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1.
人参的分析——Ⅳ.人参皂甙的高效液相色谱测定 总被引:14,自引:0,他引:14
本文报道了人参中六种主要皂甙(Rb1,Rb2,Rc,Rd,Re,Rg)的HPLC测定法,用氨基键合相柱,示差折光检测,流动相为甲醇中乙腈—乙二醇—醋酸铵(0.14 mol/L)(30:70:5:10.6),同时还改进了纯化方法,此法快速、重现性好,与薄层比色法比较结果基本一致。 相似文献
2.
Rok Grahek Lucija Zupan
i
-Kralj 《Journal of pharmaceutical and biomedical analysis》2009,50(5):1037-1043
An HPLC/MS/MS method was developed for identification of impurities in gentamicin. The HPLC was performed on a Synergy Hydro-RP column using 50 mM trifluoroacetic acid (TFA), pH 2 adjusted with ammonium solution and methanol as mobile phase. All impurities in gentamicin were separated from main gentamicin components. Atmospheric pressure chemical ionization (APCI) was used and product mass spectra of protonated molecules were acquired. Seventeen impurities were detected in gentamicin. Reference compounds: gentamicins: C2b, B, B1, G-418, sisomicin, garamine and gentamines: C1, C1a, C2, C2a were used for spectra interpretation and impurities identification. All MS/MS spectra were interpreted and fragmentation transitions for gentamicins and in general for aminoglycoside antibiotics (AG) were proposed. All impurities were identified. More than one isomere were proposed for three impurities. 相似文献
3.
D. H. CALAM J. N. T. GILBERT J. W. LIGHTBOWN J. W. POWELL A. H. THOMAS 《The Journal of pharmacy and pharmacology》1978,30(1):220-232
The proportions of the main components present in gentamicin sulphate complex, gentamicins C1, C1a and C2, can be monitored by 1H nuclear magnetic resonance (nmr) spectrometry. The method depends on measurement of the peak heights of signals for N-methyl and C-methyl groups present in all three components and of those present in C1 and C2 only, followed by calculation of peak height ratios to control composition within acceptable limits. The precision and reproducibility of the method have been established through two collaborative studies each involving seven laboratories. In the second study, with an improved procedure, the mean variance between laboratories with 10 samples was 3·4 × 10?4 for the N-methyl ratio of the peak at δ 2·75 to that at δ 2·95, and 1·25 × 10?3 for the C-methyl ratio of the peak at δ 1·25 to that at δ 1·35. Within laboratories the mean variance for triplicate determinations was 7·4 × 10?5 and 8·9 × 10?5 respectively. The data presented here form the experimental basis for the test controlling the composition of gentamicin sulphate in the British Pharmacopoeia 1973: Addendum 1975, and for the introduction into the British Pharmacopoeia of nmr spectrometry as an analytical technique. The reference standards and all batches of gentamicin sulphate intended for therapeutic use in the United Kingdom examined by this procedure comply with the limits laid down. 相似文献
4.
Pamela A. Pierce Joanne Y. Kim Stephen J. Peroutka 《Naunyn-Schmiedeberg's archives of pharmacology》1992,346(1):4-11
Summary A molecular structural criterion of ligand selectivity for the 5-HT2 versus 5-HT1C receptor was hypothesized on the basis of radioligand binding data. Despite the large number of compounds which have been tested at both receptors, analysis of published data led to the identification of only five agents which are greater than 10-fold selective for the 5-HT2 versus the 5-HT1C receptor. Comparison of the two-dimensional structures revealed that, although these five compounds represent three distinct structural classes, they share a common structural feature located in the region hypothesized to be involved in receptor binding: a carbonyl or carboxyl oxygen interposed spatially between an aromatic ring and nitrogen atom. This structural feature was used to predict the relative selectivity of compounds that had not previously been analyzed at both the 5-HT2 and 5-HT1C receptors.All six drugs tested which contain the identified reactive carbonyl or carboxyl group were found to be selective for the 5-HT2 versus the 5-HT1C receptor with selectivity ratios ranging from 26 to 380. By contrast, three agents which are structurally similar but do not contain the reactive carbonyl or carboxyl group displayed equally high affinity for both receptor binding sites. Since the physiological roles of the 5-HT2 and 5-HT1C receptor are markedly different, it would be of potential clinical and scientific value to utilize this molecular structural feature to further identify chemical compounds which would selectively interact with only one of the two receptors.
Send offprint requests to S. J. Peroutka at the current address 相似文献
5.
Diabetes mellitus is a chronic disease which affects millions of people worldwide. The prevalence of this disease is increasing annually and the number of diabetics is projected to rise above 300 million before 2025. The growing number of diabetics, coupled with the harsh side effects of some synthetic drugs has led to the increasing search for more natural products of plant origin. Vernonia amygdalina Del. (Asteraceae) is one of the plants commonly used for the treatment of diabetes in Africa. This study evaluated the effect of leaf extracts of this plant on glucose utilization in 3T3-L1, C2C12 muscle, and Chang-liver cells. Treatment of the cells with the acetone, methanol, water, and n-hexane/isopropanol extracts of V. amygdalina leaves significantly increased glucose utilization in the C2C12 muscle and Chang-liver cells but showed no effect on the 3T3-L1 cells. The water and n-hexane/isopropanol extracts were the most active in the C2C12 cells with a response of 78.3 and 95.6% above the control, respectively, while in the Chang-liver cells, water and acetone extracts had a response of 65.8 and 59.6% above the control, respectively. The results, especially of the water extract, strongly corroborate the ethnomedical uses of V. amygdalina as an antidiabetic plant. 相似文献
6.
Aflatoxins B1 (AFB1) and G1 (AFG1) are carcinogenic mycotoxins that contaminate crops such as maize and groundnuts worldwide. The broadly accepted method to assess chronic human aflatoxin exposure is by quantifying the amount of aflatoxin adducted to human serum albumin. This has been reported using ELISA, HPLC, or LC-MS/MS to measure the amount of AFB1-lysine released after proteolysis of serum albumin. LC-MS/MS is the most accurate method but requires both isotopically labelled and unlabelled AFB1-lysine standards, which are not commercially available. In this work, we report a simplified synthetic route to produce unlabelled, deuterated and 13C6 15N2 labelled aflatoxin B1-lysine and for the first-time aflatoxin G1-lysine. Additionally, we report on the stability of these compounds during storage. This simplified synthetic approach will make the production of these important standards more feasible for laboratories performing aflatoxin exposure studies. 相似文献
7.
8.
Previous studies have shown that administration of 5-HT1B, 5-HT1C or 5-HT2 agonists decreases food intake in rats. However, it has not been established whether these drugs induce satiety or decrease feeding by a non-specific mechanism. In the present study the post-prandial satiety sequence was used to characterise the actions of the 5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), the 5-HT1B/5-HT1C receptor agonists, 1-(3-chorophenyl) piperazine (mCPP) and 1-[3-(trifluoromethyl)phenyl] piperazine (TFMPP), and the 5-HT1B agonist, 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)H-indole (RU 24969), on feeding in rats. All four compounds reduced food intake in rats that had been food deprived overnight. The 5-HT1B/5-HT1C agonists, TFMPP (at a dose of 1.0 mg/kg) and mCPP (at a dose of 3.0 mg/kg), appeared to produce satiety as their effects on the satiety sequence were similar to those induced by a food pre-load. In contrast, the 5-HT1B agonist RU 24969 and the 5-HT2 agonist DOI did not produce behavioural profiles that resembled satiety. Thus, RU 24969 elevated active behaviours and did not accelerate resting whereas DOI appeared to induce hypophagia by a non-specific fragmentation of behaviour. The results suggest that simultaneous activation of 5-HT1B and 5-HT1C receptors may be sufficient to elicit behaviourally specific satiety in the rat. In contrast, selective activation of 5-HT2 receptors does not induce satiety but elicits active behaviours and decreases feeding by response competition. 相似文献
9.
Rationale To examine the functional relationship between 5-HT1B receptors (5-HT1B-R) and 5-HT2C receptors (5-HT2C-R) in the control of food intake.
Objectives To compare the hypophagic effect of the 5-HT2C/1B-R agonist m-chlorophenylpiperazine (mCPP), with that of the selective 5-HT1B-R agonist CP-94,253 in both wildtype (WT) and 5-HT2C knockout (KO) mice.
Methods The hypophagic effects of mCPP (1, 3 and 5.6 mg/kg) and CP-94,253 (5, 10 and 20 mg/kg) were assessed in WT and 5-HT2C KO mice using the behavioural satiety sequence paradigm. The effects of pre-treatment with the selective 5-HT2C-R antagonist SB 242,084 (0.5 and 1.5 mg/kg) were assessed in two groups of WT mice, with each group given only mCPP or CP-94,253.
Results The 5-HT2C/1B receptor agonist mCPP and the selective 5-HT1B receptor agonist CP-94,253 both suppressed food intake in WT mice. 5-HT2C KO mice were insensitive to the hypophagic effects of mCPP but were more sensitive to CP-94,253-induced hypophagia than WT
controls. mCPP induced a significant increase in post-prandial activity in 5-HT2C KO mice, but this effect was absent in 5-HT2C KO mice who were given CP-94,253. Data from WT mice, who were pre-treated with the 5-HT2C receptor antagonist SB 242,084 and then challenged with either mCPP or CP-94,253, were similar to those obtained from 5-HT2C KO mice.
Conclusions 5-HT2C-R and 5-HT1B-R activation are each sufficient to induce a hypophagic response. However, concurrent 5-HT2C-R inactivation can potentiate the hypophagic response to 5-HT1B-R activation, consistent with an inhibitory role for the 5-HT2C-R in behaviour mediated by the activation of other 5-HT receptors. These results also confirm that 5-HT1B-R activation alone cannot account for the hyperactive response of 5-HT2C KO mice to mCPP. 相似文献
10.
The functional role of brain 5-HT and 5-HT receptor subtypes in periaqueductal gray (PAG) induced aversion has been investigated in rats. Antiaversive effects were found with the serotonin agonists TFMPP, mCPP and DOI but not with RU 24969 which was found to facilitate PAG aversion. The first three serotonin agonists share potent 5-HT1C activity while RU 24969 differs with a high 5-HT1A activity. Proaversive effects were found with the mixed 5-HT1C/5-HT2 antagonists cyproheptadine and ritanserin; this effect was already reported for the mixed 5-HT1C/5-HT2 antagonists metergoline and mianserin and is opposite to the effects of the selective 5-HT2 antagonists ketanserin, pirenperone, trazodone and spiperone. The antiaversive effects of mCPP (1 mg/kg) could be prevented by pretreatment of the animals with mianserin (1 and 10 mg/kg). These results suggest that 5-HT1C receptors play an important role in the serotonergic control of PAG aversion. 5-HT1C receptor activation seems to mediate antiaversive effects whereas acute 5-HT1C receptor blockade appears to facilitate PAG aversion. Functional interactions take place between several receptor types in the in vivo control of PAG aversion, where 5-HT1C receptors appear to play a predominant function. 相似文献
11.
Daniel Hoyer Christian Waeber Philippe Schoeffter Jose Maria Palacios Anant Dravid 《Naunyn-Schmiedeberg's archives of pharmacology》1989,339(3):252-258
Summary 1) 5-HT (5-hydroxytryptamine, serotonin) induces inositol phosphate production in a pig choroid plexus preparation. This effect has been pharmacologically characterized and the data compared to those obtained from radioligand binding studies performed with [3H]mesulergine to 5-HT1C sites in pig choroid plexus membranes. 2) The rank order of potency of agonists stimulating inositol phosphate production was: -methyl-5-HT > 1-methyl-5-HT > DOI > bufotenine = SKF 83566 = 5-HT > 5-MeO-DMT > 5-MeOT = RU 24969> SCH 23390> 5-CT. 8-OH-DPAT was virtually devoid of activity at 100 mol/l. 3) The increase in inositol phosphate production induced by 5-HT and other agonists was surmountably antagonised by mesulergine, ketanserin and spiperone with pKB values of 8.7, 6.7 and 5.3, respectively. 4) The rank order of potency of antagonists was: metergoline > mesulergine > LY 53857 > ritanserin > methiothepin > mianserin > cyproheptadine > pirenperone > cinanserin > ketanserin > spiperone. The following antagonists were virtually devoid of activity at 100 mol/l; pindolol, 21-009 and yohimbine. 5) The results obtained both with agonists and antagonists strongly support the view that 5-HT1C receptors mediate agonist induced production of inositol phosphates in pig choroid plexus. This is illustrated by the close similarity between 5-HT1C binding and stimulation of inositol phospholipid turnover in this preparation. 6) The present data also show that compounds believed to be selective for dopamine D1 receptors (SKF 83566, SCH 23390) or 5-HT2 receptors (DOI, -methyl-5-HT, LY 53857, ritanserin, cyproheptadine) also interact with 5-HT1C receptors. 7) A case can be made for the 5-HT1C receptor, with its similarities to the 5-HT2 receptor in terms of pharmacology and second messenger coupling, being a 5-HT2 receptor subtype.These data have been presented in part at the Spring Meeting of the German Pharmacological Society, March 1987 (Hoyer et al. 1987)
Send offprint requests to D. Hoyer at the above address 相似文献
12.
Xian-Fu Wu Yong Li Hai-Ning Lu Shuang-Gang Ma Jing Liu 《Journal of Asian natural products research》2013,15(12):1056-1061
Two new prenylated C6–C3 compounds, 4-epi-illicinone E-12-shikimate (1) and 3-hydroxyillifunone B (2), together with five known prenylated C6–C3 compounds (3–7), were isolated from the fruits of Illicium simonsii. Their structures were elucidated on the basis of extensive spectroscopic methods, including 1D and 2D NMR, CD spectra, and ESI-MS analysis. 相似文献
13.
Alessandra V. Jager Fernando G. Tonin Pollyana C. M. C. Souto Rafaela T. Privatti Carlos A. F. Oliveira 《Toxins》2014,6(7):1996-2007
In the present study, a longitudinal assessment was carried out to evaluate the short-term human exposure to aflatoxins in Pirassununga region, São Paulo, Brazil, by determination of urinary aflatoxins by a liquid chromatography coupled to mass sprectrometry (UPLC-MS/MS) method. Sixteen volunteers with ages ranging from 14 to 55 years old were instructed to collect the early morning first urine four times every three months, from June 2011 to March 2012, totaling 64 samples. Aflatoxin M1 (AFM1) was found in 39 samples (61%) at levels ranging from 0.19 to 12.7 pg·mg−1 creatinine (mean: 1.2 ± 2.0 pg·mg−1 creatinine). Residues of aflatoxins B1, B2, G1, G2 and aflatoxicol were not identified in any urine sample. No significant difference was found among the AFM1 mean levels in urine samples collected in the four sampling periods. The levels of AFM1 found in urine samples indicate a low short-term exposure of the population studied to aflatoxins through the diet, although further investigations are needed to assess other long-term biomarkers of exposure to AFB1. 相似文献
14.
Inçi Sahin-Erdemli Philippe Schoeffter Daniel Hoyer 《Naunyn-Schmiedeberg's archives of pharmacology》1991,344(2):137-142
Summary The effects of several antagonists, known to interact with 5-HT2 receptors (ritanserin, LY 53857, ICI 169,369, methysergide, mesulergine and ketanserin), were tested against 5-HT-stimulated production of inositol phosphate in pig choroid plexus, a 5-HT1C receptor model. These antagonists produced dextral shifts of the concentration response curve to 5-HT in a parallel manner, without depressing significantly the maximal response. The following pA2 values (in parentheses) were obtained: mesulergine (8.88), methysergide (8.85), LY 53857 (8.69), ritanserin (8.69), ICI 169,369 (7.86), and ketanserin (6.57). These pA2 values were in good agreement with the pKD values determined in radioligand binding studies performed in pig choroid plexus with [3H]mesulergine. The present data demonstrate that several drugs described as 5-HT2 receptor selective antagonists (e.g. ritanserin, LY 53857 and ICI 169,369) are also potent, competitive and surmountable antagonists at 5-HT1C receptors. Thus, the results provide further evidence for the pharmacological similarity of 5-HT1C and 5-HT2 receptors. However, in contrast to the situation described with methysergide, ritanserin and LY 53857 in several 5-HT2 receptor models, none of these antagonists acted in a non-competitive or unsurmountable fashion at 5-HT1C receptors. These results suggest, but do not firmly rule out, that at least in the presence of the drugs tested in the present study, 5-HT1C receptors in the choroid plexus do not undergo an allosteric modulation; these findings are apparently in contrast to a model proposed previously for 5-HT2 receptors (Kaumann and Frenken 1985, Naunyn-Schmiedeberg's Arch Pharmacol 328: 295–300)
Send offprint requests to P. Schoeffter at the above address 相似文献
15.
Philippe Schoeffter Daniel Hoyer 《Naunyn-Schmiedeberg's archives of pharmacology》1989,339(6):675-683
Summary The effects of several putative 5-HT1 receptorsubtype selective ligands were investigated in biochemical models for 5-HT1A, 5-HT1B, and 5-HT1D receptors (inhibition of forskolin-stimulated adenylate cyclase activity in calf hippocampus, rat and calf substantia nigra, respectively) and 5-HT1C receptors (stimulation of inositol phosphates production in pig choroid plexus). Following compounds were studied: 5-HT (5-hydroxytryptamine), TFMPP (1-(mtrifluoromethylphenyl)piperazine), mCPP (1-m-chlorophe-nyl)piperazine, 1 CGS 12066 (7-trifluoromethyl-4-(4-methyl1-piperazinyl)-pyrrolo[1,2-a]quinoxaline 1), isamoltane (CGP 361A, 1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propranol), quipazine, 1-NP (1-(1-naphthyl)piperazine), and PAPP (LY165163, 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)-piperazine). Among reported 5-HT1B receptor selective drugs, TFMPP had similar potency at 5HT1A, 5-HT1B and 5-HT1C receptors, mCPP did not separate between 5-HT1B and 5-HT1C receptors, CGS 12066 was equipotent at 5-HT1B and 5-HT1D receptors, and isamoltane was only slightly 5-HTIB versus 5-HT1A selective. Quipazine showed equal potency at 5-HTIB and 5-HT1C receptors and 1-NP did not discriminate between the four receptor subtypes. PAPP described as 5-HT1A receptor selective, was equally potent at 5-HT1A and 5-HT1D receptors. The potencies determined in second messenger studies were in good agreement with the affinity values determined in radioligand binding studies. Thus 5-HT1A, 5-HT1B, 5-HT1C and 5-HT1D receptors have different pharmacological profiles as predicted from radioligand binding studies. Despite claims to the contrary, none of the tested compounds had actual selectivity for a given 5-HT1 receptor subtype. Of interest were the properties of several of these drugs, which behaved as agonists at some receptors and as antagonists at others (e. g. quipazine, 1-NP, PAPP and isamoltane).
Send offprint requests to D. Hoyer at the above address 相似文献
16.
Male Sprague-Dawley rats deprived of food for 18 h were injected with the 5-HT agonists RU 24969, 1-(3-chlorophenyl)piperazine
(mCPP) or 1-[3-(trifluoromethyl)phenyl)]piperazine (TFMPP) and 20 min later presented with their normal diet. Food intake was
determined 1, 2 and 4 h later. All three drugs reduced intake over 1 and 2 h. Three out of four drugs with high affinity for
5-HT1C receptors (metergoline, mianserin, and mesulergine but not cyproheptadine) opposed hypophagia caused bymCPP. Another drug reported to have high affinity for the 5-HT1C site, 1-naphthyl-piperazine (1-NP), also blocked the hypophagic response tomCPP at doses which attenuatedmCPP-induced hypolocomotion. Only one of the above drugs (metergoline) which also has high affinity for other 5-HT sites opposed
hypophagia caused by RU 24969. Two out of three 5-HT1B receptor antagonists [(±) cyanopindolol, (−) propranolol, but not (−) pindolol)] which oppose hypophagia caused by RU 24969
(Kennett et al. 1987) also opposed hypophagia caused bymCPP. The 5-HT2 antagonists ketanserin and ritanserin, the 5-HT3 antagonist ICS 205-930 and the α2 adrenoceptor antagonist idazoxan did not oppose the hypophagic effect ofmCPP. In agreement with results formCPP, hypophagia caused by TFMPP was opposed by both, mianserin and (±) cyanopindolol. Given alone, mianserin 1-NP and cyproheptadine
but not ICS 205-930 increased food consumption of normally fed rats. The results suggest that RU 24969-induced hypophagia
depends on 5-HT1B receptors but not on 5-HT1C receptors, whilemCPP (and TFMPP)-induced hypophagia may depend on both receptors. Thus, 5-HT1C and 5-HT1B receptors may evoke hypophagia via a common pathway but the effect of antagonists implies that at the doses usedmCPP and TFMPP act predominantly at 5-HT1C receptors. Since only the hypophagic response tomCPP is blocked by cyanopindolol and (−) propranolol (Kennett and Curzon 1988) it is unlikely to be secondary to hypoactivity
induced by the drug. 相似文献
17.
H. W. G. M. Boddeke B. J. Hoffman J. M. Palacios D. Hoyer 《Naunyn-Schmiedeberg's archives of pharmacology》1993,348(3):221-224
Summary Functional responses to stimulation of rat 5-HT1C receptors expressed in A9 cells were studied using whole cell voltage clamp recording technique. Stimulation of 5-HT1C receptors with serotonin (5-HT) evoked calcium-dependent outward currents of 109 pA in cells clamped at — 50 mV. Pretreatment with the protein kinase C (PKC) activator phorbol myristic acetate (PMA) reduced the 5-HT-induced current amplitude by 46% of the control value. Inclusion of inositol triphosphate (IP3) in the pipette solution induced an outward current of 84 pA. The IP3-induced response was not affected by 60 min pretreatment with PMA. In the presence of the PKC antagonist calphostin C, 60 min treatment with PMA (10–6 mol/1) reduced the 5-HT response only by 8%. In cells preincubated with PMA, injection of the calcium/calmodulin dependent serine proteinphosphatase calcineurin gradually increased the 5-HT-induced responses by 34%. In A9 cells which were incubated 24 h with the 5-HT1C receptor agonist meta chlorophenylpiperazine hydrochloride (mCPP), 5-HT-induced responses were reduced by 23% of the vehicle pretreated control value. Injection of calcineurin in mCPP treated cells enhanced the 5-HT-induced response by 24%.The results suggest that in A9 cells rat 5-HT1C receptors are desensitized after phosphorylation by PKC. This desensitization can be counteracted by calcineurin-induced: dephosphorylation.
Correspondence to H. W. G. M. Boddeke at the above address 相似文献
18.
General saponin is the major effective substance in the fibrous root of Panax notoginseng (Burk) F. H. Chen, and sanchinoside C1 is the main constitueet of this general saponin. Their effects on blood sugar were Studied on experimental animals. It was found that oral administration of sanehinoside C1 in mice, was followed, by a slight rise in fasting blood sugar and a fall to normal level in hyperglycemia. But sanchinoside C1 showed no influence on hyperglycemia induced by adrenalin.General saponin of Panax notoginseng can also raise the fasting blood sugar level in mice and decreases the hyperglycemia in mice and rabbits, but it did not influence on the ability of insulin in reducing blood sugarln rabbits. The effect of this general saporiin differs from sanchinoside C1 in that the latter increases hyperglycemia induced by adrenalin in mice and rabbits. 相似文献
19.
Ji-Fa Zhang Yu Li Feng Gao Lian-Hai Shan 《Journal of Asian natural products research》2019,21(7):716-724
Four new C20-diterpenoid alkaloids, rotundifosines D-G (1–4), along with eight known ones (5–12) were isolated from the whole plant of Aconitum rotundifolium Kar. & Kir. The structures of the compounds were elucidated on the basis of spectroscopic analyses, including HR-ESI-MS and 1D, 2D NMR. Rotundifosine F (3) is a rare C20-diterpenoid alkaloid with quaternary ammonium salt. Alkaloids 1–4, 5, 6, 9, and 12 were evaluated for cytotoxicity against MCF-7, HCT-116 and HepG2 human cancer cell lines. 相似文献
20.
Engineered fullerenes (C60) are extensively used for commercial and clinical applications based on their unique physicochemical properties. Such materials have also been recognized as byproducts of many industrial activities. Functionalization of C60 may significantly influence the nature of its interactions with biological systems, impacting its applications and raising uncertainties about its health effects. In the present study, we compared the bioimpact of two chemically modified fullerene derivatives, hexa carboxyl fullerene adduct (Hexa-C60) and tris carboxyl fullerene adduct (tris-C60) to pristine fullerene C60 encapsulated with gamma (γ)-cyclodextrin C60 (CD-C60), using human cutaneous epithelial cells (HEK) to simulate possible applications and occupational dermal exposure route. We report, for the first time, the discovery of premature senescence as a potential endpoint of nanomaterial elicited biological effects, providing a new paradigm for nanoparticle-induced toxicity in human cells. Moreover, this response appeared to be functionalization specific, in that, only tris-C60 induced senescence. We investigated key biological responses, such as cellular viability, intracellular ROS generation, cell proliferation and cell cycle responses. Our results indicate that the often observed ‘anti-apoptotic’ function of fullerene derivatives may be independent of their ‘ROS scavenging’ role as previously reported. We discovered that the tris-C60-induced responses were associated with G0/G1 cell cycle arrest and cellular senescence. On further evaluation of the molecular mechanisms underlying the senescent response, a significant decrease in the expression levels of HERC5 was noted. HERC5 is a ubiquitin ligase of the HERC family and is implicated to be involved in innate immune responses to viral and bacterial infections. 相似文献