Molecules

31 pages, 1120 KiB

Open AccessReview

Curcumin, Inflammation, and Chronic Diseases: How Are They Linked?

by Yan He^1,†, Yuan Yue^1,†, Xi Zheng^1,2, Kun Zhang¹, Shaohua Chen³ and Zhiyun Du^1,*

¹ Institute of Natural Medicine & Green Chemistry, School of Chemical Engineering and Light Industry, Guandong University of Technology, 232 Wai Huan West Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, China

² Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA

³ Department of Otorhinolaryngology, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510030, China

^† These authors contributed equally to this work.

Molecules 2015, 20(5), 9183-9213; https://doi.org/10.3390/molecules20059183 - 20 May 2015

Cited by 480 | Viewed by 72433

Abstract

It is extensively verified that continued oxidative stress and oxidative damage may lead to chronic inflammation, which in turn can mediate most chronic diseases including cancer, diabetes, cardiovascular, neurological, inflammatory bowel disease and pulmonary diseases. Curcumin, a yellow coloring agent extracted from turmeric, [...] Read more.

It is extensively verified that continued oxidative stress and oxidative damage may lead to chronic inflammation, which in turn can mediate most chronic diseases including cancer, diabetes, cardiovascular, neurological, inflammatory bowel disease and pulmonary diseases. Curcumin, a yellow coloring agent extracted from turmeric, shows strong anti-oxidative and anti-inflammatory activities when used as a remedy for the prevention and treatment of chronic diseases. How oxidative stress activates inflammatory pathways leading to the progression of chronic diseases is the focus of this review. Thus, research to date suggests that chronic inflammation, oxidative stress, and most chronic diseases are closely linked, and the antioxidant properties of curcumin can play a key role in the prevention and treatment of chronic inflammation diseases. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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7 pages, 681 KiB

Open AccessReview

Curcumin and Omega-3 Fatty Acids Enhance NK Cell-Induced Apoptosis of Pancreatic Cancer Cells but Curcumin Inhibits Interferon-γ Production: Benefits of Omega-3 with Curcumin against Cancer

by Milan Fiala

Department of Surgery, School of Medicine, University of California, Los Angeles, CA 90095, USA

Molecules 2015, 20(2), 3020-3026; https://doi.org/10.3390/molecules20023020 - 12 Feb 2015

Cited by 53 | Viewed by 15862

Abstract

STAT-3 and STAT-1 signaling have opposite effects in oncogenesis with STAT-3 acting as an oncogene and STAT-1 exerting anti-oncogenic activities through interferon-γ and interferon-α. The cytokine IL-6 promotes oncogenesis by stimulation of NFκB and STAT-3 signaling. Curcuminoids have bi-functional effects by blocking NFκB [...] Read more.

STAT-3 and STAT-1 signaling have opposite effects in oncogenesis with STAT-3 acting as an oncogene and STAT-1 exerting anti-oncogenic activities through interferon-γ and interferon-α. The cytokine IL-6 promotes oncogenesis by stimulation of NFκB and STAT-3 signaling. Curcuminoids have bi-functional effects by blocking NFκB anti-apoptotic signaling but also blocking anti-oncogenic STAT-1 signaling and interferon-γ production. In our recent study (unpublished work [1]) in pancreatic cancer cell cultures, curcuminoids enhanced cancer cell apoptosis both directly and by potentiating natural killer (NK) cell cytotoxic function. The cytotoxic effects of curcuminoids were increased by incubation of cancer cells and NK cells in an emulsion with omega-3 fatty acids and antioxidants (Smartfish), which enhanced cancer cell apoptosis and protected NK cells against degradation. However, as also shown by others, curcuminoids blocked interferon-γ production by NK cells. The combined use of curcuminoids and omega-3 in cancer immunotherapy will require deeper understanding of their in vivo interactions with the immune system. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

42 pages, 3236 KiB

Open AccessReview

The Multifaceted Role of Curcumin in Cancer Prevention and Treatment

by Muthu K. Shanmugam¹, Grishma Rane^1,2, Madhu Mathi Kanchi², Frank Arfuso³, Arunachalam Chinnathambi⁴, M. E. Zayed⁴, Sulaiman Ali Alharbi⁴, Benny K. H. Tan¹, Alan Prem Kumar^1,2,3,5,*

and Gautam Sethi^1,3,4,*

¹ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore

² Cancer Science Institute of Singapore, Centre for Translational Medicine, 14 Medical Drive, #11-01M, Singapore 117599, Singapore

³ School of Biomedical Sciences, CHIRI Biosciences Research Precinct, Curtin University, Western Australia 6009, Australia

⁴ Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia

⁵ Department of Biological Sciences, University of North Texas, Denton, TX 76203, USA

Molecules 2015, 20(2), 2728-2769; https://doi.org/10.3390/molecules20022728 - 5 Feb 2015

Cited by 438 | Viewed by 52487

Abstract

Despite significant advances in treatment modalities over the last decade, neither the incidence of the disease nor the mortality due to cancer has altered in the last thirty years. Available anti-cancer drugs exhibit limited efficacy, associated with severe side effects, and are also [...] Read more.

Despite significant advances in treatment modalities over the last decade, neither the incidence of the disease nor the mortality due to cancer has altered in the last thirty years. Available anti-cancer drugs exhibit limited efficacy, associated with severe side effects, and are also expensive. Thus identification of pharmacological agents that do not have these disadvantages is required. Curcumin, a polyphenolic compound derived from turmeric (Curcumin longa), is one such agent that has been extensively studied over the last three to four decades for its potential anti-inflammatory and/or anti-cancer effects. Curcumin has been found to suppress initiation, progression, and metastasis of a variety of tumors. These anti-cancer effects are predominantly mediated through its negative regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other oncogenic molecules. It also abrogates proliferation of cancer cells by arresting them at different phases of the cell cycle and/or by inducing their apoptosis. The current review focuses on the diverse molecular targets modulated by curcumin that contribute to its efficacy against various human cancers. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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16 pages, 1026 KiB

Open AccessArticle

Bisdemethoxycurcumin Induces Apoptosis in Activated Hepatic Stellate Cells via Cannabinoid Receptor 2

by Phil Jun Lee¹, Seung Je Woo¹, Jun-Goo Jee², Sang Hyun Sung³

and Hong Pyo Kim^1,*

¹ School of Pharmacy, Ajou University, Suwon 443-749, Korea

² College of Pharmacy, Kyungbuk National University, Daegu 702-701, Korea

³ College of Pharmacy, Seoul National University, Seoul 151-742, Korea

Molecules 2015, 20(1), 1277-1292; https://doi.org/10.3390/molecules20011277 - 14 Jan 2015

Cited by 33 | Viewed by 9514

Abstract

Activated Hepatic Stellate Cells (HSCs), major fibrogenic cells in the liver, undergo apoptosis when liver injuries cease, which may contribute to the resolution of fibrosis. Bisdemethoxycurcumin (BDMC) is a natural derivative of curcumin with anti-inflammatory and anti-cancer activities. The therapeutic potential of BDMC [...] Read more.

Activated Hepatic Stellate Cells (HSCs), major fibrogenic cells in the liver, undergo apoptosis when liver injuries cease, which may contribute to the resolution of fibrosis. Bisdemethoxycurcumin (BDMC) is a natural derivative of curcumin with anti-inflammatory and anti-cancer activities. The therapeutic potential of BDMC in hepatic fibrosis has not been studied thus far in the context of the apoptosis in activated HSCs. In the current study, we compared the activities of BDMC and curcumin in the HSC-T6 cell line and demonstrated that BDMC relatively induced a potent apoptosis. BDMC-induced apoptosis was mediated by a combinatory inhibition of cytoprotective proteins, such as Bcl₂ and heme oxygenase-1 and increased generation of reactive oxygen species. Intriguingly, BDMC-induced apoptosis was reversed with co-treatment of sr144528, a cannabinoid receptor (CBR) 2 antagonist, which was confirmed with genetic downregulation of the receptor using siCBR2. Additionally, incubation with BDMC increased the formation of death-induced signaling complex in HSC-T6 cells. Treatment with BDMC significantly diminished total intracellular ATP levels and upregulated ATP inhibitory factor-1. Collectively, the results demonstrate that BDMC induces apoptosis in activated HSCs, but not in hepatocytes, by impairing cellular energetics and causing a downregulation of cytoprotective proteins, likely through a mechanism that involves CBR2. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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16 pages, 2392 KiB

Open AccessArticle

Inhibition of the NF-κB Signaling Pathway by a Novel Heterocyclic Curcumin Analogue

by Anna-Maria Katsori¹, Ajay Palagani², Nadia Bougarne³, Dimitra Hadjipavlou-Litina¹

, Guy Haegeman³ and Wim Vanden Berghe^2,3,*

¹ Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece

² Laboratory of Protein Chemistry, Proteomics and Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp, Wilrijk 2610, Belgium

³ Laboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST), Department of Physiology, University of Ghent, Ghent 9000, Belgium

Molecules 2015, 20(1), 863-878; https://doi.org/10.3390/molecules20010863 - 8 Jan 2015

Cited by 28 | Viewed by 9306

Abstract

In this study a series of curcumin analogues were evaluated for their ability to inhibit the activation of NF-κΒ, a transcription factor at the crossroads of cancer-inflammation. Our novel curcumin analogue BAT3 was identified to be the most potent NF-κB inhibitor and EMSA [...] Read more.

In this study a series of curcumin analogues were evaluated for their ability to inhibit the activation of NF-κΒ, a transcription factor at the crossroads of cancer-inflammation. Our novel curcumin analogue BAT3 was identified to be the most potent NF-κB inhibitor and EMSA assays clearly showed inhibition of NF-κB/DNA-binding in the presence of BAT3, in agreement with reporter gene results. Immunofluorescence experiments demonstrated that BAT3 did not seem to prevent nuclear p65 translocation, so our novel analogue may interfere with NF-κB/DNA-binding or transactivation, independently of IKK2 regulation and NF-κB-translocation. Gene expression studies on endogenous NF-κB target genes revealed that BAT3 significantly inhibited TNF-dependent transcription of IL6, MCP1 and A20 genes, whereas an NF-κB independent target gene heme oxygenase-1 remained unaffected. In conclusion, we demonstrate that BAT3 seems to inhibit different cancer-related inflammatory targets in the NF-κB signaling pathway through a different mechanism in comparison to similar analogues, previously reported. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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44 pages, 1461 KiB

Open AccessReview

Eliminating the Heart from the Curcumin Molecule: Monocarbonyl Curcumin Mimics (MACs)

by Dinesh Shetty¹, Yong Joon Kim², Hyunsuk Shim^3,4 and James P. Snyder^2,4,*

¹ Center for Self–assembly and Complexity, Institute for Basic Science, Pohang 790-784, Korea

² Department of Chemistry, Emory University, Atlanta, GA 30322, USA

³ Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA 30322, USA

⁴ Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA

Molecules 2015, 20(1), 249-292; https://doi.org/10.3390/molecules20010249 - 24 Dec 2014

Cited by 60 | Viewed by 12782

Abstract

Curcumin is a natural product with several thousand years of heritage. Its traditional Asian application to human ailments has been subjected in recent decades to worldwide pharmacological, biochemical and clinical investigations. Curcumin’s Achilles heel lies in its poor aqueous solubility and rapid degradation [...] Read more.

Curcumin is a natural product with several thousand years of heritage. Its traditional Asian application to human ailments has been subjected in recent decades to worldwide pharmacological, biochemical and clinical investigations. Curcumin’s Achilles heel lies in its poor aqueous solubility and rapid degradation at pH ~ 7.4. Researchers have sought to unlock curcumin’s assets by chemical manipulation. One class of molecules under scrutiny are the monocarbonyl analogs of curcumin (MACs). A thousand plus such agents have been created and tested primarily against cancer and inflammation. The outcome is clear. In vitro, MACs furnish a 10–20 fold potency gain vs. curcumin for numerous cancer cell lines and cellular proteins. Similarly, MACs have successfully demonstrated better pharmacokinetic (PK) profiles in mice and greater tumor regression in cancer xenografts in vivo than curcumin. The compounds reveal limited toxicity as measured by murine weight gain and histopathological assessment. To our knowledge, MAC members have not yet been monitored in larger animals or humans. However, Phase 1 clinical trials are certainly on the horizon. The present review focuses on the large and evolving body of work in cancer and inflammation, but also covers MAC structural diversity and early discovery for treatment of bacteria, tuberculosis, Alzheimer’s disease and malaria. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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21 pages, 1040 KiB

Open AccessReview

Curcumin Differs from Tetrahydrocurcumin for Molecular Targets, Signaling Pathways and Cellular Responses

by Bharat B. Aggarwal^*, Lokesh Deb^† and Sahdeo Prasad

¹ Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston 77054, TX, USA

^† Present address: Medicinal Plants and Horticultural Resources Division, Institute of Bioresources and Sustainable Development (IBSD), Takyelpat Institutional Area, Imphal 795001, Manipur, India

Molecules 2015, 20(1), 185-205; https://doi.org/10.3390/molecules20010185 - 24 Dec 2014

Cited by 229 | Viewed by 24429

Abstract

Curcumin (diferuloylmethane), a golden pigment from turmeric, has been linked with antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antidiabetic properties. Most of the these activities have been assigned to methoxy, hydroxyl, α,β-unsaturated carbonyl moiety or to diketone groups present in curcumin. One of the [...] Read more.

Curcumin (diferuloylmethane), a golden pigment from turmeric, has been linked with antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antidiabetic properties. Most of the these activities have been assigned to methoxy, hydroxyl, α,β-unsaturated carbonyl moiety or to diketone groups present in curcumin. One of the major metabolites of curcumin is tetrahydrocurcumin (THC), which lacks α,β-unsaturated carbonyl moiety and is white in color. Whether THC is superior to curcumin on a molecular level is unclear and thus is the focus of this review. Various studies suggest that curcumin is a more potent antioxidant than THC; curcumin (but not THC) can bind and inhibit numerous targets including DNA (cytosine-5)-methyltransferase-1, heme oxygenase-1, Nrf2, β-catenin, cyclooxygenase-2, NF-kappaB, inducible nitric oxide synthase, nitric oxide, amyloid plaques, reactive oxygen species, vascular endothelial growth factor, cyclin D1, glutathione, P300/CBP, 5-lipoxygenase, cytosolic phospholipase A2, prostaglandin E2, inhibitor of NF-kappaB kinase-1, -2, P38MAPK, p-Tau, tumor necrosis factor-α, forkhead box O3a, CRAC; curcumin can inhibit tumor cell growth and suppress cellular entry of viruses such as influenza A virus and hepatitis C virus much more effectively than THC; curcumin affects membrane mobility; and curcumin is also more effective than THC in suppressing phorbol-ester-induced tumor promotion. Other studies, however, suggest that THC is superior to curcumin for induction of GSH peroxidase, glutathione-S-transferase, NADPH: quinone reductase, and quenching of free radicals. Most studies have indicated that THC exhibits higher antioxidant activity, but curcumin exhibits both pro-oxidant and antioxidant properties. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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27 pages, 1097 KiB

Open AccessReview

Curcumin and Inflammatory Bowel Disease: Potential and Limits of Innovative Treatments

by Liza Vecchi Brumatti^1,*, Annalisa Marcuzzi¹, Paola Maura Tricarico², Valentina Zanin¹, Martina Girardelli¹ and Anna Monica Bianco¹

¹ Institute for Maternal and Child Health—IRCCS "Burlo Garofolo"—via dell'Istria, 65/1, Trieste 34137, Italy

² Department of Medicine and Surgery and Health Sciences, University of Trieste, Piazzale Europa, 1, Trieste 34137, Italy

Molecules 2014, 19(12), 21127-21153; https://doi.org/10.3390/molecules191221127 - 16 Dec 2014

Cited by 117 | Viewed by 30152

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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16 pages, 753 KiB

Open AccessReview

Relevance of the Anti-Inflammatory Properties of Curcumin in Neurodegenerative Diseases and Depression

by Yousef Tizabi^*, Laura L. Hurley, Zakiya Qualls and Luli Akinfiresoye

Department of Pharmacology, College of Medicine, Howard University, Washington, DC 20059, USA

Molecules 2014, 19(12), 20864-20879; https://doi.org/10.3390/molecules191220864 - 12 Dec 2014

Cited by 69 | Viewed by 21539

Abstract

This review is an attempt to summarize our current understanding of curcumin’s potential as a neuroprotectant and an antidepressant. This dual property confers a unique advantage to this herbal medication, believed to be devoid of any major side effects, to combat commonly observed [...] Read more.

This review is an attempt to summarize our current understanding of curcumin’s potential as a neuroprotectant and an antidepressant. This dual property confers a unique advantage to this herbal medication, believed to be devoid of any major side effects, to combat commonly observed co-morbid conditions of a neurodegenerative and a neuropsychiatric disorder. Moreover, in line with the theme of this series, the role of inflammation and stress in these diseases and possible anti-inflammatory effects of curcumin, as well as its interaction with signal transduction proteins as a common denominator in its varied mechanisms of action, are also discussed. Thus, following a brief introduction of curcumin’s pharmacology, we present research suggesting how its anti-inflammatory properties have therapeutic potential in treating a devastating neurological disorder (Parkinson’s disease = PD) and a debilitating neuropsychiatric disorder (major depressive disorder = MDD). It is concluded that curcumin, or better yet, an analog with better and longer bioavailability could be of important therapeutic potential in PD and/or major depression. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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25 pages, 888 KiB

Open AccessReview

Hybrid Curcumin Compounds: A New Strategy for Cancer Treatment

by Marie-Hélène Teiten¹, Mario Dicato¹ and Marc Diederich^2,*

¹ Laboratory of Molecular and Cellular Biology of Cancer (LBMCC), Hôpital Kirchberg, 9, Rue Edward Steichen, Luxembourg L-2540, Luxembourg

² Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea

Molecules 2014, 19(12), 20839-20863; https://doi.org/10.3390/molecules191220839 - 12 Dec 2014

Cited by 116 | Viewed by 16400

Abstract

Cancer is a multifactorial disease that requires treatments able to target multiple intracellular components and signaling pathways. The natural compound, curcumin, was already described as a promising anticancer agent due to its multipotent properties and huge amount of molecular targets in vitro. [...] Read more.

Cancer is a multifactorial disease that requires treatments able to target multiple intracellular components and signaling pathways. The natural compound, curcumin, was already described as a promising anticancer agent due to its multipotent properties and huge amount of molecular targets in vitro. Its translation to the clinic is, however, limited by its reduced solubility and bioavailability in patients. In order to overcome these pharmacokinetic deficits of curcumin, several strategies, such as the design of synthetic analogs, the combination with specific adjuvants or nano-formulations, have been developed. By taking into account the risk-benefit profile of drug combinations, as well as the knowledge about curcumin’s structure-activity relationship, a new concept for the combination of curcumin with scaffolds from different natural products or components has emerged. The concept of a hybrid curcumin molecule is based on the incorporation or combination of curcumin with specific antibodies, adjuvants or other natural products already used or not in conventional chemotherapy, in one single molecule. The high diversity of such conjugations enhances the selectivity and inherent biological activities and properties, as well as the efficacy of the parental compound, with particular emphasis on improving the efficacy of curcumin for future clinical treatments. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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18 pages, 657 KiB

Open AccessReview

Curcumin and Chronic Kidney Disease (CKD): Major Mode of Action through Stimulating Endogenous Intestinal Alkaline Phosphatase

by Siddhartha S. Ghosh¹, Todd W. B. Gehr¹ and Shobha Ghosh^2,*

¹ Division of Nephrology, Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA

² Division of Pulmonary and Critical Care, Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA

Molecules 2014, 19(12), 20139-20156; https://doi.org/10.3390/molecules191220139 - 2 Dec 2014

Cited by 89 | Viewed by 30296

Abstract

Curcumin, an active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa), has significant anti-inflammatory properties. Chronic kidney disease (CKD), an inflammatory disease, can lead to end stage renal disease resulting in dialysis and transplant. Furthermore, it is [...] Read more.

Curcumin, an active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa), has significant anti-inflammatory properties. Chronic kidney disease (CKD), an inflammatory disease, can lead to end stage renal disease resulting in dialysis and transplant. Furthermore, it is frequently associated with other inflammatory disease such as diabetes and cardiovascular disorders. This review will focus on the clinically relevant inflammatory molecules that play a role in CKD and associated diseases. Various enzymes, transcription factors, growth factors modulate production and action of inflammatory molecules; curcumin can blunt the generation and action of these inflammatory molecules and ameliorate CKD as well as associated inflammatory disorders. Recent studies have shown that increased intestinal permeability results in the leakage of pro-inflammatory molecules (cytokines and lipopolysaccharides) from gut into the circulation in diseases such as CKD, diabetes and atherosclerosis. This change in intestinal permeability is due to decreased expression of tight junction proteins and intestinal alkaline phosphatase (IAP). Curcumin increases the expression of IAP and tight junction proteins and corrects gut permeability. This action reduces the levels of circulatory inflammatory biomolecules. This effect of curcumin on intestine can explain why, despite poor bioavailability, curcumin has potential anti-inflammatory effects in vivo and beneficial effects on CKD. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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22 pages, 454 KiB

Open AccessReview

The Chemistry of Curcumin: From Extraction to Therapeutic Agent

by Kavirayani Indira Priyadarsini

Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Mumbai 400085, India

Molecules 2014, 19(12), 20091-20112; https://doi.org/10.3390/molecules191220091 - 1 Dec 2014

Cited by 1176 | Viewed by 101558

Abstract

Curcumin, a pigment from turmeric, is one of the very few promising natural products that has been extensively investigated by researchers from both the biological and chemical point of view. While there are several reviews on the biological and pharmacological effects of curcumin, [...] Read more.

Curcumin, a pigment from turmeric, is one of the very few promising natural products that has been extensively investigated by researchers from both the biological and chemical point of view. While there are several reviews on the biological and pharmacological effects of curcumin, chemistry reviews are comparatively scarcer. In this article, an overview of different aspects of the unique chemistry research on curcumin will be discussed. These include methods for the extraction from turmeric, laboratory synthesis methods, chemical and photochemical degradation and the chemistry behind its metabolism. Additionally other chemical reactions that have biological relevance like nucleophilic addition reactions, and metal chelation will be discussed. Recent advances in the preparation of new curcumin nanoconjugates with metal and metal oxide nanoparticles will also be mentioned. Directions for future investigations to be undertaken in the chemistry of curcumin have also been suggested. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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14 pages, 4460 KiB

Open AccessArticle

Curcumin Protects against CCl₄-Induced Liver Fibrosis in Rats by Inhibiting HIF-1α Through an ERK-Dependent Pathway

by Yanling Zhao¹, Xiao Ma^1,2, Jiabo Wang¹, Xuan He³, Yan Hu⁴, Ping Zhang⁵, Ruilin Wang⁵, Ruisheng Li⁴, Man Gong⁵, Shengqiang Luo⁵ and Xiaohe Xiao^1,*

¹ China Military Institute of Chinese Medicine, 302 Military Hospital of China, Beijing 100039, China

² Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China

³ State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China

⁴ Research and Technology Service Center, 302 Military Hospital of China, Beijing 100039, China

⁵ Department of Integrative Medical Center, 302 Military Hospital of China, Beijing 100039, China

Molecules 2014, 19(11), 18767-18780; https://doi.org/10.3390/molecules191118767 - 17 Nov 2014

Cited by 71 | Viewed by 11524

Abstract

The ERK/HIF-1α signaling pathway is believed to play an important role in the genesis of progressive fibrosis. An increasing expression of HIF-1α and ERK accompanies CCl₄-induced liver fibrosis in rats. Curcumin is verified to have antifibrotic effects in several kinds of [...] Read more.

The ERK/HIF-1α signaling pathway is believed to play an important role in the genesis of progressive fibrosis. An increasing expression of HIF-1α and ERK accompanies CCl₄-induced liver fibrosis in rats. Curcumin is verified to have antifibrotic effects in several kinds of liver fibrosis models. There is no specific evidence illustrating a connection between curcumin and the HIF-1α/ERK pathway in rat liver fibrosis induced by CCl₄. In this study, liver fibrosis was induced by CCl₄ in treated rats. The data demonstrated that curcumin was able to attenuate liver fibrosis and inhibit the proliferation of HSC. Moreover, curcumin could remarkably elevate the hepatic function by decreasing serum levels of ALT, AST and ALP, and increasing levels of ALB, TP and α-SMA, Col III mRNA expression. Meanwhile, ECM status could also be reflected by curcumin treatment. The alleviation with curcumin treatment was associated with inhibition of HIF-1α and phosphor-ERK. This study indicates that curcumin alleviates fibrosis by reducing the expression of HIF-1α partly through the ERK pathway. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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13 pages, 1440 KiB

Open AccessArticle

Curcumin Reverse Methicillin Resistance in Staphylococcus aureus

by Su-Hyun Mun¹, Sung-Bae Kim¹, Ryong Kong¹, Jang-Gi Choi², Youn-Chul Kim³, Dong-Won Shin⁴, Ok-Hwa Kang² and Dong-Yeul Kwon^1,2,*

¹ BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea

² Department of Oriental Pharmacy, College of Pharmacy, Wonkwang Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570-749, Korea

³ Standardized Material Bank for New Botanical Drugs, College of Pharmacy, Wonkwang University, Iksan, Jeonbuk 570-749, Korea

⁴ Department of Oriental Medicine Resources, College of Bio Industry Science, Sunchon National University, Sunchon, Jeonnam 540-742, Korea

Molecules 2014, 19(11), 18283-18295; https://doi.org/10.3390/molecules191118283 - 10 Nov 2014

Cited by 88 | Viewed by 18806

Abstract

Curcumin, a natural polyphenolic flavonoid extracted from the rhizome of Curcuma longa L., was shown to possess superior potency to resensitize methicillin-resistant Staphylococcus aureus (MRSA) to antibiotics. Previous studies have shown the synergistic activity of curcumin with β-lactam and quinolone antibiotics. Further, to [...] Read more.

Curcumin, a natural polyphenolic flavonoid extracted from the rhizome of Curcuma longa L., was shown to possess superior potency to resensitize methicillin-resistant Staphylococcus aureus (MRSA) to antibiotics. Previous studies have shown the synergistic activity of curcumin with β-lactam and quinolone antibiotics. Further, to understand the anti-MRSA mechanism of curcumin, we investigated the potentiated effect of curcumin by its interaction in diverse conditions. The mechanism of anti-MRSA action of curcumin was analyzed by the viability assay in the presence of detergents, ATPase inhibitors and peptidoglycan (PGN) from S. aureus, and the PBP2a protein level was analyzed by western blotting. The morphological changes in the curcumin-treated MRSA strains were investigated by transmission electron microscopy (TEM). We analyzed increased susceptibility to MRSA isolates in the presence of curcumin. The optical densities at 600 nm (OD₆₀₀) of the suspensions treated with the combinations of curcumin with triton X-100 and Tris were reduced to 63% and 59%, respectively, compared to curcumin without treatment. N,N'-dicyclohexylcarbodiimide (DCCD) and sodium azide (NaN₃) were reduced to 94% and 55%, respectively. When peptidoglycan (PGN) from S. aureus was combined with curcumin, PGN (0–125 μg/mL) gradually blocked the antibacterial activity of curcumin (125 μg/mL); however, at a concentration of 125 µg/mL PGN, it did not completely block curcumin. Curcumin has a significant effect on the protein level of PBP2a. The TEM images of MRSA showed damage of the cell wall, disruption of the cytoplasmic contents, broken cell membrane and cell lysis after the treatment of curcumin. These data indicate a remarkable antibacterial effect of curcumin, with membrane permeability enhancers and ATPase inhibitors, and curcumin did not directly bind to PGN on the cell wall. Further, the antimicrobial action of curcumin involved in the PBP2a-mediated resistance mechanism was investigated. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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