共查询到20条相似文献,搜索用时 15 毫秒
1.
Yu. A. Kovalitskaya V. B. Sadovnikov Yu. A. Zolotarev E. V. Navolotskaya 《Russian Journal of Bioorganic Chemistry》2009,35(4):446-452
The CH3CO-Lys-Lys-Arg-Arg-NH2 peptide (the author has named it protectin) was synthesized, and its activity was studied during different stress actions. Protectin was found to normalize the content of corticosterone and adrenalin in adrenal glands and blood after its intranasal administration to rats one day before a cold or heat shock, or hypobaric hypoxia at doses of 1–10 μg/animal and after its intravenous administration just after acute hemorrhage at doses of 0.5–2 μg/animal. The intranasal administration of protectin at doses of 1–10 μg/rat one day before the heat or cold shock was also shown to prevent a change in the content of free histamine and the activity of diamine oxidase in myocardium, which was induced by the dramatic change in the activity of the enzyme after the temperature actions. 相似文献
2.
Z. B. Wang Y. F. Wang J. J. Zhao L. Ma Y. J. Wang X. Zhang Y. T. Nie Y. P. Guo L. X. Mei Z. Y. Zhao 《Photosynthetica》2018,56(4):1081-1092
In this study, we chose apple leaf as plant material and studied effects of GeO2 on operation of photosynthetic apparatus and antioxidant enzyme activities under strong light. When exogenous GeO2 concentration was below 5.0 mg L–1, maximum photochemical quantum yield of PSII and actual quantum yield of PSII photochemistry increased significantly compared with the control under irradiances of 800 and 1,600 μmol(photon) m–2 s–1. Photosynthetic electron transport chain capacity between QA–QB, QA–PSI acceptor, and QB–PSI acceptor showed a trend of rising up with 1.0, 2.0, and 5.0 mg(GeO2) L–1 and declining with 10.0 mg(GeO2) L–1. On the other hand, dissipated energy via both ΔpH and xanthophyll cycle decreased remarkably compared with the control when GeO2 concentration was below 5.0 mg L–1. Our results suggested that low concentrations of GeO2 could alleviate photoinhibition and 5.0 mg(GeO2) L–1 was the most effective. In addition, we found, owing to exogenous GeO2 treatment, that the main form of this element in apple leaves was organic germanium, which means chemical conversion of germanium happened. The organic germanium might be helpful to allay photoinhibition due to its function of scavenging free radicals and lowering accumulation of reactive oxygen species, which was proven by higher antioxidant enzyme activities. 相似文献
3.
MUCH of the pharmacology of the prostaglandins (PG) could be interpreted in terms of their facilitation of the movement of calcium ions into or out of biological membranes1. We have therefore investigated this possibility, taking advantage of the configurational changes and attendant changes in light-scattering which result from the binding of calcium ions to the mitochondrial inner membrane2. Preliminary findings, which we report here, provide evidence of a marked facilitation of non-energized binding of calcium to mitochondrial membranes when in the presence of PGE1 at concentrations of the order of 10?7 M. 相似文献
4.
IN view of the possibility that prostaglandins (PG) regulate local blood flow1, we are investigating this activity in the pancreas. We have already found that PGE2 reduces vascular resistance in the perfused rat pancreas whereas PGF2α has the opposite effect2. These effects were seen at low doses (0.1 µg/ml.) and with good reproducibility. 相似文献
5.
Gina A. Castiblanco Tulay Yucel-Lindberg Stefan Roos Svante Twetman 《Probiotics and antimicrobial proteins》2017,9(3):278-283
Emerging evidence suggests that probiotic therapy can play a role in the prevention and management of oral inflammatory diseases through immunomodulation and down-regulation of the inflammatory cascade. The aim of this in vitro study was to investigate the viability of human gingival fibroblasts (HGF) and its production of prostaglandin E2 (PGE2), when exposed to supernatants of two mixed Lactobacillus reuteri strains (ATCC PTA 5289 and DSM 17938). The experiments were conducted in the presence and absence of the pro-inflammatory cytokine IL-1β. L. reuteri strains were grown and the bacterial supernatant was collected. The cell-free supernatant was diluted to concentrations equivalent to the ones produced by 0.5 to 5.0 × 107 CFU/mL bacteria. Cell viability was assessed with the MTT colorimetric assay and the amount of PGE2 in the cell culture medium was determined using the monoclonal enzyme immune assay kits. Our findings showed that none of the L. reuteri supernatants were cytotoxic or affected the viability of HGF. The most concentrated bacterial supernatant stimulated the production of PGE2 by the gingival cells in a significant way in the presence of IL-1β (p < 0.05), suggesting that bacterial products secreted from L. reuteri might play a role in the resolution of inflammation in HGF. Thus, our findings justify further investigations on the influence of probiotic bacteria on gingival inflammatory reactions. 相似文献
6.
Agren P van der Sterren S Cogolludo AL Blanco CE Villamor E 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2009,179(2):133-143
Prostaglandin E2 (PGE2) is the major vasodilator prostanoid of the mammalian ductus arteriosus (DA). In the present study we analyzed the response
of isolated DA rings from 15-, 19- and 21-day-old chicken embryos to PGE2 and other vascular smooth muscle relaxing agents acting through the cyclic AMP signaling pathway. PGE2 exhibited a relaxant response in the 15-day DA, but not in the 19- and 21-day DA. Moreover, high concentrations of PGE2 (≥3 μM in 15-day and ≥1 μM in 19-day and 21-day DA) induced contraction of the chicken DA. The presence of the TP receptor
antagonist SQ29,548, unmasked a relaxant effect of PGE2 in the 19- and 21-day DA and increased the relaxation induced by PGE2 in the 15-day DA. The presence of the EP receptor antagonist AH6809 abolished PGE2-mediated relaxation. The relaxant responses induced by PGE2 and the β-adrenoceptor agonist isoproterenol, but not those elicited by the adenylate cyclase activator forskolin or the
phosphodiesterase 3 inhibitor milrinone, decreased with maturation. High oxygen concentrations (95%) decreased the relaxation
to PGE2. The relaxing potency and efficacy of isoproterenol and milrinone were higher in the pulmonary than in the aortic side of
the DA, whereas no regional differences were found in the response to PGE2. We conclude that, in contrast to the mammalian situation, PGE2 is a weak relaxant agent of the chicken DA and, with advancing incubation, it even stimulates TP vasoconstrictive receptors. 相似文献
7.
Altered oxidative stress has long been observed in cancer cells, and this biochemical property of cancer cells represents
a specific vulnerability that can be exploited for therapeutic benefit. The major role of an elevated oxidative stress for
the efficacy of molecular targeted drugs is under investigation. Menadione is considered an attractive model for the study
of oxidative stress, which can induce apoptosis in human leukemia HL-60 cell lines. Prostaglandin E2 (PGE2) via its receptors not only promotes cell survival but also reverses apoptosis and promotes cancer progression. Here, we
present evidence for the biological role of PGE2 as a protective agent of oxidative stress-induced apoptosis in monocytic cells. Pretreatment of HL-60 cells with PGE2 markedly ameliorated the menadione-induced apoptosis and inhibited the degradation of PARP and lamin B. The EP2 receptor antagonist AH6809 abrogated the inhibitory effect of PGE2, suggesting the role of the EP2/cAMP system. The PKA inhibitor H89 also reversed apoptosis and decreased the PKA activity that was elevated 10-fold by PGE2. The treatment of HL-60 cells with NAC or zinc chloride showed a similar protective effect as with PGE2 on menadione-treated cells. Furthermore, PGE2 activated the Ras/Raf/MEK pathway, which in turn initiated ERK activation, and ultimately protected menadione-induced apoptosis.
These results imply that PGE2 via cell survival pathways may protect oxidative stress-induced apoptosis in monocytic cells. This study warrants further
pre-clinical investigation as well as application towards leukemia clinics. 相似文献
8.
The COX-2 product prostaglandin E2 (PGE2) contributes to the high metastatic capacity of breast tumors. Our published data indicate that inhibiting either PGE2 production or PGE2-mediated signaling through the PGE2 receptor EP4 reduces metastasis by a mechanism that requires natural killer (NK) cells. It is known that NK cell function
is compromised by PGE2, but very little is known about the mechanism by which PGE2 affects NK effector activity. We now report the direct effects of PGE2 on the NK cell. Endogenous murine splenic NK cells express all four PGE2 receptors (EP1-4). We examined the role of EP receptors in three NK cell functions: migration, cytotoxicity, and cytokine
release. Like PGE2, the EP4 agonist PGE1-OH blocked NK cell migration to FBS and to four chemokines (ITAC, MIP-1α, SDF-1α, and CCL21). The EP2 agonist, Butaprost,
inhibited migration to specific chemokines but not in response to FBS. In contrast to the inhibitory actions of PGE2, the EP1/EP3 agonist Sulprostone increased migration. Unlike the opposing effects of EP4 vs. EP1/EP3 on migration, agonists
of each EP receptor were uniformly inhibiting to NK-mediated cytotoxicity. The EP4 agonist, PGE1-OH, inhibited IFNγ production from NK cells. Agonists for EP1, EP2, and EP3 were not as effective at inhibiting IFNγ. Agonists
of EP1, EP2, and EP4 all inhibited TNFα; EP4 agonists were the most potent. Thus, the EP4 receptor consistently contributed
to loss of function. These results, taken together, support a mechanism whereby inhibiting PGE2 production or preventing signaling through the EP4 receptor may prevent suppression of NK functions that are critical to
the control of breast cancer metastasis. 相似文献
9.
Gonzalez A Santofimia-Castaño P Rivera-Barreno R Salido GM 《Journal of physiology and biochemistry》2012,68(2):181-191
This work was designed in order to gain an insight on the mechanisms by which antioxidants prevent pancreatic disorders. We
have examined the properties of cinnamtannin B-1, which belongs to the class of polyphenols, against the effect of hydrogen
peroxide (H2O2) in mouse pancreatic acinar cells. We have studied Ca2+ mobilization, oxidative state, amylase secretion, and cell viability of cells treated with cinnamtannin B-1 in the presence
of various concentrations of H2O2. We found that H2O2 (0.1–100 μM) increased CM-H2DCFDA-derived fluorescence, reflecting an increase in oxidation. Cinnamtannin B-1 (10 μM) reduced H2O2-induced oxidation of CM-H2DCFDA. CCK-8 induced oxidation of CM-H2DCFDA in a similar way to low micromolar concentrations of H2O2, and cinnamtannin B-1 reduced the oxidant effect of CCK-8. In addition, H2O2 induced a slow and progressive increase in intracellular free Ca2+ concentration ([Ca2+]c). Cinnamtannin B-1 reduced the effect of H2O2 on [Ca2+]c, but only at the lower concentrations of the oxidant. H2O2 inhibited amylase secretion in response to cholecystokinin, and cinnamtannin B-1 reduced the inhibitory action of H2O2 on enzyme secretion. Finally, H2O2 reduced cell viability, and the antioxidant protected acinar cells against H2O2. In conclusion, the beneficial effects of cinnamtannin B-1 appear to be mediated by reducing the intracellular Ca2+ overload and intracellular accumulation of digestive enzymes evoked by ROS, which is a common pathological precursor that
mediates pancreatitis. Our results support the beneficial effect of natural antioxidants in the therapy against oxidative
stress-derived deleterious effects on cellular physiology. 相似文献
10.
[3H]Prostaglandin (PG) E2 bound specifically to several subcellular fractions from bovine myometrium. The binding was temperature dependent, rapid, and reversible. PGE2 and PGE1 competed for the [3H]PGE2 binding site. The PGs inhibited in the following decreasing order: PGE2 = PGE1 ? PGF2α > PGA2 > PGF1β > PGB2. No competitive effect could be found for oxytocin. Scatchard analysis of the binding data were interpreted as showing a single high-affinity binding constant. There was no difference in the binding constant between the various fractions. The average molar dissociation constant was 2.74 ± 0.14 × 10?9. Quantitative differences in the maximum number of binding sites were observed between fractions. One plasma membrane fraction contained 21.4 ± 2.3 × 10?11 and the sarcoplasmic reticulum contained 11.2 ± 0.8 × 10?11 mol binding sites/g. The results suggest that there is a high-affinity PGE2 receptor present in both plasma membrane and sarcoplasmic reticulum. 相似文献
11.
The development of nanotechnologies has increased the amount of manufactured metal oxide nanoparticles in the environment. In the view of nanoparticle dispersion to the environment, assessment of their toxicity becomes very crucial. Aluminum oxide (Al2O3) nanoparticles have wide range of use in industry as well as personal care products. The aim of this study was to evaluate the dose dependent effects of 13-nm-sized Al2O3 nanoparticles on wheat correlating with the appearance of enzymatic and non-enzymatic antioxidant defense response. Wheat roots were exposed to different concentrations of Al2O3 nanoparticles (5, 25 and 50 mg mL?1) for 96 h. The effects of Al2O3 nanoparticles were studied using different parameters such as H2O2 content, superoxide dismutase and catalase activity, lipid peroxidation, total proline, photosynthetic pigment and anthocyanin content. The results indicated that while Al2O3 nanoparticles caused a dose dependent increase in H2O2 content, superoxide dismutase activity, lipid peroxidation and proline contents, the catalase activity was decreased in compare the control. Moreover, total chlorophyll, chlorophyll a, carotenoids and anthocyanin contents reduced in the highest concentration 50 mg mL?1. In conclusion, Al2O3 nanoparticles caused oxidative stress in wheat after 96 h. 相似文献
12.
C. Arias-Navarro E. Díaz-Pinés P. Zuazo M. C. Rufino L. V. Verchot K. Butterbach-Bahl 《Biogeochemistry》2017,134(1-2):95-114
Increasing demand for food and fibre by the growing human population is driving significant land use (LU) change from forest into intensively managed land systems in tropical areas. But empirical evidence on the extent to which such changes affect the soil-atmosphere exchange of trace gases is still scarce, especially in Africa. We investigated the effect of LU on soil trace gas production in the Mau Forest Complex region, Kenya. Intact soil cores were taken from natural forest, commercial and smallholder tea plantations, eucalyptus plantations and grazing lands, and were incubated in the lab under different soil moisture conditions. Soil fluxes of nitrous oxide (N2O), nitric oxide (NO) and carbon dioxide (CO2) were quantified, and we approximated annual estimates of soil N2O and NO fluxes using soil moisture values measured in situ. Forest and eucalyptus plantations yielded annual fluxes of 0.3–1.3 kg N2O–N ha?1 a?1 and 1.5–5.2 kg NO–N ha?1 a?1. Soils of commercial tea plantations, which are highly fertilized, showed higher fluxes (0.9 kg N2O–N ha?1 a?1 and 4.3 kg NO–N ha?1 a?1) than smallholder tea plantations (0.1 kg N2O–N ha?1 a?1 and 2.1 kg NO–N ha?1 a?1) or grazing land (0.1 kg N2O–N ha?1 a?1 and 1.1 kg NO–N ha?1 a?1). High soil NO fluxes were probably the consequence of long-term N fertilization and associated soil acidification, likely promoting chemodenitrification. Our experimental approach can be implemented in understudied regions, with the potential to increase the amount of information on production and consumption of trace gases from soils. 相似文献
13.
Yanmei Duan Na Li Chao Liu Huiting Liu Yaling Cui Han Wang Fashui Hong 《Biological trace element research》2010,136(3):302-313
In order to study the mechanisms underlying the effects of TiO2 nanoparticles on lactate dehydrogenase (LDH, EC1.1.1.27), Institute of Cancer Research region mice were injected with nanoparticulate
anatase TiO2 (5 nm) of various doses into the abdominal cavity daily for 14 days. We then examined LDH activity in vivo and in vitro and
direct evident for interaction between nanoparticulate anatase TiO2 and LDH using spectral methods. The results showed that nanoparticulate anatase TiO2 could significantly activate LDH in vivo and in vitro; the kinetics constant (Km) and Vmax were 0.006 μM and 1,149 unit mg−1 protein min−1, respectively, at a low concentration of nanoparticulate anatase TiO2, and 3.45 and 0.031 μM and 221 unit mg−1 protein min−1, respectively, at a high concentration of nanoparticulate anatase TiO2. By fluorescence spectral assays, the nanoparticulate anatase TiO2 was determined to be directly bound to LDH, and the binding constants of the binding site were 1.77 × 108 L mol−1 and 2.15 × 107 L mol−1, respectively, and the binding distance between nanoparticulate anatase TiO2 and the Trp residue of LDH was 4.18 nm, and nanoparticulate anatase TiO2 induced the protein unfolding. It was concluded that the binding of nanoparticulate anatase TiO2 altered LDH structure and function. 相似文献
14.
Minji Kim Kumju Youn Eun‐Young Yun Jae‐Sam Hwang Mok‐Ryeon Ahn Woo‐Sik Jeong Mira Jun 《Entomological Research》2014,44(1):23-30
Amyloid‐β peptide (Aβ) generation initiated by β‐site amyloid precursor protein cleaving enzyme 1 BACE1 is a critical cause of Alzheimer's disease. In the course of our ongoing investigation of natural anti‐dementia resources, the ethyl acetate (EtOAc) fraction exerted strong BACE1‐specific inhibition with the half maximal inhibitory concentration (IC50) value of 9.2 × 10?5 μg/mL. Furthermore, Aβ(25–35)‐induced cell death was predominantly prevented by the EtOAc fraction of Allomyrina dichotoma larvae through diminishing of cellular oxidative stress and attenuating apoptosis by inhibiting caspase‐3 activity. Taken together, the present study demonstrated that A. dichotoma larvae possess novel neuroprotective properties not only via the selective and specific inhibition of BACE1 activity but also through the alleviation of Aβ(25–35)‐induced toxicity, which may raise the possibility of therapeutic application of A. dichotoma larvae for preventing and/or treating dementia. 相似文献
15.
An analysis of the effect of combinations of chlorambucil and indomethacin, or chlorambucil and prostaglandin E2 (PGE2) on the growth of alkylating agent sensitive and resistant Walker carcinoma in vitro has been made by the isobologram approach. Indomethacin alone acts as a growth inhibitor of the Walker carcinoma. High concentrations of indomethacin (5 μg/ml) act to inhibit the growth of the resistant line sub-additively with chlorambucil, whereas low concentrations act additively. For the sensitive line indomethacin acts either additively or supra-additively with chlorambucil at all concentrations employed. Both indomethacin and low concentrations of chlorambucil alone inhibit PGE2 secretion into the culture medium of both cell lines and an enhanced inhibition is seen with the combination. PGE2 itself acts as a growth inhibitor of both cell lines, although it causes greater growth inhibition of chlorambucil resistant Walker carcinoma (LD50 1.8 μg/ml) than of the sensitive line. This correlates with a greater PGE2 secretion capacity by the resistant cell line (40 pg PGE2/ml medium/105 cells for the resistant tumour and 17 pg PGE2/ml medium/105 cells for the sensitive tumour). Combinations of PGE2 with chlorambucil inhibit growth either additively or sub-additively. It seems unlikely that inhibition of PGE2 secretion is responsible for the interactive effects of chlorambucil and indomethacin, since growth inhibition produced by the combination is not reversed by PGE2 at any of the concentrations employed. Possible mechanisms of the interactive effects are discussed. 相似文献
16.
V. D. Samuilov L. A. Vasil’ev E. V. Dzyubinskaya D. B. Kiselevsky A. V. Nesov 《Biochemistry. Biokhimii?a》2010,75(2):257-263
Addition of chitosan or H2O2 caused destruction of nuclei of epidermal cells (EC) in the epidermis isolated from pea leaves. Phenol, a substrate of the
apoplastic peroxidase-oxidase, in concentrations of 10−10–10−6 M prevented the destructive effect of chitosan. Phenolic compounds 2,4-dichlorophenol, catechol, and salicylic acid, phenolic
uncouplers of oxidative phosphorylation pentachlorophenol and 2,4-dinitrophenol, and a non-phenolic uncoupler carbonyl cyanide
m-chlorophenylhydrazone, but not tyrosine or guaiacol, displayed similar protective effects. A further increase in concentrations
of the phenolic compounds abolished their protective effects against chitosan. Malate, a substrate of the apoplastic malate
dehydrogenase, replenished the pool of apoplastic NADH that is a substrate of peroxidase-oxidase, prevented the chitosan-induced
destruction of the EC nuclei, and removed the deleterious effect of the increased concentration of phenol (0.1 mM). Methylene
Blue, benzoquinone, and N,N,N′,N′-tetramethyl-p-phenylenediamine (TMPD) capable of supporting the optimal catalytic action of peroxidase-oxidase cancelled the destructive
effect of chitosan on the EC nuclei. The NADH-oxidizing combination of TMPD with ferricyanide promoted the chitosan-induced
destruction of the nuclei. The data suggest that the apoplastic peroxidase-oxidase is involved in the antioxidant protection
of EC against chitosan and H2O2. 相似文献
17.
The contribution of protein fraction and proteolytic enzyme preparation to the in vitro cardioprotective, anti-diabetic and antioxidant activity of Palmaria palmata protein hydrolysates was investigated. Aqueous, alkaline and combined aqueous and alkaline P. palmata protein fractions were hydrolysed with the food-grade proteolytic preparations, Alcalase 2.4 L, Flavourzyme 500 L and Corolase PP. The hydrolysates had angiotensin converting enzyme (ACE) and dipeptidyl peptidase (DPP) IV inhibitory activity with IC50 values in the range 0.19–0.78 and 1.65–4.60 mg mL?1, respectively. The oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) values ranged from 45.17 to 467.54 and from 1.06 to 21.59 μmol trolox equivalents/g, respectively. Furthermore, hydrolysates (1 mg mL?1) were show to inhibit renin within the range 0–50 %. In general, Alcalase 2.4 L and Corolase PP hydrolysates of aqueous protein displayed the highest in vitro activity. The results indicate that protein fraction and enzyme preparation used have significant effects on in vitro biofunctional activity of the hydrolysates. This study demonstrates the potential of P. palmata protein hydrolysates as multifunctional functional food ingredients for the prevention/control of hypertension and type II diabetes. 相似文献
18.
Do short-term fluctuations in CO2 concentrations at elevated CO2 levels affect net CO2 uptake rates of plants? When exposed to 600 μl CO2 l?1, net CO2 uptake rates in shoots or leaves of seedlings of two tropical C3 tree species, teak (Tectona grandis L. f.) and barrigon [Pseudobombax septenatum (Jacq.) Dug.], increased by 28 and 52% respectively. In the presence of oscillations with half-cycles of 20 s, amplitude of ca. 170 μl CO2 l?1 and mean of 600 μl CO2 l?1, the stimulation in net CO2 uptake by the two species was reduced to 19 and 36%, respectively, i.e. the CO2 stimulation in photosynthesis associated with a change in exposure from 370 to 600 μl CO2 l?1 was reduced by a third in both species. Similar reductions in CO2-stimulated net CO2 uptake were observed in T. grandis exposed to 40-s oscillations. Rates of CO2 efflux in the dark by whole shoots of T. grandis decreased by 4.8% upon exposure of plants grown at 370 μl CO2 l?1 to 600 μl CO2 l?1. The potential implications of the observations on CO2 oscillations and dark respiration are discussed in the context of free-air CO2 enrichment (FACE) systems in which short-term fluctuations of CO2 concentration are a common feature. 相似文献
19.
Jüri-Ott Salm Martin Maddison Sille Tammik Kaido Soosaar Jaak Truu Ülo Mander 《Hydrobiologia》2012,692(1):41-55
The aim of this study is to estimate emissions of greenhouse gases CO2, CH4 and N2O, and the effects of drainage and peat extraction on these processes, in Estonian transitional fens and ombrotrophic bogs. Closed-chamber-based sampling lasted from January to December 2009 in nine peatlands in Estonia, covering areas with different land-use practices: natural (four study sites), drained (six sites), abandoned peat mining (five sites) and active peat mining areas (five sites). Median values of soil CO2 efflux were 1,509, 1,921, 2,845 and 1,741 kg CO2-C ha?1 year?1 from natural, drained, abandoned and active mining areas, respectively. Emission of CH4-C (median values) was 85.2, 23.7, 0.07 and 0.12 kg ha?1 year?1, and N2O-N ?0.05, ?0.01, 0.18 and 0.19 kg ha?1 year?1, respectively. There were significantly higher emissions of CO2 and N2O from abandoned and active peat mining areas, whereas CH4 emissions were significantly higher in natural and drained areas. Significant Spearman rank correlation was found between soil temperature and CO2 flux at all sites, and CH4 flux with high water level at natural and drained areas. Significant increase in CH4 flux was detected for groundwater levels above 30 cm. 相似文献
20.
This study explored the effects of cucurbitacin E (CuE), a bioactive compound from Cucurbitaceae, on the metabolism/pharmacokinetic of tolbutamide, a model CYP2C9/11 probe substrate, and hepatic CYP2C11 expression in rats. Liquid chromatography-(tandem) mass spectrometry (LC-MS/MS) assay was used to detect tolbutamide as well as 4-hydroxytolbutamide, and then successfully applied to the pharmacokinetic study of tolbutamide in rats. The effect of CuE on CYP2C11 expression was determined by western blot. CuE (1.25–100 μmol L?1) competitively inhibited tolbutamide 4-hydroxylation (CYP2C11) activity only in concentration-dependent manner with a K i value of 55.5 μmol L?1 in vitro. In whole animal studies, no significant difference in metabolism/pharmacokinetic of tolbutamide was found for the single pretreatment groups. In contrast, multiple pretreatments of CuE (200 μg kg?1 d?1, 3 d, i.p.) significantly decreased tolbutamide clearance (CL) by 25% and prolonged plasma half-time (T 1/2) by 37%. Moreover, CuE treatment (50–200 μg kg?1 d?1, i.p.) for 3 d did not affect CYP2C11 expression. These findings demonstrated that CuE competitively inhibited the metabolism of CYP2C11 substrates but had no effect on rat CYP2C11 expression. This study may provide a useful reference for the reasonable and safe use of herbal or natural products containing CuE to avoid unnecessary drug-drug interactions. 相似文献