Ginsenoside Rg1 nanoparticle penetrating the blood–brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction

Abstract

Diabetic cerebral infarction is with poorer prognosis and high rates of mortality. Ginsenoside Rg1 (Rg1) has a wide variety of therapeutic values for central nervous system (CNS) diseases for the neuron protective effects. However, the blood–brain barrier (BBB) restricts Rg1 in reaching the CNS. In this study, we investigated the therapeutic effects of Rg1 nanoparticle (PHRO, fabricated with γ-PGA, L-PAE (H), Rg1, and OX26 antibody), targeting transferrin receptor, on the diabetes rats complicated with diabetic cerebral infarction in vitro and in vivo. Dynamic light scattering analysis shows the average particle size of PHRO was 79±18 nm and the polydispersity index =0.18. The transmission electron microscope images showed that all NPs were spherical in shape with diameters of 89±23 nm. PHRO released Rg1 with sustained release manner and could promote the migration of cerebrovascular endothelial cells and tube formation and even penetrated the BBB in vitro. PHRO could penetrate the BBB with high concentration in brain tissue to reduce the cerebral infarction volume and promote neuronal recovery in vivo. PHRO was promising to be a clinical treatment of diabetes mellitus with cerebral infarction.

Active ginseng components in cognitive impairment: Therapeutic potential and prospects for delivery and clinical study

“…Rg1 nanoparticles were developed to overcome the blood-brain barrier (BBB)-mediated restriction of Rg1 to reach the CNS. At a high concentration, Rg1 nanoparticles can penetrate the BBB to reduce the cerebral infarction volume and promote neuronal recovery in vivo [ 144 ]. In addition, nanoparticle formulation of Rg3 offered neuroprotective activity in an AD model.…”

Review of Ginseng Anti-Diabetic Studies

“…Several animal studies have found that ginseng processed products or individual ginsenosides regulate blood glucose in diabetic mouse or rat models, accompanied by regulating the expression of TNF-α, eNOS [46,53,56], suggesting that diabetes is associated with inflammation, and effective modulation by ginseng on inflammation may be able to prevent the development of insulin resistance. Recently, Shen et al reported that Rg1 released in brain tissue using nano-drug delivery systems reduced the volume of cerebral infarction and improved neural recovery in diabetic rats with cerebral infarction [59], indicating that the hypoglycemic effect of Rg1 may be regulated through the central nervous system. Additionally, in an STZ-induced type 1 diabetic rat model, ginsenoside Rh2 reduced fasting blood glucose and improved cardiac function via enhancing PPAR-δ signaling in diabetic rats with cardiac fibrosis [60].…”

Fabrication of a nano polymer wrapping Meg3 ShRNA plasmid for the treatment of cerebral infarction

“…The tubes were formed according to the report [25,26]. In conclusion, RBE4 cells (1 Â 10 4 ) were inoculated into 24 well plate coated with 50 ll Matrigel and cultured with 400 ll ECM culture medium with 10% FBS and 1% P/S in the presence of 10 ll PBS (Control group), Meg3-control plasmid (2 lg, CP group), Meg3 plasmid (2 lg, Meg3 group) or MPO (MPO group, containing 2 lg plasmid), respectively.…”

“…Rat cerebral infarction model was made as described before [25]. Briefly, the rats were anesthetized with 3% pentobarbital sodium (30 mg/kg).…”

“…Rats' cardiac perfusion and fixation were carried out as described before [25]. Brain tissues of different groups were acquired from the identified section of ischemic cerebral cortex, then fixed and paraffin embedded [27].…”