Colloids Surf B Biointerfaces. 2018 Aug 16;172:51-59. doi: 10.1016/j.colsurfb.2018.08.027. [Epub ahead of print]
Assessing the potential of liposomes loaded with curcumin as a therapeutic intervention in asthma.
Curcumin a component of turmeric, which is derived from Curcuma longa is used as a colouring agent and as a dietary spice for centuries. Extensive studies have been done on the anti-inflammatory activity of curcumin along with its molecular mechanism involving different signalling pathways. However, the physicochemical and biological properties such as poor solubility and rapid metabolism of curcumin have led to low bioavailability and hence limits its application. Current therapies for asthma such as bronchodilators and inhaled corticosteroids (ICS) are aimed at controlling disease symptoms and prevent asthma exacerbation. However, this approach requires lifetime therapy and is associated with a constellation of side effects. This creates a clear unmet medical need and there is an urgent demand for new and more-effective treatments. The present study is aimed to formulate liposomes containing curcumin and evaluate for its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation on BCi-NS1.1 cell line. Curcumin and salbutamol liposomes were formulated using lipid hydration method. The prepared liposomes were characterized in terms of particle size, zeta potential, encapsulation efficiency and in-vitro release profile. The liposomes were tested on BCI-NS1.1 cell line to evaluate its anti-inflammatory properties.
The various pro-inflammatory markers studied were Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-1β (IL-1β) and Tumour Necrosis Factor-a (TNF-a). Additionally, molecular mechanics simulations were used to elucidate the positioning, energy minimization, and aqueous dispersion of the liposomal architecture involving lecithin and curcumin. The prepared curcumin formulation showed an average size and zeta potential of 271.3 ± 3.06 nm and -61.0 mV, respectively. The drug encapsulation efficiency of liposomal curcumin is 81.1%.
Both curcumin-loaded liposomes formulation (1 μg/mL, 5 μg/mL) resulted in significant (p < 0.05) reduction in the level of pro-inflammatory marker expression such as IL-6, IL-8, IL-1β and TNF-a compared to positive control group. Liposomal curcumin with the dose of 1 μg/mL reduced the inflammatory markers more effectively compared to that of 5 μg/mL. Liposomal curcumin could be a promising intervention for asthma therapy showing their efficacy in suppressing the important pro-inflammatory markers involved in the pathogenesis of asthma.
BMC Cancer. 2017 Feb 4;17(1):99. doi: 10.1186/s12885-017-3058-2.
Curcumin decreases malignant characteristics of glioblastoma stem cells via induction of reactive oxygen species.
Glioblastoma Multiforme (GBM) is the most common and lethal form of primary brain tumor in adults. Following standard treatment of surgery, radiation and chemotherapy, patients are expected to survive 12-14 months. Theorized cause of disease recurrence in these patients is tumor cell repopulation through the proliferation of treatment-resistant cancer stem cells. Current research has revealed curcumin, the principal ingredient in turmeric, can modulate multiple signaling pathways important for cancer stem cell self-renewal and survival.
Following resection, tumor specimens were dissociated and glioblastoma stem cells (GSCs) were propagated in neurosphere media and characterized via immunocytochemistry. Cell viability was determined with MTS assay. GSC proliferation, sphere forming and colony forming assays were conducted through standard counting methods. Reactive oxygen species (ROS) production was examined using the fluorescent molecular probe CM-H2DCFA. Effects on cell signaling pathways were elucidated by western blot.
We evaluate the effects of curcumin on patient-derived GSC lines. We demonstrate a curcumin-induced dose-dependent decrease in GSC viability with an approximate IC50 of 25 μM. Treatment with sub-toxic levels (2.5 μM) of curcumin significantly decreased GSC proliferation, sphere forming ability and colony forming potential. Curcumin induced ROS, promoted MAPK pathway activation, downregulated STAT3 activity and IAP family members. Inhibition of ROS with the antioxidant N-acetylcysteine reversed these effects indicating a ROS dependent mechanism.
Discoveries made in this investigation may lead to a non-toxic intervention designed to prevent recurrence in glioblastoma by targeting glioblastoma stem cells.
J Mol Cell Cardiol. 2015 May 2. pii: S0022-2828(15)00141-8. doi: 10.1016/j.yjmcc.2015.04.025. [Epub ahead of print]
Curcumin induces M2 macrophage polarization by secretion IL-4 and/or IL-13
1Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
2Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China; Key Laboratory of Molecular Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
3Department of Cardiovascular Medicine, The Second Hospital of Yulin, Yulin 719000, Shaanxi, China.
4Department of Nephrology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
5Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China. Electronic address: firstname.lastname@example.org.
6Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China; Key Laboratory of Molecular Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China. Electronic address: email@example.com.
To address the underlying mechanisms by which curcumin facilitates M2 phenotype polarization of macrophages and its roles in the protective effects during experimental autoimmune myocarditis (EAM).
METHODS AND RESULTS:
The expression of classic M2 markers, including macrophage mannose receptor (MMR), arginase-1 (Arg-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ) was upregulated in curcumin-treated Raw264.7 macrophages. Curcumin increased interleukin-4 (IL-4) and interleukin-13 (IL-13) mRNA expression and protein secretion. Curcumin notably increased STAT6 phosphorylation. Leflunomide, a STAT6 inhibitor, and IL-4 and/or IL-13 neutralizing antibodies antagonized the induction of MMR, Arg-1 and PPAR-γ by curcumin in Raw264.7 cells. In vivo, 6-week old male Lewis rats were used to induce EAM and orally administrated with curcumin or corn oil for 3weeks after myosin injection. Cardiac functional parameters, including left ventricular fractional shortening (LVFS), ejection fraction (EF), left ventricular end-systolic diameter (LVEDs) and heart rate (HR) were significantly improved by curcumin treatment.
Curcumin also reduced the inflammatory cell infiltration and myocardial mRNA levels of interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS). Meanwhile, the myocardial mRNA levels of MMR and Arg-1 were markedly up-regulated by curcumin. Immunofluorescence assay showed that the number of CD68+ MMR+ and CD68+ Arg-1+ double positive macrophages in curcumin-treated myocardial tissue was significantly higher than untreated control. The number of CD68+ iNOS+ double positive macrophages was increased obviously in EAM group, but decreased markedly by curcumin treatment.
Taken together, these results show that curcumin induces macrophage M2 polarization by secretion of IL-4 and/or IL-13.
Curcumin ameliorates EAM by reducing infiltration inflammatory macrophages and by polarizing M0 and M1 macrophages to M2 phenotype.
Genet Mol Res. 2015 Apr 15;14(2):3450-8. doi: 10.4238/2015.April.15.8.
Effect of curcumin on p38MAPK expression in DSS-induced murine ulcerative colitis
1Department of Gastroenterology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan Province, China ChangPingLicn@163.com.
2West China School of Medicine, Sichuan University, Chengdu, Sichuan Province, China.
3Department of Gastroenterology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan Province, China.
4Department of Gastroenterology, People's Hospital of Ya'an City, Sichuan Province, China.
The aim of this study was to determine the therapeutic effect of curcumin on dextran sulfate sodium-induced ulcerative colitis (UC) and to explore the related mechanism. Sixty mice were randomly divided into 6 groups. A group was the normal control group; B group was the model group; C group was the 1.5 mg/kg dexamethasone group based on the B group; and D, E and F groups were 15, 30, and 60 mg/kg curcumin groups, respectively, based on the B group. The mice were killed 7 days after treatment; the expression of TNF-α and MPO in colon tissue was determined with ELISA, and colon p-p38MAPK and p38MAPK mRNA expression was evaluated by immunohistochemistry and RT-PCR, respectively. In the C, D, E, and F groups, TNF-α and MPO levels significantly decreased (P < 0.05), and the expression of p-p38MAPK also significantly decreased (P < 0.01). The expression of p38MAPK mRNA in the C, D, E, and F groups decreased (P < 0.01), and there was a statistically significant difference between the E and F groups (P < 0.01). Curcumin had a therapeutic effect, which probably played a role in UC treatment by inhibiting the p38MAPK signaling pathway, thereby reducing the release of TNF-α.
PLoS One. 2015 May 11;10(5):e0125627. doi: 10.1371/journal.pone.0125627. eCollection 2015.
Inhibition of IL-6 signaling pathway by curcumin in uterine decidual cells
1Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI, United States of America.
IL-6 is a multifunctional pro-inflammatory cytokine and has been implicated in many gestational disorders including preterm birth. Currently, there are no appropriate therapeutic interventions available to circumvent inflammatory-mediated gestational disorders. Therefore, the goal of this study was to identify a safe and effective pharmacological compound to counterbalance inflammatory responses in the uterus. Curcumin, a naturally-occuring polyphenolic compound, has been widely used in alternative medicine to treat inflammatory diseases. However, the anti-inflammatory effect of curcumin has not been explored in uterine decidual cells, a major source of IL-6.
Therefore, we examined the effect of curcumin on IL-6 expression using two types of uterine decidual cells 1) HuF cells, primary human fibroblast cells obtained from the decidua parietalis; 2) UIII cells, a rodent non-transformed decidual cell line. Curcumin treatment completely abrogated the expression of IL-1β-induced IL-6 in these cells. Curcumin also strongly inhibited the expression of gp130, a critical molecule in IL-6 signaling, whereas expression of IL-6R and sIL-6R was not affected. Curcumin also inhibited phosphorylation and nuclear localization of STAT3, a well-known downstream mediator of IL-6 signaling.
Furthermore, curcumin attenuated IL-1β-induced IL-6 promoter reporter activity suggesting transcriptional regulation. To further understand whether NF-ҡB is involved in this inhibition, we examined the effect of curcumin on the expression of p50 and p65 subunits of NF-ҡB in decidual cells. Expression of IL-1β-induced p50 mRNA was repressed by curcumin while p65 mRNA was not affected. However, curcumin treatment dramatically inhibited both p50 and p65 protein levels and prevented its nuclear localization. This effect is at least partly mediated through the deactivation of IKK, since IL-1β-induced IKKα/β phosphorylation is decreased upon curcumin treatment.
Our results not only revealed molecular mechanisms underlying curcumin action in uterine decidual cells but also suggest that this compound may have therapeutic potential for the prevention of inflammation-mediated preterm birth and other gestational disorders.