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Fulltext The Molecular Targets and Anti-Invasive Effects of 2,6-bis-(4-hydroxyl-3methoxybenzylidine) cyclohexanone or BHMC in MDA-MB-231 Human Breast Cancer Cells

Harun SNA, Israf DA, Tham CL, Lam KW, Cheema MS, Md Hashim NF

Molecules, 2018 Apr 10;23(4).
PMID: 29642589 DOI: 10.3390/molecules23040865

In order to metastasize, tumor cells need to migrate and invade the surrounding tissues. It is important to identify compound(s) capable of disrupting the metastasis of invasive cancer cells, especially for hindering invadopodia formation, so as to provide anti-metastasis targeted therapy. Invadopodia are thought to be specialized actin-rich protrusions formed by highly invasive cancer cells to degrade the extracellular matrix (ECM). A curcuminoid analogue known as 2,6-bis-(4-hydroxy-3-methoxybenzylidine)cyclohexanone or BHMC has shown good potential in inhibiting inflammation and hyperalgesia. It also possesses an anti-tumor effects on 4T1 murine breast cancer cells in vivo. However, there is still a lack of empirical evidence on how BHMC works in preventing human breast cancer invasion. In this study, we investigated the effect of BHMC on MDA-MB-231 breast cancer cells and its underlying mechanism of action to prevent breast cancer invasion, especially during the formation of invadopodia. All MDA-MB-231 cells, which were exposed to the non-cytotoxic concentrations of BHMC, expressed the proliferating cell nuclear antigen (PCNA), which indicate that the anti-proliferative effects of BHMC did not interfere in the subsequent experiments. By using a scratch migration assay, transwell migration and invasion assays, we determined that BHMC reduces the percentage of migration and invasion of MDA-MB-231 cells. The gelatin degradation assay showed that BHMC reduced the number of cells with invadopodia. Analysis of the proteins involved in the invasion showed that there is a significant reduction in the expressions of Rho guanine nucleotide exchange factor 7 (β-PIX), matrix metalloproteinase-9 (MMP-9), and membrane type 1 matrix metalloproteinase (MT1-MMP) in the presence of BHMC treatment at 12.5 µM. Therefore, it can be postulated that BHMC at 12.5 µM is the optimal concentration for preventing breast cancer invasion.

Matched MeSH terms: Curcumin/analogs & derivatives*; Curcumin/pharmacology
Thermoresponsive curcumin/DsiRNA nanoparticle gels for the treatment of diabetic wounds: synthesis and drug release

Katas H, Wen CY, Siddique MI, Hussain Z, Mohd Fadhil FH

Ther Deliv, 2017 01;8(3):137-150.
PMID: 28145827 DOI: 10.4155/tde-2016-0075

AIM: Chitosan (CS) has been extensively studied as drug delivery systems for wound healing. Results/methodology: CS nanoparticles were loaded with curcumin (Cur) and DsiRNA against prostaglandin transporter gene and they were incorporated into 20 and 25% w/v Pluronic F-127. The gels were later analyzed for their rheology, gelation temperature (Tgel), morphology, drug incorporation and in vitro drug release. The particle size was in the range of 231 ± 17-320 ± 20 nm, depending on CS concentration. The gels had Tgel of 23-28°C and exhibited sustained drug release with high accumulated amount of drugs over 48 h.
CONCLUSION: A thermo-sensitive gel containing Cur/DsiRNA CS nanoparticles was successfully developed and has a great potential to be further developed.

Matched MeSH terms: Curcumin/chemistry*
Boron removal from aqueous solution using curcumin-impregnated activated carbon

Azhar Abdul Halim, Nor Alia Roslan, Nor Shamsiah Yaacub, Mohd. Talib Latif

Sains Malaysiana, 2013;42:1293-1300.

This study was conducted to investigate the batch and fixed-bed adsorption properties of boron on curcumin-impregnated activated carbon (Cur-AC). The maximum boron removal was obtained at pH5.5 and 120 min of contact time. Langmuir and Freundlich isotherm models were applied and it was determined that the experimental data conformed to both models. The Langmuir maximum adsorption capacities for Cur-AC (5.00 mg/g) and regenerated Cur-AC (3.61 mg/g) were obviously higher than the capacity for bare activated carbon (0.59 mg/g). Kinetic studies indicated the adsorption of boron conformed to the intra-particle model. The highest boron removal in fixed-bed column adsorption was achieved up to 99% for the first 5 min at an inlet concentration of 890 mg/L and a flow rate of 8.0 mL/min. Thomas and the Yoon-Nelson models gave better fit to the experimental data. Cur-AC can be reused after elution processes with slightly lower adsorption capacity.

Matched MeSH terms: Curcumin
Fulltext Low dose triterpene-quinone fraction from Ardisia crispa root precludes chemical-induced mouse skin tumor promotion

Yeong LT, Abdul Hamid R, Saiful Yazan L, Khaza'ai H, Mohtarrudin N

BMC Complement Altern Med, 2015;15(1):431.
PMID: 26638207 DOI: 10.1186/s12906-015-0954-3

Drastic increment of skin cancer incidence has driven natural product-based chemoprevention as a promising approach in anticancer drug development. Apart from its traditional usages against various ailments, Ardisia crispa (Family: Myrsinaceae) specifically its triterpene-quinone fraction (TQF) which was isolated from the root hexane extract (ACRH) was recently reported to exert antitumor promoting activity in vitro. This study aimed at determining chemopreventive effect of TQF against chemically-induced mouse skin tumorigenesis as well as elucidating its possible pathway(s).

Matched MeSH terms: Curcumin/administration & dosage
Fulltext Potential Health Benefits of Curcumin on Female Reproductive Disorders: A Review

Kamal DAM, Salamt N, Yusuf ANM, Kashim MIAM, Mokhtar MH

Nutrients, 2021 Sep 07;13(9).
PMID: 34579002 DOI: 10.3390/nu13093126

Curcumin is one of the main polyphenolic compounds in the turmeric rhizome. It possesses antioxidant, anti-inflammatory, anti-cancer, anti-arthritis, anti-asthmatic, anti-microbial, anti-viral and anti-fungal properties. This review aims to provide an overview of the potential health benefits of curcumin to treat female reproductive disorders, including polycystic ovary syndrome (PCOS), ovarian failure and endometriosis. Comprehensive information on curcumin was retrieved from electronic databases, which were MEDLINE via EBSCOhost, Scopus and Google Scholar. The available evidence showed that curcumin reduced the high level of androgen in PCOS. Studies in rodents suggest that curcumin resulted in the disappearance of cysts and the appearance of healthy follicles and corpora lutea. Furthermore, animal studies showed curcumin improved the overall function of the ovary in ovarian diseases and reversed the disturbance in oxidative stress parameters. Meanwhile, in vitro and in vivo studies reported the positive effects of curcumin in alleviating endometriosis through anti-inflammatory, anti-proliferative, anti-angiogenic and pro-apoptotic mechanisms. Thus, curcumin possesses various effects on PCOS, ovarian diseases and endometriosis. Some studies found considerable therapeutic effects, whereas others found no effect. However, none of the investigations found curcumin to be harmful. Curcumin clinical trials in endometriosis and ovarian illness are still scarce; thus, future studies need to be conducted to confirm the safety and efficacy of curcumin before it could be offered as a complementary therapy agent.

Matched MeSH terms: Curcumin/pharmacology*
Pharmacokinetics and tissue distribution of hydrazinocurcumin in rats

Satyavert, Gupta S, Choudhury H, Jacob S, Nair AB, Dhanawat M, et al.

Pharmacol Rep, 2021 Dec;73(6):1734-1743.
PMID: 34283375 DOI: 10.1007/s43440-021-00312-5

BACKGROUND: Curcumin, a natural polyphenol from Curcuma longa, is known to possess diversified pharmacological roles including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic properties; however, its bioavailability is severely limited due to its poor solubility, poor absorption, rapid metabolism, and significant elimination. Hydrazinocurcumin (HZC), a novel analogue of curcumin has been reported to overcome the limitations of curcumin and also possesses multiple pharmacological activities. The present study aimed to evaluate the unexplored pharmacokinetic profile of this agent in experimental rats.
METHODS: Drug formulations were administered to the experimental animals via oral, intravenous and intraperitoneal routes. Blood samples were collected at different pre-determined time intervals to determine the pharmacokinetic parameters. To understand the biodistribution profile of HCZ, tissue samples were isolated from different groups of Sprague-Dawley rats at different time points. The pharmacokinetic parameters of HZC were evaluated after administration through oral (100 mg/kg), intraperitoneal (100 mg/kg) and intravenous (10 mg/kg) routes.
RESULTS: Significantly (p

Matched MeSH terms: Curcumin/administration & dosage; Curcumin/analogs & derivatives*; Curcumin/pharmacokinetics
Fulltext Regulation of microRNAs by natural agents: new strategies in cancer therapies

Phuah NH, Nagoor NH

Biomed Res Int, 2014;2014:804510.
PMID: 25254214 DOI: 10.1155/2014/804510

MicroRNAs (miRNAs) are short noncoding RNA which regulate gene expression by messenger RNA (mRNA) degradation or translation repression. The plethora of published reports in recent years demonstrated that they play fundamental roles in many biological processes, such as carcinogenesis, angiogenesis, programmed cell death, cell proliferation, invasion, migration, and differentiation by acting as tumour suppressor or oncogene, and aberrations in their expressions have been linked to onset and progression of various cancers. Furthermore, each miRNA is capable of regulating the expression of many genes, allowing them to simultaneously regulate multiple cellular signalling pathways. Hence, miRNAs have the potential to be used as biomarkers for cancer diagnosis and prognosis as well as therapeutic targets. Recent studies have shown that natural agents such as curcumin, resveratrol, genistein, epigallocatechin-3-gallate, indole-3-carbinol, and 3,3'-diindolylmethane exert their antiproliferative and/or proapoptotic effects through the regulation of one or more miRNAs. Therefore, this review will look at the regulation of miRNAs by natural agents as a means to potentially enhance the efficacy of conventional chemotherapy through combinatorial therapies. It is hoped that this would provide new strategies in cancer therapies to improve overall response and survival outcome in cancer patients.

Matched MeSH terms: Curcumin/therapeutic use
Electro-Stimulated Release of Poorly Water-Soluble Drug from Poly(Lactic Acid)/Carboxymethyl Cellulose/ZnO Nanocomposite Film

Gunathilake TMSU, Ching YC, Chuah CH, Hai ND, Nai-Shang L

Pharm Res, 2020 Aug 30;37(9):178.
PMID: 32864721 DOI: 10.1007/s11095-020-02910-z

PURPOSE: Among various types of external stimuli-responsive DDS, electric-responsive DDS are more promising carriers as they exploit less complex, easily miniaturized electric signal generators and the possibility of fine-tuning the electric signals. This study investigates the use of intrinsically biocompatible biopolymers in electro-simulative drug delivery to enhance the release of poorly-soluble/non-ionic drug.
METHODS: CMC/PLA/ZnO/CUR nanocomposite films were prepared by the dispersion of CMC and ZnO NPs in solubilized PLA/curcumin medium, followed by solvent casting step. Curcumin is poorly water-soluble and used as the model drug in this study. The films with different contents of CMC, PLA and ZnO NPs were characterized using FTIR, impedance spectroscopy, tensile testing and FESEM imaging. The in vitro drug release of the films was carried out in deionized water under DC electric field of 4.5 V.
RESULTS: The ionic conductivity of the films increased with increasing the CMC concentration of the film. The addition of a small amount of ZnO NPs (2%) successfully restored the tensile properties of the film. In response to the application of the electric field, the composite films released drug with a near-linear profile. There was no noticeable amount of passive diffusion of the drug from the film with the absence of the electric field.
CONCLUSION: The outcome of this study enabled the design of an electric-responsive nanocomposite platform for the delivery of poorly water-soluble/non-ionic drugs. Graphical abstract.

Matched MeSH terms: Curcumin
Fulltext The Curcumin Analogue 1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one Induces Apoptosis and Downregulates E6 and E7 Oncogene Expression in HPV16 and HPV18-Infected Cervical Cancer Cells

Paulraj F, Abas F, Lajis NH, Othman I, Hassan SS, Naidu R

Molecules, 2015;20(7):11830-60.
PMID: 26132907 DOI: 10.3390/molecules200711830

In an effort to study curcumin analogues as an alternative to improve the therapeutic efficacy of curcumin, we screened the cytotoxic potential of four diarylpentanoids using the HeLa and CaSki cervical cancer cell lines. Determination of their EC50 values indicated relatively higher potency of 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one (MS17, 1.03 ± 0.5 μM; 2.6 ± 0.9 μM) and 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (MS13, 2.8 ± 0.4; 6.7 ± 2.4 μM) in CaSki and HeLa, respectively, with significantly greater growth inhibition at 48 and 72 h of treatment compared to the other analogues or curcumin. Based on cytotoxic and anti-proliferative activity, MS17 was selected for comprehensive apoptotic studies. At 24 h of treatment, fluorescence microscopy detected that MS17-exposed cells exhibited significant morphological changes consistent with apoptosis, corroborated by an increase in nucleosomal enrichment due to DNA fragmentation in HeLa and CaSki cells and activation of caspase-3 activity in CaSki cells. Quantitative real-time PCR also detected significant down-regulation of HPV18- and HPV16-associated E6 and E7 oncogene expression following treatment. The overall data suggests that MS17 treatment has cytotoxic, anti-proliferative and apoptosis-inducing potential in HPV-positive cervical cancer cells. Furthermore, its role in down-regulation of HPV-associated oncogenes responsible for cancer progression merits further investigation into its chemotherapeutic role for cervical cancer.

Matched MeSH terms: Curcumin/analogs & derivatives*; Curcumin/pharmacology
Fulltext Anticancer Mechanism of Curcumin on Human Glioblastoma

Wong SC, Kamarudin MNA, Naidu R

Nutrients, 2021 Mar 16;13(3).
PMID: 33809462 DOI: 10.3390/nu13030950

Glioblastoma (GBM) is the most malignant brain tumor and accounts for most adult brain tumors. Current available treatment options for GBM are multimodal, which include surgical resection, radiation, and chemotherapy. Despite the significant advances in diagnostic and therapeutic approaches, GBM remains largely resistant to treatment, with a poor median survival rate between 12 and 18 months. With increasing drug resistance, the introduction of phytochemicals into current GBM treatment has become a potential strategy to combat GBM. Phytochemicals possess multifarious bioactivities with multitarget sites and comparatively marginal toxicity. Among them, curcumin is the most studied compound described as a potential anticancer agent due to its multi-targeted signaling/molecular pathways properties. Curcumin possesses the ability to modulate the core pathways involved in GBM cell proliferation, apoptosis, cell cycle arrest, autophagy, paraptosis, oxidative stress, and tumor cell motility. This review discusses curcumin's anticancer mechanism through modulation of Rb, p53, MAPK, P13K/Akt, JAK/STAT, Shh, and NF-κB pathways, which are commonly involved and dysregulated in preclinical and clinical GBM models. In addition, limitation issues such as bioavailability, pharmacokinetics perspectives strategies, and clinical trials were discussed.

Matched MeSH terms: Curcumin/therapeutic use*
Fulltext Proteomic Analysis on Anti-Proliferative and Apoptosis Effects of Curcumin Analog, 1,5-bis(4-Hydroxy-3-Methyoxyphenyl)-1,4-Pentadiene-3-One-Treated Human Glioblastoma and Neuroblastoma Cells

Lee YQ, Rajadurai P, Abas F, Othman I, Naidu R

Front Mol Biosci, 2021;8:645856.
PMID: 33996900 DOI: 10.3389/fmolb.2021.645856

Curcumin analogs with excellent biological properties have been synthesized to address and overcome the poor pharmacokinetic profiles of curcumin. This study aims to investigate the cytotoxicity, anti-proliferative, and apoptosis-inducing ability of curcumin analog, MS13 on human glioblastoma U-87 MG, and neuroblastoma SH-SY5Y cells, and to examine the global proteome changes in these cells following treatment. Our current findings showed that MS13 induced potent cytotoxicity and anti-proliferative effects on both cells. Increased caspase-3 activity and decreased bcl-2 concentration upon treatment indicate that MS13 induces apoptosis in these cells in a dose- and time-dependent manner. The label-free shotgun proteomic analysis has defined the protein profiles in both glioblastoma and neuroblastoma cells, whereby a total of nine common DEPs, inclusive of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), alpha-enolase (ENO1), heat shock protein HSP 90-alpha (HSP90AA1), Heat shock protein HSP 90-beta (HSP90AB1), Eukaryotic translation initiation factor 5A-1 (EFI5A), heterogenous nuclear ribonucleoprotein K (HNRNPK), tubulin beta chain (TUBB), histone H2AX (H2AFX), and Protein SET were identified. Pathway analysis further elucidated that MS13 may induce its anti-tumor effects in both cells via the common enriched pathways, "Glycolysis" and "Post-translational protein modification." Conclusively, MS13 demonstrates an anti-cancer effect that may indicate its potential use in the management of brain malignancies.

Matched MeSH terms: Curcumin
Fulltext Mechanism of Anti-Cancer Activity of Curcumin on Androgen-Dependent and Androgen-Independent Prostate Cancer

Abd Wahab NA, Lajis NH, Abas F, Othman I, Naidu R

Nutrients, 2020 Mar 02;12(3).
PMID: 32131560 DOI: 10.3390/nu12030679

Prostate cancer (PCa) is a heterogeneous disease and ranked as the second leading cause of cancer-related deaths in males worldwide. The global burden of PCa keeps rising regardless of the emerging cutting-edge technologies for treatment and drug designation. There are a number of treatment options which are effectively treating localised and androgen-dependent PCa (ADPC) through hormonal and surgery treatments. However, over time, these cancerous cells progress to androgen-independent PCa (AIPC) which continuously grow despite hormone depletion. At this particular stage, androgen depletion therapy (ADT) is no longer effective as these cancerous cells are rendered hormone-insensitive and capable of growing in the absence of androgen. AIPC is a lethal type of disease which leads to poor prognosis and is a major contributor to PCa death rates. A natural product-derived compound, curcumin has been identified as a pleiotropic compound which capable of influencing and modulating a diverse range of molecular targets and signalling pathways in order to exhibit its medicinal properties. Due to such multi-targeted behaviour, its benefits are paramount in combating a wide range of diseases including inflammation and cancer disease. Curcumin exhibits anti-cancer properties by suppressing cancer cells growth and survival, inflammation, invasion, cell proliferation as well as possesses the ability to induce apoptosis in malignant cells. In this review, we investigate the mechanism of curcumin by modulating multiple signalling pathways such as androgen receptor (AR) signalling, activating protein-1 (AP-1), phosphatidylinositol 3-kinases/the serine/threonine kinase (PI3K/Akt/mTOR), wingless (Wnt)/ß-catenin signalling, and molecular targets including nuclear factor kappa-B (NF-κB), B-cell lymphoma 2 (Bcl-2) and cyclin D1 which are implicated in the development and progression of both types of PCa, ADPC and AIPC. In addition, the role of microRNAs and clinical trials on the anti-cancer effects of curcumin in PCa patients were also reviewed.

Matched MeSH terms: Curcumin/therapeutic use*
Fulltext Molecular Mechanisms of Antiproliferative and Apoptosis Activity by 1,5-Bis(4-Hydroxy-3-Methoxyphenyl)1,4-Pentadiene-3-one (MS13) on Human Non-Small Cell Lung Cancer Cells

Wan Mohd Tajuddin WNB, Abas F, Othman I, Naidu R

Int J Mol Sci, 2021 Jul 10;22(14).
PMID: 34299042 DOI: 10.3390/ijms22147424

Diarylpentanoid (DAP), an analog that was structurally modified from a naturally occurring curcumin, has shown to enhance anticancer efficacy compared to its parent compound in various cancers. This study aims to determine the cytotoxicity, antiproliferative, and apoptotic activity of diarylpentanoid MS13 on two subtypes of non-small cell lung cancer (NSCLC) cells: squamous cell carcinoma (NCI-H520) and adenocarcinoma (NCI-H23). Gene expression analysis was performed using Nanostring PanCancer Pathways Panel to determine significant signaling pathways and targeted genes in these treated cells. Cytotoxicity screening revealed that MS13 exhibited greater inhibitory effect in NCI-H520 and NCI-H23 cells compared to curcumin. MS13 induced anti-proliferative activity in both cells in a dose- and time-dependent manner. Morphological analysis revealed that a significant number of MS13-treated cells exhibited apoptosis. A significant increase in caspase-3 activity and decrease in Bcl-2 protein concentration was noted in both MS13-treated cells in a time- and dose-dependent manner. A total of 77 and 47 differential expressed genes (DEGs) were regulated in MS13 treated-NCI-H520 and NCI-H23 cells, respectively. Among the DEGs, 22 were mutually expressed in both NCI-H520 and NCI-H23 cells in response to MS13 treatment. The top DEGs modulated by MS13 in NCI-H520-DUSP4, CDKN1A, GADD45G, NGFR, and EPHA2-and NCI-H23 cells-HGF, MET, COL5A2, MCM7, and GNG4-were highly associated with PI3K, cell cycle-apoptosis, and MAPK signaling pathways. In conclusion, MS13 may induce antiproliferation and apoptosis activity in squamous cell carcinoma and adenocarcinoma of NSCLC cells by modulating DEGs associated with PI3K-AKT, cell cycle-apoptosis, and MAPK pathways. Therefore, our present findings could provide an insight into the anticancer activity of MS13 and merits further investigation as a potential anticancer agent for NSCLC cancer therapy.

Matched MeSH terms: Curcumin/analogs & derivatives*; Curcumin/pharmacology; Curcumin/chemistry
Fulltext Mechanism of Apoptosis Induced by Curcumin in Colorectal Cancer

Ismail NI, Othman I, Abas F, H Lajis N, Naidu R

Int J Mol Sci, 2019 May 17;20(10).
PMID: 31108984 DOI: 10.3390/ijms20102454

Colorectal cancer (CRC) is among the top three cancer with higher incident and mortality rate worldwide. It is estimated that about over than 1.1 million of death and 2.2 million new cases by the year 2030. The current treatment modalities with the usage of chemo drugs such as FOLFOX and FOLFIRI, surgery and radiotherapy, which are usually accompanied with major side effects, are rarely cured along with poor survival rate and at higher recurrence outcome. This trigger the needs of exploring new natural compounds with anti-cancer properties which possess fewer side effects. Curcumin, a common spice used in ancient medicine was found to induce apoptosis by targeting various molecules and signaling pathways involved in CRC. Disruption of the homeostatic balance between cell proliferation and apoptosis could be one of the promoting factors in colorectal cancer progression. In this review, we describe the current knowledge of apoptosis regulation by curcumin in CRC with regard to molecular targets and associated signaling pathways.

Matched MeSH terms: Curcumin/pharmacology*
Fulltext Mechanistic Understanding of Curcumin's Therapeutic Effects in Lung Cancer

Wan Mohd Tajuddin WNB, Lajis NH, Abas F, Othman I, Naidu R

Nutrients, 2019 Dec 06;11(12).
PMID: 31817718 DOI: 10.3390/nu11122989

Lung cancer is among the most common cancers with a high mortality rate worldwide. Despite the significant advances in diagnostic and therapeutic approaches, lung cancer prognoses and survival rates remain poor due to late diagnosis, drug resistance, and adverse effects. Therefore, new intervention therapies, such as the use of natural compounds with decreased toxicities, have been considered in lung cancer therapy. Curcumin, a natural occurring polyphenol derived from turmeric (Curcuma longa) has been studied extensively in recent years for its therapeutic effects. It has been shown that curcumin demonstrates anti-cancer effects in lung cancer through various mechanisms, including inhibition of cell proliferation, invasion, and metastasis, induction of apoptosis, epigenetic alterations, and regulation of microRNA expression. Several invitro and invivo studies have shown that these mechanisms are modulated by multiple molecular targets such as STAT3, EGFR, FOXO3a, TGF-β, eIF2α, COX-2, Bcl-2, PI3KAkt/mTOR, ROS, Fas/FasL, Cdc42, E-cadherin, MMPs, and adiponectin. In addition, limitations, strategies to overcome curcumin bioavailability, and potential side effects as well as clinical trials were also reviewed.

Matched MeSH terms: Curcumin/adverse effects; Curcumin/pharmacokinetics; Curcumin/pharmacology*; Curcumin/therapeutic use
Antioxidative constituents of Etlingera elatior

Mohamad H, Lajis NH, Abas F, Ali AM, Sukari MA, Kikuzaki H, et al.

J Nat Prod, 2005 Feb;68(2):285-8.
PMID: 15730265

Phytochemical studies on the rhizomes of Etlingera elatior have resulted in the isolation of 1,7-bis(4-hydroxyphenyl)-2,4,6-heptatrienone (1), demethoxycurcumin (2), 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (3), 16-hydroxylabda-8(17),11,13-trien-15,16-olide (4), stigmast-4-en-3-one, stigmast-4-ene-3,6-dione, stigmast-4-en-6beta-ol-3-one, and 5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-ol. Compounds 1 and 4 are new, and their structures were elucidated by analysis of spectroscopic data. Diarylheptanoids 1-3 were found to inhibit lipid peroxidation in a more potent manner than alpha-tocopherol.

Matched MeSH terms: Curcumin/analogs & derivatives*; Curcumin/isolation & purification; Curcumin/pharmacology; Curcumin/chemistry
Effects of curcumin on crevicular levels of IL-1β and CCL28 in experimental gingivitis

Pulikkotil SJ, Nath S

Aust Dent J, 2015 Sep;60(3):317-27.
PMID: 26219195 DOI: 10.1111/adj.12340

Curcumin has anti-inflammatory properties. The aim of this study was to compare interleukin-1β (IL-1β) and chemokine (C-C motif) ligand 28 (CCL28) levels following a topical application of curcumin (CRM), chlorhexidine (CHX) and chlorhexidine-metronidazole (CHX-MTZ) in an experimental gingivitis human model.

Matched MeSH terms: Curcumin/administration & dosage; Curcumin/therapeutic use*
Fulltext Curcumin rescues Caenorhabditis elegans from a Burkholderia pseudomallei infection

Eng SA, Nathan S

Front Microbiol, 2015;6:290.
PMID: 25914690 DOI: 10.3389/fmicb.2015.00290

The tropical pathogen Burkholderia pseudomallei requires long-term parenteral antimicrobial treatment to eradicate the pathogen from an infected patient. However, the development of antibiotic resistance is emerging as a threat to this form of treatment. To meet the need for alternative therapeutics, we proposed a screen of natural products for compounds that do not kill the pathogen, but in turn, abrogate bacterial virulence. We suggest that the use of molecules or compounds that are non-bactericidal (bacteriostatic) will reduce or abolish the development of resistance by the pathogen. In this study, we adopted the established Caenorhabditis elegans-B. pseudomallei infection model to screen a collection of natural products for any that are able to extend the survival of B. pseudomallei infected worms. Of the 42 natural products screened, only curcumin significantly improved worm survival following infection whilst not affecting bacterial growth. This suggested that curcumin promoted B. pseudomallei-infected worm survival independent of pathogen killing. To validate that the protective effect of curcumin was directed toward the pathogen, bacteria were treated with curcumin prior to infection. Worms fed with curcumin-treated bacteria survived with a significantly extended mean-time-to-death (p < 0.0001) compared to the untreated control. In in vitro assays, curcumin reduced the activity of known virulence factors (lipase and protease) and biofilm formation. To determine if other bacterial genes were also regulated in the presence of curcumin, a genome-wide transcriptome analysis was performed on curcumin-treated pathogen. A number of genes involved in iron acquisition and transport as well as genes encoding hypothetical proteins were induced in the presence of curcumin. Thus, we propose that curcumin may attenuate B. pseudomallei by modulating the expression of a number of bacterial proteins including lipase and protease as well as biofilm formation whilst concomitantly regulating iron transport and other proteins of unknown function.

Matched MeSH terms: Curcumin
Fulltext Cognitive health of older persons in longitudinal ageing cohort studies

Ng TP

Sains Malaysiana, 2016;45:1351-1355.

Dementia poses a major global burden of care to society and health systems in ageing populations. The majority (over 60%) of persons with dementia in the world are found in Asia and developing countries with rapid rates of population ageing. Improving and maintaining the cognitive health of older persons is vital to national strategies for dementia prevention. Increasing numbers of population-based ageing cohort studies in the past decade have provided a better understanding of the factors that contribute to cognitive function and decline in old age. The roles of major demographic, psychosocial, lifestyle, behavioral and cardiovascular risk factors contributing to cognitive health were discussed using examples from the Singapore Longitudinal Ageing Studies. They include socio-demographic factors, particularly education and marital status, leisure time activity such as physical activity, social engagement and mental activities, psychological factors such as depression, cardiovascular and metabolic risk factors: obesity, diabetes, hypertension and dyslipidemia, and the metabolic syndrome, under-nutrition, low albumin, low hemoglobin, nutritional factors such as blood folate, B12 and homocysteine, omega-3 poly-unsaturated fatty acids, tea drinking and curcumin-rich turmeric in curry meals. These factors are found to be associated variously with cognitive functions (memory and learning, language, visuospatial, attention and information processing speed), rates of cognitive impairment and cognitive decline, or increased risk of developing MCI and progression to dementia.

Matched MeSH terms: Curcumin
Curcumin Sensitizes Cancers Towards TRAIL-induced Apoptosis via Extrinsic and Intrinsic Apoptotic Pathways

Ngai SC

Curr Drug Targets, 2020;21(9):849-854.
PMID: 32116190 DOI: 10.2174/1389450121666200302124426

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a natural protein expressed in a wide range of tissues in our body. It is a promising anti-cancer agent due to its selective killing of cancer cells, rendering normal cells unharmed. However, resistance occurs either intrinsically or develops over the course of TRAIL treatment. In view of its specificity to cancer cells, there is a pushing need to overcome TRAIL resistance. Curcumin (Cur), a natural active constituent of turmeric, has been evidenced to have anti-cancer properties. However, it is limited by its sparing solubility and low bioavailability. Combinational therapy is one of the most frequently used strategies to overcome these limitations, which has been proved to be more effective than monotherapy by achieving synergistic effects and reducing toxicity. This review aims to discuss TRAIL and its underlying apoptotic mechanisms, the combinational treatment of Cur and TRAIL in view of their respective limitations, and the underlying apoptotic mechanisms activated by the sensitization of cancers by Cur towards TRAIL-induced apoptosis. Finally, this review discusses the research gap and the author's insight into this research area in bridging the research gap from bench to bedside.

Matched MeSH terms: Curcumin/pharmacology*

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