RESUMO
The fenugreek plant (Trigonella foenum-graecum) is traditionally known for its anti-diabetic properties owing to its high content of furostanolic saponins, which can synergistically treat many human ailments. Non-enzymatic protein glycation leading to the formation of Advanced Glycation End products (AGE) is a common pathophysiology observed in diabetic or prediabetic individuals, which can initiate the development of neurodegenerative disorders. A potent cellular source of glycation is Methyl Glyoxal, a highly reactive dicarbonyl formed as a glycolytic byproduct. We demonstrate the in vitro glycation arresting potential of Fenfuro®, a novel patented formulation of Fenugreek seed extract with clinically proven anti-diabetic properties, in Methyl-Glyoxal (MGO) adducts of three abundant amyloidogenic cellular proteins, alpha-synuclein, Serum albumin, and Lysozyme. A 0.25% w/v Fenfuro® was able to effectively arrest glycation by more than 50% in all three proteins, as evidenced by AGE fluorescence. Glycation-induced amyloid formation was also arrested by more than 36%, 14% and 15% for BSA, Alpha-synuclein and Lysozyme respectively. An increase in MW by attachment of MGO was also partially prevented by Fenfuro® as confirmed by SDS-PAGE analysis. Glycation resulted in enhanced aggregation of the three proteins as revealed by Native PAGE and Dynamic Light Scattering. However, in the presence of Fenfuro®, aggregation was arrested substantially, and the normal size distribution was restored. The results cumulatively indicated the lesser explored potential of direct inhibition of glycation by fenugreek seed in addition to its proven role in alleviating insulin resistance. Fenfuro® boosts its therapeutic potential as an effective phytotherapeutic to arrest Type 2 diabetes.
Fenfuro® is a novel patented formulation of Fenugreek seed extract with more than 45% furostanolic saponins and anti-diabetic property free from any side effect as established through clinical study.In the present study, the role of Fenfuro® in arresting in vitro AGE formation and glycation-induced amyloid formation has been demonstrated with the help of three amyloidogenic proteins, namely Human Lysozyme, Human alpha-synuclein and Bovine Serum Albumin using Methyl Glyoxal as the glycating agent.A 0.25% (w/v) ethanolic solution of Fenfuro® resulted in more than 50% arrest in glycation with simultaneous prevention of aggregation as demonstrated by native PAGE, DLS and inhibition of development of Thio-T positive amyloid like entities.The studies collectively aim toward the development of a safe therapeutic method for arresting protein glycation through direct physical intervention.
RESUMO
Vanadium toxicity is a globally recognized threat to the reproductive health of man and animal. However the mechanism of vanadium-induced damage to the testicular and adrenocortical tissues is not fully characterized. It was hypothesized that prostaglandins may partially mediate the inflammatory response to vanadate damage. In this study prostaglandin (PG) mediated effects of vanadate on testicular and adrenocortical functions was substantiated by using indomethacin to block prostaglandin synthesis. Significant inhibition of spermatogenesis, decreased serum level of testosterone and gonadotropins in the vanadium-exposed group of rats indicated the damaging effects of vanadium-induced reactive oxygen species. This was also reflected in the appreciable increase in testicular lipid peroxidation (LPO) level and decline in the activities of steroidogenic and antioxidant enzymes. Histopathological studies revealed regressive and degenerative changes in testis. However, inhibition of cyclooxygenase activity by indomethacin increased steroid hormone production, gonadotropin level, elevated the specific activities of enzymes and decreased LPO level in rat testis exposed to vanadium. Vanadium also caused prostaglandin mediated adrenocortical hyperactivity, as inhibition of PG synthesis abolished these adrenal responses to vanadium. The studies showed that vanadium toxicity is directly linked to stimulation of prostaglandin synthesis. Therefore, indomethacin can be a good prospect to alleviate vanadium induced male infertility.
