- 1. Oleanane-type triterpene saponins from the bark of Aralia elata and their NF-κB inhibition and PPAR activation signal pathway.
Two new oleanane-type triterpene saponins, tarasaponin IV (1) and elatoside L (2), and four known; stipuleanoside R(2) (3), kalopanax-saponin F (4), kalopanax-saponin F methylester (5), and elatoside D (6) were isolated from the bark of Aralia elata. Kalopanax-saponin F methyl ester was isolated from nature for the first time. Their chemical structures were elucidated using the chemical and physical methods as well as good agreement with those of reported in the literature. Oleanane-type triterpene saponins are the main component of A. elata. All compounds were investigated the anti-inflammatory activity. We measured their inhibition of NF-κB and activation of PPARs activities in HepG2 cells using luciferase reporter system. As results, compounds 2 and 4 were found to inhibit NF-κB activation stimulated by TNFα in a dose-dependent manner with IC(50) values of 4.1 and 9.5 μM, respectively, when compared with that of positive control, sulfasalazine (0.9 μM). Compounds 2 and 4 also inhibited TNFα-induced expression of iNOS and COX-2 mRNA. Furthermore, compounds 1-6 were evaluated PPAR activity using PPAR subtype transactivation assays. Among of them, compounds 4-6 significantly increased PPARγ transactivation. However, compounds 4-6 did not activate in any other PPAR subtypes.
Copyright © 2011 Elsevier Ltd. All rights reserved....(more)
Nhiem NX, et al. Bioorg Med Chem Lett 2011 Oct 15;21(20):6143-7.
Related Products: Aralia Elata Extract
- 2. Activation of a casB gene encoding β-glucosidase of Pectobacterium carotovorum subsp. carotovorum LY34.
Two cas genes were isolated from Pectobacterium carotovorum subsp. carotovorum LY34 (Pcc LY34). Sequence analysis of the 4873 bp cloned DNA fragment (accession number AY866383) revealed two open reading frames (casF and casB) that are predicted to encode 658 and 467 amino acid proteins, respectively. The CasF protein is similar to other PTS enzyme II components. casB encodes β-glucosidase, a member of the glycosyl hydrolase family 1. An inverted repeat sequence was identified in the casB promoter region, and was hypothesized to have a negative effect on casB transcription. Replacement of the casB promoter of Pcc LY34 with the bglB promoter activated the casB gene, consistent with the repeats inhibiting expression of casB. Purified CasB enzyme was estimated to be 53,000 Da by SDS-PAGE, and hydrolyzed salicin, arbutin, pNPG, and MUG. CasB exhibited maximal activity toward pNPG at pH 7.0 and 40 °C, and Mg(2+) is essential for its activity. Two conserved glutamate residues (Glu(177) and Glu(366)) were shown to be important for CasB activity....(more)
Kim MK, et al. Microbiol Res 2013 Mar 30;168(3):138-46.
Related Products: Arbutin
- 3. 4-n-butylresorcinol, a highly effective tyrosinase inhibitor for the topical treatment of hyperpigmentation.
BACKGROUND:
Hyperpigmentary disorders like melasma, actinic and senile lentigines are a major cosmetic concern. Therefore, many topical products are available, containing various active ingredients aiming to reduce melanin production and distribution. The most prominent target for inhibitors of hyperpigmentation is tyrosinase, the key regulator of melanin production. Many inhibitors of tyrosinase are described in the literature; however, most of them lack clinical efficacy.
METHODS:
We were interested in evaluating the inhibition of skin pigmentation by well-known compounds with skin-whitening activity like hydroquinone, arbutin, kojic acid and 4-n-butylresorcinol. We compared the inhibition of human tyrosinase activity in a biochemical assay as well as inhibition of melanin production in MelanoDerm skin model culture. For some compounds, the in vivo efficacy was tested in clinical studies.
RESULTS:
Arbutin and hydroquinone only weakly inhibit human tyrosinase with a half maximal inhibitory concentration (IC(50)) in the millimolar range. Kojic acid is 10 times more potent with an IC(50) of approximately 500 μmol/L. However, by far the most potent inhibitor of human tyrosinase is 4-n-butylresorcinol with an IC(50) of 21 μmol/L. In artificial skin models, arbutin was least active with an IC(50) for inhibition of melanin production > 5000 μmol/L. Kojic acid inhibited with an IC(50) > 400 μmol/L. Interestingly, hydroquinone inhibited melanin production in MelanoDerms with an IC(50) below 40 μmol/L, probably due to a mechanism different from tyrosinase inhibition. Again, 4-n-butylresorcinol was the most potent inhibitor with an IC(50) of 13.5 μmol/L. In vivo efficacy of 4-n-butyl-resorcinol was confirmed in clinical studies. Subjects with age spots on the forearm treated twice daily two age spots with a formula containing 4-n-butylresorcinol and two control age spots with the corresponding vehicle. Within 8 weeks, 4-n-butylresorcinol reduced visibly the appearance of age spots, while the control spots showed no improvement. A second study showed that 4-butylresorcinol was more effective than 4-hexylresorcinol and 4-phenylethylresorcinol.
CONCLUSION:
The present in vitro and in vivo data prove the high inhibitory capacity of 4-n-butylresorcinol on human tyrosinase activity, exceeding by far the potency of hydroquinone, arbutin and kojic acid. The resulting clinical improvement of skin hyperpigmentations reveals 4-n-butylresorcinol as a very valuable active compound for the management of pigmentation disorders.
© 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology....(more)
Kolbe L, et al. J Eur Acad Dermatol Venereol 2013 Jan;27 Suppl 1:19-23.
Related Products: Arbutin
- 4. Micellar liquid chromatographic determination of arbutin and hydroquinone in medicinal plant extracts and commercial cosmetic products.
A simple micellar liquid chromatographic (MLC) procedure for simultaneous determination of arbutin and hydroquinone in medicinal plant extracts and commercial cosmetic products was proposed. This method was developed and validated. The chromatographic conditions were also optimized. All analyses were performed at room temperature in an isocratic mode, using a mixture of 1% (v/v) acetonitrile and 0.006 mol L(-1) Brij 35 (pH 6.0) as a mobile phase. The flow rate was set at 1.0 mL min(-1) . The analytical column was a 150 × 3.9 mm Nova-Pak C-18 column. The effluent from the analytical column was monitored by UV detection at 280 nm. Under the optimum conditions, arbutin and hydroquinone could be determined within a concentration range of 2-50 μg mL(-1) of arbutin, and hydroquinone was obtained with the regression equations; y = 0.045x + 0.042 (r(2) = 0.9923) and y = 0.091x + 0.050 (r(2) = 0.9930) respectively. The limits of detection were found to be 0.51 μg mL(-1) and 0.37 μg mL(-1) for arbutin and hydroquinone respectively. The proposed MLC method was applied for the determination of arbutin and hydroquinone contents in medicinal plant extracts and commercial cosmetic products. This proposed MLC method is thus suitable for routine analysis of arbutin and hydroquinone in the pharmaceutical formulations, cosmetic products and raw medicinal plant extracts....(more)
Thogchai W, et al. Int J Cosmet Sci 2013 Jan 24.
Related Products: Arbutin
- 5. Molecular inhibitory mechanism of tricin on tyrosinase.
Tricin was evaluated as a type of tyrosinase inhibitor with good efficacy compared to arbutin. Tricin functioned as a non-competitive inhibitor of tyrosinase, with an equilibrium constant of 2.30 mmol/L. The molecular mechanisms underlying the inhibition of tyrosinase by tricin were investigated by means of circular dichroism spectra, fluorescence quenching and molecular docking. These assays demonstrated that the interactions between tricin and tyrosinase did not change the secondary structure. The interaction of tricin with residues in the hydrophobic pocket of tyrosinase was revealed by fluorescence quenching; the complex was stabilized by hydrophobic associations and hydrogen bonding (with residues Asn80 and Arg267). Docking results implied that the possible inhibitory mechanisms may be attributed to the stereospecific blockade effects of tricin on substrates or products and flexible conformation alterations in the tyrosinase active center caused by weak interactions between tyrosinase and tricin. The application of this type of flavonoid as a tyrosinase inhibitor will lead to significant advances in the field of depigmentation....(more)
Mu Y, et al. Spectrochim Acta A Mol Biomol Spectrosc 2013 Apr 15;107:235-40.
Related Products: Arbutin
- 6. Tyrosinase modulation by five Rwandese herbal medicines traditionally used for skin treatment.
ETHNOPHARMACOLOGICAL RELEVANCE:
Traditional herbal medicines provide an interesting, largely unexplored source for the development of potential new drugs and skin-care cosmetics. Some herbal extracts are known to be inhibitors of melanin formation, sometimes more potent than the classical inhibitors, hydroquinone/arbutin or kojic acid, and are not associated with melanocytes cytotoxicity or mutagenicity. Such plants are used in traditional medicine in many countries, particularly in Africa, for skin lightening.
AIM OF THE STUDY:
To evaluate in vitro the ability of Rwandese medicinal plants, traditionally used for the treatment of skin (discoloration and attenuation of discolored spots), to modulate pigmentation and tyrosinase activity.
MATERIALS AND METHODS:
Based on an ethnopharmacological survey, five herbs [Brillantaisia cicatricosa Lindau (Acanthaceae), Chenopodium ugandae (Aellen) Aellen (Chenopodiaceae), Dolichopentas longiflora Oliv. (Rubiaceae), Protea madiensis Oliv. (Proteaceae) and Sesamum angolense Welw. (Pedaliaceae)] were selected. Twenty-seven extracts, obtained by treating the herbs with increasing polarities solvents, were investigated for their effects on cell viability (MTT test) and on pigmentation: inhibition of the enzyme tyrosinase (colorimetry of reaction products, measurement of enzyme activity, TLC-autography; studies on crude cellular extracts obtained from normal melanocytes and on a mushroom tyrosinase) and measurement of melanogenesis by human melanoma cells.
RESULTS:
None of the tested plant extracts were cytotoxic on tested human melanoma cell lines, except for Dolichopentas longiflora (IC50 of leaves n-hexane extract, 4μg/ml for MM028 and 4.5μg/ml for MM001; IC50 of roots ethyl acetate extract, 0.8μg/ml for MM028 and 3.9μg/ml for MM001). Almost all extracts inhibited melanogenesis in a melanoma whole cells overall pigmentation assay, a model reflecting the entire cycle of melanogenesis. All the Protea madiensis extracts quite strongly inhibited melanogenesis and, surprisingly, one of the Dolichopentas longiflora leaves extracts was found to increase melanogenesis. These results were confirmed by the modulation of pigmentation reactions by crude cellular extracts obtained from normal melanocytes; interestingly, one of the extracts (Dolichopentas longiflora ethyl acetate extract) is even more active (61% at 500μg/ml) than kojic acid (<3% at 142μg/ml and 68% at 1421μg/ml). In a mushroom tyrosinase inhibition assay, data obtained on some extracts fairly agree with pigmentation inhibition measured on melanocytes proteins as, for example, the methanol extract of Protea madiensis. While a few others extract display discording data, this probably reflects either differences between human and mushroom tyrosinase, interference with melanocytes enzymes at later steps than tyrosinase or the simultaneous presence of compounds with conflicting activities in a given extract.
CONCLUSIONS:
Ethnopharmacological data represent an efficient approach to discover active herbs. Some of the selected medicinal plants clearly show potent tyrosinase inhibitions while one extract significantly increases cell pigmentation; one extract contains potent growth melanocytes inhibitors.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved....(more)
Kamagaju L, et al. J Ethnopharmacol 2013 Apr 19;146(3):824-34.
Related Products: Arbutin
- 7. Preparation and characterization of cosmeceutical liposomes loaded with avobenzone and arbutin.
The objective of this study was to develop and characterize a liposome delivery system coencapsulating two cosmeceutical ingredients, avobenzone (AVO) and arbutin (AR). Two different liposome preparation methods, that is, thin film hydration and reverse-phase evaporation, were evaluated. To obtain the optimal formulation, various ratios of lipid to AVO or AR were tested. The effects of liposome formulation and preparation method on particle size, entrapment efficiency (EE), and skin permeation rate were studied. The mean particle size of the liposome formulations obtained by the thin film hydration method was smaller than that obtained by the reverse-phase evaporation method. The EE of AR and AVO in liposomes prepared by the thin film method, however, was lower than that prepared by the reverse-phase evaporation method. No differences in membrane permeation were observed between the two preparation methods. A large portion of AR permeated through the membrane into the receptor chamber. On the other hand, AVO remained in the donor chamber or accumulated in the membrane. The results of this study revealed that liposomes are a promising delivery system for coencapsulated AR and AVO. Liposomes may aid in retaining the sunscreen (AVO) at the surface of the skin for sun protection meanwhile facilitating the penetration of the whitening agent (AR) into the deeper layers of the skin for whitening effect....(more)
Liu JJ, et al. J Cosmet Sci 2013 Jan-Feb;64(1):9-17.
Related Products: Arbutin
- 8. Screening of high α-arbutin producing strains and production of α-arbutin by fermentation.
A mutant Xanthomonas maltophilia BT-112 with high α-anomer-selective glycosylation activity was screened by a series of mutation methods including UV light, N-methyl-N-nitro-N-nitroso-guanidine treatment and quick neutron mutation. The α-arbutin titer increased 15-folds compared with the parent strain. The optimal conditions for culture medium and the operational conditions for lab-scale fermenter were investigated. Under optimized conditions, the maximal hydroquinone (HQ) tolerance of cells and yield of α-arbutin were 120 mM and 30.6 g/l, respectively. The molar conversion yield of α-arbutin based on the amount of HQ supplied reached 93.6 %. The product was identified as α-arbutin by <sup>13</sup>C NMR and <sup>1</sup>H NMR analysis. In conclusion, the results in this work provide a one-step and cost-effective method for the large-scale production of α-arbutin....(more)
Liu CQ, et al. World J Microbiol Biotechnol 2013 Mar 1.
Related Products: Arbutin
- 9. Antioxidant, antityrosinase and antitumor activity comparison: the potential utilization of fibrous root part of Bletilla striata (Thunb.) Reichb.f.
This study was carried out to evaluate the utilization probability of the fibrous root part (FRP) of Bletilla striata, which was usually discarded and harvesting pseudobulb part (PSP). The chemical composition, total phenolic content, DPPH radical scavenging activity, Ferric-reducing antioxidant power and tyrosinase inhibition activity were compared between FRP and PSP. Antioxidant and pro-oxidant effect as well as antitumor effect of the extract of FRP and PSP were analyzed by in vitro cell system as well. Thin layer chromatography and high performance liquid chromatography analysis indicated that the chemical compositions in the two parts were similar, but the content in FRP was much higher than PSP. Meanwhile, the FRP extracts showed higher phenolic content, stronger DPPH scavenging activity, Ferric-reducing antioxidant capacity and tyrosinase inhibition activity. Sub-fraction analysis revealed that the distribution characteristic of phenolic components and other active constituents in FRP and PSP were consistent, and mainly deposited in chloroform and acetoacetate fractions. Especially, the chloroform sub-fraction (sch) of FRP showed extraordinary DPPH scavenging activity and tyrosinase inhibition activity, with IC50 0.848 mg/L and 4.3 mg/L, respectively. Besides, tyrosinase inhibition activity was even stronger than the positive compound arbutin (31.8 mg/L). Moreover, In vitro cell system analysis confirmed that FRP extract exerts comparable activity with PSP, especially, the sub-fraction sch of FRP showed better antioxidant activity at low dosage and stronger per-oxidant activity at high dosage, and both sch of FRP and PSP can dose-dependent induce HepG2 cells apoptosis, which implied tumor therapeutic effect. Considering that an additional 0.3 kg FRP would be obtained when producing 1.0 kg PSP, our work demonstrated that FRP is very potential to be used together with PSP....(more)
Jiang F, et al. PLoS One 2013;8(2):e58004.
Related Products: Arbutin
- 10. Isolation of resveratrol from vitis viniferae caulis and its potent inhibition of human tyrosinase.
Tyrosinase (TYR) catalyzes rate-limiting reactions of cellular melanin synthesis, and its inhibitors are of commercial interest as potential skin whitening agents. However, the limited availability of human TYR makes the screening of TYR inhibitors difficult. To overcome this hurdle, we transformed nonmelanocytic human embryonic kidney (HEK) 293 cells to express human TYR constitutively. Using these cells as a source of human TYR, the ethanolic extracts of 52 medicinal plants grown in Korea were tested for human TYR activity, and the extract of Vitis Viniferae Caulis (dried stems of the grape tree, Vitis vinifera L.) was found to inhibit human TYR activity potently. An active compound was isolated from this extract by solvent fractionation followed by liquid column chromatography and identified as resveratrol by spectroscopic and chromatographic analyses. Resveratrol was determined to be a highly potent inhibitor of human TYR (IC50 = 0.39 μ g mL(-1)) as compared with p-coumaric acid (IC50 = 0.66 μ g mL(-1)) and arbutin (IC50 > 100 μ g mL(-1)) and inhibited melanin synthesis by human epidermal melanocytes at subtoxic concentrations. This study suggests that resveratrol and resveratrol-containing extracts of Vitis Viniferae Caulis have a potential use as skin whitening agents....(more)
Park J, et al. Evid Based Complement Alternat Med 2013;2013:645257.
Related Products: Arbutin
- 11. Isolation of α-arbutin from Xanthomonas CGMCC 1243 fermentation broth by macroporous resin adsorption chromatography.
α-Arbutin is a glycosylated hydroquinone which has inhibitory function against tyrosinase. In this work, a one-step isolation of α-arbutin from Xanthomonas CGMCC 1243 fermentation broth by macroporous resin adsorption chromatography was investigated. The research results indicated that S-8 resin offered the best adsorption and desorption capacities for α-arbutin than others and its equilibrium adsorption data were well-fitted to the Freundlich isotherm. In order to optimize the operating parameters for separating α-arbutin, dynamic adsorption and desorption tests on S-8 column chromatography were carried out. Under optimized conditions (adsorption volume of 7 bed volume (BV), mobile phase of 25% (v/v) ethanol solution and elution volume of 3 BV), the purity and recovery of α-arbutin were 97.3% (w/w) and 90.9% (w/w), respectively. The product was identified as α-arbutin by (13)C NMR and (1)H NMR analysis. Moreover, we scaled up S-8 column from laboratory test (10cm×2cm ID) to large scale (500cm×100cm ID) without diminishing α-arbutin yield. In conclusion, the results in this work provide a one-step and cost-effective method for large-scale production of α-arbutin....(more)
Liu C, et al. J Chromatogr B Analyt Technol Biomed Life Sci 2013 Apr 15;925:104-9.
Related Products: Arbutin
- 12. The involvement of a polyphenol-rich extract of black chokeberry in oxidative stress on experimental arterial hypertension.
The aim of this study is to characterize the content of Aronia melanocarpa Elliott (black chokeberry) extract and also to estimate the influence of polyphenolic compounds contained in chokeberries on oxidative stress, on an L-NAME-induced experimental model of arterial hypertension. The rat blood pressure values were recorded using a CODA Noninvasive Blood Pressure System. HPLC/DAD coupled with ElectroSpray Ionization-Mass Spectrometry allowed identification of five phenolic compounds in berries ethanolic extract as follows: chlorogenic acid, kuromanin, rutin, hyperoside, and quercetin. The serous activity of glutathione-peroxidase (GSH-Px) has significantly lower values in the hypertensive (AHT) group as compared to the group protected by polyphenols (AHT + P). The total antioxidant capacity (TAC) values are lower in the AHT group and they are significantly higher in the AHT + P group. All the measured blood pressure components revealed a biostatistically significant blood pressure drop between the AHT group and the AHT + P group. The results reveal the normalization of the reduced glutathion (GSH) concentration as well as a considerable reduction in the malondialdehyde (MDA) serum concentration in the AHT + P group. Ethanolic extract of black chokeberry fruits not only has a potential value as a prophylactic agent but also may function as a nutritional supplement in the management of arterial hypertension....(more)
Ciocoiu M, et al. Evid Based Complement Alternat Med 2013;2013:912769.
Related Products: Aronia Chokeberry Extract
- 13. Polyphenol-rich black chokeberry (Aronia melanocarpa) extract regulates the expression of genes critical for intestinal cholesterol flux in Caco-2 cells.
Black chokeberry (Aronia melanocarpa) is a rich source of polyphenols. The hypolipidemic effects of polyphenol-rich black chokeberry extract (CBE) have been reported, but underlying mechanisms have not been well characterized. We investigated the effect of CBE on the expression of genes involved in intestinal lipid metabolism. Caco-2 cells were incubated with 50 or 100 μg/ml of CBE for 24 h for quantitative realtime polymerase chain reaction analysis. Expression of genes for cholesterol synthesis (3-hydroxy-3-methylglutaryl coenzyme A reductase and sterol regulatory element binding protein 2), apical cholesterol uptake (Niemann-Pick C1 Like 1 and scavenger receptor class B Type 1) and basolateral cholesterol efflux [ATP-binding cassette transporter A1 (ABCA1)] was significantly decreased by CBE compared with control. Western blot analysis confirmed that CBE inhibited expression of these proteins. In contrast, CBE markedly induced mRNA and/or protein levels of ABCG5 and ABCG8 that mediate apical cholesterol efflux to the intestinal lumen. Furthermore, CBE significantly increased mRNA and protein levels of low-density lipoprotein (LDL) receptor, and cellular LDL uptake. Expression of genes involved in lipid metabolism and lipoprotein assembly, including sterol regulatory element-binding protein 1c, fatty acid synthase and acyl-CoA oxidase 1, was significantly decreased by CBE in a dose-dependent manner. Concomitantly, CBE significantly increased sirtuin 1, 3 and 5 mRNA levels, while it decreased SIRT-2. Our data suggest that hypolipidemic effects of CBE may be attributed, at least in part, to increased apical efflux of LDL-derived cholesterol and to decreased chylomicron formation in the intestine; and specific isoforms of SIRT may play an important role in this process.
Copyright © 2013 Elsevier Inc. All rights reserved....(more)
Kim B, et al. J Nutr Biochem 2013 Mar 18.
Related Products: Aronia Chokeberry Extract
- 14. Chemotherapy modulates the biological activity of breast cancer patients plasma: the protective properties of black chokeberry extract.
In breast cancer patients (before and during anti-cancer therapy) oxidative/nitrative damage to various molecules is observed. Furthermore, anti-cancer treatments may also influence the hemostatic properties of blood platelets and plasma. The aim of our study was to assess the effect of oxidative/nitrative stress (estimated by measurements of the levels of carbonyl groups and 3-nitrotyrosine in proteins--ELISA and C-ELISA methods, respectively; lipid peroxidation and total antioxidant level--TAS) on the selected parameters of hemostatic activity of plasma (the process of fibrin polymerization and lysis) collected from breast cancer patients after surgery and after various phases of chemotherapy (doxorubicin and cyclophosphamide). Subsequently, we also evaluated the level of oxidative/nitrative stress and hemostatic activity in plasma from these patients in the presence of the commercial extract of Aronia melanocarpa (Aronox®) in vitro. Patients were hospitalized in Department of Oncological Surgery and Department of Chemotherapy in Medical University of Lodz, Poland. We observed increased levels of biomarkers of oxidative/nitrative stress in plasma from patients with breast cancer (before or after surgery and after various phases of chemotherapy) in comparison to healthy group. Our further experiments demonstrated the hemostatic activity of plasma from the investigated patients differs from hemostatic properties of plasma obtained from healthy volunteers. We also recognize the existence of a relationship between oxidative stress (measured by the level of carbonyl groups) and changes of hemostasis in breast cancer patients after I and IV phases of chemotherapy. Moreover, the obtained results showed that the commercial extract from A. melanocarpa berries significantly reduced, in in vitro system, the oxidative/nitrative stress and hemostasis changes in plasma from breast cancer patients, after surgery and different phases of chemotherapy. Considering the data presented in this study, we suggest that the oxidative/nitrative stress in plasma obtained from breast cancer patients (not only before or after the surgery, but also after various phases of doxorubicin and cyclophosphamide chemotherapy) may induce changes of hemostatic activity, which may contribute to thrombosis in these patients. Our results also suggest that the commercial extract of A. melanocarpa may be regarded as a promising new source of bioactive antioxidant natural compounds for breast cancer patients.
Published by Elsevier Ltd....(more)
K?dzierska M, et al. Food Chem Toxicol 2013 Mar;53:126-32.
Related Products: Aronia Chokeberry Extract
- 15. Micropropagation of chokeberry by in vitro axillary shoot proliferation.
The black chokeberry-aronia (Aronia melanocarpa Elliot) is a shrub native to North America although nowadays well known in Eastern Europe. The fruits are regarded as the richest source of antioxidant phytonutrients among fruit crops and vegetables. Chokeberries can be easily propagated by seeds but this method is not recommended. Micropropagation is far more efficient than other conventional cloning methods like layering or softwood cuttings. Aronia clones are propagated in vitro through four- or three-stage method based on subculturing of shoot explants. The double diluted MS or full strength MS medium with elevated 50% Ca(2+) and Mg(2+) content are used in the initiation and proliferation chokeberry in vitro cultures, respectively. They are supplemented with 0.5-1.0 mg LBA, and 0.05 mg LIBA. The double-phase medium is recommended in the last passage before shoot rooting. The regenerated shoots could be rooted both in vitro on double diluted MS with 0.05 mg L(-1) IBA or in vivo in peat and perlite substrate and subsequently grown in the greenhouse....(more)
Litwi¨˝czuk W. Methods Mol Biol 2013;11013:179-86.
Related Products: Aronia Chokeberry Extract
- 16. Changes in plasma thiol levels induced by different phases of treatment in breast cancer; the role of commercial extract from black chokeberry.
Different low-molecular-weight thiols, including glutathione, cysteine, and cysteinylglycine are physiological free radical scavengers. On the other hand, homocysteine may play a role as an oxidant. The aim of our present study was to establish in vitro the effects of the commercial extract of Aronia melanocarpa (Aronox(®)) on the amount of selected low-molecular-weight thiols and the activity of antioxidative enzymes (superoxide dismutase, glutathione peroxidase, and glutathione reductase) in plasma obtained from patients with invasive breast cancer during different phases of treatment [before or after the surgery and patients after different phases of chemotherapy (doxorubicin and cyclophosphamide)] and from healthy subjects. Patients were hospitalized in Department of Oncological Surgery and Department of Chemotherapy, Medical University of Lodz, Poland. The level of low-molecular-weight thiols was determined by high-performance liquid chromatography. We observed that in the presence of the Aronia extract changes in amount of thiols in plasma from breast cancer patients (at all tested groups) were significantly reduced. Our results showed that tested commercial extract reduced modifications of antioxidative enzymes activity in plasma from patients during different phases of treatment, but this effect was not statistical significant. Our results suggest that the Aronia extract supplementation in breast cancer patients has a beneficial effect on thiols concentration in plasma. Plasma, as reported in this work, could be used as an experimental model to evaluate the beneficial action of plant supplements, including phenolic extracts on thiols or other molecules during different phases of treatment....(more)
K?dzierska M, et al. Mol Cell Biochem 2013 Jan;372(1-2):47-55.
Related Products: Aronia Chokeberry Extract
- 17. The polyphenol-rich extracts from black chokeberry and grape seeds impair changes in the platelet adhesion and aggregation induced by a model of hyperhomocysteinemia.
OBJECTIVE:
The mechanism action of the polyphenol-rich extracts from berries of Aronia melanocarpa (black chokeberry) and from grape seeds in the defence against homocysteine (Hcy) and its derivatives action in blood platelets is still unknown. In this study, the influence of the aronia extract and grape seeds extract (GSE) on the platelet adhesion to collagen and fibrinogen and the platelet aggregation during a model of hyperhomocysteinemia was investigated. The aim of our study in vitro was also to investigate superoxide anion radicals (O(2) (-•) ) production after incubation of platelets with Hcy, HTL and the aronia extract and GSE during a model of hyperhomocysteinemia (induced by reduced form of homocysteine at final dose of 100 μM) and the most reactive form of Hcy-its cyclic thioester, homocysteine thiolactone (HTL, 1 μM). Moreover, the additional aim of our study was also to establish and compare the influence of the aronia extract, GSE and resveratrol (3,4',5-trihydroxystilben), a phenolic compound, which has been supposed to be beneficial for the prevention of cardiovascular events, on selected steps of platelet activation.
METHODS:
The effects of tested extracts on adhesion of blood platelets to collagen and fibrinogen were determined according to Tuszynski and Murphy. The platelet aggregation was determined by turbidimetry method using a Chrono-log Lumi-aggregometer.
RESULTS:
We have observed that HTL, like its precursor-Hcy stimulated the generation of O(2) (-•) (measured by the superoxide dismutase-inhibitable reduction of cytochrome c) in platelets and caused an augmentation of the platelet adhesion and aggregation induced by the strong physiological agonist-thrombin. Our present results in vitro also demonstrated that the aronia extract and grape seeds extract reduced the toxicity action of Hcy and HTL on blood platelet adhesion to collagen and fibrinogen, the platelet aggregation and superoxide anion radicals production in platelets, suggesting its potential protective effects on hemostasis during hyperhomocysteinemia.
CONCLUSION:
In the comparative studies, the aronia extract was found to be more effective antiplatelet factors, than GSE or resveratrol during a model of hyperhomocysteinemia. It gives hopes for development of diet supplements, which may be important during hyperhomocysteinemia....(more)
Malinowska J, et al. Eur J Nutr 2013 Apr;52(3):1049-57.
Related Products: Aronia Chokeberry Extract
- 18. Antithrombin effect of polyphenol-rich extracts from black chokeberry and grape seeds.
Thrombin is a serine protease that cleaves the peptide bonds in proteins located on the carboxyl side of arginine. Thrombin plays a central role in thromboembolic diseases, which are the major cause of mortality. The aim of the study was to estimate the effects of plant extracts on proteolytic properties of thrombin. Thrombin was incubated with polyphenol-rich extracts from berries of Aronia melanocarpa or seeds of Vitis vinifera (0.5, 5, 50 µg/mL) and with polyphenols ((+)-catechin, (-)-epicatechin, gallic acid, chlorogenic acid, procyanidin B1, cyanidin, cyanidin 3-glucoside, quercetin). The in vitro experiments showed that both extracts in all used concentrations inhibited proteolytic activity of thrombin observed as inhibition of thrombin-induced fibrinogen polymerization, stabilized fibrin formation, and platelet aggregation. Moreover, thrombin amidolytic activity was inhibited by polyphenols belonging to the flavonoid class. Results presented in this study indicate that polyphenol-rich extracts from berries of A. melanocarpa and seeds of V. vinifera may become promising dietary supplements in the prevention of thrombotic states.
Copyright © 2012 John Wiley & Sons, Ltd....(more)
Bijak M, et al. Phytother Res 2013 Jan;27(1):71-6.
Related Products: Aronia Chokeberry Extract
- 19. Antioxidant and quinone reductase-inducing constituents of black chokeberry (Aronia melanocarpa) fruits.
Using in vitro hydroxyl radical-scavenging and quinone reductase-inducing assays, bioactivity-guided fractionation of an ethyl acetate-soluble extract of the fruits of the botanical dietary supplement, black chokeberry (Aronia melanocarpa), led to the isolation of 27 compounds, including a new depside, ethyl 2-[(3,4-dihydroxybenzoyloxy)-4,6-dihydroxyphenyl] acetate (1), along with 26 known compounds (2-27). The structures of the isolated compounds were identified by analysis of their physical and spectroscopic data ([α](D), NMR, IR, UV, and MS). Altogether, 17 compounds (1-4, 9, 15-17, and 19-27) showed significant antioxidant activity in the hydroxyl radical-scavenging assay, with hyperin (24, ED(50) = 0.17 μM) being the most potent. The new compound (1, ED(50) = 0.44 μM) also exhibited potent antioxidant activity in this assay. Three constituents of black chokeberry fruits doubled quinone reductase activity at concentrations <20 μM, namely, protocatechuic acid [9, concentration required to double quinone reductase activity (CD) = 4.3 μM], neochlorogenic acid methyl ester (22, CD = 6.7 μM), and quercetin (23, CD = 3.1 μM)....(more)
Li J, et al. J Agric Food Chem 2012 Nov 21;60(46):11551-9.
Related Products: Aronia Chokeberry Extract
- 20. Composition of sugars, organic acids, and total phenolics in 25 wild or cultivated berry species.
Sugars, organic acids, and total phenolic content in fruit of 25 wild and cultivated berry species were identified and quantified with high-performance liquid chromatograph. The composition of sugars, organic acids, and total phenolic compounds in various species of Vaccinium, Rubus, Ribes, and Fragaria genus was evaluated. Additonally, total phenolics of less known berry species of the Morus, Amelanchier, Sorbus, Sambucus, Rosa, Lycium, Actinidia, and Aronia genus were determined in wild growing as well as in cultivated fruits. Significant differences in the concentration of sugars and organic acids were detected among the berry species. Glucose and fructose were the most abundant sugars in berry fruits and the major organic acids were malic and citric acid. However, in kiwi fruit, sucrose represented as much as 71.9% of total sugars. Sorbitol has been detected and quantified in chokeberry, rowanberry, and eastern shadbush fruit. The highest content of total analyzed sugars was determined in rowanberry fruit, followed by dog rose, eastern shadbush, hardy kiwifruit, American cranberry, chokeberry, and jostaberry fruit. Rowanberry stands out as the fruit with the highest content of total analyzed organic acids, followed by jostaberry, lingonberry, red gooseberry, hardy kiwifruit, and black currant. The berries of white gooseberry, black currant, red currant, and white currant had the lowest sugar/organic acid ratio and were thus perceptively the sourest species analyzed. On the other hand, the species with highest sugar/organic acid ratio were goji berry, eastern shadbush, black mulberry, and wild grown blackberry. The highest amounts of total phenols were quantified in chokeberry fruit. Wild strawberry, raspberry, and blackberry had 2- to 5-fold more total phenolics compared to cultivated plants. PRACTICAL APPLICATION: The fruit of analyzed berry species contained different levels of sugars, organic acids, and total phenolics. Moreover, it has been demonstrated that wild grown species generally contain more phenolics than cultivated ones. This information is interesting for nutritionists as well as berry growers and breeders who can promote the cultivation of species and new cultivars with higher phenolic content.
© 2012 Institute of Food Technologists®...(more)
Mikulic-Petkovsek M, et al. J Food Sci 2012 Oct;77(10):C1064-70.
Related Products: Aronia Chokeberry Extract
- 21. Antioxidant activities of chokeberry extracts and the cytotoxic action of their anthocyanin fraction on HeLa human cervical tumor cells.
The present study evaluates the antioxidant activity of two Aronia melanocarpa cultivars-Viking and Aron-and of Aronia prunifolia hybrid in relationship with their phytochemical composition regarding the contents of total phenolics, flavonoids, procyanidins, and monomeric anthocyanins. The antioxidant capacity of the mentioned extracts of chokeberries was evaluated through five complementary assays: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), H(2)O(2) scavenging potential, oxygen radical absorbance capacity, ferric reducing antioxidant power, and cupric ion reducing antioxidant capacity. A. prunifolia hybrid was found to have the highest antioxidant activity and to be the richest in polyphenols, procyanidins, and anthocyanins compared with the A. melanocarpa cultivars. A good correlation was observed between antioxidant activity and total procyanidin and anthocyanin content. Cyanidin glycosides inhibited HeLa human cervical tumor cell proliferation and increased generation of reactive oxygen species after 48 h of treatment, suggesting that they could be responsible for the antiproliferative activity. These results may be significant for industry concerning food quality and disease prevention....(more)
Rugin? D, et al. J Med Food 2012 Aug;15(8):700-6.
Related Products: Aronia Chokeberry Extract
- 22. Haemin enhances the in vivo efficacy of artemether against juvenile and adult Schistosoma mansoni in mice.
Among the potential alternatives to praziquantel, interestingly, the antimalarial artemether (Art) also exhibits antischistosomal properties. Previous invitro studies suggested that Art interacts with haemin and together produce a lethal agent against schistosomes. This study investigates the in vivoeffect of Art plus haemin on juvenile and adult Schistosoma mansoni worms and on their antioxidant enzymes. Infected mice were allocated into two batches each in four groups (I-IV): (I) untreated control; (II) injected with haemin (ip, 100 mg/kg/day) on days 26, 27, and 28 post-infection (PI) forjuvenile stage and on days 47, 48, and 49 PI for adult stage; (III) treated with a single oral dose of Art (300 mg/kg) either after 28 or 49 days PI, respectively; and (IV) received both haemin, as group (II) and Art as group (III). Half of mice for each batch were killed 72 h; meanwhile, the remaining half was killed 3 weeks after Art administration. Parasitological criteria of cure and worms' antioxidant enzymes were assessed. Glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), and superoxide dismutase (SOD) activities were lower in juvenile worms than adult ones and in females than males. Haemin plus Art at the juvenile and adult stages produced significant inhibition in worms' GST, GPx, and SOD activities 72 h after Art treatment, compared with Art-treated group, with enhanced killing of females (96.98 and 91.47 % versus 87.04 and 72.97 %, respectively) and total worms (91 and 83.39 % versus 75 and 59.01 %, respectively) 3 weeks posttreatment. In conclusion, Art plus haeminhas a higher harmful effect on juvenile and adult schistosomes and antioxidant capacity than Art alone. This gives new insights into the importance ofhaemin in the antischistosomal properties of artemether....(more)
El-Lakkany NM, et al. Parasitol Res 2013 May;112(5):2005-15.
Related Products: Artemether
- 23. Comparative evaluation of efficacy and safety of artesunate-lumefantrine vs. artemether-lumefantrine fixed-dose combination in the treatment of uncomplicated Plasmodium falciparum malaria.
OBJECTIVE:
To establish efficacy and safety of artesunate/lumefantrine fixed-dose combination (FDC) in comparison with artemether/lumefantrine FDC in treatment of uncomplicated Plasmodium falciparum malaria.
METHODS:
Confirmed cases of uncomplicated P. falciparum malaria were randomly assigned to receive artesunate (100 mg)/lumefantrine (480 mg) (ASLF FDC) or artemether (80 mg)/lumefantrine (480 mg) (AMLF FDC) tablets for 3 days. Patients were followed up on Day 7, 14, 21 and 28.
RESULTS:
Of the 158 enrolled patients, 144 completed the study. Seventy-three patients (94.8%) from the ASLF group and 71 patients (94.7%) from the AMLF group showed parasite clearance within 48 h. The mean parasite clearance time was 25.40 ± 14.82 h in the ASLF group and 24 ± 13.32 h in the AMLF group (P = 0.542). All patients showed gametocyte clearance by Day 7 and remained gametocyte free till Day 28. Sixty-five patients (84.4%) from the ASLF group and 56 patients (74.7%) from the AMLF group were afebrile within 24 h. The mean fever clearance time was 17.38 ± 12.33 h in the ASLF group and 17.2 ± 12.01 h in the AMLF group (P = 0.929). There was one early treatment failure in the AMLF group as per WHO criteria. Improvement in haemoglobin and haematocrit was comparable in both the treatment groups. In the ASLF group, of the 25 (32.47%) patients anaemic at baseline, only seven (9.09%) reported anaemia on Day 28, while in the AMLF group, of the 14 (18.67%) patients anaemic at baseline, only four (5.33%) reported anaemia on Day 28. Both study medications were well tolerated.
CONCLUSION:
Artesunate (100 mg)/lumefantrine (480 mg) fixed-dose combination could add one more option to currently available artemisinin combinations in treatment of uncomplicated P. falciparum malaria.
© 2013 Blackwell Publishing Ltd....(more)
Pareek A, et al. Trop Med Int Health 2013 May;18(5):578-87.
Related Products: Artemether
- 24. Neurotoxicity assessment of artemether in juvenile rats.
BACKGROUND:
Oral administration of artemether in combination with lumefantrine is approved for the treatment of malaria in adults and children. In adult animals, artemether can produce neurotoxicity with intramuscular, but not oral, administration. Herein, the potential of orally administered artemether to produce neurotoxicity in juvenile rats was investigated.
METHODS:
In the first study, the toxicity of artemether was evaluated in juvenile rats dosed with 0, 10, 30, and 100mg/kg/day on postpartum days (ppds) 7 to 21. In-life, clinical pathology, anatomic pathology, behavioral, and toxicokinetics evaluations were performed. The second study focused on neurotoxicity during different dosing intervals, with doses of 0, 30, and 80mg/kg/day on ppds 7 to 13, and doses of 0, 30, and 120mg/kg/day on ppds 14 to 21, 22 to 28, and 29 to 36. For each dosing interval, in-life, extensive histology, toxicokinetics, and behavioral evaluations were performed. In the third study, toxicokinetics evaluations in the adult were conducted at 20 and 200mg/kg/day.
RESULTS:
The first study demonstrated increased mortality, renal necrosis, and brain hemorrhage at ≥30mg/kg/day with no persistent effects in surviving animals. In the second study, increased mortality, body weight effects, and a trend toward increased exposure were observed in the ppd 14 and younger animals. Neither specific neurotoxicity nor persistent effects were seen. The toxicokinetic study in adults revealed lower exposures as compared to those in the younger juvenile rats.
CONCLUSIONS:
As in the adult rat, oral administration of artemether in the juvenile rat is not associated with the neurotoxicity produced by intramuscular administration.
© 2013 Wiley Periodicals, Inc....(more)
Beckman DA, et al. Birth Defects Res B Dev Reprod Toxicol 2013 Apr;98(2):183-99.
Related Products: Artemether
- 25. Appropriateness of prescribing in selected healthcare facilities in Papua New Guinea.
OBJECTIVE The objective of this study was to evaluate the level of appropriateness of prescribing to outpatients in selected healthcare facilities in Papua New Guinea (PNG), using health department guidelines as the benchmark. METHODS A prospective study was carried out at Losuia Health Centre (LHC), Alotau Provincial Hospital (APH) and Port Moresby General Hospital (PMGH) in PNG. At each setting >300 consecutive prescriptions were evaluated in 2010. Diagnosis and prescribing data were collected from written prescription orders, patient health books and by patient interview. The appropriateness of prescribing was evaluated with respect to the relevant PNG Health Department guidelines. Differences in prescribing indices were evaluated using chi-squared tests as appropriate. RESULTS There were 1090 patients (748 adults; 341 children) enrolled in the study with 356 at LHC, 318 at APH and 416 at PMGH. A total of 2495 medicines were prescribed. The most common were amoxicillins (355), paracetamol (344), artemether/artesunate (186) and chloroquine (162). The average number of drugs prescribed per patient was 2.3 (range: 1-7). The most common diseases treated were malaria (23.2%), acute soft tissue injuries (10.4%), anaemia (8.9%), respiratory problems (8.7%) and cough (5.9%). Overall, inappropriate prescribing was 33.4% in adults and 39.9% in children, the difference mainly arising from inappropriate drug dosage. There were statistically significant differences observed for the level of inappropriate prescribing by prescriber category on drug selection (P < 0.0001), drug dosage (P < 0.0001) and drug duration (P < 0.0001). CONCLUSION The level of inappropriate prescribing was as high as 53.8% in the selected locations in PNG, which is of great concern with respect to the quality of PNG healthcare delivery. Appropriate interventions such as review/upgrade of the guidelines, supervision/oversight of compliance to guidelines and/or publication of ongoing supervision/audit oversight reports need to occur to address the underlying causes....(more)
Joshua IB, et al. Health Policy Plan 2013 Mar 14.
Related Products: Artemether
- 26. Temporal trends of molecular markers associated with artemether-lumefantrine tolerance/resistance in Bagamoyo district, Tanzania.
BACKGROUND:
Development and spread of Plasmodium falciparum resistance to artemisinin-based combination therapy (ACT) constitutes a major threat to recent global malaria control achievements. Surveillance of molecular markers could act as an early warning system of ACT-resistance before clinical treatment failures are apparent. The aim of this study was to analyse temporal trends of established genotypes associated with artemether-lumefantrine tolerance/resistance before and after its deployment as first-line treatment for uncomplicated malaria in Tanzania 2006.
METHODS:
Single nucleotide polymorphisms in the P. falciparum multidrug resistance gene 1 (pfmdr1) N86Y, Y184F, D1246Y and P. falciparum chloroquine transporter gene (pfcrt) K76T were analysed from dried blood spots collected during six consecutive studies from children with uncomplicated P. falciparum malaria in Fukayosi village, Bagamoyo District, Tanzania, between 2004-2011.
RESULTS:
There was a statistically significant yearly increase of pfmdr1 N86, 184F, D1246 and pfcrt K76 between 2006-2011 from 14% to 61% (yearly OR = 1.38 [95% CI 1.25-1.52] p < 0.0001), 14% to 35% (OR = 1.17 [95% CI 1.07-1.30] p = 0.001), 54% to 85% (OR = 1.21 [95% CI 1.03-1.42] p = 0.016) and 49% to 85% (OR = 1.33 [95% CI 1.17-1.51] p < 0.0001), respectively. Unlike for the pfmdr1 SNP, a significant increase of pfcrt K76 was observed already between 2004-2006, from 26% to 49% (OR = 1.68 [95% CI 1.17-2.40] p = 0.005). From 2006 to 2011 the pfmdr1 NFD haplotype increased from 10% to 37% (OR = 1.25 [95% CI 1.12-1.39] p < 0.0001), whereas the YYY haplotype decreased from 31% to 6% (OR = 0.73 [95% CI 0.56-0.98] p = 0.018). All 390 successfully analysed samples had one copy of the pfmdr1 gene.
CONCLUSION:
The temporal selection of molecular markers associated with artemether-lumefantrine tolerance/resistance may represent an early warning sign of impaired future drug efficacy. This calls for stringent surveillance of artemether-lumefantrine efficacy in Tanzania and emphasizes the importance of molecular surveillance as a complement to standard in vivo trials....(more)
Malmberg M, et al. Malar J 2013 Mar 18;12:103.
Related Products: Artemether
- 27. The evaluation of CYP2B6 inhibition by artemisinin antimalarials in recombinant enzymes and human liver microsomes.
Artemisinin-based combination therapy (ACT) is the recommended treatment of uncomplicated P.falciparum malaria by the World Health Organisation (WHO). Some artemisinin compounds and anti-retroviral drugs have been shown to be metabolized by CYP2B6. In the African clinical settings, the likelihood of co-administration of ACTs and antiretroviral drugs is higher than elsewhere, posing the risk of drug-drug interactions (DDIs). This study aimed to investigate whether artemisinin compounds inhibit CYP2B6 activity in vitro using recombinant CYP2B6 (rCYP2B6) and human liver microsomes (HLM). Values for IC50 and Ki were determined by kinetic analyses using non-linear regression. In vitro to in vivo extrapolations of the likelihood of DDIs where done using a static [I]/Ki approach. Artemisinin and artemether were shown to inhibit CYP2B6 in vitro through a partial mixed type of inhibition, while dihydroartemisinin did not inhibit the enzymatic activity. IC50 values for artemisinin were 9.5 and 9.1 µM for rCYP2B6 and HLM, respectively, after 30 min of incubation. Corresponding values for artemether were 7.5 and 5.4 µM. Artemisinin did not show any time-dependency or requirement of NADPH in its mechanism, indicating a reversible mode of inhibition. Based on the [I]/Ki approach using rCYP2B6, the risk of DDIs for artemisinin was indicated to be medium to high, while artemether had a low risk. The findings indicate a potential but moderate risk of DDIs in the co-administration of artemisinin or artemether with efavirenz in the co-treatment of malaria and HIV/AIDS....(more)
Ericsson T, et al. Drug Metab Lett 2013 Mar 18.
Related Products: Artemether
- 28. Study protocol for a randomised controlled double-blinded trial of the dose-dependent efficacy and safety of primaquine for clearance of gametocytes in children with uncomplicated falciparum malaria in Uganda.
OBJECTIVES:
For the purpose of blocking transmission of Plasmodium falciparum malaria from humans to mosquitoes, a single dose of primaquine is recommended by the WHO as an addition to artemisinin combination therapy. Primaquine clears gametocytes but causes dose-dependent haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Evidence is needed to inform the optimal dosing of primaquine for malaria elimination programmes and for the purpose of interrupting the spread of artemisinin-resistant malaria. This study investigates the efficacy and safety of reducing doses of primaquine for clearance of gametocytes in participants with normal G6PD status.
METHODS AND ANALYSIS:
In this prospective, four-armed randomised placebo-controlled double-blinded trial, children aged 1-10 years, weighing over 10 kg, with haemoglobin ≥8 g/dl and uncomplicated P falciparum malaria are treated with artemether lumefantrine and randomised to receive a dose of primaquine (0.1, 0.4 or 0.75 mg base/kg) or placebo on the third day of treatment. Participants are followed up for 28 days. Gametocytaemia is measured by quantitative nucleic acid sequence-based analysis on days 0, 2, 3, 7, 10 and 14 with a primary endpoint of the number of days to gametocyte clearance in each treatment arm and secondarily the area under the curve of gametocyte density over time. Analysis is for non-inferiority of efficacy compared to the reference dose, 0.75 mg base/kg. Safety is assessed by pair-wise comparisons of the arithmetic mean (±SD) change in haemoglobin concentration per treatment arm and analysed for superiority to placebo and incidence of adverse events. Ethics and dissemination Approval was obtained from the ethical committees of Makerere University School of Medicine, the Ugandan National Council of Science and Technology and the London School of Hygiene and Tropical Medicine.
RESULTS:
These will be disseminated to inform malaria elimination policy, through peer-reviewed publication and academic presentations....(more)
Eziefula AC, et al. BMJ Open 2013 Mar 26;3(3).
Related Products: Artemether
- 29. Haemolytic anaemia after oral artemether-lumefantrine treatment in a patient affected by severe imported falciparum malaria.
Artemisinin and its derivatives are essential components of artemisinin-based combination therapies for treating severe falciparum malaria. In this paper, we describe the occurrence of haemolysis after oral artemether-lumefantrine treatment. To the best of our knowledge, this is the second reported case of a patient affected by severe falciparum malaria with haemolytic anaemia that is likely associated with oral artemether-lumefantrine treatment....(more)
De Nardo P, et al. Infection 2013 Apr 4.
Related Products: Artemether
- 30. Reversible audiometric threshold changes in children with uncomplicated malaria.
Background. Plasmodium falciparum malaria, as well as certain antimalarial drugs, is associated with hearing impairment in adults. There is little information, however, on the extent, if any, of this effect in children, and the evidence linking artemisinin combination therapies (ACTs) with hearing is inconclusive. Methods. Audiometry was conducted in children with uncomplicated malaria treated with artesunate-amodiaquine (n = 37), artemether-lumefantrine (n = 35), or amodiaquine (n = 8) in Accra, Ghana. Audiometry was repeated 3, 7, and 28 days later and after 9 months. Audiometric thresholds were compared with those of a control group of children (n = 57) from the same area. Findings. During the acute stage, hearing threshold levels of treated children were significantly elevated compared with controls (P < 0.001). The threshold elevations persisted up to 28 days, but no differences in hearing thresholds were evident between treated children and controls after 9 months. The hearing thresholds of children treated with the two ACT regimens were comparable but lower than those of amodiaquine-treated children during acute illness. Interpretation. Malaria is the likely cause of the elevated hearing threshold levels during the acute illness, a finding that has implications for learning and development in areas of intense transmission, as well as for evaluating potential ototoxicity of new antimalarial drugs....(more)
Adjei GO, et al. J Trop Med 2013;2013:360540.
Related Products: Artemether
- 31. Field evaluation of HRP2 and pan pLDH-based immunochromatographic assay in therapeutic monitoring of uncomplicated falciparum malaria in Myanmar.
BACKGROUND:
Malaria rapid diagnostic tests (RDT) are used for diagnostic purpose in malaria-endemic areas where reliable microscopy is not available. Persistence of the antigenaemia causes over-diagnosis and may limit the usefulness of the RDT in monitoring treatment. In this study, the usefulness of histidine-rich protein-2 (HRP2) and pan-specific or species-specific Plasmodium lactate dehydrogenase (pLDH) in treatment monitoring of uncomplicated falciparum malaria was carried out in an endemic setting in Myanmar.
METHODS:
A prospective longitudinal, single-arm, cohort study was done by microscopy to confirm Plasmodium falciparum mono-infected cases. After direct treatment with an artemether-lumefantrine combination, patients were followed up on day 3, 7, 14, 21, 28 and any other day of recurrent fever. Blood film examination and RDT were carried out on day 0 and all follow-up days.
RESULTS:
Out of 77 recruited falciparum cases, 63 became adequate clinical and parasitological response (ACPR) cases, and 60.3% of them were still positive for HRP2 up to day 28. Eleven out of 12 treatment failure cases (91.6%) were detected by pan pLDH. The mean duration required to become negative of HRP2 was 20 days (SD +/- 6.03) and that of pan pLDH was six days with or without gametocytes and 3.7 days without gametocytes.
CONCLUSION:
Although treatment monitoring cannot be performed by HRP2, it can be assessed by pan pLDH-based assay after day 3 if a gametocidal drug has been administered and after day 7 if the presence of gametocytes was not excluded. The pan pLDH-based assay was a suitable test to monitor the treatment response of uncomplicated falciparum malaria patients....(more)
Nyunt MH, et al. Malar J 2013 Apr 11;12(1):123.
Related Products: Artemether
- 32. The metabolite chemotype of Nicotiana benthamiana transiently expressing artemisinin biosynthetic pathway genes is a function of CYP71AV1 type and relative gene dosage.
Artemisia annua, which produces the anti-malaria compound artemisinin, occurs as high-artemisinin production (HAP) and low-artemisinin production (LAP) chemotypes. Understanding the basis of the difference between these chemotypes would assist breeding and optimising artemisinin biosynthesis. Here we present a systematic comparison of artemisinin biosynthesis genes that may be involved in determining the chemotype (CYP71AV1, DBR2 and ALDH1). These genes were isolated from the two chemotypes and characterized using transient expression in planta. The enzyme activity of DBR2 and ALDH1 from the two chemotypes did not differ, but structural differences in CYP71AV1 from LAP and HAP chemotypes (AMOLAP and AMOHAP, respectively) resulted in altered enzyme activity. AMOLAP displays a seven amino acids N-terminal extension compared with AMOHAP. The GFP fusion of both proteins show equal localization to the ER but AMOHAP may have reduced stability. Upon transient expression in Nicotiana benthamiana, AMOLAP displayed a higher enzyme activity than AMOHAP. However, expression in combination with the other pathway genes also resulted in a qualitatively different product profile ('chemotype'); that is, in a shift in the ratio between the unsaturated and saturated (dihydro) branch of the pathway.
© 2013 The Authors. New Phytologist © 2013 New Phytologist Trust....(more)
Ting HM, et al. New Phytol 2013 May 2.
Related Products: Artemisia Annua Extract
- 33. Dihydroartemisinin suppresses ovalbumin-induced airway inflammation in a mouse allergic asthma model.
Abstract Asthma is a complex disease characterized by reversible airway obstruction, airway hyper-responsiveness (AHR) and chronic inflammation of the airways. Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin isolated from the traditional Chinese herb Artemisia annua, has been shown to possess antimalarial and antitumor activities, but whether it can be used in asthma treatment has not been investigated. In this study, we attempted to determine whether DHA regulates inflammatory mediators in the ovalbumin (OVA)-induced mouse asthma model. BALB/c mice were sensitized and challenged by OVA to induce chronic airway inflammation. The intragastrical administration of DHA at 30 mg/kg significantly decreased the number of infiltrating inflammatory cells, T-helper type 2 (Th2) cytokines, OVA-specific immunoglobulin E (IgE) and AHR. Treatment with DHA also attenuated OVA-induced mRNA expression of Muc5ac and chitinase 3-like protein 4 (Ym2) in lung tissues. In addition, lung histopathological studies revealed that DHA inhibited inflammatory cell infiltration and mucus hypersecretion. Then signal transduction studies showed that DHA significantly inhibited extracellular signal-regulated protein kinase (ERK), p38 mitogen-activated protein kinase phosphorylation. DHA also inhibited nuclear factor-κB (NF-κB) activation via the inhibition of phosphorylation of IκBα. These findings provide new insight into the immunopharmacological role of DHA in terms of its effects in a mouse model of asthma....(more)
Wei M, et al. Immunopharmacol Immunotoxicol 2013 May 1.
Related Products: Artemisia Annua Extract
- 34. The Use of Combining Ability Analysis to Identify Elite Parents for Artemisia annua F1 Hybrid Production.
Artemisia annua is an important medicinal crop used for the production of the anti-malarial compound artemisinin. In order to assist in the production of affordable high quality artemisinin we have carried out an A. annua breeding programme aimed at improving artemisinin concentration and biomass. Here we report on a combining ability analysis of a diallel cross to identify robust parental lines for hybrid breeding. The parental lines were selected based on a range of phenotypic traits to encourage heterosis. The general combining ability (GCA) values for the diallel parental lines correlated to the positive alleles of quantitative trait loci (QTL) in the same parents indicating the presence of beneficial alleles that contribute to parental performance. Hybrids generated from crossing specific parental lines with good GCA were identified as having an increase in both artemisinin concentration and biomass when grown either in glasshouse or experimental field trials and compared to controls. This study demonstrates that combining ability as determined by a diallel cross can be used to identify elite parents for the production of improved A. annua hybrids. Furthermore, the selection of material for breeding using this approach was found to be consistent with our QTL-based molecular breeding approach....(more)
Townsend T, et al. PLoS One 2013 Apr 23;8(4):e61989.
Related Products: Artemisia Annua Extract
- 35. Toxic essential oils. Part II: Chemical, toxicological, pharmacological and microbiological profiles of Artemisia annua L. volatiles.
Botanical drugs based on Artemisia annua L. (Asteraceae) are important in the treatment of malaria. Alongside with artemisinin, this aromatic species produces high and variable amounts of other chemicals that have mostly unknown biological/pharmacological activities. Herein, we have studied the toxicological/pharmacological profile of volatile constituents of a Serbian population of A. annua. Fifty-eight components were identified, among them, artemisia ketone (35.7%), α-pinene (16.5%) and 1,8-cineole (5.5%) were the most abundant ones. Significant variability of A. annua volatile profile was confirmed by means of agglomerative hierarchical cluster analysis indicating the existence of several different A. annua chemotypes. In an attempt to connect the chemical profile of A. annua oil with its biological/toxicological effects, we have evaluated in vivo and/or in vitro toxicity (including hepato- and nephrotoxicity/protection), antinociceptive, antioxidant (DPPH, ABTS and superoxide radical scavenging activity assays), enzyme inhibiting (protein kinase A and α-amylase) and antimicrobial potential of A. annua oil and of its constituents. Our results revealed that the beneficial properties of A. annua botanical drugs are not limited only to their antimalarial properties. Taking into account its relatively low toxicity, the usage of A. annua volatiles (at least of the herein studied population) does not represent a health risk.
Copyright © 2013 Elsevier Ltd. All rights reserved....(more)
Radulovi? NS, et al. Food Chem Toxicol 2013 Apr 20.
Related Products: Artemisia Annua Extract