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 over 7 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.
Ginger, Zingiber officinale Roscoe, is a common spice and also a widely used medicinal plant in ancient China. Ginger is an ingredient of Ge-Gen-Tang (Kakkon-to; GGT). GGT has been proved to have antiviral activity against human respiratory syncytial virus (HRSV). However, it is unknown whether ginger is effective against HRSV.
- Journal of the American Board of Family Medicine : JABFM
- Published over 6 years ago
Nausea and vomiting in early pregnancy (NVEP) is commonly encountered in family medicine. Ginger (Zingiber officinale) is a popular nonpharmacological treatment but consensus of its use is lacking.
6-Gingerol, a major pungent component of ginger (Zingiber officinale Roscoe, Zingiberaceae), has been reported to have antitumor activities. However, the metabolic fate of 6-gingerol and the contribution of its metabolites to the observed activities are still unclear. In the present study, we investigated the biotransformation of 6-gingerol in different cancer cells and in mice, purified and identified the major metabolites from human lung cancer cells, and determined the effects of the major metabolites on the proliferation of human cancer cells. Our results show that 6-gingerol is extensively metabolized in H-1299 human lung cancer cells, CL-13 mouse lung cancer cells, HCT-116 and HT-29 human colon cancer cells, and in mice. The two major metabolites in H-1299 cells were purified and identified as (3R,5S)-6-gingerdiol (M1) and (3S,5S)-6-gingerdiol (M2) based on the analysis of their 1D and 2D NMR data. Both metabolites induced cytotoxicity in cancer cells after 24 h, with M1 having a comparable effect to 6-gingerol in H-1299 cells.
Members of the family Zingiberaceae including turmeric, ginger, Javanese ginger, and galangal have been used for centuries in traditional medicine. Preclinical studies of Zingiberaceae extracts have shown analgesic properties. This study aims to systematically review and meta-analyze whether extracts from Zingiberaceae are clinically effective hypoalgesic agents.
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.
The resistance of gastrointestinal nematodes to anthelmintics has increased the need to evaluate natural products that can replace or assist current strategies to control gastrointestinal nematodes. The objective of this study was to evaluate the effect of decoctions of Lantana camara (DLc), Alpinia zerumbet (DAz), Mentha villosa (DMv) and Tagetes minuta (DTm) on Haemonchus contortus by two in vitro tests. The effects of increasing concentrations of lyophilized decoctions (0.31 to 10mg/ml) were assessed using the egg hatch test (EHT). The decoctions were then tested in the larval artificial exsheathment assay. H. contortus third stage larvae (L3) were exposed to 0.31mg/ml A. zerumbet and M. villosa decoctions and 0.62mg/ml T. minuta and L. camara decoctions for 3h and then exsheathment procedure at 10min intervals. An inhibitor of tannins, polyvinyl polypyrrolidone (PVPP), was used to study if tannins were responsible for the inhibitory effect on hatching and exsheathment of larvae. A. zerumbet, M. villosa and T. minuta showed a dose-dependent effect in the EHT, which did not disappear after the addition of PVPP. No effect was observed for L. camara in the EHT. However, the decoctions inhibited the process of larval exsheathment, which may be related to tannin action because the addition of PVPP reversed the inhibitory effect. A. zerumbet, M. villosa and T. minuta decoctions showed inhibitory activity on H. contortus larvae hatching and exsheathing. The decoctions of these plants could be used to control gastrointestinal nematodes following confirmation of their anthelmintic activity in vivo.
Dehydrozingerone (1) is a pungent constituent present in the rhizomes of ginger (Zingiber officinale) and belongs structurally to the vanillyl ketone class. It is a representative of half the chemical structure of curcumin (2), which is an antioxidative yellow pigment obtained from the rhizomes of turmeric (Curcuma longa). Numerous studies have suggested that 2 is a promising phytochemical for the inhibition of malignant tumors, including colon cancer. On the other hand, there have been few studies on the potential antineoplastic properties of 1, and its mode of action based on a molecular mechanism is little known. Therefore, the antiproliferative effects of 1 were evaluated against HT-29 human colon cancer cells, and it was found that 1 dose-dependently inhibited growth at the G2/M phase with up-regulation of p21. Dehydrozingerone additionally led to the accumulation of intracellular ROS, although most radical scavengers could not clearly repress the cell-cycle arrest at the G2/M phase. Furthermore, two synthetic isomers of 1 (iso-dehydrozingerone, 3, and ortho-dehydrozingerone, 4) were also examined. On comparing of their activities, accumulation of intracellular ROS was found to be interrelated with growth-inhibitory effects. These results suggest that analogues of 1 may be potential chemotherapeutic agents for colon cancer.
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.