RESUMEN
Turmeric, derived from Curcuma longa, and Lactobacillus paracasei, a lactic acid bacteria, have been studied for their potential antiobesity effects. To date, the antiobesity effects of turmeric fermented with L. paracasei have not been sufficiently investigated. This study was conducted via oral administration of 5% L. paracasei-fermented (FT) and unfermented turmeric (UT) in diet over 16 weeks using high-fat diet (HFD)-induced obese C57BL/6J mice. Results showed that the curcuminoid content of turmeric decreased following fermentation. Furthermore, FT significantly suppressed weight gain and liver and visceral adipose tissue weight and reduced plasma metabolic parameters in both the UT and FT experimental groups. The effects of FT were more noticeable than those of the unfermented form. Moreover, FT downregulated the expression of adipogenesis, lipogenesis, and inflammatory-related protein, but upregulated liver ß-oxidation protein SIRT 1, PPARα, and PGC-1α in perigonadal adipose tissue. Additionally, FT ameliorated insulin resistance by activating insulin receptor pathway protein expressions in visceral adipose tissues. FT also modulated gut microbiota composition, particularly in two beneficial bacteria, Akkermansia muciniphila and Desulfovibrio, as well as two short-chain fatty acid-producing bacteria: Muribaculum intestinale and Deltaproteobacteria. Our findings indicate that the modulation effect of FT may be an important pathway for its antiobesity mechanisms.
Asunto(s)
Curcuma , Dieta Alta en Grasa , Fermentación , Microbioma Gastrointestinal , Lacticaseibacillus paracasei , Ratones Endogámicos C57BL , Obesidad , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Obesidad/metabolismo , Obesidad/microbiología , Ratones , Curcuma/química , Curcuma/metabolismo , Masculino , Lacticaseibacillus paracasei/metabolismo , Humanos , Fármacos Antiobesidad/administración & dosificación , Adipogénesis/efectos de los fármacos , Hígado/metabolismo , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , PPAR alfa/metabolismo , PPAR alfa/genética , Resistencia a la Insulina , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Bacterias/efectos de los fármacosRESUMEN
MAIN CONCLUSION: CaTPS2 and CaTPS3 were significantly expressed in flowers of Curcuma alismatifolia 'Shadow' and demonstrated bifunctional enzyme activity, CaTPS2 generated linalool and nerolidol as products, and CaTPS3 catalyzed ß-myrcene and ß-farnesene formation. This study presents the discovery and functional characterization of floral terpene synthase (TPS) genes in Curcuma alismatifolia 'Shadow', a cultivar renowned for its unique fragrance. Addressing the gap in understanding the genetic basis of floral scent in this species, we identified eight TPS genes through comprehensive transcriptome sequencing. Among these, CaTPS2 and CaTPS3 were significantly expressed in floral tissues and demonstrated bifunctional enzyme activity corresponding to the major volatile compounds detected in 'Shadow'. Functional analyses, including in vitro assays complemented with rigorous controls and alternative identification methods, elucidated the roles of these TPS genes in terpenoid biosynthesis. In vitro studies were conducted via heterologous expression in E. coli, followed by purification of the recombinant protein using affinity chromatography, enzyme assays were performed with GPP/FPP as the substrate, and volatile products were inserted into the GC-MS for analysis. Partially purified recombinant protein of CaTPS2 catalyzed GPP and FPP to produce linalool and nerolidol, respectively, while partially purified recombinant protein of CaTPS3 generated ß-myrcene and ß-farnesene with GPP and FPP as substrates, respectively. Real-time quantitative PCR further validated the expression patterns of these genes, correlating with terpenoid accumulation in different plant tissues. Our findings illuminate the molecular mechanisms underpinning floral fragrance in C. alismatifolia and provide a foundation for future genetic enhancements of floral scent in ornamental plants. This study, therefore, contributes to the broader understanding of terpenoid biosynthesis in plant fragrances, paving the way for biotechnological applications in horticulture plant breeding.
Asunto(s)
Monoterpenos Acíclicos , Transferasas Alquil y Aril , Curcuma , Flores , Sesquiterpenos , Transferasas Alquil y Aril/genética , Transferasas Alquil y Aril/metabolismo , Flores/genética , Flores/enzimología , Flores/metabolismo , Sesquiterpenos/metabolismo , Monoterpenos Acíclicos/metabolismo , Curcuma/genética , Curcuma/enzimología , Curcuma/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Terpenos/metabolismo , Compuestos Orgánicos Volátiles/metabolismo , Filogenia , OdorantesRESUMEN
In this study, we have investigated the effect of carbon quantum dots (FM-CQDs) synthesized from marine fungal extract on Curcuma longa to improve the plant growth and curcumin production. The isolated fungus, Aspergillus flavus has produced a high amount of indole-3-acetic acid (IAA) (0.025 mg g-1), when treated with tryptophan. CQDs were synthesized from the A. flavus extract and it was characterized using ultraviolet visible spectrophotometer (UV-Vis) and high-resolution transmission electron microscopy (HR-TEM). The synthesized CQDs were excited at 365 nm in an UV-Vis and the HR-TEM analysis showed approximately 7.4 nm in size with a spherical shape. Both fungal crude extract (FCE) at 0-100 mg L-1 and FM-CQDs 0-5 mg L-1 concentrations were tested on C. longa. About 80 mg L-1 concentration FCE treated plants has shown a maximum height of 21 cm and FM-CQDs at 4 mg L-1 exhibited a maximum height of 25 cm compared to control. The FM-CQDs significantly increased the photosynthetic pigments such as total chlorophyll (1.08 mg g-1 FW) and carotenoids (17.32 mg g-1 FW) in C. longa. Further, antioxidant enzyme analysis confirmed that the optimum concentrations of both extracts did not have any toxic effects on the plants. FM-CQDs treated plants increased the curcumin content up to 0.060 mg g-1 by HPLC analysis. Semi quantitative analysis revealed that FCE and FM-CQDs significantly upregulated ClCURS1 gene expression in curcumin production.
Asunto(s)
Aspergillus flavus , Carbono , Curcuma , Curcumina , Puntos Cuánticos , Puntos Cuánticos/química , Curcuma/metabolismo , Curcuma/microbiología , Carbono/metabolismo , Carbono/farmacología , Curcumina/metabolismo , Curcumina/farmacología , Aspergillus flavus/metabolismo , Aspergillus flavus/crecimiento & desarrollo , Ácidos Indolacéticos/metabolismo , Endófitos/metabolismoRESUMEN
Plant JASMONATE ZIM-DOMAIN (JAZ) genes play crucial roles in regulating the biosynthesis of specialized metabolites and stressful responses. However, understanding of JAZs controlling these biological processes lags due to numerous JAZ copies. Here, we found that two leaf-specific CwJAZ4/9 genes from Curcuma wenyujin are strongly induced by methyl-jasmonate (MeJA) and negatively correlated with terpenoid biosynthesis. Yeast two-hybrid, luciferase complementation imaging and in vitro pull-down assays confirmed that CwJAZ4/9 proteins interact with CwMYC2 to form the CwJAZ4/9-CwMYC2 regulatory cascade. Furthermore, transgenic hairy roots showed that CwJAZ4/9 acts as repressors of MeJA-induced terpenoid biosynthesis by inhibiting the terpenoid pathway and jasmonate response, thus reducing terpenoid accumulation. In addition, we revealed that CwJAZ4/9 decreases salt sensitivity and sustains the growth of hairy roots under salt stress by suppressing the salt-mediated jasmonate responses. Transcriptome analysis for MeJA-mediated transgenic hairy root lines further confirmed that CwJAZ4/9 negatively regulates the terpenoid pathway genes and massively alters the expression of genes related to salt stress signaling and responses, and crosstalks of multiple phytohormones. Altogether, our results establish a genetic framework to understand how CwJAZ4/9 inhibits terpenoid biosynthesis and confers salt tolerance, which provides a potential strategy for producing high-value pharmaceutical terpenoids and improving resistant C. wenyujin varieties by a genetic approach.
Asunto(s)
Acetatos , Curcuma , Ciclopentanos , Regulación de la Expresión Génica de las Plantas , Oxilipinas , Proteínas de Plantas , Tolerancia a la Sal , Terpenos , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Tolerancia a la Sal/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Terpenos/metabolismo , Acetatos/farmacología , Acetatos/metabolismo , Curcuma/metabolismo , Curcuma/genética , Plantas Modificadas Genéticamente , Reguladores del Crecimiento de las Plantas/metabolismo , Raíces de Plantas/metabolismo , Raíces de Plantas/genética , Raíces de Plantas/efectos de los fármacosRESUMEN
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.
Asunto(s)
Amina Oxidasa (conteniendo Cobre) , Antioxidantes , Lonicera , Extractos Vegetales , Animales , Antioxidantes/metabolismo , Pollos/fisiología , Curcuma/metabolismo , ARN Ribosómico 16S , Dieta/veterinaria , Endotoxinas , ARN Mensajero , Alimentación Animal/análisis , Suplementos Dietéticos/análisisRESUMEN
AIM: The aim of this study was to evaluate the protective effect of curcumin-rich turmeric (CRT) extract against isotretinoin (ISO)-induced liver damage through routine biochemical parameters and oxidative stress parameters that indicate liver damage. MATERIAL AND METHOD: 42 albino Wistar rats of 200 g were randomly grouped as Group I: Healthy control, Group II: Sunflower oil, Group III: Curcumin 200 mg/kg, Group IV: ISO control groups (7.5 mg/kg), Group V: Curcumin 50 mg/kg + ISO 7.5 mg/kg, Group VI: Curcumin 100 mg/kg + ISO 7.5 mg/kg, Group VII: Curcumin 200 mg/kg + ISO 7.5 mg/kg. At the end, after the rats were killed, their blood and liver tissues were collected. ALT and AST levels in serum; superoxide dismutase activity (SOD), GSH, and MDA levels in liver tissue were determined. RESULTS: Our results showed that ALT, AST, and MDA levels increased, and SOD and GSH levels decreased in the ISO-administered group compared to the healthy control group. CRT 50, 100, and 200 mg/kg groups were compared to ISO group. A dose-dependent increase in protective effect was observed. A decrease in ALT, AST, and MDA levels, and an increase in SOD and GSH levels were determined. A protective effect was found at all doses. The best protective effect was in the CRT 200 mg/kg group. CONCLUSION: CRT extract can be considered a candidate herbal medicine for the elimination of liver damage in individuals using ISO. However, further experimental and clinical validation should be studied.
Asunto(s)
Curcumina , Ratas , Animales , Curcumina/farmacología , Curcuma/metabolismo , Isotretinoína/toxicidad , Isotretinoína/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/metabolismo , Estrés Oxidativo , Ratas Wistar , Hígado , Superóxido Dismutasa/metabolismo , Antioxidantes/metabolismoRESUMEN
The most frequent adverse effects of AFB1 in chicken are low performance, the depression of the immune system, and a reduced quality of both eggs and meat, leading to economic losses. Since oxidative stress plays a major role in AFB1 toxicity, natural products are increasingly being used as an alternative to mineral binders to tackle AFB1 toxicosis in farm animals. In this study, an in vivo trial was performed by exposing broilers for 10 days to AFB1 at dietary concentrations approaching the maximum limits set by the EU (0.02 mg/kg feed) in the presence or absence of turmeric powder (TP) (included in the feed at 400 mg/kg). The aims were to evaluate (i) the effects of AFB1 on lipid peroxidation, antioxidant parameters, histology, and the expression of drug transporters and biotransformation enzymes in the liver; (ii) the hepatic accumulation of AFB1 and its main metabolites (assessed using an in-house-validated HPLC-FLD method); (iii) the possible modulation of the above parameters elicited by TP. Broilers exposed to AFB1 alone displayed a significant increase in lipid peroxidation in the liver, which was completely reverted by the concomitant administration of TP. Although no changes in glutathione levels and antioxidant enzyme activities were detected in any treatment group, AFB1 significantly upregulated and downregulated the mRNA expression of CYP2A6 and Nrf2, respectively. TP counteracted such negative effects and increased the hepatic gene expression of selected antioxidant enzymes (i.e., CAT and SOD2) and drug transporters (i.e., ABCG2), which were further enhanced in combination with AFB1. Moreover, both AFB1 and TP increased the mRNA levels of ABCC2 and ABCG2 in the duodenum. The latter changes might be implicated in the decrease in hepatic AFB1 to undetectable levels (Asunto(s)
Antioxidantes
, Micotoxinas
, Animales
, Antioxidantes/farmacología
, Antioxidantes/metabolismo
, Pollos/metabolismo
, Curcuma/metabolismo
, Polvos/metabolismo
, Polvos/farmacología
, Micotoxinas/metabolismo
, Aflatoxina B1/metabolismo
, Hígado
, Estrés Oxidativo
, ARN Mensajero/metabolismo
RESUMEN
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by an increased level of ß-amyloid (Aß) protein deposition in the brain, yet the exact etiology remains elusive. Nowadays, treatments only target symptoms, thus the search for novel strategies is constantly stimulated, and looking to natural substances from the plant kingdom. The aim of this study was to investigate the neuroprotective effects of a spice blend composed of cinnamon bark and two different turmeric root extracts (CCSB) in Aß-exposed THP-1 cells as a model of neuroinflammation. In abiotic assays, CCSB demonstrated an antioxidant capacity up to three times stronger than Trolox in the ORAC assay, and it reduced reactive oxygen species (ROS) induced by the amyloid fragment in THP-1 cells by up to 39.7%. Moreover, CCSB lowered the Aß stimulated secretion of the pro-inflammatory cytokines IL-1ß and IL-6 by up to 24.9% and 43.4%, respectively, along with their gene expression by up to 25.2% and 43.1%, respectively. The mechanism involved the mitogen-activated protein kinases ERK, JNK and p38, whose phosphorylation was reduced by up to 51.5%, 73.7%, and 58.2%, respectively. In addition, phosphorylation of p65, one of the five components forming NF-κB, was reduced by up to 86.1%. Our results suggest that CCSB can counteract the neuroinflammatory stimulus induced by Aß-exposure in THP-1 cells, and therefore can be considered a potential candidate for AD management.
Asunto(s)
Enfermedad de Alzheimer , Curcumina , Fármacos Neuroprotectores , Humanos , Proteínas Quinasas Activadas por Mitógenos , FN-kappa B/metabolismo , Curcumina/farmacología , Cinnamomum zeylanicum , Células THP-1 , Curcuma/metabolismo , Especias , Péptidos beta-Amiloides , Fármacos Neuroprotectores/farmacologíaRESUMEN
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.
Asunto(s)
Curcuma , Sesquiterpenos , Curcuma/metabolismo , Sesquiterpenos/farmacología , Ciclopentanos/farmacología , Ciclopentanos/metabolismoRESUMEN
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.
Asunto(s)
Curcumina , Diarilheptanoides , Humanos , Curcumina/metabolismo , Curcuma/genética , Curcuma/metabolismo , Reacción en Cadena de la Polimerasa , Perfilación de la Expresión GénicaRESUMEN
AIMS: This study aims to comprehensively review the existing evidence and conduct analysis of updated randomized controlled trials (RCTs) of turmeric (Curcuma longa, CL) and its related bioactive compounds on glycemic and metabolic parameters in patients with type 2 diabetes (T2DM), prediabetes, and metabolic syndrome (MetS) together with a sub-group analysis of different CL preparation forms. METHODS: An umbrella review (UR) and updated systematic reviews and meta-analyses (SRMAs) were conducted to evaluate the effects of CL compared with a placebo/standard treatment in adult T2DM, prediabetes, and MetS. The MEDLINE, Embase, The Cochrane Central Register of Control Trials, and Scopus databases were searched from inception to September 2022. The primary efficacy outcomes were hemoglobin A1C (HbA1C) and fasting blood glucose (FBG). The corrected covered area (CCA) was used to assess overlap. Mean differences were pooled across individual RCTs using a random-effects model. Subgroup and sensitivity analyses were performed for various CL preparation forms. RESULTS: Fourteen SRMAs of 61 individual RCTs were included in the UR. The updated SRMA included 28 studies. The CCA was 11.54%, indicating high overlap across SRMAs. The updated SRMA revealed significant reduction in FBG and HbA1C with CL supplementation, obtaining a mean difference (95% confidence interval [CI]) of -8.129 (-12.175, -4.084) mg/dL and -0.134 (-0.304, -0.037) %, respectively. FBG and HbA1C levels decreased with all CL preparation forms as did other metabolic parameters levels. The results of the sensitivity and subgroup analyses were consistent with those of the main analysis. CONCLUSION: CL supplementation can significantly reduce FBG and HbA1C levels and other metabolic parameters in T2DM and mitigate related conditions, including prediabetes and MetS. TRIAL REGISTRATION: PROSPERO (CRD42016042131).
Asunto(s)
Diabetes Mellitus Tipo 2 , Síndrome Metabólico , Estado Prediabético , Adulto , Humanos , Glucemia/metabolismo , Curcuma/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Suplementos Dietéticos , Hemoglobina Glucada , Síndrome Metabólico/tratamiento farmacológico , Estado Prediabético/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Metaanálisis como Asunto , Revisiones Sistemáticas como AsuntoRESUMEN
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.
Asunto(s)
Curcuma , FN-kappa B , Animales , Ratones , FN-kappa B/metabolismo , Curcuma/metabolismo , Factor de Necrosis Tumoral alfa , Lipopolisacáridos/farmacología , Dieta Alta en Grasa/efectos adversos , Ligandos , Interleucina-6 , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Citocinas/metabolismoRESUMEN
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.
Asunto(s)
Neoplasias Colorrectales , Curcumina , Humanos , Simulación del Acoplamiento Molecular , Curcumina/farmacología , Farmacóforo , Axitinib , Receptor 2 de Factores de Crecimiento Endotelial Vascular , Curcuma/metabolismo , Detección Precoz del Cáncer , Simulación de Dinámica Molecular , LigandosRESUMEN
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.
Asunto(s)
Toxoplasma , Toxoplasmosis , Animales , Ratones , Antioxidantes/metabolismo , Curcuma/metabolismo , Sistema Inmunológico/metabolismo , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Estrés Oxidativo , Ratones Endogámicos BALB CRESUMEN
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.
Asunto(s)
Curcumina , gamma-Ciclodextrinas , Diarilheptanoides , gamma-Ciclodextrinas/metabolismo , Micelas , Adsorción , Curcumina/metabolismo , Curcuma/metabolismoRESUMEN
Metabolic syndrome (MetS) is characterized by the presence of at least three interrelated risk factors, including central obesity, hypertension, elevated serum triglycerides, low serum high-density lipoproteins, and insulin resistance. Abdominal obesity is considered a predominant risk factor. Lifestyle changes with medications to lower cholesterol, blood sugar, and hypertension are the general treatment approaches. Functional foods and bioactive food ingredients represent versatile tools for addressing different aspects of MetS. In a randomized placebo-controlled clinical study, we evaluated the effect of Calebin A, a minor bioactive phytochemical from Curcuma longa, on metabolic syndrome in obese adults (N = 100), and 94 individuals completed the study (N = 47 in both groups). They were subjected to Calebin A supplementation for 90 days, which resulted in a statistically significant reduction in their body weight, waist circumference, body mass index, low-density lipoprotein-cholesterol, and triglyceride levels compared to those with the placebo. A small but significant increase in high-density lipoprotein-cholesterol levels was also observed in these individuals. Furthermore, Calebin A showed a positive effect on adipokines by reducing circulating leptin levels. Finally, C-reactive protein levels were significantly reduced in Calebin A-supplemented individuals, suggesting a beneficial impact on managing MetS-induced inflammation. Blood glucose levels, insulin resistance, and blood pressure levels were not affected by Calebin A. In conclusion, Calebin A may be an effective supplement for managing abdominal obesity, dyslipidemia, and systemic inflammation in individuals with metabolic syndrome. This study was prospectively registered on the Clinical Trial Registry of India (CTRI) with the registration number CTRI/2021/09/036495. https://ctri.nic.in/Clinicaltrials/advancesearchmain.php.
Asunto(s)
Hipertensión , Resistencia a la Insulina , Síndrome Metabólico , Adulto , Humanos , Síndrome Metabólico/metabolismo , Obesidad Abdominal/tratamiento farmacológico , Curcuma/metabolismo , Obesidad/tratamiento farmacológico , Colesterol , Inflamación , Método Doble Ciego , Glucemia/metabolismoRESUMEN
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.
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Curcuma , Aceites Volátiles , Curcuma/química , Curcuma/metabolismo , Aceites Volátiles/química , Cromatografía de Gases y Espectrometría de Masas/métodos , Asia , Rizoma/químicaRESUMEN
This study aimed to evaluate the effect of turmeric powder (TP) supplementation on laying hens' performance, blood biochemical parameters and egg quality parameters. In total, 144 laying hens (Hy-line W36) ageing 53 weeks were used in this study. Birds were randomly assigned to three treatments (6 replicates, 8 birds in each). The diets contained 0 (control), 0.25, and 0.5% TP based on the maize-soybean meal. It was found that the TP supplementation significantly reduced egg production, weight and mass throughout the experiment (p < 0.05). However, the feed conversion ratio increased (p < 0.05), whereas feed intake remained unaffected. Yolk percentage, height and index reduced, and the yolk colour, accompanied by the egg-shell percentage, increased (p< 0.05) during the first 4 weeks of the experiment. Interestingly, only the albumen pH was affected by TP supplementation during the second 4 weeks (p < 0.05). The serum malondialdehyde level reduced significantly, and the total antioxidant capacity increased in the groups fed on the diets supplemented with TP (p < 0.05). Serum lipids levels, including triglyceride, cholesterol and very-low-density lipoprotein (VLDL), and the yolk triglyceride level reduced due to TP supplementation (p < 0.05). The interactive effect of all three independent factors on the internal quality traits of the stored eggs was significant only for yolk pH (p < 0.05). Thus, TP could be a potential lipid reducing factor, especially triglycerides, and a natural antioxidant in laying hens' diet. However, it may significantly impair the productive performance of laying hens under normal environmental conditions.
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Antioxidantes , Curcuma , Animales , Femenino , Antioxidantes/metabolismo , Curcuma/metabolismo , Polvos/farmacología , Yema de Huevo , Pollos , Óvulo , Dieta/veterinaria , Suplementos Dietéticos , Triglicéridos , Alimentación Animal/análisis , HuevosRESUMEN
Curcumin is a dietary spice and coloring agent widely used in food and herbal medicine. Herein, we visualized the distribution of curcumin in fresh Curcuma longa (turmeric) root sections using the state-of-the-art vacuum-ultraviolet (VUV, 118 nm) single photon-postionization mass spectrometric imaging method. Compared with other mass spectrometric imaging methods, the proposed method does not require any sample pre-treatment. The proposed approach could be more conducive to in situ detection of small molecules. The mass spectroscopic imaging (MSI) images of curcumin sections with a lateral resolution of 100 µm indicated that the concentrations of curcumin decreased from the phloem to the xylem of the root. We also show MS imaging of curcumin in the turmeric root at different maturity periods, revealing the transformation of this endogenous species. The result of quantitative analysis indicates that the total curcumin content of the mature turmeric root is estimated to be 3.43%, which is consistent with the previous report that the content of curcumin in the turmeric root is estimated between 3% and 5%. The report indicated that the proposed method of VUV single photon postionization MSI can be used to explore the metabolic process of plants, which is critical for herbal farming, harvest, and its ingredient extraction.
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Curcumina , Curcumina/análisis , Curcuma/química , Curcuma/metabolismo , Espectrometría de Masas , Extractos Vegetales/químicaRESUMEN
PURPOSE: Turmeric has renop rotective effects that can act to reduce oxidative stress and inflammation in hemodialysis (HD) patients. Piperine has been indicated as a bioavailability enhancer of turmeric and consequently of its biological effects. However, data on the efficacy of the turmeric/piperine combination in HD patients are limited. We aimed to verify whether turmeric supplementation in combination with piperine has a superior effect to turmeric alone in increasing antioxidant capacity and reducing oxidative stress and inflammation in HD patients. METHODS: This randomized, double-blind clinical trial was conducted in HD patients (age 20-75 years). Patients were supplemented with turmeric (3 g/day) or turmeric/piperine (3 g turmeric + 2 mg piperine/day) for 12 weeks. Malondialdehyde (MDA), antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), high-sensitivity C-reactive protein (hs-CRP), and ferritin were evaluated at baseline and the end of the study. RESULTS: There was a reduction in the MDA and ferritin levels in the turmeric/piperine group and in the comparison between groups at the end of the study [MDA: -0.08(-0.14/0.01) nmol/mL versus -0.003(-0.10/0.26) nmol/mL, pâ¯=â¯0.003; ferritin: -193.80⯱â¯157.29â¯mg/mL versus 51.99⯱â¯293.25â¯mg/mL, pâ¯=â¯0.018]. In addition, GPx activity reduced in the turmeric group (pâ¯=â¯0.029). No changes were observed for CAT, GR, and hs-CRP. CONCLUSION: Turmeric plus piperine was superior to turmeric alone in decreasing MDA and ferritin levels. The use of a combination of turmeric and piperine as a dietary intervention may be beneficial for modulating the status oxidative and inflammation in HD patients. BRAZILIAN REGISTRY OF CLINICAL TRIALS NUMBER: RBR-2t5zpd; Registration Date: May 2, 2018.