Maintaining the Redox-Balance Intact: Gosha-Jinki-Gan but Not Insulin Activates Retinal Soluble Guanylate Cyclase in Diabetic Rats

Abstract

Strategies to prevent hyperglycemia-induced cytotoxic reactive oxygen species in the retina include the prevention of free radical production, activation of radical-scavenging capacities and inhibition of aldose reductase. This study examined the effect of the standardized Japanese herbal extract product gosha-jinki-gan (GJG) in comparison to insulin treatment in the rat retina. Diabetes was induced in male Wistar rats by single injection of streptozotocin (50 mg/kg i.p.). At 6 and 12 weeks, eyecups were removed for immunohistochemistry. At 12 weeks, lipid peroxidation (tested with the antiacrolein antibody, Ab5F6) was enhanced significantly in the untreated diabetic group. This effect was absent in both treatment groups, notably in the outer retina. A similar result was obtained for nitrotyrosine overproduction. As an early treatment effect, GJG – but not insulin – enhanced soluble guanylate cyclase (sGC) activation (using the function-sensing antibody, MoAb 3221). GJG not only reduces nitroxidative stress and lipid peroxidation in the retina, it also ameliorates glucose metabolism within the cells. We propose that the high glucose turnover in the insulin-treated model disturbs the intracellular redox equilibrium, one result of which might be the impaired sGC activation.

Imino [4+4] cycloaddition products as exclusive and biologically relevant acrolein-amine conjugates are intermediates of 3-formyl-3,4-dehydropiperidine (FDP), an acrolein biomarker

“…Acrolein-amino conjugates involving, for example, lysine d-amino groups, 3-formyl-3,4-dehydropiperidine (FDP), 7 or 3-methylpyridinium (MP) derivatives 10 have been described (see the structure of FDP illustrated in Scheme 4). Antibodies 11 to these conjugates are widely used for the immunochemical detection of a variety of disease states, such as arteriosclerosis, [11][12][13][14] Alzheimer's disease, 15,16 tumors, [17][18][19][20][21] diabetes, [22][23][24][25][26] autoimmune disease, 27,28 high blood pressure, 29 among other diseases. [30][31][32][33][34] Alternatively, acrolein can react with polyamines to produce FDP conjugates that modulate the cytotoxicity of acrolein.…”

Long‐Term Effects of Goshajinkigan in Prevention of Diabetic Complications: A Randomized Open‐Labeled Clinical Trial

“…For retinopathy, Cameron-Schaefer et al showed the protective effect of goshajinkigan against the diabetic retinopathy [22]. They showed that lipid peroxidation was enhanced by streptozotocin-induced hyperglycemia and that goshajinkigan prevented lipid peroxidation.…”

Clinical efficacy and tolerability of Gosha-jinki-gan, a Japanese traditional herbal medicine, for nocturia

“… 14 Moreover, GJG had shown protective effects against diabetic complications in the animal model or clinical setting. 15 , 16 , 17 Watanabe et al 16 showed that GJG had some beneficial effects on serum glucose and glycated hemoglobin. Comparing the medications in two groups, they found that the patients in the control group had more progressed medications in 5 years (nonmedication to medication or medication to insulin).…”