- 1. Modified Folin-Ciocalteu Antioxidant Capacity Assay for Measuring Lipophilic Antioxidants.
Folin-Ciocalteau method of total phenolics assay, originally developed for protein determination, has recently evolved as a total antioxidant capacity assay, but found to be incapable of measuring lipophilic antioxidants due to the high affinity of FC chromophore, i.e. multivalent-charged phospho-tungsto-molybdate(V), toward water. Thus, the FC method was modified and standardized so as to enable simultaneous measurement of lipophilic and hydrophilic antioxidants in NaOH-added isobutanol-water medium. Optimal conditions were: dilution ratio of aqueous FC reagent with iso-BuOH (1:2, v/v), final NaOH concentration: 3.5×10-2 M, reaction time: 20 min, and maximum absorption wavelength: 665 nm. The modified procedure was successfully applied to the total antioxidant capacity assay of trolox, quercetin, ascorbic acid, gallic acid, catechin, caffeic acid, ferulic acid, rosmarinic acid, glutathione and cysteine, as well as of lipophilic antioxidants such as α-tocopherol (vitamin E), butylated hydroxyanisole, butylated hydroxytoluene, tertiary butylhydroquinone, lauryl gallate and β-carotene. The modified FC method reliably quantified ascorbic acid whereas the conventional method could not. The modified method was reproducible and additive in terms of total antioxidant capacity values of constituents of complex mixtures such as olive oil extract and herbal tea infusion. The trolox equivalent antioxidant capacities of the tested antioxidant compounds correlated well with those found by the Cupric Reducing Antioxidant Capacity reference method....(more)
Berker KI, et al. J Agric Food Chem 2013 Apr 29.
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- 2. A novel inhibitor, 16-hydroxy-cleroda-3,13-dien-16,15-olide, blocks the autophosphorylation site of focal adhesion kinase (Y397) by molecular docking.
BACKGROUND:
Focal adhesion kinase (FAK) is a nonreceptor protein tyrosine plays an important role in a number of cell signaling pathways, including cell migration, proliferation, and cell survival. This study was aimed to identify novel and specific inhibitors from natural compounds via molecular docking of FAK (Y397).
METHODS:
The 3D structure of FAK (PDB ID: 2AL6) was used for docking 109 natural compounds. Based on high affinity and energy interaction, four of ten candidate compounds, 16-hydroxy-cleroda-3,13-dien-16,15-olide (HCD), curcumin, quercetin, and catechin hydrate, were hit, and the inhibitory activity against FAK was validated in these compounds in C6 glioma and N18 neuroblastoma cell lines.
RESULTS:
HCD showed a potential effect on cell viability by MTT assay and cell arrest in the G0-G1 phase, and a TUNEL assay confirmed further apoptosis. Treatment with HCD decreased anti-apoptotic proteins and increased pro-apoptotic proteins. Atomic force microscopy data depicted that the formation of filopodia on the intracellular surface decreased in treated cells compared with the control. Zymography showed that HCD inhibited the activity of MMP-2 and MMP-9. The protein levels of FAK, pFAK, Rac1 and Cdc42, which are the key regulators for the formation of filopodia, were decreased. Additionally, HCD regulated the expression of epithelial mesenchymal transition proteins.
CONCLUSIONS:
HCD effectively interacted at the autophosphorylation site of FAK and interaction analysis indicated an H-bond with the Arg 86 and Arg 125 residues.
GENERAL SIGNIFICANCE:
This study suggests that HCD could be a potential inhibitor of FAK and could be used for anti-tumorigenesis and anti-metastasis treatments.
Copyright © 2013. Published by Elsevier B.V....(more)
Varadharajan T, et al. Biochim Biophys Acta 2013 Apr 26.
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- 3. Effects of catechin polyphenols and preparations from the plant-parasitic nematode Heterodera glycines on protease activity and behaviour in three nematode species.
Protease activities in preparations from the plant-parasitic nematodes Heterodera glycines and Meloidogyne incognita and the free-living nematode Panagrellus redivivus were inhibited by exposure to a series of eight catechin polyphenol analogues, (+)-catechin, ( - )-epicatechin (EC), ( - )-gallocatechin (GC), ( - )-epigallocatechin (EGC), ( - )-catechin gallate (CG), ( - )-gallocatechin gallate (GCG), ( - )-epicatechin gallate (ECG) and ( - )-epigallocatechin gallate (EGCG) (1 mm each), and by a preparation from H. glycines cysts. General protease activity detected with the FRET-peptide substrate QXL520-KSAYMRF-K(5-FAM)a and proteasome chymotrypsin-like (CTL) activity detected with succinyl-LLVY-AMC were each inhibited significantly more (P< 0.05) by the gallated form of the polyphenol than by the corresponding non-gallated form. Species differences in response to inhibition across all analogues were revealed with the CTL substrate, but CG was a consistently potent inhibitor across all three species and with each substrate. A heat-stable component (CE) from H. glycines cysts inhibited M. incognita CTL activity by 92.07 ± 0.68%, significantly less (P< 0.05) in H. glycines (52.86 ± 2.77%), and by only 17.24 ± 0.55% (P< 0.05) in P. redivivus preparations. CTL activity was, however, inhibited more than 60% in all preparations by the proteasome-specific inhibitor MG-132. Hatching of M. incognita infective juveniles exposed to 1 mm CG, ECG, GCG or EGCG was reduced by 83.88 ± 4.26%, 69.98 ± 9.14%, 94.93 ± 1.71% and 87.93 ± 2.89%, respectively, while hatching of H. glycines was reduced less than 25% by each analogue. CE had no effect on nematode hatch, but did cause a 60% reduction in mobility of H. glycines infective juveniles exposed overnight to CE in vitro, which was more (P< 0.05) than the reduction of M. incognita infective juvenile mobility (20%)....(more)
Masler EP. J Helminthol 2013 May 2:1-8.
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- 4. Correlation Between Catechin Content and NF-κB Inhibition by Infusions of Green and Black Tea.
This study investigates whether infusions of green and black tea inhibit the NF-κB driven transcription in human epithelial gastric AGS cells. Water extracts were prepared from different brands of green and black tea available on the Italian market. Teas with or without caffeine were studied. An industrially prepared freeze-dried water extract of green tea was also tested. Catechin and caffeine contents were measured by HPLC analysis. The decrease in phenol and catechin content three months after the expiry date was also investigated. The NF-κB driven transcription and the free radical scavenger activity were inhibited, and this effect was related to catechin levels. The potency of epigallocatechin 3-gallate in inhibiting NF-κB driven transcription is so great that tea extracts low in epigallocatechin 3-gallate are still highly active. In one decaffeinated sample of green tea, the phenol and catechin content was very low, probably as a consequence of caffeine removal. The decrease in catechin levels after 3 months did not reduce the inhibition of NF-κB driven transcription by tea infusions. This is the first paper reporting the inhibitory effect of NF-κB of commercial green and black infusions at the gastric level, evaluating their stability as well....(more)
Di Lorenzo C, et al. Plant Foods Hum Nutr 2013 May 1.
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- 5. Experimental endometriosis reduction in rats treated with Uncaria tomentosa (cat's claw) extract.
OBJECTIVE:
The aim of this study was to analyze the macroscopic and histological changes that occur in experimental endometriosis after treatment with Uncaria tomentosa.
STUDY DESIGN:
Experimental endometriosis was induced in twenty-five female Wistar rats. After three weeks, 24 animals developed grade III experimental endometriosis and were divided into two groups. Group "U" received U. tomentosa extract orally (32 mg/day), and group "C" (control group) received a 0.9% sodium chloride solution orally (1 ml/100g of body weight/day). Both groups were treated with gavage for 14 days. At the surgical intervention and after the animal was euthanized, the implant volume was calculated with the following formula: [4π (length/2)×(width/2)×(height/2)/3]. The autotransplants were removed, dyed with hematoxylin-eosin, and analyzed by light microscopy. The Mann-Whitney test was used for the independent samples, and the Wilcoxon test analyzed the related samples, with a significance level of 5%.
RESULTS:
The difference between the initial average volumes of the autotransplants was not significant between the groups (p = 0.18). However, the final average volumes were significantly different between the groups (p = 0.001). There was a significant increase (p = 0.01) between the initial and final average volumes in the control group, and treatment with the U. tomentosa caused a marked reduction in the growth over time (p = 0.009). Histologically, in the experimental group (n = 10) six rats had a well-preserved epithelial layer, three had mildly preserved epithelium, and one had poorly preserved epithelium. The epithelial layer occasionally presented sporadic epithelial cells. The control group (n = 12) presented seven cases (58.3%) of well-preserved epithelial cells and five cases (41.7%) of mildly preserved epithelial cells.
CONCLUSIONS:
Cat's claw extract appears to be a promising alternative for treating endometriosis.
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved....(more)
Nogueira Neto J, et al. Eur J Obstet Gynecol Reprod Biol 2011 Feb;154(2):205-8.
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- 6. Chelidonium majus and its effects on uterine contractility in a perfusion model.
OBJECTIVE:
The herbal agent celandine is thought to have mainly spasmolytic effects, but in the uterus it is regarded as promoting contractions, which can offer promising and innovative options for optimizing artificial reproduction. The aim of the present study was to investigate the effect of celandine on the uterine muscle, using a perfusion model of swine uteri.
STUDY DESIGN:
Sixteen swine uteri were perfused with Krebs-Ringer solution. Celandine (Chelidonium, Paverysat; Johannes Bürger Ysatfabrik Ltd., Bad Harzburg, Germany) was administered at increasing dosages. Intrauterine pressure (IUP) was recorded using an intrauterine double-chip microcatheter (Urobar 8 DS-F, Raumedic, Rehau AG & Co., Rehau, Germany). Differences in pressure (ΔP) and area under the curve (ΔAUC) after drug administration in the uterine body and uterine horn in the various dilution series were noted. A paired Student's t-test was used to evaluate differences between groups, with significance set at P<0.05.
RESULTS:
A significant initial increase in uterine activity was visible at each dosage. Inhibition of uterine activity was seen over longer periods of 5 and 10min, particularly for a medium-dose range of 1-2mg/ml. At a dosage of 2mg/ml in particular, celandine almost always led to significant values.
CONCLUSION:
Following intra-arterial administration in a swine uterus perfusion model, celandine initially causes a significant increase in contractility, which is followed over time by a relaxation phase. This suggests interesting hypotheses on whether Chelidonium majus might be used to promote targeted sperm transport.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved....(more)
Kuenzel J, et al. Eur J Obstet Gynecol Reprod Biol 2013 Apr 19.
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- 7. Herbal hepatotoxicity: suspected cases assessed for alternative causes.
BACKGROUND AND OBJECTIVES:
Alternative explanations are common in suspected drug-induced liver injury (DILI) and account for up to 47.1% of analyzed cases. This raised the question of whether a similar frequency may prevail in cases of assumed herb-induced liver injury (HILI).
METHODS:
We searched the Medline database for the following terms: herbs, herbal drugs, herbal dietary supplements, hepatotoxic herbs, herbal hepatotoxicity, and herb-induced liver injury. Additional terms specifically addressed single herbs and herbal products: black cohosh, Greater Celandine, green tea, Herbalife products, Hydroxycut, kava, and Pelargonium sidoides. We retrieved 23 published case series and regulatory assessments related to hepatotoxicity by herbs and herbal dietary supplements with alternative causes.
RESULTS:
The 23 publications comprised 573 cases of initially suspected HILI; alternative causes were evident in 278/573 cases (48.5%). Among them were hepatitis by various viruses (9.7%), autoimmune diseases (10.4%), nonalcoholic and alcoholic liver diseases (5.4%), liver injury by comedication (DILI and other HILI) (43.9%), and liver involvement in infectious diseases (4.7%). Biliary and pancreatic diseases were frequent alternative diagnoses (11.5%), raising therapeutic problems if specific treatment is withheld; pre-existing liver diseases including cirrhosis (9.7%) were additional confounding variables. Other diagnoses were rare, but possibly relevant for the individual patient.
CONCLUSION:
In 573 cases of initially assumed HILI, 48.5% showed alternative causes unrelated to the initially incriminated herb, herbal drug, or herbal dietary supplement, calling for thorough clinical evaluations and appropriate causality assessments in future cases of suspected HILI....(more)
Teschke R, et al. Eur J Gastroenterol Hepatol 2013 Mar 18.
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- 8. Amitozyn impairs chromosome segregation and induces apoptosis via mitotic checkpoint activation.
Amitozyn (Am) is a semi-synthetic drug produced by the alkylation of major celandine (Chelidonium majus L.) alkaloids with the organophosphorous compound N,N'N'-triethylenethiophosphoramide (ThioTEPA). We show here that the treatment of living cells with Am reversibly perturbs the microtubule cytoskeleton, provoking a dose-dependent cell arrest in the M phase. Am changed the dynamics of tubulin polymerization in vitro, promoted the appearance of aberrant mitotic phenotypes in HeLa cells and induced apoptosis by the activation of caspase-9, caspase-3 and PARP, without inducing DNA breaks. Am treatment of HeLa cells induced changes in the phosphorylation of the growth suppressor pRb that coincided with maximum mitotic index. The dose-dependent and reversible anti-proliferative effect of Am was observed in several transformed cell lines. Importantly, the drug was also efficient against multidrug-resistant, paclitaxel-resistant or p53-deficient cells. Our results thus open the way to further pre-clinical evaluation of Am....(more)
Herman B, et al. PLoS One 2013;8(3):e57461.
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- 9. Capillary electrophoretic study of the synergistic biological effects of alkaloids from Chelidonium majus L. in normal and cancer cells.
In this study, the synergistic biological action of five celandine alkaloids in normal and cancer cells was investigated by capillary electrophoresis with light-emitting diode-induced native fluorescence detection. The specific capacity of each alkaloid to penetrate into the cells was estimated by monitoring alkaloid concentration decreases in the cell medium during incubation with murine fibroblast NIH/3T3, mouse melanoma B16F10, and human breast cancer MCF7 cell lines. Mixtures of isoquinoline alkaloids containing protopine, chelidonine, sanguinarine, allocryptopine, and stylopine were applied to cell cultures for 20 and 40 min, and the content of alkaloids in the cell media was measured by capillary electrophoresis (CE). CE separation of isoquinoline alkaloids was performed in 30 mM phosphate buffer (pH 2.5). As these alkaloids have native fluorescence, they were directly detected using the commercially available UV light-emitting diode without troublesome fluorescent derivatization. The results showed a differential ability of celandine alkaloids to penetrate into the normal and cancer cell interior, which was inversely proportional to their cytotoxic activity. While the most effective transport of celandine alkaloids from the cell medium to the cell interior was observed for normal murine fibroblast NIH/3T3 cells (about 55% of total content), cytotoxicity tests demonstrated selective and profound apoptotic effects of a five-alkaloid combination in the mouse melanoma B16F10 cell line....(more)
Kulp M, et al. Anal Bioanal Chem 2013 Apr;405(10):3391-7.
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- 10. Review article: herbal and dietary supplement hepatotoxicity.
BACKGROUND:
Herbal and dietary supplements are commonly used throughout the World. There is a tendency for underreporting their ingestion by patients and the magnitude of their use is underrecognised by Physicians. Herbal hepatotoxicity is not uncommonly encountered, but the precise incidence and manifestations have not been well characterised.
AIMS:
To review the epidemiology, presentation and diagnosis of herbal hepatotoxicity. This review will mainly discuss single ingredients and complex mixtures of herbs marketed under a single label.
METHODS:
A Medline search was undertaken to identify relevant literature using search terms including 'herbal', 'herbs', 'dietary supplement', 'liver injury', 'hepatitis' and 'hepatotoxicity'. Furthermore, we scanned the reference lists of the primary and review articles to identify publications not retrieved by electronic searches.
RESULTS:
The incidence rates of herbal hepatotoxicity are largely unknown. The clinical presentation and severity can be highly variable, ranging from mild hepatitis to acute hepatic failure requiring transplantation. Scoring systems for the causality assessment of drug-induced liver injury may be helpful, but have not been validated for herbal hepatotoxicity. Hepatotoxicity features of commonly used herbal products, such as Ayurvedic and Chinese herbs, black cohosh, chaparral, germander, greater celandine, green tea, Herbalife, Hydroxycut, kava, pennyroyal, pyrrolizidine alkaloids, skullcap, and usnic acid, have been individually reviewed. Furthermore, clinically significant herb-drug interactions are also discussed.
CONCLUSIONS:
A number of herbal medicinal products are associated with a spectrum of hepatotoxicity events. Advances in the understanding of the pathogenesis and the risks involved are needed to improve herbal medicine safety.
© 2012 Blackwell Publishing Ltd....(more)
Bunchorntavakul C, et al. Aliment Pharmacol Ther 2013 Jan;37(1):3-17.
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- 11. Greater Celandine hepatotoxicity: a clinical review.
Herbal hepatotoxicity is a rare and poorly described disease because reported cases are mostly scattered and lack an appropriate causality assessment. We now describe in detail the clinical picture of herbal hepatotoxicity by extracts of Greater Celandine (GC), syn. Chelidonium majus L. from the Papaveraceae family, which contain more than 20 ingredients including various biologically active isoquinoline alkaloids. For this purpose, we analyzed and reviewed published cases of 16 patients from various European countries. In all patients, herbal hepatotoxicity was of probable and highly probable causality for GC, using the original and updated scale of CIOMS (Council for International Organizations of Medical Sciences). GC associated hepatotoxicity usually has an acute clinical course exhibiting a hepatocellular pattern of injury and is correlated to an idiosyncratic reaction with its metabolic subtype. Jaundice combined with high values of serum aminotransferases was present in virtually all cases with favourable outcome despite severe clinical course. In conclusion, GC hepatotoxicity is a typical herbal hepatotoxicity with a sound causality track for GC, but there is uncertainty regarding the respective causative compound(s). The present detailed review of GC hepatotoxicity may serve as an example for clinical causality assessments of future cases of liver injury due to other herbs....(more)
Teschke R, et al. Ann Hepatol 2012 Nov-Dec;11(6):838-48. Review.
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- 12. Herbal hepatotoxicity: a tabular compilation of reported cases.
BACKGROUND:
Herbal hepatotoxicity is a field that has rapidly grown over the last few years along with increased use of herbal products worldwide.
AIMS:
To summarize the various facets of this disease, we undertook a literature search for herbs, herbal drugs and herbal supplements with reported cases of herbal hepatotoxicity.
METHODS:
A selective literature search was performed to identify published case reports, spontaneous case reports, case series and review articles regarding herbal hepatotoxicity.
RESULTS:
A total of 185 publications were identified and the results compiled. They show 60 different herbs, herbal drugs and herbal supplements with reported potential hepatotoxicity, additional information including synonyms of individual herbs, botanical names and cross references are provided. If known, details are presented for specific ingredients and chemicals in herbal products, and for references with authors that can be matched to each herbal product and to its effect on the liver. Based on stringent causality assessment methods and/or positive re-exposure tests, causality was highly probable or probable for Ayurvedic herbs, Chaparral, Chinese herbal mixture, Germander, Greater Celandine, green tea, few Herbalife products, Jin Bu Huan, Kava, Ma Huang, Mistletoe, Senna, Syo Saiko To and Venencapsan(®). In many other publications, however, causality was not properly evaluated by a liver-specific and for hepatotoxicity-validated causality assessment method such as the scale of CIOMS (Council for International Organizations of Medical Sciences).
CONCLUSIONS:
This compilation presents details of herbal hepatotoxicity, assisting thereby clinical assessment of involved physicians in the future.
© 2012 John Wiley & Sons A/S....(more)
Teschke R, et al. Liver Int 2012 Nov;32(10):1543-56.
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- 13. Pancreatic cancer cells retain the epithelial-related phenotype and modify mitotic spindle microtubules after the administration of ukrain in vitro.
The aim of this study is to characterize the phenotype of pancreatic ductal adenocarcinoma (PDAC) cells in relation to the expression of epithelial-to-mesenchymal transition (EMT) markers and determine whether ukrain, an anticancer drug based on the alkaloids extracted from greater celandine, modulates in vitro the malignant behavior of PDAC cells in order to extend our understanding of its therapeutic potential. Three cell lines (HPAF-II, HPAC, and PL45) were treated with ukrain (5, 10, and 20 μmol/l) for 48 h or left untreated (control). Cell proliferation was assessed by growth curves. Apoptosis was determined by Hoechst nuclear staining and by cytochrome c and caspase-8 expressions. The EMT markers E-cadherin, β-catenin, and vimentin, as well as actin and tubulin cytoskeletons, were analyzed by immunofluorescence. Interphase and mitotic microtubules as well as abnormal mitotic figures were studied by fluorescence microscopy after tubulin immunolabeling. Ukrain strongly suppressed cell proliferation and induced apoptosis possibly through an extrinsic pathway as cytochrome c immunoreactivity suggested that the integrity of the mitochondria was not affected. Tubulin expression indicated an antiproliferative effect of ukrain on the basis of alterations in mitotic spindle microtubule dynamics, leading to abnormal mitosis. Membranous E-cadherin/β-catenin immunoreactivity was similarly expressed in control-treated and ukrain-treated cells, although the drug upregulated E-cadherin in cell lysates. Our results suggest that ukrain exerts its chemotherapeutic action on PDAC cells targeting mitotic spindle microtubules, leading to abnormal mitosis and apoptosis, and favoring cell cohesiveness. The differentiated epithelial phenotype of HPAF-II, HPAC, and PL45 cell lines concomitant with a highly invasive potential suggests that further experiments will be necessary to definitively clarify the role of EMT in PDAC progression....(more)
Gagliano N, et al. Anticancer Drugs 2012 Oct;23(9):935-46.
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- 14. Suspected Greater Celandine hepatotoxicity: liver-specific causality evaluation of published case reports from Europe.
BACKGROUND AND OBJECTIVES:
In 21 published case reports, the use of the herb Greater Celandine (GC) (Chelidonium majus L.) has been causally related to liver injury, but a variety of confounding variables were evident that might have offset causality. This study reanalyses causality levels in these cases with a liver-specific causality evaluation method.
METHODS:
All 21 cases were submitted to the liver-specific, standardized, structured, quantitative and updated scale of the Council for International Organizations of Medical Sciences. This scale considers, among other items, latency period, course of alanine aminotransferase after treatment discontinuation, risk factors, comedication and alternative causes.
RESULTS:
Using this method for assessment, causality for GC was highly probable in two and probable in six cases, with lower causality grading in the remaining 13 cases. In these patients, causality for GC was possible in 10 cases and excluded in three cases. On the basis of the eight cases with highly probable and probable causality gradings, GC hepatotoxicity represents an idiosyncratic reaction of the metabolic type, whereas immunologic or obligatory hepatotoxic features are lacking. In some cases, alternative diagnoses and poor data quality were confounding variables that reduced causality levels.
CONCLUSION:
Confounding variables reduced causality levels for GC in reported cases of liver injury, but there is still striking evidence for herb-induced liver injury by GC with high causality gradings. GC hepatotoxicity is caused by an idiosyncratic reaction of the metabolic form, but there is uncertainty with respect to its culprit(s)....(more)
Teschke R, et al. Eur J Gastroenterol Hepatol 2012 Mar;24(3):270-80.
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- 15. Herbal hepatotoxicity by Greater Celandine (Chelidonium majus): causality assessment of 22 spontaneous reports.
Toxic liver injury due to the herb Greater Celandine (GC) (Chelidonium majus L.) has been assumed in patients originating from various European countries and created concern. Based on regulatory and liver unspecific ad hoc causality assessments in 22 spontaneous cases of Germany, causality levels for GC were considered probable in 16 and possible in 6 cases. We now analyzed the data of these 22 cases regarding their causality levels employing the liver specific, standardized, structured and quantitative assessment method of the updated scale of CIOMS (Council for International Organizations of Medical Sciences). Causality for GC was found highly probable (n=2), probable (n=6), possible (n=10), unlikely (n=1), and excluded (n=3). Thus, causality could be upgraded in 2 cases to a highly probable causality level, but had to be down graded to excluded, unlikely, or possible causality levels in 3, 1, or 9 cases, respectively. GC hepatotoxicity shows a hepatocellular pattern of liver injury with female gender predominance. On average, age of the patients was 56.4 years, treatment 36.4 days, and latency period until first symptoms and jaundice 29.8 and 35.6 days, respectively. This analysis therefore provides further evidence for the existence of GC hepatotoxicity as a distinct form of herb induced liver injury, but due to poor data quality the causal association between GC use and liver injury is less strong than hitherto assumed. We propose replacement of the regulatory organ unspecific by a liver specific causality assessment method in cases of herb induced liver injury as well as stricter pharmacovigilance strategies towards improvements of data quality. Toxicological studies are now warranted to elucidate the mechanism(s) of human GC hepatotoxicity that represents a European issue.
Copyright © 2011 Elsevier Inc. All rights reserved....(more)
Teschke R, et al. Regul Toxicol Pharmacol 2011 Dec;61(3):282-91.
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- 16. Celastrol attenuates adipokine resistin-associated matrix interaction and migration of vascular smooth muscle cells.
Obesity instigates various health problems such as atherosclerosis, diabetes, and cancer. Resistin, an adipose tissue-specific secretory adipokine, operates endocrine functions through increasing insulin resistance. Vascular smooth muscle cells (SMC) migrate into the subendothelial space and proliferate, thereby contributing to neointimal formation in atherosclerosis and restenosis. The aim of this study was to elucidate whether celastrol obtained from Tripterygium wilfordii Hook, inhibited human aortic SMC migration. Celastrol capable of antagonizing inflammatory responses attenuated the resistin secretion from THP-1-derived macrophages. The macrophage-conditioned media promoted SMC proliferation and MMP-2 production, which was dampened by 10-100 nM celastrol. Celastrol encumbered the SMC migration in response to 50 ng/ml resistin, concomitant with the inhibition of induction of connective tissue growth factor and collagen I/IV. In addition, celastrol disabled human aortic SMC exposed to resistin from migrating. The resistin-induced shedding of integrin β2/β3 expression was demoted by celastrol, thereby contributing to the inhibition of collagen matrix-SMC interaction. Next, resistin-induced Toll-like receptor-4 (TLR-4) expression was abrogated by celastrol, indicating that TLR-4 was the resistin signaling receptor that was blocked by celastrol. Collectively, these results demonstrate that anti-inflammatory celastrol blunted the macrophage secretion of the adipokine resistin, and suppressed the SMC migration by disturbing the interaction between SMC and intimal collagen matrix. Therefore, celastrol may inhibit atherogenic migration of vascular SMC upon resistin loading by intimal macrophages within atherosclerotic lesions....(more)
Kang SW, et al. J Cell Biochem 2013 Feb;114(2):398-408.
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- 17. Lipophilic stinging nettle extracts possess potent anti-inflammatory activity, are not cytotoxic and may be superior to traditional tinctures for treating inflammatory disorders.
Extracts of four plant portions (roots, stems, leaves and flowers) of Urtica dioica (the stinging nettle) were prepared using accelerated solvent extraction (ASE) involving water, hexanes, methanol and dichloromethane. The extracts were evaluated for their anti-inflammatory and cytotoxic activities in an NF-κB luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves was also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with a standard compound celastrol (1) but were moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves displayed moderate to weak anti-inflammatory activity, while the methanol and especially the water soluble extracts exhibited noticeable cytotoxicity. In contrast, the lipophilic dichloromethane extracts of the roots, stems and leaves exhibited potent anti-inflammatory effects greater than or equal to 1 with minimal cytotoxicity to RAW264.7 cells. Collectively these results suggest that using lipophilic extracts of stinging nettle may be more effective than traditional tinctures (water, methanol, ethanol) in clinical evaluations for the treatment of inflammatory disorders especially arthritis. A chemical investigation into the lipophilic extracts of stinging nettle to identify the bioactive compound(s) responsible for their observed anti-inflammatory activity is further warranted....(more)
Johnson TA, et al. Phytomedicine 2013 Jan 15;20(2):143-7.
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- 18. Celastrol suppresses breast cancer MCF-7 cell viability via the AMP-activated protein kinase (AMPK)-induced p53-polo like kinase 2 (PLK-2) pathway.
Celastrol, an anti-oxidant flavonoid that is widely distributed in the plant kingdom, has been suggested to have chemopreventive effects on cancer cells: however, the mechanism of this process is not completely understood. In this study, we found that celastrol suppressed the viability of breast cancer MCF-7 cells in an AMP-activated protein kinase (AMPK)-dependent fashion. Celastrol also induced an increase in reactive oxygen species (ROS) levels, leading to AMPK phosphorylation. Protein kinase C (PKC) zeta was also shown to play a role in celastrol-induced ROS generation. In addition, celastrol increased phosphorylation of the pro-apoptotic effector, p53. Inhibition of AMPK blocked celastrol-mediated p53 phosphorylation. Moreover, celastrol increased the expression of tumor suppressor polo like kinase-2 (PLK-2) in a p53-dependent manner. Neither celastrol-induced PLK-2 induction nor celastrol-mediated apoptosis inducing factor poly(ADP-ribose) polymerase-2 (PARP-2) induction was observed in p53 knock-out cells. Furthermore, add-back of PLK-2 resulted in an increase in both celastrol-mediated PARP-2 induction and celastrol-induced apoptotic index sub G1 population. Together, these results suggest that celastrol may have anti-tumor effects on MCF-7 cells via AMPK-induced p53 and PLK-2 pathways....(more)
Kim JH, et al. Cell Signal 2013 Apr;25(4):805-13.
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- 19. The Extent of Neurodegeneration and Neuroprotection in Two Chemical In Vitro Models Related to Parkinson's Disease is Critically Dependent on Cell Culture Conditions.
The proteasome inhibition and mitochondrial dysfunction are involved in pathomechanism of Parkinson's disease. The main aim of this study was to assess how particular culture conditions of human dopaminergic neuroblastoma SH-SY5Y cells could affect the extent of neurodegeneration induced by proteasome inhibitor-lactacystin (LC) and mitochondrial toxin-rotenone (Rot). This study revealed that induction of neuronal differentiation of SH-SY5Y cells with retinoic acid (RA-SH-SY5Y) caused a higher resistance of these cells to LC-evoked cell death when compared to undifferentiated cells (UN-SH-SY5Y). In contrast, RA-SH-SY5Y cells were more vulnerable than the UN-SH-SY5Y to Rot-induced cell damage. Furthermore, we found that a prolonged incubation of the cells under low serum condition (PLSC) significantly increased the LC toxicity in both differentiated and undifferentiated cells. Next, the effects of combined treatment with LC and Rot on cell viability were studied in RA-SH-SY5Y cells under PLSC and normal low serum condition (NLSC). At a low concentration, Rot (0.001-1 μM) attenuated the LC-evoked cell death in RA-SH-SY5Y cells exposed to NLSC. In contrast, under PLSC low concentrations of Rot lacked neuroprotective action while its higher levels (10 μM) enhanced the LC toxicity. Further, we showed that low concentrations of celastrol (Cel; 0.001 μM), a putative neuroprotective agent with antioxidant and anti-inflammatory properties, were able to partially attenuate the Rot-evoked toxicity under both PLSC and NLSC. On the other hand, Cel (0.001 and 0.01 μM) attenuated the LC-induced cell damage only under PLSC. Interestingly, higher concentrations of Cel (>1 μM) reduced cell viability in both UN- and RA-SH-SY5Y but only in UN-SH-SY5Y cells the effect was enhanced under PLSC. The obtained data indicate that toxicity of LC and Rot in SH-SY5Y cell line depends on the stage of cell differentiation and is enhanced in cells cultured for a longer time in low serum medium. Moreover, the neuroprotective properties of Rot and Cel against the LC-induced cell damage can be observed only under particular low serum conditions....(more)
Jantas D, et al. Neurotox Res 2013 Jan 10.
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- 20. Celastrol, an inhibitor of heat shock protein 90β potently suppresses the expression of matrix metalloproteinases, inducible nitric oxide synthase and cyclooxygenase-2 in primary human osteoarthritic chondrocytes.
Overexpression of matrix metalloproteinases (MMPs), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) have long been suggested to play crucial roles in the progression of osteoarthritis. Studies have showed that selective MMPs, iNOS and COX-2 inhibitors possess great potential as chondroprotective agents for osteoarthritis. Therefore, there have been intensive efforts to develop novel natural compounds that target MMPs, iNOS and COX-2 activation. As interleukin-1β (IL-1β) is one of the key proinflammatory cytokines contributing to the progression in osteoarthritis, we investigated the effect of celastrol, a triterpenoid compound extracted from the Chinese herb Tript erygium wilfordii Hook F, in neutralizing the inflammatory effects of IL-1β on MMPs, iNOS and COX-2 expression as well as nitric oxide (NO) and prostaglandin E2 (PGE2) production. Protein expression was detected by Western blotting or by enzyme-linked immunosorbent assay (ELISA); messenger RNA (mRNA) expression was examined by real-time reverse transcription-polymerase chain reaction analysis and the involvement of signal pathway was assessed by transient transfection and luciferase activity assay. We found that treatment of primary human osteoarthritic chondrocytes with various concentrations of celastrol resulted in striking decrease in the expression of MMP-1, MMP-3, MMP-13, iNOS-2 and COX-2. In addition, celastrol treatment of cells also inhibited the activation of nuclear factor-kappa B (NF-kappaB). Taken together, we provide evidence that celastrol can protect human chondrocytes by downregulating the expression of MMPs, iNOS and COX-2. We suggest that celastrol could be a useful agent for prevention and treatment of osteoarthritis....(more)
Ding QH, et al. Eur J Pharmacol 2013 Feb 8;708(1-3):1-7.
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- 21. Phenotypic identification of the redox dye methylene blue as an antagonist of heat shock response gene expression in metastatic melanoma cells.
Repurposing approved and abandoned non-oncological drugs is an alternative developmental strategy for the identification of anticancer therapeutics that has recently attracted considerable attention. Due to the essential role of the cellular heat shock response in cytoprotection through the maintenance of proteostasis and suppression of apoptosis, small molecule heat shock response antagonists can be harnessed for targeted induction of cytotoxic effects in cancer cells. Guided by gene expression array analysis and a phenotypic screen interrogating a collection of 3,7-diamino-phenothiazinium derivatives, we have identified the redox-drug methylene blue (MB), used clinically for the infusional treatment of methemoglobinemia, as a negative modulator of heat shock response gene expression in human metastatic melanoma cells. MB-treatment blocked thermal (43 °C) and pharmacological (celastrol, geldanamycin) induction of heat shock response gene expression, suppressing Hsp70 (HSPA1A) and Hsp27 (HSPB1) upregulation at the mRNA and protein level. MB sensitized melanoma cells to the apoptogenic activity of geldanamycin, an Hsp90 antagonist known to induce the counter-regulatory upregulation of Hsp70 expression underlying cancer cell resistance to geldanamycin chemotherapy. Similarly, MB-cotreatment sensitized melanoma cells to other chemotherapeutics (etoposide, doxorubicin). Taken together, these data suggest feasibility of repurposing the non-oncological redox drug MB as a therapeutic heat shock response antagonist for cancer cell chemosensitization....(more)
Davis AL, et al. Int J Mol Sci 2013 Feb 19;14(2):4185-202.
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- 22. Proteasome inhibition protects human peripheral blood mononuclear cells from radiation-induced oxidative stress.
Purpose: The study aimed to analyze the impact of the proteasome inhibitors MG132 (N-carbobenzyoxyl-L-leucyl-L-leucyl-L-leucinal), lactacystin and celastrol on manganese superoxide dismutase (MnSOD), catalase and glutathione-S-transferase-π (GST-π), and on the heat shock protein 70 (Hsp70) in human peripheral blood mononuclear cells (PBMC), exposed to ionizing radiation. Materials and methods: Changes in protein levels were analyzed by Western blot. Cellular viability, proteasome activity, level of oxidative stress and apoptosis were determined by standard colorimetric and fluorescence assays. Results: MG132 and lactacystin induced an increase in the intracellular levels of Hsp70. MnSOD was up-regulated by MG132 and celastrol, and GST-π was up-regulated by MG132 and lactacystin. Notably, the proteasome inhibitors significantly modified the protein levels in the irradiated cells and dramatically reduced the intracellular pool of oxidative species. The combined effect of radiation and proteasome inhibition was a dose-dependent up-regulation of the antioxidant enzymes and Hsp70. Conclusions: All three proteasome inhibitors showed antioxidant effects in PBMC and up-regulated the antioxidant enzymes MnSOD, catalase and GST-π and the stress protein Hsp70, modifying the early radiation response, and conferring protection against the effects of ionizing radiation....(more)
Stankova K, et al. Int J Radiat Biol 2013 Apr 16.
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- 23. Identification of novel dietary phytochemicals inhibiting the efflux transporter breast cancer resistance protein (BCRP/ABCG2).
Breast cancer resistance protein (BCRP/ABCG2) plays an important role in determining the absorption and disposition of consumed xenobiotics including various drugs and dietary phytochemicals and is also one of the prominent efflux transporters involved in multidrug resistance (MDR). In this study, we have investigated the interactions between ABCG2 and 56 naturally-occurring phytochemicals including phenolic acids, flavonoids, triterpenes and other common dietary phytochemicals, as well as two non plant-based compounds (hippuric acid and propyl gallate) using cell- and membrane-based transport inhibition assays. Of the non-flavonoid phytochemicals tested, berberine, celastrol, ellagic acid, limonin, oleanolic acid, propyl gallate, sinapic acid and ursolic acid demonstrated significant inhibition of ABCG2-mediated transport. Chrysoeriol, laricitrin, myricetin 3',4',5'-trimethylether, pinocembrin, quercitrin, tamarixetin, tricetin and tricetin 3',4',5'-trimethylether were also identified as novel flavonoid ABCG2 inhibitors. The identified inhibitory activity of dietary phytochemicals on ABCG2 provides a framework for further investigation of ABCG2-modulated phytochemical bioavailability, MDR, and possible food-drug interactions....(more)
Tan KW, et al. Food Chem 2013 Jun 15;138(4):2267-74.
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- 24. Celastrol Suppresses Tumor Cell Growth through Targeting an AR-ERG-NF-κB Pathway in TMPRSS2/ERG Fusion Gene Expressing Prostate Cancer.
The TMPRSS2/ERG (T/E) fusion gene is present in the majority of all prostate cancers (PCa). We have shown previously that NF-kB signaling is highly activated in these T/E fusion expressing cells via phosphorylation of NF-kB p65 Ser536 (p536). We therefore hypothesize that targeting NF-kB signaling may be an efficacious approach for the subgroup of PCas that carry T/E fusions. Celastrol is a well known NF-kB inhibitor, and thus may inhibit T/E fusion expressing PCa cell growth. We therefore evaluated Celastrol's effects in vitro and in vivo in VCaP cells, which express the T/E fusion gene. VCaP cells were treated with different concentrations of Celastrol and growth inhibition and target expression were evaluated. To test its ability to inhibit growth in vivo, 0.5 mg/kg Celastrol was used to treat mice bearing subcutaneous VCaP xenograft tumors. Our results show Celastrol can significantly inhibit the growth of T/E fusion expressing PCa cells both in vitro and in vivo through targeting three critical signaling pathways: AR, ERG and NF-kB in these cells. When mice received 0.5 mg/kg Celastrol for 4 times/week, significant growth inhibition was seen with no obvious toxicity or significant weight loss. Therefore, Celastrol is a promising candidate drug for T/E fusion expressing PCa. Our findings provide a novel strategy for the targeted therapy which may benefit the more than half of PCa patients who have T/E fusion expressing PCas....(more)
Shao L, et al. PLoS One 2013;8(3):e58391.
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- 25. Hsp70 silencing with siRNA in nanocarriers enhances cancer cell death induced by the inhibitor of Hsp90.
Inducers of heat shock protein 70 (Hsp70) commonly promote cancer cell viability whereas inhibitors of Hsp90 reduce it. The anticancer agent celastrol, interferes with signal transduction pathways involving these heat shock proteins. The objective of this in vitro study was to silence inducible Hsp70 and to promote celastrol-induced tumor cell death. Hsp70 siRNA loaded chitosan-TPP carriers were prepared by ionic gelation and characterized by photon correlation spectroscopy and asymmetric flow field-flow fractionation combined with dynamic light scattering. Viability of human leukemia and glioblastoma cells and Hsp70 silencing was determined following treatment with chitosan-TPP-Hsp70 siRNA particles. The results showed that silencing of Hsp70 by chitosan-TPP-Hsp70 siRNA treatment significantly reduced cell viability, and enhanced antiproliferative effects of celastrol in leukemia and glioblastoma cells. In glioblastoma spheroids, higher concentrations of celastrol and Hsp70 siRNA in chitosan-TPP nanocarriers were necessary to induce cell death....(more)
Matokanovic M, et al. Eur J Pharm Sci 2013 Apr 10.
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- 26. A toxicological investigation of a celery seed extract having anti-inflammatory activity.
BACKGROUND AND AIMS:
An extract of the seed from celery (Apium graviolens) (CSE), and fractions thereof, have been found to possess anti-inflammatory activity, gastro-protective activity, and anti-Helicobacter pylori activity. In view of the potential for employing these extracts for therapeutic use, toxicological investigations were undertaken with an alcoholic extract (A-CSE) which has previously been shown to have the above pharmacological activities.
METHODS:
A 28-day toxicity study was performed in rats according to Good Laboratory Practice (GLP) conditions. Eighteen adult male and 18 adult female rats were randomly assigned to 3 treatment groups of 6 rats/sex/group and were dosed orally with A-CSE of 0, 150 or 5,000 mg/kg per day. Daily observations of vital signs and body weights were recorded and ophthalmological investigations were performed. At autopsy, the principal organs were weighed and sections collected for histological analysis. Serum and urine samples were collected at termination for routine clinical chemistry. Under non-GLP conditions alpha-2-μ-globulin immunohistochemistry was performed on kidney tissues and hepatic cytochrome P450 protein was determined, as well as, the enzymatic activities of the principal isoforms.
RESULTS:
All animals survived treatments with no visible or behavioral signs of toxicity being observed during the study. There were no statistically significant differences in body weight gains, body weight gains per day or cumulative absolute body weight gains, for either sex, in any treatment groups when compared with controls. Slightly increased liver weight and liver to body and brain weight ratios were observed in female rats and in liver to body weight ratios in male rats given high dose A-CSE which was a test article effect, but the absence of any microscopic correlates for the liver weight increases suggests that these were not toxicologically significant. Treatment related macroscopic changes were not observed at necropsy and microscopic findings were limited to minimal increases in gastric eosinophils in several male and female rats in the 5,000 mg/kg per day treatment groups. Minimal focal degeneration of renal tubules was observed sporadically in both sexes assigned to all treatment groups including control and was consistent with early spontaneous nephropathy of laboratory rats and thus was not considered to represent a pathologic change associated with the test article. Increased serum globulin and phosphorus levels were observed in male rats given 5,000 mg/kg per day A-CSE and decreased serum triglycerides levels in female animals given 150 or 5,000 mg/kg per day A-CSE. The increase in serum globulin and phosphorus in male animals was small in magnitude and not considered toxicologically significant. The mechanism for the decrease in serum triglycerides in female rats was not apparent. Changes in urinalysis parameters were limited to small decreases in urine pH in female animals in the 150 and 5,000 mg/kg per day groups and were not deemed toxicologically significant. Alpha-2-μ-globulin immunohistochemistry was performed on kidney tissues from all animals and found to be within normal physiologic limits. Minor corneal mineralization occurred in some animals from all treatment groups. Cataracts were observed in one in the control and one in an animal that had 5,000 mg/kg per day but since the cataracts occurred in the metabolically inactive region of the lens, these were not considered indicative of test article related lesions. There were no changes in total hepatic microsomal protein or in total cytochrome P450 protein. Although male rats appeared to have to higher levels of total microsomal protein than female rats, there appeared to be no treatment effect in either male or female animals. As regards the activity of the various isoforms tested (CYP2B1/2, CYP1A1/2, CYP3A1/2), with the large range of activities detected for each P450 i...(more)
Powanda MC, et al. Inflammopharmacology 2011 Aug;19(4):227-33.
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- 27. Arabinogalactan present in the mountain celery seed extract potentiated hypolipidemic bioactivity of coexisting polyphenols in hamsters.
CONTEXT:
Previously, we showed the essential oils (EO) of the mountain celery [Cryptotaenia japonica Hass (Umbelliferae)] seeds (MCS) to be a prominent hypolipidemic agent.
/>OBJECTIVE:
We hypothesized the aqueous extract (AE) of its seeds could also exhibit a comparable nutritional effect.
MATERIALS AND METHODS:
Experiments were carried out for compositional analysis, antioxidant assay, and hypolipidaemic assay with AE in hamsters.
RESULTS:
AE contained soluble arabinogalactan (AGal) with molecular weight (MW) 878 kDa. AE also was enriched in polyphenolics and flavonoids, reaching 30.4 and 2.20 mg/100 g, respectively. AGal consisted of eight monosaccharides (in mols %), galactose (28.75), arabinose (24.84), glucose (17.91), mannose (6.93), ribose (6.03), fucose (5.83), xylose (5.30), and rhamnose (4.41), with average MW 878 kDa. In vitro, AE showed potent ferrous chelating and DPPH scavenging effects but only moderate HO scavenging capability. In hamsters, AE exhibited promising hypolipidemic bioactivity, in particular, the HDL-C and hepatic unsaturated fatty acid (UFA) biosynthesis regarding oleic, linoleic, and arachidonic acids.
DISCUSSION AND CONCLUSION:
The presence of AGal enhanced the hypolipidemic and antioxidative bioactivity of MCS. MCS is feasibly beneficial to the hepatic de novo UFA synthesis and the hypolipidemics as evidenced by hamster model....(more)
Lin LY, et al. Pharm Biol 2011 Mar;49(3):319-26.
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- 28. Molecular mechanisms of celery seed extract induced apoptosis via s phase cell cycle arrest in the BGC-823 human stomach cancer cell line.
BACKGROUND:
Mechanisms of apoptosis in tumor cells is an important field of tumor therapy and cancer molecular biology. Loss of cell cycle control, leading to uncontrolled proliferation, is common in cancer. Therefore, the identification of potent and selective cyclin dependent kinase inhibitors is a priority for anti-cancer drug discovery. There are at least two major apoptotic pathways, initiated by caspase-8 and caspase-9, respectively, which can activate caspase cascades. Apoptosis triggered by activation of the mitochondrial-dependent caspase pathway represents the main programmed cell death mechanism. This is activated by various intracellular stresses that induce permeabilization of the mitochondrial membrane. Anti-tumor effects of celery seed extract (CSE) and related mechanisms regarding apoptosis were here investigated in human gastric cancer BGC-823 cells.
METHODS:
CSE was produced by supercritical fluid extraction. Cell viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl-tetrazolium bromide (MTT) assay and apoptosis by flow cytometry using Annexin/PI staining and DAPI staining and a laser scanning confocal microscope (LSCM). Cell cycling was evaluated using PI staining with flow cytometry and expression of cell cycle and apoptosis-related proteins cyclin A, CDK2, bcl-2 and bax was assessed by immunohistochemical staining.
RESULTS:
CSE had an anti-proliferation effect on human gastric cancer BGC-823 cells in a dose- and time-dependent manner. After treatment, the apoptotic rate significantly increased, with morphological changes typical of apoptosis observed with LSCM by DAPI staining. Cell cycle and apoptosis related proteins, such as cyclin A, CDK2 and bcl-2 were all down-regulated, whereas bax was up-regulated.
CONCLUSIONS:
The molecular determinants of inhibition of cell proliferation as well as apoptosis of CSE may be associated with cycle arrest in the S phase....(more)
Gao LL, et al. Asian Pac J Cancer Prev 2011;12(10):2601-6.
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- 29. Chamomile confers protection against hydrogen peroxide-induced toxicity through activation of Nrf2-mediated defense response.
Oxidative stress plays an important role in the development of various human diseases. Aqueous chamomile extract is used as herbal medicine, in the form of tea, demonstrated to possess antiinflammatory and antioxidant properties. We demonstrate the cytoprotective effects of chamomile on hydrogen peroxide (HO)-induced cellular damage in macrophage RAW 264.7 cells. Pretreatment of cells with chamomile markedly attenuated HO-induced cell viability loss in a dose-dependent manner. The mechanisms by which chamomile-protected macrophages from oxidative stress was through the induction of several antioxidant enzymes including NAD(P)H:quinone oxidoreductase, superoxide dismutase, and catalase and increase nuclear accumulation of the transcription factor Nrf2 and its binding to antioxidant response elements. Furthermore, chamomile dose-dependently reduced HO-mediated increase in the intracellular levels of reactive oxygen species. Our results, for the first time, demonstrate that chamomile has protective effects against oxidative stress and might be beneficial to provide defense against cellular damage....(more)
Bhaskaran N, et al. Phytother Res 2013 Jan;27(1):118-25.
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- 30. Researching accessible and affordable treatment for common dermatological problems in developing countries. An Ethiopian experience.
BACKGROUND:
Skin diseases are very common in rural and urban areas of Ethiopia, and traditional preparations of plant origin might represent the only alternative to synthetic drugs. Improving knowledge of traditional medicines and assessing their safety and effectiveness is necessary.
METHODS:
We conducted a two-arm, randomized, double-blind, placebo-controlled trial assessing the efficacy of some cosmetic herbal preparations for common dermatologic problems: a 3% thyme essential oil antifungal cream and a 10% chamomile extract cream for eczema-like lesions.
RESULTS:
Ten subjects (66.5%) treated with the 3% thyme active cream were completely healed vs. four subjects (28.5%) from the placebo group (P=0.040). A large number of subjects treated with the chamomile cream were healed or improved, but no significant differences were found between active cream and placebo. A high rate of treatment acceptance was registered in both groups, no adverse effects were reported.
CONCLUSIONS:
A 3% thyme essential oil cream could represent a cheap and easily available opportunity to treat and heal mild to moderate cases of fungal infections; a common emollient cream could be a very effective intervention when treating mild to moderate cases of pityriasis alba and eczema-like lesions. Further research is needed.
© 2012 The International Society of Dermatology....(more)
Shimelis ND, et al. Int J Dermatol 2012 Jul;51(7):790-5.
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- 31. Chamomile (Matricaria recutita) may provide antidepressant activity in anxious, depressed humans: an exploratory study.
CONTEXT:
Anxiety and depression are the most commonly reported psychiatric conditions and frequently occur as comorbid disorders. While the advent of conventional drug therapies has simplified treatment, a large segment of the population goes untreated or declines conventional therapy for financial, cultural, or personal reasons. Therefore, the identification of inexpensive and effective alternative therapies for anxiety and depression is of relevance to public health.
OBJECTIVE:
The current study explores data from a 2009 clinical chamomile trial in humans to determine if chamomile provides clinically meaningful antidepressant activity versus a placebo.
DESIGN:
In the 2009 randomized, double-blind, placebo-controlled study, the research team examined the antianxiety and antidepressant action of oral chamomile (Matricaria recutita) extract in participants with symptoms of comorbid anxiety and depression.
SETTING:
In the 2009 study, all of participants' evaluations took place at the Depression Research Unit at the University of Pennsylvania. The study drew participants from patients at the Department of Family Medicine and Community Health's primary care clinic at the University of Pennsylvania, Philadelphia.
PARTICIPANTS:
Of the 57 participants in the 2009 trial, 19 had anxiety with comorbid depression; 16 had anxiety with a past history of depression; and 22 had anxiety with no current or past depression.
INTERVENTION:
The intervention and placebo groups in the 2009 trial received identically appearing 220-mg capsules containing either pharmaceutical-grade chamomile extract standardized to a content of 1.2% apigenin or a placebo (ie, lactose monohydrate NF), respectively.
OUTCOME MEASURES:
In the current study, the research team used generalized estimating equations analysis to identify clinically meaningful changes over time in scores from the Hamilton Depression Rating (HAM-D) questionnaire among treatment groups.
RESULTS:
In the current study, the research team observed a significantly greater reduction over time in total HAM-D scores for chamomile vs placebo in all participants (P < .05). The team also observed a clinically meaningful but nonsignificant trend for a greater reduction in total HAM-D scores for chamomile vs placebo in participants with current comorbid depression (P = .062). When the team examined the HAM-D core mood item scores, it observed a significantly greater reduction over time for chamomile vs placebo in all participants (P < .05) and a clinically meaningful but nonsignificant trend for a greater reduction over time for chamomile vs placebo in participants without current or past depression (P = .06).
CONCLUSION:
Chamomile may provide clinically meaningful antidepressant activity that occurs in addition to its previously observed anxiolytic activity....(more)
Amsterdam JD, et al. Altern Ther Health Med 2012 Sep-Oct;18(5):44-9.
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- 32. Preliminary examination of the efficacy and safety of a standardized chamomile extract for chronic primary insomnia: a randomized placebo-controlled pilot study.
BACKGROUND:
Despite being the most commonly used herbal for sleep disorders, chamomile's (Matricaria recutita) efficacy and safety for treating chronic primary insomnia is unknown. We examined the preliminary efficacy and safety of chamomile for improving subjective sleep and daytime symptoms in patients with chronic insomnia.
METHODS:
We performed a randomized, double-blind, placebo-controlled pilot trial in 34 patients aged 18-65 years with DSM-IV primary insomnia for ≥ 6-months. Patients were randomized to 270 mg of chamomile twice daily or placebo for 28-days. The primary outcomes were sleep diary measures. Secondary outcomes included daytime symptoms, safety assessments, and effect size of these measures.
RESULTS:
There were no significant differences between groups in changes in sleep diary measures, including total sleep time (TST), sleep efficiency, sleep latency, wake after sleep onset (WASO), sleep quality, and number of awakenings. Chamomile did show modest advantage on daytime functioning, although these did not reach statistical significance. Effect sizes were generally small to moderate (Cohen's d ≤ 0.20 to < 0.60) with sleep latency, night time awakenings, and Fatigue Severity Scale (FSS), having moderate effect sizes in favor of chamomile. However, TST demonstrated a moderate effect size in favor of placebo. There were no differences in adverse events reported by the chamomile group compared to placebo.
CONCLUSION:
Chamomile could provide modest benefits of daytime functioning and mixed benefits on sleep diary measures relative to placebo in adults with chronic primary insomnia. However, further studies in select insomnia patients would be needed to investigate these conclusions....(more)
Zick SM, et al. BMC Complement Altern Med 2011 Sep 22;11:78.
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- 33. Bisabololoxide A, one of the main constituents in German chamomile extract, induces apoptosis in rat thymocytes.
German chamomile (Matricaria recutita L.), one of the popular ingredients in herbal teas, has been traditionally used for medicinal purposes. Bisabololoxide A (BSBO) is one of the main constituents in this herb. BSBO is supposed to be principle in some bioactivities of German chamomile such as anti-inflammatory, gastrointestinal, and antipruritic actions. Although the use of German chamomile has spread, the information related to toxicity of BSBO is very limited. In present study, the cytotoxic effect of micromolar BSBO was cytometrically examined on rat thymocytes by using appropriate fluorescent dyes. When the cells were incubated with BSBO for 24 h, BSBO at concentrations of 30 microM or more significantly increased populations of dead cells, shrunken cells, and cells with phosphatidylserine exposed on membrane surface. Both cell shrinkage and externalization of membrane phosphatidylserine are general features in an early stage of apoptosis. In addition, BSBO significantly increased population of cells containing hypodiploid DNA, and the increase was completely attenuated by Z-VAD-FMK, a pan-inhibitor for caspases, indicating an involvement of caspase activation. Thus, it is likely that the type of cell death induced by BSBO is apoptosis. The significant changes in cellular parameters of rat thymocytes by BSBO were not observed when the concentration was 10 microM or less. Furthermore, the short incubation (3 h) of cells even with 30-100 microM BSBO did not significantly affect the cells. Therefore, it may be suggested that BSBO is practically safe when German chamomile is conventionally used....(more)
Ogata I, et al. Arch Toxicol 2010 Jan;84(1):45-52.
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- 34. A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorder.
OBJECTIVE:
We conducted a randomized, double-blind, placebo-controlled efficacy and tolerability trial of Matricaria recutita (chamomile) extract therapy in patients with mild to moderate generalized anxiety disorder (GAD). We hypothesized that chamomile would be superior to placebo in reducing GAD symptoms with a comparable tolerability profile.
MATERIALS AND METHODS:
Sixty-one outpatients with mild to moderate GAD were enrolled, and 57 were randomized to either double-blind chamomile extract (n = 28) or placebo therapy (n = 29) for 8 weeks. The study was powered to detect a statistically significant and clinically meaningful group difference in change over time in total Hamilton Anxiety Rating (HAM-A) scores. Secondary outcomes included change in the Beck Anxiety Inventory, Psychological Well Being, and Clinical Global Impression Severity scores and the proportion of patients with 50% reduction or more in baseline HAM-A score.
RESULTS:
We observed a significantly greater reduction in mean total HAM-A score during chamomile versus placebo therapy (P = 0.047). Although the study was not powered to identify small to moderate differences in secondary outcomes, we observed a positive change in all secondary outcomes in the same direction as the primary outcome measure. One patient in each treatment group discontinued therapy for adverse events. The proportion of patients experiencing 0, 1, 2, or 3 adverse events or more was not significantly different between groups (P = 0.417).
CONCLUSIONS:
This is the first controlled clinical trial of chamomile extract for GAD. The results suggest that chamomile may have modest anxiolytic activity in patients with mild to moderate GAD. Future studies are needed to replicate these observations....(more)
Amsterdam JD, et al. J Clin Psychopharmacol 2009 Aug;29(4):378-82.
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- 35. Chamomile, a novel and selective COX-2 inhibitor with anti-inflammatory activity.
AIMS:
Inducible cyclooxygenase (COX-2) has been implicated in the process of inflammation and carcinogenesis. Chamomile has long been used in traditional medicine for the treatment of inflammatory diseases. In this study we aimed to investigate whether chamomile interferes with the COX-2 pathway.
MAIN METHODS:
We used lipopolysaccharide (LPS)-activated RAW 264.7 macrophages as an in vitro model for our studies.
KEY FINDINGS:
Chamomile treatment inhibited the release of LPS-induced prostaglandin E(2) in RAW 264.7 macrophages. This effect was found to be due to inhibition of COX-2 enzyme activity by chamomile. In addition, chamomile caused reduction in LPS-induced COX-2 mRNA and protein expression, without affecting COX-1 expression. The non-steroidal anti-inflammatory drug, sulindac and a specific COX-2 inhibitor, NS398, were shown to act similarly in LPS-activated RAW 264.7 cells. Our data suggest that chamomile works by a mechanism of action similar to that attributed to non-steroidal anti-inflammatory drugs.
SIGNIFICANCE:
These findings add a novel aspect to the biological profile of chamomile which might be important for understanding the usefulness of aqueous chamomile extract in the form of tea in preventing inflammation and cancer....(more)
Srivastava JK, et al. Life Sci 2009 Nov 4;85(19-20):663-9.
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