Lycium Barbarum (Wolfberry) Reduces Secondary Degeneration and Oxidative Stress, and Inhibits JNK Pathway in Retina after Partial Optic Nerve Transection

Abstract

Our group has shown that the polysaccharides extracted from Lycium barbarum (LBP) are neuroprotective for retinal ganglion cells (RGCs) in different animal models. Protecting RGCs from secondary degeneration is a promising direction for therapy in glaucoma management. The complete optic nerve transection (CONT) model can be used to study primary degeneration of RGCs, while the partial optic nerve transection (PONT) model can be used to study secondary degeneration of RGCs because primary degeneration of RGCs and secondary degeneration can be separated in location in the same retina in this model; in other situations, these types of degeneration can be difficult to distinguish. In order to examine which kind of degeneration LBP could delay, both CONT and PONT models were used in this study. Rats were fed with LBP or vehicle daily from 7 days before surgery until sacrifice at different time-points and the surviving numbers of RGCs were evaluated. The expression of several proteins related to inflammation, oxidative stress, and the c-jun N-terminal kinase (JNK) pathways were detected with Western-blot analysis. LBP did not delay primary degeneration of RGCs after either CONT or PONT, but it did delay secondary degeneration of RGCs after PONT. We found that LBP appeared to exert these protective effects by inhibiting oxidative stress and the JNK/c-jun pathway and by transiently increasing production of insulin-like growth factor-1 (IGF-1). This study suggests that LBP can delay secondary degeneration of RGCs and this effect may be linked to inhibition of oxidative stress and the JNK/c-jun pathway in the retina.

Heat shock proteins in the retina: Focus on HSP70 and alpha crystallins in ganglion cell survival

“…The neuroprotective effects of LBP are associated with its ability to modulate several pathways that are activated after injury including anti-apoptotic, anti-oxidative and immune response. LBP modulates microglia activation in chronic OH model (Chiu et al, 2009), down-regulate RAGE (the receptor for advanced glycation end-products (AGEs), AGE, Aβ and endothelin-1 in the retinas of an acute OH model (Mi et al, 2012), activate antioxidant pathway by increasing Nrf2 (nuclear factor erythroid 2-related factor) nuclear accumulation and heme oxygenase-1 expression in the retina after ischemia/reperfusion injury (Li et al, 2011; He et al, 2014), reduces oxidative stress and inhibit the JNK pathway after ONT (Li et al, 2013, 2015), decrease the phosphorylation of double-stranded RNA-dependent protein kinase and inhibits the activity of caspases 3 and 2 in neurons stressed by beta-amyloid peptide induced neurotoxicity (Yu et al, 2007). LBP's capacity to modulate various pathways to increase cell resistance to stress- and injury-induced damage could be especialy benefecial in the treatment of multifactorial disorders such as glaucoma.…”

Can Goji Berry Extract Attenuate Pancreatic Structural Changes Induced by Patulin Toxin in Male Albino Rats?

“…A number of studies had found that LB can increase the expression of Bcl-2 and decrease the expression of Bax and increase the ratio of Bcl-2/Bax [38] . It was proved that LB could inhibit Jun N-terminal kinases pathway which activate apoptotic signaling by the upregulation of pro-apoptotic genes [39] . Furthermore, improvement of β-cells activity in the present work might be due to direct cytoprotective and indirect hypoglycemic effects of the extract.…”

Role of medicinal plants in neurodegenerative diseases

“…Ho et al [54] demonstrated that LB plays an active role in inhibiting glutamate induced cell death and phosporylation of c-jan N-terminal Kinase (JNK). Lycium barbarum plays a prominent role in inhibiting secondary degeneration of retinal ganglion cells and blocking the elevation of p-ERK and p-JNK [52,54,78]. Tang et al [127] suggested that active component of wolfberryZeaxanthin and Lutein is specifically involved in the retinal protection in diabetic mice model.…”