Extraction of curcumin from turmeric residue (Curcuma longa L.) using deep eutectic solvents and surfactant solvents.

Using waste materials to extract biologically active ingredients with green solvents is a new trend for sustainable development. Herein, different types of deep eutectic solvents (DESs) and surfactant solvents (SSs) were used to extract curcumin from turmeric residues (TRs), among which choline chloride-propylene glycol (ChCl-Pro) showed the highest yield. The optimized extraction conditions included a ChCl : Pro ratio of 1 : 2, water content in the DESs of 20%, solid : liquid ratio of 1 : 40 maintained for 60 min at 50 °C, and a TR particle size of 0.18 mm. The extraction yield was 54.2 mg g-1, which was 1.31 times higher than when methanol was used as a solvent. Distilled water was used to recover curcumin from the DES extract with a recovery yield of 99.7%. Furthermore, the antioxidant and acetylcholinesterase (AChE) inhibitory activities of the recovered curcumin were evaluated, with IC50 values of 25.58 ± 0.51 and 19.12 ± 0.83 µg mL-1, respectively. This study highlights the promising potential of using green solvents to extract bioactive compounds from waste materials.

Efficacy and safety of adjuvant curcumin therapy in ulcerative colitis: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcumin, an active polyphenol extracted from Traditional Chinese medicine Curcuma longa (turmeric), has shown many health-related benefits and pharmacological effects. Adjuvant curcumin therapy for ulcerative colitis has become increasingly popular, but its efficacy and safety of which is still controversial. The purpose of this study is to evaluate the efficacy and safety of adjuvant curcumin therapy in ulcerative colitis. MATERIALS AND METHODS: The Medline, EMBASE, the Cochrane Library, CNKI, VIP, WanFang, and SinoMed databases were searched from inception to June 2021, to identify all randomized controlled clinical trials with adjuvant curcumin therapy in ulcerative colitis. The primary outcomes were clinical and endoscopic remission, and subgroup analyses were also performed. RESULTS: Six randomized trials with a total of 385 participants were included in this study. Qualified trials recommended that adjuvant curcumin therapy for ulcerative colitis was effective in inducing clinical remission (RR = 2.10, 95% CI 1.13 to 3.89), but not in clinical improvement (RR = 1.62, 95% CI 1.00 to 2.61), endoscopic remission (RR = 4.17, 95% CI 0.63 to 27.71) or endoscopic improvement (RR = 4.13, 95% CI 0.20 to 87.07). Included studies showed that appropriate dosage, formation, longer duration, and topical medication may have a greater potential advantage. No severe adverse effects had been reported. CONCLUSIONS: Available evidence suggested that adjuvant curcumin therapy may be effective for clinical remission in ulcerative colitis patients without causing severe adverse effects. The appropriate methods of administration can achieve better curative effect, which requires further study to verify.

Curcumin by activation of adenosine A2A receptor stimulates protein kinase a and potentiates inhibitory effect of cangrelor on platelets.

Curcumin is a natural polyphenol derived from the turmeric plant (Curcuma longa) which exhibits numerous beneficial effects on different cell types. Inhibition of platelet activation by curcumin is well known, however molecular mechanisms of its action on platelets are not fully defined. In this study, we used laser diffraction method for analysis of platelet aggregation and Western blot for analysis of intracellular signaling mechanisms of curcumin effects on platelets. We identified two new molecular mechanisms involved in the inhibitory effects of curcumin on platelet activation. Firstly, curcumin by activation of adenosine A2A receptor stimulated protein kinase A activation and phosphorylation of Vasodilator-stimulated phosphoprotein. Secondly, we demonstrated that curcumin even at low doses, which did not inhibit platelet aggregation, potentiated inhibitory effect of ADP receptor P2Y12 antagonist cangrelor which partly could be explained by activation of adenosine A2A receptor.

Improvement of the Solubilization and Extraction of Curcumin in an Edible Ternary Solvent Mixture.

A water-free, ternary solvent mixture consisting of a natural deep eutectic solvent (NADES), ethanol, and triacetin was investigated concerning its ability to dissolve and extract curcumin from Curcuma longa L. To this purpose, 11 NADES based on choline chloride, acetylcholine, and proline were screened using UV-vis measurements. A ternary phase diagram with a particularly promising NADES, based on choline chloride and levulinic acid was recorded and the solubility domains of the monophasic region were examined and correlated with the system's structuring via light scattering experiments. At the optimum composition, close to the critical point, the solubility of curcumin could be enhanced by a factor of >1.5 with respect to acetone. In extraction experiments, conducted at the points of highest solubility and evaluated via HPLC, a total yield of ~84% curcuminoids per rhizome could be reached. Through multiple extraction cycles, reusing the extraction solvent, an enrichment of curcuminoids could be achieved while altering the solution. When counteracting the solvent change, even higher concentrated extracts can be obtained.

Curcumin in Metabolic Health and Disease.

In recent years, epidemiological studies have suggested that metabolic disorders are nutritionally dependent. A healthy diet that is rich in polyphenols may be beneficial in the treatment of metabolic diseases such as polycystic ovary syndrome, metabolic syndrome, non-alcoholic fatty liver disease, cardiovascular disease, and, in particular, atherosclerosis. Curcumin is a polyphenol found in turmeric and has been reported to have antioxidant, anti-inflammatory, hepatoprotective, anti-atherosclerotic, and antidiabetic properties, among others. This review summarizes the influence of supplementation with curcumin on metabolic parameters in selected metabolic disorders.

Antioxidant Blend of Curcumin and Broccoli Seed Extract Exhibits Protective Effect on Neurodegeneration and Promotes Drosophila Lifespan.

Antioxidants and related compounds are anti-inflammatory and exhibit great potential in promoting human health. They are also often considered to be important elements in the process of neurodegeneration. Here we describe a antioxidant blend of Curcumin and Broccoli Seed Extract (BSE). Flies treated with the blend exhibit extended lifespan. RNA-seq analysis of samples from adult fly brains reveals a wide array of new genes with differential expression upon treatment with the blend. Interestingly, abolishing expression of some of the identified genes in dopaminergic (DA) neurons does not affect DA neuron number. Taken together, our findings reveal an antioxidant blend that promotes fly longevity and exhibits protective effect over neurodegeneration, demonstrating the importance of antioxidants in health and pathology.

Active Compounds from Curcuma longa and Comparison of their Effectively Induced Apoptosis in MCF-7 Cell.

BACKGROUND AND OBJECTIVE: The natural bioactive compounds of Curcuma longa, known as curcuminoids, has been shown to exerts anticancer effects to diverse cancer cell line in vitro, including breast cancer cell line. These curcuminoids consist of curcumin (Cur), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC). Furthermore, there has never been a study to compare the extent of antiproliferative and apoptotic modulation potential between Cur, DMC and BDMC in the breast cancer cell, until now. In the present study, we explore the efficacy among Cur, DMC and BDMC to alters MCF-7 cell viability, which might lead to apoptotic modulation. MATERIALS AND METHODS: This kind of study was performed in vitro whereby the cells were maintained in an appropriate medium and the anticancer effect of curcuminoids (Cur, DMC and BDMC) was measured by using resazurin-based PrestoBlue cell viability assay. Later, MCF-7 breast cancer cells were cultured in 12 wells plate added with different concentrations of Cur, DMC and BDMC for western blotting analysis. Statistical analysis was performed with GraphPad 8, One-way ANOVA and Student's t-test. RESULTS: The result showed that Cur, DMC and BDMC inhibiting the proliferation of MCF-7 cells. In the concentration dose of 31.25 µg mL-1, the cell viability in cells treated with Cur is 27%, DMC is 31.5% and BDMC is 46%. The IC50 dose of Cur, DMC and BDMC were 25.63, 29.94 and 36.91 µg mL-1. CONCLUSION: Cur is more effective in inhibiting proliferation and apoptotic modulation in MCF-7 cells compare to DMC and BDMC. It represents the potential of Cur, DMC and BDMC as adjunctive therapy in treating breast cancer.

Solubilization and extraction of curcumin from Curcuma Longa using green, sustainable, and food-approved surfactant-free microemulsions.

Curcumin is a powerful coloring agent widely used in the food industry. Its extraction from the plant Curcuma longa is commonly done with aqueous solvent solutions. In contrast to the conventional extraction methods, the present study aimed to compare two different green and bio-based surfactant-free microemulsion (SFME) extraction systems, which are approved for food and yield a higher extracting power of curcuminoids. Two SFMEs, water/ethanol/triacetin and water/diacetin/triacetin, were investigated via dynamic light scattering. Curcumin solubility in binary mixtures consisting of ethanol/triacetin or diacetin/triacetin was studied both experimentally and theoretically using UV-Vis measurements and COSMO-RS. The SFMEs were further examined and compared to a common ethanol/water (80/20) extraction mixture with respect to their extracting ability using high performance liquid chromatography. The SFMEs containing ethanol were found to extract ~18% more curcuminoids than the SFMEs containing diacetin and ~53% more than the ordinary ethanol/water mixture.

Anti-Cancer Activity of Curcumin on Multiple Myeloma.

Multiple Myeloma (MM) is the third most common and deadly hematological malignancy, which is characterized by a progressive monoclonal proliferation within the bone marrow. MM is cytogenetically heterogeneous with numerous genetic and epigenetic alterations, which lead to a wide spectrum of signaling pathways and cell cycle checkpoint aberrations. MM symptoms can be attributed to CRAB features (hyperCalcemia, Renal failure, Anemia, and Bone lesion), which profoundly affect both the Health-Related Quality of Life (HRQoL) and the life expectancy of patients. Despite all enhancement and improvement in therapeutic strategies, MM is almost incurable, and patients suffering from this disease eventually relapse. Curcumin is an active and non-toxic phenolic compound, isolated from the rhizome of Curcuma longa L. It has been widely studied and has a confirmed broad range of therapeutic properties, especially anti-cancer activity, and others, including anti-proliferation, anti-angiogenesis, antioxidant and anti-mutation activities. Curcumin induces apoptosis in cancerous cells and prevents Multidrug Resistance (MDR). Growing evidence concerning the therapeutic properties of curcumin caused a pharmacological impact on MM. It is confirmed that curcumin interferes with various signaling pathways and cell cycle checkpoints, and with oncogenes. In this paper, we summarized the anti- MM effects of curcumin.

Phytocompounds curcumin, quercetin, indole-3-carbinol, and resveratrol modulate lactate-pyruvate level along with cytotoxic activity in HeLa cervical cancer cells.

Cancer cells meet their energy need by predominantly increased uptake of glucose, high rate of glycolysis, and increased production of lactate even in the presence of adequate oxygen.  This process was proposed by Otto Warburg and named after him as the Warburg effect. The development of drugs that target glucose intake and aerobic glycolysis or lactic acid secretion of cancer cells is a newer approach for drug discovery. We have tested five purified plants-derived compounds such as curcumin, quercetin, ellagic acid, resveratrol, and indole-3-carbinol in HeLa cells for cytotoxicity, inhibition of metastasis, and modulation of lactate-pyruvate metabolism. Standard biochemical methods were used for glucose, lactic acid, and pyruvic acid measurement. The cell viability was determined by MTT assay. Cell migration was checked by wound healing assay. A dose-dependent cytotoxic effect and inhibition of cell migration were observed in all the tested compounds. A decrease in the lactate and increase in pyruvate level was observed in all the tested compounds except ellagic acid. Our finding suggests that tested phytocompounds are associated with the metabolic reprogramming of cancer cells and execute the cytotoxic effect. These compounds could be used for cancer prevention and therapy.

Curcumin extracts from Curcuma Longa - Improvement of concentration, purity, and stability in food-approved and water-soluble surfactant-free microemulsions.

Curcumin was extracted from Curcuma Longa employing a green, bio-based, and food-agreed surfactant-free microemulsion (SFME) consisting of water, ethanol, and triacetin. Concerning the high solubility of curcumin in the examined ternary mixtures, it was attempted to produce highly concentrated tinctures of up to a total of ~130 mg/mL curcuminoids in the solvent by repeatedly extracting fresh rhizomes in the same extraction mixture. The amount of water had a significant influence on the number of cycles that could be performed as well as on the extraction of the different curcuminoids. In addition, the purity of single extracts was enhanced to 94% by investigating several purification steps, e.g. vacuum distillation and lyophilization. Through purification before extraction, the water insoluble curcumin extract could be solubilized indefinitely in an aqueous environment. Additional stability tests showed that solutions of curcumin can be stable up to five months when concealed from natural light.

Potential Therapeutic Targets of Curcumin, Most Abundant Active Compound of Turmeric Spice: Role in the Management of Various Types of Cancer.

BACKGROUND: Curcumin, an active compound of turmeric spice, is one of the most-studied natural compounds and has been widely recognized as a chemopreventive agent. Several molecular mechanisms have proven that curcumin and its analogs play a role in cancer prevention through modulating various cell signaling pathways as well as in the inhibition of the carcinogenesis process. OBJECTIVE: To study the potential role of curcumin in the management of various types of cancer through modulating cell signalling molecules based on available literature and recent patents. METHODS: A wide-ranging literature survey was performed based on Scopus, PubMed, PubMed Central, and Google scholar for the implication of curcumin in cancer management, along with a special emphasis on human clinical trials. Moreover, patents were searched through www.google.com/patents, www.freepatentsonline.com, and www.freshpatents.com. RESULT: Recent studies based on cancer cells have proven that curcumin has potential effects against cancer cells as it prevents the growth of cancer and acts as a cancer therapeutic agent. Besides, curcumin exerted anti-cancer effects by inducing apoptosis, activating tumor suppressor genes, cell cycle arrest, inhibiting tumor angiogenesis, initiation, promotion, and progression stages of tumor. It was established that co-treatment of curcumin and anti-cancer drugs could induce apoptosis and also play a significant role in the suppression of the invasion and metastasis of cancer cells. CONCLUSION: Accumulating evidences suggest that curcumin has the potential to inhibit cancer growth, induce apoptosis, and modulate various cell signaling pathway molecules. Well-designed clinical trials of curcumin based on human subjects are still needed to establish the bioavailability, mechanism of action, efficacy, and safe dose in the management of various cancers.

Curcumin's Beneficial Effects on Neuroblastoma: Mechanisms, Challenges, and Potential Solutions.

Curcumin, a natural polyphenolic compound derived from the South Asian turmeric plant (Curcuma longa), has well-characterized antioxidant, anti-inflammatory, anti-protein-aggregate, and anticancer properties. Neuroblastoma (NB) is a cancer of the nervous system that arises primarily in pediatric patients. In order to reduce the multiple disadvantages and side effects of conventional oncologic modalities and to potentially overcome cancer drug resistance, natural substances such as curcumin are examined as complementary and supportive therapies against NB. In NB cell lines, curcumin by itself promotes apoptosis and cell cycle arrest through the suppression of serine-threonine kinase Akt and nuclear factor kappa of activated B-cells (NF-κB) signaling, induction of mitochondrial dysfunction, and upregulation of p53 and caspase signaling. While curcumin demonstrates anti-NB efficacy in vitro, cross-validation between NB cell types is currently lacking for many of its specific mechanistic activities. Furthermore, curcumin's low bioavailability by oral administration, poor absorption, and relative insolubility in water pose challenges to its clinical introduction. Numerous curcumin formulations, including nanoparticles, nanocarriers, and microemulsions, have been developed, with these having some success in the treatment of NB. In the future, standardization and further basic and preclinical trials will be required to ensure the safety of curcumin formulations. While the administration of curcumin is clinically safe even at high doses, clinical trials are necessary to substantiate the practical efficacy of curcumin in the prevention and treatment of NB.

Curcumin analogs as the inhibitors of TLR4 pathway in inflammation and their drug like potentialities: a computer-based study.

Toll-like receptor 4 (TLR4) pathway is one of the major pathways that mediate the inflammation in human body. There are different anti-inflammatory drugs available in the market which specifically act on different signaling proteins of TLR4 pathway but they do have few side effects and other limitations for intended use in human body. In this study, Curcumin and its different analogs have been analyzed as the inhibitors of signaling proteins, i.e. Cycloxygenase-2 (COX-2), inhibitor of kappaß kinase (IKK) and TANK binding kinase-1 (TBK-1) of TLR4 pathway using different computational tools. Initially, three compounds were selected for respective target based on free binding energy among which different compounds were reported to have better binding affinity than commercially available drug (control). Upon continuous computational exploration with induced fit docking (IFD), 6-Gingerol, Yakuchinone A and Yakuchinone B were identified as the best inhibitors of COX-2, IKK, and TBK-1 respectively. Then their drug-like potentialities were analyzed in different experiments where they were also predicted to perform well. Hopefully, this study will uphold the efforts of researchers to identify anti-inflammatory drugs from natural sources.

Calcium and potassium channels are involved in curcumin relaxant effect on tracheal smooth muscles.

Context: Curcumin, the active component of Curcuma longa L. (Zingiberaceae), exhibits a wide variety of biological activities including vasodilation and anti-inflammation.Objective: The relaxant effect of curcumin in tracheal smooth muscle (TSM) was not examined so far, thus, this study was designed to assess the relaxant effect of curcumin on rat TSM and examine the underlying mechanism(s) responsible for this effect.Materials and methods: TSM was contracted by KCl (60 mM) or methacholine (10 µM), and cumulative concentrations of curcumin (12.5, 25, 50, and 100 mg/mL) or theophylline (0.2, 0.4, 0.6, and 0.8 mM, as positive control) were added to organ bath. The relaxant effect of curcumin was examined in non-incubated or incubated tissues with atropine (1 µM), chlorpheniramine (1 µM), indomethacin (1 µM), and papaverine (100 µM).Results: In non-incubated TSM, curcumin showed significant relaxant effects on KCl-induced contraction in a concentration-dependent manner (p < 0.001 for all concentrations). The relaxant effects of curcumin 12.5, 25, and 50 mg/mL were significantly lower in atropine-incubated tissue compared to non-incubated TSM (p < 0.05 to p < 0.001). A significant difference was observed in EC50 between atropine-incubated (48.10 ± 2.55) and non-incubated (41.65 ± 1.81) tissues (p < 0.05). Theophylline showed a significant relaxant effect on both KCl and methacholine-induced contraction in a concentration-dependent manner (p < 0.001 for all cases).Conclusions: The results indicated a relatively potent relaxant effect of curcumin on TSM, which was less marked than the effect of theophylline. Calcium channel blocking and/or potassium channel opening properties of curcumin may be responsible for TSM relaxation.

Curcumin and curcumin-loaded nanoparticles: antipathogenic and antiparasitic activities.

Introduction: Curcumin is an important bioactive compound present in Curcuma longa, and is well known for its bioactivities such as anti-inflammatory, anticancer, antimicrobial, antiparasitic and antioxidant activity. The use of curcumin is limited owing to its poor solubility in water, fast degradation, and low bioavailability. This problem can be solved by using nano-curcumin, which is soluble in water and enhances its activity against various microbial pathogens and parasites.Areas covered: We have reviewed curcumin, curcumin-loaded nanoparticles and their activities against various pathogenic microbes (antifungal, antiviral and antiprotozoal) and parasites, as curcumin has already demonstrated broad-spectrum antimicrobial activity. It has also inhibited biofilm formation by various bacteria including Pseudomonas aeruginosa. The antimicrobial activity of curcumin can be increased in the presence of light radiation due to its photo-excitation. Further, it has been found that the activity of curcumin nanoparticles is enhanced when used in combination with antibiotics. Finally, we discussed the toxicity and safety issues of curcumin.Expert opinion: Since many microbial pathogens have developed resistance to antibiotics, the combination of curcumin with different nanoparticles will prove to be a boon for their treatment. Moreover, curcumin and curcumin-loaded nanoparticles can also be used against various parasites.

Optimization extraction and purification of biological activity curcumin from Curcuma longa L by high-performance counter-current chromatography.

The extraction condition of curcumin from Curcuma longa L was optimized through four factors and three levels orthogonal experiment based on the results of single factor tests. Under the optimal conditions: the concentration of ethanol  80%, extraction temperature 70°C, the ratio of liquid to material 20, and extraction time 3 h, a crude extract with the yield of curcumin 56.8 mg/g could be obtained. The isolation and purification of curcuminoids from the crude extract was performed on high performance counter current chromatography employing an optimized solvent system n-hexane/ethyl acetate/methanol/water (2/3/3/1, v/v/v/v). From 97 mg crude sample (in which the purity of curmumin was 68.56%), 67 mg curmumin, 18 mg demethoxycurcumin, and 9.7 mg bisdemethoxycurcumin with a high-performance liquid chromatography purity of 98.26, 97.39, and 98.67%, respectively, were obtained within 70 min. The antioxidant activities and cytotoxicity of purified curcumin was comparable to that of the commercial product, indicating that the biological activity of curcumin could be maintained by this method.

The use of curcumin as an effective adjuvant to cancer therapy: A short review.

Turmeric (Curcuma longa) is a popular spice that has been used in Ayurvedic medicine for its ability to treat various common ailments. There have been statistical correlations between turmeric consumption and lower incidences of cancer development, prompting research into its primary component curcumin. Several in vitro and in vivo studies over the last decade into cancer treatment have provided experimental evidence that curcumin contains antiproliferative, antiangiogenic, and apoptotic properties. The results of human clinical trials however, have proven mostly to be inconclusive. This short review provides an insight into the properties of curcumin including its bioavailability, biological activity, and potential usage in clinical trials as a chemotherapeutic drug.

Preparation and application of alcohol based deep eutectic solvents for extraction of curcumin in food samples prior to its spectrophotometric determination.

In this study, a novel, simple and economic vortex-assisted alcohol-based deep eutectic solvent microextraction (VA-DES-ME) procedure has been developed for the preconcentration of curcumin in food samples prior to its spectrophotometric determination. A alcohol-based-DES consists of betaine hydrochloride - glycerol (1:3) as extraction solvent and acetone as aprotic solvent at pH 6.0 were used for the preconcentration of curcumin from sample matrix. Some experimental variables such as pH, DES solvent type and volume, aprotic solvent type and volume, vortex time, sample volume and matrix effect etc. were investigated and optimized in detail. Under optimized conditions, the working range, limit of detection and pre-concentration factor were determined to be as 5-300 µg L-1 and 1.5 µg L-1 and 100 respectively. Validity of the proposed method was proved by the intra-day/inter-day precision studies and addition-recovery test. Consequently, the VA-DES-ME procedure was successfully applied for the extraction and determination of curcumin in food samples.

Curcumin, as a pleiotropic agent, improves doxorubicin-induced nephrotic syndrome in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcumin, a phenolic compound extracted from the rhizome of turmeric (Curcuma longa L.), has been reported to have broad biological functions including potent antioxidant and renoprotective effects. It has been reported that Curcumin has a certain protective effect on the kidney. However, its mechanism of action needs further study. AIM OF THE STUDY: The present research aims at investigating the therapeutic effects and its underlying mechanism of curcumin on NS. MATERIALS AND METHODS: The conditionally immortalized mouse podocyte cell line was utilized to evaluate the podocyte-protective effect of curcumin and its effects on NF-κB pathway and Nrf2/ARE pathway in podocyte in vitro. Furthermore, the DOX-induced NS rats were utilized to investigate the therapeutic effects and its underlying mechanism of curcumin against NS in vivo. RESULTS: The consequences of this study revealed that curcumin activated Nrf2, inhibited NF-κB pathway and up-regulated podocin in DOX-induced podocyte. Further research results showed that curcumin can considerably alleviate proteinuria and improve hypoalbuminemia in NS rats, and lower blood lipid levels to alleviate hyperlipidemia in NS rats, indicating that curcumin has significant therapeutic effects on rat NS. Further observation by electron microscopy and detection showed that curcumin can improve renal function and podocyte injury, which may be related to the repairment of mRNA expression and podocin protein. Interestingly, the results of the blood rheology test showed that curcumin can effectively reduce whole blood viscosity (WBV) and plasma viscosity (PV), and reduce hematocrit (Hct). In addition, the oxidative stress state of kidney in NS rats was considerably reversed by curcumin, which may be achieved by activating Nrf2 and increasing the expression of antioxidant enzymes HO-1, NQO-1. We also found that NF-κB pathway is activated in the kidney of NS rats, and curcumin can inhibit the activation of NF-κB by down-regulating the expression of NF-κB p65, reducing the level of p-IκBα and up-regulating the expression of IκBα. CONCLUSION: These findings suggest that curcumin, as a multifunctional agent, exerts a protective effect on DOX-induced nephrotic syndrome in rats, which provides a pharmacological basis for the further development of curcumin and also provides a basis for the advantages of multi-targeted drugs in the processing of NS.