Search Results (78)

Turmeric oleoresin (TO), a natural pigment derived from Curcuma longa rhizomes, is valued for its health benefits, which are primarily attributed to its rich curcuminoid content (curcumin, demethoxycurcumin, and bisdemethoxycurcumin). Despite these benefits, curcuminoids are known to be light-sensitive and possess photosensitizing properties. This study investigated the impact of common light sources, fluorescent light and white LED (both at 10 W/m²), on the chemical stability, antioxidant activity, cytotoxicity, and photosensitizing properties of TO. Exposure to both light sources significantly reduced TO’s color and fluorescence intensity, with white LED causing greater instability. HPLC analysis confirmed a decrease in individual curcuminoid levels, with curcumin degrading most rapidly under both conditions. The DPPH radical scavenging activity of irradiated TO decreased compared to fresh or dark-stored turmeric, whereas its ABTS radical scavenging activity increased upon light exposure. Photosensitizing potency, measured by formazan decolorization and lipid peroxide formation, declined as TO decomposed under light. Conversely, the cytotoxicity of TO against B16F10 melanoma cells was significantly enhanced under light exposure, though this effect was diminished significantly after 24 h of pre-irradiation. These findings underscore the instability of turmeric pigment under common lighting conditions, which should be a crucial consideration when processing, storing, and distributing turmeric-containing products. Full article

Oxidative stress is a common feature of various pathological conditions, including tissue remodeling and dysfunction. Cardiac fibroblasts, which play a key role in maintaining extracellular matrix homeostasis, are sensitive to oxidative injury. Curcumin and tetrahydrocurcumin are plant-derived polyphenols with antioxidant properties, yet their relative efficacy in preventing oxidative stress–induced dysfunction in cardiac fibroblasts remains unclear. In this study, cardiac fibroblasts were treated with curcumin or tetrahydrocurcumin prior to exposure to tert-butyl hydroperoxide (t-BHP), a widely used inducer of oxidative stress. Cell viability, apoptosis, reactive oxygen species (ROS) production, and Tgfb1 expression were assessed. Both curcuminoids significantly attenuated oxidative stress–induced cell death, decreased cell viability, and reduced Tgfb1 expression. Notably, tetrahydrocurcumin demonstrated superior protective effects across most parameters. These findings suggest that both compounds help mitigate oxidative-stress–induced cellular dysfunction in cardiac fibroblasts and highlight tetrahydrocurcumin as a potentially more effective antioxidant. Further studies are needed to explore their role in the context of tissue remodeling and fibrotic progression. Full article

Background/Objectives: The anti-Leishmania potential of Curcuma longa and its derivatives, such as curcuminoids, is well-established, yet their mechanisms of action remain underexplored. This study investigates the inhibitory effects of C. longa extracts and curcumin on Leishmania infantum arginase, a key enzyme in polyamine and trypanothione biosynthesis, and evaluates their antiparasitic activity. Methods: Extracts were prepared via rhizome successive maceration with hexane (HEXCURC), dichloromethane (DCCURC), and ethanol (ETOHCURC) and chemically characterized by a combination of chromatographic and spectrometric methods. The inhibition of recombinant L. infantum arginase (LiARG) was assessed by urea quantification, while molecular docking explored interactions between the main compounds annotated in the extracts and the enzyme’s active site. Biological activity was tested against L. infantum promastigotes, intracellular amastigotes, and mammalian cells. Results: LC-MS and GC-MS revealed curcuminoids and turmerones as main compounds annotated in the extracts. DCCURC, HEXCURC, and curcumin showed the strongest LiARG inhibition (IC₅₀ = 10.04, 14.4, and 17.55 μg/mL, respectively). Docking analysis revealed that curcumin, demethoxycurcumin, and bisdemethoxycurcumin bind near the active site, with binding energies of –3.43, –4.14, and –3.99 kcal/mol, respectively. Curcumin demonstrated superior anti-promastigote activity (IC₅₀ = 15.01 μg/mL) and selectivity (SI = 12.7) compared to the extracts. It also significantly reduced amastigote burden in infected macrophages (IC₅₀ = 13.6 μg/mL). Conclusions: This is the first report demonstrating that C. longa extracts and curcumin inhibit LiARG. These findings support curcumin’s potential as a lead compound for developing multi-target therapies against leishmaniasis, combining enzyme inhibition with direct antiparasitic effects. Full article

Turmeric (Curcuma longa L. cv. Trang 1), a high-value cultivar known for its elevated curcuminoid and volatile oil content, holds significant potential in pharmaceutical and food applications. However, its commercial propagation is constrained by low rhizome productivity and the limitations of conventional vegetative propagation. This study aimed to improve the propagation efficiency of turmeric cv. Trang 1 by developing optimized protocols for explant sterilization, shoot proliferation, root induction, and acclimatization. Sprouted rhizome buds were sterilized and cultured on a Murashige and Skoog (MS) medium supplemented with various plant growth regulators, including cytokinins (benzyladenine [BA], thidiazuron [TDZ], and meta-topolin [mT]) and auxins (indole-3-butyric acid [IBA] and 1-naphthaleneacetic acid [NAA]). The shoot induction (4.60 ± 1.47 shoots per explant) and shoot height (2.34 ± 0.61 cm) were observed on the MS medium with 3.0 mg/L BA, while the TDZ, at 0.5 mg/L, also induced a high number of shoots (5.22 ± 0.64). When using single shoots derived from bud explants, mT at 1.5 mg/L significantly enhanced the shoot formation. For the root induction, 2.0 mg/L IBA yielded the highest number of roots (7.33 ± 1.49), while NAA was less effective. The plantlets acclimatized in a 1:1 soil and peat moss mixture showed the highest survival rate (86.67%). This improved protocol enables the efficient production of turmeric plantlets, supporting commercial deployment. Full article

Background/Objectives: Dental caries and candidiasis are major health problems worldwide. Dental caries is caused by cariogenic bacteria, especially those belonging to the Streptococcus genus, whereas candidiasis is caused by Candida species. In this study, the antimicrobial activity of a series of synthetic N-methyl-4-piperidone-derived monoketone curcuminoids (MKCs) against Candida albicans, C. krusei, and a representative panel of cariogenic bacteria was assessed. Methods: Fifteen MKCs were synthesized using an environmentally friendly base-catalyzed Claisen–Schmidt condensation between an aromatic aldehyde (R-PhCHO) and N-methyl-4-piperidone ethanol using NaOH as the catalyst. These compounds were evaluated for their antibacterial activity against a representative panel of cariogenic bacteria, along with their antifungal activity against Candida krusei and C. albicans. The antimicrobial activity was determined based on the Minimum Inhibitory Concentration (MIC) values. Results: Most of the compounds were obtained in about 2 h in yields ranging from 40 to 70%. None of the compounds displayed antifungal activity, even at 100 μg/mL, the highest tested concentration. Similarly, none of the compounds were active against Enterococcus faecalis. On the other hand, compounds 1 (R = H), 10 (R = 3,4,5-OMe), and 13 (R = 3-F) displayed moderate activity against Streptococcus mutans (13), S. salivarus (1), L. paracasei (1 and 10), S. mitis (1, 10, and 13), S. sanguinis (1, 10, and 13), and S. sobrinus (13), with MIC values of 250 μg/mL and 500 μg/mL. The presence of the N-methyl-4-piperidone ring was found to boost the antibacterial activity as compared to the corresponding acetone-derived MKCs. Moreover, the antibacterial activity of compounds 10 and 13 was associated with the presence and position of the fluor atom and the methoxy groups at the aromatic ring. Conclusions: This study contributed to a better understanding of the antimicrobial activity of MKCs, whose data in the literature are still scarce. Full article

The global healthcare system is increasingly challenged by the rising prevalence of multidrug-resistant bacteria and the limited therapeutic options for related infections. Efflux-mediated antibiotic resistance represents a significant obstacle, primarily due to the absence of drugs specifically designed to target bacterial efflux pumps. Recent research has identified polyphenols, a broad class of plant-derived organic compounds, as potential inhibitors of efflux pump activity. This review consolidates data on the inhibitory properties of eight widely distributed polyphenols: curcumin, quercetin, luteolin, tannic acid, naringenin, epigallocatechin-3-gallate, ellagic acid, and resveratrol. These compounds have demonstrated the capacity to inhibit efflux pumps, either through direct interference with bacterial protein function or by downregulating the expression of genes encoding pump subunits. Importantly, several polyphenols exhibit synergistic interactions with antibiotics, including colistin, ciprofloxacin, and tetracycline. For instance, quercetin has shown inhibitory potency comparable to that of established efflux pump inhibitors such as verapamil and reserpine. These findings suggest that polyphenols represent promising candidates for the development of novel efflux pump inhibitors. However, further research is required to validate their efficacy and safety and facilitate their translation into clinical applications for combating antibiotic resistance. Full article

Background: Turmeric (Curcuma longa L.) rhizomes, whose secondary metabolites include polyphenols and terpenoids, have been used medicinally for millennia. However, modern scientific inquiry has primarily focused on medicinal effects of turmeric’s polyphenolic curcuminoids, including when evaluating turmeric use to maintain bone health. Methods: Disease-specific biological effects of turmeric’s major secondary metabolites (polyphenols and/or terpenoids), with or without associated turmeric rhizome-derived polysaccharides, were determined in vivo using pre-clinical models of clinically relevant resorptive bone diseases induced by different mechanisms. These included inflammatory arthritis, cancer-driven osteolytic bone metastases, and hormone deficiency-driven post-menopausal osteoporosis. Results: In the arthritis model, the safety profile of curcuminoids alone was superior. However, curcuminoids and terpenoids each had anti-inflammatory effects and prevented bone resorption, with polysaccharide-containing curcuminoid extracts having greater effect than curcuminoids alone. In the human osteolytic breast cancer bone metastases model, curcuminoid extracts containing polysaccharides tended to yield greater effects in reducing bone osteolysis and tumor progression than curcuminoids alone or more complex extracts. In contrast, only purified curcuminoids prevented bone loss in a post-menopausal osteoporosis model, while polysaccharide-containing curcuminoid extracts were without effect. In vitro metabolite effects on disease-specific mechanistic pathways in synoviocytes, osteoclasts, or breast cancer cells were consistent with documented in vivo outcomes and included differential metabolite-specific effects. Conclusions: In summary, these findings suggest that turmeric’s potential medicinal musculoskeletal effects are complex, pathway- and target-specific, and not limited to curcuminoids, with safety concerns potentially limiting certain uses. Full article

Leukemia, one of the major causes of cancer death, ranks 11th worldwide among cancer-related deaths. The current treatment of leukemia faces challenges recently due to a high burden of side effects. It is well established that curcumin has anticancer and tumor-suppressing activities in several cancers in addition to leukemia. Accordingly, 15 derivatives were designed and prepared to improve the shortcomings of curcumin, such as poor aqueous solubility, chemical instability, and low bioavailability. All 15 were evaluated for cytotoxicity against the leukemic cell line MOLT-4, which led to the prioritization and further evaluation of compound curcuminoid (2E,5E)-2,5-bis((3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)cyclopentan-1-one 5i. 5i. Compared to curcumin, 5i was significantly more effective in inducing mitochondrial dysfunction in MOLT-4 cells; hence increased ROS production and cytotoxicity. Treatment groups showed change in mitochondrial membrane potential by flow cytometry analysis. Moreover, tumor volume reduction observed with 5i treatment in Dalton’s Lymphoma model was accompanied with low toxicity. Intrinsic pathways of apoptosis was initiated by compound 5i that lowered Bcl-2 expression while augmenting cytochrome c, Bak and Bax levels both in vivo and in vitro. These results showcase the potent antiproliferative as well as cytotoxic effects of 5i at nanomolar doses against leukemia being at least 60 times more effective than curcumin. Full article

Background: Anticancer therapies represent the primary treatment option for a significant number of cancer patients globally; however, many of these treatments are associated with severe side effects as they target molecular structures present in both cancerous and healthy cells. In a similar context, the treatment of Chagas disease, a neglected tropical illness, is hindered by the high toxicity of the currently available drugs. Researchers are increasingly focusing on the development of safer and more selective alternatives, with natural compounds being studied as potential starting points for the creation of more effective drug candidates with a favorable therapeutic index. Objectives: The aim of this study was to design simplified curcumin-derived structures that preserved or enhanced their therapeutic activity against human lung cancer cell lines and T. cruzi, while also improving bioavailability and minimizing toxicity. Methods: In this study, curcumin and two natural curcuminoids inspired the synthesis of a chalcone and a set of bis-chalcones, compound classes known for their enhanced stability compared with their natural parent derivatives. The synthetic strategy used was the acid-catalyzed aldol condensation reaction. The stability profiles, IC₅₀ values against A549 and H460 tumor cell lines, and trypanocidal activity against T. cruzi amastigotes of these derivatives were assessed. Results: The synthesized derivatives exhibited improved stability compared with the parent compounds, along with lower IC₅₀ values in both A549 and H460 tumor cell lines. Additionally, one of the new analogs showed promising trypanocidal activity against T. cruzi amastigotes. Conclusions: This study provides a potential pathway toward the development of more effective and less toxic treatments for both cancer and Chagas disease. The simplified curcumin derivatives represent a promising foundation for designing new therapeutic agents with improved bioavailability and efficacy. Full article

A major challenging problem facing effective ovarian cancer therapy is cisplatin resistance. Re-sensitization of cisplatin-resistant ovarian cancer cells to cisplatin (CDDP) has become a critical issue. Curcumin (CUR), the most abundant dietary polyphenolic curcuminoids derived from turmeric (Curcuma longa), has achieved previously significant anti-cancer effects against human ovarian adenocarcinoma SKOV-3/CDDP cisplatin-resistant cells by inhibition the gene expression of the antioxidant enzymes (SOD1, SOD2, GPX1, CAT and HO1), transcription factor NFE2L2 and signaling pathway (PIK3CA/AKT1/MTOR). However, the detailed mechanisms of curcumin-mediated re-sensitization to cisplatin in SKOV-3/CDDP cells still need further exploration. Here, a suggested curcumin pre-treatment therapeutic strategy has been evaluated to effectively overcome cisplatin-resistant ovarian cancer SKOV-3/CDDP and to improve our understanding of the mechanisms behind cisplatin resistance. The findings of the present study suggest that the curcumin pre-treatment significantly exhibited cytotoxic effects and inhibited the proliferation of the SKOV-3/CDDP cell line compared to the simultaneous addition of drugs. Precisely, apoptosis induced by curcumin pre-treatment in SKOV-3/CDDP cells is mediated by mitochondrial apoptotic pathway (cleaved caspases 9, 3 and cleaved PARP) activation as well as by inhibition of thioredoxin reductase (TRXR1) and mTOR/STAT3 signaling pathway. This current study could deepen our understanding of the anticancer mechanism of CUR pre-treatment, which not only facilitates the re-sensitization of ovarian cancer cells to cisplatin but may lead to the development of targeted and effective therapeutics to eradicate SKOV-3/CDDP cancer cells. Full article

Investigating amyloid–β (Aβ) peptides in solution is essential during the initial stages of developing lead compounds that can influence Aβ fibrillation while the peptide is still in a soluble state. The tendency of the Aβ(1–42) peptide to misfold in solution, correlated to the aetiology of Alzheimer’s disease (AD), is one of the main hindrances to characterising its aggregation kinetics in a cell-mimetic environment. Moreover, the Aβ(1–42) aggregation triggers the unfolded protein response (UPR) in the endoplasmic reticulum (ER), leading to cellular dysfunction and multiple cell death modalities, exacerbated by reactive oxygen species (ROS), which damage cellular components and trigger inflammation. Antioxidants like curcumin, a derivative of Curcuma longa, help mitigate ER stress by scavenging ROS and enhancing antioxidant enzymes. Furthermore, evidence in the literature highlights the effect of curcumin on the secondary structure of Aβ(1–42). This explorative study investigates the Aβ(1–42) peptide conformational behaviour in the presence of curcumin and six derivatives using circular dichroism (CD) to explore their interactions with lipid bilayers, potentially preventing aggregate formation. The results suggest that the synthetic tetrahydrocurcumin (THC) derivative interacts with the amyloid peptide in all the systems presented, while cyclocurcumin (CYC) and bisdemethoxycurcumin (BMDC) only interact when the peptide is in a less stable conformation. Molecular dynamics simulations helped visualise the curcuminoids’ effect in an aqueous system and hypothesise the importance of the peptide surface exposition to the solvent, differently modulated by the curcumin derivatives. Full article

Curcumin (Cur), the primary curcuminoid found in Curcuma longa L., has garnered significant attention for its potential anti-inflammatory and antibacterial properties. However, its hydrophobic nature significantly limits its bioavailability. Additionally, adipose-derived stem cells (ADSCs) possess immunomodulatory properties, making them useful for treating inflammatory and autoimmune conditions. This study aims to verify the efficacy of poly(ε-caprolactone) nanocapsules (NCs) in improving Cur’s bioavailability, antibacterial, and immunomodulatory activities. The Cur-loaded nanocapsules (Cur-NCs) were characterized for their physicochemical properties (particle size, polydispersity index, Zeta potential, and encapsulation efficiency) and stability over time. A digestion test simulated the behavior of Cur-NCs in the gastrointestinal tract. Micellar phase analyses evaluated the Cur-NCs’ bioaccessibility. The antibacterial activity of free Cur, NCs, and Cur-NCs against various Gram-positive and Gram-negative strains was determined using the microdilution method. ADSC viability, treated with Cur-NCs and Cur-NCs in the presence or absence of lipopolysaccharide, was analyzed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay. Additionally, ADSC survival was assessed through the Muse apoptotic assay. The expression of both pro-inflammatory (interleukin-1β and tumor necrosis factor-α) and anti-inflammatory (IL-10 and transforming growth factor-β) cytokines on ADSCs was evaluated by real-time polymerase chain reaction. The results demonstrated high stability post-gastric digestion of Cur-NCs and elevated bioaccessibility of Cur post-intestinal digestion. Moreover, Cur-NCs exhibited antibacterial activity against Escherichia coli without affecting Lactobacillus growth. No significant changes in the viability and survival of ADSCs were observed under the experimental conditions. Finally, Cur-NCs modulated the expression of both pro- and anti-inflammatory cytokines in ADSCs exposed to inflammatory stimuli. Collectively, these findings highlight the potential of Cur-NCs to enhance Cur’s bioavailability and therapeutic efficacy, particularly in cell-based treatments for inflammatory diseases and intestinal dysbiosis. Full article

The therapeutic effects of curcumin and its derivatives, based on research in recent years, are limited by their low bioavailability. To improve bioavailability and develop the medical field of application, different delivery systems have been developed that are adapted to certain environments or the proposed target type. This study presents some half-curcuminoids prepared by the condensation of acetylacetone with 4-hydroxybenzaldehyde (C1), 4-hydroxy-3-methoxybenzaldehyde (C2), 4-acetamidobenzaldehyde (C3), or 4-diethylaminobenzaldehyde (C4), at microwaves as a simple, solvent-free, and eco-friendly method. The four compounds obtained were characterized in terms of morphostructural and photophysical properties. Following the predictions of theoretical studies on the biological activities related to the molecular structure, in vitro tests were performed for compounds C1–C3 to evaluate the antitumor properties and for C4’s possible applications in the treatment of neurological diseases. The four compounds were encapsulated in two types of hydrogel matrices. First, the alginate–glucosamine network was generated and then the curcumin analogs were loaded (G1, G3, G5–G7, and G9). The second type of hydrogels was obtained by loading the active compound together with the generation of the hydrogel carrier matrices, by simply dissolving (G4 and G10) or by chemically binding half-curcuminoid derivatives to glucosamine (G2 and G8). Thus, two types of curcumin analog delivery systems were obtained, which could be applied in various types of medical treatments. Full article

Breast cancer is one of the leading causes of death in the female population because of the resistance of cancer cells to many anticancer drugs used. Curcumin has cytotoxic activities against breast cancer cells, although it has limited use due to its poor bioavailability and rapid metabolic elimination. The synthesis of metal complexes of curcumin and curcuminoids is a relevant topic in the search for more active and selective derivatives of these molecular scaffolds. However, solubility and bioavailability are concomitant disadvantages of these types of molecules. To overcome such drawbacks, the preparation of inclusion complexes offers a chemical and pharmacologically safe option for improving the aqueous solubility of organic molecules. Herein, we describe the preparation of the inclusion complex of dimethoxycurcumin magnesium complex (DiMeOC-Mg, (4)) with beta-cyclodextrin (DiMeOC-Mg-BCD, (5)) in the stoichiometric relationship 1:1. This new inclusion complex’s solubility in aqueous media phosphate buffer saline (PBS) was improved by a factor of 6x over the free metal complex (4). Furthermore, 5 affects cell metabolic rate, cell morphology, cell migration, induced apoptosis, and downregulation of the matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3) expression levels on MD Anderson metastasis breast-231 cancer (MDA-MB-231) cell lines. Results of an antitumor assay in an in ovo model showed up to 30% inhibition of tumor growth for breast cancer (MDA-MB-231) when using (5) (0.650 mg/kg dose) and 17.29% inhibition with the free homoleptic metal complex (1.5 mg/kg dose, (4)). While the formulation of inclusion complexes from metal complexes of curcuminoids demonstrates its usefulness in improving the solubility and bioavailability of these metallodrugs, the new compound (5) exhibits excellent potential for use as a therapeutic agent in the battle against breast cancer. Full article

Curcumae Rhizoma, a traditional Chinese medicine with a wide range of pharmacological activities, is obtained from the dried rhizomes of Curcuma phaeocaulis VaL., Curcuma kwangsiensis S. G. Lee et C. F. Liang, and Curcuma wenyujin Y. H. Chen et C. Ling. Sesquiterpenoids and curcuminoids are found to be the main constituents of Curcumae Rhizoma. Sesquiterpenoids are composed of three isoprene units and are susceptible to complex transformations, such as cyclization, rearrangement, and oxidation. They are the most structurally diverse class of plant-based natural products with a wide range of biological activities and are widely found in nature. In recent years, scholars have conducted abundant studies on the structures and pharmacological properties of components of Curcumae Rhizoma. This article elucidates the chemical structures, medicinal properties, and biological properties of the sesquiterpenoids (a total of 274 compounds) isolated from Curcumae Rhizoma. We summarized extraction and isolation methods for sesquiterpenoids, established a chemical component library of sesquiterpenoids in Curcumae Rhizoma, and analyzed structural variances among sesquiterpenoids sourced from Curcumae Rhizoma of diverse botanical origins. Furthermore, our investigation reveals a diverse array of sesquiterpenoid types, encompassing guaiane-type, germacrane-type, eudesmane-type, elemane-type, cadinane-type, carane-type, bisabolane-type, humulane-type, and other types, emphasizing the relationship between structural diversity and activity. We hope to provide a valuable reference for further research and exploitation and pave the way for the development of new drugs derived from medicinal plants. Full article