Neuroprotective Effects of Purpurin Against Ischemic Damage via MAPKs, Bax, and Oxidative Stress Cascades in the Gerbil Hippocampus

Abstract

Purpurin has various effects, including anti-inflammatory effects, and can efficiently cross the blood–brain barrier. In the present study, we investigated the effects of purpurin on oxidative stress in HT22 cells and mild brain damage in the gerbil hippocampal CA1 region induced by transient forebrain ischemia. Oxidative stress induced by H2O2 was significantly ameliorated by treatment with purpurin, based on changes in cell death, DNA fragmentation, formation of reactive oxygen species, and pro-apoptotic (Bax)/anti-apoptotic (Bcl-2) protein levels. In addition, treatment with purpurin significantly reduced the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK), and p38 signaling in HT22 cells. Transient forebrain ischemia in gerbils led to a significant increase in locomotor activity 1 day after ischemia and significant decrease in number of surviving cells in the CA1 region 4 days after ischemia. Administration of purpurin reduced the travel distance 1 day after ischemia and abrogates the neuronal death in the hippocampal CA1 region 4 days after ischemia based on immunohistochemical and histochemical staining for NeuN and Fluoro-Jade C, respectively. Purpurin treatment significantly decreased the activation of microglia and astrocytes as well as the increases of nuclear factor kappa-light-chain-enhancer of activated B cells p65 in the hippocampal CA1 region 4 days after ischemia and ameliorated the ischemia-induced transient increases of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the hippocampus 6 h after ischemia. In addition, purpurin significantly alleviated the ischemia-induced phosphorylation of JNK, ERK, and p38 in the hippocampus 1 day after ischemia. Furthermore, purpurin treatment significantly mitigated the increases of Bax in the hippocampus 1 day after ischemia and the lipid peroxidation based on malondialdehyde and hydroperoxides levels 2 days after ischemia. These results suggest that purpurin can be one of the potential candidates to reduce neuronal damage and inflammatory responses after oxidative stress in HT22 cells or ischemic damage in gerbils.

CHIP ameliorates neuronal damage in H2O2-induced oxidative stress in HT22 cells and gerbil ischemia

“…Three and six hours after ischemia induction, the animals were sacrificed, and both hippocampi were obtained to measure the antioxidant and anti-inflammatory effects of Tat-CHIP against ischemia, respectively. In previous studies, we observed the increases of malondialdehyde (MDA) and pro-inflammatory cytokines in the hippocampus 3 and 6 h after ischemia in gerbils, respectively 33 . MDA, IL-1β, IL-6, and TNF-α levels were measured in the hippocampus using their respective enzyme immunoassay kits (Abcam [Cambridge, UK] for MDA levels and BioSource International Inc. [Camarillo, CA] for IL-1β, IL-6, and TNF-α).…”

Purpurin, a Natural Anthroquinone Ameliorates Streptozotocin-induced Diabetic Nephropathy via Attenuating Hyperglycemia, Dyslipidemia, and Inflammation in Rats

“…20, 31 Antiglycemic and antihypertensive drugs, such as ACE inhibitors, Angiotensin II receptor blockers, were not so potent and still, and the incidence of diabetic nephropathy remains increasing. Most of the discovered drugs failed during the clinical Phase III trials, 32, 33 hence it is necessary to discover a potent drug to ameliorate diabetic nephropathy.…”

“…A recent study revealed that purpurin effectively ameliorated hepatotoxicity, 29 suppressed atopic dermatitis, 30 protected hepatorenal injury, 31 and demonstrated neuroprotective effects 32 in various study models.…”

Natural products for the treatment of depression: Insights into signal pathways influencing the hypothalamic–pituitary–adrenal axis

“…For instance, in HT22 cells, treatment with various purine concentrations ranging from 1 to 200 μM revealed that 25 μM of purine exhibited the least toxicity. [ 84 ] In 3T3-L1 adipocytes, concentrations of 50 μM and 100 μM purine demonstrated positive effects. [ 120 ] Furthermore, the study on pinecone chrysanthemum glycosides in rats found that both 15 mg/kg and 60 mg/kg doses reversed HPA axis overexpression.…”

“…[ 83 ] Purpurin significantly decreases the expression of NF-κB signaling and MAPK phosphorylation in astrocytes and protects damaged neurons. [ 84 ] In addition, purpurin inhibits HPA axis overactivity by decreasing serum ACTH and CORT levels, resulting in antidepressant effects. [ 107 ] Emodin is an anthraquinone compound found in Rheum palmatum L that can alleviate GR hypoexpression and increase BDNF expression levels.…”