Bisdemethoxycurcumin Research Articles

Effects of photodynamic therapy using bisdemethoxycurcumin combined with melatonin or acetyl-melatonin on C. Albicans

The current study aims to explore the efficacy of antifungal photodynamic therapy (PDT) on C. albicans biofilms by combining photosensitizers, bisdemethoxycurcumin (BDMC), and melatonin (MLT) or acetyl-melatonin (AcO-MLT). Additionally, the relationship between different types of reactive oxygen species and PDT’s antifungal efficacy was investigated. BDMC, MLT and AcO-MLT were applied, alone and in combination, to 48-hour C. albicans biofilm cultures (n = 6/group). Blue and red LED light (250 mW/cm2 with 37.5 J/cm2 for single or 75 J/cm2 for dual photosensitizer groups) were used to irradiate BDMC groups and MLT/AcO-MLT groups, respectively. For combination groups, blue LEDs and subsequently red LEDs were used. Drop plate assays were performed at 0, 1 and 6 h post-treatment. Colony forming units (CFUs) were then counted after 48 h. Hydroxyl radicals and singlet oxygen were measured using fluorescence spectroscopy and electron spin resonance (ESR) spectroscopy. Additionally, cell cytotoxicity was tested on human oral keratinocytes. Significant CFU reductions were observed with combinations 20 µM BDMC + 20 µM AcO-MLT and 60 µM BDMC + 20 µM MLT at 0 and 1 h post-treatment, respectively. Singlet oxygen production increased with the addition of MLT/AcO-MLT and had moderate-substantial correlations with inhibition at all times. Hydroxyl radical production was not significantly different from the control. Additionally, BDMC exhibited subtle cytotoxicity on human oral keratinocytes. PDT using BDMC + MLT or AcO-MLT, with blue and red LED light, effectively inhibits C. albicans biofilm through singlet oxygen generation. Melatonin acts as a photosensitizer in PDT to inhibit fungal infection.

Insights into inhibitory action and interaction of bisdemethoxycurcumin on tyrosinase: Spectroscopic and docking analysis

Bisdemethoxycurcumin (BDMC), a demethoxy derivative of curcumin, has garnered interest for its potential anti-tyrosinase properties, which are crucial for applications in food preservation and cosmetic industries. Despite its recognized bioactive effects, the detailed inhibitory action and interaction of BDMC on tyrosinase and its application in anti-browning processes remain unclear. This study aims to dissect the molecular interactions of BDMC with tyrosinase, elucidate its inhibition mechanism, and assess its efficacy in preventing browning, thereby underpinning its potential as a natural anti-browning agent. Employing a battery of spectroscopic techniques, we characterized the interaction of BDMC with tyrosinase. The anti-browning properties of BDMC were evaluated on fresh-cut apples, and its effect on enzymatic activities related to browning was also investigated. The results indicate that BDMC interacts with tyrosinase in a reversible mixed-type inhibition manner with an IC50 value of 12.5 ± 0.2 μM. Surface Plasmon Resonance (SPR) results indicated that BDMC presented good binding affinity toward tyrosinase. Fluorescence quenching results showed that BDMC could quench the fluorescence of tyrosinase in a static process. Synchronous fluorescence, circular dichroism spectra, and three-dimensional fluorescence results indicated that interaction of BDMC against tyrosinase resulted in changes of tyrosinase on microenvironment and conformation, thus causing decrease of tyrosinase activity. Copper-chelating results presented that BDMC could chelate to copper with stoichiometric ratio of 1: 2. Molecular docking provided intricate details of how BDMC interacted with tyrosinase. Moreover, BDMC exhibited anti-browning capability on fresh cut apples, and could regulate PPO, POD, and APX activities. The comprehensive analysis proposed in this study consolidated the theoretical basis of BDMC as a tyrosinase inhibitor and supported its potential anti-browning application.

Bisdemethoxycurcumin, a novel potent polyphenolic compound, effectively inhibits the formation of amyloid aggregates in ALS-associated hSOD1 mutant (L38R)

Protein misfolding is a biological process that leads to protein aggregation. Anomalous misfolding and aggregation of human superoxide dismutase (hSOD1) into amyloid aggregates is a characteristic feature of amyotrophic lateral sclerosis (ALS), a neurodegenerative illness. Thus, focusing on the L38R mutant may be a wise decision to comprehend the SOD1 disease process in ALS. We suggest that Bisdemethoxycurcumin (BDMC) may be a strong anti-amyloidogenic polyphenol against L38R mutant aggregation. Protein stability, hydrophobicity, and flexibility were altered when BDMC was bound to the L38R mutant, as shown by molecular dynamic (MD) simulations and molecular docking. FTIR data shows α-Helix dominance in BDMC-containing samples, with reduced β-sheet and disordered peaks, indicating the decrease of aggregate species. ThT aggregation kinetics curves show BDMC reduces L38R mutant aggregation dose-dependently, with higher BDMC concentrations yielding greater reductions. TEM images showed various quantities of amorphous aggregates, but notably, 60 μM BDMC markedly reduced aggregate density, underscoring BDMC's inhibitory effect. Hemolysis tests revealed aggregate species in BDMC-treated samples were less toxic than in L38R mutant samples alone at the same concentrations and exposure times. Overall, BDMC has substantial potential to develop highly effective inhibitors that mitigate the risk of fatal ALS.

Bisdemethoxycurcumin Augments Docetaxel Efficacy for Treatment of Prostate Cancer.

Bisdemethoxycurcumin (BDMC) is one of major forms of curcuminoids found in the rhizomes of turmeric. Docetaxel (DTX) is the standard of care for men diagnosed with androgen-independent prostate cancers. Here we report for the first time that BDMC could reinforce the effect of DTX against prostate cancer in vitro and in vivo. In vitro study, PC3 and LNCaP cells were cultured and treated with BDMC and DTX alone or in combination. The effects on cell viability were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was assessed by annexin V/propidium iodide (PI) staining, while cell cycle was assessed by PI staining. Bax, Bcl-2, caspase, poly(ADP-ribose)polymerase (PARP), cyclin B1 and CDK1 expression were assayed by Western blot. We found that a combination treatment of BDMC (10 µM) with DTX (10 nM) was more effective in the inhibition of PC3 and LNCaP cell growth and induction of apoptosis as well as G2/M arrest, which is accompanied with the significant inhibition of Bcl-2, cyclin B1, CDK1 expression and significant increase of Bax, cleaved caspase-9, cleaved caspase-3 and cleaved PARP, than those by treatment of BDMC or DTX alone. Moreover, in vivo evaluation further demonstrated the superior anticancer efficacy of BDMC and DTX compared to DTX alone in a murine prostate cancer model. These results suggest that BDMC can be an attractive therapeutic candidate in enhancing the efficacy of DTX in prostate cancer treatment.

Chemical fingerprint analysis for quality assessment and control of Curcuma longa L. rhizomes from Vietnam using a high-performance liquid chromatography-diode array detector (HPLC-DAD)

Turmeric, extensively cultivated across Southeast Asia, especially in Vietnam, harbors active polyphenols, primarily curcumin (2–5%), renowned for its diverse health benefits. Pharmacopoeias recognize turmeric, yet it lacks standardized quality assessments and encounters challenges in extraction and identification due to natural variations and adulteration. This analytical method is vital for verifying the authenticity, purity, and quality of turmeric products in both the pharmaceutical and nutraceutical industries. This study successfully developed an efficient extraction process for curcumin (CUR), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) from Curcuma longa L. rhizomes. The herbal powder was extracted with methanol (1:30, w/v) by the ultrasound-assisted method for 10 minutes, and this process was repeated three times. A high-performance liquid chromatography-diode array detector (HPLC-DAD) method was validated for the simultaneous quantification of three analytes, following the AOAC guideline and achieving a correlation coefficient (R2) value greater than 0.9950. Utilizing the HPLC-DAD method, the study developed a chemical fingerprint analysis for three analytes to identify the characteristic chemical components distinguishing turmeric from each region. Nineteen samples collected from various provinces across Vietnam were subjected to analysis. In all analyzed samples, the concentrations of CUR, DMC, and BDMC ranged from 0.77–10.30%, 0.33–6.92%, and 0.03–3.23%, respectively. CUR was determined to be the dominant compound in most samples, while BDMC consistently exhibited the lowest levels of content. Utilizing the findings derived from the analysis of RRT and RPA metrics, the research assessed variances across sample batches. It is suggested that this newly established approach can be applied to construct and develop raw material areas to serve the needs of each field.

DFT-assisted design of curcumin-based donor-π-bridge-acceptor molecular structures: Advancing nonlinear optical materials and sustainable organic solar cells

This study explores the theoretical design of novel curcumin-based structures with enhanced nonlinear optical (NLO) characteristics. By systematically substituting hydroxyl (OH) functionalities in bisdemethoxycurcumin (BdMC) with various donor and acceptor functionalities at the edges of the π-bridge backbone, we constructed 12 different derivatives. Density-functional theory (DFT) and time-dependent DFT (TD-DFT) calculations were performed at the B3LYP/6-311++G(d,p) and CAM-B3LYP/6-311++G(d,p) levels to analyze the optoelectronic properties. The introduction of donors and acceptors significantly improved NLO characteristics. Notably, BdMC-1 (N(C2H5)2-π-bridge-NO2) exhibited a remarkable enhancement in NLO responses, with the average polarizability (<α>) and the first hyperpolarizability (βtot) increasing from 465.3 to 660.9 (a.u.) and 14254.4 to 143487.6 (a.u.), respectively. UV–Vis spectroscopy showed BdMC-1 as the most red-shifted compound, with a maximum wavelength (λmax) of 431.1 nm, the lowest optical bandgap of 2.88 eV, and an ultrahigh light harvesting efficiency (LHE) of 97.4%. The designed compounds exhibited narrower HOMO-LUMO electronic bandgaps (as low as 2.08 eV) compared to BdMC (3.32 eV), contributing to the improved NLO responses. Natural bond orbital (NBO) analysis confirmed the formation of a charge separation state, facilitating effective electron migration from donors to acceptors through the π-bridge. Additionally, using BdMC-based materials as acceptors in organic solar cells (OSCs) yielded open-circuit voltages (Voc) from 1.62 to 2.23 V, fill factors (FF) above 90%, and low exciton binding energies (Ee−b) in the range of 0.08 to 0.80 eV.

Anti-Inflammatory, Wound Healing, and Anti-Diabetic Effects of Pure Active Compounds Present in the Ryudai Gold Variety of Curcuma longa.

Turmeric (Curcuma longa) contains curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Nevertheless, curcumin is the most researched active ingredient for its numerous pharmacological effects. We investigated the impact of these curcuminoids found in Ryudai gold, an approved cultivar of Curcuma longa, on wound healing, inflammation, and diabetes. Sub-planter injections of carrageenan induced acute paw inflammation in rats. The wound-healing ability of 1% curcuminoids was examined by making a 6 mm round wound on the shaved dorsum of the mice with a biopsy punch. A single intraperitoneal injection of streptozotocin (50 mg/kg) was used to induce diabetes in mice. Curcuminoids at a dose rate of 100 mg/kg body weight were used with feed and as a gastric gavage to treat diabetes and inflammation in experimental animals. Paw thickness was measured at 1, 3, and 6 h following carrageenan injection. After three hours, mean paw volume was 58% in carrageenan-injected mice, which was 35%, 37%, and 31% in the curcumin, DMC, and BDMC groups, respectively. Histopathology of the paw tissue demonstrated severe infiltration of inflammatory cells and thickening of the dermis, which were remarkably improved by the curcuminoids. The wound-healing abilities were significantly higher in the curcumin- (95.0%), DMC- (93.17%), and BDMC-treated (89.0%) groups, in comparison to that of the control (65.09%) group at day nine. There were no significant differences in wound-healing activity among the groups treated with 1% curcuminoids throughout the study. Streptozotocin-induced diabetes was characterized by an increased blood glucose (552.2 mg/dL) and decreased body weight (31.2 g), compared to that of the control rats (145.6 mg/dL and 46.8 g blood glucose and body weight, respectively). It also caused an increase in serum alanine aminotransferase (ALT; 44.2 U/L) and aspartate aminotransferase (AST; 55.8 U/L) compared to that of the control group (18.6 U/L and 20.1 U/L, respectively). Histopathological examination of the liver showed that diabetes caused hepatic cellular necrosis, congestion of the central vein, and parenchymatous degeneration. However, all three curcuminoids significantly decreased blood glucose levels, ALT, and AST and improved the histopathological score of the liver. These results evidenced that not only curcumin but also DMC and BDMC have potent anti-inflammatory, wound healing, and anti-diabetic efficacy, and the Ryudai gold variety of turmeric could be used as a functional food supplement.

Fabrication of Curcumin-Based Electrochemical Nanosensors for the Detection of Environmental Pollutants: 1,4-Dioxane and Hydrazine.

This work reports the development of novel curcuminoid-based electrochemical sensors for the detection of environmental pollutants from water. In this study, the first set of electrochemical experiments was carried out using curcumin-conjugated multi-walled carbon nanotubes (MWCNT-CM) for 1,4-dioxane detection. The MWCNT-CM/GCE showed good sensitivity (103.25 nA nM-1 cm-2 in the linear range 1 nM to 1 µM), with LOD of 35.71 pM and LOQ of 108.21 pM. The second set of electrochemical experiments was carried out with bisdemethoxy curcumin analog quantum dots (BDMCAQD) for hydrazine detection. The BDMCAQD/GCE exhibited good sensitivity (74.96 nA nM-1 cm-2 in the linear range 100 nM to 1 µM), with LOD of 10 nM and LOQ of 44.93 nM. Thus, this work will serve as a reference for the fabrication of metal-free electrochemical sensors using curcuminoids as the redox mediator for the enhanced detection of environmental pollutants.

Subjective biosafety assessment of bisdemethoxycurcumin from the rhizomes of Curcuma longa

Introduction/Background: Curcuma longa, a plant native to the Indian subcontinent has a variety of biological activities. Curcumin is the most abundant and biologically active compound with many therapeutic properties. Demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) – the two other bioactive components present in Curcuma longa, besides curcumin, are collectively termed curcuminoids. Apart from the well-known curcumin, BDMC also has been reported to possess promising biological and pharmacological effects, but very little scientific evidence on its safety assessment has been published.Objective: The present study was undertaken to determine the safety of pure BDMC from Curcuma longa extract in rodents which comprises of general toxicity (both four weeks and three months duration), reproductive/developmental toxicity and genotoxicity studies.Methods: The Good Laboratory Practice studies were carried out in accordance with the test guidelines established by the Organization for Economic Cooperation and Development.Results: No treatment-related adverse findings were seen in general toxicity testing and a no observed adverse effect level (NOAEL) of 1000 mg/kg/day was established after four weeks (sub-acute) and three-months (sub-chronic) dosing. Evaluation of fertility, embryo-fetal, and post-natal reproductive and developmental parameters also showed no adverse findings with a NOAEL of 1000 mg/kg/day established. The results of genotoxicity as evaluated by in vitro reverse mutation assay, and in vivo micronucleus test in mice indicate that BDMC did not induce any genotoxic effects.Conclusion: Oral administration of BDMC is safe in rodents and non-mutagenic, with no adverse effects under experimental conditions.

Comparative Study of the Effects of Curcuminoids and Tetrahydrocurcuminoids on Melanogenesis: Role of the Methoxy Groups

Curcuminoids are naturally occurring yellow-colored compounds that, when hydrogenated to remove their conjugated double bond, become colorless and are referred to as tetrahydrocurcuminoids. Curcuminoids consist of pure curcumin (PC) in major amounts and demethoxycurcumin (DC) and bisdemethoxycurcumin (BDC) in minor amounts. Tetrahydrocurcuminoids similarly consist mainly of tetrahydrocurcumin (THC), along with minor amounts of tetrahydrodemethoxycurcumin (THDC) and tetrahydrobisdemethoxycurcumin (THBDC). Previous studies have shown the inhibitory effects of PC, DC, and BDC on melanin production, but there are contradictory findings about THC. In addition, there are currently no reports on the effects of THDC and THBDC on melanogenesis. Our previous report described that, in contrast to PC, which suppressed melanin production, THC stimulated melanin production in B16F10 and MNT-1 cells; this effect was ascribed to the loss of the conjugated heptadiene moiety of PC. However, whether this finding can be generalized to the two curcumin derivatives (DC and BDC), such that THDC and THBDC might also stimulate melanogenesis, has not been addressed. Herein, a comparative study of six curcumin derivatives (PC, DC, BDC, THC, THDC, and THBDC) was undertaken to identify their effects on melanogenesis with the goal of elucidating the structure–activity relationships (SARs) focused on assessing the two regions of the parent curcumins’ structure: (i) the hydrogenation of the two double bonds bridging the phenyl rings to the β-diketone moiety, and (ii) the effect of the ortho-methoxy substituent (-OCH3) on the two phenyl rings. To determine the direct effects of the six compounds, antioxidant activity and tyrosinase activity were assessed in cell-free systems before cellular experiments utilizing the B16F10 mouse melanoma cells, MNT-1 human melanoma cells, and primary cells. Evaluations were made on cytotoxicity, melanin concentration, and cellular tyrosinase activity. The results showed that BDC inhibited melanogenesis in B16F10 and MNT-1 cells. However, it was ineffective in primary human melanocytes, while THBDC continued to exhibit anti-melanogenic capacity in normal human melanocytes. Moreover, these findings provide a novel perspective into the role of the methoxy groups of PC on the biological effects of melanogenesis and also confirm that the removal of the conjugated double bonds abolishes the anti-melanogenic capacity of PC and DC only, but not BDC, as THBDC maintained anti-melanogenic activity that was greater than BDC. However, the outcome is contingent upon the specific kind of cell involved. To the best of our knowledge, this work presents novel findings indicating that the anti-melanogenic capacity of the colored BDC is not only intact but enhanced after its hydrogenation as observed in THBDC. The findings show potential for using colorless THBDC as a pharmacological candidate to diminish the increased pigmentation characteristic of skin hyperpigmentation disorders. Future pharmacological therapeutics that incorporate pure THBDC or THBDC-enriched extracts, which retain both a colorless appearance and potent anti-melanogenic activity, can be applied to compounds for anti-melanoma therapeutics where the demand for nontoxic novel molecules is desired for established efficacies.

Bisdemethoxycurcumin, a curcumin, protects chondrocytes, and reduces cartilage inflammation via the NRF2/HO-1/NLRP3 pathway.

The objective of this thesis is to evaluate the effect of bisdemethoxycurcumin (BDMC) on osteoarthritis (OA) and comprehensively evaluate the role of the Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) signalling pathway in chondrocytes. In our study, we treated chondrocytes with BDMC in an in vitro chondrocyte assay and measured its influence on extracellular matrix (ECM) expression, downstream heme oxygenase-1 (HO-1) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) levels. Our study indicates that BDMC significantly activates the Nrf2 signaling pathway in chondrocytes in vitro. Furthermore, the expression of matrix metalloproteinase 3, interleukin 1β, recombinant a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4 and (ADAMTS)5 was significantly suppressed by BDMC. This study confirms the potential for BDMC to activate the Nrf2/HO-1/NLRP3 signalling pathway and alleviate OA symptoms. Therefore, BDMC is a promising therapeutic agent for OA that offers new insights and treatment methods.

Characterization, Antioxidant and Cytotoxic Evaluation of Demethoxycurcumin and Bisdemethoxycurcumin from Curcuma longa Cultivated in Costa Rica

The biological activities of curcuminoids, the main polyphenol constituents of Curcuma longa (turmeric), have been the subject of many studies in recent years. However, these studies have focused on the major active compound, curcumin (CUR), while other important constituents, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDM) have been less studied and reported in the literature regarding their bioactivity as well as their isolation and solid-state characterization. Hence, in this study, DMC and BDM were isolated using pressurized liquid extraction (PLE) followed by column chromatography and crystallization. HRMS and 1H and 13C NMR were used to characterize them. Solid-state characterization was performed through powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) techniques. Further, powder dissolution profiles were performed in two media, antioxidant and cytotoxic activities were determined through 2,2-diphenyl-1-picrylhidrazyl (DPPH) and an MTT assay on gastric adenocarcinoma (AGS), colorectal adenocarcinoma (SW-620), and hepatocellular carcinoma (HepG2) cell lines. DMC and BDM were extracted from Curcuma longa cultivated in Costa Rica, using pressurized liquid extraction (PLE), then isolated and purified, combining column chromatography and crystallization techniques. The highly pure solids obtained were shown to be crystalline with an amorphous component. Although the PXRD pattern of BDM suggested a high amorphous component, the crystal exhibited a well-defined and faceted shape. Meanwhile, DMC crystallized in a botryoidal habit, and this constitutes the first report for this compound. On the other hand, BDM was slightly more soluble than DMC, which in turn showed an antioxidant IC50 value 28% higher than BDM (12.46 and 17.94 µg/mL, respectively). In respect to the cytotoxic effects, DMC showed a better IC50 value than BDM for both the SW-620 and AGS cell lines, while BDM exhibited a better IC50 value than DMC against the HepG2 cell line (64.7 μM). In terms of selectivity, BDM and DMC had the highest SI value for SW-620 cells compared to non-tumoral cells, while both compounds also displayed the best cytotoxic effect against these colon adenocarcinoma SW-620 cells, indicating BDM and DMC as potential chemotherapeutic drugs.

Poly (vinyl alcohol)-gelatin-sericin copolymerized film fortified with vesicle-entrapped demethoxycurcumin/bisdemethoxycurcumin for improved stability, antibacterial, anti-inflammatory, and skin tissue regeneration

Vesicle delivery carriers, used to stabilize hydrophobic drugs, are characterized by the propensity to aggregate, and fuse, limiting its applications. Fortifying vesicle-entrapped drugs within a biodegradable polymeric film constitutes a promising solution. In this study, biodegradable poly (vinyl alcohol) copolymerized with gelatin-sericin film and integrated alongside vesicle-entrapped demethoxycurcumin (DMC) or bisdemethoxycurcumin (BDMC) was developed, extensively characterized for improve efficacy, and compared. Vesicle-entrapped DMC or BDMC was spherical in shape with no changes in size, zeta-potential, and morphology after storing at 4 °C for 30 days. Antibacterial activity of vesicle-entrapped DMC formulations against Acinetobacter baumannii and Staphylococcus epidermidis was more effective than that of its free form. DMC and BDMC demonstrated dose dependent reduction in lipopolysaccharides (LPS)-induced nitric oxide (NO) levels either in free or in entrapped form. Moreover, vesicle-entrapped DMC/BDMC suppressed NO production at lower concentrations, compared with that of their free form and significantly improved the viability of RAW264.7 and HaCaT cells. Furthermore, functionalized film with vesicle-entrapped DMC/BDMC demonstrated excellent radical scavenging, biocompatibility, and cell migration efficacy. Thus, incorporating vesicle, entrapped DMC/BDMC within biodegradable polymeric film may comprised a promising strategy for improving stability, wound healing, and inflammation attenuation efficacy.

Disruptive Effects of Two Curcuminoids (Demethoxycurcumin and Bisdemethoxycurcumin) on the Larval Development of Drosophila melanogaster.

Juvenile hormones (JHs) play a central role in insect development, reproduction, and various physiological functions. Curcuminoids generally exhibit a wide range of biological activities, such as antioxidant, anti-inflammatory, antibacterial, and insecticidal, and they exhibit insect growth inhibitory effects. However, research on insecticidal properties of curcuminoids has been limited. Moreover, to the best of our knowledge, studies on JHs of insects and curcuminoids are lacking. Therefore, this study aimed to identify the substances that act as JH disruptors (JHDs) from edible plants. Demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), two curcuminoids from the turmeric plant Curcuma longa L. inhibited the formation of a methoprene-tolerant (Met)-Taiman (Tai) heterodimer complex in Drosophila melanogaster, as shown through in vitro yeast two-hybrid assays. An artificial diet containing 1% (w/v) DMC or BDMC significantly reduced the number of D. melanogaster larvae in a concentration-dependent manner; larval development was disrupted, preventing the progression of larvae to pupal stages, resulting in an absence of adults. Building on the results obtained in this study on curcuminoids, researchers can use our study as a reference to develop eco-friendly pesticides.

Bisdemethoxycurcumin, a curcumin derivative, ameliorates adjuvant-induced arthritis by suppressing inflammatory reactions and macrophage migration

Rheumatoid arthritis (RA) is a highly prevalent and chronic inflammatory synovial joint disease manifested by hyperplasia and continuous inflammation. Curcumin (Cur) has been studied for alleviating RA. However, poor stability and oral bioavailability restrict its therapeutic value. Bisdemethoxycurcumin (BDMC), a curcumin (Cur) derivative, exerts better stability and oral bioavailability than Cur. However, the efficacy of BDMC on RA has not been fully clarified. The aim of the study was to investigate the therapeutic effects and underlying mechanisms of BDMC on RA. The in-vivo anti-arthritic activity of BDMC was determined via adjuvant-induced arthritis (AIA) rat model. Paw swelling, body weight, arthritic index, and histopathological assessments were performed. RAW264.7 cell was stimulated by lipopolysaccharides (LPS) in vitro. The cell viability were determined by CCK8 assay, while the migration ability was determined using cell wound healing and transwell assays. Furthermore, in-vivo and in-vitro levels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) were assayed by ELISA, and that of IκBα, p-NF-κB, NF-κB, and COX-2 were assessed via Western blot or immunofluorescence. In AIA rat model, it suggested a higher anti-arthritic activity of BDMC than Cur, including amelioration of swelling in hind paws, reduced arthritic index, and alleviated histopathological injury in rats. Furthermore, BDMC also substantially decreased the levels of the aforementioned pro-inflammatory cytokines in both in-vivo and in-vitro, inhibited the IκBα degradation, down-regulated the COX-2 levels and p-NF-κB/NF-κB ratio in AIA rats and LPS-stimulated RAW264.7 cells. Additionally, BDMC showed an inhibitory effect on the migration of LPS-stimulated RAW264.7 cells. BDMC could effectively ameliorate RA by suppressing inflammatory reactions and inhibiting macrophage migration, more potentially than Cur.

Preparation and Evaluation of Curcumin Derivatives Nanoemulsion Based on Turmeric Extract and Its Antidepressant Effect.

The early stage of this study verified that a turmeric extract (TUR) including 59% curcumin (CU), 22% demethoxycurcumin (DMC), and 18% bisdemethoxycurcumin (BDMC), could enhance the stability of CU and had greater antidepressant potential in vitro. The objective of the study was to develop a nano-delivery system containing TUR (TUR-NE) to improve the pharmacokinetic behavior of TUR and enhance its antidepressant effect. The antidepressant potential of TUR was explored using ABTS, oxidative stress-induced cell injury, and a high-throughput screening model. TUR-NE was fabricated, optimized and characterized. The pharmacokinetic behaviors of TUR-NE were evaluated following oral administration to normal rats. The antidepressant effect of TUR-NE was assessed within chronic unpredictable mild stress model (CUMS) mice. The behavioral and biochemical indexes of mice were conducted. The results depicted that TUR had 3.18 and 1.62 times higher antioxidant capacity than ascorbic acid and CU, respectively. The inhibition effect of TUR on ASP+ transport was significantly enhanced compared with fluoxetine and CU. TUR-NE displayed a particle size of 116.0 ± 0.31 nm, polydispersity index value of 0.121 ± 0.007, an encapsulation rate of 98.45%, and good release and stability in cold storage. The results of pharmacokinetics indicated the AUC(0-t) of TUR-NE was 8.436 and 4.495 times higher than that of CU and TUR, while the Cmax was 9.012 and 5.452 times higher than that of CU and TUR, respectively. The pharmacodynamic study confirmed that the superior antidepressant effect of TUR-NE by significantly improving the depressant-like behaviors and elevating the content of 5-hydroxytryptamine in plasma and brain in CUMS mice. TUR-NE showed good safety with repeated administration. TUR-NE, which had small and uniform particle size, enhanced the bioavailability and antidepressant effect of TUR. It could be a promising novel oral preparation against depression.

Bisdemethoxycurcumin alleviates LPS-induced acute lung injury via activating AMPKα pathway

ObjectiveInflammation and oxidative stress contribute to the pathogenesis of acute lung injury (ALI), and subsequently result in rapid deterioration in health. Considering the indispensable role of bisdemethoxycurcumin (BDMC) in inflammation and oxidative stress, the present study aims to examine the effect of BDMC on sepsis-related ALI.MethodsC57BL/6 mice were administered with BDMC (100 mg/kg) or an equal volume of vehicle, and then injected with lipopolysaccharides (LPS) to induce ALI. We assessed the parameters of lung injury, inflammatory response and oxidative stress in lung tissues. Consistently, the macrophages with or without BDMC treatment were exposed to LPS to verify the effect of BDMC in vitro.ResultsBDMC suppressed LPS-induced lung injury, inflammation and oxidative stress in vivo and in vitro. Mechanistically, BDMC increased the phosphorylation of AMPKα in response to LPS stimulation, and AMPK inhibition with Compound C almost completely blunted the protective effect of BDMC in LPS-treated mice and macrophages. Moreover, we demonstrated that BDMC activated AMPKα via the cAMP/Epac pathway.ConclusionOur study identifies the protective effect of BDMC against LPS-induced ALI, and the underlying mechanism may be related to the activation of cAMP/Epac/AMPKα signaling pathway.

Natural deep eutectic solvent extraction of xanthorrhizol and curcuminoids from Curcuma xanthorrhiza Roxb and simultaneous determination by high-performance liquid chromatography

Context: Curcuma xanthorrhiza, a native to Indonesia, has been recognized as a potential medicinal plant. Xanthorrhizol (XTZ), curcumin (Cur), bisdemethoxycurcumin (BDMC), and demethoxycurcumin (DMC) are the main major metabolites with different bioactivities. Thus, the selective extraction of these markers is required. Aims: To characterize and use natural deep eutectic solvents (NADES) for the extraction of XTZ and curcuminoids (CURS) from C. xanthorrhiza. Methods: Four NADES, comprising of glucose:lactic acid (Glu:LA, 1:3), choline chloride: malic acid (ChCl:MA, 1:1), choline chloride: glycerol (ChCl:Gly, 1:1), and choline chloride: sucrose (ChCl:Suc, 3:1) were synthesized and subjected to FTIR. The physicochemical properties of NADES were characterized, including polarity, viscosity, and density. Their antioxidant profiles were evaluated. The toxicity of NADES was assessed towards Escherichia coli by real-time growth monitoring. Tested NADES were employed to extract marker compounds from the rhizome of C. xanthorrhiza. A validated high-performance liquid chromatography (HPLC) method was applied to simultaneously quantify XTZ and CURS in NADES extracts. Results: FTIR spectra confirmed the formation of hydrogen bonds between components. Using the DPPH and FRAP methods, all NADES and NADES extracts displayed antioxidative activity, suggesting the contribution of NADES to the activity. Of the tested NADES, Glu:LA (1:3) obtained the highest content of XTZ over Cur, BDMC, and DMC, comparable to that of ethanol maceration. All tested NADES were harmless to E. coli, except for ChCl:MA (1:1). However, NADES extracts of Glu:LA (1:3) and ChCl:MA (1:1) suppressed the growth of the bacterium. Scanning electron micrographs demonstrated the destruction of the surface structure of the rhizome powder by NADES-ultrasonication. Conclusions: The study recommended the use of Glu:LA (1:3) to selectively extract XTZ to promote environmentally friendly and sustainable extraction.

DFT and Molecular Docking Investigations Curcuminoid to Tribolium castaneum Telomerase Enzyme

The natural curcumin (Curcuminoid) is an anticancer compound. DFT and molecular docking curcuminoid to Tribolium castaneum telomerase were performed for curcumin (C), demethoxycurcumin (DC), and bisdemethoxycurcumin (BDC) in two structures, diketone (dk) and keto-enol (ke). Curcuminoid as inhibitor have optimized in gas phase used DFT/B3LYP. Optimized structure of curcuminoids conducted unplanarity for diketone and planarity for keto-enol. The HOMO-LUMO of curcuminoid spread mostly in entire molecule. Three compounds of curcuminoid could dock to active side of Tribolium castaneum telomerase. Binding energy of the diketone structure has lower energy than keto-enol structure. The binding energy of the diketone structure for the three compounds is between -7.5 to -7.7kcal/mol. This molecular docking shows intermolecular interaction between curcuminoid and active side of Tribolium castaneum telomerase dominated by hydrogen bonding. Curcuminoid diketone has potency as an inhibitor to Tribolium castaneum telomerase.

Turmeric Bioactive Compounds Alleviate Spinal Nerve Ligation-Induced Neuropathic Pain by Suppressing Glial Activation and Improving Mitochondrial Function in Spinal Cord and Amygdala.

This study examined the effects of turmeric bioactive compounds, curcumin C3 complex® (CUR) and bisdemethoxycurcumin (BDMC), on mechanical hypersensitivity and the gene expression of markers for glial activation, mitochondrial function, and oxidative stress in the spinal cord and amygdala of rats with neuropathic pain (NP). Twenty-four animals were randomly assigned to four groups: sham, spinal nerve ligation (SNL, an NP model), SNL+100 mg CUR/kg BW p.o., and SNL+50 mg BDMC/kg BW p.o. for 4 weeks. Mechanical hypersensitivity was assessed by the von Frey test (VFT) weekly. The lumbosacral section of the spinal cord and the right amygdala (central nucleus) were collected to determine the mRNA expression of genes (IBA-1, CD11b, GFAP, MFN1, DRP1, FIS1, PGC1α, PINK, Complex I, TLR4, and SOD1) utilizing qRT-PCR. Increased mechanical hypersensitivity and increased gene expression of markers for microglial activation (IBA-1 in the amygdala and CD11b in the spinal cord), astrocyte activation (GFAP in the spinal cord), mitochondrial dysfunction (PGC1α in the amygdala), and oxidative stress (TLR4 in the spinal cord and amygdala) were found in untreated SNL rats. Oral administration of CUR and BDMC significantly decreased mechanical hypersensitivity. CUR decreased CD11b and GFAP gene expression in the spinal cord. BDMC decreased IBA-1 in the spinal cord and amygdala as well as CD11b and GFAP in the spinal cord. Both CUR and BDMC reduced PGC1α gene expression in the amygdala, PINK1 gene expression in the spinal cord, and TLR4 in the spinal cord and amygdala, while they increased Complex I and SOD1 gene expression in the spinal cord. CUR and BDMC administration decreased mechanical hypersensitivity in NP by mitigating glial activation, oxidative stress, and mitochondrial dysfunction.