DIABETES

I have been helpful in treating both type I and type II diabetes. Supportive therapies are very helpful in lowering insulin dependence.

J Agric Food Chem. 2005 May 4;53(9):3710-3. Related Articles, Links
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Black and green teas equally inhibit diabetic cataracts in a streptozotocin-induced rat model of diabetes.

Vinson JA, Zhang J.

Department of Chemistry, Loyola Hall, University of Scranton, Scranton, Pennsylvania 18510-4626, USA. vinson@scranton.edu

Green and black teas were given at 1.25% in the drinking water to streptozotocin-induced diabetic rats for 3 months. Normal and diabetic control groups were also studied. As expected, diabetic animals had significantly increased glucose in lens and plasma. Lens and red blood cell sorbitol were significantly increased as a result of the aldose reductase pathway activation. Plasma and lens lipid thiobarbituric acid-reactive substances and protein glycation were also significantly elevated. Both teas significantly inhibited diabetic cataracts and caused significant reductions in the biochemical pathway implicated in the development of the pathology. After corrections for glucose, it was found that the teas retard the development of diabetic cataracts by a hypoglycemic effect that in turn inhibits the biochemical indicators of pathology. There were significant correlations between glucose, cataract score, and these indicators. Green tea but not black tea caused a significant decline in triglycerides in the diabetic animals. Tea may be a simple, inexpensive means of preventing or retarding human diabetes and the ensuing complications. Tea also should be investigated as an adjunct therapy for diabetes treatment.

PMID: 15853424 [PubMed - indexed for MEDLINE]
Curr Eye Res. 2002 Jul;25(1):9-16. Related Articles, Links

Blood and lens lipid peroxidation and antioxidant status in normal individuals, senile and diabetic cataractous patients.

Donma O, Yorulmaz E, Pekel H, Suyugul N.

Department of Biochemistry, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey. odonma@hotmail.com

PURPOSE: Oxidative mechanisms are believed to play an important role in the pathogenesis of cataract, the most important cause of visual impairment at advanced age. To determine the body's antioxidant status as well as its lipid peroxidation levels, both blood and lens parameters were evaluated. METHODS: This study was performed on the blood samples and lenses obtained from 46 patients diagnosed as having cataract and 20 control subjects. The control group was composed of 10 women and 10 men who do not smoke. Control subjects without any lens opacity or vacuoles when observed with a slit lamp were recruited on the same exclusion criteria as far as disease and treatment were concerned. No antioxidant medicines were used. They were all healthy individuals without any systemic diseases. Superoxide dismutase (SOD), glucose-6-phosphate dehydrogenase (G6PD), glutathione reductase (GSSG-Red) activities in red blood cell (RBC) lysates as well as whole blood glutathione (GSH) and plasma thiobarbituric acid reactive substances (TBARS), the indicator of lipid peroxidation concentrations, were determined quantitatively both in the blood samples and the lenses of the patients with senile and diabetic cataracts. RESULTS: Whole blood GSH values, and erythrocyte SOD activities were significantly lower in the cataractous patients than those in the control group. The values in the diabetic cataractous group were also less than those in the senile cataractous group. Significantly decreased erythrocyte GSSG-Red and G6PD activities were detected in the diabetic cataractous group. Plasma TBARS values were higher both in the senile and diabetic groups when compared to those in the control group. Significantly decreased values were observed for GSSG-Red activities and TBARS values in the lenses of the senile cataractous patients in comparison with those in the diabetic cataractous patients. The lens GSH values were found to be higher in the senile cataractous group than the values obtained in the diabetic cataractous group. CONCLUSIONS: A strong correlation was found between lens GSH and lens TBARS concentrations in the diabetic group. This emphasized the vital role of GSH as an antioxidant in the lens over the other antioxidant parameters, e.g., enzymes, and the oxidative stress is at the highest level in lens.

PMID: 12518238 [PubMed - indexed for MEDLINE]
J Pharm Pharmacol. 2001 May;53(5):653-68. Related Articles, Links
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Synthesis of flavonoids and their effects on aldose reductase and sorbitol accumulation in streptozotocin-induced diabetic rat tissues.

Lim SS, Jung SH, Ji J, Shin KH, Keum SR.

Natural Products Research Institute, Seoul National University, Korea.

Aldose reductase, the key enzyme of the polyol pathway, and oxidative stress are known to play important roles in the complications of diabetes. A drug with potent inhibition of aldose reductase and oxidative stress, therefore, would be a most promising drug for the prevention of diabetic complications. The purpose of this study was to develop new compounds with these dual-effects through synthesis of chalcone derivatives and by examining the structure-activity relationships on the inhibition of rat lens aldose reductase as well as on antioxidant effects. A series of 35 flavonoid derivatives were synthesized by Winget's condensation, oxidation, and reduction of appropriate acetophenones with appropriate benzaldehydes. The inhibitory activity of these derivatives on rat lens aldose reductase and their antioxidant effects, measured using Cu2+ chelation and radical scavenging activities on 1,1-diphenyl-picrylhydrazyl in-vitro, were evaluated. Their effect on sorbitol accumulation in the red blood cells, lenses and sciatic nerves of streptozotocin-induced diabetic rats was also estimated. Among the new flavonoid derivatives synthesized, those with the 2',4'-dihydroxyl groups in the A ring such as 2,4,2',4'-tetrahydroxychalcone (22), 2,2',4'-trihydroxychalcone (11), 2',4'-dihydroxy-2,4-dimethylchalcone (21) and 3,4,2',4'-tetrahydroxychalcone (18) were found to possess the highest rat lens aldose reductase inhibitory activity in-vitro, their IC50 values (concentration of inhibitors giving 50% inhibition of enzyme activity) being 1.6 x 10(-7), 3.8 x 10(-7), 4.0 x 10(-7) and 4.6 x 10(-7) M, respectively. All of the chalcones tested except 3, 18, 23 with o-dihydroxy or hydroquinone moiety showed a weak free radical scavenging activity. In the in-vivo experiments, however, compound 18 with o-dihydroxy moiety in the B ring showed the strongest inhibitory activity in the accumulation of sorbitol in the tissues. It also showed the strongest activity in transition metal chelation and free radical scavenging activity. Of the 35 4,2'-dihydroxyl and 2',4'-dihydroxyl derivatives of flavonoid synthesized, including chalcone, flavone, flavanone, flavonol and dihydrochalcone, some chalcone derivatives synthesized were found to possess aldose reductase inhibition and antioxidant activities in-vitro as well as inhibition in the accumulation of sorbitol in the tissues in-vivo. 3,4,2',4'-Tetrahydroxychalcone (18, butein) was the most promising compound for the prevention or treatment of diabetic complications.

PMID: 11370705 [PubMed - indexed for MEDLINE]
Biochem Pharmacol. 1997 Nov 1;54(9):1047-53. Related Articles, Links
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Inhibition of glutathione reductase by plant polyphenols.

Zhang K, Yang EB, Tang WY, Wong KP, Mack P.

Department of Experimental Surgery, Singapore General Hospital, Singapore. geskai@sgh.gov.sg

The effects of forty-one plant polyphenols on the activity of glutathione reductase (GSH-RD) were studied. These polyphenols showed varying degrees of concentration-dependent inhibition on the enzyme, with IC50 values that varied from approximately 40 microM to 1 mM. 4'-Hydroxychalcone and tannic acid were among the more potent inhibitors, with IC50 values of 47.3 and 50.4 microM, respectively. Different classes of polyphenols varied in potency in the following order: chalcones > tannic acid > flavonoids > coumarins > catechins. Analysis of structure-activity relationships showed certain chemical structures to be important for the inhibition of GSH-RD: (a) C-5 and C-7 hydroxylations in the A-ring, a carbonyl group at C-4, and the B-ring attached to C-2 in flavonoids; (b) C-2' and C-4' hydroxylations in chalcones; and (c) C-6 and C-7 hydroxylations in coumarins. The inhibition of GSH-RD by tannic acid and quercetin was time dependent and irreversible, whereas that by 4'-hydroxychalcone and esculin was reversible but not time dependent. Enhanced inhibition of GSH-RD by the four polyphenols 4'-hydroxychalcone, quercetin, butein, and acacetin was observed in the presence of NADPH. Kinetic studies showed that both tannic acid and 4'-hydroxychalcone exhibited non-competitive inhibition on GSH-RD towards glutathione disulfide.

PMID: 9374426 [PubMed - indexed for MEDLINE]
Histol Histopathol. 2005 Apr;20(2):615-32. Related Articles, Links
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Functional aspects of the somatostatinergic system in the retina and the potential therapeutic role of somatostatin in retinal disease.

Casini G, Catalani E, Dal Monte M, Bagnoli P.

Dipartimento di Scienze Ambientali, Universita della Tuscia, Viterbo, Italy. gcasini@unitus.it

The somatostatinergic system of the retina has been investigated in a variety of studies. A considerable amount of experimental evidence is available concerning the patterns of expression of somatostatin (SRIF) and its receptors in vertebrate retinas. However the functional roles of this peptidergic system in retinal physiology are far from being elucidated. Nonetheless, data have been provided concerning the regulatory action of SRIF on the excitability of different retinal cell types and on the modulation of ion channels in different vertebrate retinas. The present review is focused on recent and unpublished investigations of the mouse retina relative to the involvement of specific SRIF receptors in the regulation of ion channels and transmitter release, the transduction pathways coupled to SRIF receptors, and the mechanisms regulating the expression of SRIF and its receptors as derived from studies in transgenic animal models. In these models, altered expression levels of SRIF or of specific SRIF receptors have also been found to affect the morphology of retinal cell types (namely the rod bipolar cells) and to result in functional alterations at the level of both ion channel regulation and transmitter release. These new pieces of evidence constitute an important step forward in the understanding of the functional actions of the retinal somatostatinergic system, although our current knowledge is far from being exhaustive. The ultimate goal of understanding SRIF functional actions in the retina is concerned with the possibility of using SRIF or its analogs as therapeutic agents to cure retinal diseases. Indeed, encouraging results are being obtained in clinical investigations focused on the use of SRIF analogs to treat diabetic retinopathy, a retinal disease with high social impact and originating as a complication of diabetes. The closing part of the present paper examines the evidence supporting SRIF as a promising therapeutic agent in this disease.

Publication Types:

* Review

PMID: 15736065 [PubMed - indexed for MEDLINE]
J Ocul Pharmacol Ther. 1999 Jun;15(3):233-40. Related Articles, Links

Ginkgo biloba extract increases ocular blood flow velocity.

Chung HS, Harris A, Kristinsson JK, Ciulla TA, Kagemann C, Ritch R.

Glaucoma Research and Diagnostic Center, Department of Ophthalmology, Indiana University Medical Center, Indianapolis 46202, USA.

We evaluated a possible therapeutic effect of Ginkgo biloba extract (GBE) on glaucoma patients that may benefit from improvements in ocular blood flow. A Phase I cross-over trial of GBE with placebo control in 11 healthy volunteers (8 women, 3 men: Age; 34 +/- 3 years, mean +/- SE) was performed. Patients were treated with either GBE 40 mg or placebo three times daily orally, for 2 days. Color Doppler imaging (Siemens Quantum 2000) was used to measure ocular blood flow before and after treatment. There was a two week washout period between GBE and placebo treatment. Ginkgo biloba extract significantly increased end diastolic velocity (EDV) in the ophthalmic artery (OA) (baseline vs GBE-treatment; 6.5 +/- 0.5 vs 7.7 +/- 0.5 cm/sec, 23% change, p=0.023), with no change seen in placebo (baseline vs GBE-treatment; 7.2 +/- 0.6 vs 7.1 +/- 0.5 cm/sec, 3% change, p=0.892). No side effects related to GBE were found. Ginkgo biloba extract did not alter arterial blood pressure, heart rate, or IOP. Ginkgo biloba extract significantly increased EDV in the OA and deserves further investigation in ocular blood flow and neuroprotection for possible application to the treatment of glaucomatous optic neuropathy as well as other ischemic ocular diseases.

Publication Types:

* Clinical Trial
* Clinical Trial, Phase I
* Randomized Controlled Trial

PMID: 10385132 [PubMed - indexed for MEDLINE]