- 1. Influence of broccoli extract and various essential oils on performance and expression of xenobiotic- and antioxidant enzymes in broiler chickens.
The aim of our present study was to examine the regulation of xenobiotic- and antioxidant enzymes by phytogenic feed additives in the intestine and the liver of broilers. A total of 240 male Ross-308 broiler chickens (1 d old) were fed a commercial starter diet for 2 weeks. On day 15, the birds were assigned to six treatment groups of forty birds each. The control (Con) group was fed a diet without any additive for 3 weeks. The diet of group sulforaphane (SFN) contained broccoli extract providing 0.075 g/kg SFN, whereas the diets of the other four groups contained 0.15 g/kg essential oils from turmeric (Cuo), oregano (Oo), thyme and rosemary (Ro). Weight gain and feed conversion were slightly impaired by Cuo and Oo. In the jejunum SFN, Cuo and Ro increased the expression of xenobiotic enzymes (epoxide hydrolases 1 and 2 and aflatoxin B1 aldehyde reductase) and of the antioxidant enzyme haeme oxygenase regulated by an 'antioxidant response element' (ARE) compared to group Con. In contrast to our expectations in the liver, the expression of these enzymes was decreased by all the additives. Nevertheless, all the additives increased the Trolox equivalent antioxidant capacity of the jejunum and the liver and reduced Fe-induced lipid peroxidation in the liver. We conclude that the up-regulation of ARE genes in the small intestine reduces oxidative stress in the organism and represents a novel mechanism by which phytogenic feed additives improve the health of farm animals....(more)
Mueller K, et al. Br J Nutr 2012 Aug;108(4):588-602.
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- 2. Anti toxic effect of broccoli extract on stannous dichloride toxicity.
PURPOSE:
Since Technetium-99m ((99m)Tc) has favorable physical and chemical characteristics, it is widely used radioisotope in Nuclear Medicine. However, stannous dichloride (SnCl(2)) has been widely used as a reducing agent in labeling procedure of pharmaceutical with radionuclide, it has been realized that SnCl(2) have genotoxic and cytotoxic effects on biological systems. In previous studies, it has been shown that some herbal extract can reduce genotoxic and cytotoxic effects of SnCl(2). In the present study, it is aimed to evaluate the effect of the broccoli extract on the survival of E. coli ATCC 25922 strain against to toxic effects of SnCl(2).
METHODS:
Broccoli was extracted with methanol extraction. HPLC and TLC analysis of broccoli extract were performed. Then antitoxicity and dose response assays were performed on bacterial strain.
RESULTS:
The broccoli extract had dose dependent protective effect against SnCl(2) toxic effect on E. coli.
CONCLUSIONS:
The consumption of broccoli may alter the stannous dichloride toxicity. Broccoli extract may use as a new protective strategies against the toxic effect of SnCl(2) on patients who were taken (99m)Tc radiopharmaceuticals....(more)
Cekic B, et al. Acta Cir Bras 2012 Sep;27(9):606-10.
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- 3. UV-induced fin damage in zebrafish as a system for evaluating the chemopreventive potential of broccoli and cauliflower extracts.
This study applied broccoli and cauliflower extracts (whole, floret, and stem) to zebrafish larvae in parallel to receive 100 mJ/cm(2) of UVB six times, and recorded their fin malformation phenotypes. Chemopreventive effects of each group, including UVB, whole-, floret-, and stem-extracts of broccoli and cauliflower on fin development were evaluated using Kaplan-Meier analysis, log-rank test, and Cox proportional hazards regression. Results showed that (1) zebrafish fins in the UVB + whole broccoli extract group are 6.20~9.32-times more likely to return to normal fins than ones in the UVB only group, but fins in the UVB + whole cauliflower extract group are only 5.13~11.10-times more likely to recover, indicated that whole broccoli and cauliflower extract had similar chemopreventive ability on fin development; and (2) the broccoli stem has the highest antioxidant capacity among other groups. In conclusion, zebrafish can be used as a system for evaluating the efficacy of other UVB protective compounds....(more)
Chen YH, et al. Toxicol Mech Methods 2011 Jan;21(1):63-9.
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- 4. Inhibitory effects of broccoli extract on Escherichia coli O157:H7 quorum sensing and in vivo virulence.
Broccoli extract (BE) has numerous beneficial effects on human health including anticancer activity. Quorum sensing (QS), mediated by self-produced autoinducer (AI) molecules, is a key process for the production of virulence determinants in pathogenic bacteria. BE suppressed AI-2 synthesis and AI-2-mediated bacterial motility in a dose-dependent manner in Escherichia coli O157:H7. In addition, expression of the ler gene that regulates AI-3 QS system was also diminished in response to treatment with BE. Furthermore, in an in vivo efficacy test using Caenorhabditis elegans as a host organism, C. elegans fed on E. coli O157:H7 in the presence of BE survived longer than those fed solely on the pathogenic bacteria. Quantitative real-time PCR analysis indicated that quercetin was the most active among the tested broccoli-derived compounds in downregulating virulence gene expression, while treatment with myricetin significantly suppressed the expression of the eae gene involved in type III secretion system. These data suggest that BE and its flavonoid constituents can inhibit expression of QS-associated genes, thereby downregulating the virulence attributes of E. coli O157:H7 both in vitro and in vivo. This study clearly elucidates BE's QS-inhibitory activity and suggests that BE has the potential to be developed as an anti-infective agent....(more)
Lee KM, et al. FEMS Microbiol Lett 2011 Aug;321(1):67-74.
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- 5. Effects of broccoli extract on biodistribution and labeling blood components with 99mTc-GH.
PURPOSE:
People consume vegetables without the knowledge of the side effects of the biological and chemical contents and interactions between radiopharmaceuticals and herbal extract. To this end, current study is focused on the effects of broccoli extract on biodistribution of radiolabeled glucoheptonate ((99m)Tc-GH) and radiolabeling of blood components.
METHODS:
GH was labeled with (99m)Tc. Quality control studies were done utilizing TLC method. Biodistribution studies were performed on male rats which were treated via gavage with either broccoli extract or SF as control group for 15 days. Blood samples were withdrawn from rats' heart. Radiolabeling of blood constituents performed incubating with GH, SnCl2 and (99m) Tc.
RESULTS:
Radiochemical yield of (99m)Tc-GH is 98.46±1.48 % (n=8). Biodistribution studies have shown that according to the control, the treated group with broccoli has approximately 10 times less uptake in kidney. The percentage of the radioactivity ratios of the blood components is found to be same in both groups.
CONCLUSIONS:
Although there is no considerable effect on the radiolabeling of blood components, there is an outstanding change on the biodistribution studies especially on kidneys. The knowledge of this change on kidney uptake may contribute to reduce the risk of misdiagnosis and/or repetition of the examinations in Nuclear Medicine....(more)
Cekic B, et al. Acta Cir Bras 2011 Oct;26(5):339-45.
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- 6. Effect of acidic challenge preceded by food consumption on enamel erosion.
OBJECTIVES:
This in vitro study aimed to evaluate the effect of food consumption followed by acidic challenge on enamel erosion.
METHODS:
Seventy-five enamel blocks obtained from bovine teeth were divided randomly into five groups (n=15 per group): GI - erosion with previous immersion in milk; GII - erosion with previous immersion in cheese extract; GIII - erosion with previous immersion in liver extract; GIV - erosion with previous immersion in broccoli extract; and GV - erosive effect of cola drink (control). Over 24 h, the slabs were submitted to 3 pH-cycles, each consisting of immersion in the studied food (GI to GIV) for 5 min followed by immersion in a cola drink for 5 min, and subsequently, the slabs were stored in artificial saliva (110 min). At the end of the pH-cycles, the slabs were stored in artificial saliva for 18 h. Enamel alterations were assessed by profilometry (μm). Data were tested using ANOVA and Scott-Knott's tests (P<.05).
RESULTS:
Mean erosion depths for enamel (μm) were 0.46 in GI, 0.55 in GII, 0.64 in GIII, 0.54 in GIV, and 1.18 in GVI. Enamel loss by acidic challenge alone (GV) was significantly higher than when the acidic challenges were preceded by food extract immersion.
CONCLUSIONS:
The data suggest that all studied foods could minimize the erosive effect on enamel....(more)
Honório HM, et al. Eur J Dent 2010 Oct;4(4):412-7.
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- 7. Green tea catechins and broccoli reduce fat-induced mortality in Drosophila melanogaster.
Dietary fat accelerates the ageing process and causes a greater mortality by accumulating lipid hydroperoxide (LPO) in Drosophila melanogaster. The present study found that the life span of D. melanogaster was shortened from 54 to 6 days in a dose-dependent manner when fat in diet increased from 0% to 25%. The results showed that supplementation of both green tea catechins (GTC) and broccoli extract (BE) reversed partially the fat-induced mortality. The maximum life span was 44 days for the control group fed with a 5% fat, whereas it increased to 50 and 59 days in the GTC- and BE-supplemented groups, respectively. The 50% survival time for the control flies fed with a 5% fat diet was 30 days. In contrast, it increased to 32 and 48 days when GTC and BE were supplemented in the diet. This was consistent with a significant reduction in total body LPO level in D. melanogaster maintained on the GTC- and BE-supplemented diet. Accordingly, catalase and superoxide dismutase (SOD) activities increased significantly in the flies fed with a GTC or a BE diet compared with those fed with a control 5% fat diet. Reverse transcriptase-polymerase chain reaction analysis indicated that the increase in enzymatic activities of catalase and SOD was accompanied by up-regulation of genes for catalase, copper-zinc containing SOD and manganese-containing SOD. It was concluded that GTC and BE reversed the fat-induced mortality in D. melanogaster, most likely but necessarily solely, by up-regulation of endogenous antioxidant enzymes....(more)
Li YM, et al. J Nutr Biochem 2008 Jun;19(6):376-83.
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- 8. Effects of sea buckthorn procyanidins on healing of acetic acid-induced lesions in the rat stomach.
The aim of this study was to investigate the effects of sea buckthorn procyanidins (SBPC) on healing of acetic acid-induced lesions in the rat stomach and its possible mechanism. The sea buckthorn procyanidins (SBPC) were extracted with 60% alcohol/H2O from sea buckthorn bark and purified by macropore adsorption resin column, with a purity of >96%. The chemical character of SBPC was analyzed by reverse phase high-performance liquid chromatography/mass spectrometry (HPLC/MS). Chronic gastric ulceration was induced by injecting acetic acid into the subserosa of stomach. Different concentrations of SBPC were orally administrated to gastric ulcers rats. After treatment 7d and 14d, rats were sacrificed respectively. The healing of the acetic acid induced ulcerations was measured by ulcer index (UI). The level of epidermal growth factor (EGF) in plasma was determined; the expression of epidermal growth factor receptor (EGFR) and proliferating cell nuclear antigen (PCNA) around ulcer was detected by immunohistochemical method. SBPC was found to reduce the size of the ulcers at day 7 and 14 in a dose-dependent manner. Compared with the control, the UI of SBPC group was significantly lower (p< 0.01) and the level of EGF in the plasma of SBPC group increased significantly (p< 0.01), meanwhile the expression of EGFR and PCNA around ulcer in high-dose SBPC stomach were enhanced (p< 0.05). The results implied that SBPC plays an important role in healing of acetic acid-induced gastric lesions possibly by the acceleration of the mucosal repair....(more)
Xu X, et al. Asia Pac J Clin Nutr 2007;16 Suppl 1:234-8.
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- 9. Hepatoprotective effects of a chinese herbal formula, longyin decoction, on carbon-tetrachloride-induced liver injury in chickens.
The objective of this study is to establish poultry liver injury model induced by (CCl4) and seek effective hepatoprotective herbals for clinical application. Different doses of CCl4 dissolved in vegetable oil (1 : 1, V/V) were injected via pectoral muscle to induce acute liver injury model in chickens. An herbal formula, Longyin decoction, was prepared for hepatoprotection test on chicken acute liver injury models. The pathologic changes of the liver were observed, and the activities of ALT and AST were, respectively, detected to evaluate the hepatoprotective effects of Longyin decoction on chickens. The chicken acute liver injury model was successfully established by injecting CCl4 via pectoral muscle. The best dose of CCl4 inducing chicken liver injury was 4.0 mL/kg·BW (body weight). The results of qualitative determination by HPTLC showed that the components of Longyin decoction contained Gentian, Capillaries, Gardenia, and Bupleurum root. In the high-dose Longyin group and the middle-dose Longyin group, the pathological changes of the damaged liver were mitigated and the activities of ALT and AST in serum were reduced significantly. Longyin decoction has obvious hepatoprotective effect on acute liver injury induced by CCl4....(more)
Wang C, et al. Evid Based Complement Alternat Med 2013;2013:392743.
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- 10. [Professor Wei Pin-kang's experience in treating chemotherapy induced nausea and vomiting: an analysis of herbal medication].
OBJECTIVE:
To summarize the herbal medication by Professor WEI Pin-kang's prescriptions in treating chemotherapy induced nausea and vomiting (CINV).
METHODS:
On the basis of outpatient and inpatients' medical records concerning CINV from case-database (keywords: chemotherapy and vomiting), data of 143 patients and 143 effective prescriptions were collected. The herbs and those category, nature, flavor and meridian distribution were summarized by frequency method using SPSS 13.0 Software. The couple herbs were analyzed by hierarchical cluster analysis.
RESULTS:
A total of 144 herbs were used (2 353 frequencies). Six groups of herbs [ frequency >5%, cumulative relative frequency (CRF) 58.89%] were used frequently as follow: the herbs for regulating qi (17.81%), resolving phlegm (13.51%), invigorating qi (8.07%), relieving food retention (7.44%), calming Gan to stop endogenous wind (7.05%), and warming the interior (5.01%). The most frequently used herbs ( >20 frequencies, CRF 77.31%) had 31 species as follow: the herbs for regulating qi (6 species), calming Gan to stop endogenous wind (4 species), resolving phlegm (3 species), external application (2 species), invigorating qi (2 species), warming the interior (2 species), activating blood and removing blood stasis (2 species), promoting diuresis and resolving dampness (1 species), purgation (1 species), invigorating blood (1 species), relieving exterior syndrome with pungent-warm property (1 species), relieving exterior syndrome with pungent-cool property (1 species), astringent (1 species), resolving dampness with aromatic property (1 species), calming the mind (1 species), eliminating heat and dampness (1 species), relieving food retention (1 species). Frequency of Rhizoma Pinelliae was 127 including Rhizoma Pinelliae (processed with ginger) 83 (65.35%). Frequency of prepared Radix et Rhizoma Rhei was 85 (95.51% of Prea- praed Rhizoma Rhei). These herbs were mostly of warm nature (43.99%). The total frequency of herb-nature was 3 677 and the pungent (34.76%), bitter (32.06%) and sweet herbs (18.22%) were most frequently used (CRF 85.04%). The total frequency of meridian distribution was 6 627 and these herbs were mostly attributed to Pi, Wei, Gan, and Fei meridians (CRF 71.34%). The most frequently used couple-herbs included Rhizoma Pinelliae and Rhizoma Atisaematis, Fructus Aurantii Immaturus and Submature Bitter Orange, Flos Caryophylli and Calyx Kaki, Rhizoma Coptidis and Os Sepiae, Rumulus Ginnamomi and Radix Paeoniae, Fructus Citri Sarcodactylis and Fructus Citri, aloeswood and toad skin, scorpion and centipede, earth worm and Gekko Swinhoana, bupleurum root and curcumae, fossilia ossis mastodi and oyster, large head atractylodes and poria, and so on.
CONCLUSIONS:
Professor WEI Pin-kang regarded the therapy of dissolving phlegm and regulating Wei as the fundamental treatment of CINV. He emphasized gastrointestinal metabolic disorders induced by phlegm and stagnation related to chemotherapeutics. He laid equal emphasis on regulating qi, dissolving phlegm, and removing stagnation....(more)
Shi J, et al. Zhongguo Zhong Xi Yi Jie He Za Zhi 2012 Apr;32(4):556-9, 571. Chinese.
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- 11. Sho-saiko-to-ka-kikyo-sekko as an alternative treatment for chronic tonsillitis to avoid surgery.
Sho-saiko-to-ka-kikyo-sekko (TJ-109) is composed of 9 herbs (gypsum, Bupleurum root, Pinellia tuber, Scutellaria root, Platycodon root, jujube fruit, ginseng root, Glycyrrhiza root, and ginger rhizome). It is a folk medicine that has been used to treat pharyngitis or acute tonsillitis. The efficacy of TJ-109 for treating patients with chronic tonsillitis was investigated. Ten outpatients who experienced chronic tonsillitis for more than 2 years were recruited. TJ-109 was prescribed, and after one year of daily treatment the incidence of acute tonsillitis before and after the treatment was compared. The incidence of acute tonsillitis due to chronic tonsillitis decreased in all 7 patients who were followed up. No adverse events were observed in any of the patients. In conclusion, the herbal medicine TJ-109 effectively reduced the incidence of acute tonsillitis. In some cases, planned tonsillectomy was avoided.
Copyright © 2010 Elsevier Ltd. All rights reserved....(more)
Goto F, et al. Complement Ther Clin Pract 2010 Nov;16(4):216-8.
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- 12. A novel method of protein extraction from perennial Bupleurum root for 2-DE.
The perennial Bupleurum root is thick and woody and contains high levels of interfering compounds. Common protein extraction methods have proved refractory towards the isolation of proteins suitable for 2-DE, due to the presence of interfering compounds. A novel method for extracting proteins suitable for 2-DE was established to overcome these problems. The main characteristic of this protocol is the partitioning of the proteins into the aqueous (fraction A-2), chloroform and isoamyl alcohol phases (A-3), and the interphase (A-1). The proteins are then extracted from each of these phases. From A-1, 85% (extracted protein against total proteins) proteins could be extracted and purified. For fraction A-2, a novel phenol extraction step is employed for the extraction of proteins. Based on the well-resolved 2-DE patterns, our protein preparation is free of interfering compounds. Using these methods (A-1, A-2, and A-3-3), a total of 3662 (1526 + 1128 + 1008) spots could be separated, and a protein yield of about 1.41 mg per 1.0 g fresh root material was obtained. To our knowledge, this is the first time that a protocol for protein extraction from perennial Bupleurum root has been reported that gives reproducible results. The protocol is expected to be applicable to other recalcitrant plant tissues as well....(more)
Xie H, et al. Electrophoresis 2007 Mar;28(5):871-5.
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- 13. Anti-collagenase, anti-elastase and anti-oxidant activities of extracts from 21 plants.
BACKGROUND:
Owing to their roles in tissue remodelling in health and disease, several studies have reported investigations on plant extracts as inhibitors of proteinases and as anti-oxidants.
METHODS:
The anti-ageing and anti-oxidant properties of 23 plant extracts (from 21 plant species) were assessed as anti-elastase and anti-collagenase activities and in selected anti-oxidant assays along with phenolic content.
RESULTS:
Anti-elastase activities were observed for nine of the extracts with inhibitory activity in the following order: white tea (approximately 89%), cleavers (approximately 58%), burdock root (approximately 51%), bladderwrack (approximately 50%), anise and angelica (approximately 32%). Anti-collagenase activities were exhibited by sixteen plants of which the highest activity was seen in white tea (approximately 87%), green tea (approximately 47%), rose tincture (approximately 41%), and lavender (approximately 31%). Nine plant extracts had activities against both elastase (E) and collagenase (C) and were ranked in the order of white tea (E:89%, C:87%) > bladderwrack (E:50%, C:25%) > cleavers (E:58%, C:7%) > rose tincture (E:22%, C:41%) > green tea (E:10%: C:47%) > rose aqueous (E: 24%, C:26%) > angelica (E:32%, C:17%) > anise (E:32%, C:6%) > pomegranate (E:15%, C:11%).Total phenolic content varied between 0.05 and 0.26 mg gallic acid equivalents (GAE)/mL with the exception of white tea (0.77 mg GAE/mL). For anti-oxidant assessment, the Trolox equivalent anti-oxidant capacity (TEAC) assay revealed activity for all extracts. White tea had the highest activity equivalent to approximately 21 microM Trolox for a 6.25 microg aliquot. In addition, seven extracts exhibited activities = 10 microM Trolox with witch hazel (6.25 microg = 13 microM Trolox) and rose aqueous (6.25 microg = 10 microM Trolox) showing very high activities at low concentrations. A high activity for white tea was also found in the superoxide dismutase (SOD) assay in which it exhibited ~88% inhibition of reduction of nitroblue tetrazolium. High activities were also observed for green tea (86.41%), rose tincture (82.77%), witch hazel (82.05%) and rose aqueous (73.86%).
CONCLUSION:
From a panel of twenty three plant extracts, some one dozen exhibit high or satisfactory anti-collagenase or anti-elastase activities, with nine having inhibitory activity against both enzymes. These included white tea which was found to have very high phenolic content, along with high TEAC and SOD activities....(more)
Thring TS, et al. BMC Complement Altern Med 2009 Aug 4;9:27.
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- 14. Arctigenin ameliorates inflammation in vitro and in vivo by inhibiting the PI3K/AKT pathway and polarizing M1 macrophages to M2-like macrophages.
Seeds of Arctium lappa, containing arctigenin and its glycoside arctiin as main constituents, have been used as a diuretic, anti-inflammatory and detoxifying agent in Chinese traditional medicine. In our preliminary study, arctigenin inhibited IKKβ and NF-κB activation in peptidoglycan (PGN)- or lipopolysaccharide (LPS)-induced peritoneal macrophages. To understand the anti-inflammatory effect of arctigenin, we investigated its anti-inflammatory effect in LPS-stimulated peritoneal macrophages and on LPS-induced systemic inflammation as well as 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Arctigenin inhibited LPS-increased IL-1β, IL-6 and TNF-α expression in LPS-stimulated peritoneal macrophages, but increased LPS-reduced IL-10 and CD204 expression. Arctigenin inhibited LPS-induced PI3K, AKT and IKKβ phosphorylation, but did not suppress LPS-induced IRAK-1 phosphorylation. However, arctigenin did not inhibit NF-κB activation in LPS-stimulated PI3K siRNA-treated peritoneal macrophages. Arctigenin suppressed the binding of p-PI3K antibody and the nucleus translocation of NF-κB p65 in LPS-stimulated peritoneal macrophages. Arctigenin suppressed blood IL-1β and TNF-α level in mice systemically inflamed by intraperitoneal injection of LPS. Arctigenin also inhibited colon shortening, macroscopic scores and myeloperoxidase activity in TNBS-induced colitic mice. Arctigenin inhibited TNBS-induced IL-1β, TNF-α and IL-6 expression, as well as PI3K, AKT and IKKβ phosphorylation and NF-κB activation in mice, but increased IL-10 and CD204 expression. However, it did not affect IRAK-1 phosphorylation. Based on these findings, arctigenin may ameliorate inflammatory diseases, such as colitis, by inhibiting PI3K and polarizing M1 macrophages to M2-like macrophages.
Copyright © 2013 Elsevier B.V. All rights reserved....(more)
Hyam SR, et al. Eur J Pharmacol 2013 Jan 31;708(1-3):21-29.
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- 15. UPLC and HPLC of caffeoyl esters in wild and cultivated Arctium lappa L.
Analytical methods including ultra-performance liquid chromatography (UPLC) and high-performance liquid chromatography (HPLC) with photodiode array (PDA) detector were developed for the analysis of caffeoylquinic acid derivatives in seeds, leaves and roots of Arctium lappa L. Separation was performed on C(18) column utilising 5% (v/v) acetic acid in water and acetonitrile at 330 nm. Both methodologies were validated in terms of linearity, precision, and recovery. The results showed that the major advantages of UPLC, over HPLC were the fast analysis, narrow peaks, high sensitivity, and reduction of solvent consumption. Subsequently the methods were applied for the identification and quantification of chlorogenic acid (5-CQA) and 1,5-dicaffeoylquinic acid (1,5-DCQA) as main compounds in samples. The total phenolic content of samples ranged from 3.93 to 14.13 g of 5-CQA equivalent/100g dry weight (DW). There was a significant variability from 89 to 571 mg/100g for 5-CQA and 48 to 486 mg/100g for 1,5-DCQA in dry material.
Copyright © 2012 Elsevier Ltd. All rights reserved....(more)
Haghi G, et al. Food Chem 2013 May 1;138(1):321-6.
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- 16. Arctigenin protects focal cerebral ischemia-reperfusion rats through inhibiting neuroinflammation.
Stroke is the third leading cause of death in industrialized countries and the most important cause of acquired adult disability. Many evidences suggest that inflammation accounts for the progression of cerebral ischemic injury. Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignin isolated from certain plants, has shown anti-inflammatory activity against diabetes and Alzheimer's disease. In this study, we tested whether arctigenin can protect middle cerebral artery occluded (MCAO) rats. Male Sprague-Dawley rats were pretreated with arctigenin or vehicle for 7 d before being subjected to transient occlusion of middle cerebral artery and reperfusion. Rats were evaluated at 24 h after MCAO for neurological deficit scoring. Furthermore, the mechanism of the anti-inflammatory effect of arctigenin was investigated with a focus on inflammatory cells, proinflammatory cytokines, and transcriptional factors. Arctigenin significantly reduced cerebral infarction and improved neurological outcome. Arctigenin suppressed the activation of microglia and decreased the expression of interleukin (IL)- 1β and tumor necrosis factor (TNF)-α. These results revealed that arctigenin has a promising therapeutic effect in ischemic stroke treatment through an anti-inflammatory mechanism....(more)
Fan T, et al. Biol Pharm Bull 2012;35(11):2004-9.
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- 17. Arctium lappa ameliorates endothelial dysfunction in rats fed with high fat/cholesterol diets.
BACKGROUND:
Arctium lappa L. (Asteraceae), burdock, is a medicinal plant that is popularly used for treating hypertension, gout, hepatitis, and other inflammatory disorders. This study was performed to test the effect of ethanol extract of Arctium lappa L. (EAL) seeds on vascular reactivity and inflammatory factors in rats fed a high fat/cholesterol diet (HFCD).
METHOD:
EAL-I (100 mg·kg-1/day), EAL-II (200 mg·kg-1/day), and fluvastatin (3 mg·kg-1/day) groups initially received HFCD alone for 8 weeks, with EAL supplementation provided during the final 6 weeks.
RESULTS:
Treatment with low or high doses of EAL markedly attenuated plasma levels of triglycerides and augmented plasma levels of high-density lipoprotein (HDL) in HFCD-fed rats. Chronic treatment with EAL markedly reduced impairments of acetylcholine (ACh)-induced relaxation of aortic rings. Furthermore, chronic treatment with EAL significantly lowered systolic blood pressure (SBP) and maintained smooth and flexible intimal endothelial layers in HFCD-fed rats. Chronic treatment with EAL suppressed upregulation of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin in the aorta. Chronic treatment with EAL also suppressed increases in matrix metalloproteinase (MMP)-2 expression. These results suggested that EAL can inhibit HFCD-induced vascular inflammation in the rat model.
CONCLUSION:
The present study provides evidence that EAL ameliorates HFCD-induced vascular dysfunction through protection of vascular relaxation and suppression of vascular inflammation....(more)
Lee YJ, et al. BMC Complement Altern Med 2012 Aug 6;12:116.
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- 18. Effects of arctiin on streptozotocin-induced diabetic retinopathy in Sprague-Dawley rats.
Diabetic retinopathy is one of the most common and severe complications of diabetes mellitus. Arctiin, a bioactive compound isolated from the dry seeds of Arctium lappa L., has been reported to have antidiabetic activity. In this study, we investigated the effect of arctiin on the serum glucose and HBA1c levels, the blood viscosity, and VEGF expression in the retinal tissues of rats with diabetic retinopathy. We first extracted arctiin from Fructus Arctii and then investigated its chemopreventive effect on streptozotocin-induced diabetic retinopathy in male Sprague-Dawley rats. After the induction of diabetes using streptozotocin (30 mg/kg, i. p.), the rats were randomly divided into five groups (n = 20 per group) and treated with intragastric doses of 30, 90, or 270 mg/kg/d wt of arctiin, 100 mg/kg/d wt of calcium dobesilate, or 0.5 % CMC-Na. Twenty nondiabetic sham-treated rats were treated with 0.5 % CMC-Na. The occurrence of diabetic retinopathy did not differ dramatically among the groups. However, at week 16, the glycosylated haemoglobin (HBA1c) level was significantly decreased in all of the arctiin-treated groups when compared with the control group, and the serum glucose level was also decreased in the rats treated with the highest dose of arctiin. In addition, treatment with arctiin ameliorated retinal oedema, detachment of the retina, and VEGF expression in the retina, as detected using histological and immunochemical examinations. Finally, arctiin increased the viability of retinal microvascular endothelial cells in vitro. Together, these findings demonstrate that arctiin decreases the severity of diabetic complications, demonstrating the importance of this compound as an inhibitor of diabetic retinopathy.
Georg Thieme Verlag KG Stuttgart · New York....(more)
Lu LC, et al. Planta Med 2012 Aug;78(12):1317-23.
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- 19. Comparative analysis of caffeoylquinic acids and lignans in roots and seeds among various burdock (Arctium lappa) genotypes with high antioxidant activity.
Caffeoylquinic acids and lignans in the crude extracts of both roots and seeds from different burdock ( Arctium lappa L.) genotypes were simultaneously characterized and systematically compared by LC-MS and matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight mass spectrometry (MALDI-QIT-TOF MS), and their antioxidant activities were also investigated. A total of 14 lignans were identified in burdock seeds and 12 caffeoylquinic acids in burdock roots. High levels of caffeoylquinic acids were also detected in burdock seeds, but only trace amounts of lignans were found in burdock roots. Burdock seeds contained higher concentrations of lignans and caffeoylquinic acids than burdock roots. Quantitative analysis of caffeoylquinic acids and lignans in roots and seeds of various burdock genotypes was reported for the first time. Great variations in contents of both individual and total phenolic compounds as well as antioxidant activities were found among different genotypes. Burdock as a root vegetable or medicinal plants possessed considerably stronger antioxidant activity than common vegetables and fruits....(more)
Liu J, et al. J Agric Food Chem 2012 Apr 25;60(16):4067-75.
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- 20. Optimum yields of dibenzylbutyrolactone-type lignans from Cynareae fruits, during their ripening, germination and enzymatic hydrolysis processes, determined by on-line chromatographic methods.
INTRODUCTION:
Dibenzylbutyrolactone-type lignans are the physiologically active constituents of the achene fruits of Cynareae. These lignans occur in glycoside/aglycone forms: in the highest quantity of the arctiin/arctigenin, matairesinoside/matairesinol and tracheloside/trachelogenin pairs found in the fruits of Arctium lappa L., Centaurea scabiosa L. and Cirsium arvense (L.) Scop.
OBJECTIVE:
To optimise the extraction yield of the arctiin/arctigenin, matairesinoside/matairesinol and tracheloside/trachelogenin glycoside/aglycone pairs, from the fruits of Arctium lappa, Centaurea scabiosa and Cirsium arvense, under the ripening, germination and enzymatic hydrolysis processes of the fruits.
METHODOLOGY:
Identification and quantification of lignans were performed with on-line gas chromatography-mass spectrometry (GC-MS) and with high performance liquid chromatography (HPLC), both with UV and mass selective detections (HPLC-UV/MS).
RESULTS:
As novelties to the field it was confirmed that: (i) the unripe fruits provide a high amount of lignans, similar to the ripe fruit; (ii) the fruits of Arctium lappa and Cirsium arvense do have glycosidase activity to hydrolyse their lignan glycosides into free lignans; (iii) the glycosidase of Centaurea scabiosa fruit becomes activated under its germination process only; and (iv) the overwhelming part of the fruits lignan contents (80-94%) in all three species are accumulated in the embryo.
CONCLUSION:
The best sources of (i) lignan aglycones are the enzyme-hydrolysed embryos, separating spontaneously during the germination process, and (ii) lignan glycosides are the unripe fruits.
Copyright © 2012 John Wiley & Sons, Ltd....(more)
Szokol-Borsodi L, et al. Phytochem Anal 2012 Nov-Dec;23(6):598-603.
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- 21. Arctigenin isolated from the seeds of Arctium lappa ameliorates memory deficits in mice.
The seeds of Arctium lappa L. (AL, family Asteraceae), the main constituents of which are arctiin and arctigenin, have been used as an herbal medicine or functional food to treat inflammatory diseases. These main constituents were shown to inhibit acetylcholinesterase (AChE) activity. Arctigenin more potently inhibited AChE activity than arctiin. Arctigenin at doses of 30 and 60 mg/kg (p.o.) potently reversed scopolamine-induced memory deficits by 62% and 73%, respectively, in a passive avoidance test. This finding is comparable with that of tacrine (10 mg/kg p.o.). Arctigenin also significantly reversed scopolamine-induced memory deficits in the Y-maze and Morris water maze tests. On the basis of these findings, arctigenin may ameliorate memory deficits by inhibiting AChE.
© Georg Thieme Verlag KG Stuttgart · New York....(more)
Lee IA, et al. Planta Med 2011 Sep;77(13):1525-7.
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- 22. A review of the pharmacological effects of Arctium lappa (burdock).
Arctium lappa, commonly known as burdock, is being promoted/recommended as a healthy and nutritive food in Chinese societies. Burdock has been used therapeutically in Europe, North America and Asia for hundreds of years. The roots, seeds and leaves of burdock have been investigated in view of its popular uses in traditional Chinese medicine (TCM). In this review, the reported therapeutic effects of the active compounds present in the different botanical parts of burdock are summarized. In the root, the active ingredients have been found to "detoxify" blood in terms of TCM and promote blood circulation to the skin surface, improving the skin quality/texture and curing skin diseases like eczema. Antioxidants and antidiabetic compounds have also been found in the root. In the seeds, some active compounds possess anti-inflammatory effects and potent inhibitory effects on the growth of tumors such as pancreatic carcinoma. In the leaf extract, the active compounds isolated can inhibit the growth of micro-organisms in the oral cavity. The medicinal uses of burdock in treating chronic diseases such as cancers, diabetes and AIDS have been reported. However, it is also essential to be aware of the side effects of burdock including contact dermatitis and other allergic/inflammatory responses that might be evoked by burdock....(more)
Chan YS, et al. Inflammopharmacology 2011 Oct;19(5):245-54.
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- 23. Screening of dried plant seed extracts for adiponectin production activity and tumor necrosis factor-alpha inhibitory activity on 3T3-L1 adipocytes.
To search for dried plant seeds with potent anti-diabetes activity, we conducted a large scale screening for inhibitory activity on tumor necrosis factor-alpha and facilitating activity on adiponectin production in vitro. These activities in 3T3-L1 adipocytes were screened from ethanol extracts of 20 kinds of dried plant seed marketed in Japan. komatsuna (Brassica rapa var. perviridis), common bean (Phaseolus vulgaris L.), qing geng cai (Brassica rapa var. chinensis), green soybean (Glycine max), spinach (Spinacia oleracea L.) and sugar snap pea (Pisum sativum L.) markedly enhanced adiponectin production (11.3 ~ 12.7 ng/ml) but Japanese radish (Raphanus sativus), edible burdock (Arctium lappa L.), bitter melon (Momordica charantia) and broccoli (Brassica oleracea var. italica) did not (0.9 ~ 2.7 ng/ml). All adiponectin-production-enhancing seeds except spinach (2.7 pg/ml) and okra (Abelmoschus esculentus) (6.6 pg/ml) effectively decreased tumor necrosis factor-alpha levels (0.0 pg/ml). We further examined the effects on free radical scavenging activities in the dried seed extracts. Although scavenging activity correlated well with total phenolic content of samples, no correlation was observed with adiponectin production. These results point to the potential of dried seed extracts as a means to modify the activity of tumor necrosis factor-alpha for the adiponectin production....(more)
Okada Y, et al. Plant Foods Hum Nutr 2010 Sep;65(3):225-32.
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- 24. Spirostanol saponins and esculin from Rusci rhizoma reduce the thrombin-induced hyperpermeability of endothelial cells.
Rusci rhizoma extracts are traditionally used against chronic venous disorders (CVD). To determine the effect of its secondary plant metabolites on the endothelium, phenolic compounds and saponins from Butcher's broom were isolated from a methanolic extract, and their activity on the thrombin-induced hyperpermeability of human microvascular endothelial cells (HMEC-1) was investigated in vitro. In addition to the six known spirostanol saponins deglucoruscin (5), 22-O-methyl-deglucoruscoside (6), deglucoruscoside (7), ruscin (8), ruscogenin-1-O-(α-l-rhamnopyranosyl-(1→2)-β-d-galactopyranoside (9) and 1-O-sulpho-ruscogenin (10), three new spirostanol derivatives were isolated and identified: 3'-O-acetyl-4'-O-sulphodeglucoruscin (1), 4'-O-(2-hydroxy-3-methylpentanoyl)-deglucoruscin (2) and 4'-O-acetyl-deglucoruscin (3). Furthermore, the coumarin esculin (4), which is also prominently present in other medicinal plants used in the treatment of CVD, was isolated for the first time from Rusci rhizoma. Five of the isolated steroid derivatives (2, 5, 8, 9 and 10) and esculin (4) were tested for their ability to reduce the thrombin-induced hyperpermeability of endothelial cells in vitro, and the results were compared to those of the aglycone neoruscogenin (11). The latter compound showed a slight but concentration-dependent reduction in hyperpermeability to 71.8% at 100μM. The highest activities were observed for the spirostanol saponins 5 and 8 and for esculin (4) at 10μM, and these compounds resulted in a reduction of the thrombin-induced hyperpermeability to 41.9%, 42.6% and 53.3%, respectively. For 2, 5 and 8, the highest concentration tested (100μM) resulted in a drastic increase of the thrombin effect. The effect of esculin observed at a concentration of 10μM was diminished at 100μM. These in vitro data provide insight into the pharmacological mechanism by which the genuine spirostanol saponins and esculin can contribute to the efficacy of Butcher's broom against chronic venous disorders.
Copyright © 2013 Elsevier Ltd. All rights reserved....(more)
Barbi? M, et al. Phytochemistry 2013 Jun;90:106-13.
Related Products: Butcher's Broom Extract
- 25. Novel phenyl-1-benzoxepinols from butcher's broom (Rusci rhizoma).
Two novel compounds, (3S)-2,3-dihydro-3-(4-hydroxyphenyl)-1-benzoxepin-8-ol (ruscozepine A) and (3S)-2,3-dihydro-3-(4-hydroxyphenyl)-8-methoxy-1-benzoxepin-7-ol (ruscozepine B) were isolated from butcher's broom (Rusci rhizoma) together with a biosynthetically possible phenylethanoid precursor, hydroxytyrosol. The structures were elucidated by spectroscopic methods such as 1D- and 2D-NMR (COSY, HSQC, HMBC, ROESY), and HR-EI-MS experiments. The absolute configuration of the ruscozepines was determined by electronic circular dichroism.
Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich....(more)
Barbi? M, et al. Chem Biodivers 2012 Jun;9(6):1077-83.
Related Products: Butcher's Broom Extract
- 26. Which plant for which skin disease? Part 2: Dermatophytes, chronic venous insufficiency, photoprotection, actinic keratoses, vitiligo, hair loss, cosmetic indications.
This paper continues our review of scientifically evaluated plant extracts in dermatology. After plants effective against dermatophytes, botanicals with anti-edema effects in chronic venous insufficiency are discussed. There is good evidence from randomized clinical studies that plant extracts from grape vine leaves (Vitis vinifera), horse chestnut (Aesculus hippocastanum), sea pine (Pinus maritima) and butcher's broom (Ruscus aculeatus) can reduce edema in chronic venous insufficiency. Plant extracts from witch hazel (Hamamelis virginiana), green tea (Camellia sinensis), the fern Polypodium leucotomos and others contain antioxidant polyphenolic compounds that may protect the skin from sunburn and photoaging when administered topically or systemically. Extracts from the garden spurge (Euphorbia peplus) and from birch bark (Betula alba) have been shown to be effective in the treatment of actinic keratoses in phase II studies. Some plant extracts have also been investigated in the treatment of vitiligo, various forms of hair loss and pigmentation disorders, and in aesthetic dermatology.
© The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin....(more)
Reuter J, et al. J Dtsch Dermatol Ges 2010 Nov;8(11):866-73.
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- 27. Nonpharmacologic treatments for migraine and tension-type headache: how to choose and when to use.
OPINION STATEMENT: There are a variety of nonpharmacologic treatments for headache. Educating patients about headache and its management, identifying and managing triggers (via diaries), modifying lifestyles, and understanding the importance of adopting and adhering to interventions (either pharmacologic or nonpharmacologic) are relevant to all persons with headache. In addition, specific nonpharmacologic treatments can be used either alone or in conjunction with ongoing pharmacologic intervention. Strong candidates for nonpharmacologic treatment include individuals with significant headache-related disability, comorbid mood or anxiety disorders, difficulty managing stress or other triggers, medication overuse, and patients who prefer a specific treatment. Behavioral treatments (relaxation, biofeedback, and cognitive-behavioral therapy) possess the most evidence for successful headache management. They have a long history of randomized trials showing efficacy and are considered first-line preventive options. Among complementary and alternative treatments, recent positive findings from randomized trials using acupuncture provide evidence of its potential as a first-line intervention. Other complementary and alternative techniques do not have a consistent base of research to recommend them for headache prevention, but they may be used if the patient prefers this approach or when other first-line interventions (nonpharmacologic or pharmacologic) have not provided adequate results. Among "natural" treatments, both butterbur extract and vitamin B2 have shown efficacy in more than one randomized trial and are thus potentially useful first-line preventive interventions....(more)
Nicholson RA, et al. Curr Treat Options Neurol 2011 Feb;13(1):28-40.
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- 28. Petasites extract Ze 339 (PET) inhibits allergen-induced Th2 responses, airway inflammation and airway hyperreactivity in mice.
BACKGROUND:
The herbal Petasites hybridus (butterbur) extract (Ze 339, PET) is known to have leukotriene inhibiting properties, and therefore might inhibit allergic diseases.<br/>METHODS:
The effect of PET was investigated in ovalbumin (OVA) immunized BALB/c mice given intranasally together with antigen challenge in the murine model of allergic airway disease (asthma) with the analysis of the inflammatory and immune parameters in the lung.
RESULTS:
PET given with the antigen challenge inhibited the allergic response. PET inhibited airway hyperresponsiveness (AHR) and eosinophil recruitment into the bronchoalveolar lavage (BAL) fluid upon allergen challenge, but had no effect in the saline control mice. Eosinophil recruitment was further assessed in the lung by eosinophil peroxidase (EPO) activity at a concentration of 100 microg PET. Microscopic investigations revealed less inflammation, eosinophil recruitment and mucus hyperproduction in the lung with 100 microg PET. Diminution of AHR and inflammation was associated with reduced IL-4, IL-5 and RANTES production in the BAL fluid with 30 microg PET, while OVA specific IgE and eotaxin serum levels remained unchanged.
CONCLUSION:
PET, which has been reported to inhibit leukotriene activity, reduced allergic airway inflammation and AHR by inhibiting the production of the Th2 cytokines IL-4 and IL-5, and RANTES.
Copyright (c) 2009 John Wiley & Sons, Ltd....(more)
Brattström A, et al. Phytother Res 2010 May;24(5):680-5.
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- 29. Toxicogenomics applied to cultures of human hepatocytes enabled an identification of novel petasites hybridus extracts for the treatment of migraine with improved hepatobiliary safety.
Butterbur extracts (Petasites hybridus) are recommended for the prevention of migraine, but pharmacovigilance reports may be suggestive of rare hepatobiliary toxicity. To evaluate its hepatotoxic potential, a series of in vivo and in vitro studies were carried out. Essentially, there were no signs of hepatocellular toxicity at estimated therapeutic C(max) levels of 60 ng/ml. Nonetheless, in a 28-day toxicity study at approximately 200-fold of therapeutic doses, induced liver transaminases and bilirubin elevations were observed. In a subsequent 6-month chronic toxicity study, the initial hepatobiliary effects were reproduced, but at the end of the study, liver function recovered and returned to normal as evidenced by clinical chemistry measurements. To identify possible mechanisms of hepatotoxicity, we investigated liver function in vitro at > 170-fold of therapeutic C(max) levels, including cytotoxicity (lactate dehydrogenase, MTT, and ATP), transaminase activities (alanine aminotransferase and aspartate aminotransferase), albumin synthesis, urea and testosterone metabolism to assay for cytochrome P450 monooxygenase activity. Only with extracts rich in petasin (37% petasin) and at high and well above therapeutic doses, liver toxicity was observed. A toxicogenomic approach applied to hepatocyte cultures enabled hypothesis generation and was highly suggestive for extracts high in petasin content to impair bile acid transport and lipid and protein metabolism. Importantly, neither chronic rat in vivo nor rat in vitro studies predicted reliably hepatotoxicity, therefore reemphasizing the utility of human-based in vitro investigations for the development of safe medicinal products. Finally, toxicogenomics enabled the characterization of a novel butterbur extract with no signals for hepatotoxicity....(more)
Anderson N, et al. Toxicol Sci 2009 Dec;112(2):507-20.
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- 30. Herbal medicines for the treatment of allergic rhinitis: a systematic review.
OBJECTIVE:
To evaluate the efficacy of herbal medicines for the treatment of allergic rhinitis (AR).
DATA SOURCES:
Five electronic databases until November 8, 2005; bibliographies of located articles; manufacturers of commercially available preparations; and experts in the field. Study Selection: We only included double-blind randomized clinical trials (RCTs), which tested a herbal medicine against placebo or active comparator, in patients with AR, and evaluated clinically relevant outcomes. Study selection, data extraction, and evaluation of methodological quality were performed independently by 2 reviewers. Discrepancies were resolved by discussion and by seeking the opinion of the third reviewer. Meta-analysis was only performed if data were considered suitable for pooling.
RESULTS:
Sixteen eligible RCTs, testing 10 different herbal products against placebo or active comparator, were included. Six RCTs studied Petasites hybridus (butterbur) extract for AR and suggest that P hybridus is superior to placebo or similarly effective compared with nonsedative antihistamines for intermittent AR. Two RCTs studied an Indian herbal combination, Aller-7, in patients with AR and reported positive results. Single RCTs were identified for 8 other herbal products as treatments for AR, reporting positive outcomes, except for grape seed extract. The median methodological quality score was 4 of a possible maximum of 5.
CONCLUSIONS:
There is encouraging evidence suggesting that P hybridus may be an effective herbal treatment for seasonal (intermittent) AR. However, independent replication is required before a firm conclusion can be drawn because of the financial support from the manufacturer of P hybridus extract to the 3 large trials. There are also promising results generated for other herbal products, particularly Aller-7, Tinospora cordifolia, Perilla frutescens, and several Chinese herbal medicines. Although these results are confined to the paucity of data and the small sample size, confirmation in larger and more rigorously designed clinical trials is warranted....(more)
Guo R, et al. Ann Allergy Asthma Immunol 2007 Dec;99(6):483-95.
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- 31. Arf/p53 module, which induces apoptosis, downregulates histone H2AX to allow normal cells to survive in the presence of anti-cancer drugs.
Anti-cancer drugs generally target cancer cells rather than normal somatic cells. However, the factors that determine this differential sensitivity are poorly understood. Here, we show that Arf/p53-dependent downregulation of H2AX induced the selective survival of normal cells after drug treatment, resulting in the preferential targeting of cancer cells. Treatment with camptothecin, a topoisomerase I inhibitor, caused normal cells to downregulate H2AX and become quiescent, a process mediated by both Arf and p53. By contrast, transformed cells that harbor mutations in either Arf or p53 do not downregulate H2AX and are more sensitive to drugs unless they have developed drug resistance. Such transformation-associated changes in H2AX expression rendered cancer cells more susceptible to drug-induced damage (by two orders of magnitude); thus, the expression of H2AX and γH2AX (phosphorylated form of H2AX at S139) is a critical factor that determines drug sensitivity, and should be considered when administering chemotherapy....(more)
Atsumi Y, et al. J Biol Chem 2013 Mar 27.
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- 32. The Smc5/Smc6/MAGE Complex Confers Resistance to Caffeine and Genotoxic Stress in Drosophila melanogaster.
The SMC5/6 protein complex consists of the Smc5, Smc6 and Non-Smc-Element (Nse) proteins and is important for genome stability in many species. To identify novel components in the DNA repair pathway, we carried out a genetic screen to identify mutations that confer reduced resistance to the genotoxic effects of caffeine, which inhibits the ATM and ATR DNA damage response proteins. This approach identified inactivating mutations in CG5524 and MAGE, homologs of genes encoding Smc6 and Nse3 in yeasts. The fact that Smc5 mutants are also caffeine-sensitive and that Mage physically interacts with Drosophila homologs of Nse proteins suggests that the structure of the Smc5/6 complex is conserved in Drosophila. Although Smc5/6 proteins are required for viability in S. cerevisiae, they are not essential under normal circumstances in Drosophila. However, flies carrying mutations in Smc5, Smc6 and MAGE are hypersensitive to genotoxic agents such as ionizing radiation, camptothecin, hydroxyurea and MMS, consistent with the Smc5/6 complex serving a conserved role in genome stability. We also show that mutant flies are not compromised for pre-mitotic cell cycle checkpoint responses. Rather, caffeine-induced apoptosis in these mutants is exacerbated by inhibition of ATM or ATR checkpoint kinases but suppressed by Rad51 depletion, suggesting a functional interaction involving homologous DNA repair pathways that deserves further scrutiny. Our insights into the SMC5/6 complex provide new challenges for understanding the role of this enigmatic chromatin factor in multi-cellular organisms....(more)
Li X, et al. PLoS One 2013;8(3):e59866.
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- 33. Reactive oxygen species responsive nanoprodrug to treat intracranial glioblastoma.
Chemotherapy for intracranial gliomas is hampered by limited delivery of therapeutic agents through the blood brain barrier (BBB). An optimal therapeutic agent for brain tumors would selectively cross the BBB, accumulates in the tumor tissue and be activated from an innocuous prodrug within the tumor. Here we show brain tumor-targeted delivery and therapeutic efficacy of a nanometer-sized prodrug (nanoprodrug) of camptothecin (CPT) to treat experimental glioblastoma multiforme (GBM). The CPT nanoprodrug was prepared using spontaneous nanoemulsification of a biodegradable, antioxidant CPT prodrug and α-tocopherol. The oxidized nanoprodrug was activated more efficiently than nonoxidized nanoprodrug, suggesting enhanced therapeutic efficacy in the oxidative tumor microenvironment. The in vitro imaging of U-87 MG glioma cells revealed an efficient intracellular uptake of the nanoprodrug via direct cell membrane penetration rather than via endocytosis. The in vivo study in mice demonstrated that the CPT nanoprodrug passed through the BBB and specifically accumulated in brain tumor tissue, but not in healthy brain tissue and other organs. The accumulation preferably occurred at the periphery of the tumor where cancer cells are most actively proliferating, suggesting optimal therapeutic efficacy of the nanoprodrug. The nanoprodrug was effective in treating subcutaneous and intracranial tumors. The nanoprodrug inhibited subcutaneous tumor growth more than 80% compared with control. The median survival time of mice implanted with an intracranial tumor increased from 40.5 days for control to 72.5 days for CPT nanoprodrug. This nanoprodrug approach is a versatile method for developing therapeutic nanoparticles enabling tumor-specific targeting and treatment. The nontoxic, tumor-specific targeting properties of the nanoprodrug system make it a safe, low cost, and versatile nanocarrier for pharmaceuticals, imaging agents, and diagnostic agents....(more)
Lee BS, et al. ACS Nano 2013 Apr 23;7(4):3061-77.
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- 34. Structural and Functional Interactions of the Prostate Cancer Suppressor NKX3.1 with Topoisomerase I.
NKX3.1 is a prostate tumor suppressor protein that binds to topoisomerase I and enhances its DNA cleavage activity. We show that the NKX3.1 homeodomain binds to a region of topoisomerase I spanning the junction between core and linker domains. NKX3.1 activated N-terminal truncated topoisomerase I (Topo70) in vitro. In contrast, NKX3.1 interacts with the enzyme reconstituted from peptide fragments of core domain and linker-active site domains, but inhibits the DNA unwinding activity of the reconstituted enzyme in vitro. The effect of NKX3.1 on both Topo70 and the reconstituted enzyme was seen in the presence and absence of camptothecin. Neither NKX3.1 nor camptothecin had an effect on the interaction of the other with topoisomerase I. Therefore the interactions of NKX3.1 and camptothecin with the linker domain of topoisomerase I are mutually exclusive. However, in cells the effect of NKX3.1 on topoisomerase binding to DNA sensitized cells to cellular toxicity and induction of apoptosis by low dose CPT. Lastly, topoisomerase I is important for the effect of NKX3.1 on cell survival after DNA damage as topoisomerase knockdown blocked the effect of NKX3.1 on clonogenicity after DNA damage. Therefore, NKX3.1 and topoisomerase I interact in vitro and in cells to affect CPT sensitivity and DNA repair functions of NKX3.1....(more)
Song LN, et al. Biochem J 2013 Apr 5.
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- 35. Structure-specific endonucleases Xpf and Mus81 play overlapping but essential roles in DNA repair by homologous recombination.
DNA double-strand breaks (DSBs) occur frequently during replication in sister chromatids, and are dramatically increased when cells are exposed to chemotherapeutic agents including camptothecin. Such DSBs are efficiently repaired specifically by homologous recombination (HR) with the intact sister chromatid. HR hence plays pivotal roles in cellular proliferation and cellular tolerance to camptothecin. Mammalian cells carry several structure-specific endonucleases, such as Xpf-Ercc1 and Mus81-Eme1, in which Xpf and Mus81 are the essential subunits for enzymatic activity. Here we show the functional overlap between Xpf and Mus81 by conditionally inactivating Xpf in the chicken DT40 cell line, which has no Mus81 ortholog. Although mammalian cells deficient in either Xpf or Mus81 are viable, Xpf inactivation in DT40 cells was lethal, resulting in a marked increase in the number of spontaneous chromosome breaks. Similarly, inactivation of both Xpf and Mus81 in human HeLa cells and murine embryonic stem cells caused numerous spontaneous chromosome breaks. Furthermore, the phenotype of Xpf-deficient DT40 cells was reversed by ectopic expression of human Mus81-Eme1 or human Xpf-Ercc1 heterodimers. These observations indicate the functional overlap of Xpf-Ercc1 and Mus81-Eme1 in the maintenance of genomic DNA. Both Mus81-Eme1 and Xpf-Ercc1 contribute to the completion of HR as evidenced by the following data that the expression of Mus81-Eme1 or Xpf-Ercc1 diminished the number of camptothecin-induced chromosome breaks in Xpf-deficient DT40 cells, and preventing early steps in HR by deleting XRCC3 suppressed the inviability of Xpf-deficient DT40 cells. In summary, Xpf and Mus81 have a substantially overlapping function in completion of HR....(more)
Kikuchi K, et al. Cancer Res 2013 Apr 10.
Related Products: Camptothecin