Activity Of Curcumin Research Articles

Curcumin Inhibits Lysophosphatidic Acid Mediated MCP-1 Expression via Blocking ROCK Signalling.

Curcumin is a natural compound that has been widely used as a food additive and medicine in Asian countries. Over several decades, diverse biological effects of curcumin have been elucidated, such as anti-inflammatory and anti-oxidative activities. Monocyte chemoattractant protein-1 (MCP-1) is a key inflammatory marker during the development of atherosclerosis, and curcumin blocks MCP-1 expression stimulated by various ligands. Hence, we studied the action of curcumin on lysophosphatidic acid (LPA) mediated MCP-1 expression and explored the specific underlying mechanisms. In human vascular smooth muscle cells, LPA induces Rho-associated protein kinase (ROCK) dependent transforming growth factor receptor (TGFBR1) transactivation, leading to glycosaminoglycan chain elongation. We found that LPA also signals via the TGFBR1 transactivation pathway to regulate MCP-1 expression. Curcumin blocks LPA mediated TGFBR1 transactivation and subsequent MCP-1 expression by blocking the ROCK signalling. In the vasculature, ROCK signalling regulates smooth muscle cell contraction, inflammatory cell recruitment, endothelial dysfunction and vascular remodelling. Therefore, curcumin as a ROCK signalling inhibitor has the potential to prevent atherogenesis via multiple ways.

The Diarylheptanoid Curcumin Induces MYC Inhibition and Cross-Links This Oncoprotein to the Coactivator TRRAP.

The c-Myc protein (MYC) is a transcription factor with strong oncogenic potential controlling fundamental cellular processes. In most human tumors, MYC is overexpressed by enhanced transcriptional activation, gene amplification, chromosomal rearrangements, or increased protein stabilization. To pharmacologically suppress oncogenic MYC functions, multiple approaches have been applied either to inhibit transcriptional activation of the endogenous MYC gene, or to interfere with biochemical functions of aberrantly activated MYC. Other critical points of attack are targeted protein modification, or destabilization leading to a non-functional MYC oncoprotein. It has been claimed that the natural compound curcumin representing the principal curcumoid of turmeric (Curcuma longa) has anticancer properties although its specificity, efficacy, and the underlying molecular mechanisms have been controversially discussed. Here, we have tested curcumin’s effect on MYC-dependent cell transformation and transcriptional activation, and found that this natural compound interferes with both of these MYC activities. Furthermore, in curcumin-treated cells, the endogenous 60-kDa MYC protein is covalently and specifically cross-linked to one of its transcriptional interaction partners, namely the 434-kDa transformation/transcription domain associated protein (TRRAP). Thereby, endogenous MYC levels are strongly reduced and cells stop to proliferate. TRRAP is a multidomain adaptor protein of the phosphoinositide 3-kinase-related kinases (PIKK) family and represents an important component of many histone acetyltransferase (HAT) complexes. TRRAP is important to mediate transcriptional activation executed by the MYC oncoprotein, but on the other hand TRRAP also negatively regulates protein stability of the tumor suppressor p53 (TP53). Curcumin-mediated covalent binding of MYC to TRRAP reduces the protein amounts of both interaction partners but does not downregulate TP53, so that the growth-arresting effect of wild type TP53 could prevail. Our results elucidate a molecular mechanism of curcumin action that specifically and irreversibly targets two crucial multifunctional cellular players. With regard to their broad impact in cancer, our findings contribute to explain the pleiotropic functions of curcumin, and suggest that this natural spice, or more bioavailable derivatives thereof, may constitute useful adjuvants in the therapy of MYC-dependent and TRRAP-associated human tumors.

Impact of curcumin on fatty acid metabolism.

Free fatty acids (FFAs) and fatty acid synthesis (FAS) activity have significantly contributed to disease states such as insulin resistance, obesity, type 2 diabetes, myocardial infarction, blood pressure, and several types of cancer. Currently, several treatment options are available for patients with these conditions. Due to safety concerns, adverse effects, limited efficacy, and low tolerability associated with many medications, the identification of novel agents with less toxicity and a more favorable outcome is warranted. Curcumin is a phenolic compound derived from the turmeric plant with various biological activities, including anticarcinogenic, antioxidant, antiinflammatory, and hypolipidemic properties. PubMed, Scopus, and Web of Science were searched up to February 2020 for studies that demonstrated the efficacy and mechanisms of curcumin action on FFAs, FAS, and β-oxidation activity, as well as the desaturation system. Most of the evidence is in-vivo and in-vitro studies that demonstrate that curcumin possesses regulatory properties on FFAs levels through its effects on FAS and β-oxidation activity as well as desaturation system, which could improve insulin resistance, obesity, and other FFAs-related disorders. The present study provides a review of the existing in-vitro, in-vivo, and clinical evidence on the effect of curcumin on FFAs and FAS activity, β-oxidation, and desaturation system.

Curcumin relieves mice gastric emptying dysfunction induced by L-arginine and atropine through interstitial cells of Cajal.

Curcumin is natural polyphenol from Curcuma longa rhizomes with several biological properties. Our previous studies demonstrated that curcumin inhibited functional gastric emptying disorders induced by L-arginine, the precursor of nitric oxide (NO), and atropine, an acetylcholine receptor (AChR) blocker. However, the mechanism of action of curcumin remains unclear. In the present study, mouse models of functional gastric emptying disorders induced by L-arginine and atropine were used to examine changes in interstitial cells of Cajal (ICC) and NO- and ACh-mediated regulation of gastrointestinal motility. Curcumin pre-treatment ameliorated the gastric emptying rate in mice treated with L-arginine or atropine (P<0.01). NO content and NO synthase activity significantly increased in the stomachs of L-arginine-treated mice, compared with controls (P<0.01). Acetylcholinesterase activity (P<0.01) and mRNA expression (P<0.01), as well as AChR mRNA levels (P<0.05) significantly decreased following atropine treatment. Moreover, in both models, the levels of c-kit, anoctamin 1 and connexin 43 significantly decreased in the stomach (P<0.01). Conversely, curcumin pre-treatment inhibited the changes induced by L-arginine and atropine (P<0.01 or P<0.05). By affecting the production of exogenous NO, the effects of Ach-AchR and the biomarkers of ICC, curcumin relieves the gastric emptying dysfunction in mice.

Curcumin and Its Derivatives: A Review of Their Biological Activities

Curcumin is a bright yellow phytochemical derived from the rhizome of Curcuma longa. Since its initial extraction from this plant, curcumin is attaining great attention from the researchers of the medical field. Curcumin possesses a wide range of biological effects such as antimicrobial, antiproliferative, antioxidant, anti-inflammatory, antidiabetic and neuroprotective activities. Such versatility makes curcumin a promising lead compound for the development of new derivatives that may have a role in the management of numerous illnesses like cancer, diabetes and Alzheimer’s disease. In this paper, the focus was concentrated on some of the currently available animal and clinical studies which revealed the potential pharmacological actions of curcumin and its derivatives.

The effects of nano-curcumin supplementation on Th2/tregulatory axis in migraine patients: a randomized, double-blind, placebo-controlled trial

Aim In the present study we aimed to investigate the effects of nano-curcumin supplementation on gene expression and serum levels of IL-4 and TGF-β in migraine patients. Methods Forty participants with episodic migraine were randomly allocated to receive 80 mg nano-curcumin (n = 20) or placebo (n = 20) in a randomized double-blind clinical trial for two months. At the beginning and the end of the study, the interictal serum levels and gene expression of IL-4 and TGF-β in peripheral blood mononuclear cells (PBMCs) isolated from migraine patients were measured, using ELISA and real-time PCR methods, respectively. Results Intra-group assays showed a significant rise in the gene expression of both IL-4 and TGF-β (p < 0.05) in nano-curcumin group after two months of treatment, however the serum levels were only significantly changed for IL-4 (p < 0.05). On the contrast, inter-group assays revealed no statistical differences between nano-curcumin and placebo group in terms of IL-4 and TGF-β gene expression, while the serum levels of IL-4 was observed to be increased significantly (p = 0.03) following two month nano-curcumin supplementation. Conclusion The findings of the present trial suggest that the treatment with nano-curcumin could induce significant levels of IL-4, in favour of anti-inflammatory effects, while has a minimal effects on the both gene expression and serum levels of TGF-β. Further studies are required to determine the exact mechanism of action of curcumin in patients with migraine.

TAp63α Is Involved in Tobacco Smoke-Induced Lung Cancer EMT and the Anti-cancer Activity of Curcumin via miR-19 Transcriptional Suppression.

As a key risk factor for lung cancer, tobacco smoke (TS) influences several cellular processes, including epithelial-mesenchymal transition (EMT). TAp63α is a crucial transcription factor involved in tumor progression. The present study was designed to investigate the potential role and underlying mechanisms of TAp63α in TS-induced lung cancer EMT. We found that compared to normal tissues, the tumor tissues collected from lung cancer patients showed a lower level of TAp63α expression, along with downregulated E-cadherin expression and upregulated Vimentin expression. Results of treatment with TAp63α and TAp63α siRNA as well as with tumor growth factor-β (TGF-β) showed that TAp63α acted as a tumor suppressor gene, and its upregulated expression suppressed lung cancer EMT. Significantly, TS exposure altered expression of EMT-related markers, enhanced cell migratory and invasive capacities, and decreased the TAp63α expression level in lung cancer cells. Overexpression of TAp63α significantly alleviated TS-stimulated lung cancer EMT. Mechanistically, TAp63α expression transcriptionally reduced the miR-19 level, which resulted in the suppression of lung cancer EMT. Additionally, as a natural compound possessing anti-cancer effects, curcumin inhibited TS-induced lung cancer EMT by increasing TAp63α expression and reducing miR-19 expression. Collectively, our results indicate that TAp63α inhibits TS-induced lung cancer EMT via transcriptionally suppressing miR-19 and the inhibitory effect of TAp63α on miR-19 mediates the anti-cancer action of curcumin. These findings provide new insights into novel targets for lung cancer prevention.

Curcumin promotes oligodendrocyte differentiation and their protection against TNF-\u03b1 through the activation of the nuclear receptor PPAR-\u03b3

Curcumin is a compound found in the rhizome of Curcuma longa (turmeric) with a large repertoire of pharmacological properties, including anti-inflammatory and neuroprotective activities. The current study aims to assess the effects of this natural compound on oligodendrocyte progenitor (OP) differentiation, particularly in inflammatory conditions. We found that curcumin can promote the differentiation of OPs and to counteract the maturation arrest of OPs induced by TNF-α by a mechanism involving PPAR-γ (peroxisome proliferator activated receptor), a ligand-activated transcription factor with neuroprotective and anti-inflammatory capabilities. Furthermore, curcumin induces the phosphorylation of the protein kinase ERK1/2 known to regulate the transition from OPs to immature oligodendrocytes (OLs), by a mechanism only partially dependent on PPAR-γ. Curcumin is also able to raise the levels of the co-factor PGC1-α and of the cytochrome c oxidase core protein COX1, even when OPs are exposed to TNF-α, through a PPAR-γ-mediated mechanism, in line with the known ability of PPAR-γ to promote mitochondrial integrity and functions, which are crucial for OL differentiation to occur. Altogether, this study provides evidence for a further mechanism of action of curcumin besides its well-known anti-inflammatory properties and supports the suggested therapeutic potential of this nutraceutical in demyelinating diseases.

Effects of Curcumin Treatment in a Diabetic Neuropathic Pain Model of Rats: Involvement of c-Jun N-Terminal Kinase Located in the Astrocytes and Neurons of the Dorsal Root Ganglion.

Curcumin (diferuloylmethane) is a major component of turmeric, which is isolated from the rhizomes of Curcuma longa L. from the family Zingiberaceae. It is used as a dietary pigment for curry and in traditional Indian medicine for its anti-inflammatory and attenuating pain effects. This study aimed to evaluate the beneficial effects of curcumin in a rat model of diabetic neuropathic pain. Additionally, we investigated the involvement of the phosphorylated form of c-Jun N-terminal kinase (pJNK) located in the neurons and astrocytes of the dorsal root ganglion (DRG). To induce diabetic neuropathic pain in rats, 50 mg/kg of streptozotocin (STZ) was intraperitoneally injected. After 4 weeks, rats were administered the vehicle, 10 mg/kg/day curcumin, or 50 mg/kg/day curcumin orally for 4 consecutive weeks. One day after the final drug administration, we performed behavioral tests to measure responses of rats to mechanical, heat, cold, and acetone-induced cold stimuli. After behavioral tests, pJNK expression in the DRG was evaluated using western blot assay and immunohistochemistry. Curcumin treatment for 4 consecutive weeks in STZ-induced diabetic neuropathic pain rats improved behavioral responses to mechanical, cold, and thermal stimuli. Increased pJNK expression in the astrocytes and neurons of the DRG in STZ-induced diabetic neuropathic pain rats was reduced by curcumin treatment for 4 consecutive weeks. We suggest that curcumin can be an option for the treatment of diabetes-related neuropathic pain, and one of the mechanisms that underlie the action of curcumin may involve pJNK expression in the astrocytes and neurons of the DRG.

The Multifaced Actions of Curcumin in Pregnancy Outcome.

Curcumin, also known as diferuloylmethane, is the main polyphenolic substance present in the rhizomes of Curcuma longa L. This plant showed many beneficial effects and has been used since ancient times for both food and pharmaceutical purposes. Due to its pleiotropic functions, curcumin consumption in the human diet has become very common thanks also to the fact that this natural compound is considered quite safe as it does not have serious side effects. Its functions as an anti-inflammatory, anti-oxidant, neuroprotective, immunomodulatory, anti-toxicant, anti-apoptotic, and anti-diabetic compound are already known and widely demonstrated. There are numerous studies concerning its effects on various human pathologies including cancer, diabetes and arthritis while the studies on curcumin during pregnancy have been performed only in animal models. Data concerning the role of curcumin as anti-inflammatory compound suggest a possible use of curcumin in managing pregnancy complications such as Preeclampsia (PE), Gestational Diabetes Mellitus (GDM), Fetal Growth Restriction (FGR), PreTerm Birth (PTB), and exposure to toxic agents and pathogens. The aim of this review is to present data to support the possible use of curcumin in clinical trials on human gestation complications.

The Multifaceted Actions of Curcumin in Obesity.

Obesity remains a pervasive health concern worldwide with concomitant comorbidities such as cardiovascular diseases, diabetes, inflammation, and other metabolic disorders. A wealth of data validates dietary and lifestyle modifications such as restricting caloric intake and increasing physical activity to slow the obesity development. Recently, the advent of phytochemicals such as curcumin, the active ingredient in turmeric, has attracted considerable research interest in tracking down their possible effects in protection against obesity and obesity-related comorbidities. According to the existing literature, curcumin may regulate lipid metabolism and suppress chronic inflammation interacting with white adipose tissue, which plays a central role in the complications associated with obesity. Curcumin also inhibits the differentiation of adipocyte and improves antioxidant properties. In the present review, we sought to deliberate the possible effects of curcumin in downregulating obesity and curtailing the adverse health effects of obesity.

Administration of curcumin affects the anxiety behavior in Wistar rats after formaldehyde injected

The curcumin is part of the curcuminoids family. Present in the spice turmeric is a vegetable alkaloid obtained from Curcuma longa. Many studies have been carried out to describe the multiple biological actions of curcumin. The positive antidepressant and anti-anxiety effects of curcumin are most likely due to its ability to normalize specific physiological mechanisms, in addition to being a potent antioxidant and anti-inflammatory agent. Curcumin also protects the brain and simultaneously acts on several mechanisms related to depression. It is considered to be the most promising therapeutic target for treating depressive behaviors. Through this work, we will prove the protective effect of curcumin on the anxious behavior of Wistar rats and the complications induced by the administration of a toxic product that is formaldehyde. To this fact, 25 white rats of Wistar strains (250±50 g) were separated into five experimental batches: control batch (T; n = 5), vehicle control batch (CV; n = 5), Curcumin control batch (CC; n = 5), one batch formaldehyde vehicle (FV; n = 5) and one batch formaldehyde Curcumin (FC; n = 5). A single intraperitoneal injection carried out the formaldehyde administration diluted in distilled water at a dose of 10 mg/kg. Turmeric dissolved in olive oil was administered by gastric gavage at a dose of (60 mg/kg). Our results show the therapeutic benefits of curcumin against the deficits caused by formaldehyde reflected in a disturbance in rat behavior and degree of anxiety using the open-field test and the light and dark box test.

Effect of curcumin on the contraction of isolated goat uterus

Background: The aim of the study was to investigate the effect and mechanism of action of curcumin on potassium chloride (KCl) induced contraction of isolated goat uterine tissue.Methods: KCl induced contraction in the presence and absence of log doses of curcumin were obtained with the help of force transducer and student physiograph. Also, the effect of glibenclamide (K+ATP channel blocker) and methylene blue v (nitric oxide blocker) on the contractility of uterus tissue in presence of curcumin was recorded. Wilcoxon Signed Rank test was used for statistical analysis. The percentage inhibition of height and area under curve were calculated.Results: There was decrease in the height of KCl induced contraction in the presence of curcumin 4 µM (p value 0.046) 40 µM (p value=0.028) and 400 µM (p value=0.028). There was reduction in area under curve of KCl induced contraction in presence of curcumin 4 µM (p value=0.463) 40µM (p value=0.027) and 400 µM (p value=0.028). There was decrease in the height (p value=0.046) and significant decrease in area (p value=0.046) of KCl induced contraction in the presence of curcumin 100 µM and glibenclamide. There was decrease in height (p value=0.027) and area (p value=0.028) of KCl induced contraction in the presence of curcumin 100 µM and methylene blue.Conclusions: Curcumin causes relaxation of goat uterus. Since methylene blue and glibenclamide were not able to reverse the inhibition produced by curcumin it implies curcumin may not act via the nitric oxide pathway nor does it interact with K+ATP channels to relax the uterus.

Curcumin Innovative Delivery Forms: Paving the ‘Yellow Brick Road’ of Antitumoral Phytotherapy

This review deals with the various aspects involved in the medicinal action of curcumin, from the photosensitivity and its relevance to storage and shelf-life, to the different routes of administration, which influence the bioavailability. The focus of the review is on the antitumor properties of curcumin and the currently available solutions for their amelioration. The work starts by presenting a brief historical perspective on the origins and uses of curcumin, from early days until the present time. The following sections describe the physico-chemical properties of curcumin and their impact on the biological activity and pharmacokinetics, raising awareness to the need for formulations able to improve the bioavailability. The last section is focused on research efforts being made to circumvent curcumin’s instability and low availability due to the extensive hepatic first pass metabolism, describing innovative scientific advances and new patented formulations and emerging products on the market.

Curcumin in Depression: Potential Mechanisms of Action and Current Evidence—A Narrative Review

Major depressive disorder (MDD) is one of the most prevalent and debilitating disorders. Current available treatments are somehow limited, so alternative therapeutic approaches targeting different biological pathways are being investigated to improve treatment outcomes. Curcumin is the main active component in the spice turmeric that has been used for centuries in Ayurvedic medicine to treat a variety of conditions, including anxiety and depressive disorders. In the past decades, curcumin has drawn researchers' attention and displays a broad range of properties that seem relevant to depression pathophysiology. In this review, we break down the potential mechanisms of action of curcumin with emphasis on the diverse systems that can be disrupted in MDD. Curcumin has displayed, in a number of studies, a potency in modulating neurotransmitter concentrations, inflammatory pathways, excitotoxicity, neuroplasticity, hypothalamic–pituitary–adrenal disturbances, insulin resistance, oxidative and nitrosative stress, and endocannabinoid system, all of which can be involved in MDD pathophysiology. To date, a handful of clinical trials have been published and suggest a benefit of curcumin in MDD. With evidence that is progressively growing, curcumin appears as a promising alternative option in the management of MDD.

Curcumin Attenuates Hypoxia-Induced Oxidative Neurotoxicity, Apoptosis, Calcium, and Zinc Ion Influxes in a Neuronal Cell Line: Involvement of TRPM2 Channel.

Apoptosis/cell death and reactive oxygen species (ROS) via overload free Ca2+ and Zn2+ uptake into mitochondria are emerging as crucial events in the etiology of hypoxia (HPX)-induced neurodegenerative diseases. The neuroprotective actions of curcumin (CURC) via modulation of oxidative stress and the PARP1-dependent activated TRPM2 cation channel on the ROS generation and cell death in several neurons have been recognized. However, the molecular mechanisms underlying CURC's neuroprotection remain elusive. We investigated the role of CURC via modulation of TRPM2 on cell death and oxidative cytotoxicity in SH-SY5Y neuronal cells. The SH-SY5Y cells were divided into five groups as follows: CURC (10µM for 24h), HPX (200µM CoCl2 for 24h), CURC+HPX, and HPX+TRPM2 blockers (2-APB-100µM or ACA-25µM for 30min). In some experiments, the cells in the HPX groups were additionally incubated with PARP1 (PJ34) and Zn2+ (TPEN) inhibitors. The exposure of CoCl2 induced increases of TRPM2 current density and Ca2+ fluorescence intensity with an increase of mitochondrial membrane depolarization and ROS generation. When HPX-induced TRPM2 activity was blocked by 2-APB and ACA, or the cells were treated with CURC, the increase of ROS generation, the expression levels of TRPM2 and PARP1 were restored. The levels of apoptosis and cell death in the cells were enriched with increases of caspase-3 and -9 activations, although they were decreased by CURC treatment. HPX-induced increase of cytosolic Zn2+ was attenuated by the TPEN and CURC treatments. In conclusion, CURC attenuates HPX-induced mitochondrial ROS generation, apoptosis, cell death, and TRPM2-mediated Ca2+ signaling and may provide an avenue for treating HPX-induced neurological diseases associated with the ROS, Ca2+, and Zn2+.

Effects of the Use of Curcumin on Ulcerative Colitis and Crohn's Disease: A Systematic Review.

Inflammatory bowel disease (IBD) is an umbrella term used to describe chronic inflammatory disorders related to a substantial reduction in the quality of life of patients. Some patients with Crohn's disease (CD) and ulcerative colitis (UC) are refractory to conventional therapies, and Curcuma longa derivatives have been considered as adjuvants. Owing to the anti-inflammatory and antioxidant effects, some clinical trials used this plant in the therapeutic approach of IBD, and some meta-analyses evaluated the outcomes found in these studies. Owing to controversial findings, our systematic review aimed to evaluate these studies to show whether C. longa compounds can still be considered in the therapeutic approach of patients with CD and UC. MEDLINE-PubMed, EMBASE, and Cochrane were searched, and Preferred Reporting Items for a Systematic Review and Meta-Analysis guidelines were followed. The results of the randomized clinical trials (RCTs) showed promising results with the use of curcumin in the therapeutic approach of both UC and CD patients. Some meta-analyses show controversial results, possibly due to the presence of bias in the included studies. The actions of curcumin are achieved by several mechanisms, such as reducing the expression of interleukin (IL)-1, IL-6, IL-12, and tumor necrosis factor-α. Moreover, it reduces the levels of reactive oxygen species, such as superoxide anions and malondialdehyde. The results of using curcumin in CD and UC patients are challenging to be evaluated because RCTs are variable in the dose and the formulations of curcumin, in the time of treatment, and the route of administration. The number of patients in the samples is also usually small.

Curcumin: Could This Compound Be Useful in Pregnancy and Pregnancy-Related Complications?

Curcumin, the main polyphenol contained in turmeric root (Curcuma longa), has played a significant role in medicine for centuries. The growing interest in plant-derived substances has led to increased consumption of them also in pregnancy. The pleiotropic and multi-targeting actions of curcumin have made it very attractive as a health-promoting compound. In spite of the beneficial effects observed in various chronic diseases in humans, limited and fragmentary information is currently available about curcumin’s effects on pregnancy and pregnancy-related complications. It is known that immune-metabolic alterations occurring during pregnancy have consequences on both maternal and fetal tissues, leading to short- and long-term complications. The reported anti-inflammatory, antioxidant, antitoxicant, neuroprotective, immunomodulatory, antiapoptotic, antiangiogenic, anti-hypertensive, and antidiabetic properties of curcumin appear to be encouraging, not only for the management of pregnancy-related disorders, including gestational diabetes mellitus (GDM), preeclampsia (PE), depression, preterm birth, and fetal growth disorders but also to contrast damage induced by natural and chemical toxic agents. The current review summarizes the latest data, mostly obtained from animal models and in vitro studies, on the impact of curcumin on the molecular mechanisms involved in pregnancy pathophysiology, with the aim to shed light on the possible beneficial and/or adverse effects of curcumin on pregnancy outcomes.

Functional analysis of an upregulated calmodulin gene related to the acaricidal activity of curcumin against Tetranychus cinnabarinus (Boisduval).

Curcumin is a promising botanical acaricidal compound with activity against Tetranychus cinnabarinus. Calmodulin (CaM) is a key calcium ion (Ca2+ ) sensor that plays a vital role in calcium signaling. Overexpression of the CaM gene with inducible character occurs in curcumin-treated mites, but its functional role remains to be further analyzed by RNA interference (RNAi) and protein expression. A CaM gene was cloned from T. cinnabarinus (designated TcCaM). TcCaM was upregulated and the protein was activated in mites by curcumin. The susceptibility of mites to curcumin was decreased after inhibiting CaM function with anti-CaM drug trifluoperazine (TFP) and silencing CaM transcription with RNAi, suggesting that the CaM gene is involved in the acaricidal activity of curcumin against mites. Moreover, the TFP pre-treated Sf9 cells were resistant to curcumin-mediated increase in [Ca2+ ]i levels, indicating that CaM-mediated Ca2+ homeostasis was disturbed by curcumin. TcCaM was then re-engineered for heterologous expression in Escherichia coli. Strikingly, our results showed that the recombinant CaM protein was directly activated by curcumin via inducing its conformational changes, its half-maximal effective concentration (EC50 ) value is 0.3 μmol L-1 in vitro, which is similar to curcumin against CaM-expressing Sf9 cells (0.76 μmol L-1 ) in vivo. These results confirm that the overexpressed CaM gene is involved in the acaricidal activity of curcumin, and the mode of action of curcumin may be via activating CaM function, and thereby disrupting Ca2+ homeostasis in T. cinnabarinus. This study highlights the novel target mechanism of new acaricides, promoting our understanding of the molecular mechanism of CaM-mediated acaricide targets in mites.

CURCUMIN ACTIVITY AS A PHYTOTHERAPEUTIC AGENT IN THE PREVENTION AND TREATMENT OF SQUAMOUS CELL CANCER: A SCOPING REVIEW

Objective: To analyze the phytotherapeutic action of curcumin (CUR) in the prevention of and antineoplastic therapy for squamous cell cancer (SCC). Study Design: Two researchers (E.G.F.S. and Y.L.N.) performed electronic searches independently on Medline via PubMed, LILACS, and Web of Science using the search strategy (curcumin AND oral cancer). A total of 967 initial results were identified, and 21 articles were selected for the study. Results: CUR is a bioactive polyphenol component with chemopreventive, photodynamic, and therapeutic properties in the treatment of SCC. A study analyzed the performance of nanocurcumin as a chemoprotective agent, increasing the expression of pro-apoptotic proteins compared with the group treated with chemotherapeutic agents, demonstrating that the association of CUR with chemotherapeutic agents can improve apoptosis in malignant cells, thereby regulating the mortality rate of cancer cells. Analyzing the use of nanoformulations, a study revealed that the pharmaceutical association of CUR and silicon nanoparticles increased cell absorption by 5 times that compared to free CUR, thereby increasing its photodynamic activity and having a better effect on oral malignancies. Conclusion: Recent preclinical studies recommend the use of CUR related to adjuvants as the main unit in antitumor activity, however, additional research studies are needed to clarify its molecular mechanism.