Effect of Conduritol A, a Polyol from Gymnema sylvestre, on the Development of Diabetic Cataracts in Streptozotocin-treated Rats and on Aldose Reductase

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Streptozotocin-diabetic rats were maintained on a stock diet for 16 weeks and some were given conduritol A (10 mg/kg/day). The administration of conduritol A, having a hypoglycemic effect, markedly prevented the diabetic rats from getting cataracts. In practice, conduritol A inhibited aldose reductase (EC that is capable of catalyzing the conversion of aldoses to sugar alcohols in the polyol pathway. In an in vitro assay, lens aldose reductase was most effectively inhibited by conduritol A when α,β-d-glucose was used as a substrate. Some enzymes from the rats were not inhibited by conduritol A. Neither an intraperitoneal injection nor oral dosage of conduritol A caused acute toxicity in the rats. These findings suggest that the inhibition of lens aldose reductase by conduritol A may be responsible for its cataract-suppressing effect.

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... The ethanol extract of Radix Purerariae inhibits glycosylation of rat lens protein (Hirakura et al., 1989) 7-(6-O-malonyl-b-D-glucopyranosyloxy)-3-(4-hydroxyphenyl)-4H-1benzopyran-4-one Discovery of a new key chemical constituent proven to be useful in DR by inhibiting aldose reductase (Duan et al., 2000) Gymnema sylvestre A polyol, conduritol A Beneficial effect on cataract by inhibiting lens aldose reductase (Miyatake et al., 1994) Astragalis radix Astragalosides Potentially useful for the prevention of clinical diabetic complications such as diabetic retinopathy by inhibiting AGE product (Motomura et al., 2009) Hachimi-Jio-gan (Trhmannia Eight Formula) ...
... Not known Controls the balance of sodium, potassium and calcium ions for maintenance of lens transparency. This finding may lead the possibility of prophylactic use in eye diseases such as diabetic cataract (Kamei et al., 1987) Trigonella foenum graecum (Fenugreek) Saponins, Flavanoids, 4-hydroxyisoleucine Beneficial effect for abnormal accumulation of sorbitol and fructose in the diabetic lens Restore disintegration of the inner nuclear layer cells with reduction in rough endoplasmic reticulum and swelling of mitochondria in the diabetic retina Cataract-suppressing effect by inhibiting lens aldose reductase (Miyatake et al., 1994) (Preet et al., 2006) Vaccinium myrtillus (billbery) ...
... A polyol, conduritol A from Gymnema sylvestre may be responsible for the cataract-suppressing effect by inhibiting lens aldose reductase (Miyatake et al., 1994). ...
Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and remains a major cause of preventable blindness among adults at working age. DR involves an abnormal pathology of major retinal cells, including retinal pigment epithelium, microaneurysms, inter-retinal oedema, haemorrhage, exudates (hard exudates) and intraocular neovascularization. The biochemical mechanisms associated with hyperglycaemic-induced DR are through multifactorial processes. Peroxisome proliferator-activated receptor-γ (PPAR-γ) plays an important role in the pathogenesis of DR by inhibiting diabetes-induced retinal leukostasis and leakage. Despite DR causing eventual blindness, only a few visual or ophthalmic symptoms are observed until visual loss develops. Therefore, early medical interventions and prevention are the current management strategies. Laser photocoagulation therapy is the most common treatment. However, this therapy may cause retinal damage and scarring. Herbal and traditional natural medicines may provide an alternative to prevent or delay the progression of DR. This review provides an analysis of the therapeutic potential of herbal and traditional natural medicines or their active components for the slowdown of progression of DR and their possible mechanism through the PPAR-γ pathway.
... Experimental trials have been conducted in animal models with G. sylvestre active constituents of which insulin-like activity and mechanism of action of hypoglycemic principles have been investigated in detail [23]. Amid many, Gymnemic acids III, IV, V, and VII and Gymnemoside B were recognized as antihyperglycemic active constituents while Conduritol A was found to have cataractsuppressing effect [24]. Moreover, it has been reported that another active ingredient from G. sylvestre leaves extract, GS4, plays a very significant role in the regulation of both type 1 and type 2 diabetes [24,25]. ...
... Amid many, Gymnemic acids III, IV, V, and VII and Gymnemoside B were recognized as antihyperglycemic active constituents while Conduritol A was found to have cataractsuppressing effect [24]. Moreover, it has been reported that another active ingredient from G. sylvestre leaves extract, GS4, plays a very significant role in the regulation of both type 1 and type 2 diabetes [24,25]. ...
... Among many, Gymnema sylvestre, a plant common in South Asia, were selected for the current study. A total of ten compounds ( Figure 2) were selected from Gymnema sylvestre based on the following criteria: (i) tested compounds having antidiabetic (T2DM) effect (Gymnemoside B and Conduritol A) and their analogues (Gymnemoside A and Conduritol B tetraacetate, Conduritol C cis-epoxide analogue, Conduritol D, and Conduritol E tetranitro), (ii) tested compounds with no antidiabetic effect (Gymnemic acid I, Gymnemic acid II), and (iii) one unique compound, GS4, having antidiabetic effects against both types (T1DM and T2DM) [24,25]. The two-dimensional (2D) structure of the selected active compounds of this plant was retrieved from Click2drug (, ...
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Diabetes mellitus (DM) is one of the most prevalent metabolic disorders which can affect the quality of life severely. Injectable insulin is currently being used to treat DM which is mainly associated with patient inconvenience. Small molecules that can act as insulin receptor (IR) agonist would be better alternatives to insulin injection. Herein, ten bioactive small compounds derived from Gymnema sylvestre ( G. sylvestre ) were chosen to determine their IR binding affinity and ADMET properties using a combined approach of molecular docking study and computational pharmacokinetic elucidation. Designing structural analogues were also performed for the compounds associated with toxicity and less IR affinity. Among the ten parent compounds, six were found to have significant pharmacokinetic properties with considerable binding affinity towards IR while four compounds were associated with toxicity and less IR affinity. Among the forty structural analogues, four compounds demonstrated considerably increased binding affinity towards IR and less toxicity compared with parent compounds. Finally, molecular interaction analysis revealed that six parent compounds and four analogues interact with the active site amino acids of IR. So this study would be a way to identify new therapeutics and alternatives to insulin for diabetic patients.
... 101,107 These compounds are also synthetic precursors for the preparation of cyclitols of biological interest, exemplified by inositol phosphate, quercitols, cyclophellitol, pseudosugars, pancratistatine, licoridinei, aminoglycosidic antibiotics, sugar amino acid analogues, etc. 101 Conduritol A (103) is particularly important in this class of compounds because of its ability to inhibit intestinal glucose absorption and its potential use as an agent in the treatment of obesity and diabetes. Although the mechanism of its action remains unclear, Miyatake et al. 108 showed that the hypoglycemic effect of 103 prevented diabetic rats developing cataracts as a consequence of the inhibition of lens aldose reductase, the enzyme that converts aldoses to sugar alcohols. Furthermore, the hypoglycemic activity of 103 was also shown by conduritol B (104) having the all trans hydroxyl configuration and it was also able to modulate insulin release from isolated pancreatic islets. ...
Glycoside trimming enzymes are crucially important in a broad range of metabolic pathways, including glycoprotein and glycolipid processing and carbohydrate digestion in the intestinal tract. Amongst the large array of enzymes, glucosidases are postulated to be a powerful therapeutic target since they catalyze the cleavage of glycosidic bonds releasing glucose from the non-reducing end of an oligo- or polysaccharide chain involved in glycoprotein biosynthesis. Glucosidase inhibitors are currently of interest owing to their promising therapeutic potential in the treatment of disorders such as diabetes, human immunodeficiency virus (HIV) infection, metastatic cancer, and lysosomal storage diseases. Glucosidase inhibitors have also been useful in probing biochemical pathways and understanding structure-activity relationship patterns required for mimicking the enzyme transition state. Amongst the various types of glucosidase inhibitors, disaccharides, iminosugars, carbasugars, thiosugars, and non-sugar derivatives have received great attention. This review is, aimed at highlighting the main chemical classes of glucosidase inhibitors, as well as their biological activities toward alpha- and beta-glucosidases, but it is not intended to be an exhaustive review on the subject. Inhibition data on the compounds covered in this review are included in a tabular form as an Appendix, where the type of each glucosidase associated with a specific inhibitor is also given. (c) 2006 Elsevier Ltd. All rights reserved.
... Gymnema sylvestre (Asclepiadeaceae) is a promising plant to be developed into a new drug for diabetes therapy. G54 and extract from the leaves of Gymnama sylvestre has an excellent effect in controlling hyperglyceamia of both types 1 and 2 diabetes patients, Miyatake et al. 1994. ...
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Résumé : L’huile essentielle de Filipendula hexapetala Gibb. (Rosaceae), obtenue par hydrodistillation est analysée par chromatographie à phase gazeuse couplée au spectrophotomètre de masse et évaluée in vitro pour son activité antimicrobienne. Les souches microbiennes les plus sensibles sont Candida albicans, Escherichia coli ATCC 9739, Staphylococcus aureus ATTC 6538 et Enterococcus faecalis CIP 102712.
Diabetes is characterized by hyperglycemia, a serious chronic disease, which has become an important public health problem worldwide and affecting human health severely. These days, the use of modern drugs for the control of glycemia is causing many negative side effects, and therefore, the demand for safer and more affordable treatments is increasing day by day. Most of the antidiabetic plants contain phyto-components, capable of exhibiting strong antihyperglycemic activity. Studies have reported that alkaloids interact with proteins involved in glucose homeostasis and can be used as an alternative in the treatment of diabetes. Based on the previously published studies, this chapter mentioned and discussed various significant antidiabetic plant species with their active ingredients. Furthermore, biotechnological methods were reviewed in details that were used for increasing the production of antidiabetic bioactive compounds using these plants. Moreover, these biotechnological methods can be categorized into two groups: (1) plant cell, tissue, and organ cultures (callus, cell and root cultures, suspension cultures, and single-cell culture lines) and (2) metabolic engineering (-omics analysis, gene-editing techniques, and synthetic biology). The outcomes of previous studies discussed in this chapter suggested that biotechnological methods could be potential, profitable, and novel for large-scale production of effective active ingredients from several plant species for the purpose of diabetes mellitus.
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Cataract is the leading reason of blindness worldwide and is defined by the presence of any lens opacities or loss of transparency. The most common symptoms of cataract are impaired vision, decreased contrast sensitivity, color disturbance, and glare. Oxidative stress is among the main mechanisms involved in the development of age-related cataract. Surgery through phacoemulsification and intraocular lens implantation is the most effective method for cataract treatment, however, there are chances of serious complications and irreversible loss of vision associated with the surgery. Natural compounds consisting of antioxidant or anti-inflammatory secondary metabolites can serve as potential leads for anticataract agents. In this review, we tried to document medicinal plants and plant-based natural products used for cataract treatment worldwide, which are gathered from available ethnopharmacological/ethnobotanical data. We have extensively explored a number of recognized databases like Scifinder, PubMed, Science Direct, Google Scholar, and Scopus by using keywords and phrases such as “cataract”, “blindness”, “traditional medicine”, “ethnopharmacology”, “ethnobotany”, “herbs”, “medicinal plants”, or other relevant terms, and summarized the plants/phytoconstituents that are evaluated in different models of cataract and also tabulated 44 plants that are traditionally used in cataract in various folklore medical practices. Moreover, we also categorized the plants according to scientific studies carried out in different cataract models with their mechanisms of action.
The rapidly increasing diabetes mellitus is becoming a serious threat to mankind health in all parts of the world. The control and treatment of diabetes and its complications mainly depend on the chemical or biochemical agents, but the fact is that it has never been reported that someone had recovered totally from diabetes. With the distinctive traditional medical opinions and natural medicines mainly originated in herbs, the traditional Chinese medicine performed a good clinical practice and is showing a bright future in the therapy of diabetes mellitus and its complications. Based on a large number of chemical and pharmacological research work, numerous bioactive compounds have been found in Chinese medicinal plants for diabetes. The present paper reviews 86 natural medicines with regards to their origin, anti-diabetic active principles and/or pharmacological test results, which are commonly used in the traditional Chinese medical system and have demonstrated experimental or/and clinical anti-diabetic effectiveness. Among these natural medicines, 82 originate from plants and 4 from animals or insects, which covers 45 families. It is strongly significant to pay close attention to traditional Chinese medical therapeutics and natural medicines for treatment of diabetes mellitus and its complications.
This chapter discusses the determination of crystalline lactic dehydrogenases. The methods developed in the laboratories for the purification of lactic dehydrogenases involve several basic steps: (1) fractionation by solubility, (2) separation by charge, and (3) separation by molecular size. The mainstay of all the procedures is fractionation by solubility, using ammonium sulfate. Gross precipitations for the purpose of concentrating and for purification are used in most of our procedures. Repeated ammonium sulfate fractionations using finer cuts as the purification progresses are utilized in most procedures. Separation by charge using cation and anion exchange celluloses is the other main purification step. During the course of electrophoretic investigation, it was noted that some proteins had their mobility changed drastically while others were unaffected by changes in pH. This helped greatly in determining the exchanger and pH to use in the procedure. Proteins which chromatograph as one symmetrical peak may be separated on a subsequent column simply by changing the pH conditions for equilibration and running of the column. Sephadex molecular sieves and sucrose density gradient centrifugations are used for separation by molecular size.