Neuroprotective activities of catalpol against CaMKII‐dependent apoptosis induced by LPS in PC12 cells

Abstract

Background and Purpose Neurodegenerative diseases present progressive neurological disorder induced by cell death or apoptosis. Catalpol, an iridoid glucoside isolated from the root of Rehmannia glutinosa Libosch, is present in a wide range of plant families. Although catalpol is an effective anti‐apoptotic agent in LPS‐induced neurodegeneration, the underlying mechanism has not been established. Here we have identified some of the mechanisms involved the prevention by catalpol of apoptosis induced by LPS in an experimental model of neurodegeneration in vitro. Experimental Approach Apoptosis was induced by adding LPS (80 ng·mL−1) to pheochromocytoma (PC12) cells, pretreated with catalpol for 12 h. We measured intracellular reactive oxygen species (ROS), apoptosis and intracellular calcium concentration ( [Ca2+]i) by flow cytometry or laser confocal scanning microscopy. We also analysed the protein expression of Bcl‐2, Bax and Ca2+‐calmodulin‐dependent protein kinase II (CaMKII)‐dependent apoptosis signal‐regulating kinase‐1 (ASK‐1)/JNK/p38 signalling pathway in PC12 cells by Western blot. Key Results Catalpol stimulated expression of Bcl‐2 and inhibited the expression of Bax. Catalpol also attenuated the increase in Ca2+ concentration induced by LPS in PC12 cells and down‐regulated CaMK phosphorylation. The CaMKII‐dependent ASK‐1/JNK/p38 signalling cascade was blocked by catalpol. All these changes were accompanied by a decrease of apoptosis induced by LPS in PC12 cells. Conclusions and Implications The data presented here provide new mechanistic insights into the links between the CaMKII‐dependent ASK‐1/JNK/p38 signalling pathway and the protective effect of catalpol on apoptosis induced by LPS in PC12 cells.

Involvement of the central monoaminergic system in the antidepressant-like effect of catalpol in mice

“…Catalpol ( Figure 1A) is a major bioactive compound that is found in abundance in the dried root of R. glutinosa. This compound has been found to have neuroprotective action, ameliorate cognition deficits, and have potential as a treatment for inflammationrelated neurodegenerative diseases (4)(5)(6). A previous study reported that the powdered dried root of R. glutinosa had an antidepressant-like effect in mice (7).…”

Autophagy Regulates Colistin-Induced Apoptosis in PC-12 Cells

“…The PC-12 cell line is derived from a pheochromocytoma in a rat adrenal medulla and contains both neuroblastic and eosinophilic cells (20,21). It is commonly employed as a model system for neuronal differentiation and neurosecretion and is one of the most widely used neuronal cell lines for examining mechanisms associated with neurotoxicity and neurodegenerative disorders (20,21).…”

“…It is commonly employed as a model system for neuronal differentiation and neurosecretion and is one of the most widely used neuronal cell lines for examining mechanisms associated with neurotoxicity and neurodegenerative disorders (20,21). In this study, we employed PC-12 cells to investigate whether colistin treatment causes autophagy and its potential neuroprotective effect against colistin-induced neurotoxicity.…”

p-JAK2 plays a key role in catalpol-induced protection against rat intestinal ischemia/reperfusion injury

“…15,16 Catalpol, an iridoid glucoside of the main active component in the radix from Rehmannia glutinosa Libosch, 17,18 is found to have a wide variety of biological activities including anti-oxidative, anti-inammatory, anti-cancer, hypoglycemic, and analgesic effects. 19,20 Catalpol is found to have protective effects against tissue injuries including liver, kidney, and brain injuries. 19,21,22 Catalpol also shows a strong anti-microbial effect against intestinal infection caused by pathogens during intestinal I/R.…”

“…19,20 Catalpol is found to have protective effects against tissue injuries including liver, kidney, and brain injuries. 19,21,22 Catalpol also shows a strong anti-microbial effect against intestinal infection caused by pathogens during intestinal I/R. 19,23 However, whether catalpol can effectively protect against intestinal I/R injury remains unknown.…”