Immunomodulatory effects of curcumin: In-vivo

Research Square (Research Square), 2023

The current study aims to appreciate curcumin's anti-in ammatory and immuno-modulation properties through the investigation of its effect on the neutrophil enzymes (MPO and elastase) activities. The toxicity of pure curcumin was studied using three cell types: human neutrophils, NOD mouse Langerhans β cell line (NIT-1), and mouse breast cancer carcinoma cell line (EMT-6). Neutrophil isolation from whole blood was assessed using the histopaque gradient density method. After the MPO and elastase extraction from isolated neutrophils, the modulatory effect of curcumin on the activity of these enzymes was assayed using 3,3′,5,5′-tétramethylbenzidine and le N-Methoxy-Suc-(Ala)2-Pro-Val-p-Nitroanilide as speci c substrates, respectively. Also, the Cytotoxic of curcumin was investigated on the EMT6, NIT-1, and neutrophils cells using XTT and trypan blue exclusion assays, respectively. Results indicate that curcumin modulates the neutrophil's activity by inhibiting its enzymes. In effect, curcumin exerts a signi cant dosedependent inhibitory effect on both MPO and elastase activities with IC 50 of 14.41± 1.74 μg/ml and 6.06± 3.67 μg/ml. On the other hand, we reveal that curcumin signi cantly decreases neutrophil viability in a dose-dependent manner with IC50 = 25.60 ± 7.88 μg/ml. Moreover, no signi cant cytotoxic effect on EMT6 and NIT-1cells lines was shown. The IC 50 of EMT6 breast cancer cell and NIT-1cell lines were higher than 30 μg/ml and 60 μg/ml, respectively. While, doxorubicin, an anti-cancer drug used as a positive control, signi cantly reduces EMT6 viability with IC 50 of 4.885± 0.063 μg/ml. These results indicate that curcumin has a potential anti-in ammatory effect considering neutrophil viability and some of its activities. Moreover, curcumin has shown selective cytotoxicity toward neutrophils with no prominent cytotoxic effect on EMT6 and NIT-1 cell lines. Given these results, we can think of proposing curcumin for anti-in ammatory and immunomodulatory use.

FEBS Letters, 2000

Curcumin, the yellow pigment from Curcuma longa, has been shown to possess tumoricidal activity. We have earlier reported the induction of apoptosis in AK-5, rat histiocytic cells by curcumin leading to the inhibition of tumor growth in vivo. In this study we have observed differential activation status in host macrophages and NK cells induced by curcumin during the spontaneous regression of subcutaneously transplanted AK-5 tumors. Closer scrutiny of the cytokine profile and nitric oxide (NO) production by immune cells showed an initial downregulation of Th1 cytokine response and NO production by macrophages, and their upregulation in NK cells, which pickedup upon prolonged treatment with curcumin, culminating in a stronger tumoricidal effect. These studies suggest that the host macrophages and NK cells play an important modulatory role in the remission of AK-5 tumor.

Cancer Detection and Prevention, 2005

Background: The true therapeutic benefit of the use of natural products, especially acceptable dietary components such as curcumin, which can spare the normal cells and boost host immunity, has opened new horizons in cancer prevention and treatment. Methods: In our model system we used Ehrlich's ascites carcinoma cells grown in peritoneal carity of Swiss albino mice and curcumin was fed every alternative day. Results: Here, we report that curcumin administration to tumor-bearing mice decreased tumor cell number significantly in a dose-dependent manner. Furthermore, tumor-induced depletion of immune cell number of the host, as was evidenced from the decrease in bone marrow progenitor as well as thymic and splenic mononuclear cell numbers, was reintrated by curcumin. In fact, curcumin inhibited tumor-induced apoptosis of both thymocytes and splenocytes thereby restoring immune cell numbers to normal level in treated Ehrlich's ascites carcinoma-bearing mice. Moreover, curcumin was not toxic to the host; rather in tumor-bearing mice it inhibited hematopoietic toxicity, acted as a hepatoprotective agent and activated depressed anti-oxidant and detoxification systems. Conclusion: The ability of curcumin to regress tumor as well as to protect the host from tumor-induced immunosuppression and toxicity strongly supports the candidacy of curcumin as a potential agent for the dietary therapy of cancer.

International Immunopharmacology, 2011

Inflammation is a disease of vigorous uncontrolled activated immune responses. Overwhelming reports have suggested that the modulation of immune responses by curcumin plays a dominant role in the treatment of inflammation and metabolic diseases. Observations from both in-vitro and in-vivo studies have provided strong evidence towards the therapeutic potential of curcumin. These studies have also identified a plethora of biological targets and intricate mechanisms of action that characterize curcumin as a potent 'drug' for numerous ailments. During inflammation the functional influence of lymphocytes and the related cross-talk can be modulated by curcumin to achieve the desired immune status against diseases. This review describes the regulation of immune responses by curcumin and effectiveness of curcumin in treatment of diseases of diverse nature.

Cellular and Molecular Immunology, 2010

Immune dysfunction is well documented during tumor progression and likely contributes to tumor immune evasion. CD8 1 cytotoxic T lymphocytes (CTLs) are involved in antigen-specific tumor destruction and CD4 1 T cells are essential for helping this CD8 1 T cell-dependent tumor eradication. Tumors often target and inhibit T-cell function to escape from immune surveillance. This dysfunction includes loss of effector and memory T cells, bias towards type 2 cytokines and expansion of T regulatory (Treg) cells. Curcumin has previously been shown to have antitumor activity and some research has addressed the immunoprotective potential of this plant-derived polyphenol in tumor-bearing hosts. Here we examined the role of curcumin in the prevention of tumor-induced dysfunction of T cell-based immune responses. We observed severe loss of both effector and memory T-cell populations, downregulation of type 1 and upregulation of type 2 immune responses and decreased proliferation of effector T cells in the presence of tumors. Curcumin, in turn, prevented this loss of T cells, expanded central memory T cell (T CM)/effector memory T cell (T EM) populations, reversed the type 2 immune bias and attenuated the tumor-induced inhibition of T-cell proliferation in tumor-bearing hosts. Further investigation revealed that tumor burden upregulated Treg cell populations and stimulated the production of the immunosuppressive cytokines transforming growth factor (TGF)-b and IL-10 in these cells. Curcumin, however, inhibited the suppressive activity of Treg cells by downregulating the production of TGF-b and IL-10 in these cells. More importantly, curcumin treatment enhanced the ability of effector T cells to kill cancer cells. Overall, our observations suggest that the unique properties of curcumin may be exploited for successful attenuation of tumor-induced suppression of cell-mediated immune responses.

Frontiers in Oncology, 2021

The components of the immune system play a very sincere and crucial role in combating tumors. However, despite their firm efforts of elimination, tumor cells cleverly escape the surveillance process by adopting several immune evasion mechanisms. The conversion of immunogenicity of tumor microenvironment into tolerogenic is considered as a prime reason for tumor immune escape. Therapeutically, different immunotherapies have been adopted to block such immune escaping routes along with better clinical outcomes. Still, the therapies are haunted by several drawbacks. Over time, curcumin has been considered as a potential anti-cancer molecule. Its potentialities have been recorded against the standard hallmarks of cancer such as continuous proliferation, escaping apoptosis, continuous angiogenesis, insensitivity to growth inhibitors, tissue invasion, and metastasis. Hence, the diversity of curcumin functioning has already been established and exploration of its application with immunotherapies might open up a new avenue for scientists and clinicians. In this review, we briefly discuss the tumor's way of immune escaping, followed by various modern immunotherapies that have been used to encounter the escaping paths and their minute flaws. Finally, the conclusion has been drawn with the application of curcumin as a potential immune-adjuvant, which fearlessly could be used with immunotherapies for best outcomes.

2011

Phytomedicine, 2009

Curcumin is a phenolic natural product isolated from the rhizome of Curcuma longa (tumeric). It was previously described that curcumin had a potent anti-inflammatory effect and inhibited the proliferation of a variety of tumor cells. In the present study, we investigated the inhibitory effects of curcumin on the response of normal murine splenic B cells. Curcumin inhibited the proliferative response of purified splenic B cells from BALB/c mice stimulated with the Toll-like receptor ligands LPS and CpG oligodeoxynucleotides. LPS-induced IgM secretion was also inhibited by curcumin. The proliferative response induced by either the T-independent type 2 stimuli anti-delta-dextran or anti-IgM antibodies was relatively resistant to the effect of curcumin. We investigated the intracellular signaling events involved in the inhibitory effects of curcumin on murine B cells. Curcumin did not inhibit the increase in calcium levels induced by anti-IgM antibody. Western blotting analysis showed that curcumin inhibited TLR ligands and anti-IgMinduced phosphorylation of ERK, IκB and p38. Curcumin also decreased the nuclear levels of NFκB. Our results suggested that curcumin is an important inhibitor of signaling pathways activated upon B cell stimulation by TLR ligands. These data indicate that curcumin could be a potent pharmacological inhibitor of B cell activation.

Journal of Surgical Research, 2004

Background. T cell mediated acute rejection of transplanted organ continues to be a noticeable problem in solid organ transplantation. We showed that Curcumin is a potent inhibitor of Cyclosporin A resistant T cell CD28 co-stimulation pathway. Here we report the inhibitory effects of Curcumin on mitogenstimulated lymphocyte proliferation, IL-2 synthesis/ signaling, and NFB (transcription factor of IL-2 promoter) activation. Materials and methods. Human lymphocytes were isolated from fresh human spleen (SP-L). Mitogens [final concentrations of 2 g/ml concanavalin A (Con A), 5 g/ml phytohemagglutinin (PHA), and 20 ng/ml of phorbol-12-myristate-13-acetate (PMA)] were added to the designated wells in a 96-well plate with 0.2 million SP-L and cultured for 48 h and then assayed for IL-2 synthesis by ELISA and 3 H-thymidine uptake. In another parallel experiment we added IL-2 (0.5 nM) to stimulate the cells to check if Curcumin's inhibition of IL-2 synthesis is the sole reason for inhibition of cell proliferation. Electrophoretic mobility shift assay (EMSA) was performed in PMA (20 ng/ml, 1 h) stimulated cells with or without Curcumin to assay NFB activation. Results. Curcumin at 2.5 g/ml inhibited Con A, PHA, and PMA stimulated SP-L proliferation at 77, 23, and 48%, respectively, over controls and Curcumin at 5 g/ml completely (nearly 100%) inhibited the mitogen stimulated proliferation. Curcumin inhibited IL-2 synthesis in Con A, PHA, and PMA stimulated SP-L in a concentration-dependent manner with an ED50 (concentration required for 50% inhibition) measured at 3.5 g/ml. Exogenous IL-2 stimulated SP-L proliferation was also inhibited by Curcumin in a concentration-dependent manner with an ED50 of 2 g/ml. EMSA assay indicated that PMA at 20 ng/ml stimulated NFB activation 253% over control, which was inhibited by 24, 38, and 73%, respectively, with Curcumin at final concentrations of 2.5, 5, and 10 g/ml, respectively. Conclusion. Curcumin has profound immunosuppressive effects mediated via inhibition of IL-2 synthesis, mitogen, and IL-2 induced activation of human lymphocytes. This effect may be mediated via NFB inhibition.

Journal of Biological Research, 2020

Curcumin, an active substance contained in an Indian spice called turmeric or curcuma, is well known for its anti-inflammatory and antioxidant properties. In recent times, it was taken into account and studied as an antitumoral molecule, by relying on its interference on several biological mechanisms, such as the inhibition of inflammatory mediators, the enhancement of detoxifying enzymes' action and processes of cell growth and proliferation. Studies show how the high dosage of curcumin in vitro inhibits colorectal tumor cells, pancreatic tumor cells, lung cancer cells and glioblastoma's cells, interfering in signaling pathways as Wnt/β-catenin, NF-kB and PI3K/Akt and leading to cell cycle arrest and apoptosis. Furthermore, the association between curcumin and chemothera-peutic agents such as 5-fluorouracil strengthens the drug's cytotox-icity and cells' susceptibility towards the chemotherapeutic agent.