Protective Effect Of Astragaloside IV And Bendazac Lysine On Diabetic Peripheral Neuropathy In Rats: Pharmacodynamic, Pharmacokinetic And Mechanism-based PD-PK Combination Modeling

BackgroundDiabetic peripheral neuropathy (DPN) is one of the most prevalent complications that develop from diabetes mellitus and it causes significant morbidity and mortality. Some 30% of hospitalized and 20% of community-dwelling diabetic patients suffered from peripheral neuropathy. Diabetic neuropathy has been shown to involve several biochemical and functional abnormalities both in diabetic patients and in animal models. Decreased nerve blood flow resulting in endoneurial hypoxia may be a key mechanism responsible for the observed decrease in nerve conduction velocity. Other factors that contribute to microvascular disease and nerve dysfunction include the accumulation of sorbitol induced by polyol pathway flux, oxidative stress, advanced glycation end products, depletion of myo-inositols, decreased Na~+,K~+-ATPase activity, decreasesd endothelial nitric oxide synthase, alterations in fatty acid metabolism, and nerve growth factors. Few means could affect or slow natural progression of DPN due to inadequate drug therapy. Despite the challenges ahead, the future holds the promise of more effective treatments including preventive drugs for diabetes complications.Astragaloside â…£ (AGS-â…£), the pure saponin isolated from the root of Astragalus membranaceus (Fisch.) Bunge, is an effective compound that demonstrates distinct pharmacological effects including anti-inflammation and regulation of immunological function, anti-hypertension, anti-oxidation, protection from myocardial damage, liver injury and and diabetic nephropathy (DN). As the mechanism of DN and DPN was similar, the present study was designed to explore the inhibitory effects of AGS-â…£ on diabetic peripheral neuropathy by using STZ induced diabetes in rats.