Effects of Lonicerae flos and Turmeric extracts on growth performance and intestinal health of yellow-feathered broilers.

This experiment aimed to investigate the effect of Lonicerae flos and Turmeric extracts (LTE) added to diets on growth performance and intestinal health of broilers. A total of 720 healthy 21-day-old yellow-feathered broilers were randomly divided into 3 treatment groups, with 6 replicates and 40 broilers per replicate. These 3 dietary treatments included a basal diet + 0 g/t LTE (CON), a basal diet + 300 g/t LTE (LTE300), and a basal diet + 500 g/t LTE (LTE500). The results showed that dietary supplementation of LTE linearly increased (P < 0.05) average daily gain (d 21-38) and average daily feed intake (d 21-60). At d 60, LTE300 had the highest serum total antioxidant capacity and total superoxide dismutase (P < 0.05), and LTE500 had the lowest malondialdehyde level (P < 0.05) among the three groups. Moreover, compared to CON, LTE300 significantly (P < 0.05) reduced endotoxin (d 38 and d 60) and diamine oxidase activity (d 38); LTE500 significantly (P < 0.05) reduced endotoxin (d 38 and d 60) and diamine oxidase levels (d 60) in the serum. LTE groups significantly (P < 0.05) increased ileal the ratio of villus height to crypt depth and serum immunoglobulin G. Furthermore, dietary supplementation of LTE also improved the intestinal epithelial barrier by the up-regulated mRNA expression of Claudin-1, Occludin and zonula occludens-1, and decreased the mRNA expression of interleukin-2, interleukin-8, tumor necrosis factor-α, nuclear factor κB, myeloid differentiation factor 88 and toll-like receptor 4. Compared to CON, 16S rRNA sequencing analysis showed that LTE300 had a better effect on the microbial diversity and composition in the ileum, and Bacillus and Lactobacillus_agilis were significantly enriched in LTE300. PICRUSt results showed that LTE300 was significantly (P < 0.05) enriched in four pathway pathways at KEGG level 2. In conclusion, dietary supplementation with LTE improved growth performance and intestinal health by enhancing antioxidant capacity, intestinal barrier and immune function, and regulating intestinal flora of yellow-feathered broilers.

An Investigation of the JAZ Family and the CwMYC2-like Protein to Reveal Their Regulation Roles in the MeJA-Induced Biosynthesis of ß-Elemene in Curcuma wenyujin.

ß-Elemene (C15H24), a sesquiterpenoid compound isolated from the volatile oil of Curcuma wenyujin, has been proven to be effective for multiple cancers and is widely used in clinical treatment. Unfortunately, the ß-elemene content in C. wenyujin is very low, which cannot meet market demands. Our previous research showed that methyl jasmonate (MeJA) induced the accumulation of ß-elemene in C. wenyujin. However, the regulatory mechanism is unclear. In this study, 20 jasmonate ZIM-domain (JAZ) proteins in C. wenyujin were identified, which are the core regulatory factors of the JA signaling pathway. Then, the conservative domains, motifs composition, and evolutionary relationships of CwJAZs were analyzed comprehensively and systematically. The interaction analysis indicated that CwJAZs can form homodimers or heterodimers. Fifteen out of twenty CwJAZs were significantly induced via MeJA treatment. As the master switch of the JA signaling pathway, the CwMYC2-like protein has also been identified and demonstrated to interact with CwJAZ2/3/4/5/7/15/17/20. Further research found that the overexpression of the CwMYC2-like gene increased the accumulation of ß-elemene in C. wenyujin leaves. Simultaneously, the expressions of HMGR, HMGS, DXS, DXR, MCT, HDS, HDR, and FPPS related to ß-elemene biosynthesis were also up-regulated by the CwMYC2-like protein. These results indicate that CwJAZs and the CwMYC2-like protein respond to the JA signal to regulate the biosynthesis of ß-elemene in C. wenyujin.

Differential gene expression analysis under salinity stress in the selected turmeric (Curcuma longa L.) cultivars for curcuminoid biosynthesis.

BACKGROUND: Curcuminoids are the phenolic compounds found exclusively in turmeric. Their presence is known to increase immunity and resistance against certain cancers and neurological disorders in humans also, protecting the plant itself against salinity stress. METHODS: In this experiment, we studied the expression levels of MAPK1 and DCS genes, their curcuminoid biosynthesis under salinity stress conditions so that the impact of individual genes can be understood using semi- quantitative PCR. RESULTS: The expressions of the genes with respect to curcuminoid biosynthesis showed fluctuations in their band intensity values due to the production of curcuminoids, which is initiated first in the leaves followed by the rhizomes. Not all the genes responsible for the curcuminoid biosynthesis show positive regulation under salt stress conditions which is observed in response to the severity of the stress imposed on the cultivars. CONCLUSIONS: In our findings, both the genes MAPK1 and DCS were down-regulated for curcuminoid biosynthesis compared to their controls in both the cultivars Vallabh Sharad and Selection 1.

Hypolipidemic and Anti-Inflammatory Effects of Curcuma longa-Derived Bisacurone in High-Fat Diet-Fed Mice.

Turmeric (Curcuma longa) contains various compounds that potentially improve health. Bisacurone is a turmeric-derived compound but has been less studied compared to other compounds, such as curcumin. In this study, we aimed to evaluate the anti-inflammatory and lipid-lowering effects of bisacurone in high-fat diet (HFD)-fed mice. Mice were fed HFD to induce lipidemia and orally administered bisacurone daily for two weeks. Bisacurone reduced liver weight, serum cholesterol and triglyceride levels, and blood viscosity in mice. Splenocytes from bisacurone-treated mice produced lower levels of the pro-inflammatory cytokines IL-6 and TNF-α upon stimulation with a toll-like receptor (TLR) 4 ligand, lipopolysaccharide (LPS), and TLR1/2 ligand, Pam3CSK4, than those from untreated mice. Bisacurone also inhibited LPS-induced IL-6 and TNF-α production in the murine macrophage cell line, RAW264.7. Western blot analysis revealed that bisacurone inhibited the phosphorylation of IKKα/ß and NF-κB p65 subunit, but not of the mitogen-activated protein kinases, p38 kinase and p42/44 kinases, and c-Jun N-terminal kinase in the cells. Collectively, these results suggest that bisacurone has the potential to reduce serum lipid levels and blood viscosity in mice with high-fat diet-induced lipidemia and modulate inflammation via inhibition of NF-κB-mediated pathways.

Pharmacophore-Based Virtual Screening and In-Silico Explorations of Biomolecules (Curcumin Derivatives) of Curcuma longa as Potential Lead Inhibitors of ERBB and VEGFR-2 for the Treatment of Colorectal Cancer.

The newly FDA-approved drug, Axitinib, is an effective therapy against RTKs, but it possesses severe adverse effects like hypertension, stomatitis, and dose-dependent toxicity. In order to ameliorate Axitinib's downsides, the current study is expedited to search for energetically stable and optimized pharmacophore features of 14 curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione) derivatives. The rationale behind the selection of curcumin derivatives is their reported anti-angiogenic and anti-cancer properties. Furthermore, they possessed a low molecular weight and a low toxicity profile. In the current investigation, the pharmacophore model-based drug design, facilitates the filtering of curcumin derivatives as VEGFR2 interfacial inhibitors. Initially, the Axitinib scaffold was used to build a pharmacophore query model against which curcumin derivatives were screened. Then, top hits from pharmacophore virtual screening were subjected to in-depth computational studies such as molecular docking, density functional theory (DFT) studies, molecular dynamics (MD) simulations, and ADMET property prediction. The findings of the current investigation revealed the substantial chemical reactivity of the compounds. Specifically, compounds S8, S11, and S14 produced potential molecular interactions against all four selected protein kinases. Docking scores of -41.48 and -29.88 kJ/mol for compounds S8 against VEGFR1 and VEGFR3, respectively, were excellent. Whereas compounds S11 and S14 demonstrated the highest inhibitory potential against ERBB and VEGFR2, with docking scores of -37.92 and -38.5 kJ/mol against ERBB and -41.2 and -46.5 kJ/mol against VEGFR-2, respectively. The results of the molecular docking studies were further correlated with the molecular dynamics simulation studies. Moreover, HYDE energy was calculated through SeeSAR analysis, and the safety profile of the compounds was predicted through ADME studies.

The role of Curcuma longa essential oil in controlling acute toxoplasmosis by improving the immune system and reducing inflammation and oxidative stress.

Background: Chemotherapy with synthetic drugs is the principal approach for toxoplasmosis treatment; however, recent studies reported the limitations and adverse side effects of these chemical drugs. Objective: This study aimed to examine the in vitro and in vivo effects of Curcuma longa essential oil (CLE) against the Toxoplasma gondii RH strain. Methods: The in vitro effect of different concentrations of CLE on T. gondii tachyzoites was assessed by cell viability assay. Flow cytometry and apoptosis analysis were performed, and nitric oxide production by CLE was also evaluated in tachyzoites. BALB/c mice were orally treated with various doses (1.25, 2.5, and 5 mg·kg-1·day-1) of CLE for 2 weeks. After the induction of acute toxoplasmosis in the mice, their survival rate and the mean number of peritoneal parasites were checked. The hepatic level of antioxidant enzymes and oxidative stress markers was evaluated by commercial kits. The mRNA expression level of proinflammatory cytokines such as interleukin 1-beta (IL-1ß) and interferon-gamma (IFN-γ) was evaluated by quantitative real-time PCR. Results: CLE, especially at 50 µg/ml, showed potent inhibitory effects on T. gondii tachyzoites. It increased the survival rate (ninth day) and reduced the mean number of peritoneal tachyzoites in the infected mice. CLE dependently increased (p < 0.01) the number of necrotic and apoptotic cells as well as NO production. CLE significantly (p < 0.05) reduced the hepatic level of oxidative stress markers but increased (p < 0.001) the antioxidant enzymes and proinflammatory cytokines in the infected mice, with no important toxicity for vital organs. Conclusion: The findings of this survey revealed the significant in vitro inhibitory effects of CLE on T. gondii tachyzoites. The results also exhibited promising in vivo effects of CLE. CLE improved the survival rate of infected mice and reduced the parasite number in them. Although the mechanisms of action of CLE are not clear, our study demonstrated its beneficial effects on acute toxoplasmosis by strengthening the immune system and reducing inflammation and oxidative stress. Still, more studies are required to confirm these results.

The Incorporation of Curcuminoids in Gamma-Cyclodextrins Improves Their Poor Bioaccessibility, Which Is due to Both Their Very Low Incorporation into Mixed Micelles and Their Partial Adsorption on Food.

SCOPE: Turmeric curcuminoids mainly consist of curcumin (CUR), demethoxycurcumin (dCUR), and bisdemethoxycurcumin (bdCUR). CUR displays low bioavailability, partly due to poor solubilization in the intestinal lumen during digestion, while data for dCUR and bdCUR are scarce. The study aims to investigate the bioaccessibility of curcuminoids from turmeric extracts or from gamma-cyclodextrins, considering potential interactions with food. METHODS AND RESULTS: Using an in vitro digestion model (correlation with CUR bioavailability: r = 0.99), the study shows that curcuminoid bioaccessibility from turmeric extract without food is low: bdCUR (11.5 ± 0.6%) > dCUR (1.8 ± 0.1%) > CUR (0.8 ± 0.1%). Curcuminoids incorporated into gamma-cyclodextrins display higher bioaccessibilities (bdCUR: 21.1 ± 1.6%; dCUR: 14.3 ± 0.9%; CUR: 11.9 ± 0.7%). Curcuminoid bioaccessibility is highest without food (turmeric extract: 2.0 ± 0.1%; gamma-cyclodextrins: 12.4 ± 0.8%) and decreases with a meat- and potato-based meal (turmeric extract: 1.1 ± 0.2%; gamma-cyclodextrins: 2.4 ± 0.3%) or a wheat-based meal (turmeric extract: 0.1 ± 0.0%; gamma-cyclodextrins: 0.3 ± 0.1%). Curcuminoids exhibit low (<10%) incorporation efficiencies into synthetic mixed micelles (bdCUR > dCUR > CUR). CONCLUSIONS: bdCUR and dCUR show greater bioaccessibilities versus CUR. Food diminishes curcuminoid bioaccessibility, likely by adsorption mechanisms. Gamma-cyclodextrins improve curcuminoid bioaccessibility.

Essential oil composition of Curcuma species and drugs from Asia analyzed by headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry.

Essential oils (EOs) comprised of various bioactive compounds have been widely detected in the Curcuma species. Due to the widespread distribution and misidentification of Curcuma species and differences in processing methods, inconsistent reports on major compounds in rhizomes of the same species from different geographical regions are not uncommon. This inconsistency leads to confusion and inaccuracy in compound detection of each species and also hinders comparative study based on EO compositions. The present study aimed to characterize EO compositions of 12 Curcuma species, as well as to detect the compositional variation among different species, and between the plant specimens and their related genetically validated crude drug samples using headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry. The plant specimens of the same species showed similar EO patterns, regardless of introducing from different geographical sources. Based on the similarity of EO compositions, all the specimens and samples were separated into eight main groups: C. longa; C. phaeocaulis, C. aeruginosa and C. zedoaria; C. zanthorrhiza; C. aromatica and C. wenyujin; C. kwangsiensis; C. amada and C. mangga; C. petiolata; C. comosa. From EOs of all the specimens and samples, 54 major compounds were identified, and the eight groups were chemically characterized. Most of the major compounds detected in plant specimens were also observed in crude drug samples, although a few compounds converted or degraded due to processing procedures or over time. Orthogonal partial least squares-discriminant analysis allowed the marker compounds to discriminate each group or each species to be identified.

Curcumin and Its Derivatives Induce Apoptosis in Human Cancer Cells by Mobilizing and Redox Cycling Genomic Copper Ions.

Turmeric spice contains curcuminoids, which are polyphenolic compounds found in the Curcuma longa plant's rhizome. This class of molecules includes curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Using prostate cancer cell lines PC3, LNCaP, DU145, and C42B, we show that curcuminoids inhibit cell proliferation (measured by MTT assay) and induce apoptosis-like cell death (measured by DNA/histone ELISA). A copper chelator (neocuproine) and reactive oxygen species scavengers (thiourea for hydroxyl radical, superoxide dismutase for superoxide anion, and catalase for hydrogen peroxide) significantly inhibit this reaction, thus demonstrating that intracellular copper reacts with curcuminoids in cancer cells to cause DNA damage via ROS generation. We further show that copper-supplemented media sensitize normal breast epithelial cells (MCF-10A) to curcumin-mediated growth inhibition, as determined by decreased cell proliferation. Copper supplementation results in increased expression of copper transporters CTR1 and ATP7A in MCF-10A cells, which is attenuated by the addition of curcumin in the medium. We propose that the copper-mediated, ROS-induced mechanism of selective cell death of cancer cells may in part explain the anticancer effects of curcuminoids.

Multiple anti-inflammatory mechanisms of Zedoary Turmeric Oil Injection against lipopolysaccharides-induced acute lung injury in rats elucidated by network pharmacology combined with transcriptomics.

BACKGROUND: Prospects for the drug treatment of acute lung injury (ALI) is unpromising. Managing inflammation can prevent ALI from progressing and minimize further deterioration. Zedoary turmeric oil injection (ZTOI), a patented traditional Chinese medicine (TCM) that has been used against ALI, has shown significant anti-inflammatory effects. However, the mechanisms underlying these effects remain unclear. PURPOSE: Elucidate the anti-inflammatory mechanism by which ZTOI acts against ALI in rats using an ingredients-targets-pathways (I-T-P) interaction network. STUDY DESIGN AND METHODS: The key ingredients of ZTOI were characterized using UPLC-MS/MS combined with literature mining. The target profiles of each ingredient were established using drug-target databases. The anti-inflammatory activity of ZTOI against lipopolysaccharides (LPS)-induced rat ALI was validated using histopathology and inflammatory factor assessments. The therapeutic targets of ZTOI were screened by integrating transcriptomic results of lung tissues with protein-protein interaction (PPI) expansion. Using KEGG pathway enrichment, an I-T-P network was established to determine the essential interactions among ingredients, targets, and pathways of ZTOI against lung inflammation in ALI. Molecular docking and immunofluorescence staining were utilized to confirm the accuracy of the I-T-P network. RESULTS: A total of 11 sesquiterpenes, whose target profiles may characterize the potential function of ZTOI, were identified as key ingredients. In the ALI rat model, ZTOI can alleviate lung inflammation by decreasing the levels of C-reactive protein, interleukin-6, interleukin-1ß, and tumor necrosis factor α both in serum and lung tissues. Based on our biological samples, transcriptomics, PPI network expansion, and KEGG pathway enrichment, 11 ingredients, 174 targets, and 8 signaling pathways were linked in the I-T-P networks. From these results, ZTOI could be inferred to exert multiple anti-inflammatory effects against ALI through Toll-like receptor, NF-kappa B, RIG-I-like receptor, TNF, NOD-like receptor, IL-17, MAPK, and the Toll and Imd signaling pathways. In addition, two significantly regulated targets in the transcriptome, Usp18 and Map3k7, could be the essential anti-inflammatory targets of ZTOI. CONCLUSION: By integrating network pharmacology with ingredient identification and transcriptomics, we show the multiple anti-inflammatory mechanisms by which ZTOI acts against ALI on an I-T-P level. This work also provides a methodological reference for related research into TCM.

Effects of Turmeric Powder on Aflatoxin M1 and Aflatoxicol Excretion in Milk from Dairy Cows Exposed to Aflatoxin B1 at the EU Maximum Tolerable Levels.

Due to the climatic change, an increase in aflatoxin B1 (AFB1) maize contamination has been reported in Europe. As an alternative to mineral binders, natural phytogenic compounds are increasingly used to counteract the negative effects of AFB1 in farm animals. In cows, even low dietary AFB1 concentrations may result in the milk excretion of the genotoxic carcinogen metabolite aflatoxin M1 (AFM1). In this study, we tested the ability of dietary turmeric powder (TP), an extract from Curcuma longa (CL) rich in curcumin and curcuminoids, in reducing AFM1 mammary excretion in Holstein-Friesian cows. Both active principles are reported to inhibit AFM1 hepatic synthesis and interact with drug transporters involved in AFB1 absorption and excretion. A crossover design was applied to two groups of cows (n = 4 each) with a 4-day washout. Animals received a diet contaminated with low AFB1 levels (5 ± 1 µg/kg) for 10 days ± TP supplementation (20 g/head/day). TP treatment had no impact on milk yield, milk composition or somatic cell count. Despite a tendency toward a lower average AFM1 milk content in the last four days of the treatment (below EU limits), no statistically significant differences with the AFB1 group occurred. Since the bioavailability of TP active principles may be a major issue, further investigations with different CL preparations are warranted.

Synergistic Anti-Inflammatory Activity of Ginger and Turmeric Extracts in Inhibiting Lipopolysaccharide and Interferon-γ-Induced Proinflammatory Mediators.

This study aims to investigate the combined anti-inflammatory activity of ginger and turmeric extracts. By comparing the activities of individual and combined extracts in lipopolysaccharide and interferon-γ-induced murine RAW 264.7 cells, we demonstrated that ginger-turmeric combination was optimal at a specific ratio (5:2, w/w) in inhibiting nitric oxide, tumour necrosis factor and interleukin 6 with synergistic interaction (combination index < 1). The synergistic inhibitory effect on TNF was confirmed in human monocyte THP-1 cells. Ginger-turmeric combination (5:2, w/w) also upregulated nuclear factor erythroid 2−related factor 2 activity and heme oxygenase-1 protein expression. Additionally, 6-shogaol, 8-shogaol, 10-shogaol and curcumin were the leading compounds in reducing major proinflammatory mediators and cytokines, and a simplified compound combination of 6-s, 10-s and curcumin showed the greatest potency in reducing LPS-induced NO production. Our study provides scientific evidence in support of the combined use of ginger and turmeric to alleviate inflammatory processes.

Guaiane-type sesquiterpenes from Curcumawenyujin.

Eight undescribed sesquiterpenes including seven guaianes and one pseudoguaiane which were named as wenyujinols A-H, along with ten known guaianes, were isolated from rhizomes of Curcuma wenyujin Y. H. Chen et C. Ling. The structures of wenyujinols A-H were elucidated by 1D and 2D nuclear magnetic resonance (NMR) data, high resolution mass spectrum (HRMS), electronic circular dichroism (ECD) spectra, and X-ray single crystallographic analysis. All of the isolated compounds were evaluated for antioxidant activity via activation of the Nrf2-ARE pathway in human embryonic kidney (HEK) 293 cells, for inhibitory effects on NO production in RAW 264.7 cells, and for cytotoxicity against three human cancer cell lines A549, HL60, and MCF7 in vitro. The results indicated that procurcumenol (50-200 µM) and 9-oxo-neoprocurcumenol (25-200 µM) exhibited antioxidant activity via activation of the Nrf2-ARE pathway in a dose-dependent manner.

Curcumin as a Natural Modulator of B Lymphocytes: Evidence from In Vitro and In Vivo Studies.

B cells are the only player of humoral immune responses by the production of various types of antibodies. However, B cells are also involved in the pathogenesis of several immune-mediated diseases. Moreover, different types of B cell lymphoma have also been characterized. Selective depletion of B cells by anti-CD20 and other B cell-depleting agents in the clinic can improve a wide range of immune-mediated diseases. B cells' capacity to act as cytokine-producing cells explains how they can control immune cells' activity and contribute to disease pathogenesis. Thus, researchers investigated a safe, low-cost, and effective treatment modality for targeting B cells. In this respect, curcumin, the biologically active ingredient of turmeric, has a wide range of pharmacological activities. Evidence showed that curcumin could affect various immune cells, such as monocytes and macrophages, dendritic cells, and T lymphocytes. However, there are few pieces of evidence about the effects of curcumin on B cells. This study aims to review the available evidence about curcumin's modulatory effects on B cells' proliferation, differentiation, and function in different states. Apart from normal B cells, the modulatory effects of curcumin on B cell lymphoma will also be discussed.

The Effect of Curcuma phaeocaulis Valeton (Zingiberaceae) Extract on Prion Propagation in Cell-Based and Animal Models.

Prion diseases are neurodegenerative disorders in humans and animals for which no therapies are currently available. Here, we report that Curcuma phaeocaulis Valeton (Zingiberaceae) (CpV) extract was partly effective in decreasing prion aggregation and propagation in both in vitro and in vivo models. CpV extract inhibited self-aggregation of recombinant prion protein (PrP) in a test tube assay and decreased the accumulation of scrapie PrP (PrPSc) in ScN2a cells, a cultured neuroblastoma cell line with chronic prion infection, in a concentration-dependent manner. CpV extract also modified the course of the disease in mice inoculated with mouse-adapted scrapie prions, completely preventing the onset of prion disease in three of eight mice. Biochemical and neuropathological analyses revealed a statistically significant reduction in PrPSc accumulation, spongiosis, astrogliosis, and microglia activation in the brains of mice that avoided disease onset. Furthermore, PrPSc accumulation in the spleen of mice was also reduced. CpV extract precluded prion infection in cultured cells as demonstrated by the modified standard scrapie cell assay. This study suggests that CpV extract could contribute to investigating the modulation of prion propagation.

Curcuma as an adjuvant in colorectal cancer treatment.

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide and mostly affects men. Around 20% of its incidence is by familiar disposition due to hereditary syndromes. The CRC treatment involves surgery and chemotherapy; however, the side effects of treatments and the fast emergence of drug resistance evidence the necessity to find more effective drugs. Curcumin is the main polyphenol pigment present in Curcuma longa, a plant widely used as healthy food with antioxidant properties. Curcumin has synergistic effects with antineoplastics such as 5-fluorouracil and oxaliplatin, as well anti-inflammatory drugs by inhibiting cyclooxygenase-2 and the Nuclear factor kappa B. Furthermore, curcumin shows anticancer properties by inhibition of the Wnt/ß-catenin, Hedgehog, Notch, and the phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathways implicated in the progression of CRC. However, the consumption of pure curcumin is less suitable, as the absorption is poor, and the metabolism and excretion are high. Pharmacological formulations and essential oils of the plant improve the curcumin absorption, resulting in therapeutical dosages. Despite the evidence obtained in vitro and in vivo, clinical studies have not yet confirmed the therapeutic potential of curcumin against CRC. Here we reviewed the last scientific information that supports the consumption of curcumin as an adjuvant for CRC therapy.

Synthetic curcumin analog: inhibiting the invasion, angiogenesis, and metastasis in human laryngeal carcinoma cells via NF-kB pathway.

BACKGROUND: Laryngeal carcinoma, the most common among head and neck squamous cell carcinoma (HNSCC), induces 1% of all cancer deaths. Curcumin the active constituent of turmeric, is shown to be effective in the treatment of various cancers. In the present study, we explored the mechanistic role of bis-demethoxy curcumin analog (BDMC-A) as a chemotherapeutic agent. We investigated its inhibitory effect on invasion, angiogenesis, and metastasis in human laryngeal carcinoma (Hep-2) cells in comparison with curcumin. METHODS: The effect of curcumin and BDMC-A on transcription factors (NF-κB, p65, c-Jun, c-Fos, STAT3, 5, PPAR-γ, ß-catenin, COX-2, MMP-9, VEGF, TIMP-2) involved in signal transduction cascade, invasion, and angiogenesis in Hep-2 cells were quantified using Western blotting and RT-PCR technique. ELISA was used to measure the pro-inflammatory markers in Hep-2 cells treated with curcumin and BDMC-A. RESULTS: The results showed that BDMC-A inhibits the transcription factors NF-κB, p65, c-Jun, c-Fos, STAT3, STAT5, PPAR-γ and ß-catenin, which are responsible for tumor progression and malignancy. Moreover, BDMC-A treatment downregulated MMP-9, VEGF, TGF- ß, IL-6 and IL-8 and upregulated TIMP-2 levels. The effects were more significant compared to curcumin. CONCLUSION: Our overall results revealed that BDMC-A more effectively inhibited the markers of invasion, angiogenesis and metastasis in comparison with curcumin.

Curcumin Attenuates Environment-Derived Osteoarthritis by Sox9/NF-kB Signaling Axis.

Inflammation has a fundamental impact on the pathophysiology of osteoarthritis (OA), a common form of degenerative arthritis. It has previously been established that curcumin, a component of turmeric (Curcuma longa), has anti-inflammatory properties. This research evaluates the potentials of curcumin on the pathophysiology of OA in vitro. To explore the anti-inflammatory efficacy of curcumin in an inflamed joint, an osteoarthritic environment (OA-EN) model consisting of fibroblasts, T-lymphocytes, 3D-chondrocytes is constructed and co-incubated with TNF-α, antisense oligonucleotides targeting NF-kB (ASO-NF-kB), or an IkB-kinase (IKK) inhibitor (BMS-345541). Our results show that OA-EN, similar to TNF-α, suppresses chondrocyte viability, which is accompanied by a significant decrease in cartilage-specific proteins (collagen II, CSPG, Sox9) and an increase in NF-kB-driven gene proteins participating in inflammation, apoptosis, and breakdown (NF-kB, MMP-9, Cox-2, Caspase-3). Conversely, similar to knockdown of NF-kB at the mRNA level or at the IKK level, curcumin suppresses NF-kB activation, NF-kB-promotes gene proteins derived from the OA-EN, and stimulates collagen II, CSPG, and Sox9 expression. Furthermore, co-immunoprecipitation assay shows that curcumin reduces OA-EN-mediated inflammation and chondrocyte apoptosis, with concomitant chondroprotective effects, due to modulation of Sox-9/NF-kB signaling axis. Finally, curcumin selectively hinders the interaction of p-NF-kB-p65 directly with DNA-this association is disrupted through DTT. These results suggest that curcumin suppresses inflammation in OA-EN via modulating NF-kB-Sox9 coupling and is essential for maintaining homeostasis in OA by balancing chondrocyte survival and inflammatory responses. This may contribute to the alternative treatment of OA with respect to the efficacy of curcumin.

Effect of turmeric on adiponectin, sexual function and sexual hormones in stressed mice.

Sexual function is essential for species survival. Melanocortin, progesterone, and estrogen can improve sexual function and they are modulated by adiponectin hormone which can be increased by Turmeric. In various studies shows Turmeric ability that is easily accessible to increase serum adiponectin levels. Therefore, the researchers decided to conduct a study to determine the effect of turmeric on serum adiponectin levels, sexual behavior, and profile of steroid hormones in stressed mice. Thirty female mice, six in each group (1. control group, 2. mice that received stress, 3. stress mice received 100 mg/kg turmeric (extract daily) for 4 weeks, 4. stress mice received turmeric (extract daily) for 4 weeks and also received adiponectin antagonist, and 5. stress groups received adiponectin antagonist), were used in the current study. The mice first underwent blood sampling. Then all mice were subjected to stress testing before the intervention except one group, which considered as a control group. The intervention in this study was done as a 100 mg/kg turmeric extract that was gavaged daily for each mouse. After the intervention, all mice were tested for sexual behavior, and then blood samples were taken to check serum levels of adiponectin, estradiol, progesterone and prolactin. So, the results showed before the intervention there were no significant difference among 5 group in levels of adiponectin (p = 0.145), estradiol (p = 0.148), progesterone (p = 0.166) and prolactin (p = 0.206) but after intervention there were significant difference between 5 group in levels of adiponectin, estradiol and progesterone (p < 0.001). Also there was significant difference among 5 groups in sexual behavior (p < 0.001). Therefore, consumption of turmeric, which increases serum adiponectin in the stressed mice, can improve sexual function and estradiol hormones profiling.

Anti-Tumor Drug Discovery Based on Natural Product ß-Elemene: Anti-Tumor Mechanisms and Structural Modification.

Natural products are important sources for drug discovery, especially anti-tumor drugs. ß-Elemene, the prominent active ingredient extract from the rhizome of Curcuma wenyujin, is a representative natural product with broad anti-tumor activities. The main molecular mechanism of ß-elemene is to inhibit tumor growth and proliferation, induce apoptosis, inhibit tumor cell invasion and metastasis, enhance the sensitivity of chemoradiotherapy, regulate the immune system, and reverse multidrug resistance (MDR). Elemene oral emulsion and elemene injection were approved by the China Food and Drug Administration (CFDA) for the treatment of various cancers and bone metastasis in 1994. However, the lipophilicity and low bioavailability limit its application. To discover better ß-elemene-derived anti-tumor drugs with satisfying drug-like properties, researchers have modified its structure under the premise of not damaging the basic scaffold structure. In this review, we comprehensively discuss and summarize the potential anti-tumor mechanisms and the progress of structural modifications of ß-elemene.