Development of a validated UPLC-qTOF-MS Method for the determination of curcuminoids and their pharmacokinetic study in mice
- Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences
- Published almost 6 years ago
BACKGROUND: A specific and sensitive UPLC-qTOF-MS/MS method has been developed for the simultaneous determination of curcuminoids. These Curcuminoids comprises of curcumin, a principal curcuminoid and other two namely, demethoxycurcumin, and bisdemethoxycurcumin obtained from rhizomes of Curcuma longa an ancient Indian curry spice turmeric, family (Zingiberaceae), METHODS: These analytes were separated on a reverse phase C18 column by using a mobile phase of acetonitrile: 5% acetonitrile in water with 0.07% acetic acid (75:25 v/v), flow rate of 100 muL/min was maintained. The qTOF-MS was operated under multiple reaction monitoring (MRM) mode using electro-spray ionization (ESI) technique with positive ion polarity. The major product ions in the positive mode for curcuminoids were at m/z 369.1066, 339.1023 and 309.0214 respectively. The recovery of the analytes from mouse plasma was optimized using solid phase extraction technique. RESULTS: The total run time was 5 min and the peaks of the compounds, bisdemethoxycurcumin, demethoxycurcumin and curcumin occurred at 2.06, 2.23 and 2.40 min respectively. The calibration curves of bisdemethoxycurcumin, demethoxycurcumin and curcumin were linear over the concentration range of 2–1000 ng/mL (r2, 0.9951), 2–1000 ng/mL (r2, 0.9970) and 2-1000 ng/mL (r2, 0.9906) respectively.Intra-assay and inter-assay accuracy in terms of% bias for curcumin was in between -7.95to +6.21, and -7.03 to + 6.34; for demethoxycurcumin was -6.72 to +6.34, and -7.86 to +6.74 and for bisdesmetoxycurcumin was -8.23 to +6.37 and -8.47 to +7.81. The lower limit of quantitation for curcumin, demethoxycurcumin and bisdemethoxycurcumin was 2.0 ng/mL. Analytes were stable under various conditions (in autosampler, during freeze-thaw, at room temperature, and under deep-freeze conditions). This validated method was used during pharmacokinetic studies of curcumin in the mouse plasma. CONCLUSIONS: A specific, accurate and precise UPLC-qTOF-MS/MS method for the determination of curcumin, demethoxycurcumin and bisdemethoxycurcumin both individually and simultaneously was optimized.
Context: Curcumin is a yellow-orange polyphenol derived from turmeric [Curcuma longa L. (Zingiberaceaerhizomes)]. Turmeric is a main ingredient of Indian, Persian, and Thai dishes. Extensive studies within the last half a century have demonstrated the protective action of curcumin in many disorders of the body. Objective: This study evaluated the protective effect of curcumin on dexamethasone-induced spermatogenesis defects in mice. Materials and methods: Thirty-two NMRI mice were randomly divided into 4 groups. The first (control) group received 1 mL/day of distilled water by intraperitoneal (i.p.) injection for 7 days. The second group received 200 mg/kg/day of curcumin (Cur) for 10 days. Third group received 7 mg/kg/day of dexamethasone (Dex) for 7 days. Forth group received 200 mg/kg of curcumin for 10 days after dexamethasone treatment. Testicular histopathology, morphometric analysis, head sperm counting, and immunohistochemistry assessments were performed for evaluation of the dexamethasone and curcumin effects. Results: Expression of Bcl-2 was significantly increased in the curcumin + dexamethasone group compared with dexamethasone-treated animals (p < 0.05). Dexamethasone induced spermatogenesis defects including epithelial vacuolizations, sloughing of germ cells, reduction of seminiferous tubule diameter, reduction in the number of sperm heads and significant maturation arrest (p < 0.001). Curcumin + dexamethasone treatment significantly prevented these changes (p < 0.05). Discussion and conclusion: The results of this study demonstrate that curcumin increases the expression of Bcl-2 protein, an important anti-apoptotic factor, and improves the spermatogenesis defects in dexamethasone treated mice. Curcumin has a potent protective effect against the testicular toxicity and might be clinically useful.
Aflatoxins are highly toxic, mutagenic, teratogenic and carcinogenic mycotoxins. Consumption of aflatoxin-contaminated food and commodities poses serious hazards to the health of humans and animals. Turmeric, Curcuma longa L., is a native plant of Southeast Asia and has antimicrobial, antioxidant and antifungal properties. This paper reports the antiaflatoxigenic activities of the essential oil of C. longa and curcumin. The medium tests were prepared with the oil of C. longa, and the curcumin standard at concentrations varied from 0.01% to 5.0%. All doses of the essential oil of the plant and the curcumin standard interfered with mycotoxin production. Both the essential oil and curcumin significantly inhibited the production of aflatoxins; the 0.5% level had a greater than 96% inhibitory effect. The levels of aflatoxin B(1) (AFB(1)) production were 1.0 and 42.7 μg/mL, respectively, for the samples treated with the essential oil of C. longa L. and curcumin at a concentration of 0.5%.
Curcumin (diferuloylmethane) is the yellow-orange pigment of dried Curcuma longa L. rhizomes (turmeric). During the past two decades, there has been a large volume of published studies describing the biological and pharmacological properties of this phytochemical including anticancer, anti-inflammatory, antioxidant, antithrombotic, antiatherosclerotic, cardioprotective, neuroprotective, memory enhancing, antiparkinsonism, antirheumatic, anti-infectious, antiaging, antipsoriatic, and anticonvulsant activities. In addition, curcumin has been shown to be extremely safe and interact with multiple molecular targets that are involved in the pathogenesis of metabolic syndrome. Curcumin could favorably affect all leading components of metabolic syndrome including insulin resistance, obesity, hypertriglyceridemia, decreased HDL-C and hypertension, and prevent the deleterious complications of MetS including diabetes and cardiovascular disease. Owing to its antioxidant and anti-inflammatory properties, curcumin can also exert several pleiotropic effects and improve endothelial dysfunction, adipokine imbalances, and hyperuricemia which usually accompany MetS. Despite the potential tremendous benefit of this multifaceted phytopharmaceutical, no trial result has yet been publicized on this issue. This review seeks to briefly summarize the ample scientific evidence that supports the therapeutic efficacy of curcumin, at least as an adjunctive treatment, in patients with MetS. © 2012 BioFactors, 2013.
The present study investigated the acute, subchronic and genotoxicity of turmeric essential oil (TEO) from Curcuma longa L. Acute administration of TEO was done as single dose up to 5 g of TEO per kg body weight and subchronic toxicity study for thirteen weeks was done by daily oral administration of TEO at doses 0.1, 0.25 and 0.5 g/kg b.wt. in Wistar rats. There were no mortality, adverse clinical signs or changes in body weight; water and food consumption during acute as well as subchronic toxicity studies. Indicators of hepatic function such as aspartate aminotransferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) were unchanged in treated animals compared to untreated animals. Oral administration of TEO for 13 weeks did not alter total cholesterol, triglycerides, markers of renal function, serum electrolyte parameters and histopathology of tissues. TEO did not produce any mutagenicity to Salmonella typhimurium TA-98, TA-100, TA-102 and TA-1535 with or without metabolic activation. Administration of TEO to rats (1 g/kg b.wt) for 14 days did not produce any chromosome aberration or micronuclei in rat bone marrow cells and did not produce any DNA damage as seen by comet assay confirming the non toxicity of TEO.
Terpecurcumins A-I (1-9), together with three known analogues (10-12), were isolated from the rhizomes of Curcuma longa (turmeric). They were derived from the hybridization of curcuminoids and bisabolanes. The structures and absolute configurations of 1-9 were elucidated on the basis of extensive spectroscopic data analysis, including NMR and electronic circular dichroism spectra. The configuration of 10 was further confirmed by X-ray crystallography. A plausible biogenetic relationship for 1-12 is proposed. Compounds 4, 6, 7, 10, and 11 showed higher cytotoxic activities (IC(50), 10.3-19.4 μM) than curcumin (IC(50), 31.3-49.2 μM) against human cancer cell lines (A549, HepG2, and MDA-MB-231).
The three curcuminoid components commonly isolated from Curcuma longa, curcumin (1), demethoxycurcumin (2), and bis-demethoxycurcumin (3) were separated and isolated from a commercially available turmeric extract product in high purity and sufficient amounts. Three more derivatives of curcumin, the di-O-demethylcurcumin (4), di-O-methylcurcumin (5) and the di-O-acetylcurcumin (6) were also synthesized and characterized. All six compounds were evaluated for their larvicidal effect against the mosquito Culex pipiens. Curcumin (1) exhibited highly potent larvicidal activity with LC(50) value of 19.07mgL(-1). Moreover, di-O-demethylcurcumin (4), was found to be equally active with LC(50) value of 12.42mgL(-1). Based on the LC(90) values of the two compounds, di-O-demethylcurcumin (4) was the most active of all, resulting in an LC(90) value of 29.40mgL(-1), almost half of the LC(90) value 61.63mgL(-1) found for compound 1. The rest of the compounds were inactive at concentrations even as high as 150mgL(-1) indicating a dependence of the larvicidal activity upon the substitution patent and the presence of aromatic hydroxyl and methoxy moieties. These results show for the first time the potential of this valuable natural product regarding its use as vector control agent.
The essential oils of ginger (Zingiber officinale) and turmeric (Curcuma longa) contain a large variety of terpenoids, some of which possess anticancer, antiulcer, and antioxidant properties. Despite their importance, only four terpene synthases have been identified from the Zingiberaceae family: (+)-germacrene D synthase and (S)-β-bisabolene synthase from ginger rhizome, and α-humulene synthase and β-eudesmol synthase from shampoo ginger (Zingiber zerumbet) rhizome. We report the identification of 25 mono- and 18 sesquiterpene synthases from ginger and turmeric, with 13 and 11, respectively, being functionally characterized. Novel terpene synthases, (-)-caryolan-1-ol synthase and α-zingiberene/β-sesquiphellandrene synthase, which is responsible for formation of the major sesquiterpenoids in ginger and turmeric rhizomes, were also discovered. These suites of enzymes are responsible for formation of the majority of the terpenoids present in these two plants. Structures of several were modeled, and a comparison of sets of paralogs suggests how the terpene synthases in ginger and turmeric evolved. The most abundant and most important sesquiterpenoids in turmeric rhizomes, (+)-α-turmerone and (+)-β-turmerone, are produced from (-)-α-zingiberene and (-)-β-sesquiphellandrene, respectively, via α-zingiberene/β-sesquiphellandrene oxidase and a still unidentified dehydrogenase.
Turmeric (Curcuma longa), a commonly used spice throughout the world, has been shown to exhibit antiinflammatory, antimicrobial, antioxidant, and anti-neoplastic properties. Growing evidence shows that an active component of turmeric, curcumin, may be used medically to treat a variety of dermatologic diseases. This systematic review was conducted to examine the evidence for the use of both topical and ingested turmeric/curcumin to modulate skin health and function. The PubMed and Embase databases were systematically searched for clinical studies involving humans that examined the relationship between products containing turmeric, curcumin, and skin health. A total of 234 articles were uncovered, and a total of 18 studies met inclusion criteria. Nine studies evaluated the effects of ingestion, eight studies evaluated the effects of topical, and one study evaluated the effects of both ingested and topical application of turmeric/curcumin. Skin conditions examined include acne, alopecia, atopic dermatitis, facial photoaging, oral lichen planus, pruritus, psoriasis, radiodermatitis, and vitiligo. Ten studies noted statistically significant improvement in skin disease severity in the turmeric/curcumin treatment groups compared with control groups. Overall, there is early evidence that turmeric/curcumin products and supplements, both oral and topical, may provide therapeutic benefits for skin health. However, currently published studies are limited and further studies will be essential to better evaluate efficacy and the mechanisms involved.
The management of osteoarthritis represents a real challenge. This complex and multi-factorial disease evolves over decades and requires not only the alleviation of symptoms, i.e. pain and joint function but also the preservation of articular structure without side effects. Nutraceuticals are good candidates for the management of OA due to their safety profile and potential efficacy. However, they are not part of the treatment guidelines and published recommendations. Curcumin is the yellow pigment isolated from the rhizomes of Curcuma longa, commonly known as turmeric. Curcumin is a highly pleiotropic molecule with an excellent safety profile. Strong molecular evidence has been published for its potency to target multiple inflammatory diseases. However, naturally occurring curcumin cannot achieve its optimum therapeutic outcomes due to its low solubility and poor bioavailability. Nevertheless, curcumin presents great potential for treating OA and has been categorized as having preclinical evidence of efficacy. This review aimed at gathering most of the available information to document the potential efficacy of curcumin based on the results obtained in in vitro models of cartilage and osteoarthritis and in other diseases.