Inhibitory effects of 2'-hydroxychalcones on rat lens aldose reductase and rat platelet aggregation

Inhibitory effects of synthetic 2'-hydroxychalcone derivatives on rat lens aldose reductase (RLAR) and on platelet aggregation were investigated for the prevention or the treatment of chronic diabetic complications. 5'-chloro-4,2'-dihydroxychalcone (8) and 5'-chloro-3,2'-dihydroxychalcone (27) exhibited a potent inhibitory effect on rat platelet aggregation induced by ADP (IC50=0.10 and 0.06 mg/ml, respectively) and collagen (IC50=44 and 16 microg/ml, respectively) but showed relatively weak inhibitory activities on RLAR.     

Water leaves extracts of <Emphasis Type="Italic">Cornus mas</Emphasis> and <Emphasis Type="Italic">Cornus kousa</Emphasis> as aldose reductase inhibitors: the potential therapeutic agents

The Cornaceae family is mainly known for the research connected with its fruits and flowers, but the biological activities of leaves of Cornus species are not very intensively studied. Present work is focused on inhibition of rat lens aldose reductase, cytotoxicity, and study of oxidant efficacy on NIH-3T3 cells of the water extracts of the leaves of Cornus mas and Cornus kousa. The obtained results showed effective inhibition of isolated rat lens aldose reductase in low µg/mL level, antioxidant properties at lower concentration (50 µg/mL), and slight prooxidant properties at higher concentration (100 µg/mL). The prooxidant properties could contribute to cytotoxicity when the cells incubated with the extracts of concentration 100 µg/mL reduced 10% of MTT of control cells. The biological activities of two Cornus species were quite similar in all our tests. Low concentrations of both water leaves extracts could be perspective agents for potential treatment of chronic diabetic complications, inflammation, and another diseases connected with aldose reductase enzyme.     

Delaying of cataract through intervention of Hemidesmus indicus in STZ induced diabetic rats

Hemidesmus indicus (L.) R. Br. was extensively used as hypoglycaemic agent and significance of this plant on secondary complications of diabetes remained unknown. The present study was to investigate the anti-cataractous activity of H. indicus against streptozotocin (STZ)-induced diabetic cataract in rodent model. Root extracts have been prepared and tested for inhibition of rat lens aldose reductase (AR) activity. In addition, its pharmacological potential has been investigated in STZ-induced diabetic cataract. Methanol extract of H. indicus-inhibited AR activity in vitro decreased the blood glucose levels, inhibited the AR activity and delayed the onset and progression of cataract in a dose-dependent manner in in vivo and the antioxidant markers have been normalised. Our results demonstrate that H. indicus has decrease the osmotic stress by inhibiting the AR activity and prevented the loss of antioxidants and delayed the progression of diabetic cataract in STZ-induced diabetic rats.     

Comparative analysis of phytochemical profile,antioxidant and anti-inflammatory activity from Hibiscus manihot L. flower

Hibiscus manihot L. is a kind of healthy plant with edible value and health benefits, which possesses multiple pharmacological activities that are closely related to antioxidant and anti-inflammatory activities. The dynamic changes of main active components and biological activities in Hibiscus manihot L. flower (HMLF) during its flowering period were systematically studied to determine the appropriate harvest time. Chemopreventive efficacies of the investigated HMLF extracts, by means of their anti-inflammatory and antioxidant activities, were assessed. The sample harvested on early August had the supreme total flavonoid content, total phenolic content and the strongest antioxidant activity (DPPH radical scavenging activity (IC₅₀ 0.160 mg/mL), ABTS radical scavenging activity (1.570 mmol/g Trolox), reducing power (IC₅₀ 0.101 mg/mL) and FRAP (3.644 mmol FeSO₄/g)). The results of principal component analysis indicated that the primary active components included hyperin, isoquercetin, hibifolin and quercetin-3′-O-glucoside, which were strongly associated with the antioxidant activity in the early August sample, while neochlorogenic acid, chlorogenic acid and caffeic acid were associated with the anti-inflammatory activity. The extracts significantly inhibited lipopolysaccharide-induced nitric oxide production in RAW264.7 cells, especially the samples harvested around August, which was only 3.569 μΜ with the inhibition ratio of>50%. This study indicated that HMLF harvested on the early August possessed the highest antioxidant and anti-inflammatory potential and could be used as high bioactive resources for healthy production.     

Studies on aldose reductase inhibitors from natural products. IV. Constituents and aldose reductase inhibitory effect of Chrysanthemum morifolium, Bixa orellana and Ipomoea batatas.

The hot water extracts of Chrysanthemum morifolium, Bixa orellana and Ipomoea batatas, were found to have potent inhibitory activity towards lens aldose reductase (AR). Ellagic acid (4) was isolated from C. morifolium and I. batatas, isoscutellarein (7) from B. orellana and 3,5-dicaffeoylquinic acid (10) from I. batatas, respectively, as potent inhibitors.     

Synthesis and activity of a new series of (Z)-3-phenyl-2-benzoylpropenoic acid derivatives as aldose reductase inhibitors

During the course of studies directed towards the discovery of novel aldose reductase inhibitors for the treatment of diabetic complications, we synthesized a series of new (Z)-3-phenyl-2-benzoylpropenoic acid derivatives and tested their in vitro inhibitory activities on rat lens aldose reductase. Of these compounds, (Z)-3-(3,4-dihydroxyphenyl)-2-(4-methylbenzoyl)propenoicacid (3k) was identified as the most potent inhibitor, with an IC50 of 0.49 microM. The theoretical binding mode of 3k was obtained by simulation of its docking into the active site of the human aldose reductase crystal structure.     

Antimicrobial,DPPH scavenging and tyrosinase inhibitory activities of Thymus vulgaris,Helichrysum arenarium and Rosa damascena mill. ethanol extracts by using TLC bioautography and chemical screening methods

Antimicrobial, DPPH scavenging and tyrosinase inhibitory activities of Thymus vulgaris, Helichrysum arenarium and Rosa damascena Mill. ethanol extracts by using TLC bioautography and chemical screening methods. The ethanol extracts of Thymus vulgaris (Tv), Helichrysum arenarium (Ha) and Rosa damascena Mill. (Rm) (red) were screened for their antimicrobial, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and tyrosinase inhibitory activities. The test microorganisms included bacteria of Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 25923). Thin Layer Chromatography (TLC) - bioautography, disk diffusion and well diffusion methods were used for the antimicrobial activity assays. Rosa damascena Mill. extract was effective against E. coli and all plant extracts showed antimicrobial activity against S. aureus. The phenolic acids in the structure of the extracts were also identified by LC-MS analysis. Human blood agar well diffusion method and TLC-DPPH assays were used to identify the hemolytic and antioxidant activity of plant extracts, respectively, along with 10 compounds including phenolic acids as a standard. Among these compounds, caffeic acid (Rf = 0.68) was detected in all extracts while vanillic acid (Rf = 0.75), and gallic acid (Rf = 0.51) was found in Tv extract. Kojic acid (Rf = 0.36), on the other hand, was detected in Rm extract as a tyrosinase inhibitor. All plant extracts presented tyrosinase inhibitory activities on TLC-bioautography assay.     

Structural requirements of flavonoids and related compounds for aldose reductase inhibitory activity

The methanolic extracts of several natural medicines and medicinal foodstuffs were found to show an inhibitory effect on rat lens aldose reductase. In most cases, flavonoids were isolated as the active constituents by bioassay-guided separation, and among them, quercitrin (IC(50)=0.15 microM), guaijaverin (0.18 microM), and desmanthin-1 (0.082 microM) exhibited potent inhibitory activity. Desmanthin-1 showed the most potent activity, which was equivalent to that of a commercial synthetic aldose reductase inhibitor, epalrestat (0.072 microM). In order to clarify the structural requirements of flavonoids for aldose reductase inhibitory activity, various flavonoids and related compounds were examined. The results suggested the following structural requirements of flavonoid: 1) the flavones and flavonols having the 7-hydroxyl and/or catechol moiety at the B ring (the 3',4'-dihydroxyl moiety) exhibit the strong activity; 2) the 5-hydroxyl moiety does not affect the activity; 3) the 3-hydroxyl and 7-O-glucosyl moieties reduce the activity; 4) the 2-3 double bond enhances the activity; 5) the flavones and flavonols having the catechol moiety at the B ring exhibit stronger activity than those having the pyrogallol moiety (the 3',4',5'-trihydroxyl moiety).     

Flavonoids from <Emphasis Type="Italic">Cirsium japonicum</Emphasis> var. <Emphasis Type="Italic">maackii</Emphasis> pappus as inhibitors of aldose reductase and their simultaneous determination

Aldose reductase is an enzyme in the polyol pathway which is associated in the progression of diabetic complications. In this study, we evaluated the inhibitory activity of Cirsium japonicum var. maackii pappus (CJP) against rat lens aldose reductase (RLAR). The ethanolic extract, fractions and isolated flavonoids were subjected to an RLAR assay. Isolation of chloroform (CHCl₃) and ethyl acetate (EtOAc) fractions led to the identification of four flavonoids: hispidulin (1), cirsimaritin (2), apigenin (3), and cirsimarin (4). The RLAR assay results suggested that the EtOAc fraction and flavonoids 1 and 3 promoted better AR inhibition than did TMG (control). The half-maximal inhibitory concentration (IC₅₀) of compounds 1 and 3 was 0.77 and 3.19 μM, respectively. A simultaneous determination of flavonoid content using HPLC–UV indicated that CJP contained large amounts of compounds 2 and 3 (1.65 and 1.84 mg/g, respectively). Flavonoids from Cirsium species have been widely reported to show various pharmacological activities. This study indicated that CJP has the potential to prevent diabetic complications and was a potential source of flavonoids.     

Bioactive constituents from Chinese natural medicines. XV. Inhibitory effect on aldose reductase and structures of Saussureosides A and B from Saussurea medusa

The 80% aqueous acetone extract from the whole plant of Saussurea medusa MAXIM. was found to inhibit rat lens aldose reductase (IC50=1.4 microg/ml). From this extract, flavonoids, lignans, and quinic acid derivatives were isolated together with two new ionone glycosides, saussureosides A and B. Their absolute stereostructures were elucidated on the basis of chemical and physicochemical evidence including the application of modified Mosher's method. In addition, some isolates were found to show an inhibitory effect on aldose reductase.     

Changes in antioxidant metabolism of Vigna unguiculata (L.) Walp. by propiconazole under water deficit stress

In the present study, a pot culture experiment was conducted to estimate the ameliorating effect of propiconazole (PCZ) on drought stress in cowpea (Vigna unguiculata (L.) Walp.) plants. From 30 days after sowing (DAS), the plants were subjected to 3, 6 and 9 days interval drought (DID) stress and drought stress with PCZ at 15 and 15 mg l(-1) PCZ alone and 1 day interval irrigation was kept as control. The plant samples were collected on 34 DAS (3 DID), 37 DAS (6 DID) and 40 DAS (9 DID). The plants were separated into root, stem and leaf for estimating the antioxidant contents and activities of antioxidant enzymes. Individual and combined drought stress and PCZ treatments increased ascorbic acid (AA), alpha-tocopherol (alpha-toc) contents, superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT) and polyphenol oxidase (PPO) activities when compared to control. The PCZ treatment mitigated the adverse effects of drought stress by increasing the antioxidant potentials and thereby paved the way for overcoming drought stress in V. unguiculata plants.     

Antioxidant activities of extracts and fractions from Eupatorium lindleyanum DC

The antioxidant activities of water extract (WE), ethanol extract (EE), residue water extract (RWE) and petroleum ether (PF), ethyl acetate (EF), n-BuOH (BF) and water (WF) fractions of the ethanol extract from Eupatorium Lindley DC were investigated for the first time. Total phenolics content, DPPH radical scavenging activities, superoxide radical scavenging activities, total reduction capability, and ferrous ions chelating activities were determined for all the extracts and fractions. The results showed that all the extracts and fractions exhibited antioxidant activities with different magnitudes of potency. Among all the samples, WE and RWE exhibited the best antioxidant capacities, the BF also exhibited high antioxidant abilities in all tests except for the metal chelating activity, while the other extracts and fractions were relatively weak antioxidants. The BF had the highest total phenolics contents in all extracts and fractions, and the WE and RWE were found to be rich in tannins. Furthermore, the content of total phenolics showed good correlation with DPPH radical scavenging activity, superoxide anion radical scavenging activity, and the reducing power. Phenolic composition of all the extracts and fractions was identified and quantified by HPLC. The results indicate that the extracts of E. Lindley DC might be a useful potential source of natural antioxidant ingredients.     

Antimicrobial and antioxidant activities of the methanolic extracts of three Salvia species from Tunisia

This study examines the in vitro antimicrobial and antioxidant activities of the methanolic extracts of three Salvia species from Tunisia: Salvia aegyptiaca L., S. argentea L. and S. verbenaca Ssp. clandestina L. Pugsley. The extracts inhibited the growth of dermatophytes and of bacteria responsible for unpleasant odours to varying degrees; the pathogenic yeasts Candida albicans and Cryptococcus neoformans, the filamentous fungi Aspergillus fumigatus and selected dog otitis bacteria were all resistant to each of the extracts. The extracts were screened for their antioxidant activities using 2,2-diphenyl-1-picrylhydrazyl free radical scavenging and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) test systems, and gave positive results in both tests. The extracts of S. aegyptiaca were the most active in both tests, followed by those of S. verbenaca, then S. argentea. These results confirm the antimicrobial and antioxidant activities of the genus Salvia and underline the potential of these plants either as natural preservatives or in pharmaceutical applications.     

Comparison of fatty acid profile and antioxidant potential of extracts of seven Citrus rootstock seeds

The extracts of seven Citrus rootstock seeds have been compared regarding fatty acid profile and antioxidant potential. Sour orange (Citrus aurantium L.) was found to contain the highest oil amount (34%), while the Poncirus trifoliata cultivars contained the highest percentage of unsaturated fatty acids (84-87%). In addition, the antioxidant properties of the extracts from defatted seeds have been evaluated by measuring their radical scavenging activity against 2,2'-diphenyl-1-picrylhydrazyl. The highest antioxidant activities were observed in the case of the acetone extract of sour orange and Citrumelo Swingle (76% and 75%, respectively), at a concentration of 0.17?mg?mL(-1). Moreover, the total phenolic content of the extracts, determined using the Folin-Ciocalteau reagent, was found to be correlated with the radical scavenging activity results. The acetone extracts of sour orange and Citrumelo Swingle exhibited the highest phenolic content [112.3 and 103.4?mg gallic acid equivalent?g(-1) dry sample weight, respectively].     

Comparative analysis of radical scavenging and antioxidant activity of phenolic compounds present in everyday use spice plants by means of spectrophotometric and chromatographic methods

Comparative analysis of radical scavenging and antioxidant activities of phenolic compounds present in everyday use spice plants was carried out by means of spectrophotometric and chromatographic methods. Six spice plant samples, namely onion (Allium cepa), parsley (Petroselinum crispum) roots and leaves, celery (Apium graveolens) roots and leaves and leaves of dill (Anethum graveolens) were analyzed. Total amount of phenolic compounds and radical scavenging activity (RSA) was the highest in celery leaves and dill extracts and was the lowest in celery roots. Comparing commonly used spectrophotometric analysis of 2,2-diphenyl-1-picrylhydrazyl (DPPH) RSA of extracts with the results obtained using reversed-phase chromatographic separation with on-line post-column radical scavenging reaction detection, good correlation was obtained (R(2)=0.848). Studies using HPLC system with electrochemical detector showed that bioactive phytochemicals can be separated and antioxidant activities of individual compounds evaluated without the need of a complex HPLC system with reaction detector. The results obtained using electrochemical detection correlate with the RSA assayed using spectrophotometric method (R(2)=0.893).     

Antioxidant activity of extracts from Euryale ferox seed

Euryale ferox has been widely used in traditional oriental medicine to treat a variety of illness. However, very little is known about the cellular actions by which this plant mediates its therapeutic effects. Various aspects of antioxidant activity were evaluated in total extracts and fractions derived from Euryale ferox. Total extracts (IC50 5.6 microg/ml) showed relatively high level radical scavenging activity toward 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and also enhanced viability of Chinese hamster lung fibroblast (V79-4) cells under exposure to oxidative agents. Upon further fractionation, the highest levels of DPPH radical scavenging and lipid peroxidation inhibitory activities were found in the ethyl acetate and butanol fractions. The ethyl acetate fractions, the butanol fractions, and total extracts of Euryale ferox also dose-dependently enhanced the activities of superoxide dismutase, catalase and glutathione peroxidase in V79-4 cells. Of these three antioxidant enzymes, glutathione peroxidase activity was most strongly induced. Taken together, our findings show that Euryale ferox contains a significant antioxidant activity and that specific components in the ethyl acetate and butanol fractions may play an important role in mediating these antioxidant properties.     

In Vitro Antidiabetic and Antioxidant Effects of Different Extracts of Catharanthus roseus and Its Indole Alkaloid,Vindoline

The Catharanthus roseus plant has been used traditionally to treat diabetes mellitus. Scientific evidence supporting the antidiabetic effects of this plant’s active ingredient-vindoline has not been fully evaluated. In this study, extracts of C. roseus and vindoline were tested for antioxidant activities, alpha amylase and alpha glucosidase inhibitory activities and insulin secretory effects in pancreatic RIN-5F cell line cultured in the absence of glucose, at low and high glucose concentrations. The methanolic extract of the plant showed the highest antioxidant activities in addition to the high total polyphenolic content (p < 0.05). The HPLC results exhibited increased concentration of vindoline in the dichloromethane and the ethylacetate extracts. Vindoline showed noticeable antioxidant activity when compared to ascorbic acid at p < 0.05 and significantly improved the in vitro insulin secretion. The intracellular reactive oxygen species formation in glucotoxicity-induced cells was significantly reduced following treatment with vindoline, methanolic and the dichloromethane extracts when compared to the high glucose untreated control (p < 0.05). Plant extracts and vindoline showed weaker inhibitory effects on the activities of carbohydrate metabolizing enzymes when compared to acarbose, which inhibited the activities of the enzymes by 80%. The plant extracts also exhibited weak alpha amylase and alpha glucosidase inhibitory effects.     

Medicinal flowers. I. Aldose reductase inhibitors and three new eudesmane-type sesquiterpenes, kikkanols A, B, and C, from the flowers of Chrysanthemum indicum L

The methanolic extract from the flowers of Chrysanthemum indicum L., Chrysanthemi Indici Flos, was found to show inhibitory activity against rat lens aldose reductase. By bioassay-guided separation, the active components, such as flavone and flavone glycosides, were isolated from the extract together with three new eudesmane-type sesquiterpenes, kikkanols A, B, and C. The structures of kikkanols A, B, and C were elucidated on the basis of chemical and physicochemical evidence, which included application of the modified Mosher's method.     

A Study on the In Vitro Antioxidant Activity of Juniper (Juniperus communis L.) Fruit Extracts

Abstract

This study aimed at evaluating the in vitro antioxidant activity of water and ethanol extracts of juniper (Juniperus communis L., Family Cupressaceae) fruit. The antioxidant properties of both Juniper extracts were studied using different antioxidant assays, including reducing power, free radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, and metal chelating activities. Both the water and the ethanol extracts exhibited strong total antioxidant activity. The concentrations of 20, 40, and 60 µg/mL of water and ethanol extracts of juniper fruit showed 75%, 88%, 93%, 73%, 84%, and 92% inhibition on peroxidation of linoleic acid emulsion, respectively. On the other hand, 60 µg/mL of standard antioxidant such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and α‐tocopherol exhibited 96, 96, and 61 inhibitions on peroxidation of linoleic acid emulsion, respectively. However, both extracts of juniper had effective reducing power, free radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, and metal chelating activities at these same concentrations (20, 40, and 60 µg/mL). Those various antioxidant activities were compared to BHA, BHT, and α‐tocopherol as standard antioxidants. In addition, total phenolic compounds in both aqueous and ethanolic juniper extracts were determined as gallic acid equivalents. Accordingly, these results indicate that juniper has in vitro antioxidant properties and these may be major reasons for the inhibition of lipid peroxidation properties.     

Evaluation of in vivo and in vitro biological activities of different extracts of Cuscuta arvensis

In the present study, the potential effects of extracts from the whole plant of Cuscuta arvensis were studied in mice using the carrageenan-induced hind paw edema model for antiinflammatory activity and the p-benzoquinone-induced writhing reflex for the assessment of antinociceptive activity. In order to obtain the extracts, the whole plant of C. arvensis was extracted with different solvents such as n-hexane, dichloromethane, ethyl acetate, methanol and distilled water. Antioxidant activity was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The methanolic and water extracts inhibited the carrageenan-induced paw edema and p-benzoquinone-induced writhing reflex, whereas the other extracts showed only mild inhibitory antinociceptive and antiinflammatory activities in these in vivo models. Additionally, the methanol and ethyl acetate extracts had higher scavenging ability then the non polar extracts.