals Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
| | - Chengyue Zhang
- Center for Phytochemicals Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
- Graduate Program in Pharmaceutical Sciences, Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
| | - Renyi Wu
- Center for Phytochemicals Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
| | - Shan Su
- Center for Phytochemicals Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
| | - Chao Wang
- Center for Phytochemicals Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
| | - Linbo Gao
- Center for Phytochemicals Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
| | - Ran Yin
- Center for Phytochemicals Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA
| | - Ah-Ng Kong
- Center for Phytochemicals Epigenome Studies, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA.
- Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA.
- Graduate Program in Pharmaceutical Sciences, Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA.
- Ernest Mario School of Pharmacy, Room 228, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey, 08854, USA.
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Yashin A, Yashin Y, Xia X, Nemzer B. Antioxidant Activity of Spices and Their Impact on Human Health: A Review. Antioxidants (Basel) 2017; 6:E70. [PMID: 28914764 PMCID: PMC5618098 DOI: 10.3390/antiox6030070] [Citation(s) in RCA: 168] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Revised: 08/14/2017] [Accepted: 09/08/2017] [Indexed: 02/07/2023] Open
Abstract
Antioxidants are substances that prevent oxidation of other compounds or neutralize free radicals. Spices and herbs are rich sources of antioxidants. They have been used in food and beverages to enhance flavor, aroma and color. Due to their excellent antioxidant activity, spices and herbs have also been used to treat some diseases. In this review article, the chemical composition and antioxidant activity of spices and culinary herbs are presented. The content of flavonoids and total polyphenols in different spices and herbs are summarized. The applications of spices and their impacts on human health are briefly described. The extraction and analytical methods for determination of antioxidant capacity are concisely reviewed.
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Affiliation(s)
- Alexander Yashin
- International Analytical Center of Zelinsky Institute of Organic Chemistry of Russian, Academy of Science, 119991 Moscow, Russia.
| | - Yakov Yashin
- International Analytical Center of Zelinsky Institute of Organic Chemistry of Russian, Academy of Science, 119991 Moscow, Russia.
| | - Xiaoyan Xia
- Department of Research & Development, VDF FutureCeuticals, Inc., Momence, IL 60954, USA.
| | - Boris Nemzer
- Department of Research & Development, VDF FutureCeuticals, Inc., Momence, IL 60954, USA.
- Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
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40
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Kumar P, Barua CC, Sulakhiya K, Sharma RK. Curcumin Ameliorates Cisplatin-Induced Nephrotoxicity and Potentiates Its Anticancer Activity in SD Rats: Potential Role of Curcumin in Breast Cancer Chemotherapy. Front Pharmacol 2017; 8:132. [PMID: 28420987 PMCID: PMC5378776 DOI: 10.3389/fphar.2017.00132] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2016] [Accepted: 03/02/2017] [Indexed: 12/12/2022] Open
Abstract
Breast malignant neoplastic disease is one of the most complex diseases, as it is a multifactorial disease in which virtually all the targets are instantly or indirectly inter-reliant on each other. Cisplatin (CIS), an inorganic antineoplastic agent is widely utilized in the treatment of various solid tumors including breast cancer. Despite everything, its clinical use is limited, due to ototoxicity, peripheral neuropathy, and nephrotoxicity. The present work was directed to assess the combined result of curcumin (CUR) and CIS in 7, 12-dimethyl benz[a]anthracene (DMBA) induced breast cancer in rats and the prevention of nephrotoxicity induced by the latter. CIS-induced nephrotoxicity was assessed by change in body weight, kidney weight, altered levels of BUN, creatinine, TNF-α, IL-6, IL-8, IL-10, and histopathology of the kidney. Anticancer activity was assessed by measurement of tumor weight, tumor volume, % tumor inhibition, levels of PPAR-γ, and BDNF in mammary tumors and histopathology of mammary tumors. CUR pre-treatment mitigated nephrotoxicity by reducing the inflammatory markers (TNF-α, IL-6, and IL-8; p < 0.001). Further, it reduced mammary cancer via increasing the expression of PPAR-γ (p < 0.001) and decreasing the expression of BDNF (p < 0.001) in mammary tumors. It also reduced tumor volume, further postulating that CUR might adjunct the anticancer activity of the CIS. To the best of our knowledge, this is the first report, which showed that CUR ameliorated CIS-induced nephrotoxicity and improved its anticancer activity in DMBA induced breast cancer in female Sprague-Dawley rats.
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Affiliation(s)
- Parveen Kumar
- Laboratory of Molecular Pharmacology and Toxicology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, GMCHGuwahati, India
| | - Chandana C. Barua
- Department of Pharmacology and Toxicology, College of Veterinary ScienceGuwahati, India
| | - Kunjbihari Sulakhiya
- Laboratory of Molecular Pharmacology and Toxicology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, GMCHGuwahati, India
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Alginate-Based Composite Sponges as Gastroretentive Carriers for Curcumin-Loaded Self-Microemulsifying Drug Delivery Systems. Sci Pharm 2017; 85:scipharm85010011. [PMID: 28294964 PMCID: PMC5388148 DOI: 10.3390/scipharm85010011] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Revised: 03/08/2017] [Accepted: 03/08/2017] [Indexed: 12/01/2022] Open
Abstract
Alginate-based composite sponges were developed as carriers to prolong the gastric retention time and controlled release of curcumin-loaded self-microemulsifying drug delivery systems (Cur-SMEDDS). Liquid Cur-SMEDDS was incorporated into a solution made up of a mixture of polymers and converted into a solid form by freeze-drying. The ratio of alginate as the main polymer, adsorbent (colloidal silicon dioxide), and additional polymers—sodium carboxymethyl cellulose (SCMC), hydroxypropyl methylcellulose (HPMC)—was varied systematically to adjust the drug loading and entrapment efficiency, sponge buoyancy, and the release profile of Cur-SMEDDS. The optimum composite sponge was fabricated from a 4% alginate and 2% HPMC mixed solution. It immediately floated on simulated gastric fluid (SGF, pH 1.2) and remained buoyant over an 8 h period. The formulation exhibited an emulsion droplet size of approximately 30 nm and provided sustained release of Cur-SMEDDS in SGF, reaching 71% within 8 h compared with only 10% release from curcumin powder. This study demonstrates the potential of alginate-based composite sponges combined with self-microemulsifying formulations for gastroretention applications involving poorly soluble compounds.
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Kljun J, Turel I. β-Diketones as Scaffolds for Anticancer Drug Design - From Organic Building Blocks to Natural Products and Metallodrug Components. Eur J Inorg Chem 2017. [DOI: 10.1002/ejic.201601314] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Jakob Kljun
- Faculty of Chemistry and Chemical Technology; University of Ljubljana; Večna pot 113 1000 Ljubljana Slovenia
| | - Iztok Turel
- Faculty of Chemistry and Chemical Technology; University of Ljubljana; Večna pot 113 1000 Ljubljana Slovenia
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Curcumin, mitochondrial biogenesis, and mitophagy: Exploring recent data and indicating future needs. Biotechnol Adv 2016; 34:813-826. [DOI: 10.1016/j.biotechadv.2016.04.004] [Citation(s) in RCA: 69] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Revised: 04/11/2016] [Accepted: 04/28/2016] [Indexed: 11/23/2022]
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Sarkar A, De R, Mukhopadhyay AK. Curcumin as a potential therapeutic candidate for Helicobacter pylori associated diseases. World J Gastroenterol 2016; 22:2736-2748. [PMID: 26973412 PMCID: PMC4777996 DOI: 10.3748/wjg.v22.i9.2736] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Revised: 01/01/2016] [Accepted: 01/18/2016] [Indexed: 02/06/2023] Open
Abstract
Curcumin, a yellow pigment and principal polyphenolic Curcuminoid obtained from the turmeric rhizome Curcuma longa, is commonly used as a food-coloring agent. Studies suggest that curcumin has a wide range of beneficial properties e.g., anti-inflammatory, anti-oxidant, anti-cancer, anti-proliferative, anti-fungal and anti-microbial. These pleiotropic activities prompted several research groups to elucidate the role of curcumin in Helicobacter pylori (H. pylori) infection. This is the first review with this heading where we discussed regarding the role of curcumin as an anti-H. pylori agent along with its potential in other gastrointestinal diseases. Based on several in vitro, early cell culture, animal research and few pre-clinical trials, curcumin projected as a potential therapeutic candidate against H. pylori mediated gastric pathogenesis. This review sheds light on the anti-H. pylori effects of curcumin in different models with meticulous emphasis on its anti-oxidant, anti-inflammatory and anti-carcinogenic effects as well as some critical signaling and effecter molecules. Remarkably, non-toxic molecule curcumin fulfills the characteristics for an ideal chemopreventive agent against H. pylori mediated gastric carcinogenesis but the foremost challenge is to obtain the optimum therapeutic levels of curcumin, due to its low solubility and poor bioavailability. Further, we have discussed about the possibilities for improving its efficacy and bioavailability. Lastly, we concluded with the anticipation that in near future curcumin may be used to develop a therapeutic drug against H. pylori mediated gastric ailments through improved formulation or delivery systems, facilitating its enhanced absorption and cellular uptake.
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Natural Nuclear Factor Kappa Beta Inhibitors: Safe Therapeutic Options for Inflammatory Bowel Disease. Inflamm Bowel Dis 2016; 22:719-23. [PMID: 26717321 DOI: 10.1097/mib.0000000000000655] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Inflammatory bowel disease (IBD) is a chronic and debilitating condition classified as ulcerative colitis and Crohn's disease. IBD usually happens as result of immune dysfunction in the intestinal mucosa resulting in epithelial barrier dysfunction, which leads to exposure of the mucosal immune system to luminal antigenic material. This results in activation of inflammation, which is our bodies natural defense system; however, chronic inflammation leads to barrier dysfunction, which triggers a cycle of inflammation and further barrier dysfunction. This barrier breakdown results in the uncontrolled progression of IBD throughout the intestine. Despite the therapeutic advances made over the last decade, the current first line of treatment of IBD is limited to immunosuppressive and anti-inflammatory drugs, which need to be taken regularly and have significant side effects to the patients. Prolonged inflammation may increase the risk of intestinal malignancy. The role of nuclear factor kappa beta (NF-κβ) has been established in the regulation of innate immunity and inflammation. NF-κβ has also shown to be involved in critical events linking inflammation and cancer development. Recent investigations suggest that the NF-κβ signaling cascade may be the central mediator of gastrointestinal inflammation in IBD and malignancies including esophageal, gastric, and colorectal cancers. In this review, the therapeutic potential of natural NF-κβ inhibitors as safe therapeutic options for the treatment of IBD will be discussed.
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Patial V, S M, Sharma S, Pratap K, Singh D, Padwad YS. Synergistic effect of curcumin and piperine in suppression of DENA-induced hepatocellular carcinoma in rats. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2015; 40:445-452. [PMID: 26278679 DOI: 10.1016/j.etap.2015.07.012] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/23/2015] [Revised: 07/16/2015] [Accepted: 07/18/2015] [Indexed: 06/04/2023]
Abstract
Curcumin has been reported to suppress different types of clinical and experimentally-induced tumors, but due to less absorption and quick metabolism it show poor bioavailability. The present study was envisaged to investigate the possible synergistic effect of combined treatment of curcumin with piperine in suppression of diethylnitrosamine (DENA)-induced hepatocellular carcinoma (HCC) in rats, owing to permeability enhancing effect of latter. HCC was induced by supplying DENA (0.01%) in drinking water for 10 weeks. The rats were treated with curcumin (100mg/kg; p.o.) per se and curcumin along with piperine (20mg/kg; p.o.) for 4 weeks post HCC induction. The combined treatment significantly attenuated the morphological, histopathological, biochemical, apoptotic and proliferative changes in the liver and serum in comparison to curcumin per se and vehicle control group. The results of present study concluded that curcumin in combination with piperine shows better suppression of DENA-induced HCC in contrast to curcumin per se.
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Affiliation(s)
- Vikram Patial
- Regulatory Research Centre, CSIR - Institute of Himalayan Bioresource Technology, Palampur, H.P. 176061, India.
| | - Mahesh S
- Regulatory Research Centre, CSIR - Institute of Himalayan Bioresource Technology, Palampur, H.P. 176061, India
| | - Supriya Sharma
- Regulatory Research Centre, CSIR - Institute of Himalayan Bioresource Technology, Palampur, H.P. 176061, India
| | - Kunal Pratap
- Regulatory Research Centre, CSIR - Institute of Himalayan Bioresource Technology, Palampur, H.P. 176061, India
| | - Damanpreet Singh
- Regulatory Research Centre, CSIR - Institute of Himalayan Bioresource Technology, Palampur, H.P. 176061, India
| | - Yogendra S Padwad
- Regulatory Research Centre, CSIR - Institute of Himalayan Bioresource Technology, Palampur, H.P. 176061, India
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Sangiovanni E, Di Lorenzo C, Colombo E, Colombo F, Fumagalli M, Frigerio G, Restani P, Dell'Agli M. The effect of in vitro gastrointestinal digestion on the anti-inflammatory activity of Vitis vinifera L. leaves. Food Funct 2015; 6:2453-63. [PMID: 26102216 DOI: 10.1039/c5fo00410a] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Botanicals are widely consumed all over the world for health purposes, with increased usage in the general population, in many different types of products, including foods and plant food supplements. Several reports support for the beneficial effects of botanicals against gastrointestinal inflammation. However, no studies regarding the anti-inflammatory activity in the gastrointestinal tract of red vine leaves have been reported so far. The present work investigates the biological activity of Vitis vinifera L. water extract (VVWE) from dried leaves in two in vitro models of gastric and intestinal inflammation. The extract was characterized by a validated HPLC-DAD method, and tested on human epithelial gastric (AGS) and intestinal (Caco-2) cells with the aim to investigate the inhibitory effect on IL-8 secretion and promoter activity, before and after in vitro gastric or gastrointestinal digestion. Our results show that the water extract from red vine leaves inhibits TNFα-induced IL-8 secretion and expression in human gastric epithelial cells; the effect should be maintained, although to a lesser extent, after gastric digestion. In contrast, the effect after intestinal digestion is dramatically decreased since degradation of the active components in the gut does not allow the extract to efficiently counteract TNFα or IL-1β induced IL-8 expression and the NF-κB pathway. The main molecular target of VVWE at the gastric level includes TNFα-induced activation of NF-κB and occurs at concentrations easily reachable after PFS consumption based on red vine leaf water extract as the ingredient. Our findings suggest that PFS containing water extracts from Vitis vinifera L. leaves could be useful to inhibit/attenuate gastric inflammation inhibiting IL-8 secretion and expression through impairment of the NF-κB pathway.
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Affiliation(s)
- E Sangiovanni
- Dipartimento di Scienze Farmacologiche e Biomolecolari; Università degli Studi di Milano, Via Balzaretti, 9, 20133, Milano, Italy.
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Moorthi C, Krishnan K, Manavalan R, Kathiresan K. Preparation and characterization of curcumin-piperine dual drug loaded nanoparticles. Asian Pac J Trop Biomed 2015; 2:841-8. [PMID: 23569859 DOI: 10.1016/s2221-1691(12)60241-x] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2012] [Revised: 08/29/2012] [Accepted: 11/28/2012] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE To prepare curcumin-piperine (Cu-Pi) nanoparticles by various methods and to study the effect of various manufacturing parameters on Cu-Pi nanoparticles and to identify a suitable method for the preparation of Cu-Pi nanoparticles to overcome oral bioavailability and cancer cell targeting limitations in the treatment of cancer. METHODS Cu-Pi nanoparticles were prepared by thin film hydration method, solid dispersion method, emulsion polymerization method and Fessi method. Optimization was carried out to study the effect of various manufacturing parameter on the Cu-Pi nanoparticles. RESULTS Out of four methods, Fessi method produced a minimum average particle size of 85.43 nm with a polydispersity index of 0.183 and zeta potential of 29.7 mV. Change of organic solvent (acetone or ethanol) did not have any significant effect on Cu-Pi nanoparticles. However, increase in sonication time, stirring speed, viscosity, use of 1:10:10 ratio of drug/polymer/surfactant, and use of anionic surfactant or combination of anionic surfactant with cationic polymer or combination of non-ionic surfactant with cationic polymer had a significant effect on Cu-Pi nanoparticles. CONCLUSIONS Cu-Pi nanoparticles coated with PEG containing copolymer produced by Fessi method had a minimum average particle size, excellent polydispersity index and optimal zeta potential which fall within the acceptable limits of the study. This dual nanoparticulate drug delivery system appears to be promising to overcome oral bioavailability and cancer cell targeting limitations in the treatment of cancer.
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Affiliation(s)
- C Moorthi
- Department of Pharmacy, Annamalai University, Annamalai Nagar, Chidambaram, Tamil Nadu, India
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Curcumin and inflammatory bowel disease: potential and limits of innovative treatments. Molecules 2014; 19:21127-53. [PMID: 25521115 PMCID: PMC6271352 DOI: 10.3390/molecules191221127] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2014] [Revised: 12/08/2014] [Accepted: 12/09/2014] [Indexed: 02/08/2023] Open
Abstract
Curcumin belongs to the family of natural compounds collectively called curcuminoids and it possesses remarkable beneficial anti-oxidant, anti-inflammatory, anti-cancer, and neuroprotective properties. Moreover it is commonly assumed that curcumin has also been suggested as a remedy for digestive diseases such as inflammatory bowel diseases (IBD), a chronic immune disorder affecting the gastrointestinal tract and that can be divided in two major subgroups: Crohn’s disease (CD) and Ulcerative Colitis (UC), depending mainly on the intestine tract affected by the inflammatory events. The chronic and intermittent nature of IBD imposes, where applicable, long-term treatments conducted in most of the cases combining different types of drugs. In more severe cases and where there has been no good response to the drugs, a surgery therapy is carried out. Currently, IBD-pharmacological treatments are generally not curative and often present serious side effects; for this reason, being known the relationship between nutrition and IBD, it is worthy of interesting the study and the development of new dietary strategy. The curcumin principal mechanism is the suppression of IBD inflammatory compounds (NF-κB) modulating immune response. This review summarizes literature data of curcumin as anti-inflammatory and anti-oxidant in IBD, trying to understand the different effects in CD e UC.
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Verma S, Kesh K, Ganguly N, Jana S, Swarnakar S. Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants. World J Biol Chem 2014; 5:355-376. [PMID: 25225603 PMCID: PMC4160529 DOI: 10.4331/wjbc.v5.i3.355] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2014] [Revised: 05/07/2014] [Accepted: 06/11/2014] [Indexed: 02/05/2023] Open
Abstract
The process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases (MMPs). Degradation of extracellular matrix (ECM) proteins like collagen, proteoglycan, laminin, elastin and fibronectin is considered to be the prerequisite for tumor invasion and metastasis. MMPs can degrade essentially all of the ECM components and, most MMPs also substantially contribute to angiogenesis, differentiation, proliferation and apoptosis. Hence, MMPs are important regulators of tumor growth both at the primary site and in distant metastases; thus the enzymes are considered as important targets for cancer therapy. The implications of MMPs in cancers are no longer mysterious; however, the mechanism of action is yet to be explained. Herein, our major interest is to clarify how MMPs are tied up with gastrointestinal cancers. Gastrointestinal cancer is a variety of cancer types, including the cancers of gastrointestinal tract and organs, i.e., esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The activity of MMPs is regulated by its endogenous inhibitor tissue inhibitor of metalloproteinase (TIMP) which bind MMPs with a 1:1 stoichiometry. In addition, RECK (reversion including cysteine-rich protein with kazal motifs) is a membrane bound glycoprotein that inhibits MMP-2, -9 and -14. Moreover, α2-macroglobulin mediates the uptake of several MMPs thereby inhibit their activity. Cancerous conditions increase intrinsic reactive oxygen species (ROS) through mitochondrial dysfunction leading to altered protease/anti-protease balance. ROS, an index of oxidative stress is also involved in tumorigenesis by activation of different MAP kinase pathways including MMP induction. Oxidative stress is involved in cancer by changing the activity and expression of regulatory proteins especially MMPs. Epidemiological studies have shown that high intake of fruits that rich in antioxidants is associated with a lower cancer incidence. Evidence indicates that some antioxidants inhibit the growth of malignant cells by inducing apoptosis and inhibiting the activity of MMPs. This review is discussed in six subchapters, as follows.
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