Anticataract Properties Research Articles

Effectiveness of Syzygium aromaticum Extract in Prevention of Diabetic Retinopathy in Experimental Animals

Aim of the study: Syzygium aromaticum has been reported to possess aphrodisiac, stomachic, carminative, antispasmodic and anti-cataract properties in traditional ayurvedic medicine. The current study determined the efficacy of S. aromaticum alcoholic extract in the prevention of diabetic retinopathy in rats with type 2 diabetes. Materials and Methods: Type 2 diabetes was induced in neonatal rats with streptozotocin. The effect of S. aromaticum alcoholic extract in different doses on glycemic parameters, lenticular changes, vessel diameter, antioxidant enzymes, inflammatory markers and thickness basement membrane of retinal capillaries was assessed with electron microscopy. The results of the treatment groups was compared with that of the diabetes control group. Results: The treatment of diabetic rats with S. aromaticum alcoholic extract at different doses significantly reduced blood glucose, glycated hemoglobin, lenticular changes, vessel diameter, inflammatory markers and thickness of basement membrane of retinal capillaries and antioxidant enzymes status. Conclusion: S. aromaticum alcoholic extract may be used strategically to prevent diabetic retinopathy.

α-Crystallin chaperone mimetic drugs inhibit lens γ-crystallin aggregation: Potential role for cataract prevention

Γ-Crystallins play a major role in age-related lens transparency. Their destabilization by mutations and physical chemical insults are associated with cataract formation. Therefore, drugs that increase their stability should have anticataract properties. To this end, we screened 2560 Federal Drug Agency–approved drugs and natural compounds for their ability to suppress or worsen H2O2 and/or heat-mediated aggregation of bovine γ-crystallins. The top two drugs, closantel (C), an antihelminthic drug, and gambogic acid (G), a xanthonoid, attenuated thermal-induced protein unfolding and aggregation as shown by turbidimetry fluorescence spectroscopy dynamic light scattering and electron microscopy of human or mouse recombinant crystallins. Furthermore, binding studies using fluorescence inhibition and hydrophobic pocket–binding molecule bis-8-anilino-1-naphthalene sulfonic acid revealed static binding of C and G to hydrophobic sites with medium-to-low affinity. Molecular docking to HγD and other γ-crystallins revealed two binding sites, one in the “NC pocket” (residues 50–150) of HγD and one spanning the “NC tail” (residues 56–61 to 168–174 in the C-terminal domain). Multiple binding sites overlap with those of the protective mini αA-crystallin chaperone MAC peptide. Mechanistic studies using bis-8-anilino-1-naphthalene sulfonic acid as a proxy drug showed that it bound to MAC sites, improved Tm of both H2O2 oxidized and native human gamma D, and suppressed turbidity of oxidized HγD, most likely by trapping exposed hydrophobic sites. The extent to which these drugs act as α-crystallin mimetics and reduce cataract progression remains to be demonstrated. This study provides initial insights into binding properties of C and G to γ-crystallins.

Effects of Binahong (Anredera cordifolia (Tenore) Steenis) Extracts on the Levels of Malondialdehyde (MDA) in Cataract Goat Lenses.

Cataracts are one of the most causes of blindness in the world. Oxidative stress can form pathological conditions such as cataracts. This oxidative stress ability can be measured by the malondialdehyde (MDA) biomarker. Binahong leaves (Anredera cordifolia (Tenore) Steenis) are native plants from Indonesia that are used to treat various diseases including cataract treatment. Binahong leaf (Anredera cordifolia (Tenore) Steenis) has a high amount of flavonoids and is rich in antioxidants that can be used to treat cataracts. Objective. The purpose of this study was to assess the effect of binahong leaf extract on the levels of MDA in a goat lens with cataract-induced material. Method. As many as possible, 40 goat eye lenses were divided into several groups, namely, group I normal lenses as controls (glucose 5.5 mM), group II lenses were cataract induced with glucose concentration of 55 mM, group III lenses with glucose 55 mM + binahong leaf extract (100 μg/ml), group IV lens with glucose 55 mM + binahong leaf extract (200 μg/ml), and group V lens with glucose 55 mM + quercetin (positive control). Biochemical parameters measured in the lens homogenate are malondialdehyde lens morphology in all groups' observations and comparisons made. Results. The results of the study found that the lens group with the addition of binahong extract showed more results transparency compared to lens groups induced by glucose concentrations of 55 mM). This shows that the diabetic cataract group experienced high oxidative stress due to the accumulation of sorbitol compounds derived from glucose which caused turbidity in the goat eye lens and increased levels of lens MDA. Binahong levels at concentrations of 100 or 200 can inhibit MDA production. Conclusion. Binahong (Anredera cordifolia (Tenore) Steenis) extract has the ability to inhibit the production of MDA levels. In glucose-induced goat lenses, binahong extract and quercetin show antioxidant and anticataract properties.

Oral consumption of α-glucosyl-hesperidin could prevent lens hardening, which causes presbyopia

Presbyopia is one of the most well-known diseases of the eye, predominantly affecting the adult population after 50 years’. Due to hardening of the lens and failure of accommodative change, patients lose the ability to focus on near objects. This eye symptom is reported to be an early symptom of age-related nuclear cataract, and we have previously reported that hesperetin treatment could delay the onset of nuclear cataractogenesis induced by sodium selenite. In this study, we examined whether oral intake of α-glucosyl-hesperidin (G-Hsd), which has greater water solubility than hesperetin, could delay the onset of presbyopia. G-Hsd treatment protected lens elasticity, upregulated the mRNA expression of anti-oxidative enzymes like glutathione reductase and thioredoxin reductase 1 in the plasma and lens, and prevented premature cataract symptoms in selenite-induced cataract rat lens. Thus, the anti-presbyopic effects of G-Hsd were attributed, at least in part, to its antioxidant effects. G-Hsd represents the first oral treatment agent with anti-presbyopia and/or anti-cataract properties.

Anticataract effects of S. cumini and A. marmelos on goat lenses in an experimental diabetic cataract model

BackgroundCataractogenesis in diabetes mellitus is mainly due to generation of free radicals causing oxidative stress. Antioxidants are known to delay cataractogenesis. Indigenous plants are potential promising sources of antioxidants. ObjectivesThe present study was done in goat lenses for exploring local antioxidant and anticataract potential of Syzygium cumini (Jamun) and Aegle marmelos (Bael) and comparing their activities. Material and methods“Lens organ culture technique” was employed using “tissue culture medium 199” (TC 199). Lenses were divided into four groups of 30 each. Group 1 was “Normal Control”. In remaining 3 groups, experimental diabetic cataract was produced using dextrose (110 mM). Group 2: “Toxic Control” (untreated experimental diabetic cataract lenses). Group 3: S. cumini seed extract (0.25%) treated lenses. Group 4: A. marmelos leaf extract (0.25%) treated lenses. Biochemical parameters measured in lens homogenates included total soluble lens proteins (index of cataractogenesis), malondialdehyde (index of lipid peroxidation), and superoxide dismutase, glutathione reductase, and glutathione peroxidase (indices of antioxidant enzyme activity). Lens morphology was compared in all groups. ResultsS. cumini and A. marmelos showed significantly increased activity of all three antioxidant enzymes, preserved total soluble proteins and decreased malondialdehyde (MDA). Lens morphology was well preserved with these extracts. S. cumini aqueous seed extract scored better over A. marmelos. ConclusionIn goat lenses with dextrose-induced experimental diabetic cataract, S. cumini and A. marmelos showed antioxidant and anticataract properties and preservation of lens morphology (p < 0.0001 to 0.05). S. cumini showed better anticataract activity than A. marmelos.

On the Anticataractogenic Effects of L-Carnosine: Is It Best Described as an Antioxidant, Metal-Chelating Agent or Glycation Inhibitor?

Purpose. L-Carnosine is a naturally occurring dipeptide which recently gained popularity as an anticataractogenic agent due to its purported antioxidant activities. There is a paucity of research and conclusive evidence to support such claims. This work offers compelling data that help clarify the mechanism(s) behind the anticataract properties of L-carnosine. Methods. Direct in vitro antioxidant free radical scavenging properties were assayed using three different antioxidant (TEAC, CUPRAC, and DPPH) assays. Indirect in vitro and ex vivo antioxidant assays were studied by measuring glutathione bleaching capacity and total sulfhydryl (SH) capacity of bovine lens homogenates as well as hydrogen-peroxide-stress assay using human lens epithelial cells. Whole porcine lenses were incubated in high galactose media to study the anticataract effects of L-carnosine. MTT cytotoxicity assays were conducted on human lens epithelial cells. Results. The results showed that L-carnosine is a highly potent antiglycating agent but with weak metal chelating and antioxidant properties. There were no significant decreases in lens epithelial cell viability compared to negative controls. Whole porcine lenses incubated in high galactose media and treated with 20 mM L-carnosine showed a dramatic inhibition of advanced glycation end product formation as evidenced by NBT and boronate affinity chromatography assays. Conclusion. L-Carnosine offers prospects for investigating new methods of treatment for diabetic cataract and any diseases that are caused by glycation.

The Claim of Anti-Cataract Potential of Heliotropium indicum: A Myth or Reality?

Introduction Heliotropium indicum has several uses in traditional medicine attributable to its numerous bioactive compounds. It is used as a traditional remedy for cataracts in Ghana without any scientific verification. This study aimed at verifying the anti-cataract properties of an aqueous whole plant extract of H. indicum.MethodsThe effect (cataract score) of 30, 100, and 300 mg kg−1 extract (bid for 21 days, per os) on the development of 30 µmol kg−1 sodium selenite-induced cataract in 10-day-old rat pups was investigated. Soluble lens proteins alpha A and alpha B crystallins, total lens protein, total lens glutathione, and aquaporin 0 in enucleated lens homogenates were determined spectrophotometrically using commercially available kits. Histopathological studies on the lenses were also performed. The 2,2-diphenyl-1-picrylhydrazyl scavenging effect and linoleic acid autoxidation (antioxidant properties) of the extract (0.1–3.0 mg ml−1), compared to n-propyl gallate, were ascertained using standard procedures.ResultsCataract scores showed that the extract, at all dose levels, significantly alleviated selenite-induced cataracts (P ≤ 0.001). Markers of lens transparency (aquaporin 0, alpha A and B crystallins), as well as total lens proteins and lens glutathione levels, were significantly preserved (P ≤ 0.01–0.001). The extract exhibited activity relevant for scavenging free radicals and inhibition of lipid peroxidation. Epithelial and lens fiber integrity in the histopathological assessment were maintained with HIE treatment.ConclusionThe aqueous whole plant extract of H. indicum significantly inhibited the development of cataracts in rats via multiple mechanisms.

Liquid chromatography–tandem mass spectrometry analysis allows the simultaneous characterization of C-glycosyl and O-glycosyl flavonoids in stingless bee honeys

The analysis of the phytochemicals present in stingless bee honey samples has been a difficult task due to the small amounts of samples available and to the complexity of the phytochemical composition that often combines flavonoid glycosides and aglycones. Honey samples produced in Venezuela from Melipona species were analyzed using a combination of solid-phase extraction and HPLC-DAD-MSn/ESI methodologies with specific study of the fragment ions produced from flavonoid glycosides. The analyses revealed that flavonoid glycosides were the main constituents. The honey samples analyzed contained a consistent flavonoid pattern composed of flavone- C-glycosides, flavonol- O-glycosides and flavonoid aglycones. The HPLC-DAD-MSn/ESI analysis and the study of the fragment ions obtained allowed the characterization and quantification for the first time of five apigenin-di- C-glycosides, and ten quercetin, kaempferol and isorhamnetin O-glycosides (di- and tri- glycosides), and the aglycones pinobanksin, quercetin, kaempferol and isorhamnetin in the different samples. This is the first report of flavonoid- C-glycosides in honey. The results show that the content of flavonoid-glycosides (mean values of 2712 μg/100 g) in stingless bee honeys is considerably higher than the content of flavonoid aglycones (mean values of 315 μg/100 g). This differs from previous studies on Apis mellifera honeys that consistently showed much higher aglycone content and smaller flavonoid glycoside content. The occurrence of relevant amounts of flavonoid glycosides, and particularly C-glycosides, in stingless bee honeys could be associated with their putative anticataract properties.

Putative Anticataract Properties of Honey Studied by the Action of Flavonoids on a Lens Culture Model

Stingless bee (Meliponini) honey is a bioresource used to treat cataracts in traditional medicine. The anticataract activity of twenty flavonoids was explored in an osmotic cataract model, to find a probable link between the putative anti-cataract properties of stingless bee honey eyedrops and their flavonoids. Osmotic cataracts were induced in ovine lenses to produce a model to test anti-cataract drugs in cultured lenses by digital image analysis. Digital images were taken every 4 hr to monitor progressive opacification by measurements of grey level. In 24 hr. the opacification was stable. Osmotic cataracts were induced by incubating ovine lenses in 45% hypotonic HBS for 24 hr to test the anticataract action of twenty synthetic flavonoids at a concentration of 10-5 M. Luteolin tetramethyl ether, luteolin 4'-glucoside, luteolin 3'-7-diglucoside and orientin, significantly inhibited cataracts induced in ovine lenses incubated in 45% hypotonic HBS for 24 hr. Different degrees of opacification were produced by hypotonic stress in ovine lenses. The significant inhibition of cataracts caused by four derivatives of luteolin in vitro may be considered as a preliminary evidence for the putative anticataract properties of stingless bee honeys.

Peptidic Aldehydes Based on α- and β-Amino Acids: Synthesis, Inhibition of m-Calpain, and Anti-Cataract Properties

We present a new synthesis of SJA6017 (a potent m-calpain inhibitor) and its adaptation in order to prepare analogues in which the constituent Leu and Val residues are systematically replaced with their corresponding β-amino acids and/or the N-terminal fluorophenylsulfonyl group is replaced by a water solubilizing N-pyridin-3-ylmethoxycarbonyl group. All compounds have been assayed against m-calpain, and the best inhibitor, SJA6017, has been shown to inhibit the development of opacity in a lens culture system design to mimic cataract.

Chemistry at the Interface

The theme for the most recent New Zealand Institute of Chemistry (NZIC) conference held in Nelson was ‘Chemistry at the Interface’ and that’s exactly what the twelve plenary speakers, invited speakers, section lecturers, and hundreds of posters presented. Close to 400 delegates, from a range of chemical backgrounds, were treated to the best of international and local speakers in a programme that provided a glimpse into the future of chemistry and also, importantly, an insight into the discipline’s past and evolution. This issue of theAustralian Journal of Chemistry compiles some of the outstanding science presented within the framework of the conference symposia; the interface of chemistry and biology, techniques of chemistry at the interface, the interface of chemistry with the commercial sector, and the interface of chemistry with materials and nanotechnology (Fig. 1). Bill Denny[1] provides an insightful discussion on the design of drugs that target tumor hypoxia. This approach to tumour-selective agents has lead to some internationally important findings and a deeper understanding of the biology of tumours. Ted Baker[2] reviews recent advances in the area of structural analysis in his article. This work highlights a critical link between advances in molecular biology and in structural determination by X-ray crystallography. David Fairlie[3] continues the theme of the biology/chemistry interface, presenting an outstanding summary of some minimalistic approaches to structural mimetics of amino acids and of strand, turn, and helix segments of proteins. Gary Evans[4] presents an overview on the design and synthesis of transition state analogue inhibitors of N-ribosyl transferases and their current therapeutic uses and potential. This is a real success story in New Zealand-based medicinal chemistry.The medicinal chemistry theme continues in a paper by Andrew Abell and coworkers[5] on the synthesis and anti-cataract properties of peptidic aldehydes. A true highlight of the conference was a presentation by Dieter Seebach[6] on his pioneering work on the creation of new secondary structures derived from βand γ-peptides, and aspects of this work are discussed here. This special issue also contains two papers that present work at the interface of organic and inorganic chemistry. Peter Steel and coworkers[7] present the first examples of 2,2′-bipyrimidine ligands incorporating bulky or chiral substituents, and Jonathan White and coworkers[8] present Fig. 1. The interface of chemists with the Nelson environment.

Antioxidant activity of l-carnosine, a natural histidine-containing dipeptide in crystalline lens

Lipid peroxidation was shown to be an initiatory cause of cataract development in some cases. It has been established that injection into the vitreous body of the rabbit eye of a suspension of liposomes prepared from phospholipids containing lipid peroxidation products induces the development of posterior subcapsular cataract. Such modelling of cataract is based on a type of clouding of the crystalline lens similar to that observed in cataract resulting from diffusion of toxic lipid peroxidation products from the retina to the lens through the vitreous body on degeneration of the photoreceptors. Saturated liposomes (prepared from dipalmitoylphosphatidylcholine) did not cause clouding of the lens, which demonstrated the peroxide mechanism of the genesis of this form of cataract. Clouding of the lens was accompanied by accumulation of fluorescing lipid peroxidation products in the vitreous body, aqueous humor and the lens and also by a fall in the concentration of reduced glutathione in the lens. The ability of l-carnosine (β-alanyl- l-histidine) to interact directly with lipid peroxidation products suggested its anticataract properties. The effect of l-carnosine on inhibiting or reversing the formation of cataract induced by the administration of lipid peroxidation products was discovered. This phenomenon appeared to be related with normalization of the peroxide metabolism parameters in the crystalline lens. In view of the data, an aqueous solution of l-carnosine is physiologically acceptable in effective nonsurgical treatment for cataracts.